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1. Aging impairs the osteocytic regulation of collagen integrity and bone quality.

Author: Schurman, Charles, Kaya, Serra, Dole, Neha, Luna, Nadja, Castillo, Natalia, Potter, Ryan, Rose, Jacob, Bons, Joanna, King, Christina, Burton, Jordan, Schilling, Birgit, Melov, Simon, Tang, Simon, Schaible, Eric, and Alliston, Tamara
Subjects: Humans, Aged, Male, Animals, Mice, Osteocytes, Bone Remodeling, Collagen, Aging, Transforming Growth Factor beta
Abstract: Poor bone quality is a major factor in skeletal fragility in elderly individuals. The molecular mechanisms that establish and maintain bone quality, independent of bone mass, are unknown but are thought to be primarily determined by osteocytes. We hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling (PLR), which maintains bone material properties. We examined bones from young and aged mice with osteocyte-intrinsic repression of TGFβ signaling (TβRIIocy-/-) that suppresses PLR. The control aged bone displayed decreased TGFβ signaling and PLR, but aging did not worsen the existing PLR suppression in male TβRIIocy-/- bone. This relationship impacted the behavior of collagen material at the nanoscale and tissue scale in macromechanical tests. The effects of age on bone mass, density, and mineral material behavior were independent of osteocytic TGFβ. We determined that the decline in bone quality with age arises from the loss of osteocyte function and the loss of TGFβ-dependent maintenance of collagen integrity.
Published: 2024

2. Surgery for post-prostatectomy urinary incontinence: Update from the 7th ICI

Author: M.A. Averbeck, E. Chung, A. Collado Serra, C. Comiter, M. Guralnick, S. Herschorn, A. Singla, and H.B. Goldman
Subjects: Artificial sphincter, Male, Male sling, Urinary stress incontinence, Diseases of the genitourinary system. Urology, RC870-923
Abstract: Objective:: To present the recommendations for post-prostatectomy urinary incontinence from the 7th International Consultation on Incontinence (ICI). Methods:: This review was based on hand- and electronically-searched literature, abstracts from scientific meetings, and articles from peer-reviewed publications. Results:: Bladder diary and pad tests are useful in determining the amount of leaking. Treatment planning may benefit from cystoscopy and/or urodynamics, depending on underlying comorbidities and subtype of LUTS. Men with SUI have a low success rate with injectable bulking agents. The artificial sphincter is the preferred treatment for properly selected men who have moderate to severe stress incontinence after radical prostatectomy as the AUS has the longest record of safety and efficacy. This recommendation relates exclusively to the AMS 800 as newer devices do not have a similar evidence base or experience. Male slings are an acceptable surgical approach with several-year follow-up data supporting their safety and efficacy in men with mild to moderate degrees of PPI, particularly if there is no prior history of radiation. Conclusions:: Prospective randomized clinical trials are still needed, even though there are a number of series detailing the results of various surgical procedures for PPUI. Standardized workup and outcome metrics, as well as comprehensive long-term reporting of adverse events, are among the recommendations for future research.
Published: 2024
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3. Lipoprotein(a) levels in a global population with established atherosclerotic cardiovascular disease

Author: Nissen, Steven E, Wolski, Kathy, Cho, Leslie, Nicholls, Stephen J, Kastelein, John, Leitersdorf, Eran, Landmesser, Ulf, Blaha, Michael, Lincoff, A Michael, Morishita, Ryuichi, Tsimikas, Sotirios, Liu, Junhao, Manning, Brian, Kozlovski, Plamen, Lesogor, Anastasia, Thuren, Tom, Shibasaki, Taro, Matei, Florin, Silveira, Fábio Serra, Meunch, Andreas, Bada, Aysha, Vijan, Vinod, Bruun, Niels Eske, Nordestgaard, Borge G, and Investigators, For the LpHERITAGE
Subjects: Clinical Research, Atherosclerosis, Cardiovascular, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Good Health and Well Being, Female, Humans, Male, Middle Aged, Brain Ischemia, Cardiovascular Diseases, Cholesterol, LDL, Cross-Sectional Studies, Lipoprotein(a), Stroke, Aged, Lp(a)HERITAGE Investigators, atherosclerosis, global burden of disease, hyperlipidemias
Abstract: ObjectiveLipoprotein(a) (Lp(a)) is an important genetically determined risk factor for atherosclerotic vascular disease (ASCVD). With the development of Lp(a)-lowering therapies, this study sought to characterise patterns of Lp(a) levels in a global ASCVD population and identify racial, ethnic, regional and gender differences.MethodsA multicentre cross-sectional epidemiological study to estimate the prevalence of elevated Lp(a) in patients with a history of myocardial infarction, ischaemic stroke or peripheral artery disease conducted at 949 sites in 48 countries in North America, Europe, Asia, South America, South Africa and Australia between April 2019 and July 2021. Low-density lipoprotein cholesterol (LDL-C) and Lp(a) levels were measured either as mass (mg/dL) or molar concentration (nmol/L).ResultsOf 48 135 enrolled patients, 13.9% had prior measurements of Lp(a). Mean age was 62.6 (SD 10.1) years and 25.9% were female. Median Lp(a) was 18.0 mg/dL (IQR 7.9-57.1) or 42.0 nmol/L (IQR 15.0-155.4). Median LDL-C was 77 mg/dL (IQR 58.4-101.0). Lp(a) in women was higher, 22.8 (IQR 9.0-73.0) mg/dL, than in men, 17.0 (IQR 7.1-52.2) mg/dL, p50 mg/dL, 20.7% had levels >70 mg/dL, 12.9% were >90 mg/dL and 26.0% of patients exceeded 150 nmol/L.ConclusionsGlobally, Lp(a) is measured in a small minority of patients with ASCVD and is highest in black, younger and female patients. More than 25% of patients had levels exceeding the established threshold for increased cardiovascular risk, approximately 50 mg/dL or 125 nmol/L.Trial registration number
Published: 2022

4. Influence of gender and sexual hormones on outcomes after pituitary surgery: a systematic review and meta-analysis

Author: Theiler, Sven, Hegetschweiler, Saskia, Staartjes, Victor E., Spinello, Antonio, Brandi, Giovanna, Regli, Luca, and Serra, Carlo
Published: 2023
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5. The Wnt signaling receptor Fzd9 is essential for Myc-driven tumorigenesis in pancreatic islets

Author: Zacarías-Fluck, Mariano F, Jauset, Toni, Martínez-Martín, Sandra, Kaur, Jastrinjan, Casacuberta-Serra, Sílvia, Massó-Vallés, Daniel, del Pozo, Erika Serrano, Martín-Fernández, Génesis, González-Larreategui, Íñigo, López-Estévez, Sergio, Brown-Swigart, Lamorna, Beaulieu, Marie-Eve, Whitfield, Jonathan R, Madan, Babita, Virshup, David M, Evan, Gerard I, and Soucek, Laura
Subjects: Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Rare Diseases, Genetics, Pancreatic Cancer, Digestive Diseases, Cancer, Aetiology, 2.1 Biological and endogenous factors, Adenoma, Islet Cell, Animals, Carcinogenesis, Cell Movement, Cell Proliferation, Female, Frizzled Receptors, Genes, myc, Islets of Langerhans, Male, Mice, Wnt Signaling Pathway, beta Catenin, Biological sciences, Biomedical and clinical sciences
Abstract: The huge cadre of genes regulated by Myc has obstructed the identification of critical effectors that are essential for Myc-driven tumorigenesis. Here, we describe how only the lack of the receptor Fzd9, previously identified as a Myc transcriptional target, impairs sustained tumor expansion and β-cell dedifferentiation in a mouse model of Myc-driven insulinoma, allows pancreatic islets to maintain their physiological structure and affects Myc-related global gene expression. Importantly, Wnt signaling inhibition in Fzd9-competent mice largely recapitulates the suppression of proliferation caused by Fzd9 deficiency upon Myc activation. Together, our results indicate that the Wnt signaling receptor Fzd9 is essential for Myc-induced tumorigenesis in pancreatic islets.
Published: 2021

6. Can Short Psychological Interventions Affect Educational Performance? Revisiting the Effect of Self-Affirmation Interventions

Author: Serra-Garcia, Marta, Hansen, Karsten T, and Gneezy, Uri
Subjects: Psychology, Gender Equality, Academic Performance, Educational Status, Female, Humans, Male, Psychosocial Intervention, Regression Analysis, Self Concept, Sex Factors, self-affirmation, gender gap, education, open data, Cognitive Sciences, Experimental Psychology
Abstract: Large amounts of resources are spent annually to improve educational achievement and to close the gender gap in sciences with typically very modest effects. In 2010, a 15-min self-affirmation intervention showed a dramatic reduction in this gender gap. We reanalyzed the original data and found several critical problems. First, the self-affirmation hypothesis stated that women's performance would improve. However, the data showed no improvement for women. There was an interaction effect between self-affirmation and gender caused by a negative effect on men's performance. Second, the findings were based on covariate-adjusted interaction effects, which imply that self-affirmation reduced the gender gap only for the small sample of men and women who did not differ in the covariates. Third, specification-curve analyses with more than 1,500 possible specifications showed that less than one quarter yielded significant interaction effects and less than 3% showed significant improvements among women.
Published: 2020

7. The Hippo Effector Transcriptional Coactivator with PDZ-Binding Motif Cooperates with Oncogenic β-Catenin to Induce Hepatoblastoma Development in Mice and Humans

Author: Zhang, Shu, Zhang, Jie, Evert, Katja, Li, Xiaolei, Liu, Pin, Kiss, Andras, Schaff, Zsuzsa, Ament, Cindy, Zhang, Yi, Serra, Monica, Evert, Matthias, Chen, Nianyong, Xu, Feng, Chen, Xin, Tao, Junyan, Calvisi, Diego F, and Cigliano, Antonio
Subjects: Biomedical and Clinical Sciences, Digestive Diseases, Biotechnology, Pediatric, Cancer, Liver Disease, Aetiology, 2.1 Biological and endogenous factors, Animals, Carcinogenesis, Child, Child, Preschool, Female, Hepatoblastoma, Humans, Liver Neoplasms, Male, Mice, Trans-Activators, Transcriptional Coactivator with PDZ-Binding Motif Proteins, beta Catenin, Medical and Health Sciences, Pathology, Biomedical and clinical sciences, Health sciences
Abstract: Hepatoblastoma (HB) is the most common pediatric liver tumor. Though Wnt/β-catenin and Hippo cascades are implicated in HB development, studies on crosstalk between β-catenin and Hippo downstream effector transcriptional coactivator with PDZ-binding motif (TAZ) in HB are lacking. Expression levels of TAZ and β-catenin in human HB specimens were assessed by immunohistochemistry. Functional interplay between TAZ and β-catenin was determined by overexpression of an activated form of TAZ (TAZS89A), either alone or combined with an oncogenic form of β-catenin (ΔN90-β-catenin), in mouse liver via hydrodynamic transfection. Activation of TAZ often co-occurred with that of β-catenin in clinical specimens. Although the overexpression of TAZS89A alone did not induce hepatocarcinogenesis, concomitant overexpression of TAZS89A and ΔN90-β-catenin triggered the development of HB lesions exhibiting both epithelial and mesenchymal features. Mechanistically, TAZ/β-catenin-driven HB development required TAZ interaction with transcriptional enhanced associate domain factors. Blockade of the Notch cascade did not inhibit TAZ/β-catenin-dependent HB formation in mice but suppressed the mesenchymal phenotype. Neither Yes-associated protein nor heat shock factor 1 depletion affected HB development in TAZ/β-catenin mice. In human HB cell lines, silencing of TAZ resulted in decreased cell growth, which was further reduced when TAZ knockdown was associated with suppression of either β-catenin or Yes-associated protein. Overall, our study identified TAZ as a crucial oncogene in HB development and progression.
Published: 2020

8. Early exercise induces long-lasting morphological changes in cortical and hippocampal neurons throughout of a sedentary period of rats.

Author: Serra, Fernando, Carvalho, Andrea, Araujo, Bruno, Torres, Laila, Cardoso, Fabrizio, Henrique, Jéssica, Placencia, Eduardo, Lent, Roberto, Arida, Ricardo, Gomes da Silva, Sérgio, and Gomez-Pinilla, Fernando
Subjects: Adrenocorticotropic Hormone, Animals, Brain-Derived Neurotrophic Factor, Cell Shape, Cerebral Cortex, Corticosterone, Dendrites, Hippocampus, Male, Neuronal Plasticity, Neurons, Physical Conditioning, Animal, Rats, Rats, Wistar, TOR Serine-Threonine Kinases
Abstract: Life experiences at early ages, such as physical activity in childhood and adolescence, can result in long-lasting brain effects able to reduce future risk of brain disorders and to enhance lifelong brain functions. However, how early physical exercise promotes these effects remains unclear. A possible hypothesis is that physical exercise increases the expression of neurotrophic factors and stimulates neuronal growth, resulting in a neural reserve to be used at later ages. Basing our study on this hypothesis, we evaluated the absolute number and morphology of neuronal cells, as well as the expression of growth, proliferation and survival proteins (BDNF, Akt, mTOR, p70S6K, ERK and CREB) in the cerebral cortex and hippocampal formation throughout of a sedentary period of rats who were physically active during youth. To do this, male Wistar rats were submitted to an aerobic exercise protocol from the 21st to the 60th postnatal days (P21-P60), and evaluated at 0 (P60), 30 (P90) and 60 (P120) days after the last exercise session. Results showed that juvenile exercise increased, and maintained elevated, the number of cortical and hippocampal neuronal cells and dendritic arborization, when evaluated at the above post-exercise ages. Hippocampal BDNF levels and cortical mTOR expression were found to be increased at P60, but were restored to control levels at P90 and P120. Overall, these findings indicate that, despite the short-term effects on growth and survival proteins, early exercise induces long-lasting morphological changes in cortical and hippocampal neurons even during a sedentary period of rats.
Published: 2019

9. Hybrid Assembly of the Genome of the Entomopathogenic Nematode Steinernema carpocapsae Identifies the X-Chromosome.

Author: Serra, Lorrayne, Macchietto, Marissa, Macias-Muñoz, Aide, McGill, Cassandra, Rodriguez, Isaryhia, Rodriguez, Bryan, Murad, Rabi, and Mortazavi, Ali
Subjects: Genetics of Sex, S. carpocapsae, Steinernema, Steinernema genome, Animals, Computational Biology, Female, Gene Expression Profiling, Genome, Genomics, High-Throughput Nucleotide Sequencing, Male, Nematoda, Phylogeny, X Chromosome
Abstract: Entomopathogenic nematodes from the genus Steinernema are lethal insect parasites that quickly kill their insect hosts with the help of their symbiotic bacteria. Steinernema carpocapsae is one of the most studied entomopathogens due to its broad lethality to diverse insect species and its effective commercial use as a biological control agent for insect pests, as well as a genetic model for studying parasitism, pathogenesis, and symbiosis. In this study, we used long-reads from the Pacific Biosciences platform and BioNano Genomics Irys system to assemble the most complete genome of the S. carpocapsae ALL strain to date, comprising 84.5 Mb in 16 scaffolds, with an N50 of 7.36 Mb. The largest scaffold, with 20.9 Mb, was identified as chromosome X based on sex-specific genome sequencing. The high level of contiguity allowed us to characterize gene density, repeat content, and GC content. RNA-seq data from 17 developmental stages, spanning from embryo to adult, were used to predict 30,957 gene models. Using this improved genome, we performed a macrosyntenic analysis to Caenorhabditis elegans and Pristionchus pacificus and found S. carpocapsaes chromosome X to be primarily orthologous to C. elegans and P. pacificus chromosome II and IV. We also investigated the expansion of protein families and gene expression differences between adult male and female stage nematodes. This new genome and more accurate set of annotations provide a foundation for additional comparative genomic and gene expression studies within the Steinernema clade and across the Nematoda phylum.
Published: 2019

10. Coordinating Tissue Regeneration Through Transforming Growth Factor‐β Activated Kinase 1 Inactivation and Reactivation

Author: Hsieh, Hsiao Hsin Sung, Agarwal, Shailesh, Cholok, David J, Loder, Shawn J, Kaneko, Kieko, Huber, Amanda, Chung, Michael T, Ranganathan, Kavitha, Habbouche, Joe, Li, John, Butts, Jonathan, Reimer, Jonathan, Kaura, Arminder, Drake, James, Breuler, Christopher, Priest, Caitlin R, Nguyen, Joe, Brownley, Cameron, Peterson, Jonathan, Ozgurel, Serra Ucer, Niknafs, Yashar S, Li, Shuli, Inagaki, Maiko, Scott, Greg, Krebsbach, Paul H, Longaker, Michael T, Westover, Kenneth, Gray, Nathanael, Ninomiya‐Tsuji, Jun, Mishina, Yuji, and Levi, Benjamin
Subjects: Biomedical and Clinical Sciences, Stem Cell Research, Regenerative Medicine, Musculoskeletal, Good Health and Well Being, Animals, Bone Regeneration, Cell Differentiation, Cell Proliferation, DNA Nucleotidyltransferases, Female, Founder Effect, Fractures, Bone, Gene Expression Regulation, Integrases, MAP Kinase Kinase Kinases, Male, Mesenchymal Stem Cells, Mice, Mice, Inbred C57BL, Mice, Transgenic, Osteoblasts, Primary Cell Culture, Protein Kinase Inhibitors, Signal Transduction, Skull, Wound Healing, Cellular proliferation, Differentiation, Progenitor cells, Proliferation, Stem, progenitor cell, Tissue regeneration, Stem/progenitor cell, Biological Sciences, Technology, Medical and Health Sciences, Immunology, Biological sciences, Biomedical and clinical sciences
Abstract: Aberrant wound healing presents as inappropriate or insufficient tissue formation. Using a model of musculoskeletal injury, we demonstrate that loss of transforming growth factor-β activated kinase 1 (TAK1) signaling reduces inappropriate tissue formation (heterotopic ossification) through reduced cellular differentiation. Upon identifying increased proliferation with loss of TAK1 signaling, we considered a regenerative approach to address insufficient tissue production through coordinated inactivation of TAK1 to promote cellular proliferation, followed by reactivation to elicit differentiation and extracellular matrix production. Although the current regenerative medicine paradigm is centered on the effects of drug treatment ("drug on"), the impact of drug withdrawal ("drug off") implicit in these regimens is unknown. Because current TAK1 inhibitors are unable to phenocopy genetic Tak1 loss, we introduce the dual-inducible COmbinational Sequential Inversion ENgineering (COSIEN) mouse model. The COSIEN mouse model, which allows us to study the response to targeted drug treatment ("drug on") and subsequent withdrawal ("drug off") through genetic modification, was used here to inactivate and reactivate Tak1 with the purpose of augmenting tissue regeneration in a calvarial defect model. Our study reveals the importance of both the "drug on" (Cre-mediated inactivation) and "drug off" (Flp-mediated reactivation) states during regenerative therapy using a mouse model with broad utility to study targeted therapies for disease. Stem Cells 2019;37:766-778.
Published: 2019

11. Synthetic, non-intoxicating 8,9-dihydrocannabidiol for the mitigation of seizures.

Author: Mascal, Mark, Hafezi, Nema, Wang, Deping, Hu, Yuhan, Serra, Gessica, Dallas, Mark L, and Spencer, Jeremy PE
Subjects: Animals, Rats, Rats, Wistar, Seizures, Disease Models, Animal, Cannabinoids, Cannabidiol, Pentylenetetrazole, Anticonvulsants, Treatment Outcome, Male
Abstract: There can be a fine line between therapeutic intervention and substance abuse, and this point is clearly exemplified in herbal cannabis and its products. Therapies involving cannabis have been the treatment of last resort for some cases of refractory epilepsy, and this has been among the strongest medical justifications for legalization of marijuana. In order to circumvent the narcotic effects of Δ9-tetrahydrocannabinol (THC), many studies have concentrated on its less intoxicating isomer cannabidiol (CBD). However, CBD, like all natural cannabinoids, is a controlled substance in most countries, and its conversion into THC can be easily performed using common chemicals. We describe here the anticonvulsant properties of 8,9-dihydrocannibidiol (H2CBD), a fully synthetic analogue of CBD that is prepared from inexpensive, non-cannabis derived precursors. H2CBD was found to have effectiveness comparable to CBD both for decreasing the number and reducing the severity of pentylenetetrazole-induced seizures in rats. Finally, H2CBD cannot be converted by any reasonable synthetic route into THC, and thus has the potential to act as a safe, noncontroversial drug for seizure mitigation.
Published: 2019

12. Advancing global health and strengthening the HIV response in the era of the Sustainable Development Goals: the International AIDS Society-Lancet Commission.

Author: Bekker, Linda-Gail, Alleyne, George, Baral, Stefan, Cepeda, Javier, Daskalakis, Demetre, Dowdy, David, Dybul, Mark, Eholie, Serge, Esom, Kene, Garnett, Geoff, Grimsrud, Anna, Hakim, James, Havlir, Diane, Isbell, Michael T, Johnson, Leigh, Kamarulzaman, Adeeba, Kasaie, Parastu, Kazatchkine, Michel, Kilonzo, Nduku, Klag, Michael, Klein, Marina, Lewin, Sharon R, Luo, Chewe, Makofane, Keletso, Martin, Natasha K, Mayer, Kenneth, Millett, Gregorio, Ntusi, Ntobeko, Pace, Loyce, Pike, Carey, Piot, Peter, Pozniak, Anton, Quinn, Thomas C, Rockstroh, Jurgen, Ratevosian, Jirair, Ryan, Owen, Sippel, Serra, Spire, Bruno, Soucat, Agnes, Starrs, Ann, Strathdee, Steffanie A, Thomson, Nicholas, Vella, Stefano, Schechter, Mauro, Vickerman, Peter, Weir, Brian, and Beyrer, Chris
Subjects: Humans, HIV Infections, Anti-HIV Agents, International Cooperation, Healthy People Programs, Societies, Medical, Female, Male, Global Health, General & Internal Medicine, Medical and Health Sciences
Published: 2018

13. Prehospital Acute ST-Elevation Myocardial Infarction Identification in San Diego: A Retrospective Analysis of the Effect of a New Software Algorithm

Author: Coffey, Christanne, Serra, John, Goebel, Mat, Espinoza, Sarah, Castillo, Edward, and Dunford, James
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Cardiovascular, Clinical Research, Heart Disease, Adult, Aged, Aged, 80 and over, Algorithms, California, Electrocardiography, Emergency Medical Services, Female, Humans, Male, Middle Aged, Retrospective Studies, ST Elevation Myocardial Infarction, Software Design, Time Factors, computer interpretation, ECG, false positive, paramedic, prehospital, STEMI, Emergency & Critical Care Medicine, Clinical sciences
Abstract: BACKGROUND:A significant increase in false positive ST-elevation myocardial infarction (STEMI) electrocardiogram interpretations was noted after replacement of all of the City of San Diego's 110 monitor-defibrillator units with a new brand. These concerns were brought to the manufacturer and a revised interpretive algorithm was implemented. OBJECTIVES:This study evaluated the effects of a revised interpretation algorithm to identify STEMI when used by San Diego paramedics. METHODS:Data were reviewed 6 months before and 6 months after the introduction of a revised interpretation algorithm. True-positive and false-positive interpretations were identified. Factors contributing to an incorrect interpretation were assessed and patient demographics were collected. RESULTS:A total of 372 (234 preimplementation, 138 postimplementation) cases met inclusion criteria. There was a significant reduction in false positive STEMI (150 preimplementation, 40 postimplementation; p
Published: 2018

14. Impact of Pretreatment Neutrophil Count on Chemotherapy Administration and Toxicity in Dogs with Lymphoma Treated with CHOP Chemotherapy.

Author: Fournier, Q, Serra, J-C, Handel, I, and Lawrence, J
Subjects: Antimicrobials, Chemotherapeutics, Hematology, Lymphoma, Oncology, Animals, Antibiotic Prophylaxis, Antineoplastic Combined Chemotherapy Protocols, Blood Cell Count, Chemotherapy-Induced Febrile Neutropenia, Cyclophosphamide, Dog Diseases, Dogs, Doxorubicin, Female, Lymphoma, Male, Neutropenia, Prednisolone, Vincristine
Abstract: BACKGROUND: Prechemotherapy absolute neutrophil count (ANC) cutoffs are arbitrary and vary across institutions and clinicians. Similarly, subjective guidelines are utilized for the administration of prophylactic antibiotics in neutropenic dogs. OBJECTIVES: To evaluate the impact of various ANC cutoffs on chemotherapy administration in dogs with lymphoma treated with CHOP chemotherapy and to determine whether an association between prechemotherapy ANC and subsequent toxicity exists. The secondary objective was to evaluate a currently used ANC cutoff to indicate prescription of prophylactic antibiotics. ANIMALS: Dogs diagnosed with lymphoma treated with CHOP chemotherapy (n = 64). METHODS: Six hundred and fifteen ANCs were stratified into 6 classes. The 3 ANC cutoffs 1.5 × 103 /μL, 2.0 × 103 /μL, and 2.5 × 103 /μL were assessed. The presence of an association between prechemotherapy ANC class and toxicity was determined. Afebrile neutropenic dogs with ANC
Published: 2018

15. Aerobic exercise in adolescence results in an increase of neuronal and non-neuronal cells and in mTOR overexpression in the cerebral cortex of rats

Author: Victorino, Angélica Begatti, Serra, Fernando Tadeu, Piñero, Pâmella Pimentel, de Almeida, Alexandre Aparecido, Lopim, Glauber Menezes, Matias, Ivair, Machado, Helio Rubens, Lent, Roberto, Cabral, Francisco Romero, Gomez-Pinilla, Fernando, Arida, Ricardo Mario, and da Silva, Sérgio Gomes
Subjects: Biological Psychology, Psychology, Prevention, Mental Health, Basic Behavioral and Social Science, Brain Disorders, Neurosciences, Pediatric, Behavioral and Social Science, Neurological, Aging, Animals, Cerebral Cortex, Hippocampus, Male, Memory, Neuronal Plasticity, Neurons, Physical Conditioning, Animal, Rats, Wistar, Signal Transduction, TOR Serine-Threonine Kinases, physical exercise, adolescent, brain, cerebral cortex, hippocampus, mTOR, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract: Better cognitive performance and greater cortical and hippocampal volume have been observed in individuals who undertook aerobic exercise during childhood and adolescence. One possible explanation for these beneficial effects is that juvenile physical exercise enables better neural development and hence more cells and neuronal circuitries. It is probable that such effects occur through intracellular signaling proteins associated with cell growth, proliferation and survival. Based on this information, we evaluated the number of neuronal and non-neuronal cells using isotropic fractionation and the expression and activation of intracellular proteins (ERK, CREB, Akt, mTOR and p70S6K) in the cerebral cortex and hippocampal formation of the rats submitted to a physical exercise program on a treadmill during adolescence. Results showed that physical exercise increases the number of neuronal and non-neuronal cortical cells and hippocampal neuronal cells in adolescent rats. Moreover, mTOR overexpression was found in the cortical region of exercised adolescent rats. These findings indicate a significant cellular proliferative effect of aerobic exercise on the cerebral cortex in postnatal development.
Published: 2017

16. Genetic analysis, in silico prediction, and family segregation in long QT syndrome

Author: Riuró, Helena, Campuzano, Oscar, Berne, Paola, Arbelo, Elena, Iglesias, Anna, Pérez-Serra, Alexandra, Coll-Vidal, Mònica, Partemi, Sara, Mademont-Soler, Irene, Picó, Ferran, Allegue, Catarina, Oliva, Antonio, Gerstenfeld, Edward, Sarquella-Brugada, Georgia, Castro-Urda, Víctor, Fernández-Lozano, Ignacio, Mont, Lluís, Brugada, Josep, Scornik, Fabiana S, and Brugada, Ramon
Subjects: Rare Diseases, Cardiovascular, Genetic Testing, Heart Disease, Genetics, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Adolescent, Adult, Computational Biology, Female, Genotype, Humans, KCNQ Potassium Channels, Long QT Syndrome, Male, Middle Aged, Mutation, Pedigree, Phenotype, Voltage-Gated Sodium Channels, Young Adult, Clinical Sciences, Genetics & Heredity
Abstract: The heritable cardiovascular disorder long QT syndrome (LQTS), characterized by prolongation of the QT interval on electrocardiogram, carries a high risk of sudden cardiac death. We sought to add new data to the existing knowledge of genetic mutations contributing to LQTS to both expand our understanding of its genetic basis and assess the value of genetic testing in clinical decision-making. Direct sequencing of the five major contributing genes, KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2, was performed in a cohort of 115 non-related LQTS patients. Pathogenicity of the variants was analyzed using family segregation, allele frequency from public databases, conservation analysis, and Condel and Provean in silico predictors. Phenotype-genotype correlations were analyzed statistically. Sequencing identified 36 previously described and 18 novel mutations. In 51.3% of the index cases, mutations were found, mostly in KCNQ1, KCNH2, and SCN5A; 5.2% of cases had multiple mutations. Pathogenicity analysis revealed 39 mutations as likely pathogenic, 12 as VUS, and 3 as non-pathogenic. Clinical analysis revealed that 75.6% of patients with QTc≥500 ms were genetically confirmed. Our results support the use of genetic testing of KCNQ1, KCNH2, and SCN5A as part of the diagnosis of LQTS and to help identify relatives at risk of SCD. Further, the genetic tools appear more valuable as disease severity increases. However, the identification of genetic variations in the clinical investigation of single patients using bioinformatic tools can produce erroneous conclusions regarding pathogenicity. Therefore segregation studies are key to determining causality.
Published: 2015

17. Combined administration of testosterone plus an ornithine decarboxylase inhibitor as a selective prostate‐sparing anabolic therapy

Author: Jasuja, Ravi, Costello, James C, Singh, Rajan, Gupta, Vandana, Spina, Catherine S, Toraldo, Gianluca, Jang, Hyeran, Li, Hu, Serra, Carlo, Guo, Wen, Chauhan, Pratibha, Narula, Navjot S, Guarneri, Tyler, Ergun, Ayla, Travison, Thomas G, Collins, James J, and Bhasin, Shalender
Subjects: Prostate Cancer, Cancer, Biotechnology, Urologic Diseases, Aging, Anabolic Agents, Animals, Body Weight, Eflornithine, Enzyme Inhibitors, Follistatin, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Muscle, Skeletal, Oligonucleotide Array Sequence Analysis, Organ Size, Organ Sparing Treatments, Ornithine Decarboxylase, Ornithine Decarboxylase Inhibitors, Prostate, Recombinant Proteins, Signal Transduction, Testosterone, aging, anti-aging, sarcopenia, sex hormones, skeletal muscle, steroids, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract: Because of its anabolic effects on muscle, testosterone is being explored as a function-promoting anabolic therapy for functional limitations associated with aging; however, concerns about testosterone's adverse effects on prostate have inspired efforts to develop strategies that selectively increase muscle mass while sparing the prostate. Testosterone's promyogenic effects are mediated through upregulation of follistatin. We show here that the administration of recombinant follistatin (rFst) increased muscle mass in mice, but had no effect on prostate mass. Consistent with the results of rFst administration, follistatin transgenic mice with constitutively elevated follistatin levels displayed greater muscle mass than controls, but had similar prostate weights. To elucidate signaling pathways regulated differentially by testosterone and rFst in prostate and muscle, we performed microarray analysis of mRNAs from prostate and levator ani of castrated male mice treated with vehicle, testosterone, or rFst. Testosterone and rFst shared the regulation of many transcripts in levator ani; however, in prostate, 593 transcripts in several growth-promoting pathways were differentially expressed after testosterone treatment, while rFst showed a negligible effect with only 9 transcripts differentially expressed. Among pathways that were differentially responsive to testosterone in prostate, we identified ornithine decarboxylase (Odc1), an enzyme in polyamine biosynthesis, as a testosterone-responsive gene that is unresponsive to rFst. Accordingly, we administered testosterone with and without α-difluoromethylornithine (DFMO), an Odc1 inhibitor, to castrated mice. DFMO selectively blocked testosterone's effects on prostate, but did not affect testosterone's anabolic effects on muscle. Co-administration of testosterone and Odc1 inhibitor presents a novel therapeutic strategy for prostate-sparing anabolic therapy.
Published: 2014

18. Exome sequencing identifies nonsegregating nonsense ATM and PALB2variants in familial pancreatic cancer

Author: Grant, Robert C, Al-Sukhni, Wigdan, Borgida, Ayelet E, Holter, Spring, Kanji, Zaheer S, McPherson, Treasa, Whelan, Emily, Serra, Stefano, Trinh, Quang M, Peltekova, Vanya, Stein, Lincoln D, McPherson, John D, and Gallinger, Steven
Subjects: Biological Sciences, Genetics, Pancreatic Cancer, Rare Diseases, Digestive Diseases, Human Genome, Clinical Research, Cancer, 2.1 Biological and endogenous factors, Aetiology, Alleles, Ataxia Telangiectasia Mutated Proteins, Base Sequence, Carcinoma, Chromosome Segregation, Codon, Nonsense, Exome, Fanconi Anemia Complementation Group N Protein, Female, Genetic Predisposition to Disease, Humans, Male, Molecular Sequence Data, Nuclear Proteins, Pancreatic Neoplasms, Pedigree, Reproducibility of Results, Sequence Analysis, DNA, Tumor Suppressor Proteins, Hereditary cancer, Pancreas cancer, Germline variants, Genetic counseling, Carcinogenesis, Genetics & Heredity, Biochemistry and cell biology
Abstract: We sequenced 11 germline exomes from five families with familial pancreatic cancer (FPC). One proband had a germline nonsense variant in ATM with somatic loss of the variant allele. Another proband had a nonsense variant in PALB2 with somatic loss of the variant allele. Both variants were absent in a relative with FPC. These findings question the causal mechanisms of ATM and PALB2 in these families and highlight challenges in identifying the causes of familial cancer syndromes using exome sequencing.
Published: 2013

19. Exome sequencing identifies nonsegregating nonsense ATM and PALB2 variants in familial pancreatic cancer.

Author: Grant, Robert C, Al-Sukhni, Wigdan, Borgida, Ayelet E, Holter, Spring, Kanji, Zaheer S, McPherson, Treasa, Whelan, Emily, Serra, Stefano, Trinh, Quang M, Peltekova, Vanya, Stein, Lincoln D, McPherson, John D, and Gallinger, Steven
Subjects: Humans, Carcinoma, Pancreatic Neoplasms, Genetic Predisposition to Disease, Tumor Suppressor Proteins, Nuclear Proteins, Codon, Nonsense, Reproducibility of Results, Pedigree, Sequence Analysis, DNA, Chromosome Segregation, Base Sequence, Alleles, Molecular Sequence Data, Female, Male, Exome, Ataxia Telangiectasia Mutated Proteins, Fanconi Anemia Complementation Group N Protein, Hereditary cancer, Pancreas cancer, Germline variants, Genetic counseling, Carcinogenesis, Codon, Nonsense, Sequence Analysis, DNA, Genetics & Heredity
Abstract: We sequenced 11 germline exomes from five families with familial pancreatic cancer (FPC). One proband had a germline nonsense variant in ATM with somatic loss of the variant allele. Another proband had a nonsense variant in PALB2 with somatic loss of the variant allele. Both variants were absent in a relative with FPC. These findings question the causal mechanisms of ATM and PALB2 in these families and highlight challenges in identifying the causes of familial cancer syndromes using exome sequencing.
Published: 2013

20. Multicenter Study of the Validity and Reliability of Subjective Global Assessment in the Hemodialysis Population

Author: Steiber, Alison, Leon, Janeen B, Secker, Donna, McCarthy, Maureen, McCann, Linda, Serra, Monica, Sehgal, Ashwini R, and Kalantar-Zadeh, Kamyar
Subjects: Nutrition, Kidney Disease, Prevention, Clinical Research, Metabolic and endocrine, Zero Hunger, Anthropometry, Body Mass Index, Female, Humans, Kidney Failure, Chronic, Male, Malnutrition, Middle Aged, Nutrition Assessment, Nutritional Status, Observer Variation, Renal Dialysis, Sensitivity and Specificity, Serum Albumin, Clinical Sciences, Nutrition and Dietetics, Urology & Nephrology
Abstract: ObjectiveSubjective Global Assessment (SGA) is a nutrition assessment tool recommended by the 2000 NKF K/DOQI Nutrition Guidelines. However, the validity and reliability of this tool have not been established in hemodialysis (HD) patients. The purpose of this observational study was to determine the reliability and validity of SGA in the HD population. Renal dietitians (RD) were recruited to perform SGA (7-point scale version) and collect data on demographics, clinical status, biochemistries, dietary intake, and quality of life (Medical Outcomes Short Form-36) on 3 HD patients at baseline and 6 months later.DesignThe 54 participating RDs were trained to perform SGA and collect data via a website created for this study. Interrater reliability for SGA was tested in a subset of 76 patients, via an SGA performed by a second RD at baseline, while intrarater reliability was assessed by the original RD repeating the SGA at 1 month. Data collection occurred at HD facilities in the United States (109 patients), Canada (35 patients), and New Zealand (9 patients).ResultsOf the 153 patients, 46% were female, 64% were Caucasian, 6% were Hispanic, 21% were African American, and 6% were Asian. The primary etiologies were hypertension (33%), type 2 diabetes mellitus (DM) (27%), type 1 DM (10%), and glomerular nephritis (10%); 59% had cardiovascular disease. The mean age, body mass index (BMI), serum albumin, and duration on HD were 64 +/- 14 years (mean +/- SD), 28 +/- 7 kg/m(2), 3.7 +/- 0.4 mg/dL, and 41 +/- 34 months, respectively. SGA scores were well nourished (7)-30%; mildly malnourished (MN 6)-41%; moderately MN 5-21%, 4-7%, and 3-2%; and severely MN (2 and 1)-0%. SGA training via the Internet achieved fair interrater reliability (weighted Kappa = 0.5, Spearman's Rho = 0.7) and substantial intrarater reliability (weighted Kappa = 0.7, Spearman's Rho = 0.8) (P < .001). Validity was demonstrated through statistically significant differences in mean BMI and serum albumin across the 5 categories of SGA (7-28 +/- 7, 6-29 +/- 7, 5-28 +/- 8, 4-21 +/- 4, 3-24 +/- 2, P < .05; and 7-3.8 +/- 0.3, 6-3.8 +/- 0.4, 5-37 +/- 0.05, 4-3.4 +/- 0.07, 3-2.9 +/- 1.2, P < .001, respectively). Nutritional status varied by age (P < .05), but not ethnicity or nationality.ConclusionWe conclude that the 7-point scale SGA is a reliable and valid tool for nutritional assessment in adults on HD.
Published: 2007

21. Arterial lactate as a predictor of postoperative complications in head and neck squamous cell carcinoma

Author: Mauricio Gomes da Silva Serra, Neyara Dos Santos Oliveira, Suzane Pereira de Souza, Tércio Guimarães Reis, Márcio Campos Oliveira, and José de Bessa Júnior
Subjects: Male, medicine.medical_specialty, medicine.medical_treatment, Complicações pós‐operatórias, 030204 cardiovascular system & hematology, Head and neck neoplasms, Hypoxemia, Postoperative complications, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, medicine, Humans, Initial treatment, In patient, Lactic Acid, Prospective Studies, Prospective cohort study, Monobloc, Squamous Cell Carcinoma of Head and Neck, business.industry, Neck dissection, medicine.disease, Head and neck squamous-cell carcinoma, Surgery, Neoplasias de cabeça e pescoço, Otorhinolaryngology, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Lactato, Lactate, Female, medicine.symptom, Complication, business
Abstract: Introduction Surgery is one of the most frequently used options in the treatment of head and neck squamous cell carcinoma. In surgical patients, the use of arterial lactate to assess hypoxemia and severe inflammatory states is well-founded. However, there are few studies on its use in patients with head and neck squamous cell carcinoma. The aim of this study was to investigate whether the serum arterial lactate level on the 1st postoperative day would be a predictor of postoperative complications in head and neck squamous cell carcinoma surgeries. Methods This is a prospective cohort, which evaluated 44 adult patients of both genders, with HNSCC, who underwent surgery associated with monobloc neck dissection as an initial treatment. Patients were divided into two groups, according to the presence or absence of postoperative complications: with complication (Clavien-Dindo II-V) and without complications (Clavien-Dindo 0-I). Student’s t-test and its variants were used to compare continuous data. Pearson’s or Spearman’s test was used to correlate the data and p values 1.7 mmoL/L was identified, with a sensitivity of 65.38% and specificity of 66.67%. Conclusion Arterial lactate measured on the first postoperative day is a good predictor of postoperative complications in patients with head and neck squamous cell carcinoma. Resumo Introdução A cirurgia é uma das opções mais usadas no tratamento do carcinoma epidermoide de cabeça e pescoço. Nos pacientes cirúrgicos, o uso do lactato arterial para avaliação de hipoxemia e de quadros inflamatórios graves é bem fundamentado. Entretanto, existem poucos estudos sobre o seu uso em pacientes com carcinoma epidermoide de cabeça e pescoço. O objetivo deste estudo foi investigar se o lactato arterial sérico no 1° dia de pós‐operatório seria um preditor de complicações pós‐operatórias nas cirurgias do carcinoma epidermoide de cabeça e pescoço. Método Trata‐se de uma coorte prospectiva, que avaliou 44 pacientes adultos, de ambos os gêneros, com carcinoma epidermoide de cabeça e pescoço, submetidos a cirurgia associada ao esvaziamento cervical em monobloco como tratamento inicial. Os pacientes foram divididos em dois grupos, segundo a presença ou não de complicações pós‐operatórias: complicados (Clavien‐Dindo II a V) e sem complicações (Clavien‐Dindo 0-I). Na comparação dos dados contínuos, foi usado o teste t de Student e as suas variantes. Na correlação dos dados, usou‐se o teste de Pearson ou Spearman. Valores de p inferiores a 0,05 (p < 0,05) foram considerados estatisticamente significativos. Resultados Dos pacientes, 59% (n = 26/44) desenvolveram complicações pós‐operatórias. O lactato sérico foi significantemente maior no grupo com complicações em relação aos pacientes sem complicações, respectivamente 2,15 mmoL/L (1,10-3,90) e 1,59 mmoL/L (0,70-3,44); p = 0,03. A acurácia prognóstica do lactato arterial foi de 69% (95% IC 54%-82%; p = 0,03), estimada pela curva ROC. Foi identificado um cut‐off> 1,7 mmoL/L, com sensibilidade de 65,38% e especificidade de 66,67%. Conclusão O lactato arterial do primeiro dia de pós‐operatório é um bom preditor de complicações pós‐operatórias nos pacientes com carcinoma epidermoide de cabeça e pescoço.
Published: 2022

22. FUSE-ML

Author: Victor E. Staartjes, Vittorio Stumpo, Luca Ricciardi, Nicolai Maldaner, Hubert A. J. Eversdijk, Moira Vieli, Olga Ciobanu-Caraus, Antonino Raco, Massimo Miscusi, Andrea Perna, Luca Proietti, Giorgio Lofrese, Michele Dughiero, Francesco Cultrera, Nicola Nicassio, Seong Bae An, Yoon Ha, Aymeric Amelot, Irene Alcobendas, Jose M. Viñuela-Prieto, Maria L. Gandía-González, Pierre-Pascal Girod, Sara Lener, Nikolaus Kögl, Anto Abramovic, Nico Akhavan Safa, Christoph J. Laux, Mazda Farshad, Dave O’Riordan, Markus Loibl, Anne F. Mannion, Alba Scerrati, Granit Molliqaj, Enrico Tessitore, Marc L. Schröder, W. Peter Vandertop, Martin N. Stienen, Luca Regli, Carlo Serra, Neurosurgery, Amsterdam Neuroscience - Neurovascular Disorders, and Amsterdam Neuroscience - Systems & Network Neuroscience
Subjects: Male, Lumbar Vertebrae, Models, Statistical, Neurosurgery, Outcome prediction, Predictive analytics, Middle Aged, Prognosis, NO, Treatment Outcome, Back Pain, Machine learning, Humans, Orthopedics and Sports Medicine, Surgery, Female, Spinal fusion, Clinical prediction model
Abstract: Background Indications and outcomes in lumbar spinal fusion for degenerative disease are notoriously heterogenous. Selected subsets of patients show remarkable benefit. However, their objective identification is often difficult. Decision-making may be improved with reliable prediction of long-term outcomes for each individual patient, improving patient selection and avoiding ineffective procedures. Methods Clinical prediction models for long-term functional impairment [Oswestry Disability Index (ODI) or Core Outcome Measures Index (COMI)], back pain, and leg pain after lumbar fusion for degenerative disease were developed. Achievement of the minimum clinically important difference at 12 months postoperatively was defined as a reduction from baseline of at least 15 points for ODI, 2.2 points for COMI, or 2 points for pain severity. Results Models were developed and integrated into a web-app (https://neurosurgery.shinyapps.io/fuseml/) based on a multinational cohort [N = 817; 42.7% male; mean (SD) age: 61.19 (12.36) years]. At external validation [N = 298; 35.6% male; mean (SD) age: 59.73 (12.64) years], areas under the curves for functional impairment [0.67, 95% confidence interval (CI): 0.59–0.74], back pain (0.72, 95%CI: 0.64–0.79), and leg pain (0.64, 95%CI: 0.54–0.73) demonstrated moderate ability to identify patients who are likely to benefit from surgery. Models demonstrated fair calibration of the predicted probabilities. Conclusions Outcomes after lumbar spinal fusion for degenerative disease remain difficult to predict. Although assistive clinical prediction models can help in quantifying potential benefits of surgery and the externally validated FUSE-ML tool may aid in individualized risk–benefit estimation, truly impacting clinical practice in the era of “personalized medicine” necessitates more robust tools in this patient population.
Published: 2022

23. Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Author: Pisani, Luigi, Algera, Anna Geke, Neto, Ary Serpa, Azevedo, Luciano, Pham, Tài, Paulus, Frederique, de Abreu, Marcelo Gama, Pelosi, Paolo, Dondorp, Arjen M, Bellani, Giacomo, Laffey, John G, Schultz, Marcus J, Martinez, Amadeu, Leal, Livia, Jorge Pereira, Antonio, de Oliveira Maia, Marcelo, Neto, Josè Aires, Piras, Claudio, Caser, Eliana Bernadete, Moreira, Cora Lavigne, Braga Gusman, Pablo, Dalcomune, Dyanne Moysés, Ribeiro de Carvalho, Alexandre Guilherme, Gondim, Louise Aline Romão, Castelo Branco Reis, Lívia Mariane, da Cunha Ribeiro, Daniel, de Assis Simões, Leonardo, Campos, Rafaela Siqueira, Fernandez Versiani dos Anjos, José Carlos, Bruzzi Carvalho, Frederico, Alves, Rossine Ambrosio, Nunes, Lilian Batista, Réa-Neto, Álvaro, de Oliveira, Mirella Cristine, Tannous, Luana, Cardoso Gomes, Brenno, Rodriguez, Fernando Borges, Abelha, Priscila, Lugarinho, Marcelo E, Japiassu, Andre, de Melo, Hélder Konrad, Lopes, Elton Afonso, Varaschin, Pedro, de Souza Dantas, Vicente Cés, Freitas Knibel, Marcos, Ponte, Micheli, de Azambuja Rodrigues, Pedro Mendes, Costa Filho, Rubens Carmo, Saddy, Felipe, Wanderley Castellões, Théia Forny, Silva, Suzana Alves, Osorio, Luiz Antonio Gomes, Mannarino, Dora, Espinoza, Rodolfo, Righy, Cassia, Soares, Marcio, Salluh, Jorge, Tanaka, Lilian, Aragão, Daniel, Tavares, Maria Eduarda, Kehdi, Maura Goncalves Pereira, Rezende, Valéria Maria Campos, Carbonell, Roberto Carlos Cruz, Teixeira, Cassiano, de Oliveira, Roselaine Pinheiro, Maccari, Juçara Gasparetto, Castro, Priscylla Souza, Berto, Paula, Schwarz, Patricia, Torelly, André Peretti, Lisboa, Thiago, Moraes, Edison, Dal-Pizzol, Felipe, Tomasi Damiani, Cristiane, Ritter, Cristiane, Ferreira, Juliana Carvalho, Teixeira Costa, Ramon, Caruso, Pedro, Amendola, Cristina Prata, de Oliveira, Amanda Maria R R, Silva, Ulysses V A, Sanches, Luciana Coelho, Almeida, Rosana D S, Azevedo, Luciano Cesar, Park, Marcelo, Schettino, Guilherme, Assunção, Murillo Santucci, Silva, Eliezer, Barboza, Carlos Eduardo, Junior, Antonio Paulo Nassar, Marzocchi Tierno, Paulo Fernando G M, Malbouisson, Luis Marcelo, Oliveira, Lucas, Cristovao, Davi, Neto, Manoel Leitão, Rego, Ênio, Fernandes, Fernanda Eugênia, Romano, Marcelo Luz Pereira, Cavalcanti, Alexandre Biasi, de Souza Barros, Dalton, Suzumura, Érica Aranha, Meira, Karla Loureiro, de Oliveira, Gustavo Affonso, Luciano, Paula Menezes, Pacheco, Evelin Drociunas, Mazza, Bruno Franco, Machado, Flavia Ribeiro, Ferreira, Elaine, dos Santos, Ronaldo Batista, Colombo, Alexandra Siqueira, Nogueira, Antonio Carlos, Fernandes, Juliana Baroni, Nóbrega, Raquel Siqueira, do CS Martins, Barbara, Soriano, Francisco, Morsch, Rafaela Deczka, Nunes, Andre Luiz Baptiston, de Almeida, Juliano Pinheiro, Hajjar, Ludhmila, Moulin, Sílvia, Giannini, Fábio Poianas, Baptiston Nunes, Andre Luiz, Rios, Fernando, Van Haren, Frank, Sottiaux, T, Lora, Fredy S, Azevedo, Luciano C, Depuydt, P, Fan, Eddy, Bugedo, Guillermo, Qiu, Haibo, Gonzalez, Marcos, Silesky, Juan, Cerny, Vladimir, Nielsen, Jonas, Jibaja, Manuel, Wrigge, Hermann, Matamis, Dimitrios, Ranero, Jorge Luis, Hashemian, S M, Amin, Pravin, Clarkson, Kevin, Kurahashi, Kiyoyasu, Villagomez, Asisclo, Zeggwagh, Amine Ali, Heunks, Leo M, Laake, Jon Henrik, Palo, Jose Emmanuel, do Vale Fernandes, Antero, Sandesc, Dorel, Arabi, Yaasen, Bumbasierevic, Vesna, Lorente, Jose A, Larsson, Anders, Piquilloud, Lise, Abroug, Fekri, McAuley, Daniel F, McNamee, Lia, Hurtado, Javier, Bajwa, Ed, Démpaire, Gabriel, Francois, Guy M, Sula, Hektor, Nunci, Lordian, Cani, Alma, Zazu, Alan, Dellera, Christian, Insaurralde, Carolina S, Alejandro, Risso V, Daldin, Julio, Vinzio, Mauricio, Fernandez, Ruben O, Cardonnet, Luis P, Bettini, Lisandro R, Bisso, Mariano Carboni, Osman, Emilio M, Setten, Mariano G, Lovazzano, Pablo, Alvarez, Javier, Villar, Veronica, Milstein, Cesar, Pozo, Norberto C, Grubissich, Nicolas, Plotnikow, Gustavo A, Vasquez, Daniela N, Ilutovich, Santiago, Tiribelli, Norberto, Chena, Ariel, Pellegrini, Carlos A, Saenz, María G, Estenssoro, Elisa, Brizuela, Matias, Gianinetto, Hernan, Gomez, Pablo E, Cerrato, Valeria I, Bezzi, Marco G, Borello, Silvina A, Loiacono, Flavia A, Fernandez, Adriana M, Knowles, Serena, Reynolds, Claire, Inskip, Deborah M, Miller, Jennene J, Kong, Jing, Whitehead, Christina, Bihari, Shailesh, Seven, Aylin, Krstevski, Amanda, Rodgers, Helen J, Millar, Rebecca T, Mckenna, Toni E, Bailey, Irene M, Hanlon, Gabrielle C, Aneman, Anders, Lynch, Joan M, Azad, Raman, Neal, John, Woods, Paul W, Roberts, Brigit L, Kol, Mark R, Wong, Helen S, Riss, Katharina C, Staudinger, Thomas, Wittebole, Xavier, Berghe, Caroline, Bulpa, Pierre A, Dive, Alain M, Verstraete, Rik, Lebbinck, Herve, Depuydt, Pieter, Vermassen, Joris, Meersseman, Philippe, Ceunen, Helga, Rosa, Jonas I, Beraldo, Daniel O, Ampinelli, Adenilton M R, Nassar Jr, Antonio P, Mataloun, Sergio, Moock, Marcelo, Thompson, Marlus M, Gonçalves, Claudio H, Antônio, Ana Carolina P, Ascoli, Aline, Biondi, Rodrigo S, Fontenele, Danielle C, Nobrega, Danielle, Sales, Vanessa M, Shindhe, Suresh, Ismail, Dk Maizatul Aiman B Pg Hj, Laffey, John, Beloncle, Francois, Davies, Kyle G, Cirone, Rob, Manoharan, Venika, Ismail, Mehvish, Goligher, Ewan C, Jassal, Mandeep, Nishikawa, Erin, Javeed, Areej, Curley, Gerard, Rittayamai, Nuttapol, Parotto, Matteo, Ferguson, Niall D, Mehta, Sangeeta, Knoll, Jenny, Pronovost, Antoine, Canestrini, Sergio, Bruhn, Alejandro R, Garcia, Patricio H, Aliaga, Felipe A, Farías, Pamela A, Yumha, Jacob S, Ortiz, Claudia A, Salas, Javier E, Saez, Alejandro A, Vega, Luis D, Labarca, Eduardo F, Martinez, Felipe T, Carreño, Nicolás G, Lora, Pilar, Liu, Haitao, Liu, Ling, Tang, Rui, Luo, Xiaoming, An, Youzhong, Zhao, Huiying, Gao, Yan, Zhai, Zhe, Ye, Zheng L, Wang, Wei, Li, Wenwen, Li, Qingdong, Zheng, Ruiqiang, Yu, Wenkui, Shen, Juanhong, Li, Xinyu, Yu, Tao, Lu, Weihua, Wu, Ya Q, Huang, Xiao B, He, Zhenyang, Lu, Yuanhua, Han, Hui, Zhang, Fan, Sun, Renhua, Wang, Hua X, Qin, Shu H, Zhu, Bao H, Zhao, Jun, Liu, Jian, Li, Bin, Liu, Jing L, Zhou, Fa C, Li, Qiong J, Zhang, Xing Y, Li-Xin, Zhou, Xin-Hua, Qiang, Jiang, Liangyan, Gao, Yuan N, Zhao, Xian Y, Li, Yuan Y, Li, Xiao L, Wang, Chunting, Yao, Qingchun, Yu, Rongguo, Chen, Kai, Shao, Huanzhang, Qin, Bingyu, Huang, Qing Q, Zhu, Wei H, Hang, Ai Y, Hua, Ma X, Li, Yimin, Xu, Yonghao, Di, Yu D, Ling, Long L, Qin, Tie H, Wang, Shou H, Qin, Junping, Han, Yi, Zhou, Suming, Vargas, Monica P, Silesky Jimenez, Juan I, González Rojas, Manuel A, Solis-Quesada, Jaime E, Ramirez-Alfaro, Christian M, Máca, Jan, Sklienka, Peter, Gjedsted, Jakob, Christiansen, Aage, Villamagua, Boris G, Llano, Miguel, Burtin, Philippe, Buzancais, Gautier, Beuret, Pascal, Pelletier, Nicolas, Mortaza, Satar, Mercat, Alain, Chelly, Jonathan, Jochmans, Sébastien, Terzi, Nicolas, Daubin, Cédric, Carteaux, Guillaume, de Prost, Nicolas, Chiche, Jean-Daniel, Daviaud, Fabrice, Pham, Tai, Fartoukh, Muriel, Barberet, Guillaume, Biehler, Jerome, Dellamonica, Jean, Doyen, Denis, Arnal, Jean-Michel, Briquet, Anais, Hraiech, Sami, Papazian, Laurent, Follin, Arnaud, Roux, Damien, Messika, Jonathan, Kalaitzis, Evangelos, Dangers, Laurence, Combes, Alain, Au, Siu-Ming, Béduneau, Gaetan, Carpentier, Dorothée, Zogheib, Elie H, Dupont, Herve, Ricome, Sylvie, Santoli, Francesco L, Besset, Sebastien L, Michel, Philippe, Gelée, Bruno, Danin, Pierre-Eric, Goubaux, Bernard, Crova, Philippe J, Phan, Nga T, Berkelmans, Frantz, Badie, Julio C, Tapponnier, Romain, Gally, Josette, Khebbeb, Samy, Herbrecht, Jean-Etienne, Schneider, Francis, Declercq, Pierre-Louis M, Rigaud, Jean-Philippe, Duranteau, Jacques, Harrois, Anatole, Chabanne, Russell, Marin, Julien, Bigot, Charlene, Thibault, Sandrine, Ghazi, Mohammed, Boukhazna, Messabi, Ould Zein, Salem, Richecoeur, Jack R, Combaux, Daniele M, Grelon, Fabien, Le Moal, Charlene, Sauvadet, Elise P, Robine, Adrien, Lemiale, Virginie, Reuter, Danielle, Dres, Martin, Demoule, Alexandre, Goldgran-Toledano, Dany, Baboi, Loredana, Guérin, Claude, Lohner, Ralph, Kraßler, Jens, Schäfer, Susanne, Zacharowski, Kai D, Meybohm, Patrick, Reske, Andreas W, Simon, Philipp, Hopf, Hans-Bernd F, Schuetz, Michael, Baltus, Thomas, Papanikolaou, Metaxia N, Papavasilopoulou, Theonymfi G, Zacharas, Giannis A, Ourailogloy, Vasilis, Mouloudi, Eleni K, Massa, Eleni V, Nagy, Eva O, Stamou, Electra E, Kiourtzieva, Ellada V, Oikonomou, Marina A, Avila, Luis E, Cortez, Cesar A, Citalán, Johanna E, Jog, Sameer A, Sable, Safal D, Shah, Bhagyesh, Gurjar, Mohan, Baronia, Arvind K, Memon, Mohammedfaruk, Muthuchellappan, Radhakrishnan, Ramesh, Venkatapura J, Shenoy, Anitha, Unnikrishnan, Ramesh, Dixit, Subhal B, Rhayakar, Rachana V, Ramakrishnan, Nagarajan, Bhardwaj, Vallish K, Mahto, Heera L, Sagar, Sudha V, Palaniswamy, Vijayanand, Ganesan, Deeban, Mohammadreza Hashemian, Seyed, Jamaati, Hamidreza, Heidari, Farshad, Meaney, Edel A, Nichol, Alistair, Knapman, Karl M, O'Croinin, Donall, Dunne, Eimhin S, Breen, Dorothy M, Clarkson, Kevin P, Jaafar, Rola F, Dwyer, Rory, Amir, Fahd, Ajetunmobi, Olaitan O, O'Muircheartaigh, Aogan C, Black, Colin S, Treanor, Nuala, Collins, Daniel V, Altaf, Wahid, Zani, Gianluca, Fusari, Maurizio, Spadaro, Savino, Volta, Carlo A, Graziani, Romano, Brunettini, Barbara, Palmese, Salvatore, Formenti, Paolo, Umbrello, Michele, Lombardo, Andrea, Pecci, Elisabetta, Botteri, Marco, Savioli, Monica, Protti, Alessandro, Mattei, Alessia, Schiavoni, Lorenzo, Tinnirello, Andrea, Todeschini, Manuel, Giarratano, Antonino, Cortegiani, Andrea, Sher, Sara, Rossi, Anna, Antonelli, Massimo M, Montini, Luca M, Casalena, Paolo, Scafetti, Sergio, Panarello, Giovanna, Occhipinti, Giovanna, Patroniti, Nicolò, Pozzi, Matteo, Biscione, Roberto R, Poli, Michela M, Raimondi, Ferdinando, Albiero, Daniela, Crapelli, Giulia, Beck, Eduardo, Pota, Vincenzo, Schiavone, Vincenzo, Molin, Alexandre, Tarantino, Fabio, Monti, Giacomo, Frati, Elena, Mirabella, Lucia, Cinnella, Gilda, Fossali, Tommaso, Colombo, Riccardo, Terragni, Pierpaolo, Pattarino, Ilaria, Mojoli, Francesco, Braschi, Antonio, Borotto, Erika E, Cracchiolo, Andrea N, Palma, Daniela M, Raponi, Francesco, Foti, Giuseppe, Vascotto, Ettore R, Coppadoro, Andrea, Brazzi, Luca, Floris, Leda, Iotti, Giorgio A, Venti, Aaron, Yamaguchi, Osamu, Takagi, Shunsuke, Maeyama, Hiroki N, Watanabe, Eizo, Yamaji, Yoshihiro, Shimizu, Kazuyoshi, Shiozaki, Kyoko, Futami, Satoru, Ryosuke, Sekine, Saito, Koji, Kameyama, Yoshinobu, Ueno, Keiko, Izawa, Masayo, Okuda, Nao, Suzuki, Hiroyuki, Harasawa, Tomofumi, Nasu, Michitaka, Takada, Tadaaki, Ito, Fumihito, Nunomiya, Shin, Koyama, Kansuke, Abe, Toshikazu, Andoh, Kohkichi, Kusumoto, Kohei, Hirata, Akira, Takaba, Akihiro, Kimura, Hiroyasu, Matsumoto, Shuhei, Higashijima, Ushio, Honda, Hiroyuki, Aoki, Nobumasa, Imai, Hiroshi, Ogino, Yasuaki, Mizuguchi, Ichiko, Ichikado, Kazuya, Nitta, Kenichi, Mochizuki, Katsunori, Hashida, Tomoaki, Tanaka, Hiroyuki, Nakamura, Tomoyuki, Niimi, Daisuke, Ueda, Takeshi, Kashiwa, Yozo, Uchiyama, Akinori, Sabelnikovs, Olegs, Oss, Peteris, Haddad, Youssef, Liew, Kong Y, Ñamendys-Silva, Silvio A, Jarquin-Badiola, Yves D, Sanchez-Hurtado, Luis A, Gomez-Flores, Saira S, Marin, Maria C, Villagomez, Asisclo J, Lemus, Jordana S, Fierro, Jonathan M, Cervantes, Mavy Ramirez, Mejia, Francisco Javier Flores, Gonzalez, Daniel R, Dector, Dulce M, Estrella, Claudia R, Sanchez-Medina, Jorge R, Ramirez-Gutierrez, Alvaro, George, Fernando G, Aguirre, Janet S, Buensuseso, Juan A, Poblano, Manuel, Dendane, Tarek, Balkhi, Hicham, Elkhayari, Mina, Samkaoui, Nacer, Ezzouine, Hanane, Benslama, Abdellatif, Amor, Mourad, Maazouzi, Wajdi, Cimic, Nedim, Beck, Oliver, Bruns, Monique M, Schouten, Jeroen A, Rinia, Myra, Raaijmakers, Monique, Van Wezel, Hellen M, Heines, Serge J, Buise, Marc P, Simonis, Fabienne D, Goodson, Jennifer C, rowne, Troy S B, Navarra, Leanlove, Hunt, Anna, Hutchison, Robyn A, Bailey, Mathew B, Newby, Lynette, Mcarthur, Colin, Kalkoff, Michael, Mcleod, Alex, 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Tharwat M, Al Jabbary, Ahmed S, Tabhan, Edgardo, Arabi, Yaseen M, Trinidad, Olivia A, Al Dorzi, Hasan M, Tabhan, Edgardo E, Bolon, Stefan, Smith, Oliver, Mancebo, Jordi, Aguirre-Bermeo, Hernan, Lopez-Delgado, Juan C, Esteve, Francisco, Rialp, Gemma, Forteza, Catalina, De Haro, Candelaria, Artigas, Antonio, Albaiceta, Guillermo M, De Cima-Iglesias, Sara, Seoane-Quiroga, Leticia, Ceniceros-Barros, Alexandra, Ruiz-Aguilar, Antonio L, Claraco-Vega, Luis M, Soler, Juan Alfonso, Lorente, Maria del Carmen, Hermosa, Cecilia, Gordo, Federico, Prieto-González, Miryam, López-Messa, Juan B, Perez, Manuel P, Pere, Cesar P, Allue, Raquel Montoiro, Roche-Campo, Ferran, Ibañez-Santacruz, Marcos, Temprano, Susana, Pintado, Maria C, De Pablo, Raul, Gómez, Pilar Ricart Aroa, Ruiz, Silvia Rodriguez, Moles, Silvia Iglesias, Jurado, Mª Teresa, Arizmendi, Alfons, Piacentini, Enrique A, Franco, Nieves, Honrubia, Teresa, Perez Cheng, Meisy, Perez Losada, Elena, Blanco, Javier, Yuste, Luis J, Carbayo-Gorriz, 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Joanna, Persson, Linnea, Schiöler, Fredrik, Kedelv, Hans, Tibblin, Anna Oscarsson, Appelberg, Henrik, Hedlund, Lars, Helleberg, Johan, Eriksson, Karin E, Glietsch, Rita, Larsson, Niklas, Nygren, Ingela, Nunes, Silvia L, Morin, Anna-Karin, Kander, Thomas, Adolfsson, Anne, Zender, Hervé O, Leemann-Refondini, Corinne, Elatrous, Souheil, Bouchoucha, Slaheddine, Chouchene, Imed, Ouanes, Islem, Ben Souissi, Asma, Kamoun, Salma, Demirkiran, Oktay, Aker, Mustafa, Erbabacan, Emre, Ceylan, Ilkay, Girgin, Nermin Kelebek, Ozcelik, Menekse, Ünal, Necmettin, Meco, Basak Ceyda, Akyol, Onat O, Derman, Suleyman S, Kennedy, Barry, Parhar, Ken, Srinivasa, Latha, McAuley, Danny, Steinberg, Jack, Hopkins, Phil, Mellis, Clare, Stansil, Frank, Kakar, Vivek, Hadfield, Dan, Brown, Christine, Vercueil, Andre, Bhowmick, Kaushik, Humphreys, Sally K, Ferguson, Andrew, Mckee, Raymond, Raj, Ashok S, Fawkes, Danielle A, Watt, Philip, Twohey, Linda, Thomas, Rajeev R Jha Matthew, Morton, Alex, Kadaba, Varsha, Smith, 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Ryan, Christine, Mellinghoff, Johannes Mellinghoff, Prudden, Sarah Prudden, Green, Helen Green, Roy, Alistair Roy, Furneval, Julie Furneval, Bell, Adam Bell, Lakhani, Sandeep Lakhani, Fasting, Lousie Fasting, Murray, Lorna Murray, Preller, Kobu, McInerney, Amy, Beavis, Sarah, Whileman, Amanda, Toms, Julie, Glenn, Sue, Ramali, Mohamed, Ghosh, Alison, Bullock, Clare, Barrell, Lisa, Young, Eoin, Robertson, Helen, Faulkner, Maria, MacNaughton, Peter, Tyson, Susan, Pulak, Paul, Sewell, Terri-Ann, Smalley, Christopher, Jacob, Reni, Alzugaray, Pedro, Vidal Melo, Marcos F, Joyce, Kristen, Needleman, Joseph, Ahsan, Areef, Faiz, Abul, Alam, AKM Shamsul, Khatoon, Syeda Nafisa, Nath, Ranjan Kumer, Rahman Chowdhury, Mohammed Abdur, Banik, Debabrata, Mondol, Montosh Kumar, Bhuiyan, Sakibur Rahman, Nazneed, Suraiya, Sultana, Rozina, Hamid, Tarikul, Hossain, Mozaffer, Reza, Syed Tariq, Asaduzzaman, Muhammad, Salim, Mohammad, Mostafa Kamal, Abu Hena, Taher, Sheikh Mohammed, Taohid, Taohidul Majid, Karmaker, Pranab, Roy, Sabyasachi, Das, Shantanu, Sarkar, Sohel Ahmed, Dutta, Monju Lal, Roy, Poulomi, Iyer, Shivakumar, Krishna, Bhuvana, Sampath, Sriram, Pattnaik, Rajyabardhan, Kasi, Chinni Krishna, Shah, Jignesh, Dongre, Anand, Reza Hashemian, Seyed Mohammad, Nooraei, Navid, Raessi Estabragh, Reza, Malekmohammad, Majid, Khoundabi, Batoul, Mobasher, Maziar, Mohd Yunos, Nor'azim, Kassim, Mahazir, Voon, Chern Min, Das, Stanis Sutharsa, Azauddin, Siti Nur Suhaila, Dorasamy, Dharshinie, Tai, Li Ling, Mat Nor, Mohd Basri, Zarudin, Nurhafizah, Hasan, Mohd Shahnaz, Jamaluddin, Mohamad Fadhil Hadi, Othman Jailani, Mohamad Irfan, Kayashta, Gyan, Adhikari, Aaradhana, Pangeni, Raju, Hashmi, Madiha, Joseph, Sonia, Akhtar, Aftab, Qadeer, Aayesha, Memon, Iqbal, Ali, Syed Muneeb, Idrees, Farah, Kamal, Saima, Hanif, Sadaf, Rehman, Atta Ur, Taqi, Arshad, Hussain, Tanveer, Farooq, Ahmed, Khaskheli, Saleh, Hayat, Muhammad, Indraratna, Kanishka, Beane, Abigail, Haniffa, Rashan, Samaranayake, Upeka, Mathanalagan, Sathiyamoorthy, Gunaratne, Asoka, Mithraratne, Nimangee, Thilakasiri, Kaushila, Pilimatalawwe, Chamila, Dilhani, Y A Hasitha, Fernando, Marie, Ranatunge, Kumudini, Samarasinghe, Loranthi, Vaas, Manori, Edirisooriya, Manoj, Sigera, Chathurani, Arumoli, Janaki, De Silva, Kesharie, Kudavidanage, Bimal, Pinto, Visanthi, Dissanayake, Lakshman, Chittawatanarat, Kaweesak, Kongpolprom, Napplika, Silachamroon, Udomsak, Pornsuriyasak, Prapaporn, Petnak, Tananchai, Singhatas, Pongsasit, Tangsujaritvijit, Viratch, Rungruanghiranya, Suthat, Piriyapatsom, Annop, Juntaping, Kanokkarn, Trongtrakul, Konlawij, Thungtitigul, Poungrat, Tajarernmuang, Pattraporn, Chatmongkolchart, Sunisa, Bhurayanontachai, Rungsun, Akaraborworn, Osaree, Navasakulpong, Asma, Surasit, Karjbundid, Thwaites, Louise, Nadjm, Behzad, Vu Quoc, Dat, Nguyen Thi Thanh, Ha, Nguyen Van, Kinh, Duong Bich, Thuy, Lam Minh, Yen, Anesthesiology, Intensive care medicine, ACS - Pulmonary hypertension & thrombosis, ACS - Diabetes & metabolism, Graduate School, Intensive Care Medicine, AII - Inflammatory diseases, Nursing, and ACS - Microcirculation
Subjects: Male, Sociodemographic Factors, Respiration, Artificial/methods, ARDS, mechanical ventilation, Severity of Illness Index, NO, Settore MED/41 - ANESTESIOLOGIA, 80 and over, Tidal Volume, Humans, Hospital Mortality, Prospective Studies, ddc:610, Developing Countries, Aged, Hospital Mortality/trends, Aged, 80 and over, Developed Countries/statistics & numerical data, Developing Countries/statistics & numerical data, Respiration, Developed Countries, Articles, General Medicine, acute respiratory distress syndrome, Length of Stay, Middle Aged, Respiration, Artificial, Intensive Care Units, Observational Studies as Topic, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Length of Stay/statistics & numerical data, Artificial, Intensive Care Units/statistics & numerical data, Income, Female
Abstract: Contains fulltext : 252214.pdf (Publisher’s version ) (Open Access) BACKGROUND: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. METHODS: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. FINDINGS: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference -1·69 [-9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5-8] vs 6 [5-8] cm H(2)O; p=0·0011). ICU mortality was higher in MICs than in HICs (30·5% vs 19·9%; p=0·0004; adjusted effect 16·41% [95% CI 9·52-23·52]; p
Published: 2022

24. Etrolizumab versus infliximab for the treatment of moderately to severely active ulcerative colitis (GARDENIA): a randomised, double-blind, double-dummy, phase 3 study

Author: Silvio Danese, Jean-Frederic Colombel, Milan Lukas, Javier P Gisbert, Geert D'Haens, Bu'hussain Hayee, Remo Panaccione, Hyun-Soo Kim, Walter Reinisch, Helen Tyrrell, Young S Oh, Swati Tole, Akiko Chai, Kirsten Chamberlain-James, Meina Tao Tang, Stefan Schreiber, Nazimuddin Aboo, Tariq Ahmad, Xavier Aldeguer Mante, Matthieu Allez, Sven Almer, Romain Altwegg, Montserrat Andreu Garcia, Ramesh Arasaradnam, Sandro Ardizzone, Alessandro Armuzzi, Ian Arnott, Guy Aumais, Irit Avni-Biron, Peter Barrow, Ian Beales, Fernando Bermejo San Jose, Abraham Bezuidenhout, Livia Biancone, Michael Blaeker, Stuart Bloom, Bernd Bokemeyer, Fabrizio Bossa, Peter Bossuyt, Guillaume Bouguen, Yoram Bouhnik, Gerd Bouma, Raymond Bourdages, Arnaud Bourreille, Christian Boustiere, Tomas Brabec, Stephan Brand, Carsten Buening, Anthony Buisson, Guillaume Cadiot, Xavier Calvet Calvo, Franck Carbonnel, Daniel Carpio, Jae Hee Cheon, Naoki Chiba, Camelia Chioncel, Nicoleta-Claudia Cimpoeru, Martin Clodi, Gino Roberto Corazza, Rocco Cosintino, Jose Cotter, Thomas Creed, Fraser Cummings, Gian Luigi de' Angelis, Marc De Maeyer, Milind Desai, Etienne Desilets, Pierre Desreumaux, Olivier Dewit, Johanna Dinter, Ecaterina Daniela Dobru, Tomas Douda, Dan Lucian Dumitrascu, Matthias Ebert, Ana Echarri Piudo, Magdy Elkhashab, Chang Soo Eun, Brian Feagan, Roland Fejes, Catarina Fidalgo, Sigal Fishman, Bernard Flourié, Sharyle Fowler, Walter Fries, Csaba Fulop, Mathurin Fumery, Gyula G Kiss, Sonja Gassner, Daniel Gaya, Bastianello Germanà, Liliana Simona Gheorghe, Cyrielle Gilletta de Saint Joseph, Paolo Gionchetti, Adrian-Eugen Goldis, Raquel Gonçalves, Jean-Charles Grimaud, Tibor Gyökeres, Herve Hagege, Andrei Haidar, Heinz Hartmann, Peter Hasselblatt, Buhussain Hayee, Xavier Hebuterne, Per Hellström, Pieter Hindryckx, Helena Hlavova, Frank Hoentjen, Stefanie Howaldt, Ludek Hrdlicka, Kyu Chan Huh, Maria Isabel Iborra Colomino, Florentina Ionita-Radu, Peter Irving, Jørgen Jahnsen, ByungIk Jang, Jeroen Jansen, Seong Woo Jeon, Rodrigo Jover Martinez, Pascal Juillerat, Per Karlén, Arthur Kaser, Radan Keil, Deepak Kejariwal, Dan Keret, Reena Khanna, Dongwoo Kim, Duk Hwan Kim, Hyo-Jong Kim, Joo Sung Kim, Kueongok Kim, Kyung-Jo Kim, Sung Kook Kim, Young-Ho Kim, Jochen Klaus, Anna Kohn, Vladimir Kojecky, Ja Seol Koo, Robert Kozak, Milan Kremer, Tunde Kristof, Frederik Kruger, David Laharie, Adi Lahat-zok, Evgeny Landa, Jonghun Lee, Kang-Moon Lee, Kook Lae Lee, YooJin Lee, Frank Lenze, Wee Chian Lim, Jimmy Limdi, James Lindsay, Pilar Lopez Serrano, Edouard Louis, Stefan Lueth, Giovanni Maconi, Fazia Mana, Steven Mann, John Mansfield, Santino Marchi, Marco Marino, John Marshall, Maria Dolores Martin Arranz, Radu-Bogdan Mateescu, John McLaughlin, Simon McLaughlin, Ehud Melzer, Jessica Mertens, Paul Mitrut, Tamas Molnar, Vinciane Muls, Pushpakaran Munuswamy, Charles Murray, Timna Naftali, Visvakuren Naidoo, Yusuf Nanabhay, Lucian Negreanu, Augustin Nguyen, Thomas Ochsenkuehn, Ambrogio Orlando, Julian Panes Diaz, Maya Paritsky, Dong Il Park, Jihye Park, Luca Pastorelli, Markus Peck-Radosavljevic, Farhad Peerani, Javier Perez Gisbert, Laurent Peyrin-Biroulet, Laurence Picon, Marieke Pierik, Terry Ponich, Francisco Portela, Maartens Jeroen Prins, Istvan Racz, Khan Fareed Rahman, Jean-Marie Reimund, Max Reinshagen, Xavier Roblin, Rodolfo Rocca, Francesca Rogai, Gerhard Rogler, Agnes Salamon, Ennaliza Salazar, Zoltan Sallo, Sunil Samuel, Miquel de los Santos Sans Cuffi, Edoardo Vincenzo Savarino, Vincenzo Savarino, Guillaume Savoye, Andrada Seicean, Christian Selinger, David Martins Serra, Hang Hock Shim, SungJae Shin, Britta Siegmund, Jesse Siffledeen, Wayne Simmonds, Jan Smid, Jose Sollano, Geun Am Song, Alexander Speight, Ioan Sporea, Dirk Staessen, George Stancu, Alan Steel, David Stepek, Victor Stoica, Andreas Sturm, Gyorgy Szekely, Teck Kiang Tan, Carlos Taxonera Samso, John Thomson, Michal Tichy, Gabor Tamas Toth, Zsolt Tulassay, Marcello Vangeli, Marta Varga, Ana Vieira, Stephanie Viennot, Erica Villa, Petr Vitek, Harald Vogelsang, Petr Vyhnalek, Peter Wahab, Jens Walldorf, Byong Duk Ye, Christopher Ziady, Danese S., Colombel J.-F., Lukas M., Gisbert J.P., D'Haens G., Hayee B., Panaccione R., Kim H.-S., Reinisch W., Tyrrell H., Oh Y.S., Tole S., Chai A., Chamberlain-James K., Tang M.T., Schreiber S., Aboo N., Ahmad T., Aldeguer Mante X., Allez M., Almer S., Altwegg R., Andreu Garcia M., Arasaradnam R., Ardizzone S., Armuzzi A., Arnott I., Aumais G., Avni-Biron I., Barrow P., Beales I., Bermejo San Jose F., Bezuidenhout A., Biancone L., Blaeker M., Bloom S., Bokemeyer B., Bossa F., Bossuyt P., Bouguen G., Bouhnik Y., Bouma G., Bourdages R., Bourreille A., Boustiere C., Brabec T., Brand S., Buening C., Buisson A., Cadiot G., Calvet Calvo X., Carbonnel F., Carpio D., Cheon J.H., Chiba N., Chioncel C., Cimpoeru N.-C., Clodi M., Corazza G.R., Cosintino R., Cotter J., Creed T., Cummings F., de' Angelis G.L., De Maeyer M., Desai M., Desilets E., Desreumaux P., Dewit O., Dinter J., Dobru E.D., Douda T., Dumitrascu D.L., Ebert M., Echarri Piudo A., Elkhashab M., Eun C.S., Feagan B., Fejes R., Fidalgo C., Fishman S., Flourie B., Fowler S., Fries W., Fulop C., Fumery M., G Kiss G., Gassner S., Gaya D., Germana B., Gheorghe L.S., Gilletta de Saint Joseph C., Gionchetti P., Goldis A.-E., Goncalves R., Grimaud J.-C., Gyokeres T., Hagege H., Haidar A., Hartmann H., Hasselblatt P., Hebuterne X., Hellstrom P., Hindryckx P., Hlavova H., Hoentjen F., Howaldt S., Hrdlicka L., Huh K.C., Iborra Colomino M.I., Ionita-Radu F., Irving P., Jahnsen J., Jang B., Jansen J., Jeon S.W., Jover Martinez R., Juillerat P., Karlen P., Kaser A., Keil R., Kejariwal D., Keret D., Khanna R., Kim D., Kim D.H., Kim H.-J., Kim J.S., Kim K., Kim K.-J., Kim S.K., Kim Y.-H., Klaus J., Kohn A., Kojecky V., Koo J.S., Kozak R., Kremer M., Kristof T., Kruger F., Laharie D., Lahat-zok A., Landa E., Lee J., Lee K.-M., Lee K.L., Lee Y., Lenze F., Lim W.C., Limdi J., Lindsay J., Lopez Serrano P., Louis E., Lueth S., Maconi G., Mana F., Mann S., Mansfield J., Marchi S., Marino M., Marshall J., Martin Arranz M.D., Mateescu R.-B., McLaughlin J., McLaughlin S., Melzer E., Mertens J., Mitrut P., Molnar T., Muls V., Munuswamy P., Murray C., Naftali T., Naidoo V., Nanabhay Y., Negreanu L., Nguyen A., Ochsenkuehn T., Orlando A., Panes Diaz J., Paritsky M., Park D.I., Park J., Pastorelli L., Peck-Radosavljevic M., Peerani F., Perez Gisbert J., Peyrin-Biroulet L., Picon L., Pierik M., Ponich T., Portela F., Prins M.J., Racz I., Rahman K.F., Reimund J.-M., Reinshagen M., Roblin X., Rocca R., Rogai F., Rogler G., Salamon A., Salazar E., Sallo Z., Samuel S., Sans Cuffi M.D.L.S., Savarino E.V., Savarino V., Savoye G., Seicean A., Selinger C., Serra D.M., Shim H.H., Shin S., Siegmund B., Siffledeen J., Simmonds W., Smid J., Sollano J., Song G.A., Speight A., Sporea I., Staessen D., Stancu G., Steel A., Stepek D., Stoica V., Sturm A., Szekely G., Tan T.K., Taxonera Samso C., Thomson J., Tichy M., Toth G.T., Tulassay Z., Vangeli M., Varga M., Vieira A., Viennot S., Villa E., Vitek P., Vogelsang H., Vyhnalek P., Wahab P., Walldorf J., Ye B.D., and Ziady C.
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Population, Antibodies, Monoclonal, Humanized, Injections, Subcutaneou, Placebo, Severity of Illness Index, Gastroenterology, Young Adult, Double-Blind Method, Internal medicine, Gastrointestinal Agent, Clinical endpoint, medicine, education, Adverse effect, Aged, Aged, 80 and over, education.field_of_study, Hepatology, business.industry, Middle Aged, medicine.disease, Ulcerative colitis, Infliximab, Treatment Outcome, Etrolizumab, Concomitant, Colitis, Ulcerative, Female, business, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5], Human, medicine.drug
Abstract: Item does not contain fulltext BACKGROUND: Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to compare the safety and efficacy of etrolizumab with infliximab in patients with moderately to severely active ulcerative colitis. METHODS: We conducted a randomised, double-blind, double-dummy, parallel-group, phase 3 study (GARDENIA) across 114 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. Participants were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or intravenous infliximab 5 mg/kg at 0, 2, and 6 weeks and every 8 weeks thereafter for 52 weeks. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants, and baseline disease activity. All participants and study site personnel were masked to treatment assignment. The primary endpoint was the proportion of patients who had both clinical response at week 10 (MCS ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) and clinical remission at week 54 (MCS ≤2, with individual subscores ≤1); efficacy was analysed using a modified intention-to-treat population (all randomised patients who received at least one dose of study drug). GARDENIA was designed to show superiority of etrolizumab over infliximab for the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT02136069, and is now closed to recruitment. FINDINGS: Between Dec 24, 2014, and June 23, 2020, 730 patients were screened for eligibility and 397 were enrolled and randomly assigned to etrolizumab (n=199) or infliximab (n=198). 95 (48%) patients in the etrolizumab group and 103 (52%) in the infliximab group completed the study through week 54. At week 54, 37 (18·6%) of 199 patients in the etrolizumab group and 39 (19·7%) of 198 in the infliximab group met the primary endpoint (adjusted treatment difference -0·9% [95% CI -8·7 to 6·8]; p=0·81). The number of patients reporting one or more adverse events was similar between treatment groups (154 [77%] of 199 in the etrolizumab group and 151 [76%] of 198 in the infliximab group); the most common adverse event in both groups was ulcerative colitis (55 [28%] patients in the etrolizumab group and 43 [22%] in the infliximab group). More patients in the etrolizumab group reported serious adverse events (including serious infections) than did those in the infliximab group (32 [16%] vs 20 [10%]); the most common serious adverse event was ulcerative colitis (12 [6%] and 11 [6%]). There was one death during follow-up, in the infliximab group due to a pulmonary embolism, which was not considered to be related to study treatment. INTERPRETATION: To our knowledge, this trial is the first phase 3 maintenance study in moderately to severely active ulcerative colitis to use infliximab as an active comparator. Although the study did not show statistical superiority for the primary endpoint, etrolizumab performed similarly to infliximab from a clinical viewpoint. FUNDING: F Hoffmann-La Roche.
Published: 2022

25. Sequential Minimally Invasive Treatment of Concomitant Abdominal Aortic Aneurysm and Colorectal Cancer: A Single-Center Experience

Author: Carlo De Werra, Umberto Bracale, Maria Michela Di Nuzzo, Luca del Guercio, Raffaele Serra, Maurizio Sodo, Rosa Maria Terracciano, Marco Panagrosso, Roberto Peltrini, Francesco Corcione, Bracale, Umberto, Di Nuzzo, Maria Michela, Bracale, Umberto Marcello, Del Guercio, Luca, Panagrosso, Marco, Serra, Raffaele, Terracciano, Rosa Maria, De Werra, Carlo, Corcione, Francesco, Peltrini, Roberto, and Sodo, Maurizio
Subjects: Male, Laparoscopic surgery, medicine.medical_specialty, Time Factors, Percutaneous, medicine.medical_treatment, Endovascular aneurysm repair, Blood Vessel Prosthesis Implantation, Postoperative Complications, Aneurysm, medicine.artery, medicine, Humans, Colectomy, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Abdominal aortic aneurysm, Endovascular aneurysm repair, Colorectal cancer, Laparoscopic surgery, Endovascular Procedures, General Medicine, Perioperative, Length of Stay, medicine.disease, Common iliac artery, Abdominal aortic aneurysm, Surgery, Treatment Outcome, Concomitant, Female, Laparoscopy, Colorectal Neoplasms, Cardiology and Cardiovascular Medicine, business, Aortic Aneurysm, Abdominal
Abstract: Background The surgical management of concomitant occurrence of abdominal aortic aneurysm (AAA) and colorectal cancer (CRC) is still controversial. Conversely, benefits from a minimally invasive approach are well known concerning the treatment of both AAA and CRC. The aim of this study is to assess safety and feasibility of a sequential 2-staged minimally invasive during the same recovery by endovascular aneurysm repair (EVAR) technique and laparoscopic colorectal resection. Methods From January 2008 to December 2020, all patients with concomitant AAA and CRC were consecutively treated by EVAR and laparoscopic colorectal resection. Perioperative data were retrospectively collected in order to evaluate short- and long-term outcomes following the sequential 2-staged procedures. Results A total of 24 patients were included. The localization of the aneurysm was infrarenal abdominal aortic in 23 cases and in one case of common iliac artery. EVAR procedure has always been performed first. In 18 patients, a percutaneous access has been used while in 6 patients a surgical access has been adopted. Twelve patients had cancer in the left colon, 9 in the right colon, and 3 patients had rectal cancer. No conversions or intraoperative complications had occurred during laparoscopic surgery. The major complications rate after EVAR and CRC surgery was 8.3% and 12.5%, respectively. The mean interval between EVAR and CRC treatment was 7.8 ± 1 and the mean length of stay was 15.4 ± 3.6. No deaths occurred during hospitalization and between the procedures. Overall mortality was 20.8% with a mean follow-up of 39.41 ± 19.2 months. Conclusion Elective sequential 2-staged minimally invasive treatment is a safe and feasible approach with acceptable morbidity and mortality rates and it should be adopted in current clinical practice to manage concomitant AAA and CRC.
Published: 2022

26. Hyperglycemia at admission, comorbidities, and in-hospital mortality in elderly patients hospitalized in internal medicine wards: data from the RePoSI Registry

Author: Salvatore, Corrao, Alessandro, Nobili, Giuseppe, Natoli, Pier Mannuccio Mannucci, Francesco, Perticone, Antonello, Pietrangelo, Christiano, Argano, Giuseppe, Licata, Francesco, Violi, Gino Roberto Corazza, Alessandra, Marengoni, Francesco, Salerno, Matteo, Cesari, Mauro, Tettamanti, Luca, Pasina, Carlotta, Franchi, Laura, Cortesi, Gabriella, Miglio, Ilaria, Ardoino, Alessio, Novella, Domenico, Prisco, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Cenci, Caterina, Gianni, Biolo, Michela, Zanetti, Martina, Guadagni, Michele, Zaccari, Massimiliano, Chiuch, Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi, Mauro, Bernardi, Silvia Li Bassi, Luca, Santi, Giacomo, Zaccherini, Graziana, Lupattelli, Elmo, Mannarino, Vanessa, Bianconi, Francesco, Paciullo, Riccardo, Alcidi, Ranuccio, Nuti, Roberto, Valenti, Martina, Ruvio, Silvia, Cappelli, Alberto, Palazzuoli, Domenico, Girelli, Fabiana, Busti, Giacomo, Marchi, Mario, Barbagallo, Ligia, Dominguez, Floriana, Cocita, Vincenza, Beneduce, Lidia, Plances, Salvatore, Mularo, Massimo, Raspanti, Marco, Zoli, Ilaria, Lazzari, Mattia, Brunori, Elisa, Fabbri, Donatella, Magalotti, Raffaella, Arnò, Franco Laghi Pasini, Pier Leopoldo Capecchi, Giuseppe, Palasciano, Maria Ester Modeo, Carla Di Gennaro, Maria Domenica Cappellini, Diletta, Maira, Valeria Di Stefano, Giovanna, Fabio, Sonia, Seghezzi, Marta, Mancarella, Margherita Migone De Amicis, Giacomo De Luca, Natalia, Scaramellini, Paolo Dionigi Rossi, Sarah, Damanti, Marta, Clerici, Federica, Conti, Giulia, Bonini, Barbara Brignolo Ottolini, Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Costanza Caccia Dominioni, Giovanni, Murialdo, Alessio, Marra, Federico, Cattaneo, Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Maria Beatrice Secchi, Davide, Ghelfi, Luigi, Anastasio, Lucia, Sofia, Maria, Carbone, Francesco, Cipollone, Maria Teresa Guagnano, Emanuele, Valeriani, Ilaria, Rossi, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Giuseppe, Delitala, Maria, Berria, Chiara, Pes, Alessandro, Delitala, Maurizio, Muscaritoli, Alessio, Molfino, Enrico, Petrillo, Giuseppe, Zuccalà, Gabriella, D'Aurizio, Giuseppe, Romanelli, Alberto, Zucchelli, Francesca, Manzoni, Andrea, Volpini, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Chiara, Dell'Unto, Giorgio, Annoni, Maurizio, Corsi, Giuseppe, Bellelli, Sara, Zazzetta, Paolo, Mazzola, Hajnalka, Szabo, Alessandra, Bonfanti, Franco, Arturi, Elena, Succurro, Mariangela, Rubino, Bruno, Tassone, Giorgio, Sesti, Maria Grazia Serra, Maria Antonietta Bleve, Laura, Gasbarrone, Maria Rosaria Sajeva, Antonio, Brucato, Silvia, Ghidoni, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Elisabetta, Cosi, Paolo, Scarinzi, Annalisa, Amabile, Elisabetta, Omenetto, Tancredi, Prandini, Manfredini, Roberto, Fabbian, Fabio, Boari, Benedetta, DE GIORGI, Alfredo, Tiseo, Ruana, DE GIORGIO, Roberto, Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Andrea, Schilardi, Francesca, Loparco, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Emanuele, Amoruso, Luigi, Fenoglio, Andrea, Falcetta, Christian, Bracco, Anna, L Fracanzani Silvia Fargion, Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Flora, Peyvandi, Raffaella, Rossio, Barbara, Ferrari, Giulia, Colombo, Pasquale, Agosti, Valter, Monzani, Valeria, Savojardo, Christian, Folli, Giuliana, Ceriani, Giada, Pallini, Franco, Dallegri, Luciano, Ottonello, Luca, Liberale, Lara, Caserza, Kassem, Salam, Nicola Lucio Liberato, Tiziana, Tognin, Giovanni Battista Bianchi, Sabrina, Giaquinto, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Elena, Spazzini, Camillo, Ferrandina, Giuseppe, Montrucchio, Paolo, Petitti, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Raffaella, Salmi, Piergiorgio, Gaudenzi, Ludovica, Perri, Raffaele, Landolfi, Massimo, Montalto, Antonio, Mirijello, Luigina, Guasti, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Leonardo, Campiotti, Alessandra, Grossi, Marco, Bertolotti, Chiara, Mussi, Giulia, Lancellotti, Maria Vittoria Libbra, Giulia, Dondi, Elisa, Pellegrini, Lucia, Carulli, Matteo, Galassi, Yasmine, Grassi, Maria, Perticone, Rosa, Battaglia, Marco, Filice, Raffaele, Maio, Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara Del Vecchio, Andrea, Salvi, Roberto, Leonardi, Giampaolo, Damiani, William, Capeci, Armando, Gabrielli, Massimo, Mattioli, Giuseppe Pio Martino, Lorenzo, Biondi, Pietro, Pettinari, Riccardo, Ghio, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo, Labbadia, Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Luca, Zanoli, Samuele, Pignataro, Alfio, Gennaro, Julien, Blanco, Valter, Saracco, Marisa, Fogliati, Carlo, Bussolino, Francesca, Mete, Miriam, Gino, Antonio, Cittadini, Carlo, Vigorito, Michele, Arcopinto, Andrea, Salzano, Emanuele, Bobbio, Alberto Maria Marra, Domenico, Sirico, Guido, Moreo, Francesca, Gasparini, Silvia, Prolo, Gloria, Pina, Alberto, Ballestrero, Fabio, Ferrando, Sergio, Berra, Simonetta, Dassi, Maria Cristina Nava, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella, Gruden, Giorgio, Galanti, Gabriele, Mascherini, Cristian, Petri, Laura, Stefani, Margherita, Girino, Valeria, Piccinelli, Francesco, Nasso, Vincenza, Gioffrè, Maria, Pasquale, Giuseppe, Scattolin, Sergio, Martinelli, Mauro, Turrin, Leonardo, Sechi, Cristina, Catena, Gianluca, Colussi, Nicola, Passariello, Luca, Rinaldi, Franco, Berti, Giuseppe, Famularo, Patrizia, Tarsitani, Roberto, Castello, Michela, Pasino, Gian Paolo Ceda, Marcello Giuseppe Maggio, Simonetta, Morganti, Andrea, Artoni, Stefano Del Giacco, Davide, Firinu, Francesca, Losa, Giovanni, Paoletti, Giulia, Costanzo, Giuseppe, Montalto, Anna, Licata, Valentina, Malerba, Filippo Alessandro Montalto, Antonino, Lasco, Giorgio, Basile, Antonino, Catalano, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella, Caruso, Patrizia, Mecocci, Carmelinda, Ruggiero, Virginia, Boccardi, Tiziana, Meschi, Fulvio, Lauretani, Andrea, Ticinesi, Antonio, Nouvenne, Pietro, Minuz, Luigi, Fondrieschi, Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Massimo, Porta, Piero, Riva, Roberto, Quadri, Erica, Larovere, Marco, Novelli, Giorgio, Scanzi, Caterina, Mengoli, Stella, Provini, Laura, Ricevuti, Emilio, Simeone, Rosa, Scurti, Fabio, Tolloso, Roberto, Tarquini, Alice, Valoriani, Silvia, Dolenti, Giulia, Vannini, Alberto, Tedeschi, Lucia, Trotta, Riccardo, Volpi, Pietro, Bocchi, Alessandro, Vignali, Sergio, Harari, Chiara, Lonati, Mara, Cattaneo, Federico, Napoli., Corrao S, Nobili A, Natoli G, Mannucci PM, Perticone F, Pietrangelo A, Argano C, REPOSI Investigator, Borghi C, Corrao S., Nobili A., Natoli G., Mannucci P.M., Perticone F., Pietrangelo A., Argano C., Licata G., Violi F., Corazza G.R., Marengoni A., Salerno F., Cesari M., Tettamanti M., Pasina L., Franchi C., Cortesi L., Miglio G., Ardoino I., Novella A., Prisco D., Silvestri E., Emmi G., Bettiol A., Caterina C., Biolo G., Zanetti M., Guadagni M., Zaccari M., Chiuch M., Vanoli M., Grignani G., Pulixi E.A., Bernardi M., Bassi S.L., Santi L., Zaccherini G., Lupattelli G., Mannarino E., Bianconi V., Paciullo F., Alcidi R., Nuti R., Valenti R., Ruvio M., Cappelli S., Palazzuoli A., Girelli D., Busti F., Marchi G., Barbagallo M., Dominguez L., Cocita F., Beneduce V., Plances L., Mularo S., Raspanti M., Zoli M., Lazzari I., Brunori M., Fabbri E., Magalotti D., Arno R., Pasini F.L., Capecchi P.L., Palasciano G., Modeo M.E., Di Gennaro C., Cappellini M.D., Maira D., Di Stefano V., Fabio G., Seghezzi S., Mancarella M., De Amicis M.M., De Luca G., Scaramellini N., Rossi P.D., Damanti S., Clerici M., Conti F., Bonini G., Ottolini B.B., Di Sabatino A., Miceli E., Lenti M.V., Pisati M., Dominioni C.C., Murialdo G., Marra A., Cattaneo F., Pontremoli R., Beccati V., Nobili G., Secchi M.B., Ghelfi D., Anastasio L., Sofia L., Carbone M., Cipollone F., Guagnano M.T., Valeriani E., Rossi I., Mancuso G., Calipari D., Bartone M., Delitala G., Berria M., Pes C., Delitala A., Muscaritoli M., Molfino A., Petrillo E., Zuccala G., D'Aurizio G., Romanelli G., Zucchelli A., Manzoni F., Volpini A., Picardi A., Gentilucci U.V., Gallo P., Dell'Unto C., Annoni G., Corsi M., Bellelli G., Zazzetta S., Mazzola P., Szabo H., Bonfanti A., Arturi F., Succurro E., Rubino M., Tassone B., Sesti G., Serra M.G., Bleve M.A., Gasbarrone L., Sajeva M.R., Brucato A., Ghidoni S., Fabris F., Bertozzi I., Bogoni G., Rabuini M.V., Cosi E., Scarinzi P., Amabile A., Omenetto E., Prandini T., Manfredini R., Fabbian F., Boari B., De Giorgi A., Tiseo R., De Giorgio R., Paolisso G., Rizzo M.R., Borghi C., Strocchi E., Ianniello E., Soldati M., Sabba C., Vella F.S., Suppressa P., Schilardi A., Loparco F., De Vincenzo G.M., Comitangelo A., Amoruso E., Fenoglio L., Falcetta A., Bracco C., Fargion A.L.F.S., Tiraboschi S., Cespiati A., Oberti G., Sigon G., Peyvandi F., Rossio R., Ferrari B., Colombo G., Agosti P., Monzani V., Savojardo V., Folli C., Ceriani G., Pallini G., Dallegri F., Ottonello L., Liberale L., Caserza L., Salam K., Liberato N.L., Tognin T., Bianchi G.B., Giaquinto S., Purrello F., Di Pino A., Piro S., Rozzini R., Falanga L., Spazzini E., Ferrandina C., Montrucchio G., Petitti P., Peasso P., Favale E., Poletto C., Salmi R., Gaudenzi P., Perri L., Landolfi R., Montalto M., Mirijello A., Guasti L., Castiglioni L., Maresca A., Squizzato A., Campiotti L., Grossi A., Bertolotti M., Mussi C., Lancellotti G., Libbra M.V., Dondi G., Pellegrini E., Carulli L., Galassi M., Grassi Y., Perticone M., Battaglia R., FIlice M., Maio R., Stanghellini V., Ruggeri E., del Vecchio S., Salvi A., Leonardi R., Damiani G., Capeci W., Gabrielli A., Mattioli M., Martino G.P., Biondi L., Pettinari P., Ghio R., Col A.D., Minisola S., Colangelo L., Cilli M., Labbadia G., Afeltra A., Marigliano B., Pipita M.E., Castellino P., Zanoli L., Pignataro S., Gennaro A., Blanco J., Saracco V., Fogliati M., Bussolino C., Mete F., Gino M., Cittadini A., Vigorito C., Arcopinto M., Salzano A., Bobbio E., Marra A.M., Sirico D., Moreo G., Gasparini F., Prolo S., Pina G., Ballestrero A., Ferrando F., Berra S., Dassi S., Nava M.C., Graziella B., Baldassarre S., Fragapani S., Gruden G., Galanti G., Mascherini G., Petri C., Stefani L., Girino M., Piccinelli V., Nasso F., Gioffre V., Pasquale M., Scattolin G., Martinelli S., Turrin M., Sechi L., Catena C., Colussi G., Passariello N., Rinaldi L., Berti F., Famularo G., Tarsitani P., Castello R., Pasino M., Ceda G.P., Maggio M.G., Morganti S., Artoni A., Del Giacco S., Firinu D., Losa F., Paoletti G., Costanzo G., Montalto G., Licata A., Malerba V., Montalto F.A., Lasco A., Basile G., Catalano A., Malatino L., Stancanelli B., Terranova V., Di Marca S., Di Quattro R., La Malfa L., Caruso R., Mecocci P., Ruggiero C., Boccardi V., Meschi T., Lauretani F., Ticinesi A., Nouvenne A., Minuz P., Fondrieschi L., Pirisi M., Fra G.P., Sola D., Porta M., Riva P., Quadri R., Larovere E., Novelli M., Scanzi G., Mengoli C., Provini S., Ricevuti L., Simeone E., Scurti R., Tolloso F., Tarquini R., Valoriani A., Dolenti S., Vannini G., Tedeschi A., Trotta L., Volpi R., Bocchi P., Vignali A., Harari S., Lonati C., Cattaneo M., Napoli F., Corrao, S., Nobili, A., Natoli, G., Mannucci, P. M., Perticone, F., Pietrangelo, A., Argano, C., Licata, G., Violi, F., Corazza, G. R., Marengoni, A., Salerno, F., Cesari, M., Tettamanti, M., Pasina, L., Franchi, C., Cortesi, L., Miglio, G., Ardoino, I., Novella, A., Prisco, D., Silvestri, E., Emmi, G., Bettiol, A., Caterina, C., Biolo, G., Zanetti, M., Guadagni, M., Zaccari, M., Chiuch, M., Vanoli, M., Grignani, G., Pulixi, E. A., Bernardi, M., Bassi, S. L., Santi, L., Zaccherini, G., Lupattelli, G., Mannarino, E., Bianconi, V., Paciullo, F., Alcidi, R., Nuti, R., Valenti, R., Ruvio, M., Cappelli, S., Palazzuoli, A., Girelli, D., Busti, F., Marchi, G., Barbagallo, M., Dominguez, L., Cocita, F., Beneduce, V., Plances, L., Mularo, S., Raspanti, M., Zoli, M., Lazzari, I., Brunori, M., Fabbri, E., Magalotti, D., Arno, R., Pasini, F. L., Capecchi, P. L., Palasciano, G., Modeo, M. E., Di Gennaro, C., Cappellini, M. D., Maira, D., Di Stefano, V., Fabio, G., Seghezzi, S., Mancarella, M., De Amicis, M. M., De Luca, G., Scaramellini, N., Rossi, P. D., Damanti, S., Clerici, M., Conti, F., Bonini, G., Ottolini, B. B., Di Sabatino, A., Miceli, E., Lenti, M. V., Pisati, M., Dominioni, C. C., Murialdo, G., Marra, A., Cattaneo, F., Pontremoli, R., Beccati, V., Nobili, G., Secchi, M. B., Ghelfi, D., Anastasio, L., Sofia, L., Carbone, M., Cipollone, F., Guagnano, M. T., Valeriani, E., Rossi, I., Mancuso, G., Calipari, D., Bartone, M., Delitala, G., Berria, M., Pes, C., Delitala, A., Muscaritoli, M., Molfino, A., Petrillo, E., Zuccala, G., D'Aurizio, G., Romanelli, G., Zucchelli, A., Manzoni, F., Volpini, A., Picardi, A., Gentilucci, U. V., Gallo, P., Dell'Unto, C., Annoni, G., Corsi, M., Bellelli, G., Zazzetta, S., Mazzola, P., Szabo, H., Bonfanti, A., Arturi, F., Succurro, E., Rubino, M., Tassone, B., Sesti, G., Serra, M. G., Bleve, M. A., Gasbarrone, L., Sajeva, M. R., Brucato, A., Ghidoni, S., Fabris, F., Bertozzi, I., Bogoni, G., Rabuini, M. V., Cosi, E., Scarinzi, P., Amabile, A., Omenetto, E., Prandini, T., Manfredini, R., Fabbian, F., Boari, B., De Giorgi, A., Tiseo, R., De Giorgio, R., Paolisso, G., Rizzo, M. R., Borghi, C., Strocchi, E., Ianniello, E., Soldati, M., Sabba, C., Vella, F. S., Suppressa, P., Schilardi, A., Loparco, F., De Vincenzo, G. M., Comitangelo, A., Amoruso, E., Fenoglio, L., Falcetta, A., Bracco, C., Fargion, A. L. F. S., Tiraboschi, S., Cespiati, A., Oberti, G., Sigon, G., Peyvandi, F., Rossio, R., Ferrari, B., Colombo, G., Agosti, P., Monzani, V., Savojardo, V., Folli, C., Ceriani, G., Pallini, G., Dallegri, F., Ottonello, L., Liberale, L., Caserza, L., Salam, K., Liberato, N. L., Tognin, T., Bianchi, G. B., Giaquinto, S., Purrello, F., Di Pino, A., Piro, S., Rozzini, R., Falanga, L., Spazzini, E., Ferrandina, C., Montrucchio, G., Petitti, P., Peasso, P., Favale, E., Poletto, C., Salmi, R., Gaudenzi, P., Perri, L., Landolfi, R., Montalto, M., Mirijello, A., Guasti, L., Castiglioni, L., Maresca, A., Squizzato, A., Campiotti, L., Grossi, A., Bertolotti, M., Mussi, C., Lancellotti, G., Libbra, M. V., Dondi, G., Pellegrini, E., Carulli, L., Galassi, M., Grassi, Y., Perticone, M., Battaglia, R., Filice, M., Maio, R., Stanghellini, V., Ruggeri, E., del Vecchio, S., Salvi, A., Leonardi, R., Damiani, G., Capeci, W., Gabrielli, A., Mattioli, M., Martino, G. P., Biondi, L., Pettinari, P., Ghio, R., Col, A. D., Minisola, S., Colangelo, L., Cilli, M., Labbadia, G., Afeltra, A., Marigliano, B., Pipita, M. E., Castellino, P., Zanoli, L., Pignataro, S., Gennaro, A., Blanco, J., Saracco, V., Fogliati, M., Bussolino, C., Mete, F., Gino, M., Cittadini, A., Vigorito, C., Arcopinto, M., Salzano, A., Bobbio, E., Marra, A. M., Sirico, D., Moreo, G., Gasparini, F., Prolo, S., Pina, G., Ballestrero, A., Ferrando, F., Berra, S., Dassi, S., Nava, M. C., Graziella, B., Baldassarre, S., Fragapani, S., Gruden, G., Galanti, G., Mascherini, G., Petri, C., Stefani, L., Girino, M., Piccinelli, V., Nasso, F., Gioffre, V., Pasquale, M., Scattolin, G., Martinelli, S., Turrin, M., Sechi, L., Catena, C., Colussi, G., Passariello, N., Rinaldi, L., Berti, F., Famularo, G., Tarsitani, P., Castello, R., Pasino, M., Ceda, G. P., Maggio, M. G., Morganti, S., Artoni, A., Del Giacco, S., Firinu, D., Losa, F., Paoletti, G., Costanzo, G., Montalto, G., Licata, A., Malerba, V., Montalto, F. A., Lasco, A., Basile, G., Catalano, A., Malatino, L., Stancanelli, B., Terranova, V., Di Marca, S., Di Quattro, R., La Malfa, L., Caruso, R., Mecocci, P., Ruggiero, C., Boccardi, V., Meschi, T., Lauretani, F., Ticinesi, A., Nouvenne, A., Minuz, P., Fondrieschi, L., Pirisi, M., Fra, G. P., Sola, D., Porta, M., Riva, P., Quadri, R., Larovere, E., Novelli, M., Scanzi, G., Mengoli, C., Provini, S., Ricevuti, L., Simeone, E., Scurti, R., Tolloso, F., Tarquini, R., Valoriani, A., Dolenti, S., Vannini, G., Tedeschi, A., Trotta, L., Volpi, R., Bocchi, P., Vignali, A., Harari, S., Lonati, C., Cattaneo, M., Napoli, F., Corrao, S, Nobili, A, Natoli, G, Mannucci, P, Perticone, F, Pietrangelo, A, Argano, C, Licata, G, Violi, F, Corazza, G, Marengoni, A, Salerno, F, Cesari, M, Tettamanti, M, Pasina, L, Franchi, C, Cortesi, L, Miglio, G, Ardoino, I, Novella, A, Prisco, D, Silvestri, E, Emmi, G, Bettiol, A, Caterina, C, Biolo, G, Zanetti, M, Guadagni, M, Zaccari, M, Chiuch, M, Vanoli, M, Grignani, G, Pulixi, E, Bernardi, M, Bassi, S, Santi, L, Zaccherini, G, Lupattelli, G, Mannarino, E, Bianconi, V, Paciullo, F, Alcidi, R, Nuti, R, Valenti, R, Ruvio, M, Cappelli, S, Palazzuoli, A, Girelli, D, Busti, F, Marchi, G, Barbagallo, M, Dominguez, L, Cocita, F, Beneduce, V, Plances, L, Mularo, S, Raspanti, M, Zoli, M, Lazzari, I, Brunori, M, Fabbri, E, Magalotti, D, Arno, R, Pasini, F, Capecchi, P, Palasciano, G, Modeo, M, Di Gennaro, C, Cappellini, M, Maira, D, Di Stefano, V, Fabio, G, Seghezzi, S, Mancarella, M, De Amicis, M, De Luca, G, Scaramellini, N, Rossi, P, Damanti, S, Clerici, M, Conti, F, Bonini, G, Ottolini, B, Di Sabatino, A, Miceli, E, Lenti, M, Pisati, M, Dominioni, C, Murialdo, G, Marra, A, Cattaneo, F, Pontremoli, R, Beccati, V, Nobili, G, Secchi, M, Ghelfi, D, Anastasio, L, Sofia, L, Carbone, M, Cipollone, F, Guagnano, M, Valeriani, E, Rossi, I, Mancuso, G, Calipari, D, Bartone, M, Delitala, G, Berria, M, Pes, C, Delitala, A, Muscaritoli, M, Molfino, A, Petrillo, E, Zuccala, G, D'Aurizio, G, Romanelli, G, Zucchelli, A, Manzoni, F, Volpini, A, Picardi, A, Gentilucci, U, Gallo, P, Dell'Unto, C, Annoni, G, Corsi, M, Bellelli, G, Zazzetta, S, Mazzola, P, Szabo, H, Bonfanti, A, Arturi, F, Succurro, E, Rubino, M, Tassone, B, Sesti, G, Serra, M, Bleve, M, Gasbarrone, L, Sajeva, M, Brucato, A, Ghidoni, S, Fabris, F, Bertozzi, I, Bogoni, G, Rabuini, M, Cosi, E, Scarinzi, P, Amabile, A, Omenetto, E, Prandini, T, Manfredini, R, Fabbian, F, Boari, B, De Giorgi, A, Tiseo, R, De Giorgio, R, Paolisso, G, Rizzo, M, Borghi, C, Strocchi, E, Ianniello, E, Soldati, M, Sabba, C, Vella, F, Suppressa, P, Schilardi, A, Loparco, F, De Vincenzo, G, Comitangelo, A, Amoruso, E, Fenoglio, L, Falcetta, A, Bracco, C, Fargion, A, Tiraboschi, S, Cespiati, A, Oberti, G, Sigon, G, Peyvandi, F, Rossio, R, Ferrari, B, Colombo, G, Agosti, P, Monzani, V, Savojardo, V, Folli, C, Ceriani, G, Pallini, G, Dallegri, F, Ottonello, L, Liberale, L, Caserza, L, Salam, K, Liberato, N, Tognin, T, Bianchi, G, Giaquinto, S, Purrello, F, Di Pino, A, Piro, S, Rozzini, R, Falanga, L, Spazzini, E, Ferrandina, C, Montrucchio, G, Petitti, P, Peasso, P, Favale, E, Poletto, C, Salmi, R, Gaudenzi, P, Perri, L, Landolfi, R, Montalto, M, Mirijello, A, Guasti, L, Castiglioni, L, Maresca, A, Squizzato, A, Campiotti, L, Grossi, A, Bertolotti, M, Mussi, C, Lancellotti, G, Libbra, M, Dondi, G, Pellegrini, E, Carulli, L, Galassi, M, Grassi, Y, Perticone, M, Battaglia, R, Filice, M, Maio, R, Stanghellini, V, Ruggeri, E, del Vecchio, S, Salvi, A, Leonardi, R, Damiani, G, Capeci, W, Gabrielli, A, Mattioli, M, Martino, G, Biondi, L, Pettinari, P, Ghio, R, Col, A, Minisola, S, Colangelo, L, Cilli, M, Labbadia, G, Afeltra, A, Marigliano, B, Pipita, M, Castellino, P, Zanoli, L, Pignataro, S, Gennaro, A, Blanco, J, Saracco, V, Fogliati, M, Bussolino, C, Mete, F, Gino, M, Cittadini, A, Vigorito, C, Arcopinto, M, Salzano, A, Bobbio, E, Sirico, D, Moreo, G, Gasparini, F, Prolo, S, Pina, G, Ballestrero, A, Ferrando, F, Berra, S, Dassi, S, Nava, M, Graziella, B, Baldassarre, S, Fragapani, S, Gruden, G, Galanti, G, Mascherini, G, Petri, C, Stefani, L, Girino, M, Piccinelli, V, Nasso, F, Gioffre, V, Pasquale, M, Scattolin, G, Martinelli, S, Turrin, M, Sechi, L, Catena, C, Colussi, G, Passariello, N, Rinaldi, L, Berti, F, Famularo, G, Tarsitani, P, Castello, R, Pasino, M, Ceda, G, Maggio, M, Morganti, S, Artoni, A, Del Giacco, S, Firinu, D, Losa, F, Paoletti, G, Costanzo, G, Montalto, G, Licata, A, Malerba, V, Montalto, F, Lasco, A, Basile, G, Catalano, A, Malatino, L, Stancanelli, B, Terranova, V, Di Marca, S, Di Quattro, R, La Malfa, L, Caruso, R, Mecocci, P, Ruggiero, C, Boccardi, V, Meschi, T, Lauretani, F, Ticinesi, A, Nouvenne, A, Minuz, P, Fondrieschi, L, Pirisi, M, Fra, G, Sola, D, Porta, M, Riva, P, Quadri, R, Larovere, E, Novelli, M, Scanzi, G, Mengoli, C, Provini, S, Ricevuti, L, Simeone, E, Scurti, R, Tolloso, F, Tarquini, R, Valoriani, A, Dolenti, S, Vannini, G, Tedeschi, A, Trotta, L, Volpi, R, Bocchi, P, Vignali, A, Harari, S, Lonati, C, Cattaneo, M, and Napoli, F
Subjects: Registrie, Male, Comorbidity, Diabetes, Disability, Elderly, Hyperglycemia, Mortality, Aged, Aged, 80 and over, Female, Hospital Mortality, Hospitals, Humans, Internal Medicine, Registries, Hospitalization, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Socio-culturale, Renal function, 030204 cardiovascular system & hematology, Diabete, Hospital, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Rating scale, Internal medicine, Diabetes mellitus, 80 and over, medicine, LS4_4, 030212 general & internal medicine, Class III obesity, business.industry, Mortality rate, Comorbidity, Diabetes, Disability, Elderly, Hyperglycemia, Mortality, General Medicine, medicine.disease, Mood disorders, Geriatric Depression Scale, Original Article, business, Human
Abstract: Aims The association between hyperglycemia at hospital admission and relevant short- and long-term outcomes in elderly population is known. We assessed the effects on mortality of hyperglycemia, disability, and multimorbidity at admission in internal medicine ward in patients aged ≥ 65 years. Methods Data were collected from an active register of 102 internal medicine and geriatric wards in Italy (RePoSi project). Patients were recruited during four index weeks of a year. Socio-demographic data, reason for hospitalization, diagnoses, treatment, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), renal function, functional (Barthel Index), and cognitive status (Short Blessed Test) and mood disorders (Geriatric Depression Scale) were recorded. Mortality rates were assessed in hospital 3 and 12 months after discharge. Results Of the 4714 elderly patients hospitalized, 361 had a glycemia level ≥ 250 mg/dL at admission. Compared to subjects with lower glycemia level, patients with glycemia ≥ 250 mg/dL showed higher rates of male sex, smoke and class III obesity. These patients had a significantly lower Barthel Index (p = 0.0249), higher CIRS-SI and CIRS-CI scores (p = 0.0025 and p = 0.0013, respectively), and took more drugs. In-hospital mortality rate was 9.2% and 5.1% in subjects with glycemia ≥ 250 and p = 0.0010). Regression analysis showed a strong association between in-hospital death and glycemia ≥ 250 mg/dL (OR 2.07; [95% CI 1.34–3.19]), Barthel Index ≤ 40 (3.28[2.44–4.42]), CIRS-SI (1.87[1.27–2.77]), and male sex (1.54[1.16–2.03]). Conclusions The stronger predictors of in-hospital mortality for older patients admitted in general wards were glycemia level ≥ 250 mg/dL, Barthel Index ≤ 40, CIRS-SI, and male sex.
Published: 2021

27. The global impact of the COVID-19 pandemic on the management and course of chronic urticaria

Author: Kocatürk, Emek, Salman, Andaç, Cherrez-Ojeda, Ivan, Criado, Paulo Ricardo, Peter, Jonny, Comert-Ozer, Elif, Abuzakouk, Mohamed, Câmara Agondi, Rosana, Al-Ahmad, Mona, Altrichter, Sabine, Arnaout, Rand, Arruda, Luisa Karla, Asero, Riccardo, Bauer, Andrea, Ben-Shoshan, Moshe, Bernstein, Jonathan, Bizjak, Mojca, Boccon-Gibod, Isabelle, Bonnekoh, Hanna, Bouillet, Laurence, Brzoza, Zenon, Busse, Paula, Campos, Regis A., Carne, Emily, Conlon, Niall, Criado, Roberta Fachini Jardim, De Souza Lima, Eduardo Magalhães, Demir, Semra, Dissemond, Joachim, Doğan Günaydın, Sibel, Dorofeeva, Irina, Ensina, Luis Felipe, Ertaş, Ragip, Ferrucci, Silvia Mariel, Figueras-Nart, Ignasi, Fomina, Daria, Franken, Sylvie M., Fukunaga, Atsushi, Giménez Arnau, Ana M, Godse, Kiran, Gonçalo, Margarida, Gotua, Maia, Grattan, Clive, Guillet, Carole, Inomata, Naoko, Jakob, Thilo, Karakaya, Gul, Kasperska-Zając, Alicja, Katelaris, Constance H., Košnik, Mitja, Krasowska, Dorota, Kulthanan, Kanokvalai, Kumaran, M.Sendhil, Lang, Claudia, Larco-Sousa, José Ignacio, Lazaridou, Elisavet, Leslie, Tabi Anika, Lippert, Undine, Calderón llosa, Oscar, Makris, Michael, Marsland, Alexander, Medina, Iris V., Meshkova, Raisa, Bastos Palitot, Esther, Parisi, Claudio A.S., Pickert, Julia, Ramon, Germán D., Rodríguez-Gonzalez, Mónica, Rosario, Nelson, Rudenko, Michael, Rutkowski, Krzysztof, Sánchez Caraballo, Jorge Mario, Schliemann, Sibylle, Sekerel, Bulent Enis, Serpa, Faradiba S., Serra-Baldrich, E, Song, Zhiqiang, Soria, Angèle, Staevska, Maria, Staubach, Petra, Tagka, Anna, Takahagi, Shunsuke, Thomsen, Simon Francis, Treudler, Regina, Vadasz, Zahava, Rodrigues Valle, Solange Oliveira, Van Doorn, Martijn B.A., Vestergaard, Christian, Wagner, Nicola, Wang, Dahu, Wang, Liangchun, Wedi, Bettina, Xepapadaki, Paraskevi, Yücel, Esra, Zalewska-Janowska, Anna, Zhao, Zuotao, Zuberbier, Torsten, Maurer, Marcus, Universitat Autònoma de Barcelona, Dermatology, Göncü, Özgür Emek Kocatürk (ORCID 0000-0003-2801-0959 & YÖK ID 217219), Salman, A., Cherrez-Ojeda, I., Criado, P. R., Peter, J., Comert-Ozer, E., Abuzakouk, M., Agondi, R. C., Al-Ahmad, M., Altrichter, S., Arnaout, R., Arruda, L. K., Asero, R., Bauer, A., Ben-Shoshan, M., Bernstein, J. A., Bizjak, M., Boccon-Gibod, I., Bonnekoh, H., Bouillet, L., Brzoza, Z., Busse, P., Campos, R. A., Carne, E., Conlon, N., Criado, R. F., Lima, E. M. D., Demir, S., Dissemond, J., Gunaydin, S. D., Dorofeeva, I., Ensina, L. F., Ertas, R., Ferrucci, S. M., Figueras-Nart, I., Fomina, D., Franken, S. M., Fukunaga, A., Gimenez-Arnau, A. M., Godse, K., Goncalo, M., Gotua, M., Grattan, C., Guillet, C., Inomata, N., Jakob, T., Karakaya, G., Kasperska-Zajac, A., Katelaris, C. H., Kosnik, M., Krasowska, D., Kulthanan, K., Kumaran, M. S., Lang, C., Larco-Sousa, J. I., Lazaridou, E., Leslie, T. A., Lippert, U., Llosa, O. C., Makris, M., Marsland, A., Medina, I. V., Meshkova, R., Palitot, E. B., Parisi, C. A. S., Pickert, J., Ramon, G. D., Rodriguez-Gonzalez, M., Rosario, N., Rudenko, M., Rutkowski, K., Sanchez, J., Schliemann, S., Sekerel, B. E., Serpa, F. S., Serra-Baldrich, E., Song, Z. Q., Soria, A., Staevska, M., Staubach, P., Tagka, A., Takahagi, S., Thomsen, S. F., Treudler, R., Vadasz, Z., Valle, S. O. R., Van Doorn, M. B. A., Vestergaard, C., Wagner, N., Wang, D. H., Wang, L. C., Wedi, B., Xepapadaki, P., Yücel, E., Zalewska-Janowska, A., Zhao, Z. T., Zuberbier, T., Maurer, M., School of Medicine, AII - Infectious diseases, Kocaturk, Emek, Salman, Andac, Cherrez-Ojeda, Ivan, Criado, Paulo Ricardo, Peter, Jonny, Comert-Ozer, Elif, Abuzakouk, Mohamed, Agondi, Rosana Camara, Al-Ahmad, Mona, Altrichter, Sabine, Arnaout, Rand, Arruda, Luisa Karla, Asero, Riccardo, Bauer, Andrea, Ben-Shoshan, Moshe, Bernstein, Jonathan A., Bizjak, Mojca, Boccon-Gibod, Isabelle, Bonnekoh, Hanna, Bouillet, Laurence, Brzoza, Zenon, Busse, Paula, Campos, Regis A., Carne, Emily, Conlon, Niall, Criado, Roberta F., de Souza Lima, Eduardo M., Demir, Semra, Dissemond, Joachim, Gunaydin, Sibel Dogan, Dorofeeva, Irina, Ensina, Luis Felipe, Ertas, Ragip, Ferrucci, Silvia Mariel, Figueras-Nart, Ignasi, Fomina, Daria, Franken, Sylvie M., Fukunaga, Atsushi, Gimenez-Arnau, Ana M., Godse, Kiran, Goncalo, Margarida, Gotua, Maia, Grattan, Clive, Guillet, Carole, Inomata, Naoko, Jakob, Thilo, Karakaya, Gul, Kasperska-Zajac, Alicja, Katelaris, Constance H., Kosnik, Mitja, Krasowska, Dorota, Kulthanan, Kanokvalai, Kumaran, M. Sendhil, Lang, Claudia, Ignacio Larco-Sousa, Jose, Lazaridou, Elisavet, Leslie, Tabi Anika, Lippert, Undine, Llosa, Oscar Calderon, Makris, Michael, Marsland, Alexander, Medina, Iris, V, Meshkova, Raisa, Palitot, Esther Bastos, Parisi, Claudio A. S., Pickert, Julia, Ramon, German D., Rodriguez-Gonzalez, Monica, Rosario, Nelson, Rudenko, Michael, Rutkowski, Krzysztof, Sanchez, Jorge, Schliemann, Sibylle, Sekerel, Bulent Enis, Serpa, Faradiba S., Serra-Baldrich, Esther, Song, Zhiqiang, Soria, Angele, Staevska, Maria, Staubach, Petra, Tagka, Anna, Takahagi, Shunsuke, Thomsen, Simon Francis, Treudler, Regina, Vadasz, Zahava, Rodrigues Valle, Solange Oliveira, Van Doorn, Martijn B. A., Vestergaard, Christian, Wagner, Nicola, Wang, Dahu, Wang, Liangchun, Wedi, Bettina, Xepapadaki, Paraskevi, Yucel, Esra, Zalewska-Janowska, Anna, Zhao, Zuotao, Zuberbier, Torsten, and Maurer, Marcus
Subjects: Male, 0301 basic medicine, STRESS, Exacerbation, UCARE, pandemije, Medizin, Omalizumab, SERUM, chronic urticaria, 0302 clinical medicine, Pandemic, Health care, Immunology and Allergy, Chronic Urticaria, treatment, Chronic urticaria, COVID-19, Cyclosporine, SARS-CoV-2, Treatment, zdravljenje, ASSOCIATION, Middle Aged, cyclosporine, omalizumab, pandemic, kronična urtikarija, INFECTIONS, GA(2)LEN, Female, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Coronavirus disease 2019 (COVID-19), Immunology, udc:616-097, pandemics, ciklosporin, Young Adult, 03 medical and health sciences, Patient referral, medicine, Humans, In patient, Patient Reported Outcome Measures, Aged, Internet, business.industry, DEFINITION, Medicine, Allergy, Cross-Sectional Studies, 030104 developmental biology, 030228 respiratory system, Emergency medicine, business
Abstract: Introduction: the COVID-19 pandemic dramatically disrupts health care around the globe. The impact of the pandemic on chronic urticaria (CU) and its management are largely unknown. Aim: to understand how CU patients are affected by the COVID-19 pandemic; how specialists alter CU patient management; and the course of CU in patients with COVID-19. Materials and methods: our cross-sectional, international, questionnaire-based, multicenter UCARE COVID-CU study assessed the impact of the pandemic on patient consultations, remote treatment, changes in medications, and clinical consequences. Results: the COVID-19 pandemic severely impairs CU patient care, with less than 50% of the weekly numbers of patients treated as compared to before the pandemic. Reduced patient referrals and clinic hours were the major reasons. Almost half of responding UCARE physicians were involved in COVID-19 patient care, which negatively impacted on the care of urticaria patients. The rate of face-to-face consultations decreased by 62%, from 90% to less than half, whereas the rate of remote consultations increased by more than 600%, from one in 10 to more than two thirds. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic. CU does not affect the course of COVID-19, but COVID-19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID-19. Conclusions: the COVID-19 pandemic brings major changes and challenges for CU patients and their physicians. The long-term consequences of these changes, especially the increased use of remote consultations, require careful evaluation., Novartis; Sanofi; Menarini Universidad Espiritu Santo; Takeda; Allakos; AstraZeneca; CSL Behring; Genentech; Pharming; GSK; Shire/Takada; BioCryst; ResTORbio; Pearl Therapeutics, CVS Health; Law offices of Levin; Riback; Adelman; Flangel; Vedder Price; Fresenius; Taiho; Kyowa Kirin; Tanabe; Korin; Uriach Pharma; Instituto Carlos III FEDER; Menarini; Amgen; Thermo Fisher; Avene; ALK‐Abello; Bencard/Allergy Therapeutics; Celgene; Allergopharma; Faes Farma; AbbVie; Janssen; Leo Pharma; Lilly; Roche; Genesis; Menlo Therapeutics; UCB; Pfizer; Almirall; Galderma; Allergika; Beiersdorf; Biocryst; Biogen Idec; BMS; Boehringer‐Ingelheim; Eli‐Lilly; Galderma; Hexal; Klosterfrau; LEO‐Pharma; LETI‐Pharma; L´Oreal; Medice; Octapharma; Pflüger; Pharming; Regeneron; Shire; ALK‐Abello; Fraunhofer‐IZI Leipzig; Hautnetz Leipzig/Westsachsen; MSD; HAL‐Allergy; Bencard; Nestle; Nutricia; Bayer Health Care; FAES; Henkel; Allakos; Argenx; Genentech Menarini; Moxie; Aralez; Celldex
Published: 2021

28. Autoimmune Primary Adrenal Insufficiency in Children

Author: Nádia, Mourinho Bala, Raquel S, Gonçalves, Joana, Serra Caetano, Rita, Cardoso, Isabel, Dinis, and Alice, Mirante
Subjects: Male, Endocrinology, Addison Disease, Adolescent, Adrenocorticotropic Hormone, Hydrocortisone, Endocrinology, Diabetes and Metabolism, Pediatrics, Perinatology and Child Health, Humans, Female, Adrenal Insufficiency, Retrospective Studies
Abstract: Primary adrenal insufficiency (PAI) is a rare condition in children, and is potentially life-threatening. The most common cause is congenital adrenal hyperplasia, and autoimmune etiology is the most frequent acquired cause in this age group. Symptoms are usually non-specific and, when suspected, investigation should include adrenocorticotropin hormone (ACTH) and morning serum cortisol measurement and, in some cases, a cosyntropin test to confirm the diagnosis. Prompt treatment is essential to prevent an adverse outcome.We retrospectively collected clinical and laboratory data from adrenal insufficiency due to autoimmune adrenalitis, observed from 2015 to 2020 in a pediatric endocrinology department of a tertiary care hospital.Eight patients were identified, seven males and one female, with age at diagnosis between 14 and 17 years. The symptoms at presentation ranged from non-specific symptoms, such as chronic fatigue and weight loss, to a severe presentation, with altered mental status and seizures. The median duration of symptoms was 4.5 months. The diagnosis was confirmed by serum cortisol and plasma ACTH measurement and all were confirmed to have autoimmune etiology (positive anti-adrenal antibodies). At diagnosis, the most common laboratory abnormality was hyponatremia. All patients were treated with hydrocortisone and fludrocortisone. One patient presented with evidence of type 2 autoimmune polyglandular syndrome.PAI is a rare condition in the pediatric age group. Due to non-specific symptoms, a high index of suspicion is necessary to establish a prompt diagnosis. Once an autoimmune etiology is confirmed, it is important to initiate the appropriate treatment and search for signs and symptoms of other autoimmune diseases during follow-up.
Published: 2022

29. Sex estimation with morphometric and morphological characteristics of the crista galli

Author: Murat Golpinar, Hande Salim, Serra Ozturk, Erdal Komut, and Muzaffer Sindel
Subjects: Adult, Male, Ethmoid Bone, Sex Characteristics, Logistic Models, Skull, Forensic Anthropology, Humans, Female, Radiology, Nuclear Medicine and imaging, Surgery, Anatomy, Pathology and Forensic Medicine
Abstract: The purpose of the present study was to analyze the dimensions of the crista galli (CG) in preserved skulls, and to examine the role of the morphometry and morphology of the CG on the sex estimation.Anteroposterior, superoinferior, and laterolateral diameters of the CG were measured of 207 preserved adult skulls of Anatolia origin with known sex (108 males, 99 females) in the Anatolian population. CG were morphologically classified into three types according to the dimensions. The success of CG dimensions in sex determination was evaluated with ROC analysis, and univariate and multivariate binary logistic regression analysis. The relationship between morphological types of the CG and sex was analyzed with the Chi-square test.The anteroposterior and superoinferior diameters of the CG significantly were longer in males than females while the laterolateral diameter of the CG was wider in females (p 0.001). Superoposterior diameter (88.4%) of the CG showed higher sex classification accuracy for sex estimation compared to the laterolateral (82.6%) and anteroposterior diameters (80.6%). When all three parameters were used together, the sex classification accuracy rate was 94.2%. The presence of ossified and tubular types of CG identified the male sex with 85% and 74.6% accuracy rates, respectively while teardrop type CG identified female sex with a 72.2% accuracy rate.CG exhibits sexual dimorphism both morphometrically and morphologically. The height, length, and width measurements and the morphological types of CG can be used in sex determination directly from the skull with high accuracy rates.
Published: 2022

30. A Specialized Therapeutic Approach to Chronic Urticaria Refractory to H1-Antihistamines Improves Disease Burden: The Spanish AWARE Experience

Author: J Borbujo, M A Tejedor-Alonso, P Terradas, Marta Ferrer, Manuel Velasco, Joan Bartra, E. Serra-Baldrich, Ignacio Jáuregui, F J Muñoz-Bellido, J Pedraz, M Labrador, A. Giménez-Arnau, and I Figueras
Subjects: Male, Quality of life, medicine.medical_specialty, Adolescent, Urticaria, Immunology, Disease, Clinical practice, Therapeutic approach, Cost of Illness, Refractory, Internal medicine, medicine, Humans, Immunology and Allergy, Chronic Urticaria, Prospective Studies, Angioedema, Chronic urticaria, Disease burden, business.industry, Dermatology Life Quality Index, Middle Aged, Spain, Chronic Disease, Histamine H1 Antagonists, Quality of Life, Female, medicine.symptom, business, Copper
Abstract: Objective: During its first year, the AWARE study assessed disease activity, patient quality of life (QOL), and treatment patterns in chronic urticaria (CU) refractory to H1-antihistamines (H1-AH) in clinical practice. Methods: We performed an observational, prospective (24 months), international, multicenter study. The inclusion criteria were age ≥18 years and H1-AH–refractory CU (>2 months). At each visit, patients completed questionnaires to assess disease burden (Urticaria Control Test [UCT]), disease activity (7 day-Urticaria Activity Score [UAS7]), and QOL (Dermatology Life Quality index [DLQI], Chronic Urticaria Quality of Life Questionnaire [CU-Q2oL], and Angioedema Quality of Life Questionnaire [AE-QoL]). We present data for Spain. Results: The study population comprised 270 evaluable patients (73.3% female, mean [SD] age, 48.9 [14.7] years). At baseline, 89.3% were prescribed a CU treatment. After 1 year, first- and second-line treatments became less frequent and third-line treatments became more frequent. At baseline, 47.0% of patients experienced angioedema; at 1 year, this percentage had fallen to 11.8%. The mean (SD) AE-QoL score decreased from 45.2 (28.7) to 24.0 (25.8). The mean (SD) UCT score decreased from 7.0 (4.5) to 12.1 (4.1). According to UAS7, 38.2% of patients reported absence of wheals and itch in the previous 7 days at 1 year compared with 8.3% at baseline. The mean (SD) DLQI score decreased from 8.0 (7.4) to 2.8 (4.6). At the 1-year visit, the percentage of patients reporting a high or very high impact on QOL fell from 29.9% to 9.6%. Conclusions: H1-AH–refractory CU in Spain is characterized by absence of symptoms and a considerable impact on QOL. Continuous follow-up of CU patients and third-line therapies reduce disease burden and improve patients’ QOL.
Published: 2022

31. 'Swab Team' in the SARS-CoV-2 outbreak containment among healthcare workers

Author: Francesco Bussu, Davide Rizzo, Laura Saderi, Antonio Piras, Laura Maria De Luca, Giacomo De Riu, Luigi Angelo Vaira, Antonello Serra, Paola Altrudo, Domenico Delogu, Ignazio Dettori, Francesco Giuseppe Riu, Flavia Angioj, Laura Firino, Rosalba Govoni, Gabriele Ibba, Vincenzo Lai, Erica Mura, Bianca Paglietti, Claudia Piu, Anna Puggioni, Elena Rimini, Giulia Rocca, Caterina Serra, Sergio Uzzau, Salvatore Rubino, and Giovanni Sotgiu
Subjects: Adult, Male, Patient Care Team, SARS-CoV-2, COVID-19, General Medicine, Middle Aged, Microbiology, Specimen Handling, Occupational Diseases, Infectious Diseases, Italy, Virology, Medical Staff, Hospital, Humans, Female, Parasitology, Pandemics, Retrospective Studies
Abstract: Introduction: To analyze the virus spread among Sassari Hospital staff in the first Covid-19 wave and the impact of the Swab Team, a multidisciplinary task force entitled of nasopharyngeal swab collection and testing. Methodology: Nasopharyngeal swabs from HCWs between March 6 and May 28 2020 are evaluated. Results: 4919 SARS-CoV-2 tests were performed on 3521 operators. Nurses and doctors are the categories at highest risk. After the Swab Team institution, the average number of swabs raised from 47/day to 86/day (p = 0.007). Positive samples decreased from 18.6% to 1.7% (p < 0.0001). Conclusions: The Swab Team is effective in increasing the cases tested and in reducing the reporting time. Procedure standardization reduces the risk for all the subjects involved (no transmission among swab team members, nor during the sample collection).
Published: 2021

32. Efficacy and Safety of Jotec E-Ventus BX Stent Graft for Iliac Branch Device Procedure: A Retrospective Clinical Study

Author: Giancarlo Accarino, Anna Petrone, Giuseppe Filiberto Serraino, Pasquale Mastroroberto, Michele Andreucci, Giovanni Fornino, Raffaele Serra, Umberto Bracale, Davide Turchino, Nicola Ielapi, Luca del Guercio, Maurizio Sodo, Giulio Accarino, Michele Provenzano, Bracale, Umberto Marcello, Turchino, Davide, Accarino, Giancarlo, Petrone, Anna, Del Guercio, Luca, Sodo, Maurizio, Fornino, Giovanni, Accarino, Giulio, Ielapi, Nicola, Serraino, Giuseppe Filiberto, Mastroroberto, Pasquale, Provenzano, Michele, Andreucci, Michele, and Serra, Raffaele
Subjects: Male, endovascular treatment, medicine.medical_specialty, Time Factors, Endoleak, medicine.medical_treatment, Prosthesis Design, Endovascular aneurysm repair, aorto-iliac aneurysm, endoleaks, iliac branch device, prognosis, Retrospective data, Blood Vessel Prosthesis Implantation, Occlusion, medicine, Clinical endpoint, Humans, Vascular Patency, Aged, Retrospective Studies, business.industry, Endovascular Procedures, Graft Occlusion, Vascular, Stent, General Medicine, Middle Aged, Vascular surgery, Aortic Aneurysm, Blood Vessel Prosthesis, Surgery, Cross-Sectional Studies, Treatment Outcome, Italy, Iliac Aneurysm, Cohort, cardiovascular system, Female, Stents, Cardiology and Cardiovascular Medicine, business
Abstract: Background The endovascular aneurysm repair (EVAR) is a successful treatment for aorto-iliac aneurysms. The success of EVAR is enhanced by the use of devices that maintain the patency of targeted arteries namely the iliac branch device (IBD) With this study we aimed to evaluate the association between the use of Jotec E-ventus during EVAR with IBD and prognosis in patients with aorto-iliac aneurysms. Methods This is a retrospective, multicentric study enrolling patients referred to our Vascular Surgery Units from January 2015 to January 2020. All patients underwent EVAR with IBD using Jotec E-ventus as bridging stent. Primary endpoint was the development of types I and III endoleaks. Secondary endpoint was the onset of device occlusion with loss of vascular patency. Results We studied 32 patients (mean age 71.7±4.5y). Of these, 25 patients were treated with standard EVAR procedure whereas 7 were treated with isolated IBD due to extension of disease involving iliac bifurcation. Median follow-up lasted 15[IQR11-27] months. During follow-up, incidence rates for endoleaks and occlusion were 3.98(95%CI 0.48-14.41) and 1.99(95%CI 0.05-11.12) per 100 pts/year. Conclusions Jotec E-ventus during EVAR is associated with a low rate of severe complications in a small cohort of patients with aorto-iliac aneurysms.
Published: 2021

33. Large-Scale Postmarketing Surveillance of Biological Drugs for Immune-Mediated Inflammatory Diseases Through an Italian Distributed Multi-Database Healthcare Network: The VALORE Project

Author: Trifiro, G., Isgro, V., Ingrasciotta, Y., Ientile, V., L'Abbate, L., Foti, S. S., Belleudi, V., Poggi, F., Fontana, A., Moretti, U., Lora, R., Sabaini, A., Senesi, I., Sorrentino, C., Puzo, M. R., Padula, A., Fusco, M., Giordana, R., Solfrini, V., Puccini, A., Rossi, P., Del Zotto, S., Leoni, O., Zanforlini, M., Ancona, D., Bavaro, V., Garau, D., Ledda, S., Scondotto, S., Allotta, A., Tuccori, M., Gini, R., Bucaneve, G., Franchini, D., Cavazzana, A., Biasi, V., Spila Alegiani, S., Massari, M., Andretta, I., Tanaglia, M., Carriero, A., Sassano, S., De Sarro, G., Mirarchi, S., Palleria, C., Sarro, C., Balestrieri, M., Rostan, S., Capuano, A., Bernardi, F. F., Trama, U., Russo, A., Fumo, M. G., Addis, A., Musicco, F., Sapigni, E., Mazzetti, I., Podetti, D., Potenza, A. M., Nikitina, V., Ricciardelli, R., Mogheiseh, N., Croce, S., Pettinelli, A., Ejlli, L., Fortino, I., Ercolanoni, M., Mazzone, A., Nisic, A., Schiatti, S., Ludergnani, M., Mancini, M., Patregnani, L., Fabbietti, P., Antonicelli, E., Mangano, A., Campomori, A., Urru, S. A., Costa, G., Guarrera, G. M., Stella, P., Serra, E., Carta, P., Vannacci, A., Lucenteforte, E., Parrilli, M., Convertino, I., De Giorgi, M., Rocchi, R. E., Rossi, M., Scroccaro, G., Deambrosis, P., Grindelli, G., Ferroni, E., Trifiro, G., Isgro, V., Ingrasciotta, Y., Ientile, V., L'Abbate, L., Foti, S. S., Belleudi, V., Poggi, F., Fontana, A., Moretti, U., Lora, R., Sabaini, A., Senesi, I., Sorrentino, C., Puzo, M. R., Padula, A., Fusco, M., Giordana, R., Solfrini, V., Puccini, A., Rossi, P., Del Zotto, S., Leoni, O., Zanforlini, M., Ancona, D., Bavaro, V., Garau, D., Ledda, S., Scondotto, S., Allotta, A., Tuccori, M., Gini, R., Bucaneve, G., Franchini, D., Cavazzana, A., Biasi, V., Spila Alegiani, S., Massari, M., Andretta, I., Tanaglia, M., Carriero, A., Sassano, S., De Sarro, G., Mirarchi, S., Palleria, C., Sarro, C., Balestrieri, M., Rostan, S., Capuano, A., Bernardi, F. F., Trama, U., Russo, A., Fumo, M. G., Addis, A., Musicco, F., Sapigni, E., Mazzetti, I., Podetti, D., Potenza, A. M., Nikitina, V., Ricciardelli, R., Mogheiseh, N., Croce, S., Pettinelli, A., Ejlli, L., Fortino, I., Ercolanoni, M., Mazzone, A., Nisic, A., Schiatti, S., Ludergnani, M., Mancini, M., Patregnani, L., Fabbietti, P., Antonicelli, E., Mangano, A., Campomori, A., Urru, S. A., Costa, G., Guarrera, G. M., Stella, P., Serra, E., Carta, P., Vannacci, A., Lucenteforte, E., Parrilli, M., Convertino, I., De Giorgi, M., Rocchi, R. E., Rossi, M., Scroccaro, G., Deambrosis, P., Grindelli, G., and Ferroni, E.
Subjects: Male, medicine.medical_specialty, Population, Postmarketing surveillance, Rate ratio, REGISTRIES, Retrospective Studie, Internal medicine, BIOSIMILARS, medicine, Adalimumab, Humans, Pharmacology (medical), Original Research Article, education, Adverse effect, ANTI-TNF THERAPY, RHEUMATOID-ARTHRITIS, RISK, PHARMACOVIGILANCE, BIOSIMILARS, EXPERIENCE, REGISTRIES, PSORIASIS, MEDICINES, ACCESS, Biosimilar Pharmaceuticals, Retrospective Studies, RISK, Delivery of Health Care, Female, Infliximab, Italy, SARS-CoV-2, COVID-19, Pharmacology, education.field_of_study, PSORIASIS, business.industry, Biosimilar, ANTI-TNF THERAPY, General Medicine, medicine.disease, RHEUMATOID-ARTHRITIS, PHARMACOVIGILANCE, MEDICINES, EXPERIENCE, Immune-mediated inflammatory diseases, ACCESS, business, Human, Biosimilar Pharmaceutical, Biotechnology, medicine.drug
Abstract: Background Biological drugs have improved the management of immune-mediated inflammatory diseases (IMIDs) despite being associated with important safety issues such as immunogenicity, infections, and malignancies in real-world settings. Objective The aim of this study was to explore the potential of a large Italian multi-database distributed network for use in the postmarketing surveillance of biological drugs, including biosimilars, in patients with IMID. Methods A retrospective cohort study was conducted using 13 Italian regional claims databases during 2010–2019. A tailor-made R-based tool developed for distributed analysis of claims data using a study-specific common data model was customized for this study. We measured the yearly prevalence of biological drug users and the frequency of switches between originator and biosimilars for infliximab, etanercept, and adalimumab separately and stratified them by calendar year and region. We then calculated the cumulative number of users and person-years (PYs) of exposure to individual biological drugs approved for IMIDs. For a number of safety outcomes (e.g., severe acute respiratory syndrome coronavirus 2 [SARS-COV-2] infection), we conducted a sample power calculation to estimate the PYs of exposure required to investigate their association with individual biological drugs approved for IMIDs, considering different strengths of association. Results From a total underlying population of almost 50 million inhabitants from 13 Italian regions, we identified 143,602 (0.3%) biological drug users, with a cumulative exposure of 507,745 PYs during the entire follow-up. The mean age ± standard deviation of biological drug users was 49.3 ± 16.3, with a female-to-male ratio of 1.2. The age-adjusted yearly prevalence of biological drug users increased threefold from 0.7 per 1000 in 2010 to 2.1 per 1000 in 2019. Overall, we identified 40,996 users of biosimilars of tumor necrosis factor (TNF)-α inhibitors (i.e., etanercept, adalimumab, and infliximab) in the years 2015–2019. Of these, 46% (N = 18,845) switched at any time between originator and biosimilars or vice versa. To investigate a moderate association (incidence rate ratio 2) between biological drugs approved for IMIDs and safety events of interest, such as optic neuritis (lowest background incidence rate 10.4/100,000 PYs) or severe infection (highest background incidence rate 4312/100,000 PYs), a total of 43,311 PYs and 104 PYs of exposure to individual biological drugs, respectively, would be required. As such, using this network, of 15 individual biological drugs approved for IMIDs, the association with those adverse events could be investigated for four (27%) and 14 (93%), respectively. Conclusion The VALORE project multi-database network has access to data on more than 140,000 biological drug users (and > 0.5 million PYs) from 13 Italian regions during the years 2010–2019, which will be further expanded with the inclusion of data from other regions and more recent calendar years. Overall, the cumulated amount of person-time of exposure to biological drugs approved for IMIDs provides enough statistical power to investigate weak/moderate associations of almost all individual compounds and the most relevant safety outcomes. Moreover, this network may offer the opportunity to investigate the interchangeability of originator and biosimilars of several TNFα inhibitors in different therapeutic areas in real-world settings. Supplementary Information The online version contains supplementary material available at 10.1007/s40259-021-00498-3.
Published: 2021

34. Cannabinoids: an Effective Treatment for Chemotherapy-Induced Peripheral Neurotoxicity?

Author: Susan G. Dorsey, Paola Marmiroli, Cynthia L. Renn, Cristina Meregalli, Marina Quartu, Maria Pina Serra, Guido Cavaletti, Cavaletti, G, Marmiroli, P, Renn, C, Dorsey, S, Serra, M, Quartu, M, and Meregalli, C
Subjects: Male, medicine.medical_specialty, Neurology, Cannabinoid receptor, Endocannabinoid system, medicine.medical_treatment, Antineoplastic Agents, Review, Bioinformatics, medicine, Chemotherapy, Humans, Pharmacology (medical), Cannabinoid receptors, Multiple myeloma, Pharmacology, Cannabinoids, business.industry, Neurotoxicity, Peripheral Nervous System Diseases, medicine.disease, Neuropathy, Treatment, Clinical trial, Leukemia, Treatment Outcome, Neurotoxicity Syndromes, Neurology (clinical), business
Abstract: Chemotherapy-induced peripheral neurotoxicity (CIPN) is one of the most frequent side effects of antineoplastic treatment, particularly of lung, breast, prostate, gastrointestinal, and germinal cancers, as well as of different forms of leukemia, lymphoma, and multiple myeloma. Currently, no effective therapies are available for CIPN prevention, and symptomatic treatment is frequently ineffective; thus, several clinical trials are addressing this unmet clinical need. Among possible pharmacological treatments of CIPN, modulation of the endocannabinoid system might be particularly promising, especially in those CIPN types where analgesia and neuroinflammation modulation might be beneficial. In fact, several clinical trials are ongoing with the specific aim to better investigate the changes in endocannabinoid levels induced by systemic chemotherapy and the possible role of endocannabinoid system modulation to provide relief from CIPN symptoms, a hypothesis supported by preclinical evidence but never consistently demonstrated in patients. Interestingly, endocannabinoid system modulation might be one of the mechanisms at the basis of the reported efficacy of exercise and physical therapy in CIPN patients. This possible virtuous interplay will be discussed in this review. Supplementary Information The online version contains supplementary material available at 10.1007/s13311-021-01127-1.
Published: 2021

35. An Evaluation of Glucagon Injection Anxiety and Its Association with the Fear of Hypoglycemia among the Parents of Children with Type 1 Diabetes

Author: Ecem Can, Gül Yeşiltepe Mutlu, Tuğba Gökçe, Şükrü Hatun, Serra Muradoğlu, Muradoğlu, Serra, Gökçe, Tuğba, Can, Ecem, Mutlu, Gül Yeşiltepe (ORCID 0000-0003-3919-7763 & YÖK ID 153511), Hatun, Şükrü (ORCID 0000-0003-1633-9570 & YÖK ID 153504), Koç University Hospital, School of Medicine, and Graduate School of Health Sciences
Subjects: Blood Glucose, Male, Parents, diabetes mellitus type 1, Health Knowledge, Attitudes, Practice, endocrine system, Generalized anxiety disorder, Hypoglycemia, Glucagon, Anxiety, Diabetes mellitus type 1, Adolescent, Endocrinology, Diabetes and Metabolism, Pilot Projects, Injections, Intramuscular, Pediatrics, RJ1-570, Diseases of the endocrine glands. Clinical endocrinology, Competence (law), Endocrinology, Surveys and Questionnaires, medicine, Humans, Hypoglycemic Agents, Child, Association (psychology), Type 1 diabetes, business.industry, Fear, medicine.disease, anxiety, RC648-665, Diabetes Mellitus, Type 1, hypoglycemia, Endocrinology and metabolism, Caregivers, glucagon, Child, Preschool, Pediatrics, Perinatology and Child Health, Glucagon Injection, Female, Original Article, medicine.symptom, business, Biomarkers, Clinical psychology
Abstract: Objective: Hypoglycemia is a common acute complication of type 1 diabetes (T1D), which may cause seizure, loss of consciousness, and temporary motor or sensory impairment. Glucagon administration is an effective way of treating severe hypoglycemia, especially in a free-living setting. Nonetheless, families have difficulties in managing severe hypoglycemia due to their anxiety and challenges with current glucagon administration techniques. The aim of the current study was to explore the associations between parental fear of hypoglycemia (FoH) and their general anxiety level, and in particular, their attitudes towards and thoughts on glucagon administration. Methods: Parents of children with T1D completed questionnaires assessing background and clinical information, FoH, generalized anxiety disorder (GAD) and parental anxiety for glucagon administration (PAGA). Results: sixty-eight parents participated. Positive correlations were found between parental GAD-7 score and both FoH and the number of night-time blood glucose measurements and there was a negative correlation with the child's age. Parents mean self-evaluation score of their competence in glucagon administration was 6 (standard deviation +/- 2.9) on a scale of 0 to 10. Unsurprisingly, this score was negatively correlated with the PAGA scores. There was no significant difference between children using continuous glucose monitoring system and self-monitoring of blood glucose in terms of parental FoH, anxiety and misconceptions about glucagon administration. Conclusion: the results showed that parents of children with T1D had anxiety and fear connected with hypoglycemia and glucagon administration. Structured and practical training should be implemented to increase parents' self-confidence including annual refresher training for home glucagon administration., NA
Published: 2021

36. Delay eyeblink conditioning performance and brain-wide c-Fos expression in male and female mice

Author: Maria Roa Oyaga, Ines Serra, Devika Kurup, Sebastiaan K. E. Koekkoek, Aleksandra Badura, Neurosciences, and Netherlands Institute for Neuroscience (NIN)
Subjects: Male, Mice, Inbred C57BL, Mice, General Neuroscience, Cerebellum, Immunology, Animals, Brain, Female, Inbred C57BL, General Biochemistry, Genetics and Molecular Biology, Locomotion
Abstract: Delay eyeblink conditioning has been extensively used to study associative learning and the cerebellar circuits underlying this task have been largely identified. However, there is a little knowledge on how factors such as strain, sex and innate behaviour influence performance during this type of learning. In this study, we used male and female mice of C57BL/6J (B6) and B6CBAF1 strains to investigate the effect of sex, strain and locomotion in delay eyeblink conditioning. We performed a short and a long delay eyeblink conditioning paradigm and used a c-Fos immunostaining approach to explore the involvement of different brain areas in this task. We found that both B6 and B6CBAF1 females reach higher learning scores compared to males in the initial stages of learning. This sex-dependent difference was no longer present as the learning progressed. Moreover, we found a strong positive correlation between learning scores and voluntary locomotion irrespective of the training duration. c-Fos immunostainings after the short paradigm showed positive correlations between c-Fos expression and learning scores in the cerebellar cortex and brainstem, as well as previously unreported areas. By contrast, after the long paradigm, c-Fos expression was only significantly elevated in the brainstem. Taken together, we show that differences in voluntary locomotion and activity across brain areas correlate with performance in delay eyeblink conditioning across strains and sexes.
Published: 2023

37. X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19

Author: Asano, Takaki, Boisson, Bertrand, Onodi, Fanny, Matuozzo, Daniela, Moncada-Velez, Marcela, Maglorius Renkilaraj, Majistor Raj Luxman, Zhang, Peng, Meertens, Laurent, Bolze, Alexandre, Materna, Marie, Korniotis, Sarantis, Gervais, Adrian, Talouarn, Estelle, Bigio, Benedetta, Seeleuthner, Yoann, Bilguvar, Kaya, Zhang, Yu, Neehus, Anna-Lena, Ogishi, Masato, Pelham, Simon J., Le Voyer, Tom, Rosain, Jérémie, Philippot, Quentin, Soler-Palacín, Pere, Colobran, Roger, Martin-Nalda, Andrea, Rivière, Jacques G., Tandjaoui-Lambiotte, Yacine, Chaïbi, Khalil, Shahrooei, Mohammad, Darazam, Ilad Alavi, Olyaei, Nasrin Alipour, Mansouri, Davood, Hatipoğlu, Nevin, Palabiyik, Figen, Ozcelik, Tayfun, Novelli, Giuseppe, Novelli, Antonio, Casari, Giorgio, Aiuti, Alessandro, Carrera, Paola, Bondesan, Simone, Barzaghi, Federica, Rovere-Querini, Patrizia, Tresoldi, Cristina, Franco, Jose Luis, Rojas, Julian, Reyes, Luis Felipe, Bustos, Ingrid G., Arias, Andres Augusto, Morelle, Guillaume, Kyheng, Christèle, Troya, Jesús, Planas-Serra, Laura, Schlüter, Agatha, Gut, Marta, Pujol, Aurora, Allende, Luis M., Rodriguez-Gallego, Carlos, Flores, Carlos, Cabrera-Marante, Oscar, Pleguezuelo, Daniel E., Pérez de Diego, Rebeca, Keles, Sevgi, Aytekin, Gokhan, Metin Akcan, Ozge, Bryceson, Yenan T., Bergman, Peter, Brodin, Petter, Smole, Daniel, Smith, C. I. Edvard, Norlin, Anna-Carin, Campbell, Tessa M., Covill, Laura E., Hammarström, Lennart, Pan-Hammarström, Qiang, Abolhassani, Hassan, Mane, Shrikant, Marr, Nico, Ata, Manar, Al Ali, Fatima, Khan, Taushif, Spaan, András N., Dalgard, Clifton L., Bonfanti, Paolo, Biondi, Andrea, Tubiana, Sarah, Burdet, Charles, Nussbaum, Robert, Kahn-Kirby, Amanda, Snow, Andrew L., Bustamante, Jacinta, Puel, Anne, Boisson-Dupuis, Stéphanie, Zhang, Shen-Ying, Béziat, Vivien, Lifton, Richard P., Bastard, Paul, Notarangelo, Luigi D., Abel, Laurent, Su, Helen C., Jouanguy, Emmanuelle, Amara, Ali, Soumelis, Vassili, Cobat, Aurélie, Zhang, Qian, Casanova, Jean-Laurent, Al-Muhsen, Saleh, Al-Mulla, Fahd, Anderson, Mark S., Andreakos, Evangelos, Arias, Andrés A., Feldman, Hagit Baris, Belot, Alexandre, Biggs, Catherine M., Bogunovic, Dusan, Bondarenko, Anastasiia, Bousfiha, Ahmed A., Bryceson, Yenan, Bustamante, Carlos D., Butte, Manish J., Chakravorty, Samya, Christodoulou, John, Condino-Neto, Antonio, Constantinescu, Stefan N., Cooper, Megan A., Desai, Murkesh, Drolet, Beth A., El Baghdadi, Jamila, Espinosa-Padilla, Sara, Fellay, Jacques, Franco, José Luis, Froidure, Antoine, Gregersen, Peter K., Haerynck, Filomeen, Hagin, David, Halwani, Rabih, Heath, James R., Henrickson, Sarah E., Hsieh, Elena W.Y., Husebye, Eystein, Imai, Kohsuke, Itan, Yuval, Jarvis, Erich D., Karamitros, Timokratis, Kisand, Kai, Ku, Cheng-Lung, Lau, Yu-Lung, Ling, Yun, Lucas, Carrie L., Maniatis, Tom, Maródi, László, Meyts, Isabelle, Milner, Joshua D., Mironska, Kristina, Mogensen, Trine H., Morio, Tomohiro, Ng, Lisa F.P., O'Farrelly, Cliona, Okada, Satoshi, de Diego, Rebeca Perez, Planas, Anna M., Prando, Carolina, Quintana-Murci, Lluis, Renia, Laurent, Resnick, Igor, Rodríguez-Gallego, Carlos, Sancho-Shimizu, Vanessa, Sediva, Anna, Seppänen, Mikko R.J., Shahrooei, Mohammed, Shcherbina, Anna, Slaby, Ondrej, Tancevski, Ivan, Tangye, Stuart G., Abou Tayoun, Ahmad, Ramaswamy, Sathishkumar, Turvey, Stuart E, Uddin, K M Furkan, Uddin, Mohammed J., van de Beek, Diederik, Vinh, Donald C., von Bernuth, Horst, Zatz, Mayana, Zawadzki, Pawel, Foti, Giuseppe, Bellani, Giacomo, Citerio, Giuseppe, Contro, Ernesto, Pesci, Alberto, Valsecchi, Maria Grazia, Cazzaniga, Marina, Abad, Jorge, Accordino, Giulia, Achille, Cristian, Aguilera-Albesa, Sergio, Aguiló-Cucurull, Aina, Özkan, Esra Akyüz, Roblero Albisures, Jonathan Antonio, Aldave, Juan C, Ramos, Miquel Alfonso, Khan, Taj Ali, Aliberti, Anna, Nadji, Seyed Alireza, Alkan, Gulsum, AlKhater, Suzan A., Allardet-Servent, Jerome, Allende, Luis M, Alonso-Arias, Rebeca, Alshahrani, Mohammed S, Alsina, Laia, Alyanakian, Marie-Alexandra, Borrero, Blanca Amador, Amoura, Zahir, Antolí, Arnau, Arrestier, Romain, Aubart, Mélodie, Auguet, Teresa, Avramenko, Iryna, Aytekin, Gökhan, Azot, Axelle, Bahram, Seiamak, Bajolle, Fanny, Baldanti, Fausto, Baldolli, Aurélie, Ballester, Maite, Barrou, Benoit, Barzagh, Federica, Basso, Sabrina, Bayhan, Gulsum Iclal, Bezrodnik, Liliana, Bilbao, Agurtzane, Blanchard-Rohner, Geraldine, Blanco, Ignacio, Blandinières, Adeline, Blázquez-Gamero, Daniel, Bleibtreu, Alexandre, Bloomfield, Marketa, Bolivar-Prados, Mireia, Borghesi, Alessandro, Borie, Raphael, Botdhlo-Nevers, Elisabeth, Bousfiha, Ahmed A, Bousquet, Aurore, Boutolleau, David, Bouvattier, Claire, Boyarchuk, Oksana, Bravais, Juliette, Briones, M. Luisa, Brunner, Marie-Eve, Bruno, Raffaele, Bueno, Maria Rita P, Bukhari, Huda, Cáceres Agra, Juan José, Capra, Ruggero, Carapito, Raphael, Carrabba, Maria, Casasnovas, Carlos, Caseris, Marion, Cassaniti, Irene, Castelle, Martin, Castelli, Francesco, de Vera, Martín Castillo, Castro, Mateus V, Catherinot, Emilie, Celik, Jale Bengi, Ceschi, Alessandro, Chalumeau, Martin, Charbit, Bruno, Cheng, Matthew P., Clavé, Père, Clotet, Bonaventura, Codina, Anna, Cohen, Yves, Comarmond, Cloé, Combes, Alain, Comoli, Patrizia, Corsico, Angelo G, Coşkuner, Taner, Cvetkovski, Aleksandar, Cyrus, Cyril, Dalmau, David, Danion, François, Darley, David Ross, Das, Vincent, Dauby, Nicolas, Dauger, Stéphane, De Munter, Paul, de Pontual, Loic, Dehban, Amin, Delplancq, Geoffroy, Demoule, Alexandre, Desguerre, Isabelle, Di Sabatino, Antonio, Diehl, Jean-Luc, Dobbelaere, Stephanie, Domínguez-Garrido, Elena, Dubost, Clément, Ekwall, Olov, Bozdemir, Şefika Elmas, Elnagdy, Marwa H, Emiroglu, Melike, Endo, Akifumi, Erdeniz, Emine Hafize, Aytekin, Selma Erol, Lasa, Maria Pilar Etxart, Euvrard, Romain, Fabio, Giovanna, Faivre, Laurence, Falck, Antonin, Fartoukh, Muriel, Faure, Morgane, Arquero, Miguel Fernandez, Ferrer, Ricard, Ferreres, Jose, Francois, Bruno, Fumadó, Victoria, Fung, Kitty S C, Fusco, Francesca, Gagro, Alenka, Solis, Blanca Garcia, Gaussem, Pascale, Gayretli, Zeynep, Gil-Herrera, Juana, Gilardin, Laurent, Gatineau, Audrey Giraud, Girona-Alarcón, Mònica, Cifuentes Godínez, Karen Alejandra, Goffard, Jean-Christophe, Gonzales, Nacho, Gonzalez-Granado, Luis I, González-Montelongo, Rafaela, Guerder, Antoine, Gülhan, Belgin, Gumucio, Victor Daniel, Hanitsch, Leif Gunnar, Gunst, Jan, Hadjadj, Jérôme, Hancerli, Selda, Hariyan, Tetyana, Hatipoglu, Nevin, Heppekcan, Deniz, Hernandez-Brito, Elisa, Ho, Po-ki, Holanda-Peña, María Soledad, Horcajada, Juan P, Hraiech, Sami, Humbert, Linda, Hung, Ivan F N, Iglesias, Alejandro D., Íñigo-Campos, Antonio, Jamme, Matthieu, Arranz, María Jesús, Jimeno, Marie-Thérèse, Jordan, Iolanda, Yüksek, Saliha Kanık, Kara, Yalcin Burak, Karahan, Aydın, Karbuz, Adem, Yasar, Kadriye Kart, Kasapcopur, Ozgur, Kashimada, Kenichi, Demirkol, Yasemin Kendir, Kido, Yasutoshi, Kizil, Can, Kılıç, Ahmet Osman, Klocperk, Adam, Koutsoukou, Antonia, Król, Zbigniew J., Ksouri, Hatem, Kuentz, Paul, Kwan, Arthur M C, Kwan, Yat Wah M, Kwok, Janette S Y, Lagier, Jean-Christophe, Lam, David S Y, Lampropoulou, Vicky, Lanternier, Fanny, LAU, Yu-Lung, Le Bourgeois, Fleur, Leo, Yee-Sin, Lopez, Rafael Leon, Leung, Daniel, Levin, Michael, Levy, Michael, Lévy, Romain, Li, Zhi, Lilleri, Daniele, Bolanos Lima, Edson Jose Adrian, Linglart, Agnes, López-Collazo, Eduardo, Lorenzo-Salazar, José M., Louapre, Céline, Lubetzki, Catherine, Lung, Kwok-Cheung, Luyt, Charles-Edouard, Lye, David C, Magnone, Cinthia, Marchioni, Enrico, Marioli, Carola, Marjani, Majid, Marques, Laura, Pereira, Jesus Marquez, Martín-Nalda, Andrea, Pueyo, David Martínez, Martinez-Picado, Javier, Marzana, Iciar, Mata-Martínez, Carmen, Mathian, Alexis, Matos, Larissa RB, Matthews, Gail V, Mayaux, Julien, McLaughlin-Garcia, Raquel, Meersseman, Philippe, Mège, Jean-Louis, Mekontso-Dessap, Armand, Melki, Isabelle, Meloni, Federica, Meritet, Jean-François, Merlani, Paolo, Akcan, Özge Metin, Mezidi, Mehdi, Migeotte, Isabelle, Millereux, Maude, Million, Matthieu, Mirault, Tristan, Mircher, Clotilde, Mirsaeidi, Mehdi, Mizoguchi, Yoko, Modi, Bhavi P, Mojoli, Francesco, Moncomble, Elsa, Melián, Abián Montesdeoca, Martinez, Antonio Morales, Morandeira, Francisco, Morange, Pierre-Emmanuel, Mordacq, Cléemence, Mouly, Stéphane J, Muñoz-Barrera, Adrián, Nafati, Cyril, Nagashima, Shintaro, Nakagama, Yu, Neven, Bénédicte, Neves, João Farela, Ng, Lisa FP, Ng, Yuk-Yung, Nielly, Hubert, Medina, Yeray Novoa, Cuadros, Esmeralda Nuñez, Ocejo-Vinyals, J. Gonzalo, Okamoto, Keisuke, Oualha, Mehdi, Ouedrani, Amani, Özçelik, Tayfun, Ozkaya-Parlakay, Aslinur, Pagani, Michele, Papadaki, Maria, Parizot, Christophe, Parola, Philippe, Pascreau, Tiffany, Paul, Stéphane, Paz-Artal, Estela, Pedraza, Sigifredo, González Pellecer, Nancy Carolina, Pellegrini, Silvia, de Diego, Rebeca Pérez, Pérez-Fernández, Xosé Luis, Philippe, Aurélien, Picod, Adrien, de Chambrun, Marc Pineton, Piralla, Antonio, Ploin, Dominique, Poissy, Julien, Poncelet, Géraldine, Poulakou, Garyphallia, Pouletty, Marie S, Pourshahnazari, Persia, Qiu-Chen, Jia Li, Quentric, Paul, Rambaud, Thomas, Raoult, Didier, Raoult, Violette, Rebillat, Anne-Sophie, Redin, Claire, Resmini, Léa, Ricart, Pilar, Richard, Jean-Christophe, Rigo-Bonnin, Raúl, Rivet, Nadia, Rivière, Jacques G, Rocamora-Blanch, Gemma, Rodero, Mathieu P, Rodrigo, Carlos, Rodriguez, Luis Antonio, Rodriguez-Palmero, Agustí, Romero, Carolina Soledad, Rothenbuhler, Anya, Roux, Damien, Rovina, Nikoletta, Rozenberg, Flore, Ruch, Yvon, Ruiz, Montse, Ruiz del Prado, Maria Yolanda, Ruiz-Rodriguez, Juan Carlos, Sabater-Riera, Joan, Saks, Kai, Salagianni, Maria, Sanchez, Oliver, Sánchez-Montalvá, Adrián, Sánchez-Ramón, Silvia, Schidlowski, Laire, Schluter, Agatha, Schmidt, Julien, Schmidt, Matthieu, Schuetz, Catharina, Schweitzer, Cyril E, Scolari, Francesco, Seijo, Luis, Seminario, Analia Gisela, Sene, Damien, Seng, Piseth, Senoglu, Sevtap, Seppänen, Mikko, Llovich, Alex Serra, Siguret, Virginie, Siouti, Eleni, Smadja, David M, Smith, Nikaia, Sobh, Ali, Solanich, Xavier, Solé-Violán, Jordi, Soler, Catherine, Sözeri, Betül, Stella, Giulia Maria, Stepanovskiy, Yuriy, Stoclin, Annabelle, Taccone, Fabio, Taupin, Jean-Luc, Tavernier, Simon J, Tello, Loreto Vidaur, Terrier, Benjamin, Thiery, Guillaume, Thorball, Christian, Thorn, Karolina, Thumerelle, Caroline, Tipu, Imran, Tolstrup, Martin, Tomasoni, Gabriele, Toubiana, Julie, Alvarez, Josep Trenado, Triantafyllia, Vasiliki, Trouillet-Assant, Sophie, Tsang, Owen T Y, Tserel, Liina, Tso, Eugene Y K, Tucci, Alessandra, Tüter Öz, Şadiye Kübra, Ursini, Matilde Valeria, Utsumi, Takanori, Uzunhan, Yurdagul, Vabres, Pierre, Valencia-Ramos, Juan, Van Den Rym, Ana Maria, Vandernoot, Isabelle, Velez-Santamaria, Valentina, Zuniga Veliz, Silvia Patricia, Vidigal, Mateus C, Viel, Sébastien, Vilain, Cédric, Vilaire-Meunier, Marie E, Villar-García, Judit, Vincent, Audrey, Vogt, Guillaume, Voiriot, Guillaume, Volokha, Alla, Vuotto, Fanny, Wauters, Els, Wauters, Joost, Wu, Alan K L, Wu, Tak-Chiu, Yahşi, Aysun, Yesilbas, Osman, Yildiz, Mehmet, Young, Barnaby E, Yükselmiş, Ufuk, Zecca, Marco, Zuccaro, Valentina, Jens, Van Praet, Lambrecht, Bart N., Eva, Van Braeckel, Cédric, Bosteels, Levi, Hoste, Eric, Hoste, Bauters, Fré, De Clercq, Jozefien, Cathérine, Heijmans, Hans, Slabbynck, Leslie, Naesens, Florkin, Benoit, Boulanger, Cécile, Vanderlinden, Dimitri, Annereau, Jean-Philippe, Briseño-Roa, Luis, Gribouval, Olivier, Pelet, Anna, Andrejak, Claire, Angoulvant, 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Quentin, Le Mestre, Soizic, Le Nagard, Hervé, Lescure, François-Xavier, Letrou, Sophie, Levy, Yves, Lina, Bruno, Lingas, Guillaume, Lucet, Jean Christophe, Malvy, Denis, Mambert, Marina, Mentré, France, Meziane, Amina, Mouquet, Hugo, Mullaert, Jimmy, Neant, Nadège, Nguyen, Duc, Noret, Marion, Nseir, Saad, Papadopoulos, Aurélie, Paul, Christelle, Peiffer-Smadja, Nathan, Perpoint, Thomas, Petrov-Sanchez, Ventzislava, Peytavin, Gilles, Pham, Huong, Picone, Olivier, Piquard, Valentine, Puéchal, Oriane, Rabaud, Christian, Rosa-Calatrava, Manuel, Rossignol, Bénédicte, Rossignol, Patrick, Roy, Carine, Schneider, Marion, Su, Richa, Tardivon, Coralie, Tellier, Marie-Capucine, Téoulé, François, Terrier, Olivier, Timsit, Jean-François, Tual, Christelle, Van Der Werf, Sylvie, Vanel, Noémie, Veislinger, Aurélie, Visseaux, Benoit, Wiedemann, Aurélie, Yazdanpanah, Yazdan, Alavoine, Loubna, Behillil, Sylvie, Charpentier, Charlotte, Dechanet, Aline, Ecobichon, Jean-Luc, Frezouls, Wahiba, Houhou, Nadhira, Lehacaut, Jonathan, Lucet, Jean-Christophe, Manchon, Pauline, Nouroudine, Mariama, Quintin, Caroline, Thy, Michael, van der Werf, Sylvie, Vignali, Valérie, Chahine, Abir, Waucquier, Nawal, Migaud, Maria-Claire, Djossou, Félix, Mergeay-Fabre, Mayka, Lucarelli, Aude, Demar, Magalie, Bruneau, Léa, Gérardin, Patrick, Maillot, Adrien, Payet, Christine, Laviolle, Bruno, Laine, Fabrice, Paris, Christophe, Desille-Dugast, Mireille, Fouchard, Julie, Pistone, Thierry, Perreau, Pauline, Gissot, Valérie, Le Goas, Carole, Montagne, Samatha, Richard, Lucie, Bouiller, Kévin, Desmarets, Maxime, Meunier, Alexandre, Lefévre, Benjamin, Jeulin, Hélène, Legrand, Karine, Lomazzi, Sandra, Tardy, Bernard, Gagneux-Brunon, Amandine, Bertholon, Frédérique, Botelho-Nevers, Elisabeth, Kouakam, Christelle, Leturque, Nicolas, Roufai, Layidé, Amat, Karine, Espérou, Hélène, Hendou, Samia, van Agtmael, Michiel, Algera, Anne Geke, Appelman, Brent, van Baarle, Frank, Bax, Diane, Beudel, Martijn, Bogaard, Harm 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Marry, Stijnis, Cornelis S., Stilma, Willemke, Teunissen, Charlotte, Thoral, Patrick, Tsonas, Anissa M, Tuinman, Pieter R., van der Valk, Marc, Veelo, Denise, Volleman, Carolien, de Vries, Heder, Vught, Lonneke A., van Vugt, Michèle, Wouters, Dorien, Zwinderman, A. H (Koos), Brouwer, Matthijs C., Wiersinga, W. Joost, Vlaar, Alexander P.J., Tompkins, Miranda F., Alba, Camille, Hupalo, Daniel N., Rosenberger, John, Sukumar, Gauthaman, Wilkerson, Matthew D., Zhang, Xijun, Lack, Justin, Oler, Andrew J., Dobbs, Kerry, Delmonte, Ottavia M., Danielson, Jeffrey J., Bettini, Laura Rachele, D’Angio, Mariella, Beretta, Ilaria, Imberti, Luisa, Sottini, Alessandra, Quaresima, Virginia, Quiros-Roldan, Eugenia, Rossi, Camillo, Children's Hospital, HUS Children and Adolescents, Clinicum, Department of Medicine, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, AII - Infectious diseases, ANS - Neuroinfection & -inflammation, Neurology, Infectious diseases, Center of Experimental and Molecular Medicine, APH - Aging & Later Life, APH - Global Health, APH - Quality of Care, AII - Amsterdam institute for Infection and Immunity, APH - Health Behaviors & Chronic Diseases, Global Health, APH - Methodology, Graduate School, ACS - Heart failure & arrhythmias, Anesthesiology, ACS - Diabetes & metabolism, APH - Digital Health, APH - Personalized Medicine, ACS - Microcirculation, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Laboratory of Human Genetics of Infectious Diseases (Necker Branch - INSERM U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Rockefeller University [New York], Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Helix [San Mateo, CA], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Özçelik, Tayfun, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Pathology, Asano, T., Boisson, B., Onodi, F., Matuozzo, D., Moncada-Velez, M., Renkilaraj, M. R. L. M., Zhang, P., Meertens, L., Bolze, A., Materna, M., Korniotis, S., Gervais, A., Talouarn, E., Bigio, B., Seeleuthner, Y., Bilguvar, K., Zhang, Y., Neehus, A. -L., Ogishi, M., Pelham, S. J., Le Voyer, T., Rosain, J., Philippot, Q., Soler-Palacin, P., Colobran, R., Martin-Nalda, A., Riviere, J. G., Tandjaoui-Lambiotte, Y., Chaibi, K., Shahrooei, M., Darazam, I. A., Olyaei, N. A., Mansouri, D., Hatipoglu, N., Palabiyik, F., Ozcelik, T., Novelli, G., Novelli, A., Casari, G., Aiuti, A., Carrera, P., Bondesan, S., Barzaghi, F., Rovere-Querini, P., Tresoldi, C., Franco, J. L., Rojas, J., Reyes, L. F., Bustos, I. G., Arias, A. A., Morelle, G., Kyheng, C., Troya, J., Planas-Serra, L., Schluter, A., Gut, M., Pujol, A., Allende, L. M., Rodriguez-Gallego, C., Flores, C., Cabrera-Marante, O., Pleguezuelo, D. E., Diego, R. P. D., Keles, S., Aytekin, G., Akcan, O. M., Bryceson, Y. T., Bergman, P., Brodin, P., Smole, D., Smith, C. I. E., Norlin, A. -C., Campbell, T. M., Covill, L. E., Hammarstrom, L., Pan-Hammarstrom, Q., Abolhassani, H., Mane, S., Marr, N., Ata, M., Ali, F. A., Khan, T., Spaan, A. N., Dalgard, C. L., Bonfanti, P., Biondi, A., Tubiana, S., Burdet, C., Nussbaum, R., Kahn-Kirby, A., Snow, A. L., Bustamante, J., Puel, A., Boisson-Dupuis, S., Zhang, S. -Y., Beziat, V., Lifton, R. P., Bastard, P., Notarangelo, L. D., Abel, L., Su, H. C., Jouanguy, E., Amara, A., Soumelis, V., Cobat, A., Zhang, Q., Casanova, J. -L., Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, French COVID cohort study group, The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, Rockefeller University, the St. Giles Foundation, the NIH (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at the George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the 'Investments for the Future' program (ANR-10-IAHU-01) and the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project, the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 Research and Innovation Program under grant agreement no. 824110 (EASI-genomics), the Square Foundation, Grandir–Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, Fondation du Souffle, Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the University of Paris. The French COVID Cohort study group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). The Neurometabolic Diseases Laboratory received funding from the European Union’s Horizon 2020 Research and Innovation Program (EasiGenomics grant no. 824110 COVID-19/PID12342). A.P., R.P.d.D., C.R.-G., and C.F. were funded by Instituto de Salud Carlos III (COV20_01333 and COV20_01334), the Spanish Ministry of Science and Innovation (RTC-2017-6471-1, AEI/FEDER, UE), Fundación DISA (OA18/017), and Cabildo Insular de Tenerife (CGIEU0000219140 and 'Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19'). The laboratories of G.N. and A.N. were supported by a grant awarded to Regione Lazio (PROGETTI DI GRUPPI DI RICERCA 2020) no. A0375-2020-36663, GecoBiomark. A. Amara’s laboratory was supported by ANR under the 'Investments for the Future' program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the FRM (EQU202003010193), ANR (ANR-20-COVI-000 project IDISCOVR and ANR-20-CO11-0004 project FISHBP), and the University of Paris (Plan de Soutien Covid-19: RACPL20FIR01-COVID-SOUL). This work was supported, in part, by the Division of Intramural Research, NIAID, NIH (grants 1ZIAAI001265 to H.C.S. and ZIA AI001270 to L.D.N.). The G.C. laboratory was supported by the Italian Ministry of Health (grant COVID-2020-12371617) and the intramural COVID Host Genetics program. The J.L.F. laboratory was supported, in part, by the Coopération Scientifique France-Colciencias (ECOS-Nord/COLCIENCIAS/MEN/ICETEX, 806-2018) and Colciencias contract 713-2016 (no. 111574455633). The V.S. laboratory was supported by ANR DENDRISEPSIS (ANR-17-CE15-0003) and ANR APCOD (ANR-17-CE15-0003-01), a Fast Grant from the Mercatus Center, FRM, University of Paris PLAN D’URGENCE COVID19. The N.M. laboratory was supported by Sidra Medicine (SDR400048) and the Qatar National Research Fund (grant No. NPRP9-251-3-045). A.-L.N. was supported by the Bettencourt Schueller Foundation and the International PhD program of the Imagine Institute. P. Bergman and C.I.E.S received support from the Center for Medical Innovation (CIMED), the Swedish Medical Research Council and the Stockholm County Council (ALF-project). Part of this work was generated within the European Reference Network for rare primary immunodeficiency, autoinflammatory and autoimmune diseases (RITA)., Members of French COVID Cohort Study Group: Laurent Abel1, Claire Andrejak2, François Angoulvant3, Delphine Bachelet4, Marie Bartoli5, Romain Basmaci6, Sylvie Behilill7, Marine Beluze8, Dehbia Benkerrou9, Krishna Bhavsar4, Lila Bouadma4, Sabelline Bouchez10, Maude Bouscambert11, Minerva Cervantes-Gonzalez4, Anissa Chair4, Catherine Chirouze12, Alexandra Coelho13, Camille Couffignal4, Sandrine Couffin-Cadiergues14, Eric d’Ortenzio5, Marie-Pierre Debray4, Lauren Deconinck4, Dominique Deplanque15, Diane Descamps4, Mathilde Desvallée16, Alpha Diallo5, Alphonsine Diouf13, Céline Dorival9, François Dubos17, Xavier Duval4, Brigitte Elharrar18, Philippine Eloy4, Vincent Enouf7, Hélène Esperou14, Marina Esposito-Farese4, Manuel Etienne19, Eglantine Ferrand Devouge19, Nathalie Gault4, Alexandre Gaymard11, Jade Ghosn4, Tristan Gigante20, Morgane Gilg20, Jérémie Guedj21, Alexandre Hoctin13, Isabelle Hoffmann4, Ikram Houas14, Jean-Sébastien Hulot22, Salma Jaafoura14, Ouifiya Kafif4, Florentia Kaguelidou23, Sabrina Kali4, Antoine Khalil4, Coralie Khan16, Cédric Laouénan4, Samira Laribi4, Minh Le4, Quentin Le Hingrat4, Soizic Le Mestre5, Hervé Le Nagard24, François-Xavier Lescure4, Sophie Letrou4, Yves Levy25, Bruno Lina11, Guillaume Lingas24, Jean Christophe Lucet4, Denis Malvy26, Marina Mambert13, France Mentré4, Amina Meziane9, Hugo Mouquet7, Jimmy Mullaert4, Nadège Neant24, Duc Nguyen26, Marion Noret27, Saad Nseir17, Aurélie Papadopoulos14, Christelle Paul5, Nathan Peiffer-Smadja4, Thomas Perpoint28, Ventzislava Petrov-Sanchez5, Gilles Peytavin4, Huong Pham4, Olivier Picone6, Valentine Piquard4, Oriane Puéchal29, Christian Rabaud30, Manuel Rosa-Calatrava11, Bénédicte Rossignol20, Patrick Rossignol30, Carine Roy4, Marion Schneider4, Richa Su4, Coralie Tardivon4, Marie-Capucine Tellier4, François Téoulé9, Olivier Terrier11, Jean-François Timsit4, Christelle Tual31, Sarah Tubiana4, Sylvie Van Der Werf7, Noémie Vanel32, Aurélie Veislinger31, Benoit Visseaux4, Aurélie Wiedemann25, Yazdan Yazdanpanah4, ANR-17-CE15-0003,DENDRISEPSIS,Analyse systémique des cellules présentatrices d'antigène dans le sepsis humain(2017), ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), Asano, T, Boisson, B, Onodi, F, Matuozzo, D, Moncada-Velez, M, Maglorius Renkilaraj, M, Zhang, P, Meertens, L, Bolze, A, Materna, M, Korniotis, S, Gervais, A, Talouarn, E, Bigio, B, Seeleuthner, Y, Bilguvar, K, Zhang, Y, Neehus, A, Ogishi, M, Pelham, S, Le Voyer, T, Rosain, J, Philippot, Q, Soler-Palacín, P, Colobran, R, Martin-Nalda, A, Rivière, J, Tandjaoui-Lambiotte, Y, Chaïbi, K, Shahrooei, M, Darazam, I, Olyaei, N, Mansouri, D, Hatipoğlu, N, Palabiyik, F, Ozcelik, T, Novelli, G, Novelli, A, Casari, G, Aiuti, A, Carrera, P, Bondesan, S, Barzaghi, F, Rovere-Querini, P, Tresoldi, C, Franco, J, Rojas, J, Reyes, L, Bustos, I, Arias, A, Morelle, G, Christèle, K, Troya, J, Planas-Serra, L, Schlüter, A, Gut, M, Pujol, A, Allende, L, Rodriguez-Gallego, C, Flores, C, Cabrera-Marante, O, Pleguezuelo, D, de Diego, R, Keles, S, Aytekin, G, Akcan, O, Bryceson, Y, Bergman, P, Brodin, P, Smole, D, Smith, C, Norlin, A, Campbell, T, Covill, L, Hammarström, L, Pan-Hammarström, Q, Abolhassani, H, Mane, S, Marr, N, Ata, M, Al Ali, F, Khan, T, Spaan, A, Dalgard, C, Bonfanti, P, Biondi, A, Tubiana, S, Burdet, C, Nussbaum, R, Kahn-Kirby, A, Snow, A, Bustamante, J, Puel, A, Boisson-Dupuis, S, Zhang, S, Béziat, V, Lifton, R, Bastard, P, Notarangelo, L, Abel, L, Su, H, Jouanguy, E, Amara, A, Soumelis, V, Cobat, A, Zhang, Q, and Casanova, J
Subjects: Male, SUBSETS, [SDV]Life Sciences [q-bio], Penetrance, REDUNDANT, COVID-19 (Malaltia), 0302 clinical medicine, Resposta immunitària, 80 and over, Medicine and Health Sciences, Medicine, Young adult, Child, X-linked recessive inheritance, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, 0303 health sciences, education.field_of_study, PYOGENIC BACTERIAL-INFECTIONS, virus diseases, Genetic Diseases, X-Linked, HUMANS, General Medicine, Middle Aged, PROTECTIVE IMMUNITY, 3. Good health, Pedigree, Settore MED/03, Immune System Diseases, Genetic Diseases, Child, Preschool, Cohort, medicine.symptom, SINGLE-STRANDED RNA, Adult, Adolescent, Aged, Alleles, COVID-19, Humans, Infant, Toll-Like Receptor 7, Young Adult, Immunology, Population, Asymptomatic, Article, 03 medical and health sciences, HOST-DEFENSE, Immune response, Allele, Preschool, education, 030304 developmental biology, TOLL-LIKE RECEPTORS, business.industry, RECOGNITION, Proteins, X-Linked, medicine.disease, Pneumonia, 3121 General medicine, internal medicine and other clinical medicine, PLASMACYTOID DENDRITIC CELLS, business, Proteïnes, 030215 immunology
Abstract: Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% of critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean: 36.7 years) from a cohort of 1,202 male patients aged 0.5 to 99 years (mean: 52.9 years) with unexplained critical COVID-19 pneumonia. None of the 331 asymptomatically or mildly infected male individuals aged 1.3 to 102 years (mean: 38.7 years) tested carry such TLR7 variants (p = 3.5 × 10-5). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (n=2, 5 and 38 years), or moderate (n=1, 5 years), severe (n=1, 27 years), or critical (n=1, 29 years) pneumonia. Two boys (aged 7 and 12 years) from a cohort of 262 male patients with severe COVID-19 pneumonia (mean: 51.0 years) are hemizygous for a deleterious TLR7 variant. The cumulative allele frequency for deleterious TLR7 variants in the male general population is < 6.5x10-4 We also show that blood B cell lines and myeloid cell subsets from the patients do not respond to TLR7 stimulation, a phenotype rescued by wild-type TLR7 The patients' blood plasmacytoid dendritic cells (pDCs) produce low levels of type I IFNs in response to SARS-CoV-2. Overall, X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years. Human TLR7 and pDCs are essential for protective type I IFN immunity against SARS-CoV-2 in the respiratory tract. Funding: The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, Rockefeller University; the St. Giles Foundation; the NIH (R01AI088364), the National Center for Advancing Translational Sciences (NCATS); NIH Clinical and Translational Science Award (CTSA) program (UL1TR001866); a Fast Grant from Emergent Ventures; Mercatus Center at the George Mason University; the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956); the Meyer Foundation; the JPB Foundation; the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01) and the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID); the French Foundation for Medical Research (FRM) (EQU201903007798); the FRM and ANR GENCOVID project, the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), and ANR AABIFNCOV (ANR-20-CO11-0001) projects; the European Union’s Horizon 2020 Research and Innovation Program under grant agreement no. 824110 (EASI-genomics). The French COVID Cohort study group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). The Neurometabolic Diseases Laboratory received funding from the European Union’s Horizon 2020 Research and Innovation Program (EasiGenomics grant no. 824110 COVID-19/PID12342). A.P., R.P.d.D., C.R.-G., and C.F. were funded by Instituto de Salud Carlos III (COV20_01333 and COV20_01334), the Spanish Ministry of Science and Innovation (RTC-2017-6471-1; AEI/FEDER, UE), Fundación DISA (OA18/017), and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). The laboratories of G.N. and A.N. were supported by a grant awarded to Regione Lazio (PROGETTI DI GRUPPI DI RICERCA 2020) no. A0375-2020-36663, GecoBiomark. A. Amara’s laboratory was supported by ANR under the “Investments for the Future” program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the FRM (EQU202003010193), ANR (ANR-20-COVI-000 project IDISCOVR and ANR-20-CO11-0004 project FISHBP), and the University of Paris (Plan de Soutien Covid-19: RACPL20FIR01-COVID-SOUL). This work was supported, in part, by the Division of Intramural Research, NIAID, NIH (grants 1ZIAAI001265 to H.C.S. and ZIA AI001270 to L.D.N.). The G.C. laboratory was supported by the Italian Ministry of Health (grant COVID-2020-12371617) and the intramural COVID Host Genetics program. The J.L.F. laboratory was supported, in part, by the Coopération Scientifique France-Colciencias (ECOS-Nord/COLCIENCIAS/MEN/ICETEX; 806-2018) and Colciencias contract 713-2016 (no. 111574455633). The V.S. laboratory was supported by ANR DENDRISEPSIS (ANR-17-CE15-0003) and ANR APCOD (ANR-17-CE15-0003-01), a Fast Grant from the Mercatus Center, FRM, University of Paris PLAN D’URGENCE COVID19. The N.M. laboratory was supported by Sidra Medicine (SDR400048) and the Qatar National Research Fund (grant No. NPRP9-251-3-045)
Published: 2021

38. Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Author: Labeau, Sonia O, Afonso, Elsa, Benbenishty, Julie, Blackwood, Bronagh, Boulanger, Carole, Brett, Stephen J, Calvino-Gunther, Silvia, Chaboyer, Wendy, Coyer, Fiona, Deschepper, Mieke, François, Guy, Honore, Patrick M, Jankovic, Radmilo, Khanna, Ashish K, Llaurado-Serra, Mireia, Lin, Frances, Rose, Louise, Rubulotta, Francesca, Saager, Leif, Williams, Ged, Blot, Stijn I, Dritan, Muzha, Antoni Margarit Ribas, Fernando, Lipovesty, Cecilia, Loudet, Fiona, Coyer, Philipp, Eller, Nafseen, Mostafa, Patrick, M Honoré, Vanesa Mercado Telleria, Jasmina, Smajic, Paula Cristina Nogueira, Khalid Mahmood Khan Nafees, Romuald, Hentchoya, Louise, Rose, Javiera, Soledad, Frances, Lin, Yenny, Cardenas, Amylkar Garay Reyes, Alan, Sustic, Meropi, Mpouzika, Tamas, Vymazal, Hanne Irene Jensen, Hernan, Aguirre-Bermeo, Liivi, Maddison, Maija, Valta, Silvia, Calvino-Gunther, Frank, Bloos, Faustina Excel Adipa, Vasilios, Koulouras, Judy, Enamorado, Zsuzsann, Ágoston, Hrönn, Birgisdóttir, Amit, Gupta, Mohan, Gurjar, Bram, Kilapong, Seyed Mohammadreza Hashemian, Ignacio, Martin-Loeches, Julie, Benbenishty, Andrea, Cortegiani, Kelly, Fletcher, Yoshiro, Hayashi, Wangari, Waweru-Siika, Khalid, Abidi, Sang-Min, Lee, Burhan, Hadri, Mihails, Dolgusevs, Fayez François Abillama, Tomas, Jovaisa, Cyril, Thix, Muhammed, Elhadi, Basri Mat Nor, Shanti, Ratnam, Mohd Zulfakar Mazlan, Sundaresan, Maiyalagan, Luis, Sánchez-Hurtado, Adrian, Belii, Mendsaikhan, Naranpurev, Prabha, Gautam, Dylan De Lange, Rachael, Parke, Rose Ekama Ilesanmi, Mirjana, Shosholcheva, Antonija, Petosic, Ranveig, Lind, Madiha Hashmi Ffarcsi, Javier, Bogarin, Aaron Mark Hernandez, Malgorzata, Mikaszewska-Sokolewicz, Bruno, Sousa, Dana, Tomescu, Dorel, Sandesc, Theogene, Twagirumugabe, Vitaly, Gusarov, Maie, Ebaid, Radmilo, Jankovic, Gari, Slobodianiuk, Andrea, Martonova, Rihard, Knafelj, Mervyn, Mer, Emilio, Maseda, Bernardo, Panka, Joerg, C Schefold, Eva, Joelsson-Alm, Konlawij, Trongtrakul, Lorna, Merritt-Charles, Lamia Ouanes Besbes, Yalım, Dikmen, Lesia, Zgrzheblovska, Mark, Fielding, Francesca, Rubulotta, Ashish, K Khanna, Leif, Saager, Ingrid von der Osten, Alban, Greca, Alma, Cani, Nordian, Xhindi, Genci, Hyska, Antonio Margarit Ribas, Susana, Pinto, Paulo, Alves, Romina, Esposito, Emanuel, Valgolio, John Thomas Sanchez Minope, Antonio, Abdala, Maria, Ayala, Silvina, Bravo, Ana, Bantar, Patricia, Delgado, Gustavo, Badariotti, Fernando, Lipovestky, Ana, Diaz, Pablo, Saul, Mariano, Setten, Alejandra, Aucapina, Ysica, Acosta, Victor, Gonzalez, Luis, Camputaro, Fernando, Baccaro, Robert, Villa, Marcela, Mastantuono, Emiliano, Dean, Oscar Fernández Rostello, Patricia, Brizuela, Julio Ricardo Bartoli, Matias, Guereschi, Cristian, Quiroga, Sofia, Putruele, Paula, Villegas, Veronica, Curilen, Ruben, Fernandez, Mariangeles Gabriela Nocheretti, Rosana Gabriela Escalante, Cecilia Inés Loudet, Silvia, Fernandez, Ana Laura Gonzalez, Gustavo Andres Alvarez, Federico, Iglesias, Silvia, Chaparro, Graciela, Zakalik, Gonzalo, Pagella, Matías, Baini, Pierina Arias Campos, Ignacio, Sabbag, Armando, Schmukler, Imelda Perdomo Fonseca, Gonzalo Martín Alvarez, Mario, Ramirez, Fernando, Tapia, Carlos Alejandro Bascary, Graciela Del Valle Gimenez, Fernando Pablo Bertoletti, Esteban, Milioto, Pablo Julio Maldonaldo Bonsignore, Maria Alejandra Fernandez, Julie, Smith, Tim, Chimunda, Lorraine, Thompson, Teena, Maguire, Wendy, Chaboyer, Stacey, Watts, Marion, Mitchell, Madeleine, Powell, India, Lye, Leanne, Parsons, Nerilee, Baker, Claire, Reynolds, Amy, Thompson, Kristy, Masters, Kellie, Sosnowski, Lynette, Morrison, Gavin, D Leslie, Ramanathan, Lakshmanan, Alexis, Tabah, Wendy, Brown, Sharon, McDowell-Skaines, Andrea, Mclucas, Chris, Smith, Mandy, Tallot, Sarah, Jones, Michelle, Barakat-Johnson, Thomas, Leong, Rand, Butcher, Kerrie, Martin, Philipp, Douschan, Dirk von Lewinski, René, Schmutz, Uta, Kolussi, Fatema, Salman, Zainab, Ateya, Koen De Decker, Niels Van Regenmortel, Anita, Jans, Patricia, Wijnands, Stefano, Coremans, Patrick, M Honore, David De Bels, Tanja, Depuydt, Caroline, Paillet, Luc-Marie, Jacquet, Walter, Swinnen, Francis, Hannes, Matthia, Mergeay, Stijn Van de Velde, Silvie, Allaert, Pieter, Hoste, Christophe, Borin, Sandrine, Balon, Vincent, Fraipont, Patrick, Biston, Nicolas De Schryver, Thierry, Dugernier, Ilse Van Cotthem, Angelica Olivetto de Almeida, Silvia Angelica Jorge, Delmiro, Becker, Raysa Cristina Schmidt, Evellyn, Oliveira, Aline, Ramalho, Eliane, Mazocoli, Audrey, Fioretti, Elaine, Barros, Leticia, Serpa, Suzana, Bianchini, Ticiane, Campanili, Taís, Pantaleao, Paulo Carlos Garcia, Ana Lucia Vitti Ronchini, Rayanne, Santos, Nurulhuda Binti, A Manap, Sean, Bagshaw, Dominic, Carney, Jon, Davidow, Ella, Rokosh, Andréa Maria Laizner, Samantha, Smith, Megan, Mcquirter, Betty Star Kampayana, René, Favre, Martin, Sills, Julie, Dallaire, Cathy, Becker, Sherissa, Microys, Bonnie, Bowes, Jennifer, Lajeunesse, Rishi, Ghosh, Jacqueline, Baptiste-Savoie, Rose, Raizman, Gabriel, Suen, Noushin, Taghavi, Orla, Smith, Clare, Fielding, Julieta, Canales, Pia, Molina, Javiera, Chaparro, Maria Idalia Sepulveda, Matias Jesús Flamm Zamorano, Pamela, Rocha, Ximena, Villanueva, Paola, Araya, Meneses, Dayan, Fernando, Avalos, Xiaohan, Li, Liu, Yu, Xinxia, Li, Xiaoyan, Chen, Zhixia, Jiang, Jing, Yang, Jingfang, Chen, Lei, Yang, Kefang, Wang, Jie, Gao, Xiuhua, Fang, Ronghua, Zhao, Xinhua, Xia, Hongmei, Liu, Jing, Li, Haiyan, Wang, Gen, Meng, Yanhong, Di, Damei, Wang, Rong Hua Zhao, Li Ping Hu, Peipei, Xu, Qing Feng Jiao, Hai Yun Wang, Chun Jie Xia, Yan, Liu, Mei, Ye, Yan, Wan, Wenmei, Wang, Yajun, Ding, Aiua, Ren, Yan, Gao, Qi, Li, Guifang, Du, Yanling, Shen, Yanming, Ding, Ning, Li, Cui, Yuan, Lei, Tan, Qiang, Lin, Hailing, Guo, Howe, Yan, Xiao, Xu, Wei, Zhang, Jinxian, Liang, Libing, Zhang, Eryun, Tian, Qian, Zhao, Lin, Insu, Jingwen, Dong, Yanmei, Gu, Ying, Liu, Lina, Zhao, Wei, Wang, Hongmei, Qiao, Lili, Tuo, Mengmeng, Lv, Jin Yu Zhu, Jifen, Zhu, Ying, Wei, Man, Liu, Yin, He, Jiyin, Cheng, Jin, Liu, Jia, Na, Dongfang, Wei, Qing, Li, Xiaoying, Wu, Huan, Duan, Dongliang, Lin, Qiong, Liang, Xiaofang, Luo, Yunfeng, Xiong, Rong Fen Huang, Jing, Fu, Tao, Zan, Man, Ye, Zeya, Shi, Yanfei, Long, Yang, Lei, Xiaodi, Liu, Chen, Yumei, Lingling, Wang, Yali, Zhang, Yan, Xu, Cheng, Wang, Zhijuan, Chengxia, Sun, Jinhui, Song, Yingli, Wang, Xiumei, Liu, Yupeng, Liu, Yuxia, Yuan, Qingping, Huang, Fengling, Yang, Yun, Wu, Xianping, Luo, Xiaowu, Bai, Hong, Zheng, Min, Song, Yue, Sun, Zhangshuangzi, Li, Feifei, Luo, Miao, Liu, Li Chuntang Li, Xinjian, Li, Guiping, Zhang, Lina, Xiao, Tingting, Yu, Guangyuan, Gao, Wei, Wei, Fanglan, Wang, Ting, Han, Tingting, Li, Zeng, Qi, Jing Mei Zeng, Yan, Long, Fuqun, Pan, Jing, Wang, Guoxue, He, Haiyan, Chen, Feifei, Zhang, Chao, Yu, Gao, Chunhua, Xiuying, Yao, Dongmei, Bai, Liu, Lu, Xuelian, Xu, Yan, Wang, Xuejuan, Liang, Zhang, Na, Aizhi, Zhang, Xiaochun, Hu, Hui, Zhang, Ruixia, Wang, Poon Shing Tak, Sung Wai Ho, Qun Xia Jiang, Xinran, Ding, Liu, Hong, Limei, Miao, Zhaoxia, Feng, Liping, Huang, Juan, Wu, Yuping, Wang, Jiye, Guo, Baoke, Zhang, Chaoqun, Ma, Han, Yu, Congcong, Liu, Min, Ding, Linlin, Luan, Jing, Zheng, Shanshan, Lv, Shumin, Jiang, Wenzhen, Cao, Xiujuan, Xue, Guangyan, Liu, Xiyan, Wei, Youru, Jiang, Zhiru, Yao, Gao, Li, Jinhua, Li, Wenwen, Zhao, Mei, Jiang, Junping, Hao, Jing, Zhang, Caiju, Song, Feifei, Chen, Shuhui, Wang, Lili, Hu, Deyan, Cao, Jianhong, Wan, Xiaomin, Wang, Hongyan, Shao, Zhenxia, Zhang, Xia, Cui, Jingyu, Liu, Lijuan, Zhao, Xingguo, Li, Limei, Fan, Ling, Zhang, Min, Yu, Biyan, Li, Chunxia, Li, Ling, Liu, Xuelian, Liu, Wenmin, Chen, Yan, Li, Zhang, Zhigang, Yuchen, Wu, Chenghau, Mu, Guoyan, Zhu, Fan, Yang, Qi, Bo, Ling, Li, Meili, Chen, Jing Hua Jiang, Hai, Yin, Xuelian, Pang, Yue Ying Gong, Shunzhu, Yang, Xiaoli, Yan, Xianhong, Zheng, Dehong, Lei, Lei, Lei, Yinhua, Guo, Lihong, Liu, Jing, Yu, Wei, Sun, Aiping, Bi, Weiwei, Li, Yang, Wu, Ji, Li, Dongshu, Ni, Zijing, 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Mar Diaz Salcedo, Javier, Ripolles-Melchor, Eugenio, Martinez-Hurtado, Jorge Duerto Alvarez, María Luisa Bravo Arcas, Juan Ignacio Torres Gonzalez, Ana Belén Sánchez de la Ventana, Pablo Lopez-Arcas Calleja, Raquel Garcia Alvarez, Purificacion Sanchez Zamora, Alvaro Ortega Guerrero, Rosario, Cosano, Jonathan, Perez-Vacas, Margarita, Campos-Perez, Emma Moreno Barreiro, Losune Cano Sanchez, Monica Garcia Diaz, Raquel, Jimenez, Lorena Del Rio Cabajo, Daniel Sancho Muriel, Helena Fernandez Alonso, Ana Wensell Fernández, Isabel Santín Piñan, Guillermo Muñiz Albaiceta, Maria Cristina Iglesias Fernandez, Francisco Javier Saenz Abos, Pablo, Monedero, Ramon Molina Chueca, Lydia Gallego Aguirre, Silvia Call Manosa, Carmen Partera Luque, Neus, Calpe, Monica Recio Losilla, Meritxell Tapia Fores, Olga, Farre, Oscar, Fernandez, M Del Rosario Villar Redondo, Donaldo, S Arteta Arteta, Maria Angeles Hurtado Sanchez, Cristina Paños Espinosa, Laura Martinez Reyes, Laura Claramunt Domenech, Carmen Velasco Guillén, Josep Trenado Alvarez, Mercedes Del Cotillo, Jesus Emilio Barrueco-Francioni, Belen Burgos Conde, Maria Pilar Sogues Blanco, Maria Luisa Blasco, Ana Isabel Clement, Clara, Hurtado, Luz Coronado Sanz, David, Perez-Torres, Estefanía, Prol-Silva, Jorge, Pereira, Iván Areán González, Anastasio Espejo Cano, Cesar Rodriguez Nuñez, Inmaculada Lorenzo Fernadez, Alejandra Azahara Marguello Fernandez, Rosa Del Bosque Diez, Badiola, Hilario, Begoña, Zalba-Etayo, Ana, Pascual-Bielsa, Preveen, Banwarie, Dick, Nahar, Alisha van Axel, Naraindath, N Boedjawan, Erika Backlund Jansson, Ann-Sofie, Malvemyr, Lotta, Johansson, Ulla, Sandberg, Catarina, Tingsvik, Gunilla, Mattsson, Gun, Löf, Martin, Spångfors, Mona, Ringdal, Sebastian, Geijer, Lotti, Orvelius, Mia, Hylen, Caroline, Lagerhäll, Eva, Åkerman, Viveca Hamback Hellkvist, Ulrica, Mickelsson, Ewa, Wahlbom, Ing-Marie, Larsson, Ewa, Wallin, Filippo, Boroli, Solenne, Ory, Margaret Lynn Jong, Alexander, Dullenkopf, Martin, Lang, Yvan, Fleury, Marianne, Maus, Nawfel, Ben-Hamouda, Anne, Fishman, Mei Yu Hsu, Shu Chuan Chang, Konlawij, Trongtratul, Chaiwut, Sawawiboon, Sunthiti, Morakul, Bodin, Khwannimit, Keevan, Singh, Dale, Ventour, Dianne, Figaro-Barclay, Sasha, Sankar-Maharaj, Mhamed Sami Mebazaa, Salma, Kamoun, Souheil, Elatrous, Lamia, Besbes, Fekri, Abroug, Walid, Naija, Youssef Zied Elhechmi, Walid, Sellami, Zied, Hajjej, Takoua, Merhabene, Imen, Talik, Ozlem Ozkan Kuscu, Ozcengiz, Dilek, Avşar, Zerman, Hayriye Cankar Dal, Sema, Turan, Semih, Aydemir, Hakan, Yilmaz, Duygu Kayar Calili, Seval, İzdes, Melike, Cengiz, Ayça, Gümüş, Banu, Taşdemir, Ali, Kağnıcı, Mustafa, Ay, Serap Avcı Ay, Gulbahar, Caliskan, Turkay, Akbas, Abidin Oner Balbay, Serdar, Efe, Volkan, Inal, Gülseren, Elay, Pınar, Karabacak, Boğaç, Özserezli, Evren, Şentürk, Oktay, Demirkiran, Suha, Bozbay, Elif, Erdogan, Mustafa, Akker, Nebia, Peker, Asu, Ozgultekin, Sibel Ocak Serin, Can, Turan, Gulsah, Karaoren, Senay, Goksu, Sait, Karakurt, Huseyin, Arikan, Fethi, Gül, İsmail, Cinel, Iskender, Kara, Hasan Nabi Undar, Yesim Serife Bayraktar, Jale Bengi Çelik, Murat Emre Tokur, Demet Tok Aydin, İsmail, Yildiz, Beysim, Özcan, Başar, Erdivanli, Ahmet, Eroglu, Devrim, Akdağ, Nurdan, Ünlü, Adonis, Dungca, Ashwaq, Ali, Bindu, Thankamma, Paul Eric Reyes, Sini, John, Ajitha, Rajendran, Fatima Kasem El Ahmad, Kathleen Ann Smiley, Susanna, Hojden, Mia Thorning Miller, Vishnu Das Sasidharan Nair, Maria Gracia San Antonio, Khaled Al Qawasmeh, Sabah Abu Shawish, Hilary, Twiggs, Ines, Rosado, Volodymyr, Babych, Faye, Morren, Charlotte, Young, Nicola, Vaughan-Jones, Stephanie, Harris, Karen, Burns, Carmel, Georgiev, Rosina, Shayamano, Ian, Kerslake, Peter, Creber, Ana, Vochin, Catherine, O'Brien, Paul, Caddell, Samantha, Hagan, Mandy, Hughes, Tomasz, Torlinski, James, Sherwin, Santhana, Kannan, Amber, Markham, Richard, Lebon, Jason, Cupitt, Julius, Cranshaw, Nigel, White, Victoria, Marriott, Wendy, Milner, Casiano Barrera Groba, Joao, Azoia, Petra, Polgarova, Shaly, George, Ritoo, Kapoor, Ceri, Lynch, Nathalie, Fox, Karen, Cranmer, Natalie, Fox, Thomas, Llewellym, Kelly, Matthews, Louise, Maltby, Jowena, Ibao, Karen, Boulton, Rachel, Jarman, Karen, Baxter, Ashok Sundai Raj, Arif, Moghal, Joanne, White, Suzanne, Barrowcliffe, Mark, Pulletz, Vaarisan, Ganeshalingam, Rosaleen, Baruah, Carole, Boulanger, Helen, Baker, Justin, Woods, Poe Poe Ei, Vongayi, Ogbeide, Paul, Hayden, Jennifer, Hughes, Madhu, Balasubramanian, Armorel, Salberg, Rajnish, Saha, Dagmar, Holmquist, Claire, Derbyshire, Neil, Smith, Elizabeth, Stones, Jane, Ademokun, Monica, Popescu, Maria Schofield Legorburo, Samantha, North, Carole, Brett, Helen, Jaundoo, Jayne, Craig, Simon, Whiteley, Clare, Howcroft, Liz, Wilby, Peter, Delve, David, Shaw, Karen, Williams, Ingeborg, D Welters, Jane, Mcmullen, Stephen, Brett, Leah, Flores, Treiza, Trueman-Dawkins, Mae, Templeton, John, Adams, Catherine, Smith, John, Prowle, Heather, Byers, Andrea, Mcdonnell, Bernd Oliver Rose, Rosie, Reece-Anthony, Luis, Mendes, Marcela, Vizcaychipi, Rhian, Bull, Grace, Lacaden, Eleanor, Santiago, Carlos Castro Delgado, Sarah, Farnell-Ward, Elaine, Thorpe, Justine, Somerville, Anne, Williams, Donna, Cummings, Helen, Derrick, Sarah, Brumwell, Claire, Randell, Nicola, Mccann, Emma, Aves, Gillian, Berry, Tamas, Szakmany, Una, Gunter, Paul, Pulak, Nikki, Sarkar, Kerry, Wright, Vitor, Gomes, Jones, Jo, Ruth, Palfrey, Julie, Camsooksai, Abby, Lewis, Antony, Eneas, Ascanio, Tridente, Louise, Barr, Beverley, Thomas, Emma, Parkin, Daniel, Horner, Christian, Frey, Suzanne, Bench, Rachel, Baumber, Phil, Broadhurst, Matthew, Jackson, Lynne, Williams, Michele, Clark, Jonathan, Paddle, Sarah, Bean, Sarah, Buckley, Christopher, Palfreeman, Sophie, Liu, Nicola, Allison, Ben, Attwood, Penny, Parsons, Victoria, Houghton, Sarah Jane Turner, David, Higgins, Egidija, Bielskute, Nicola, Horrigan, Reni, Jacob, Karen, Habgood, Ahmed, Zaki, Amy, Collins, Jenny, Lord, Charalice, Ramiro, Agnieszka, 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A.S., Goller, S., Afonso, E., Larina, E., Labeau, Sonia O. 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Bielskute E., Horrigan N., Jacob R., Habgood K., Zaki A., Collins A., Lord J., Ramiro C., Kubisz-Pudelko A., Kotze M., Williams H., Iovenko I., Tsarev A., Briva A., Mendez G., Napolitano L., Teig M., Rodriguez G.E., Ben-Jacob T., Potestio C., Eng T., Mahanes D., Khanna A., Duggal A., Nananmori M., Lois M., Karamchandani K., Bealer C., Barefield C., Terry D., Fivecoat P., Idowu O., Cata J., Clesi T., Peterson J., Hatton K., Dhaliwal J., Mueller D., Tao J., Eltorai A.S., Pastores S.M., Remor N., Salazar J., Barkas D., Joffe A., Barnes C., Sona C., Schallom M., Short J., Lorenzo J., Von Der Osten I., Borkowska M., Demarre L., Pleitinckx V., Xing C., Debue A.-S., Goller S., Larina E., Labeau, S. O., Blackwood, B., Brett, S. J., Deschepper, M., Francois, G., Honore, P. M., Khanna, A. K., Williams, G., Blot, S. I., Ribas, A. M., Telleria, V. M., Nogueira, P. C., Nafees, K. M. K., Reyes, A. G., Jensen, H. I., Adipa, F. E., Agoston, Z., Hashemian, S. M., Lee, S. -M., Abillama, F. F., Nor, B. M., Mazlan, M. Z., Sanchez-Hurtado, L., De lange, D., Ilesanmi, R. E., Ffarcsi, M. H., Hernandez, A. M., Schefold, J. C., Besbes, L. O., Minope, J. T. S., Rostello, O. F., Bartoli, J. R., Nocheretti, M. G., Escalante, R. G., Loudet, C. I., Gonzalez, A. L., Alvarez, G. A., Campos, P. A., Fonseca, I. P., Alvarez, G. M., Bascary, C. A., del Valle Gimenez, G., Bertoletti, F. P., Bonsignore, P. J. M., Fernandez, M. A., Leslie, G. D., Mclucas, A., Jacquet, L. -M., de Almeida, A. O., Jorge, S. A., Schmidt, R. C., Garcia, P. C., Ronchini, A. L. V., Manap, N. B. A., Laizner, A. M., Mcquirter, M., Kampayana, B. S., Sepulveda, M. I., Zamorano, M. J. F., Zhao, R. H., Hu, L. P., Jiao, Q. F., Wang, H. Y., Xia, C. J., Insu, L., Zhu, J. Y., Zhu, J. F., Huang, R. F., Wang, L. L., Song, J. H., Liu, X. M., Li, Z. S., Li, L. C., Zeng, J. M., Hu, X. C., Wang, R. X., Tak, P. S., Ho, S. W., Jiang, Q. X., Huang, L. P., Liu, X. L., Jiang, J. H., Gong, Y. Y., Lei, D. H., Bi, A. P., Zhao, H. M., Cao, Z. Q., Wu, S. F., Tian, X. F., Feng, Z. X., Liu, X. Z., Jiang, Z. X., Wang, G. X., Hu, R. L., Li, X. Q., Yu, Z. J., Yang, Y. X., Gama, L. M. S., Hernandez, J. S., Ochoa, M. -E., Reyes, A. J. G., Filipovic-Grcic, I., Vukovic, A., Pecenkovic, S., Suput, A., Radivojevic, R. C., Culjak, H., Adam, V. N., Pedersen, K. R., Kjaergard, I. E., Kodal, A. M., Hansen, T. C. B., Pedersen, A. S. B., Thomsen, T. D., Frandsen, T. M., Bliksted, I. A., Tamayo, L. M., Tutillo, D. R. M., Hurtado, C. V., Garcia, M. F., Kutimets, M., Lofqvist, C., Sakki, J. -K., Valta, M. A., Plantefeve, G., Deserts, M. D., Gunther, S. C., Timsit, J. -F., Farkas, J. -C., Bosl, K., Schuppel, S., Stubner, A., Osei, I. P., Kusi-Appiah, A. -C., Yakubu, Y. H., Patsiou, E. -C., Stalika, K. M. M., Enamorado, J. E., Jonasdottir, R. J., Lestari, M. I., Finn, D. O. C. R., Mcpherson, S., Ghioldi, D. M., Bruno, A. V., Maggiore, S. M., Volta, C. A., Taibi, M. R., Tranello, F. P., Giusti, G. D., Martin, M. A., Correia, M. C., Kim, J. H., Kim, K. C., Bae, J. -M., Park, S. Y., Park, T. S., Lee, H. B., Kim, S. C., Chee, H. K., Huh, J. W., Sim, Y. S., Ahn, J. -J., Kang, B. J., Lee, W. -Y., Lee, S. J., Feghaly, M. E., Belkhair, W. A., Tababa, O. W. E., Alkhumsi, S. I. R., Alshrif, A. I., Aboufray, A. A., Triki, A. R., Zahra, H. B., Al-Alawi, M. M. S., Ghula, M. A. A., Bahrin, L. K. K., Deva, S. R., Rahim, A. H. A., Hassan, W. N. W., Ismail, W. N. W., Ali, M. N., Khoo, T. M., Samat, N. M., Tong, J. M. G., Adib, N. A. N., Nor, M. B. M., Sulaiman, S. R., Foong, K. W., Hua, N. P., Zermeno, J. M., Nava, C. L. L., Nandyelly, S. J. R., Sanchez-Hurtado, L. A., Nava, L. P. A., Herrera, J. G., de Anda, G. F. V., Namendys-Silva, S. A., Romero-Gonzalez, J. P., Sosa, M. A., de Molina Serrano, J. I. R., Iburrigarro, S. R., Padilla, N. R. C., Pineda, A. A. V., Villafuerte, M. V. E., Herrera, M. O. G., Subedi, N. B., Pathak, S. D., Vermeijden, J. W., Gerritsen, R. T., Fijen, J. -W., Adejumo, P. O., Sankey, B. J., Olsen, B. F., Jensen, K. D., Johansen, B. F., Finnstrom, I. J., Skorstad, E. M., Lunde, G. A., Akselsen, G. R., Monstad, K. R., Hogvall, L., Malmin, S. K., Andersen, M. H., Hargott, R. F., de Jesus Ortiz, A., Cabral, D. M. B., Rivas, J. C., Moreira, M. L., Ellazar, C. G., Cerezo, F. D., Palo, J. E., Aperocho, C. A. J., Figueiredo, M. F., Pinheiro, C. M., Rita, C. S., Feranandes, A. M., Pinto, V. M. V., Bispo, B. M., Lima, A., Alsheikhly, A. S., Guran, C. T., Filipescu, D. C., Scutariu, M. A., Ebaid, M. S., Velickovic, D., Rajkovic, M., Stanojevic, M., Turcan, A., Lancaricova, D., Yeni, N. P., Syed, M. R., Navarro, J. A., De Pablo, A. M., Llinas, A. A., Lajara, M. A. G., Nieto, M. V., Pena, J. M. G., Gorgolas, M. C., Isasi, M. A., Salva-Costa, V., Garzon-Tovar, C., Olivares, P. G., de Ceballos, J. P. G., Polo, A. B. C., del Mar Diaz Salcedo, M., Alvarez, J. D., Arcas, M. L. B., Gonzalez, J. I. T., de la Ventana, A. B. S., Calleja, P. L. -A., Alvarez, R. G., Zamora, P. S., Guerrero, A. O., Barreiro, E. M., Sanchez, L. C., Diaz, M. G., Muriel, D. S., Alonso, H. F., Fernandez, A. W., Pinan, I. S., Albaiceta, G. M., Fernandez, M. C. I., Abos, F. J. S., Chueca, R. M., Aguirre, L. G., Manosa, S. C., Luque, C. P., Losilla, M. R., Fores, M. T., del Rosario Villar Redondo, M., Arteta Arteta, D. S., Sanchez, M. A. H., Espinosa, C. P., Reyes, L. M., Domenech, L. C., Guillen, C. V., Alvarez, J. T., del Cotillo, M., Barrueco-Francioni, J. E., Conde, B. B., Blanco, M. P. S., Blasco, M. L., Clement, A. I., Sanz, L. C., Gonzalez, I. A., Cano, A. E., Nunez, C. R., Fernadez, I. L., Fernandez, A. A. M., Boedjawan, N. N., Jansson, E. B., Malvemyr, A. -S., Lof, G., Spangfors, M., Lagerhall, C., Akerman, E., Hellkvist, V. H., Larsson, I. -M., Jong, M. L., Hsu, M. Y., Chang, S. C., Mebazaa, M. S., Elhechmi, Y. Z., Kuscu, O. O., Dal, H. C., Calili, D. K., Izdes, S., Gumus, A., Tasdemir, B., Kagnici, A., Ay, S. A., Balbay, A. O., Ozserezli, B., Senturk, E., Serin, S. O., Gul, F., Cinel, I., Undar, H. N., Bayraktar, Y. S., Celik, J. B., Tokur, M. E., Aydin, D. T., Yildiz, I., Ozcan, B., Akdag, D., Unlu, N., Reyes, P. E., Ahmad, F. K. E., Smiley, K. A., Miller, M. T., Antonio, M. G. S., Qawasmeh, K. A., Shawish, S. A., Groba, C. B., Raj, A. S., Ei, P. P., Legorburo, M. S., Welters, I. D., Mcmullen, J., Mcdonnell, A., Rose, B. O., Delgado, C. C., Mccann, N., Turner, S. J., Rodriguez, G. E., Eltorai, A. S., Pastores, S. M., Demarre, L., and Debue, A. -S.
Subjects: Male, Original, medicine.medical_treatment, artificial, Critical Care and Intensive Care Medicine, Medical and Health Sciences, Pressure ulcer, law.invention, Decubitus epidemiology, ICU, Morbidity, Mortality, Outcome, Pressure injury, Risk factors, Adult, Aged, Hospital Mortality, Humans, Patient Discharge, Prevalence, Risk Factors, Intensive Care Units, Respiration, Artificial, 0302 clinical medicine, decubitus epidemiology, pressure injury, pressure ulcer, outcome, risk factors, morbidity, mortality, law, Medicine and Health Sciences, adults, Medicine, Simplified Acute Physiology Score, icu, ziekenhuissterfte, Immunodeficiency, intensive care, European Society of Intensive Care Medicine (ESICM) Trials Group Collaborators, mannen, volwassenen, COST, Intensive care unit, STATE, ULCERS, Underweight, medicine.symptom, Life Sciences & Biomedicine, Human, medicine.medical_specialty, risicofactoren, Decubitus epidemiology, ICU, Pressure injury, Pressure ulcer, Outcome, Risk factors, Morbidity, Mortality, pressure injuries, Intensive Care Unit, prevalentie, NO, 1117 Public Health and Health Services, DecubICUs Study Team, 03 medical and health sciences, Critical Care Medicine, Anesthesiology, General & Internal Medicine, Health Sciences, ouderen, Mechanical ventilation, Science & Technology, business.industry, decubitus, Risk Factor, 030208 emergency & critical care medicine, 1103 Clinical Sciences, Odds ratio, medicine.disease, Emergency & Critical Care Medicine, Confidence interval, 030228 respiratory system, Emergency medicine, kunstmatige ademhaling, RISK-FACTORS, business, respiration
Abstract: Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347, Funder: Flemish Society for Critical Care Nurses, Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score < 19, ICU stay > 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat.
Published: 2021
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39. Polyphenol intake and cardiovascular risk in the PREDIMED-Plus trial. A comparison of different risk equations

Author: Pilar Matía-Martín, Rafael Bartolomé Resano, José María Manzanares, J Alfredo Martínez, Ángel M. Alonso-Gómez, Álvaro Hernáez, Dora Romaguera, José J. Gaforio, Itziar Abete, Anna Tresserra-Rimbau, Ramon Estruch, Andrés González-Botella, Jesús Vioque, José V. Sorlí, Rosa M. Lamuela-Raventós, Michelle M. Murphy, Clotilde Vázquez, Josep A. Tur, Elena Rayó, Lucas Tojal-Sierra, Julia Wärnberg, José Manuel Santos-Lozano, Jordi Salas-Salvadó, Carolina Sorto-Sánchez, Maria Angeles Zulet, E. Ros, Alfredo Gea, Facundo Vitelli-Storelli, Helmut Schröder, José Lapetra, Luis Serra-Majem, Josep Vidal, Aurora Bueno-Cavanillas, Casimira Medrano, Xavier Pintó, Ana María Gómez-Pérez, Vicente Martín-Sánchez, Predimed-Plus Trial Investigators, María Rubín-García, Monstserrat Fitó, M. Rosa Bernal-Lopez, Nancy Babio, Dolores Corella, Laura Álvarez-Álvarez, Sara Castro-Barquero, Edelys Crespo-Oliva, Jose Lopez-Miranda, Miguel Ángel Martínez-González, Estefanía Toledo, Antonio Garcia-Rios, Lidia Daimiel, and Carolina Ortega-Azorín
Subjects: Male, medicine.medical_specialty, Polifenoles, Riesgo cardiovascular, Inflammatory response, Cardiovascular score, Risk Factors, Internal medicine, Linear regression, medicine, Humans, Ecuación cardiovascular, Total energy, Framingham Risk Score, business.industry, Polyphenols, food and beverages, Food frequency questionnaire, General Medicine, Cardiovascular risk, Predimed, Residual method, Cross-Sectional Studies, Cardiovascular Diseases, Heart Disease Risk Factors, Polyphenol, Female, business
Abstract: Introduction and objectives Quantification of cardiovascular risk has been based on scores such as Framingham, Framingham-REGICOR, SCORE or Life's Simple 7 (LS7). In vitro, animal, and randomized clinical studies have shown that polyphenols may provide benefits to the vascular system and reduce the inflammatory response. However, some clinical-epidemiological studies have yielded inconsistent results. Our aim was to assess the possible association between intake of the various polyphenol classes and established cardiovascular scores. Methods This cross-sectional analysis involved 6633 PREDIMED-Plus study participants. Food polyphenol content was estimated by a semiquantitative food frequency questionnaire , adjusted for total energy intake according to the residual method. The association between polyphenol intake and cardiovascular risk was tested using linear regression analyses. Results Total polyphenol and flavonoid intake were directly and significantly associated only with the LS7 scale. Intake of lignans was directly and significantly associated with SCORE and LS7 scales, stilbene intake with SCORE, and phenolic acid intake with Framingham and Framingham-REGICOR scores. Other polyphenol classes were associated in a protective and significant manner in Framingham, SCORE and LS7 scores. In women, intake of all the polyphenol classes, except phenolic acids, showed a protective trend in the results of the Framingham, Framingham-REGICOR scores and LS7 scale. Conclusions An inverse association was found between consumption of the ‘other polyphenols’ class and, especially among women, with estimated cardiovascular risk. The results were similar to those of Framingham, Framingham-REGICOR and LS7 (after eliminating the diet component) and differed from those of SCORE, but the predictors included were limited in the latter case.
Published: 2022

40. One-year changes in fruit and vegetable variety intake and cardiometabolic risk factors changes in a middle-aged Mediterranean population at high cardiovascular risk

Author: López-González, Leyre, Becerra-Tomás, Nerea, Babio, Nancy, Martínez-González, Miguel Ángel, Nishi, Stephanie K, Corella, Dolores, Goday, Albert, Romaguera, Dora, Vioque, Jesús, Alonso-Gómez, Ángel M, Wärnberg, Julia, Martínez, J Alfredo, Serra-Majem, Luís, Estruch, Ramon, Bernal-López, M Rosa, Lapetra, José, Pintó, Xavier, Tur, Josep A, López-Miranda, José, Bueno-Cavanillas, Aurora, Delgado-Rodríguez, Miguel, Matía-Martín, Pilar, Daimiel, Lidia, Martín-Sánchez, Vicente, Vidal, Josep, Vázquez, Clotilde, Ros, Emilio, Vázquez-Ruiz, Zenaida, Martín-Luján, Francisco M, Sorlí, José V, Castañer, Olga, Zulet, M Angeles, Tojal-Sierra, Lucas, Carabaño-Moral, Rosa, Román-Maciá, Josefa, Rayó, Elena, García-Ríos, Antonio, Casas, Rosa, Gómez-Pérez, Ana M, Santos-Lozano, José M, Buil-Cosiales, Pilar, Asensio, Eva M, Lassale, Camille, Abete, Itziar, Salaverria-Lete, Itziar, Sayón-Orea, Carmen, Schröder, Helmut, Salas-Salvadó, Jordi, and PREDIMED-Plus Investigators
Subjects: Male, QUESTIONNAIRE, 1106 Human Movement and Sports Sciences, Medicine (miscellaneous), Risk Factors, Vegetables, Humans, PREDIMED-Plus Investigators, Triglycerides, Aged, Science & Technology, Nutrition and Dietetics, Nutrition & Dietetics, HYPERTENSION, Body Weight, PHYTOCHEMICALS, Cardiometabolic Risk Factors, CONSUMPTION, ASSOCIATION, ADULTS, QUANTITY, Middle Aged, HEALTH-BENEFITS, Diet, Glucose, Cardiovascular Diseases, Heart Disease Risk Factors, Fruit, Female, 1111 Nutrition and Dietetics, Life Sciences & Biomedicine, 0908 Food Sciences
Abstract: BACKGROUND AND AIMS: Previous studies have shown beneficial associations between fruit and vegetable (FV) consumption and cardiometabolic risk factors. However, variety in FV, which may play an important role on cardiovascular health due to the different nutrient and phytochemical content among the different groups and subgroups of FV has been poorly investigated. We longitudinally investigated associations between 1-year changes in variety and quantity of FV and concurrent changes in cardiometabolic risk factors in elderly subjects with overweight/obesity and metabolic syndrome. METHODS: a one-year data longitudinal analysis of 6647 PREDIMED-plus study participants (48% women) was conducted. Data were collected at baseline, six months and 1-year of follow-up. Variety and quantity of FV were estimated using a food frequency questionnaire and continuous scores for variety were created based on items/month of FV. Linear mixed-models adjusted for potential confounders were performed to estimate associations (ß-coefficients and 95% confidence interval) between 1-year changes in FV variety and/or quantity and concurrent changes in cardiometabolic risk factors. RESULTS: Two points increment in the FV variety score over one year was associated with a concurrent decrease in glucose (-0.33 mg/dL (0.58, -0.07)), body weight (-0.07 kg (-0.13, -0.02)) and waist circumference (WC) (-0.08 cm (-0.16, -10.01)). An increment of 100 g/d of FV over one year was associated with a concurrent decrease in triglycerides (-0.50 mg/dL (-0.93, -0.08)), glucose (-0.21 mg/dL (-0.32, -0.11)), body weight (-0.11 kg (-0.15, -0.07)) and WC (-0.10 cm (-0.14, -0.06)) over 1-year. Changes in FV consumption which led to higher quantity and variety over one year were associated with downward changes in glucose (-1.26 mg/dL (-2.09, -0.43)), body weight (-0.40 kg (-0.58, -0.23)) and WC (-0.50 cm (-0.73, -0.28)). CONCLUSION: Greater variety, in combination with higher quantity of FV was significantly associated with a decrease in several cardiometabolic risk factors among elderly subjects at high cardiovascular risk.
Published: 2022

41. Behavioural alterations induced by intermittent ethanol intake and noise exposure in adolescent rats

Author: Gustavo Ezequiel Buján, Luciana D'Alessio, Héctor Alejandro Serra, Sonia Jazmín Molina, and Laura Ruth Guelman
Subjects: Male, Alcohol Drinking, Ethanol, General Neuroscience, Animals, Female, Anxiety, Rats, Wistar, Rats
Abstract: Alcohol intake and exposure to noise are common activities of human adolescents performed in entertainment contexts worldwide that can induce behavioural disturbances. Therefore, the aim of the present work was to investigate in an experimental model of adolescent animals whether noise exposure and intermittent ethanol intake, when present individually or sequentially, might be able to modify different behaviours. Adolescent Wistar rats of both sexes were subjected to voluntary intermittent ethanol intake for 1 week followed by exposure to noise for 2 h and tested in a battery of behavioural tasks. Data show that males exposed to noise experienced a deficit in associative memory (AM), increase in anxiety-like behaviours (ALB) and altered reaction to novelty (RN) when compared with sham animals, whereas females also showed an increase in risk assessment behaviours (RABs) and a decrease in exploratory activity (EA). In contrast, ethanol intake induced an increase in RAB and RN in males and females, whereas females also showed a deficit in AM and EA as well as an increase in ALB. When ethanol was ingested before noise exposure, most parameters were counteracted both in male and females, but differed among sexes. In consequence, it could be hypothesized that an environmental acute stressor like noise might trigger a behavioural counteracting induced by a previous repeated exposure to a chemical agent such as ethanol, leading to a compensation of a non-adaptive behaviour and reaching a better adjustment to the environment.
Published: 2022

42. Clinical characteristics and risk factors associated with severe disease and outcome of patients with COVID-19

Author: Ayse Serra Ozel, Lutfiye Nilsun Altunal, Mehtap Aydin, Busra Unal, Gulsum Cam, Merve Caglar Ozer, Volkan Korten, and Ozel A. S., Altunal L. N., Aydin M., Unal B., Cam G., Ozer M. C., KORTEN V.
Subjects: Male, Immunology, Life Sciences (LIFE), Sağlık Bilimleri, Microbiology, Genel İmmünoloji ve Mikrobiyoloji, Risk Factors, Lymphopenia, Virology, Yaşam Bilimleri, Health Sciences, INFECTION, Humans, Mortality, PREDICTORS, Outcome, Retrospective Studies, İmmünoloji, General Immunology and Microbiology, SARS-CoV-2, Temel Bilimler, Life Sciences, COVID-19, General Medicine, Middle Aged, Bulaşıcı hastalıklar, Hospitalization, C-Reactive Protein, Infectious Diseases, BULAŞICI HASTALIKLAR, Yaşam Bilimleri (LIFE), &nbsp, Female, Parasitology, Natural Sciences, Procalcitonin
Abstract: Introduction: Since the beginning of the pandemic, factors associated with mortality in patients with corona virus infection disease 2019 (COVID-19) have been investigated. Comorbidities and increased age have been frequently reported to be associated with mortality. We aimed to evaluate the factors associated with unfavorable outcome of patients with COVID-19 at an early period of the pandemic. Methodology: This single center, retrospective, observational study was conducted among laboratory confirmed COVID-19 patients hospitalized between March 11 and May 5, 2020, at Umraniye Training and Research Hospital, Istanbul, Turkey. The effects of the severity of illness, comorbidities, symptoms, and laboratory findings on the clinical outcome were evaluated. Factors associated with unfavorable outcome (necessity of mechanical ventilation or death) were examined using Cox proportional hazards models. Results: Out of a total of 728 patients, 53.8% were men and median age 54 years. The 30-day mortality rate was 4.9% among all hospitalized patients. A logistic regression model identified six predictors of unfavorable clinical outcome: age, severity of illness, the numbers of comorbidities, lymphopenia, high levels of C-reactive protein, and procalcitonin. Conclusions: The mortality rate was lower among the patients with COVID-19, hospitalized during the early period of the pandemic. Older age, higher severity score on admission, the numbers of comorbidities, higher levels of C-reactive protein, procalcitonin, and lymphopenia were identified to be associated with unfavorable outcome of the hospitalized patients with COVID-19.
Published: 2022

43. Depressive symptom severity is a major risk factor for frailty in community-dwelling older adults with depression. A prospective study

Author: Joaquim Oyon, Mateu Serra-Prat, Esther Limon, Mariona Ferrer, Núria Pastor, Elisabet Palomera, and Emili Burdoy
Subjects: Male, Frailty, Depression, Risk Factors, Frail Elderly, Humans, Pain, Female, Independent Living, Prospective Studies, Family Practice, Geriatric Assessment, Aged
Abstract: Background Depression and frailty are closely related, but the mechanisms by which depressed older adults are at an increased risk of becoming frail are still not well understood. Aim To assess socioeconomic and depression-related risk factors for frailty in older adults with depression. Methods Observational and prospective cohort study, with 12-month follow-up, of nonfrail community-dwelling subjects aged ≥70 years old with depression. The main study factors were clinical characteristics of depression, including symptom severity (Hamilton Depression Rating Scale), accompanying anxiety and cognitive symptoms, pharmacological treatment, and social factors including educational level, income, housing conditions and living circumstances, and social network. Frailty status was established according to Fried criteria. Results We recruited and analysed 216 subjects (mean age 76.5 years; 74% women), 65 (30%) of whom were lost to follow-up. Annual incidence of frailty was 23.2 new cases/100 persons. Age, female gender, osteoarthritis, pain, number of medications, major depression, first-degree family history of depression, depressive symptom severity, low educational level, and low-income level were risk factors for frailty. The multivariate analysis showed that age (odds ratio [OR] = 1.16; 95% confidence interval [CI]: 1.04–1.29), visual analogue scale (VAS)-pain (OR = 1.25; 95% CI: 1.01–1.55), and severe or very severe depressive symptoms (OR = 37.36; 95% CI: 2.68–518.53) were significantly associated with incident frailty at 12 months of follow-up. Conclusions Both clinical and social characteristics are risk factors for frailty, but severity of depressive symptoms had the highest independent effect on frailty in depressed aged subjects. Frailty requires a multidisciplinary approach that pays special attention to pain and depressed mood.
Published: 2022

44. An investigation on parenting stress of children with cystic fibrosis

Author: Silvia Toscano, Nicola Serra, Angela Sepe, Grazia Isabella Continisio, Maria Rosaria Esposito, Valeria Raia, Teresa Rea, Gianpaolo Gargiulo, Assunta Guillari, Maria Teresa Civitella, Silvio Simeone, Continisio, G. I., Serra, N., Guillari, A., Civitella, M. T., Sepe, A., Simeone, S., Gargiulo, G., Toscano, S., Esposito, M. R., Raia, V., Rea, T., Grazia Isabella, Continisio, Nicola, Serra, Assunta, Guillari, Maria Teresa, Civitella, Angela, Sepe, Simeone, S, Gianpaolo, Gargiulo, Silvia, Toscano, Maria Rosaria, Esposito, and Valeria Raia andTeresa, Rea
Subjects: Biopsychosocial model, Adult, Male, Parents, Multivariate analysis, Adolescent, Psychological intervention, Disease, Cystic fibrosis, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Sex Factors, 030225 pediatrics, 0502 economics and business, Medicine, Humans, Sibling, Child, Univariate analysis, Parenting, business.industry, Clinical management, Research, 05 social sciences, lcsh:RJ1-570, Infant, lcsh:Pediatrics, Middle Aged, medicine.disease, Birth order, Italy, Socioeconomic Factors, Child, Preschool, Cystic fibrosi, Female, Parenting stress index, business, 050203 business & management, Stress, Psychological, Clinical psychology
Abstract: Background: The management of chronic diseases, particularly in children, requires an integrated physical and psychological approach to both sick children and their family. This is the case of Cystic Fibrosis (CF), a complex genetic chronic disease, where, a comprehensive evaluation of the emotional impact and an effective multidimensional approach are indicated. Aim: This study investigates on parenting stress in children and adolescents with CF and its determinants related to parents, children and the disease severity. Methods: The study involved 34.04% adult males and 65.96% adult females (range 21-55 years) and 47 children with CF, 54.35% males and 45.65% females (range 1-17 years). The data were obtained through a Parenting Stress Index - Short Form (PSI-SF) questionnaire. According to the PSI-SF scoring system, three types of stress were detected: a typical stress pattern (normal), a high stress pattern (increased) and a defensive response, which may be considered as a high stress feature in children which requires monitoring and clinical evaluation. Results: This study shows a significant presence of stress in females (60.23%), of subject married (84.62%), unemployed (69.23%) and with education level such as "middle School" (61.54%). Concerning children of parents with high stress, it resulted most frequent children with one sibling (53.85%). Finally, by univariate analysis, it resulted a significant positive correlation between parenting stress and disease degree of children. Instead by multivariate analysis, we found that the variables: Number of siblings and Birth order were a significant positive and negative predictor of parenting stress respectively. Conclusion: An increased stress level was detected in less than one third of parents of subjects with CF. These data may be related to the psychological support which is part of the routine management of CF care team. However, as children's features seem to act as a determinant of stress more than parental ones, the parental-child dysfunction should be the target for further integrated interventions. Background: The management of chronic diseases, particularly in children, requires an integrated physical and psychological approach to both sick children and their family. This is the case of Cystic Fibrosis (CF), a complex genetic chronic disease, where, a comprehensive evaluation of the emotional impact and an effective multidimensional approach are indicated. Aim: This study investigates on parenting stress in children and adolescents with CF and its determinants related to parents, children and the disease severity. Methods: The study involved 34.04% adult males and 65.96% adult females (range 21-55 years) and 47 children with CF, 54.35% males and 45.65% females (range 1-17 years). The data were obtained through a Parenting Stress Index – Short Form (PSI-SF) questionnaire. According to the PSI-SF scoring system, three types of stress were detected: a typical stress pattern (normal), a high stress pattern (increased) and a defensive response, which may be considered as a high stress feature in children which requires monitoring and clinical evaluation. Results: This study shows a significant presence of stress in females (60.23%), of subject married (84.62%), unemployed (69.23%) and with education level such as “middle School” (61.54%). Concerning children of parents with high stress, it resulted most frequent children with one sibling (53.85%). Finally, by univariate analysis, it resulted a significant positive correlation between parenting stress and disease degree of children. Instead by multivariate analysis, we found that the variables: Number of siblings and Birth order were a significant positive and negative predictor of parenting stress respectively. Conclusion: An increased stress level was detected in less than one third of parents of subjects with CF. These data may be related to the psychological support which is part of the routine management of CF care team. However, as children’s features seem to act as a determinant of stress more than parental ones, the parental-child dysfunction should be the target for further integrated interventions.
Published: 2020

45. Smoking habit as a risk amplifier in chronic kidney disease patients

Author: Pasquale Mastroroberto, Raffaele Serra, Francesco Locatelli, Giuseppe Filiberto Serraino, Ashour Michael, Nicola Ielapi, Davide Bolignano, Giuseppe Coppolino, Luca De Nicola, Michele Provenzano, Michele Andreucci, Provenzano, M., Serra, R., Michael, A., Bolignano, D., Coppolino, G., Ielapi, N., Serraino, G. F., Mastroroberto, P., Locatelli, F., De Nicola, L., and Andreucci, M.
Subjects: Male, medicine.medical_specialty, Smoking habit, Science, 030232 urology & nephrology, smoking habit, Renal function, 030204 cardiovascular system & hematology, urologic and male genital diseases, Article, 03 medical and health sciences, Medical research, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Cardiovascular Disease, medicine, Humans, Significant risk, Stage (cooking), Renal Insufficiency, Chronic, Aged, Aged, 80 and over, Multidisciplinary, Proteinuria, business.industry, Risk Factor, Smoking, Middle Aged, medicine.disease, Former Smoker, Survival Analysis, Risk factors, Italy, Cardiovascular Diseases, Nephrology, Medicine, Female, medicine.symptom, business, Kidney disease, Glomerular Filtration Rate, Human
Abstract: Several studies showed the association between non-traditional risk factors [proteinuria and estimated Glomerular Filtration Rate (eGFR)] and cardiovascular (CV) and renal outcomes. Nevertheless, the etiologic role of traditional CV risk factors in referred CKD patients is less defined. Herein, we examined the association between smoking habit and CV events, mortality and CKD progression. We undertook an observational analysis of 1306 stage III–V CKD patients. Smoking habit was modeled as a categorical (never, current or former smokers) and continuous (number of cigarettes/day) variable. Mean eGFR was 35.8 ± 12.5 mL/min/1.73 m2. Never, current and former smokers were 61.1%, 10.8% and 28.1%. During a median follow-up of 2.87 years, current and former smokers were at significant risk for CV events (HRs of 1.93 [95% CI, 1.18–3.16] and 1.44 [95% CI, 1.01–2.05]) versus never smokers. Current smokers were at increased mortality risk (HR 2.13 [95% CI, 1.10–4.11]). Interactions were found between former smokers and proteinuria (p = 0.007) and diabetes (p = 0.041) for renal risk, and between current smokers and male gender (p = 0.044) and CKD stage V (p = 0.039) for renal and mortality risk. In referred CKD patients, smoking habit is independently associated with CV events and mortality. It acts as a risk “amplifier” for the association between other risk factors and renal outcomes.
Published: 2021

46. Novel SCNN1A gene splicing-site mutation causing autosomal recessive pseudohypoaldosteronism type 1 (PHA1) in two Italian patients belonging to the same small town

Author: Gregorio Serra, Vincenzo Verde, Maria Cristina Maggio, Vincenzo Antona, Giovanni Corsello, Maria Michela D’Alessandro, Serra G., Antona V., D'Alessandro M.M., Maggio M.C., Verde V., and Corsello G.
Subjects: Male, Hyperkalemia, Pseudohypoaldosteronism, ENaC, Case Report, Gene mutation, Bioinformatics, Pediatrics, RJ1-570, chemistry.chemical_compound, Consanguinity, Young Adult, Next generation sequencing, medicine, Humans, Family history, Epithelial Sodium Channels, Sicily, ENaC, Next generation sequencing, SCNN1A gene, Splicing mutation, Consanguinity, Epithelial Sodium Channels, Female, Humans, Infant, Newborn, Male, Mutation, Pseudohypoaldosteronism, Sicily, Young Adult, Aldosterone, business.industry, Infant, Newborn, medicine.disease, chemistry, SCNN1A gene, Mutation (genetic algorithm), Mutation, Female, medicine.symptom, business, Hyponatremia, Splicing mutation, Aunt
Abstract: Introduction Pseudohypoaldosteronism type 1 (PHA1) is a rare genetic disease due to the peripheral resistance to aldosterone. Its clinical spectrum includes neonatal salt loss syndrome with hyponatremia and hypochloraemia, hyperkalemia, metabolic acidosis and increased plasmatic levels of aldosterone. Two genetically distinct forms of disease, renal and systemic, have been described, showing a wide clinical expressivity. Mutations in the genes encoding for the subunits of the epithelial sodium channels (ENaC) are responsible for generalized PHA1. Patients’ presentation We hereby report on two Italian patients with generalized PHA1, coming from the same small town in the center of Sicily. The first patient is a male child, born from the first pregnancy of healthy consanguineous Sicilian parents. A novel SCNN1A (sodium channel epithelial subunit alpha) gene mutation, inherited from both heterozygous parents, was identified by next generation sequencing (NGS) in the homozygous child (and later, also in the heterozygous maternal aunt). A more detailed family history disclosed a possible related twenty-year-old girl, belonging to the same Sicilian small town, with referred neonatal salt loss syndrome associated to hyperkalemia, and subsequent normal growth and neurodevelopment. This second patient had a PHA1 clinical diagnosis when she was about 1 year old. The genetic investigation was, then, extended to her and to her family, revealing the same mutation in the homozygous girl and in the heterozygous parents. Conclusions The neonatologist should consider PHA1 diagnosis in newborns showing hyponatremia, hyperkalemia and metabolic acidosis, after the exclusion of a salting-loss form of adrenogenital syndrome. The increased plasmatic levels of aldosterone and aldosterone/renin ratio, associated to a poor response to steroid administration, confirmed the diagnosis in the first present patient. An accurate family history may be decisive to identify the clinical picture. A multidisciplinary approach and close follow-up evaluations are requested, in view of optimal management, adequate growth and development of patients. Next generation sequencing (NGS) techniques allowed the identification of the SCNN1A gene mutation either in both patients or in other heterozygous family members, enabling also primary prevention of disease. Our report may broaden the knowledge of the genetic and molecular bases of PHA1, improving its clinical characterization and providing useful indications for the treatment of patients. Clinical approach must be personalized, also in relation to long-term survival and potential multiorgan complications.
Published: 2021

47. Spontaneous Breathing in Early Acute Respiratory Distress Syndrome

Author: van Haren F., Pham T., Brochard L., Bellani G., Laffey J., Dres M., Fan E., Goligher E. C., Heunks L., Lynch J., Wrigge H., McAuley D, Pesenti A, Laffey JG, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Rios F, Sottiaux T, Depuyd P, Lora FS, Azevedo LC, Fan E, Bugedo G, Qiu H, Gonzalez M, Silesky J, Cerny V, Nielsen J, Jibaja M, Pham T, Matamis D, Ranero JL, Amin P, Hashemian SM, Clarkson K, Bellani G, Kurahashi K, Villagomez A, Zeggwagh AA, Heunks LM, Laake JH, Palo JE, Fernandes ADV, Sandesc D, Arabi Y, Bumbasierevic V, Nin N, Lorente JA, Piquilloud L, Abroug F, McNamee L, Hurtado J, Bajwa E, Démpaire G, Sula H, Nunci L, Cani A, Zazu A, Dellera C, Insaurralde CS, Alejandro RV, Daldin J, Vinzio M, Fernandez RO, Cardonnet LP, Bettini LR, Bisso MC, Osman EM, Setten MG, Lovazzano P, Alvarez J, Villar V, Pozo NC, Grubissich N, Plotnikow GA, Vasquez DN, Ilutovich S, Tiribelli N, Chena A, Pellegrini CA, Saenz MG, Estenssoro E, Brizuela M, Gianinetto H, Gomez PE, Cerrato VI, Bezzi MG, Borello SA, Loiacono FA, Fernandez AM, Knowles S, Reynolds C, Inskip DM, Miller JJ, Kong J, Whitehead C, Bihari S, Seven A, Krstevski A, Rodgers HJ, Millar RT, Mckenna TE, Bailey IM, Hanlon GC, Aneman A, Lynch JM, Azad R, Neal J, Woods PW, Roberts BL, Kol MR, Wong HS, Riss KC, Staudinger T, Wittebole X, Berghe C, Bulpa PA, Dive AM, Verstraete R, Lebbinck H, Depuydt P, Vermassen J, Meersseman P, Ceunen H, Rosa JI, Beraldo DO, Piras C, Rampinelli AM, Nassar AP Jr, Mataloun S, Moock M, Thompson MM, Gonçalves CH, Antônio ACP, Ascoli A, Biondi RS, Fontenele DC, Nobrega D, Sales VM, Shindhe S, Pg Hj Ismail DMAB, Laffey J, Beloncle F, Davies KG, Cirone R, Manoharan V, Ismail M, Goligher EC, Jassal M, Nishikawa E, Javeed A, Curley G, Rittayamai N, Parotto M, Ferguson ND, Mehta S, Knoll J, Pronovost A, Canestrini S, Bruhn AR, Garcia PH, Aliaga FA, Farías PA, Yumha JS, Ortiz CA, Salas JE, Saez AA, Vega LD, Labarca EF, Martinez FT, Carreño NG, Lora P, Liu L, Tang R, Luo X, An Y, Zhao H, Gao Y, Zhai Z, Ye ZL, Wang W, Li W, Li Q, Zheng R, Yu W, Shen J, Li X, Yu T, Lu W, Wu YQ, Huang XB, He Z, Lu Y, Han H, Zhang F, Sun R, Wang HX, Qin SH, Zhu BH, Zhao J, Liu J, Li B, Liu JL, Zhou FC, Li QJ, Zhang XY, Li-Xin Z, Xin-Hua Q, Jiang L, Gao YN, Zhao XY, Li YY, Li XL, Wang C, Yao Q, Yu R, Chen K, Shao H, Qin B, Huang QQ, Zhu WH, Hang AY, Hua MX, Li Y, Xu Y, Di YD, Ling LL, Qin TH, Wang SH, Qin J, Han Y, Zhou S, Vargas MP, Silesky Jimenez JI, González Rojas MA, Solis-Quesada JE, Ramirez-Alfaro CM, Máca J, Sklienka P, Gjedsted J, Christiansen A, Villamagua BG, Llano M, Burtin P, Buzancais G, Beuret P, Pelletier N, Mortaza S, Mercat A, Chelly J, Jochmans S, Terzi N, Daubin C, Carteaux G, de Prost N, Chiche JD, Daviaud F, Fartoukh M, Barberet G, Biehler J, Dellamonica J, Doyen D, Arnal JM, Briquet A, Hraiech S, Papazian L, Follin A, Roux D, Messika J, Kalaitzis E, Dangers L, Combes A, Au SM, Béduneau G, Carpentier D, Zogheib EH, Dupont H, Ricome S, Santoli FL, Besset SL, Michel P, Gelée B, Danin PE, Goubaux B, Crova PJ, Phan NT, Berkelmans F, Badie JC, Tapponnier R, Gally J, Khebbeb S, Herbrecht JE, Schneider F, Declercq PM, Rigaud JP, Duranteau J, Harrois A, Chabanne R, Marin J, Bigot C, Thibault S, Ghazi M, Boukhazna M, Zein SO, Richecoeur JR, Combaux DM, Grelon F, Le Moal C, Sauvadet EP, Robine A, Lemiale V, Reuter D, Dres M, Demoule A, Goldgran-Toledano D, Baboi L, Guérin C, Lohner R, Kraßler J, Schäfer S, Zacharowsk KD, Meybohm P, Reske AW, Simon P, Hopf HF, Schuetz M, Baltus T, Papanikolaou MN, Papavasilopoulou TG, Zacharas GA, Ourailogloy V, Mouloudi EK, Massa EV, Nagy EO, Stamou EE, Kiourtzieva EV, Oikonomou MA, Avila LE, Cortez CA, Citalán JE, Jog SA, Sable SD, Shah B, Gurjar M, Baronia AK, Memon M, Muthuchellappan R, Ramesh VJ, Shenoy A, Unnikrishnan R, Dixit SB, Rhayakar RV, Ramakrishnan N, Bhardwaj VK, Mahto HL, Sagar SV, Palaniswamy V, Ganesan D, Mohammadreza Hashemian S, Jamaati H, Heidari F, Meaney EA, Nichol A, Knapman KM, O'Croinin D, Dunne ES, Breen DM, Clarkson KP, Jaafar RF, Dwyer R, Amir F, Ajetunmobi OO, O'Muircheartaigh AC, Black CS, Treanor N, Collins DV, Altaf W, Zani G, Fusari M, Spadaro S, Volta CA, Graziani R, Brunettini B, Palmese S, Formenti P, Umbrello M, Lombardo A, Pecci E, Botteri M, Savioli M, Protti A, Mattei A, Schiavoni L, Tinnirello A, Todeschini M, Giarratano A, Cortegiani A, Sher S, Rossi A, Antonelli MM, Montini LM, Casalena P, Scafetti S, Panarello G, Occhipinti G, Patroniti N, Pozzi M, Biscione RR, Poli MM, Raimondi F, Albiero D, Crapelli G, Beck E, Pota V, Schiavone V, Molin A, Tarantino F, Monti G, Frati E, Mirabella L, Cinnella G, Fossali T, Colombo R, Ilaria Pattarino PT, Mojoli F, Braschi A, Borotto EE, Cracchiolo AN, Palma DM, Raponi F, Foti G, Vascotto ER, Coppadoro A, Brazzi L, Floris L, Iotti GA, Venti A, Yamaguchi O, Takagi S, Maeyama HN, Watanabe E, Yamaji Y, Shimizu K, Shiozaki K, Futami S, Ryosuke S, Saito K, Kameyama Y, Ueno K, Izawa M, Okuda N, Suzuki H, Harasawa T, Nasu M, Takada T, Ito F, Nunomiya S, Koyama K, Abe T, Andoh K, Kusumoto K, Hirata A, Takaba A, Kimura H, Matsumoto S, Higashijima U, Honda H, Aoki N, Imai H, Ogino Y, Mizuguchi I, Ichikado K, Nitta K, Mochizuki K, Hashida T, Tanaka H, Nakamura T, Niimi D, Ueda T, Kashiwa Y, Uchiyama A, Sabelnikovs O, Oss P, Haddad Y, Liew KY, Ñamendys-Silva SA, Jarquin-Badiola YD, Sanchez-Hurtado LA, Gomez-Flores SS, Marin MC, Villagomez AJ, Lemus JS, Fierro JM, Ramirez Cervantes M, Mejia FJF, Dector D, Dector DM, Gonzalez DR, Estrella CR, Sanchez-Medina JR, Ramirez-Gutierrez A, George FG, Aguirre JS, Buensuseso JA, Poblano M, Dendane T, Balkhi H, Elkhayari M, Samkaoui N, Ezzouine H, Benslama A, Amor M, Maazouzi W, Cimic N, Beck O, Bruns MM, Schouten JA, Rinia M, Raaijmakers M, Van Wezel HM, Heines SJ, Strauch U, Buise MP, Simonis FD, Schultz MJ, Goodson JC, Browne TS, Navarra L, Hunt A, Hutchison RA, Bailey MB, Newby L, Mcarthur C, Kalkoff M, Mcleod A, Casement J, Hacking DJ, Andersen FH, Dolva MS, Barratt-Due A, Noremark KAL, Søreide E, Sjøbø BÅ, Guttormsen AB, Leon Yoshido HH, Aguilar RZ, Montes Oscanoa FA, Alisasis AU, Robles JB, Pasanting-Lim RAB, Tan BC, Andruszkiewicz P, Jakubowska K, Coxo CM, Alvarez AM, Oliveira BS, Montanha GM, Barros NC, Pereira CS, Messias AM, Monteiro JM, Araujo AM, Catorze NT, Marum SM, Bouw MJ, Gomes RM, Brito VA, Castro S, Estilita JM, Barros FM, Serra IM, Martinho AM, Tomescu DR, Marcu A, Bedreag OH, Papurica M, Corneci DE, Negoita SI, Grigoriev E, Gritsan AI, Gazenkampf AA, Almekhlaf G, Albarrak MM, Mustafa GM, Maghrabi KA, Salahuddin N, Aisa TM, Al Jabbary AS, Tabhan E, Arabi YM, Trinidad OA, Al Dorzi HM, Tabhan EE, Bolon S, Smith O, Mancebo J, Aguirre-Bermeo H, Lopez-Delgado JC, Esteve F, Rialp G, Forteza C, De Haro C, Artigas A, Albaiceta GM, De Cima-Iglesias S, Seoane-Quiroga L, Ceniceros-Barros A, Ruiz-Aguilar AL, Claraco-Vega LM, Soler JA, Lorente MDC, Hermosa C, Gordo F, Prieto-González M, Perez MP, Perez CP, Allue RM, Roche-Campo F, Ibañez-Santacruz M, Temprano S, Pintado MC, De Pablo R, Gómez PRA, Ruiz SR, Iglesias Moles S, Jurado MT, Arizmendi A, Piacentini EA, Franco N, Honrubia T, Cheng MP, Losada EP, Blanco J, Yuste LJ, Carbayo-Gorriz C, Cazorla-Barranquero FG, Alonso JG, Alda RS, Algaba Á, Navarro G, Cereijo E, Diaz-Rodriguez E, Marcos DP, Montero LA, Para LH, Sanchez RJ, Navalpotro MAB, Abad RD, González RM, Toribio DP, Castro AG, Artiga MJD, Penuelas O, Roser TP, Olga MF, Curto EG, Sánchez RM, Imma VP, Elisabet GM, Claverias L, Magret M, Pellicer AM, Rodriguez LL, Sánchez-Ballesteros J, González-Salamanca Á, Jimenez AG, Huerta FP, Sotillo Diaz JCJ, Lopez EB, Llinares Moya DD, Tallet Alfonso AA, Eugenio Luis PS, Cesar PS, Rafael SI, Virgilio CG, Recio NN, Adamsson RO, Rylander CC, Holzgraefe B, Broman LM, Wessbergh J, Persson L, Schiöler F, Kedelv H, Tibblin AO, Appelberg H, Hedlund L, Helleberg J, Eriksson KE, Glietsch R, Larsson N, Nygren I, Nunes SL, Morin AK, Kander T, Adolfsson A, Zender HO, Leemann-Refondini C, Elatrous S, Bouchoucha S, Chouchene I, Ouanes I, Ben Souissi A, Kamoun S, Demirkiran O, Aker M, Erbabacan E, Ceylan I, Girgin NK, Ozcelik M, Ünal N, Meco BC, Akyol OO, Derman SS, Kennedy B, Parhar K, Srinivasa L, Hopkins P, Mellis C, Kakar V, Hadfield D, Vercueil A, Bhowmick K, Humphreys SK, Ferguson A, Mckee R, Raj AS, Fawkes DA, Watt P, Twohey L, Jha RR, Thomas M, Morton A, Kadaba V, Smith MJ, Hormis AP, Kannan SG, Namih M, Reschreiter H, Camsooksai J, Kumar A, Rugonfalvi S, Nutt C, O'Neill O, Seasman C, Dempsey G, Scott CJ, Ellis HE, Mckechnie S, Hutton PJ, Di Tomasso NN, Vitale MN, Griffin RO, Dean MN, Cranshaw JH, Willett EL, Ioannou N, Gillis S, Csabi P, Macfadyen R, Dawson H, Preez PD, Williams AJ, Boyd O, De Gordoa LO, Bramall J, Chau SK, Wenham T, Szakmany T, Toth-Tarsoly P, McCalman KH, Alexander P, Stephenson L, Collyer T, Chapman R, Cooper R, Allan RM, Sim M, Wrathall DW, Irvine DA, Zantua KS, Adams JC, Burtenshaw AJ, Sellors GP, Welters ID, Williams KE, Hessell RJ, Oldroyd MG, Battle CE, Pillai S, Kajtor I, Sivashanmugavel M, O'Kane SC, Donnelly A, Frigyik AD, Careless JP, May MM, Stewart R, Trinder TJ, Hagan SJ, Wise MP, Cole JM, MacFie CC, Dowling AT, Nuñez E, Pittini G, Rodriguez R, Imperio MC, Santos C, Deicas A, Serra C, Uppalapati A, Kamel G, Banner-Goodspeed VM, Beitler JR, Mukkera SR, Kulkarni S, Lee J, Mesar T, Shinn JO 3rd, Gomaa D, Tainter C, Yeatts DJ, Warren J, Lanspa MJ, Miller RR, Grissom CK, Brown SM, Bauer PR, Gosselin RJ, Kitch BT, Cohen JE, Beegle SH, Gueret RM, Tulaimat A, Choudry S, Stigler W, Batra H, Huff NG, Lamb KD, Oetting TW, Mohr NM, Judy C, Saito S, Kheir FM, Kheir F, Schlichting AB, Delsing A, Crouch DR, Elmasri M, Ismail D, Dreyer KR, Blakeman TC, Baron RM, Grijalba CQ, Hou PC, Seethala R, Aisiku I, Henderson G, Frendl G, Hou SK, Owens RL, Schomer A, Bumbasirevic V, Jovanovic B, Surbatovic M, Veljovic M., Intensive Care Medicine, ACS - Diabetes & metabolism, ACS - Pulmonary hypertension & thrombosis, ACS - Microcirculation, van Haren F., Pham T., Brochard L., Bellani G., Laffey J., Dres M., Fan E., Goligher E.C., Heunks L., Lynch J., Wrigge H., McAuley D, Pesenti A, Laffey JG, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Rios F, Sottiaux T, Depuyd P, Lora FS, Azevedo LC, Fan E, Bugedo G, Qiu H, Gonzalez M, Silesky J, Cerny V, Nielsen J, Jibaja M, Pham T, Wrigge H, Matamis D, Ranero JL, Amin P, Hashemian SM, Clarkson K, Bellani G, Kurahashi K, Villagomez A, Zeggwagh AA, Heunks LM, Laake JH, Palo JE, Fernandes ADV, Sandesc D, Arabi Y, Bumbasierevic V, Nin N, Lorente JA, Larsson A, Piquilloud L, Abroug F, McAuley DF, McNamee L, Hurtado J, Bajwa E, Démpaire G, Sula H, Nunci L, Cani A, Zazu A, Dellera C, Insaurralde CS, Alejandro RV, Daldin J, Vinzio M, Fernandez RO, Cardonnet LP, Bettini LR, Bisso MC, Osman EM, Setten MG, Lovazzano P, Alvarez J, Villar V, Pozo NC, Grubissich N, Plotnikow GA, Vasquez DN, Ilutovich S, Tiribelli N, Chena A, Pellegrini CA, Saenz MG, Estenssoro E, Brizuela M, Gianinetto H, Gomez PE, Cerrato VI, Bezzi MG, Borello SA, Loiacono FA, Fernandez AM, Knowles S, Reynolds C, Inskip DM, Miller JJ, Kong J, Whitehead C, Bihari S, Seven A, Krstevski A, Rodgers HJ, Millar RT, Mckenna TE, Bailey IM, Hanlon GC, Aneman A, Lynch JM, Azad R, Neal J, Woods PW, Roberts BL, Kol MR, Wong HS, Riss KC, Staudinger T, Wittebole X, Berghe C, Bulpa PA, Dive AM, Verstraete R, Lebbinck H, Depuydt P, Vermassen J, Meersseman P, Ceunen H, Rosa JI, Beraldo DO, Piras C, Rampinelli AM, Nassar AP Jr, Mataloun S, Moock M, Thompson MM, Gonçalves CH, Antônio ACP, Ascoli A, Biondi RS, Fontenele DC, Nobrega D, Sales VM, Shindhe S, Pg Hj Ismail DMAB, Laffey J, Beloncle F, Davies KG, Cirone R, Manoharan V, Ismail M, Goligher EC, Jassal M, Nishikawa E, Javeed A, Curley G, Rittayamai N, Parotto M, Ferguson ND, Mehta S, Knoll J, Pronovost A, Canestrini S, Bruhn AR, Garcia PH, Aliaga FA, Farías PA, Yumha JS, Ortiz CA, Salas JE, Saez AA, Vega LD, Labarca EF, Martinez FT, Carreño NG, Lora P, Qiu H, Liu L, Tang R, Luo X, An Y, Zhao H, Gao Y, Zhai Z, Ye ZL, Wang W, Li W, Li Q, Zheng R, Yu W, Shen J, Li X, Yu T, Lu W, Wu YQ, Huang XB, He Z, Lu Y, Han H, Zhang F, Sun R, Wang HX, Qin SH, Zhu BH, Zhao J, Liu J, Li B, Liu JL, Zhou FC, Li QJ, Zhang XY, Li-Xin Z, Xin-Hua Q, Jiang L, Gao YN, Zhao XY, Li YY, Li XL, Wang C, Yao Q, Yu R, Chen K, Shao H, Qin B, Huang QQ, Zhu WH, Hang AY, Hua MX, Li Y, Xu Y, Di YD, Ling LL, Qin TH, Wang SH, Qin J, Han Y, Zhou S, Vargas MP, Silesky Jimenez JI, González Rojas MA, Solis-Quesada JE, Ramirez-Alfaro CM, Máca J, Sklienka P, Gjedsted J, Christiansen A, Nielsen J, Villamagua BG, Llano M, Burtin P, Buzancais G, Beuret P, Pelletier N, Mortaza S, Mercat A, Chelly J, Jochmans S, Terzi N, Daubin C, Carteaux G, de Prost N, Chiche JD, Daviaud F, Pham T, Fartoukh M, Barberet G, Biehler J, Dellamonica J, Doyen D, Arnal JM, Briquet A, Hraiech S, Papazian L, Follin A, Roux D, Messika J, Kalaitzis E, Dangers L, Combes A, Au SM, Béduneau G, Carpentier D, Zogheib EH, Dupont H, Ricome S, Santoli FL, Besset SL, Michel P, Gelée B, Danin PE, Goubaux B, Crova PJ, Phan NT, Berkelmans F, Badie JC, Tapponnier R, Gally J, Khebbeb S, Herbrecht JE, Schneider F, Declercq PM, Rigaud JP, Duranteau J, Harrois A, Chabanne R, Marin J, Bigot C, Thibault S, Ghazi M, Boukhazna M, Zein SO, Richecoeur JR, Combaux DM, Grelon F, Le Moal C, Sauvadet EP, Robine A, Lemiale V, Reuter D, Dres M, Demoule A, Goldgran-Toledano D, Baboi L, Guérin C, Lohner R, Kraßler J, Schäfer S, Zacharowsk KD, Meybohm P, Reske AW, Simon P, Hopf HF, Schuetz M, Baltus T, Papanikolaou MN, Papavasilopoulou TG, Zacharas GA, Ourailogloy V, Mouloudi EK, Massa EV, Nagy EO, Stamou EE, Kiourtzieva EV, Oikonomou MA, Avila LE, Cortez CA, Citalán JE, Jog SA, Sable SD, Shah B, Gurjar M, Baronia AK, Memon M, Muthuchellappan R, Ramesh VJ, Shenoy A, Unnikrishnan R, Dixit SB, Rhayakar RV, Ramakrishnan N, Bhardwaj VK, Mahto HL, Sagar SV, Palaniswamy V, Ganesan D, Mohammadreza Hashemian S, Jamaati H, Heidari F, Meaney EA, Nichol A, Knapman KM, O'Croinin D, Dunne ES, Breen DM, Clarkson KP, Jaafar RF, Dwyer R, Amir F, Ajetunmobi OO, O'Muircheartaigh AC, Black CS, Treanor N, Collins DV, Altaf W, Zani G, Fusari M, Spadaro S, Volta CA, Graziani R, Brunettini B, Palmese S, Formenti P, Umbrello M, Lombardo A, Pecci E, Botteri M, Savioli M, Protti A, Mattei A, Schiavoni L, Tinnirello A, Todeschini M, Giarratano A, Cortegiani A, Sher S, Rossi A, Antonelli MM, Montini LM, Casalena P, Scafetti S, Panarello G, Occhipinti G, Patroniti N, Pozzi M, Biscione RR, Poli MM, Raimondi F, Albiero D, Crapelli G, Beck E, Pota V, Schiavone V, Molin A, Tarantino F, Monti G, Frati E, Mirabella L, Cinnella G, Fossali T, Colombo R, Ilaria Pattarino PT, Mojoli F, Braschi A, Borotto EE, Cracchiolo AN, Palma DM, Raponi F, Foti G, Vascotto ER, Coppadoro A, Brazzi L, Floris L, Iotti GA, Venti A, Yamaguchi O, Takagi S, Maeyama HN, Watanabe E, Yamaji Y, Shimizu K, Shiozaki K, Futami S, Ryosuke S, Saito K, Kameyama Y, Ueno K, Izawa M, Okuda N, Suzuki H, Harasawa T, Nasu M, Takada T, Ito F, Nunomiya S, Koyama K, Abe T, Andoh K, Kusumoto K, Hirata A, Takaba A, Kimura H, Matsumoto S, Higashijima U, Honda H, Aoki N, Imai H, Ogino Y, Mizuguchi I, Ichikado K, Nitta K, Mochizuki K, Hashida T, Tanaka H, Nakamura T, Niimi D, Ueda T, Kashiwa Y, Uchiyama A, Sabelnikovs O, Oss P, Haddad Y, Liew KY, Ñamendys-Silva SA, Jarquin-Badiola YD, Sanchez-Hurtado LA, Gomez-Flores SS, Marin MC, Villagomez AJ, Lemus JS, Fierro JM, Ramirez Cervantes M, Mejia FJF, Dector D, Dector DM, Gonzalez DR, Estrella CR, Sanchez-Medina JR, Ramirez-Gutierrez A, George FG, Aguirre JS, Buensuseso JA, Poblano M, Dendane T, Zeggwagh AA, Balkhi H, Elkhayari M, Samkaoui N, Ezzouine H, Benslama A, Amor M, Maazouzi W, Cimic N, Beck O, Bruns MM, Schouten JA, Rinia M, Raaijmakers M, Heunks LM, Van Wezel HM, Heines SJ, Strauch U, Buise MP, Simonis FD, Schultz MJ, Goodson JC, Browne TS, Navarra L, Hunt A, Hutchison RA, Bailey MB, Newby L, Mcarthur C, Kalkoff M, Mcleod A, Casement J, Hacking DJ, Andersen FH, Dolva MS, Laake JH, Barratt-Due A, Noremark KAL, Søreide E, Sjøbø BÅ, Guttormsen AB, Leon Yoshido HH, Aguilar RZ, Montes Oscanoa FA, Alisasis AU, Robles JB, Pasanting-Lim RAB, Tan BC, Andruszkiewicz P, Jakubowska K, Coxo CM, Alvarez AM, Oliveira BS, Montanha GM, Barros NC, Pereira CS, Messias AM, Monteiro JM, Araujo AM, Catorze NT, Marum SM, Bouw MJ, Gomes RM, Brito VA, Castro S, Estilita JM, Barros FM, Serra IM, Martinho AM, Tomescu DR, Marcu A, Bedreag OH, Papurica M, Corneci DE, Negoita SI, Grigoriev E, Gritsan AI, Gazenkampf AA, Almekhlaf G, Albarrak MM, Mustafa GM, Maghrabi KA, Salahuddin N, Aisa TM, Al Jabbary AS, Tabhan E, Arabi YM, Trinidad OA, Al Dorzi HM, Tabhan EE, Bolon S, Smith O, Mancebo J, Aguirre-Bermeo H, Lopez-Delgado JC, Esteve F, Rialp G, Forteza C, De Haro C, Artigas A, Albaiceta GM, De Cima-Iglesias S, Seoane-Quiroga L, Ceniceros-Barros A, Ruiz-Aguilar AL, Claraco-Vega LM, Soler JA, Lorente MDC, Hermosa C, Gordo F, Prieto-González M, Perez MP, Perez CP, Allue RM, Roche-Campo F, Ibañez-Santacruz M, Temprano S, Pintado MC, De Pablo R, Gómez PRA, Ruiz SR, Iglesias Moles S, Jurado MT, Arizmendi A, Piacentini EA, Franco N, Honrubia T, Cheng MP, Losada EP, Blanco J, Yuste LJ, Carbayo-Gorriz C, Cazorla-Barranquero FG, Alonso JG, Alda RS, Algaba Á, Navarro G, Cereijo E, Diaz-Rodriguez E, Marcos DP, Montero LA, Para LH, Sanchez RJ, Navalpotro MAB, Abad RD, González RM, Toribio DP, Castro AG, Artiga MJD, Penuelas O, Roser TP, Olga MF, Curto EG, Sánchez RM, Imma VP, Elisabet GM, Claverias L, Magret M, Pellicer AM, Rodriguez LL, Sánchez-Ballesteros J, González-Salamanca Á, Jimenez AG, Huerta FP, Sotillo Diaz JCJ, Lopez EB, Llinares Moya DD, Tallet Alfonso AA, Eugenio Luis PS, Cesar PS, Rafael SI, Virgilio CG, Recio NN, Adamsson RO, Rylander CC, Holzgraefe B, Broman LM, Wessbergh J, Persson L, Schiöler F, Kedelv H, Tibblin AO, Appelberg H, Hedlund L, Helleberg J, Eriksson KE, Glietsch R, Larsson N, Nygren I, Nunes SL, Morin AK, Kander T, Adolfsson A, Piquilloud L, Zender HO, Leemann-Refondini C, Elatrous S, Bouchoucha S, Chouchene I, Ouanes I, Ben Souissi A, Kamoun S, Demirkiran O, Aker M, Erbabacan E, Ceylan I, Girgin NK, Ozcelik M, Ünal N, Meco BC, Akyol OO, Derman SS, Kennedy B, Parhar K, Srinivasa L, McNamee L, McAuley D, Hopkins P, Mellis C, Kakar V, Hadfield D, Vercueil A, Bhowmick K, Humphreys SK, Ferguson A, Mckee R, Raj AS, Fawkes DA, Watt P, Twohey L, Jha RR, Thomas M, Morton A, Kadaba V, Smith MJ, Hormis AP, Kannan SG, Namih M, Reschreiter H, Camsooksai J, Kumar A, Rugonfalvi S, Nutt C, O'Neill O, Seasman C, Dempsey G, Scott CJ, Ellis HE, Mckechnie S, Hutton PJ, Di Tomasso NN, Vitale MN, Griffin RO, Dean MN, Cranshaw JH, Willett EL, Ioannou N, Gillis S, Csabi P, Macfadyen R, Dawson H, Preez PD, Williams AJ, Boyd O, De Gordoa LO, Bramall J, Chau SK, Wenham T, Szakmany T, Toth-Tarsoly P, McCalman KH, Alexander P, Stephenson L, Collyer T, Chapman R, Cooper R, Allan RM, Sim M, Wrathall DW, Irvine DA, Zantua KS, Adams JC, Burtenshaw AJ, Sellors GP, Welters ID, Williams KE, Hessell RJ, Oldroyd MG, Battle CE, Pillai S, Kajtor I, Sivashanmugavel M, O'Kane SC, Donnelly A, Frigyik AD, Careless JP, May MM, Stewart R, Trinder TJ, Hagan SJ, Wise MP, Cole JM, MacFie CC, Dowling AT, Hurtado J, Nin N, Hurtado J, Nuñez E, Pittini G, Rodriguez R, Imperio MC, Santos C, Deicas A, Serra C, Uppalapati A, Kamel G, Banner-Goodspeed VM, Beitler JR, Mukkera SR, Kulkarni S, Lee J, Mesar T, Shinn JO 3rd, Gomaa D, Tainter C, Mesar T, Yeatts DJ, Warren J, Lanspa MJ, Miller RR, Grissom CK, Brown SM, Bauer PR, Gosselin RJ, Kitch BT, Cohen JE, Beegle SH, Gueret RM, Tulaimat A, Choudry S, Stigler W, Batra H, Huff NG, Lamb KD, Oetting TW, Mohr NM, Judy C, Saito S, Kheir FM, Kheir F, Schlichting AB, Delsing A, Crouch DR, Elmasri M, Ismail D, Dreyer KR, Blakeman TC, Gomaa D, Baron RM, Grijalba CQ, Hou PC, Seethala R, Aisiku I, Henderson G, Frendl G, Hou SK, Owens RL, Schomer A, Bumbasirevic V, Jovanovic B, Surbatovic M, Veljovic M., Van Haren, F, Pham, T, Brochard, L, Bellani, G, Laffey, J, Dres, M, Fan, E, Goligher, E, Heunks, L, Lynch, J, Wrigge, H, Mcauley, D, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - (MGD) Services des soins intensifs, and Intensive care medicine
Subjects: Male, Respiratory rate, medicine.medical_treatment, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Clinical Investigations, Respiration, Artificial/methods, mechanical ventilation, Critical Care and Intensive Care Medicine, NO, Positive-Pressure Respiration, 03 medical and health sciences, 0302 clinical medicine, acute respiratory distress syndrome, controlled mechanical ventilation, spontaneous breathing, supported ventilation, Respiratory Rate, medicine, Humans, Prospective Studies, Prospective cohort study, Artificial/methods, Mechanical ventilation, Respiratory Distress Syndrome, business.industry, Respiration, Confounding, 030208 emergency & critical care medicine, Odds ratio, Tidal Waves, acute respiratory distress syndrome, Middle Aged, Respiration, Artificial, 3. Good health, controlled mechanical ventilation, Treatment Outcome, 030228 respiratory system, Anesthesia, supported ventilation, Breathing, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, spontaneous breathing, Respiratory Distress Syndrome, Adult/physiopathology, Observational study, ARDS, Female, Adult/physiopathology, business, Respiratory Insufficiency, Cohort study
Abstract: Supplemental Digital Content is available in the text., Objectives: To describe the characteristics and outcomes of patients with acute respiratory distress syndrome with or without spontaneous breathing and to investigate whether the effects of spontaneous breathing on outcome depend on acute respiratory distress syndrome severity. Design: Planned secondary analysis of a prospective, observational, multicentre cohort study. Setting: International sample of 459 ICUs from 50 countries. Patients: Patients with acute respiratory distress syndrome and at least 2 days of invasive mechanical ventilation and available data for the mode of mechanical ventilation and respiratory rate for the 2 first days. Interventions: Analysis of patients with and without spontaneous breathing, defined by the mode of mechanical ventilation and by actual respiratory rate compared with set respiratory rate during the first 48 hours of mechanical ventilation. Measurements and Main Results: Spontaneous breathing was present in 67% of patients with mild acute respiratory distress syndrome, 58% of patients with moderate acute respiratory distress syndrome, and 46% of patients with severe acute respiratory distress syndrome. Patients with spontaneous breathing were older and had lower acute respiratory distress syndrome severity, Sequential Organ Failure Assessment scores, ICU and hospital mortality, and were less likely to be diagnosed with acute respiratory distress syndrome by clinicians. In adjusted analysis, spontaneous breathing during the first 2 days was not associated with an effect on ICU or hospital mortality (33% vs 37%; odds ratio, 1.18 [0.92–1.51]; p = 0.19 and 37% vs 41%; odds ratio, 1.18 [0.93–1.50]; p = 0.196, respectively ). Spontaneous breathing was associated with increased ventilator-free days (13 [0–22] vs 8 [0–20]; p = 0.014) and shorter duration of ICU stay (11 [6–20] vs 12 [7–22]; p = 0.04). Conclusions: Spontaneous breathing is common in patients with acute respiratory distress syndrome during the first 48 hours of mechanical ventilation. Spontaneous breathing is not associated with worse outcomes and may hasten liberation from the ventilator and from ICU. Although these results support the use of spontaneous breathing in patients with acute respiratory distress syndrome independent of acute respiratory distress syndrome severity, the use of controlled ventilation indicates a bias toward use in patients with higher disease severity. In addition, because the lack of reliable data on inspiratory effort in our study, prospective studies incorporating the magnitude of inspiratory effort and adjusting for all potential severity confounders are required.
Published: 2019

48. Intestinal malrotation in a female newborn affected by Osteopathia Striata with Cranial Sclerosis due to a de novo heterozygous nonsense mutation of the AMER1 gene

Author: Gregorio Serra, Vincenzo Antona, Maria Rita Di Pace, Mario Giuffrè, Giusy Morgante, Ettore Piro, Roberto Pirrello, Sergio Salerno, Ingrid Anne Mandy Schierz, Vincenzo Verde, Giovanni Corsello, Serra, Gregorio, Antona, Vincenzo, Di Pace, Maria Rita, Giuffre, Mario, Morgante, Giusy, Piro, Ettore, Pirrello, Roberto, Salerno, Sergio, Schierz, Ingrid Anne Mandy, Verde, Vincenzo, and Corsello, Giovanni
Subjects: Male, Sclerosis, Case report, Next generation sequencing, OS-CS, Skeletal dysplasia, X-inactivation, Cleft Lip, Tumor Suppressor Proteins, Infant, Newborn, General Medicine, Megalencephaly, Cleft Palate, Codon, Nonsense, Humans, Female, Bone Diseases, Adaptor Proteins, Signal Transducing
Abstract: Background Osteopathia Striata with Cranial Sclerosis (OS-CS), also known as Horan-Beighton Syndrome, is a rare genetic disease; about 90 cases have been reported to date. It is associated with mutations (heterozygous for female subjects and hemizygous for males) of the AMER1 gene, located at Xq11.2, and shows an X-linked pattern of transmission. Typical clinical manifestations include macrocephaly, characteristic facial features (frontal bossing, epicanthal folds, hypertelorism, depressed nasal bridge, orofacial cleft, prominent jaw), hearing loss and developmental delay. Males usually present a more severe phenotype than females and rarely survive. Diagnostic suspicion is based on clinical signs, radiographic findings of cranial and long bones sclerosis and metaphyseal striations, subsequent genetic testing may confirm it. Case presentation Hereby, we report on a female newborn with frontal and parietal bossing, narrow bitemporal diameter, dysplastic, low-set and posteriorly rotated ears, microretrognathia, cleft palate, and rhizomelic shortening of lower limbs. Postnatally, she manifested feeding intolerance with biliary vomiting and abdominal distension. Therefore, in the suspicion of bowel obstruction, she underwent surgery, which evidenced and corrected an intestinal malrotation. Limbs X-ray and skull computed tomography investigations did not show cranial sclerosis and/or metaphyseal striations. Array-CGH analysis revealed normal findings. Then, a target next generation sequencing (NGS) analysis, including the genes involved in skeletal dysplasias, was performed and revealed a de novo heterozygous nonsense mutation of the AMER1 gene. The patient was discharged at 2 months of age and included in a multidisciplinary follow-up. Aged 9 months, she now shows developmental and growth (except for relative macrocephaly) delay. The surgical correction of cleft palate has been planned. Conclusions Our report shows the uncommon association of intestinal malrotation in a female newborn with OS-CS. It highlights that neonatologists have to consider such a diagnosis, even in absence of cranial sclerosis and long bones striations, as these usually appear over time. Other syndromes with cranial malformations and skeletal dysplasia must be included in the differential diagnosis. The phenotypic spectrum is wide and variable in both genders. Due to variable X-inactivation, females may also show a severe and early-onset clinical picture. Multidisciplinary management and careful, early and long-term follow-up should be offered to these patients, in order to promptly identify any associated morbidities and prevent possible complications or adverse outcomes.
Published: 2022

49. Satisfaction with group-based appointments among patients with opioid use disorder in an urban buprenorphine clinic

Author: Serra Akyar, Amesika Nyaku, Kristyn Lao, Stephanie Ruthberg, and Erin A. Zerbo
Subjects: Analgesics, Opioid, Male, Psychiatry and Mental health, Patient Satisfaction, Ethnicity, Opiate Substitution Treatment, Humans, Medicine (miscellaneous), Personal Satisfaction, Middle Aged, Opioid-Related Disorders, Minority Groups, Buprenorphine
Published: 2022

50. Neurofibromatosis type 1 families with first-degree relatives harbouring distinct NF1 pathogenic variants. Genetic counselling and familial diagnosis: what should be offered?

Author: Belen Garcia, Nuria Catasus, Andrea Ros, Inma Rosas, Alejandro Negro, Mercedes Guerrero-Murillo, Ana Maria Valero, Anna Duat-Rodriguez, Juan Luis Becerra, Sandra Bonache, Conxi Lázaro Garcia, Carmina Comas, Isabel Bielsa, Eduard Serra, Concepción Hernández-Chico, Yolanda Martin, Elisabeth Castellanos, and Ignacio Blanco
Subjects: Male, congenital, hereditary, and neonatal diseases and abnormalities, Neurofibromatosis 1, Neurofibromin 1, Genes, Neurofibromatosis 1, Genetics, Humans, Genetic Counseling, Genetic Testing, neoplasms, eye diseases, Genetics (clinical), nervous system diseases
Abstract: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder caused by pathogenic variants in NF1. Recently, NF1 testing has been included as a clinical criterion for NF1 diagnosis. Additionally, preconception genetic counselling in patients with NF1 focuses on a 50% risk of transmitting the familial variant as the risk of having a sporadic NF1 is considered the same as the general population.Methods829 individuals, 583 NF1 sporadic cases and 246 patients with NF1 with documented family history, underwent genetic testing for NF1. Genotyping and segregation analysis of NF1 familial variants was determined by microsatellite analysis and NF1 sequencing.ResultsThe mutational analysis of NF1 in 154 families with two or more affected cases studied showed the co-occurrence of two different NF1 germline pathogenic variants in four families. The estimated mutation rate in those families was 3.89×10–3, 20 times higher than the NF1 mutation rate (~2×10−4) (p=0.0008). Furthermore, the co-occurrence of two different NF1 germline pathogenic variants in these families was 1:39, 60 times the frequency of sporadic NF1 (1:2500) (p=0.003). In all cases, the de novo NF1 pathogenic variant was present in a descendant of an affected male. In two cases, variants were detected in the inherited paternal wild-type allele.ConclusionsOur results, together with previous cases reported, suggest that the offspring of male patients with NF1 could have an increased risk of experiencing de novo NF1 pathogenic variants. This observation, if confirmed in additional cohorts, could have relevant implications for NF1 genetic counselling, family planning and NF1 genetic testing.
Published: 2022

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