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1. Timing of Smarcb1 and Nf2 inactivation determines schwannoma versus rhabdoid tumor development.

Author: Vitte, Jeremie, Gao, Fuying, Coppola, Giovanni, Judkins, Alexander R, and Giovannini, Marco
Subjects: Animals, Mice, Transgenic, Mice, Knockout, Humans, Rhabdoid Tumor, Neurilemmoma, Disease Models, Animal, Neurofibromin 2, Gene Expression Profiling, Germ-Line Mutation, Time Factors, Child, Female, Male, Kaplan-Meier Estimate, SMARCB1 Protein, Mice, Transgenic, Knockout, Disease Models, Animal
Abstract: Germline mutations of the SMARCB1 gene predispose to two distinct tumor syndromes: rhabdoid tumor predisposition syndrome, with malignant pediatric tumors mostly developing in brain and kidney, and familial schwannomatosis, with adulthood benign tumors involving cranial and peripheral nerves. The mechanisms by which SMARCB1 germline mutations predispose to rhabdoid tumors versus schwannomas are still unknown. Here, to understand the origin of these two types of SMARCB1-associated tumors, we generated different tissue- and developmental stage-specific conditional knockout mice carrying Smarcb1 and/or Nf2 deletion. Smarcb1 loss in early neural crest was necessary to initiate tumorigenesis in the cranial nerves and meninges with typical histological features and molecular profiles of human rhabdoid tumors. By inducing Smarcb1 loss at later developmental stage in the Schwann cell lineage, in addition to biallelic Nf2 gene inactivation, we generated the first mouse model developing schwannomas with the same underlying gene mutations found in schwannomatosis patients. SMARCB1 mutations predispose to rhabdoid tumors and schwannomas but the mechanisms underlying the tumor type specificity are unknown. Here the authors present new mouse models and show that early Smarcb1 loss causes rhabdoid tumors whereas loss at later stages combined with Nf2 gene inactivation causes shwannomas.
Published: 2017

2. Expanding the mutational spectrum of LZTR1 in schwannomatosis

Author: Paganini, Irene, Chang, Vivian Y, Capone, Gabriele L, Vitte, Jeremie, Benelli, Matteo, Barbetti, Lorenzo, Sestini, Roberta, Trevisson, Eva, Hulsebos, Theo JM, Giovannini, Marco, Nelson, Stanley F, and Papi, Laura
Subjects: Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Cancer, Cancer Genomics, Human Genome, Rare Diseases, Pediatric, Neurofibromatosis, Neurosciences, Clinical Research, 2.1 Biological and endogenous factors, Adult, Aged, Amino Acid Sequence, Exome, Family Health, Female, Genetic Predisposition to Disease, Humans, Immunohistochemistry, Male, Middle Aged, Molecular Sequence Data, Mutation, Neurilemmoma, Neurofibromatoses, Pedigree, Sequence Analysis, DNA, Sequence Homology, Amino Acid, Skin Neoplasms, Transcription Factors, Young Adult, Clinical Sciences, Genetics & Heredity, Clinical sciences
Abstract: Schwannomatosis is characterized by the development of multiple non-vestibular, non-intradermal schwannomas. Constitutional inactivating variants in two genes, SMARCB1 and, very recently, LZTR1, have been reported. We performed exome sequencing of 13 schwannomatosis patients from 11 families without SMARCB1 deleterious variants. We identified four individuals with heterozygous loss-of-function variants in LZTR1. Sequencing of the germline of 60 additional patients identified 18 additional heterozygous variants in LZTR1. We identified LZTR1 variants in 43% and 30% of familial (three of the seven families) and sporadic patients, respectively. In addition, we tested LZTR1 protein immunostaining in 22 tumors from nine unrelated patients with and without LZTR1 deleterious variants. Tumors from individuals with LZTR1 variants lost the protein expression in at least a subset of tumor cells, consistent with a tumor suppressor mechanism. In conclusion, our study demonstrates that molecular analysis of LZTR1 may contribute to the molecular characterization of schwannomatosis patients, in addition to NF2 mutational analysis and the detection of chromosome 22 losses in tumor tissue. It will be especially useful in differentiating schwannomatosis from mosaic Neurofibromatosis type 2 (NF2). However, the role of LZTR1 in the pathogenesis of schwannomatosis needs further elucidation.
Published: 2015

3. Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export.

Author: Legati, Andrea, Giovannini, Donatella, Nicolas, Gaël, López-Sánchez, Uriel, Quintáns, Beatriz, Oliveira, João RM, Sears, Renee L, Ramos, Eliana Marisa, Spiteri, Elizabeth, Sobrido, María-Jesús, Carracedo, Ángel, Castro-Fernández, Cristina, Cubizolle, Stéphanie, Fogel, Brent L, Goizet, Cyril, Jen, Joanna C, Kirdlarp, Suppachok, Lang, Anthony E, Miedzybrodzka, Zosia, Mitarnun, Witoon, Paucar, Martin, Paulson, Henry, Pariente, Jérémie, Richard, Anne-Claire, Salins, Naomi S, Simpson, Sheila A, Striano, Pasquale, Svenningsson, Per, Tison, François, Unni, Vivek K, Vanakker, Olivier, Wessels, Marja W, Wetchaphanphesat, Suppachok, Yang, Michele, Boller, Francois, Campion, Dominique, Hannequin, Didier, Sitbon, Marc, Geschwind, Daniel H, Battini, Jean-Luc, and Coppola, Giovanni
Subjects: Humans, Brain Diseases, Metabolic, Inborn, Neurodegenerative Diseases, Calcinosis, Genetic Predisposition to Disease, Receptors, G-Protein-Coupled, Receptors, Virus, Pedigree, DNA Mutational Analysis, Lod Score, Mutation, Missense, Middle Aged, Female, Male, Genetic Association Studies, HEK293 Cells, Xenotropic and Polytropic Retrovirus Receptor, Neurosciences, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract: Primary familial brain calcification (PFBC) is a neurological disease characterized by calcium phosphate deposits in the basal ganglia and other brain regions and has thus far been associated with SLC20A2, PDGFB or PDGFRB mutations. We identified in multiple families with PFBC mutations in XPR1, a gene encoding a retroviral receptor with phosphate export function. These mutations alter phosphate export, implicating XPR1 and phosphate homeostasis in PFBC.
Published: 2015

4. Phase II study of mTORC1 inhibition by everolimus in neurofibromatosis type 2 patients with growing vestibular schwannomas

Author: Goutagny, Stéphane, Raymond, Eric, Esposito-Farese, Marina, Trunet, Stéphanie, Mawrin, Christian, Bernardeschi, Daniele, Larroque, Béatrice, Sterkers, Olivier, Giovannini, Marco, and Kalamarides, Michel
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Pediatric, Brain Disorders, Neurofibromatosis, Cancer, Rare Diseases, Neurosciences, Clinical Research, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Adolescent, Adult, Antineoplastic Agents, Biomarkers, Tumor, Cranial Nerve Neoplasms, Disease Progression, Disease-Free Survival, Everolimus, Female, Follow-Up Studies, Humans, Male, Mechanistic Target of Rapamycin Complex 1, Multiprotein Complexes, Neurilemmoma, Neurofibromatosis 2, Prospective Studies, TOR Serine-Threonine Kinases, Treatment Outcome, Tumor Burden, Vestibulocochlear Nerve Diseases, Young Adult, Tumor stabilization, Time to tumor progression, Vestibular schwannoma, Meningioma, Oncology and Carcinogenesis, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract: Neurofibromatosis type 2 (NF2) is a genetic disorder with bilateral vestibular schwannomas (VS) as the most frequent manifestation. Merlin, the NF2 tumor suppressor, was identified as a negative regulator of mammalian target of rapamycin complex 1. Pre-clinical data in mice showed that mTORC1 inhibition delayed growth of NF2-schwannomas. We conducted a prospective single-institution open-label phase II study to evaluate the effects of everolimus in ten NF2 patients with progressive VS. Drug activity was monitored every 3 months. Everolimus was administered orally for 12 months and, if the decrease in tumor volume was >20 % from baseline, treatment was continued for 12 additional months. Other patients stopped when completed 12 months of everolimus but were allowed to resume treatment when VS volume was >20 % during 1 year follow-up. Nine patients were evaluable. Safety was evaluated using CTCAE 3.0 criteria. After 12 months of everolimus, no reduction in volume ≥20 % was observed. Four patients had progressive disease, and five patients had stable disease with a median annual growth rate decreasing from 67 %/year before treatment to 0.5 %/year during treatment. In these patients, tumor growth resumed within 3-6 months after treatment discontinuation. Everolimus was then reintroduced and VS decreased by a median 6.8 % at 24 months. Time to tumor progression increased threefold from 4.2 months before treatment to > 12 months. Hearing was stable under treatment. The safety of everolimus was manageable. Although the primary endpoint was not reached, further studies are required to confirm the potential for stabilization of everolimus.
Published: 2015

5. Merlin Isoforms 1 and 2 Both Act as Tumour Suppressors and Are Required for Optimal Sperm Maturation.

Author: Zoch, Ansgar, Mayerl, Steffen, Schulz, Alexander, Greither, Thomas, Frappart, Lucien, Rübsam, Juliane, Heuer, Heike, Giovannini, Marco, and Morrison, Helen
Subjects: Muscles, Liver, Testis, Spermatozoa, Neuroglia, Animals, Mice, Inbred C57BL, Mice, Knockout, Mice, Neoplasms, Neurilemmoma, Brain Neoplasms, Neurofibromin 2, Protein Isoforms, Flow Cytometry, Cell Separation, In Situ Hybridization, Signal Transduction, Spermatogenesis, Gene Deletion, Fertility, Genotype, Phenotype, Female, Male, General Science & Technology
Abstract: The tumour suppressor Merlin, encoded by the gene NF2, is frequently mutated in the autosomal dominant disorder neurofibromatosis type II, characterised primarily by the development of schwannoma and other glial cell tumours. However, NF2 is expressed in virtually all analysed human and rodent organs, and its deletion in mice causes early embryonic lethality. Additionally, NF2 encodes for two major isoforms of Merlin of unknown functionality. Specifically, the tumour suppressor potential of isoform 2 remains controversial. In this study, we used Nf2 isoform-specific knockout mouse models to analyse the function of each isoform during development and organ homeostasis. We found that both isoforms carry full tumour suppressor functionality and can completely compensate the loss of the other isoform during development and in most adult organs. Surprisingly, we discovered that spermatogenesis is strictly dependent on the presence of both isoforms. While the testis primarily expresses isoform 1, we noticed an enrichment of isoform 2 in spermatogonial stem cells. Deletion of either isoform was found to cause decreased sperm quality as observed by maturation defects and head/midpiece abnormalities. These defects led to impaired sperm functionality as assessed by decreased sperm capacitation. Thus, we describe spermatogenesis as a new Nf2-dependent process. Additionally, we provide for the first time in vivo evidence for equal tumour suppressor potentials of Merlin isoform 1 and isoform 2.
Published: 2015

6. A general model of dioxin contamination in breast milk: results from a study on 94 women from the Caserta and Naples areas in Italy.

Author: Rivezzi, Gaetano, Piscitelli, Prisco, Scortichini, Giampiero, Giovannini, Armando, Diletti, Gianfranco, Migliorati, Giacomo, Ceci, Roberta, Rivezzi, Giulia, Cirasino, Lorenzo, Carideo, Pietro, Black, Dennis M, Garzillo, Carmine, and Giani, Umberto
Subjects: Milk, Human, Humans, Polychlorinated Biphenyls, Dioxins, Environmental Pollutants, Environmental Exposure, Environmental Monitoring, Models, Biological, Adult, Italy, Female, Young Adult, Milk, Human, Models, Biological, Toxicology
Abstract: BackgroundThe Caserta and Naples areas in Campania Region experience heavy environmental contamination due to illegal waste disposal and burns, thus representing a valuable setting to develop a general model of human contamination with dioxins (PCDDs-PCDFs) and dioxin-like-PCBs (dl-PCBs).Methods94 breastfeeding women (aged 19-32 years; mean age 27.9 ± 3.0) were recruited to determine concentrations of PCDDs-PCDFs and dl-PCBs in their milk. Individual milk samples were collected and analyzed according to standard international procedures. A generalized linear model was used to test potential predictors of pollutant concentration in breast milk: age, exposure to waste fires, cigarette smoking, diet, and residence in high/low risk area (defined at high/low environmental pressure by a specific 2007 WHO report). A Structural Equation Model (SEM) analysis was carried out by taking into account PCDDs-PCDFs and dl-PCBs as endogenous variables and age, waste fires, risk area and smoking as exogenous variables.ResultsAll milk samples were contaminated by PCDDs-PCDFs (8.6 pg WHO-TEQ/98g fat ± 2.7; range 3.8-19) and dl-PCBs (8.0 pg WHO-TEQ/98g fat ± 3.7; range 2.5-24), with their concentrations being associated with age and exposure to waste fires (p < 0.01). Exposure to fires resulted in larger increases of dioxins concentrations in people living in low risk areas than those from high risk areas (p < 0.01).ConclusionsA diffuse human exposure to persistent organic pollutants was observed in the Caserta and Naples areas. Dioxins concentration in women living in areas classified at low environmental pressure in 2007 WHO report was significantly influenced by exposure to burns.
Published: 2013

7. MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors

Author: Jessen, Walter J, Miller, Shyra J, Jousma, Edwin, Wu, Jianqiang, Rizvi, Tilat A, Brundage, Meghan E, Eaves, David, Widemann, Brigitte, Kim, Mi-Ok, Dombi, Eva, Sabo, Jessica, Dudley, Atira Hardiman, Niwa-Kawakita, Michiko, Page, Grier P, Giovannini, Marco, Aronow, Bruce J, Cripe, Timothy P, and Ratner, Nancy
Subjects: Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Biotechnology, Pediatric, Cancer, Rare Diseases, Neurofibromatosis, Pediatric Cancer, Neurosciences, Animals, Benzamides, Child, Child, Preschool, Diphenylamine, Extracellular Signal-Regulated MAP Kinases, Female, Humans, Male, Mice, Mice, Mutant Strains, Mitogen-Activated Protein Kinase Kinases, Neoplasm Transplantation, Neurofibromatosis 1, Oncogene Protein p21(ras), Peripheral Nervous System Neoplasms, Transcriptome, Transplantation, Heterologous, Xenograft Model Antitumor Assays, raf Kinases, Medical and Health Sciences, Immunology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract: Neurofibromatosis type 1 (NF1) patients develop benign neurofibromas and malignant peripheral nerve sheath tumors (MPNST). These incurable peripheral nerve tumors result from loss of NF1 tumor suppressor gene function, causing hyperactive Ras signaling. Activated Ras controls numerous downstream effectors, but specific pathways mediating the effects of hyperactive Ras in NF1 tumors are unknown. We performed cross-species transcriptome analyses of mouse and human neurofibromas and MPNSTs and identified global negative feedback of genes that regulate Ras/Raf/MEK/ERK signaling in both species. Nonetheless, ERK activation was sustained in mouse and human neurofibromas and MPNST. We used a highly selective pharmacological inhibitor of MEK, PD0325901, to test whether sustained Ras/Raf/MEK/ERK signaling contributes to neurofibroma growth in a neurofibromatosis mouse model (Nf1(fl/fl);Dhh-Cre) or in NF1 patient MPNST cell xenografts. PD0325901 treatment reduced aberrantly proliferating cells in neurofibroma and MPNST, prolonged survival of mice implanted with human MPNST cells, and shrank neurofibromas in more than 80% of mice tested. Our data demonstrate that deregulated Ras/ERK signaling is critical for the growth of NF1 peripheral nerve tumors and provide a strong rationale for testing MEK inhibitors in NF1 clinical trials.
Published: 2013

8. Possible Strategies to Optimize a Biomarker Discovery Approach to Correlate with Neurological Outcome in Patients with Spinal Cord Injury: A Pilot Study

Author: Luciana Giardino, Vito Antonio Baldassarro, Tiziana Giovannini, Mercedes Fernandez, Giulia Giovannini, Gordini Giovanni, Maura Cescatti, Roberto Montevecchi, Rita Capirossi, Laura Calzà, Mariella Uneddu, Jacopo Bonavita, Fernandez M., Baldassarro V.A., Capirossi R., Montevecchi R., Bonavita J., Cescatti M., Giovannini T., Giovannini G., Uneddu M., Giovanni G., Giardino L., and Calza' L.
Subjects: Adult, Male, inflammatory cytokine, 030506 rehabilitation, Oligodendrocyte progenitor, Pilot Projects, CSF, Bioinformatics, oligodendrocyte precursor cell, Proinflammatory cytokine, Mice, 03 medical and health sciences, 0302 clinical medicine, Neural Stem Cells, Animals, Humans, Medicine, In patient, Biomarker discovery, Spinal cord injury, Spinal Cord Injuries, Aged, IL-8, business.industry, multi-parametric assay, Recovery of Function, Middle Aged, Spinal cord, medicine.disease, RAW 264.7 Cells, Treatment Outcome, medicine.anatomical_structure, SCI, biomarker, Female, Neurology (clinical), 0305 other medical science, business, Biomarkers, 030217 neurology & neurosurgery
Abstract: The lack of reliable diagnostic and prognostic markers for spinal cord injured (SCI) patients is a severe obstacle in development and testing of new therapies, and it also impairs appropriate rehabilitation care. The sparse available data on the biochemical composition of cerebrospinal fluid (CSF) during the acute and/or chronic phase of the lesion provide, up until now, inconsistent results. In this pilot study, we then explored the possibility of combining a multi-parametric and bioinformatic analysis of CSF for its biological properties tested on different cells types, suitable for investigating inflammation and re-myelination. The patient enrollment was based on stringent inclusion criteria; that is, cervical and thoracic SCI trauma, CSF collection within 24 h of trauma, type of surgical approach for spine stabilization, and absence of steroid therapy before CSF collection. Eleven SCI patients and four healthy controls were included, and in three patients, CSF was also collected at 3 months after lesion. We identified 19 proteins among the 60 investigated cytokines, chemokines, growth factors, and structural biomarkers, which are transiently regulated 24 h after SCI. A bioinformatic analysis indicated that interleukin (IL)-6 and IL-10 are in the core of the interconnected net of activated proteins. Cell-based experiments indicate that CSF from SCI patients stimulates astroglia derivation from neural precursor cells, and an inverse correlation between IL-8 CSF level and oligodendrocyte precursor cells generated from neural stem cells was also observed. Results from this pilot study suggest that using a combined bioanalytic and biological approach to analyze SCI CSF at different times after injury could be a useful approach for identifying reliable diagnostic and prognostic markers in SCI.
Published: 2020
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9. EUS-guided radiofrequency ablation for pancreatic insulinoma: experience in 2 tertiary centers

Author: Mariola, Marx, Toni, Trosic-Ivanisevic, Fabrice, Caillol, Nicolas, Demartines, Alain, Schoepfer, Christian, Pesenti, Jean-Philippe, Ratone, Maxime, Robert, Marc, Giovannini, and Sébastien, Godat
Subjects: Pancreatic Neoplasms, Radiofrequency Ablation, Catheter Ablation, Gastroenterology, Humans, Female, Insulinoma, Radiology, Nuclear Medicine and imaging, Aged, Endosonography
Abstract: Insulinoma is the most frequent functional neuroendocrine tumor of the pancreas, and preserving surgery is the treatment of choice. EUS-guided radiofrequency ablation (EUS-RFA) is a novel and promising technique that induces tissue necrosis of localized lesions. This article presents a preliminary clinical experience in treating pancreatic insulinomas 2 cm by EUS-RFA, focusing on safety and efficacy.The clinical course of patients with pancreatic insulinoma treated by EUS-RFA at 2 tertiary referral centers was analyzed.Between November 2017 and December 2020, 7 patients were included (6 women; mean age, 66 years). EUS-RFA was feasible in all patients with immediate hypoglycemia relief after only 1 single treatment session; 6 of 7 achieved complete response by cross-sectional imaging and remained asymptomatic (median follow-up, 21 months; range, 3-38). Three patients had minor adverse events. One elderly patient developed a large retrogastric collection 15 days after treatment and died 1 month after EUS-RFA.Management of pancreatic neuroendocrine tumors 2 cm by EUS-RFA seems to be effective with an acceptable safety profile. However, further evidence focusing on long-term survival and recurrence is needed.
Published: 2022
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10. Coarazuphium bambui (Carabidae: Zuphiini), a new cave-dwelling beetle from the threatened region of Serra do Ramalho, Brazil

Author: THAIS GIOVANNINI PELLEGRINI, MARIA ELINA BICHUETTE, and LETÍCIA VIEIRA
Subjects: Male, Insecta, Arthropoda, Biodiversity, Coleoptera, Caves, Animalia, Animals, Female, Animal Science and Zoology, Carabidae, Brazil, Ecology, Evolution, Behavior and Systematics, Taxonomy
Abstract: To date, 20 species of obligate cave-dwelling beetles are known from Brazil, and 12 belong to the Coarazuphium genus. In this paper, we describe Coarazuphium bambui sp. n., from two specimens, one male and one female, collected in the Gruna Boca da Lapa cave located in the municipality of Feira da Mata (Bahia state, Brazil). The most striking difference between C. bambui and other species of the genus is the presence of three pairs of fixed setae posteriorly on the head, combined with the slightly elytral sinuosity. We also provide an updated key for species identification of the Coarazuphium genus. Finally, we highlight the importance of the Serra do Ramalho karst area for the conservation of troglobite diversity in the Brazilian context.
Published: 2022
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11. Regional Survey in Lombardy, Northern Italy, on Vascular Surgery Intervention Outcomes During The COVID-19 Pandemic

Author: Raffaello Bellosta, Gabriele Piffaretti, Stefano Bonardelli, Patrizio Castelli, Roberto Chiesa, Dalmazio Frigerio, Gaetano Lanza, Stefano Pirrelli, Giovanni Rossi, Santi Trimarchi, Franco Briolini, Pietro Cefali, Roberto Caronno, Aldo Arzini, Domenico Diaco, Vittorio Baratta, Stefano Aiello, Alessandro C.L. Molinari, Francesca Giovannini, Anna Maria Socrate, Matteo Ferraris, Antonino Silvestro, Gianluca Canu, Emidio Costantini, Davide Logaldo, Federico Romani, Alfredo Lista, Cristina Busoni, Marco Setti, Roberto Mezzetti, Piergiorgio Sala, Luca Bassi, Luca Luzzani, Matteo A. Pegorer, Luca Attisani, Claudio Carugati, Monica Vescovi, Piero Trabattoni, Stefano Zoli, Andrea Rignano, Clara Magri, Pierluigi Vandone, Sergio Losa, Efrem Civilini, Giovanni Nano, Daniela Mazzaccaro, Valerio Tolva, Jessica Lanza, Ruggiero Curci, Giovanna Simonetti, Chiara Lomazzi, Viviana Grassi, Daniele Bissacco, Andrea Kahlberg, Daniele Mascia, Raffaello Dallatana, Michele Carmo, Franco Ragni, Enrico M. Marone, Antonio Bozzani, Matteo Tozzi, Marco Franchin, Gianluca Lussardi, Vittorio Segramora, Gaetano Deleo, Matteo Crippa, Tiziano Porretta, Marco Viani, Silvia Stegher, Davide Foresti, Giovanni Bonalumi, Bellosta, R., Piffaretti, G., Bonardelli, S., Castelli, P., Chiesa, R., Frigerio, D., Lanza, G., Pirrelli, S., Rossi, G., Trimarchi, S., Briolini, F., Cefali, P., Caronno, R., Arzini, A., Diaco, D., Baratta, V., Aiello, S., Molinari, A. C. L., Giovannini, F., Socrate, A. M., Ferraris, M., Silvestro, A., Canu, G., Costantini, E., Logaldo, D., Romani, F., Lista, A., Busoni, C., Setti, M., Mezzetti, R., Sala, P., Bassi, L., Luzzani, L., Pegorer, M. A., Attisani, L., Carugati, C., Vescovi, M., Trabattoni, P., Zoli, S., Rignano, A., Magri, C., Vandone, P., Losa, S., Civilini, E., Nano, G., Mazzaccaro, D., Tolva, V., Lanza, J., Curci, R., Simonetti, G., Lomazzi, C., Grassi, V., Bissacco, D., Kahlberg, A., Mascia, D., Dallatana, R., Carmo, M., Ragni, F., Marone, E. M., Bozzani, A., Tozzi, M., Franchin, M., Lussardi, G., Segramora, V., Deleo, G., Crippa, M., Porretta, T., Viani, M., Stegher, S., Foresti, D., and Bonalumi, G.
Subjects: Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), COVID-19, acute limb ischaemia, vascular surgery activities, Cohort Studies, Postoperative Complications, Intervention (counseling), Pandemic, Humans, Medicine, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Outbreak, Middle Aged, Vascular surgery, Northern italy, Treatment Outcome, Italy, Health Care Surveys, Emergency medicine, Female, Surgery, Cardiology and Cardiovascular Medicine, business, Complication, Vascular Surgical Procedures, Cohort study
Abstract: Objective: The characteristics and outcomes of patients undergoing vascular surgery hospitalised and managed in Lombardy are described with a comparison of patients tested positive for COVID-19 (CV19-pos) vs. those tested negative (CV19-neg). Methods: This was a multicentre, retrospective, observational cohort study which involved all vascular surgery services in Lombardy, Northern Italy. Data were retrospectively merged into a combined dataset covering the nine weeks of the Italian COVID-19 pandemic phase 1 (8 March 2020 to 3 May 2020). The primary outcome was freedom from in hospital death, secondary outcomes were re-thrombosis rate after peripheral revascularisation, and freedom from post-operative complication. Results: Among 674 patients managed during the outbreak, 659 (97.8%) were included in the final analysis: 121 (18.4%) were CV19-pos. CV19-pos status was associated with a higher rate of complications (OR 4.5; p < .001, 95% CI 2.64 – 7.84), and a higher rate of re-thrombosis after peripheral arterial revascularisation (OR 2.2; p = .004, 95% CI 1.29 – 3.88). In hospital mortality was higher in CV19-pos patients (24.8% vs. 5.6%; OR 5.4, p < .001;95% CI 2.86 – 8.92). Binary logistic regression analysis identified CV19-pos status (OR 7.6; p < .001, 95% CI 3.75 – 15.28) and age > 80 years (OR 3.2; p = .001, 95% CI 1.61 – 6.57) to be predictors of in hospital death. Conclusion: In this experience of the vascular surgery group of Lombardy, COVID-19 infection was a marker of poor outcomes in terms of mortality and post-operative complications for patients undergoing vascular surgery treatments.
Published: 2021
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12. Scalpel Sign in Spine Pathology: Presentation in 3 Different Rare Diagnoses

Author: Francisco Marcó del Pont, Sebastian J.M. Giovannini, Aguilar Martin, Andrés Cervio, Mauro Ruella, and Tomás Ries Centeno
Subjects: Male, medicine.medical_specialty, Surgical planning, Spinal Cord Diseases, Thoracic Vertebrae, Pathognomonic, medicine, Back pain, Humans, Aged, Retrospective Studies, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, Middle Aged, Spinal cord, Magnetic Resonance Imaging, Sagittal plane, Arachnoid Cysts, body regions, medicine.anatomical_structure, Female, Surgery, Neurology (clinical), Radiology, medicine.symptom, Presentation (obstetrics), business, Myelography, Intervertebral Disc Displacement
Abstract: Background The scalpel sign is a radiological finding observed on sagittal magnetic resonance imaging and computed tomography myelography corresponding to an indentation in the dorsal aspect of the spinal cord resembling a surgical scalpel blade. It is said to be a pathognomonic imaging discovery linked to dorsal arachnoid webs. However, other spine-related conditions may mimic dorsal arachnoid webs on magnetic resonance imaging, such as spinal arachnoid cysts or ventral spinal cord herniation, leading to misdiagnosis. Methods A retrospective review was performed of cases involving 3 different diagnoses at our institution in the last 5 years that shared in common the characteristic focal dorsal indentation of the spinal cord. Results Of 7 cases identified, all but 1 were treated and confirmed intraoperatively. All lesions were located at the dorsal spinal cord. Magnetic resonance imaging was the study of choice for evaluation. Clinical manifestations included back pain and lower extremity numbness and weakness together with compressive myelopathy signs and urinary symptoms. Mean follow-up was 16.8 months with satisfactory postoperative results. Conclusions Isolated radiological presentation of the scalpel sign is not sufficient to distinguish between dorsal arachnoid webs, arachnoid cysts, and ventral herniation of the spine. However, awareness of its importance is relevant for accurate curative surgical planning.
Published: 2022
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13. Machine Learning Model to Predict Diagnosis of Mild Cognitive Impairment by Using Radiomic and Amyloid Brain PET

Author: Andrea, Ciarmiello, Elisabetta, Giovannini, Sara, Pastorino, Ornella, Ferrando, Franca, Foppiano, Antonio, Mannironi, Antonio, Tartaglione, and Giampiero, Giovacchini
Subjects: Male, Machine Learning, Amyloid, Clinical Trials as Topic, Alzheimer Disease, Positron Emission Tomography Computed Tomography, Humans, Brain, Female, Cognitive Dysfunction, Middle Aged, Aged
Abstract: The study aimed to develop a deep learning model for predicting amnestic mild cognitive impairment (aMCI) diagnosis using radiomic features and amyloid brain PET.Subjects (n = 328) from the Alzheimer's Disease Neuroimaging Initiative database and the EudraCT 2015-001184-39 trial (159 males, 169 females), with a mean age of 72 ± 7.4 years, underwent PET/CT with 18 F-florbetaben. The study cohort consisted of normal controls (n = 149) and subjects with aMCI (n = 179). Thirteen gray-level run-length matrix radiomic features and amyloid loads were extracted from 27 cortical brain areas. The least absolute shrinkage and selection operator regression was used to select features with the highest predictive value. A feed-forward neural multilayer network was trained, validated, and tested on 70%, 15%, and 15% of the sample, respectively. Accuracy, precision, F1-score, and area under the curve were used to assess model performance. SUV performance in predicting the diagnosis of aMCI was also assessed and compared with that obtained from the machine learning model.The machine learning model achieved an area under the receiver operating characteristic curve of 90% (95% confidence interval, 89.4-90.4) on the test set, with 80% and 78% for accuracy and F1-score, respectively. The deep learning model outperformed SUV performance (area under the curve, 71%; 95% confidence interval, 69.7-71.4; 57% accuracy, 48% F1-score).Using radiomic and amyloid PET load, the machine learning model identified MCI subjects with 84% specificity at 81% sensitivity. These findings show that a deep learning algorithm based on radiomic data and amyloid load obtained from brain PET images improves the prediction of MCI diagnosis compared with SUV alone.
Published: 2022

14. NIR Laser Photobiomodulation Induces Neuroprotection in an In Vitro Model of Cerebral Hypoxia/Ischemia

Author: Elettra Sereni, Daniele Lana, Daniele Nosi, Elisabetta Gerace, Maria Grazia Giovannini, Francesca Cialdai, Monica Monici, and Guido Mannaioni
Subjects: Male, 0301 basic medicine, NIR laser, Neuroscience (miscellaneous), Ischemia, Hippocampal formation, Hippocampus, Neuroprotection, Article, law.invention, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Organ Culture Techniques, Oxygen and glucose deprivation, 0302 clinical medicine, Confocal microscopy, law, medicine, Animals, Propidium iodide, Low-Level Light Therapy, Rats, Wistar, Neurodegeneration, Neuroinflammation, Chemistry, Neurotoxicity, Photobiomodulation, Hypoxia (medical), Organotypic hippocampal slices, medicine.disease, Rats, 030104 developmental biology, nervous system, Microscopy, Fluorescence, Neurology, Hypoxia-Ischemia, Brain, Biophysics, Female, Glia activation, Laser Therapy, medicine.symptom, 030217 neurology & neurosurgery
Abstract: Brain photobiomodulation (PBM) is an innovative treatment for a variety of neurological conditions, including cerebral ischemia. However, the capability of PBM for ischemic stroke needs to be further explored and its mechanisms of action remain currently unclear. The aim of the present research was to identify a treatment protocol capable of inducing neuroprotection and to investigate the molecular mechanisms activated by a dual-wavelength near infrared (NIR) laser source in an organotypic hippocampal slice model of hypoxia/ischemia. Hippocampal slices were exposed to oxygen and glucose deprivation (OGD) for 30 min followed by NIR laser light (fluence 3.71, 7.42, or 14.84 J/cm2; wavelengths 808 nm and 905 nm) delivered immediately or 30 min or 60 min after OGD, in order to establish a therapeutic window. Neuronal injury was assessed by propidium iodide fluorescence 24 h later. Our results show that NIR laser irradiation attenuates OGD neurotoxicity once applied immediately or 30 min after OGD. Western blot analysis of proteins involved in neuroinflammation (iNOS, COX-2, NFkB subunit p65, and Bcl-2) and in glutamatergic-mediated synaptic activity (vGluT1, EAAT2, GluN1, and PSD95) showed that the protein modifications induced by OGD were reverted by NIR laser application. Moreover, CA1 confocal microscopy revealed that the profound morphological changes induced by OGD were reverted by NIR laser radiation. In conclusion, NIR laser radiation attenuates OGD neurotoxicity in organotypic hippocampal slices through attenuation of inflammatory mechanisms. These findings shed light on molecular definition of NIR neuroprotective mechanisms, thus underlining the potential benefit of this technique for the treatment of cerebral ischemia.
Published: 2021
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15. Endoscopic radiofrequency ablation or surveillance in patients with Barrett’s oesophagus with confirmed low-grade dysplasia: a multicentre randomised trial

Author: Jean Escourrou, Frédéric Prat, Romain Legros, Nadira Kaddour, Edouard Chabrun, Marc Le Rhun, Michael Bensoussan, Hendy Abdoul, Frank Zerbib, Thierry Ponchon, Maximilien Barret, E Metivier-Cesbron, Stanislas Chaussade, Gabriel Rahmi, Fabrice Caillol, P. Bauret, Lea Jilet, Geoffroy Vanbiervliet, Jérémie Jacques, Marc Giovannini, Julien Branche, Benoit Terris, Mathieu Pioche, René Laugier, Christian Boustière, Franck Cholet, Emmanuel Coron, and Sarah Leblanc
Subjects: Male, medicine.medical_specialty, Hospitals, Low-Volume, Time Factors, Esophageal Neoplasms, Radiofrequency ablation, Adenocarcinoma, Endoscopy, Gastrointestinal, law.invention, Barrett Esophagus, law, medicine, Humans, In patient, Prospective Studies, Watchful Waiting, Trial registration, Aged, Radiofrequency Ablation, business.industry, Gastroenterology, Intestinal metaplasia, Middle Aged, medicine.disease, Endoscopic ablation, Surgery, Low grade dysplasia, Treatment Outcome, Dysplasia, Barrett's oesophagus, Disease Progression, Female, business, Hospitals, High-Volume
Abstract: ObjectiveDue to an annual progression rate of Barrett’s oesophagus (BO) with low-grade dysplasia (LGD) between 9% and 13% per year endoscopic ablation therapy is preferred to surveillance. Since this recommendation is based on only one randomised trial, we aimed at checking these results by another multicentre randomised trial with a similar design.DesignA prospective randomised study was performed in 14 centres comparing radiofrequency ablation (RFA) (maximum of 4 sessions) to annual endoscopic surveillance, including patients with a confirmed diagnosis of BO with LGD. Primary outcome was the prevalence of LGD at 3 years. Secondary outcomes were the prevalence of LGD at 1 year, the complete eradication of intestinal metaplasia (CE-IM) at 3 years, the rate of neoplastic progression at 3 years and the treatment-related morbidity.Results125 patients were initially included, of whom 82 with confirmed LGD (76 men, mean age 62.3 years) were finally randomised, 40 patients in the RFA and 42 in the surveillance group. At 3 years, CE-IM rates were 35% vs 0% in the RFA and surveillance groups, respectively (pConclusionRFA modestly reduced the prevalence of LGD as well as progression risk at 3 years. The risk-benefit balance of endoscopic ablation therapy should therefore be carefully weighted against surveillance in patients with BO with confirmed LGD.Trial registration numberNCT01360541.
Published: 2021
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16. Surgical Treatment of IV Ventricle Calcifying Pseudoneoplasm of the Neuraxis (CAPNON) Operative Nuances

Author: Sebastian J, M Giovannini, Mauro, Ruella, Facundo, Villamil, Emiliano, Lorefice, Guido, Caffaratti, and Andrés, Cervio
Subjects: Adult, Central Nervous System, Calcinosis, Humans, Female, Tomography, X-Ray Computed, Cerebral Ventricles, Hydrocephalus
Abstract: Calcifying pseudoneoplasm of the neuroaxis (CAPNON) is a rare, slow growing, and generally benign fibro osseous mass that can emerge throughout the entire central nervous system (CNS). When diagnosed, prompt surgical treatment can determine a good neurological outcome and possibly curative resolution. The objective of the present work is to present a step by step technical report with its video. We present a 37 year old female presented with occipital headache and cervical pain associated with dysphagia, nausea, and gait disturbances. Computed tomography (CT) scan showed a focal calcified lesion on the floor of the IV ventricle projecting toward the vermis with associated supratentorial hydrocephalus and transependymal edema. The telovelar approach was chosen for the procedure. The outcome was favorable, with no complications. Postoperative CT was performed, which revealed no residual lesion. A step by step report of a IV ventricle CAPNON that manifested with hydrocephalus is described.
Published: 2022

17. RObotic-Assisted Rehabilitation for balance and gait in Stroke patients (ROAR-S): study protocol for a preliminary randomized controlled trial

Author: Silvia Giovannini, Chiara Iacovelli, Fabrizio Brau, Claudia Loreti, Augusto Fusco, Pietro Caliandro, Lorenzo Biscotti, Luca Padua, Roberto Bernabei, and Letizia Castelli
Subjects: Male, Stroke Rehabilitation, Medicine (miscellaneous), State Medicine, Exercise Therapy, Stroke, Treatment Outcome, Robotic Surgical Procedures, Activities of Daily Living, Quality of Life, Humans, Pharmacology (medical), Female, Gait, Postural Balance, Fatigue, Aged, Randomized Controlled Trials as Topic
Abstract: Background Stroke, the incidence of which increases with age, has a negative impact on motor and cognitive performance, quality of life, and the independence of the person and his or her family, leading to a number of direct and indirect costs. Motor recovery is essential, especially in elderly patients, to enable the patient to be independent in activities of daily living and to prevent falls. Several studies have shown how robotic training associated with physical therapy influenced functional and motor outcomes of walking after stroke by improving endurance and walking strategies. Considering data from previous studies and patients’ needs in gait and balance control, we hypothesized that robot-assisted balance treatment associated with physical therapy may be more effective than usual therapy performed by a physical therapist in terms of improving static, dynamic balance and gait, on fatigue and cognitive performance. Methods This is an interventional, single-blinded, preliminary randomized control trial. Twenty-four patients of both sexes will be recruited, evaluated, and treated at the UOC Rehabilitation and Physical Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome from January to December 2022. Patients will be randomized into two groups: the experimental group will perform specific rehabilitation for balance disorder using the Hunova® robotic platform (Movendo Technology srl, Genoa, IT) for 3 times a week, for 4 weeks (12 total sessions), and for 45 min of treatment, in addition to conventional treatment, while the conventional group (GC) will perform only conventional treatment as per daily routine. All patients will undergo clinical and instrumental evaluation at the beginning and end of the 4 weeks of treatment. Conclusions The study aims to evaluate the improvement in balance, fatigue, quality of life, and motor and cognitive performance after combined conventional and robotic balance treatment with Hunova® (Movendo Technology srl, Genoa, IT) compared with conventional therapy alone. Robotic assessment to identify the most appropriate and individualized rehabilitation treatment may allow reducing disability and improving quality of life in the frail population. This would reduce direct and indirect social costs of care and treatment for the National Health Service and caregivers. Trial registration ClinicalTrials.gov NCT05280587. Registered on March 15, 2022.
Published: 2022

18. Allergy to Gibberellin-Regulated Proteins (Peamaclein) in Children

Author: Lucrezia Sarti, Francesca Mori, Mattia Giovannini, Francesco Citera, Leonardo Tomei, Benedetta Biagioni, Claudia Valleriani, Giulia Liccioli, and Simona Barni
Subjects: Male, medicine.medical_specialty, Allergy, Adolescent, Immunology, Allergic condition, Cross Reactions, Immunoglobulin E, Culprit, Allergy Unit, Food allergy, Clinical Decision Rules, Internal medicine, medicine, Humans, Immunology and Allergy, Child, Sensitization, Plant Proteins, Retrospective Studies, Skin Tests, Prunus persica, biology, business.industry, General Medicine, European population, Allergens, Antigens, Plant, medicine.disease, Gibberellins, medicine.anatomical_structure, Child, Preschool, Fruit, biology.protein, Pollen, Female, business, Algorithms, Biomarkers, Food Hypersensitivity
Abstract: Background: Gibberellin-regulated proteins (GRPs, Peamaclein) are allergens recently identified in plant-derived food allergy (FA), and little is known about the clinical manifestations of this allergic condition in the European population, especially in children. Objective: Our study aimed to identify and characterize pediatric patients with pollen-FA due to GRP sensitization. Methods: We retrospectively analyzed the charts of patients referred to the Allergy Unit of the Meyer Children’s Hospital in Florence for suspected FA. Three main eligibility criteria based on the actual knowledge of GRP allergy were used to select patients deserving further investigations: (1) systemic reactions after consumption of fruit or an unknown culprit food, (2) positive skin prick tests to both cypress pollen and Pru p 3-enriched peach peel extracts, (3) negative in vitro test results for Pru p 3 serum-specific Immunoglobulin E (sIgE). We performed the in vitro test to determine the anti-rPru p 7 (Peamaclein) sIgE levels in the selected patients. Results: We identified 10 pediatric patients with Pru p 7 allergy and described their characteristics. The use of our eligibility criteria showed a high accuracy in identifying these patients: 100% of the selected patients had positive in vitro results for Pru p 7. We therefore proposed a diagnostic algorithm for Pru p 7 allergy. Conclusion: This is the first case series of European pediatric patients with a demonstrated Peamaclein allergy. These findings broaden our knowledge on GRP allergy in pediatric populations and could help clinicians to suspect, diagnose, and manage this recently discovered plant-derived FA.
Published: 2021
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19. An Italian experience with mechanochemical ablation of the saphenous vein since 2012

Author: Tania Francesca Cappellari, Mattia Mirandola, Bruno Migliara, Andrea Griso, Marcello Lino, and Francesca Giovannini
Subjects: Ablation Techniques, Adult, Male, medicine.medical_specialty, Time Factors, Polidocanol, 030204 cardiovascular system & hematology, Varicose Veins, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Sclerotherapy, Occlusion, Varicose veins, medicine, Humans, Saphenous Vein, 030212 general & internal medicine, Vein, Aged, Retrospective Studies, Aged, 80 and over, Mechanochemical ablation, business.industry, Endovascular Procedures, Endovenous ablation, Middle Aged, Sclerosing Solutions, Surgery, Catheter, Treatment Outcome, medicine.anatomical_structure, Italy, Venous Insufficiency, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Saphenous veins, Vascular Access Devices, medicine.drug
Abstract: Objective Mechanochemical endovenous ablation is a nonthermal method to ablate superficial incompetent veins. The aim of this paper was to assess short-term complications and 5-year follow-up outcomes. Methods This is a retrospective single-center study of data collected prospectively. We treated, in an outpatient setting, 395 primary, symptomatic, unilateral, incompetent varicose saphenous veins. No patients were treated bilaterally in the same session. The majority were great saphenous veins (92.3%), and the others were small saphenous veins. Procedures were performed with a mechanochemical endovenous occlusion catheter (ClariVein endovenous occlusion catheter; Merit Medical, South Jordan, Utah) and polidocanol 2% in liquid form. Results Follow-up was available for 329 patients treated between September 2012 and September 2017 with a mean follow-up time of 20 ± 18 months (range, 6-60 months). Technical success was achieved in 99.5%; in two patients, we were unable to complete the procedures because of vein spasm leading to catheter damage and inability to infuse the sclerosant. Follow-up was performed with clinical evaluation and duplex ultrasound scan at 1 week, 1 month, 6 months, and 1 year and then once every year. The overall survival rate free from recanalization was 92.4%. Anatomic success is 94% at 1 year, 91% at 2 years, 88% at 3 years, 88% at 4 years, and 84% at 5 years. The follow-up at 5 years includes 23 patients, 5 of whom presented with recanalization; moreover, in this series, in 36% of cases, the veins completely disappeared on duplex ultrasound scan. Conclusions The ClariVein catheter is associated with a good occlusion rate, comparable with other techniques including thermal techniques, without major complications.
Published: 2020
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20. Ultrasound-guided core needle biopsy compared with open biopsy: a new diagnostic approach to salivary gland enlargement in Sjögren’s syndrome?

Author: Ivan Giovannini, Michele Lorenzon, Alen Zabotti, Enrico Pegolo, Cathryn Anne Scott, Alessandro Tel, Chiara Zuiani, Carla Di Loreto, Sara Zandonella Callegher, Massimo Robiony, and Salvatore De Vita
Subjects: Male, medicine.medical_specialty, Open biopsy, Biopsy, Submandibular Gland, salivary gland, Salivary Glands, Sialadenitis, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Major Salivary Gland, Humans, Parotid Gland, Medicine, Pharmacology (medical), Prospective Studies, Ultrasonography, Interventional, 030203 arthritis & rheumatology, medicine.diagnostic_test, business.industry, US-guided core needle biopsy, ultrasonography, Middle Aged, medicine.disease, Submandibular gland, Parotid gland, Sjogren's Syndrome, medicine.anatomical_structure, Sjögren’s syndrome, histopathology, 030220 oncology & carcinogenesis, Female, Histopathology, Biopsy, Large-Core Needle, Sarcoidosis, Radiology, business
Abstract: Objective Persistent (≥2 months) major salivary gland enlargement in primary SS (pSS) patients is a well-known sign of possible involvement by B cell lymphoma. The study aimed to evaluate the diagnostic accuracy and safety of US-guided core needle biopsy (CNB) of major salivary glands compared with open surgical biopsy. Methods Prospective pSS patients (cases) with clinically persistent salivary gland enlargement underwent US-guided CNB and were compared with retrospective pSS patients (controls) submitted to open surgical biopsy. The features analysed were pre-biopsy clinical and laboratory findings, adequacy of the material for histology and diagnostic-rendered and biopsy-related complications (reported by the patient with a questionnaire and clinically verified). Results Thirteen cases underwent US-guided CNB: in nine, biopsy was performed on the parotid gland and in four it was performed on the submandibular gland. Sufficient material was obtained for pathological diagnosis in all samples. The final diagnoses were 5 (38.5%) B cell lymphoma, 1 (7.7%) lymphoepithelial sialadenitis, 4 (30.7%) other sialadenitis (granulomatous consistent with sarcoidosis, IgG4-related disease, chronic sclerosing, diffuse chronic) and 3/13 (23.1%) miscellaneous lesions. Thirteen controls underwent open surgical biopsy of the parotid. In one, inadequate material was obtained, while in 12 (92.3%) the pathologic diagnoses were 4 (33.3%) B cell lymphoma, 2 (16.7%) lymphoepithelial sialadenitis, 4 (33.3%) uncertain lymphoproliferative lesions and 2 (16.7%) miscellaneous lesions. Six cases (46.1%) reported six transient complications and 12/13 (92.3%) controls had 2 persistent and 14 transient complications. Conclusion US-guided CNB represents a novel, clinically relevant and safe approach for the management of pSS patients with parotid or submandibular persistent enlargement.
Published: 2020
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21. Borderline or locally advanced pancreatic adenocarcinoma: A single center experience on the FOLFIRINOX induction regimen

Author: Jacques Ewald, Flora Poizat, Marc Giovannini, Ugo Marchese, Laurence Moureau-Zabotto, Olivier Turrini, Jean-Robert Delpero, Jonathan Garnier, and Marine Gilabert
Subjects: Adult, Male, medicine.medical_specialty, FOLFIRINOX, medicine.medical_treatment, Leucovorin, Locally advanced, Irinotecan, Single Center, 03 medical and health sciences, 0302 clinical medicine, Pancreatic cancer, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Neoadjuvant therapy, Aged, Aged, 80 and over, business.industry, Mortality rate, Induction Chemotherapy, General Medicine, Middle Aged, medicine.disease, Surgery, Oxaliplatin, Pancreatic Neoplasms, Regimen, Oncology, 030220 oncology & carcinogenesis, Adenocarcinoma, Female, 030211 gastroenterology & hepatology, Fluorouracil, business, Carcinoma, Pancreatic Ductal
Abstract: This study aimed to determine the impact of FOLFIRINOX neoadjuvant therapy on patients with non-metastatic borderline/locally advanced (BL/LA) pancreatic ductal adenocarcinoma (PDAC), in current practice.From 2010 to 2017, 258 patients with BL/LA PDAC from a single high-volume institution received FOLFIRINOX neoadjuvant treatment.The 258 patients received a median number of 6 cycles of FOLFIRINOX (range, 3-16); 98 (38%) patients underwent curative surgery, and 160 (62%) continued medical treatment. A venous resection was performed in 57 patients (58%), and an arterial resection in 12 (12%). The postoperative 30- and 90-day mortality rates were 6.1% and 8.2%, respectively. Adjuvant chemotherapy was performed in 57 patients (59%). The median overall survival (OS) in patients who did (n = 98) or did not (n = 160) undergo surgical resection were 39 months and 19 months, respectively (P 0.001). In resected patients, the ASA 3 score (P 0.01), venous resection (P 0.01), hemorrhage (P 0.01), and R1 margin status (P = 0.03) were found to negatively influence the OS. The median OS was significantly higher in patients who did not require a venous resection (not reached vs. 26.5 months, P 0.001).Neoadjuvant FOLFIRINOX provided a survival benefit in BL/LA PDAC patients, particularly in those who did not ultimately require venous resection.
Published: 2020
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22. Thalamic tumors in children: case series from our institution and literature review

Author: Agustín Ruiz Johnson, Daniela Renedo, Florencia Ferraro, Joaquín Pérez Zabala, Sebastian Giovannini, Romina Argañaraz, Elena Zemma, and Beatriz Mantese
Subjects: Male, medicine.medical_specialty, Stereotactic biopsy, medicine.medical_treatment, Ventriculoperitoneal Shunt, Ventriculostomy, Thalamic Tumors, 03 medical and health sciences, 0302 clinical medicine, Biopsy, medicine, Humans, Child, Retrospective Studies, Chemotherapy, Temozolomide, medicine.diagnostic_test, Brain Neoplasms, business.industry, Endoscopic third ventriculostomy, General Medicine, medicine.disease, Surgery, Hydrocephalus, Observational Studies as Topic, Treatment Outcome, 030220 oncology & carcinogenesis, Pediatrics, Perinatology and Child Health, Female, Neurology (clinical), Neurosurgery, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: To describe a case series of children with thalamic tumors treated at our institution in a 5-year period. A retrospective and observational study was performed. The records of 15 patients between 2013 and 2018 were analyzed. From 2013 to 2018, 15 patients were treated at our institution. The male to female index was 1.5, and the median age was 8.9 (IQR 4.75–13). Seven (46%) tumors were left-sided, seven (46%) were right-sided, and one (6%) was bilateral. All patients were symptomatic at the time of treatment. Motor deficit was the most common form of presentation (73%). Gross-total resection was performed in two (13.3%) patients, subtotal resection was performed in two other patients (13.3%), and for the rest of the patients (73.3%), the chosen surgical approach was a stereotactic-guided biopsy. The average of procedures was 3.4, mostly related to the treatment for hydrocephalus. Twelve patients (80%) received treatment for hydrocephalus. Nine patients (75%) were treated with ventriculoperitoneal shunts, and four patients (33%) underwent endoscopic third ventriculostomy. High-grade tumors predominated. Grade IV tumors were diagnosed in six patients (40%), followed by grade III in four patients (26.6%), grade II in three (20%) patients, and grade I in two (13.3%) patients. Chemotherapy was given in 93% of the cases, being temozolomide, the most used drug. The clinical and surgical approaches for thalamic tumors in children have changed over time. At our institution, the lesser invasive surgical procedures are now being used more frequently.
Published: 2020
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23. Awareness of major cardiovascular risk factors and its relationship with markers of vascular aging: Data from the Brisighella Heart Study

Author: Elisabetta Rizzoli, Claudio Borghi, Sergio D'Addato, Matteo Landolfo, P. Coppola, E. Rizzoli, Mario Soldati, G. Derosa, Federica Fogacci, Stefano Bacchelli, F. Fogacci, Giuliano Tocci, Martina Rosticci, Arrigo F G Cicero, Arrigo Fg Cicero, Fulvio Ventura, Ilaria Ricci Iamino, S. Palmisano, Elisa Grandi, F. Ventura, Federica Piani, E. Grandi, Marina Giovannini, Vivianne Presta, and Arrigo F G Cicero , Federica Fogacci , Giuliano Tocci , Fulvio Ventura , Vivianne Presta , Elisa Grandi , Elisabetta Rizzoli , Sergio D'Addato , Claudio Borghi , Brisighella Heart Study group
Subjects: Blood Glucose, Male, Aging, Epidemiology, Endocrinology, Diabetes and Metabolism, Arterial aging, Medicine (miscellaneous), Blood Pressure, Type 2 diabetes, 030204 cardiovascular system & hematology, 0302 clinical medicine, Risk Factors, awareness, Pulse wave velocity, Aged, 80 and over, Hypertriglyceridemia, education.field_of_study, Awareness, Risk factors, Arterial aging, Pulse wave velocity, Epidemiology, Nutrition and Dietetics, Age Factors, Middle Aged, Cholesterol, Italy, Cardiovascular Diseases, Hypertension, Cardiology, Female, Vascular aging, Cardiology and Cardiovascular Medicine, Adult, medicine.medical_specialty, Adolescent, arterial aging, epidemiology, pulse wave velocity, risk factors, Hypercholesterolemia, Population, 030209 endocrinology & metabolism, Risk Assessment, Young Adult, 03 medical and health sciences, Vascular Stiffness, Internal medicine, Diabetes Mellitus, medicine, Risk factors, Humans, education, Triglycerides, Aged, business.industry, Awarene, medicine.disease, Cross-Sectional Studies, Blood pressure, Arterial stiffness, business, Biomarkers
Abstract: Background and aim: General population awareness about cardiovascular risk factors is usually low. The aim of the present study was to evaluate the vascular aging of subjects aware and not aware to be hypertensive, hypercholesterolemic, hypertriglyceridemic or diabetics in a general population sample. Methods and results: We interviewed 1652 subjects without atherosclerotic cardiovascular diseases (M: 46.6%, F: 53.4%) about their awareness of hypertension, hypercholesterolemia, hypertriglyceridemia or type 2 diabetes. Then we compared the augmentation index and pulse wave velocity of subjects aware and not aware of the investigated cardiovascular risk factors. 1049 participants declared not to be hypertensive, while 32 were not sure. Among them, respectively, 23.5% and 50% were hypertensive. Subjects not aware of their hypertension had significantly higher aortic blood pressure than aware ones (p < 0.001). 841 participants declared not to be hypercholesterolemic, while 60 were not sure. Among them, respectively, 18.1% and 40% were hypercholesterolemic. Subjects not aware of their hypercholesterolemia had significantly higher augmentation index than the aware ones (p < 0.05). 1226 participants declared not to be hypertriglyceridemic, while 200 were not sure. Among them, respectively, 19.2% and 44% were hypertriglyceridemic. Subjects not aware of their hypertriglyceridemia had significantly higher TG levels aware ones (p < 0.05), although this seemed to not related to increased arterial stiffness. 1472 participants declared not to be diabetic, while 20 were not sure. Among them, respectively, 2.0% and 25.0% were diabetics. Subjects not aware of their diabetes had significantly higher augmentation index than the aware ones (p < 0.05). Conclusions: In conclusion, the lack of awareness of hypertension and hypercholesterolemia is relatively frequent in the general population and is associated to significantly higher arterial stiffness.
Published: 2020
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24. A caregiver-reported global severity assessment in pediatric atopic eczema: the Comano score

Author: Riccardo Pertile, Elio Novembre, Ermanno Baldo, Mario Cristofolini, Gabriele Barlocco, Davide Geat, Cesare Filippeschi, Mattia Giovannini, and Francesca Mori
Subjects: Male, Balneotherapy, Modern medicine, Pediatrics, medicine.medical_specialty, Scoring system, Adolescent, medicine.medical_treatment, Severity of Illness Index, Dermatitis, Atopic, 030207 dermatology & venereal diseases, 03 medical and health sciences, Severity assessment, 0302 clinical medicine, Rating scale, Humans, Medicine, SCORAD, Child, Letter to the Editor, Atopic dermatitis, medicine.diagnostic_test, business.industry, lcsh:RJ1-570, Infant, lcsh:Pediatrics, medicine.disease, Clinical trial, Cross-Sectional Studies, Caregivers, Italy, 030228 respiratory system, Child, Preschool, Children, Person-centered care, Female, Observational study, business, Comano score
Abstract: Atopic eczema (AE) is the most common inflammatory skin disease in infancy and its prevalence is rising worldwide. It has a wide social impact on the affected children and their families’ lives. AE can have a chronic and heterogeneous course, with periods of remission and relapse of the clinical manifestations. For this reason, its severity assessment through standardized outcome measures becomes a fundamental guide for health professionals, who can manage AE following evidence-based medicine principles in their everyday clinical practice or in clinical trials.Several scoring systems have been recognized to assess the clinical manifestations of AE, both from the physician’s and the patient’s point of view. Despite the scoring systems standardized for adults, there are very few published options about the expression of a patient/caregiver-centered global severity assessment specifically for pediatric AE. For this reason, the aim of our study was to evaluate a new, quick, user-friendly and feasible caregiver-reported global severity assessment for pediatric AE. Based on a 0–10 numerical rating scale in pediatric AE, we named this scoring system the Comano score.We carried out a cross-sectional observational study enrolling a total of 867 patients aged from 1 to 16 years (males 49.5%, mean patient’s age 5.9 years, standard deviation ±3.6 years) with a previous doctor-confirmed diagnosis of AE, who underwent balneotherapy at Comano Thermal Center (Comano, Trentino, Italy). A strong correlation between Comano score and SCORing Atopic Dermatitis (SCORAD) was observed (r = 0.74, p According to our results, the Comano score may be a promising new tool for the expression of a caregiver-reported global severity assessment in pediatric AE. However, further data are needed to confirm our preliminary findings before health professionals can use this scoring system in their everyday clinical practice to manage pediatric AE. Still, as a patient-focused measure, the Comano score may facilitate delivering person-centered care so as to define a measure for a clinical impact that can be meaningful to the subject, which is gaining importance in modern medicine.
Published: 2020
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25. Patient outcome according to the 2017 international consensus on the definition of borderline resectable pancreatic ductal adenocarcinoma

Author: Jean-Robert Delpero, Jacques Ewald, Jonathan Garnier, Marine Gilabert, Marc Giovannini, U. Marchese, S. Launay, Olivier Turrini, Flora Poizat, and J. Medrano
Subjects: Adult, Male, medicine.medical_specialty, Consensus, Pancreatic ductal adenocarcinoma, FOLFIRINOX, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Leucovorin, Irinotecan, 03 medical and health sciences, Pancreatectomy, 0302 clinical medicine, Borderline resectable, Regional lymph node metastasis, Antineoplastic Combined Chemotherapy Protocols, medicine, Back pain, Humans, Aged, Neoplasm Staging, Aged, 80 and over, Hepatology, Performance status, business.industry, Gastroenterology, Induction chemotherapy, Middle Aged, Reference Standards, Survival Analysis, Oxaliplatin, Pancreatic Neoplasms, Treatment Outcome, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Fluorouracil, Radiology, medicine.symptom, business, Carcinoma, Pancreatic Ductal
Abstract: We evaluated the usefulness of the 2017 definition of borderline pancreatic ductal adenocarcinoma (BR-PDAC) in fit patients (performance status 0-1) based on anatomical (A) and biological dimensions (B).From 2011 to 2018, 139 resected patients with BR-PDAC according to the 2017 definition were included: 18 patients underwent upfront pancreatectomy (CA 19-9 500 U/mL and/or regional lymph node metastasis; BR-B group), and 121 received FOLFIRINOX (FX) induction chemotherapy and were divided into BR-A (CA 19-9 500 U/mL, no regional lymph node metastasis; n = 68) and BR-AB (CA 19-9 500 U/mL and/or regional lymph node metastasis; n = 53) groups.The 3 groups were comparable according to patient characteristics (except for back pain (P .01) and CA 19-9 (P .01)), intraoperative data, and postoperative courses. BR-AB patients required more venous resections (P .01). The 3 groups were comparable on pathologic findings, except that BR-B patients had more lymph node invasions (P = .02). Median overall survival (OS) of the 121 patients was 45 months. In multivariate analysis, venous resection (P = .039) and R1 resection (P = .012) were poorly linked with OS, whereas BR-A classification (P .01) independently favored OS. Median survival times of BR-A, BR-AB, and BR-B groups were undetermined, 27 months, and 20 months (P.001), respectively.The 2017 definition was relevant for sub-classifying patients with BR-PDAC. The anatomical dimension (BR-A) was a favorable prognostic factor, whereas the biological dimension (BR-AB and BR-B) poorly impacted survival.
Published: 2020
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26. Management of non-functional pancreatic neuroendocrine tumors by endoscopic ultrasound-guided radiofrequency ablation: Retrospective study in two tertiary centers

Author: Mariola Marx, Sébastien Godat, Fabrice Caillol, Flora Poizat, Jean‐Philippe Ratone, Christian Pesenti, Alain Schoepfer, Solène Hoibian, Yanis Dahel, and Marc Giovannini
Subjects: Male, Radiofrequency Ablation, Gastroenterology, Pancreatic Neoplasms, Neuroendocrine Tumors, Treatment Outcome, Pancreatitis, Acute Disease, Humans, Neuroectodermal Tumors, Primitive, Radiology, Nuclear Medicine and imaging, Female, Ultrasonography, Interventional, Aged, Retrospective Studies
Abstract: Recently, there has been growing interest in investigating endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) for the management of small non-functional pancreatic neuroendocrine tumors (nf pNETs).A bicentric retrospective study was performed that included patients with histologically confirmed nf pNETs who were consecutively treated by EUS-RFA between December 2015 and March 2021 at two tertiary referral centers.In 27 patients (mean age 65.0 years, 52% male), EUS-RFA was successfully performed. All patients had sporadic G1 lesions (mean size 14.0 ± 4.6 mm, 7% uncinated process, 22% head, 11% body, 19% body/tail junction, and 41% tail). Overall, 9/27 lesions (33%) were cystic. The mean hospital stay was 3.2 days. Complete treatment response was confirmed in 25/27 patients (93%) on cross-sectional imaging (mean follow-up 15.7 ± 12.2 months, range 2-41 months). Two patients had two EUS-RFA sessions until complete necrosis was observed. Periprocedural acute pancreatitis occurred in 4/27 (14.8%), three of them were treated by endoscopic cystogastrostomy (11.1%). One patient underwent secondary surgery. The histopathology of the resected specimen revealed 3 mm of residual tumor tissue.EUS-RFA seems to be a promising treatment strategy for the management of small nf pNETs with excellent efficacy. Further evidence focusing on long-term survival, safety profile and recurrence is needed.
Published: 2021

27. Tocilizumab and Active Antibody-Mediated Rejection in Kidney Transplantation: A Literature Review

Author: Lara Cabezas, Thomas Jouve, Paolo Malvezzi, Benedicte Janbon, Diane Giovannini, Lionel Rostaing, and Johan Noble
Subjects: Graft Rejection, Inflammation, Male, HLA Antigens, Isoantibodies, Immunology, Graft Survival, Immunology and Allergy, Humans, Female, Antibodies, Monoclonal, Humanized, Kidney Transplantation
Abstract: IntroductionChronic kidney disease (CKD) is a major public-health problem that increases the risk of end-stage kidney disease (ESKD), cardiovascular diseases, and other complications. Kidney transplantation is a renal-replacement therapy that offers better survival compared to dialysis. Antibody-mediated rejection (ABMR) is a significant complication following kidney transplantation: it contributes to both short- and long-term injury. The standard-of-care (SOC) therapy combines plasmapheresis and Intravenous Immunoglobulins (IVIg) with or without steroids, with or without rituximab: however, despite this combined treatment, ABMR remains the main cause of graft loss. IL-6 is a key cytokine: it regulates inflammation, and the development, maturation, and activation of T cells, B cells, and plasma cells. Tocilizumab (TCZ) is the main humanized monoclonal aimed at IL-6R and appears to be a safe and possible strategy to manage ABMR in sensitized recipients. We conducted a literature review to assess the place of the anti-IL-6R monoclonal antibody TCZ within ABMR protocols.Materials and MethodsWe systematically reviewed the PubMed literature and reviewed six studies that included 117 patients and collected data on the utilization of TCZ to treat ABMR.ResultsMost studies report a significant reduction in levels of Donor Specific Antibodies (DSAs) and reduced inflammation and microvascular lesions (as found in biopsies). Stabilization of the renal function was observed. Adverse events were light to moderate, and mortality was not linked with TCZ treatment. The main side effect noted was infection, but infections did not occur more frequently in patients receiving TCZ as compared to those receiving SOC therapy.ConclusionTCZ may be an alternative to SOC for ABMR kidney-transplant patients, either as a first-line treatment or after failure of SOC. Further randomized and controlled studies are needed to support these results.
Published: 2021

28. Amoxicillin Adverse Cutaneous Reaction Versus Post Streptococcal Vasculitis: Lymphocyte Transformation Test Solved the Question

Author: Simona Barni, Manuela Capone, Valerio Maniscalco, Mattia Giovannini, Giulia Liccioli, Gabriele Simonini, Lucrezia Sarti, Paola Parronchi, Francesca Mori, and Edoardo Marrani
Subjects: Microbiology (medical), Drug, Vasculitis, Allergy, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, medicine.drug_class, media_common.quotation_subject, Antibiotics, Lymphocyte Activation, Drug Hypersensitivity, medicine, Humans, Child, media_common, Skin Tests, business.industry, Amoxicillin, Streptococcus, medicine.disease, Dermatology, Hypersensitivity reaction, Infectious Diseases, Lymphocyte transformation, Child, Preschool, Pediatrics, Perinatology and Child Health, Female, Differential diagnosis, business, medicine.drug
Abstract: In children, skin rashes are a frequent manifestation of infectious diseases, or they could also be the result of a drug hypersensitivity reaction, especially after antibiotic intake. We report the case of a 5-year-old girl investigated for a suspected post streptococcal vasculitis where differential diagnosis was improved by an allergy work-up and confirmed by lymphocyte transformation test.
Published: 2021

29. Prehabilitation and heart failure: perspective in primary outcomes, a randomized controlled trial

Author: S, Giovannini, D, Coraci, F, Di Caro, L, Castelli, C, Loreti, A, Chicco, M, Fiori, A, Bellieni, L, Gerardino, C, Nigito, A, Laudisio, F, Brau, E, D'Angelo, P, Caliandro, L, Biscotti, L, Padua, G, Zuccalà, and R, Bernabei
Subjects: Aged, 80 and over, Heart Failure, Male, Stroke Volume, Exercise Therapy, Nutrition Assessment, Treatment Outcome, Patient Education as Topic, Chronic Disease, Quality of Life, Humans, Female, Single-Blind Method, Nutrition Therapy, Life Style, Aged
Abstract: Prehabilitation, intended as a multidisciplinary approach where physical training is combined with educational and counselling training, in cardiology could optimizing care, and has been shown to be able to reduce morbidity and mortality in several diseases. The present study aims to assess the effectiveness of a prehabilitation program in elderly patients (over 65) with chronic heart failure and to evaluate functional and quality indices of life.This is randomized, single blind controlled trial. Fourteen older adult patients diagnosed with chronic heart failure were enrolled. Patients were randomly assigned into the study or the control group. Patients in the study group underwent physical training organized into 10 twice-weekly meetings, nutritional and lifestyle counseling.In the Study Group, the quality of life improved significantly (EQoL-5D), and between the two groups there is a statistically significant difference in the motor dimension of SF-36.Because of our preliminary results, prehabilitation program should be included among the management strategies of in elderly patients with chronic heart failure to better manage their disease and to improve their Quality of Life.
Published: 2021

30. Safety of hospital discharge before return of bowel function after elective colorectal surgery

Author: J Chapman, S, Blanco-Colino, R, Pérez-Ajates, S, O Anabitarte Bautista, Hodson, J, C Glasbey, J, Pata, F, Pellino, G, Sgrò, A, Soares, A, T van Elst, S Van Straten, Nepogodiev, D, Borakati, A, F Bath, M, H Yasin, I, Mclean, K, Arthur, T, Kovacevic, M, Delibegovic, S, Karamanliev, M, Swamad, M, Žebrák, R, Paramasivam, R, Martensen, A, M Larsen, H, Rädeker, L, E Frey, P, Kechagias, A, Venara, A, Duchalais, E, Ioannidis, A, Pasquali, S, Simioni, A, Farina, V, Podda, M, Lorenzon, L, Schaeff, V, Otto, A, Jakubauskas, M, R van Elst, T, Chu, M, Pvb, Fagan, I Wells, C, A Alagoa João, Juloski, J, Y El Kasmy El Kasmi, Espin-Basany, E, Clerc, D, Ciubotaru, C, Popescu, S, Yanishev, A, Lee, S, B Ozkan, B, A Yagız Sen, K Aktas, M, E Baki, B, Yüksek, B, Kamarajah, S, A Khaw, R, Mills, E, Goodson, R, Thakral, N, D Ablett, A, Adra, M, Kwek, I, M Khan, S, Quinn, P, R Manley, L, Badran, A, Ramjeeawon, A, Campbell, A, L Tan, H, S Rye, D, Rajaraman, N, G Norman, J, Vutipongsatorn, K, Solomou, G, Akhbari, M, Ali, A, Murray, V, M Baker, D, D Brandao, B, Stainer, B, Thavayogan, R, Jones, D, O Onafowokan, O, Gharooni, A, Dabab, N, Carlton-Carew, S, Kungwengwe, G, Gabriel, M, Sewart, E, C Shortland, T, Lawday, S, Pockney, P, Dawson, A, D Brumfitt, C, Stewart, P, B, Ng, K Luong, J, Ivanov, V, Borisova, A, Neykov, V, Kunčarová, K, Kološová, B, Antonova, T, Farkašová, M, L Harbjerg, J, Brandsborg, S, Brinck, S, D Kjaer, M, Mark-Christensen, A, P Unbehaun, K, Dalsgaard, P, D Lycke, K, Lenaoures, P, Brigand, C, Dumange, E, Gout, M, Moehwald, C, Prem, M, Alhalabi, O, Sliwinski, S, Krupp, J, Gablenz, E, Schmitzer, L, Kopp, A, Steinle, J, Gsenger, J, J Pohl, L, Riccardi, M, M Christodoulou, I, Konstantinidis, M, Machairas, N, Zoikas, A, Balalis, D, K Manatakis, D, L Aguilera, M, Marano, L, Fleres, F, Lovisetto, F, Sasia, D, Segalini, E, Pata, G, Lucchi, A, Sagnotta, A, Campagnaro, T, Petrelli, F, Gallo, G, Papandrea, M, Testa, V, Sinibaldi, G, F Di Candido, Colombo, F, Perrone, G, Aresu, S, Biancafarina, A, Canonico, G, Pagnanelli, M, Curletti, G, Bini, R, A de Manzoni Garberini, Impellizzeri, H, Cillara, N, Tutino, R, Picciariello, A, Coletta, D, Savino, G, Ferrara, F, Tamini, N, Talamo, G, Parini, D, Giamundo, P, A Lo Conte, Pagano, G, Ripetti, V, Pesce, A, Menduni, N, Giudicissi, R, Goldin, E, Rega, D, Belli, A, Andriola, V, Gordini, L, Foppa, C, Piccolo, G, Birindelli, A, Ferrari, C, Ballarini, Z, Tirelli, F, Milone, M, M De Rosa, S Pipitone Federico, N, Molteni, B, L Tilocca, P, Sancini, G, N Piozzi, G, Lauretta, A, Poillucci, G, Mulas, S, Simcikas, D, Portelli, L, Jwm van Wijnbergen, L Dinger, T, Sfh Ten Doesschate, Ashm van Dalen, D van den Bos, D, Hansmann, M, J Medina Feliz, Z Kuiper, S, Abdulrahman, Z, R Pruijssers, S, Farik, S, M Elliott, B, P Geneta, V, Wilton, S, Kandelaki, H, L Peng, S, Campbell, S, K Lim, Y, S Yassaie, S, Murray, M, Haran, C, Tan, J, Castro, J, Laranjeira, A, Catarino, S, Neves-Marques, C, G Correia, J, N Vieira, B, C Quintela, A, L Serra, M, Maciel, J, Cunha, M, J Aparício, D, Neves, J, Azevedo, J, Romano, M, Eiró, F, Romano, J, Monteiro, C, Claro, M, R Almeida, M, Peyroteo, M, D Machado, N, Capote, H, Ferreira, M, Sousa, X, Devesa, H, Cavadas, D, Guerreiro, I, Costa, M, Rosete, M, Salman, M, English, C, Mohammed, N, Litvin, A, V Ćuk, V, Mészárosová, K, Jaich, R, H De Lima, Brooks, S, Marx, M, M Nshalati Salvation, J García Cardo, Mora-Guzmán, I, J Sancho Muriel, U de Andres Olabarria, Muriel, P, C Jimenez Viñas, Alconchel, F, O Esteban Sinovas, C Fairén Oro, M López Otero, S Figueroa Jiménez, O Claramonte Bellmunt, J Martínez Caballero, Rubio-Pérez, I, M Aguilar-Martínez, M, J Segura-Sampedro, J, C Olmedo Moreno, D Negre Parra, M Estévez Diz, A, Martín-Balbuena, R, C Bustamante Recuenco, E Licardie Bolaños, R, Fernández, P, A Díaz Padillo, Forero-Torres, A, I Alberdi San Román, H Salvador Rosés, M Merayo Álvarez, P Villarejo Campos, C Lopes Moreira, C, P Uriol Peralta, M Serrano Navidad, Ripollés-Melchor, J, Garcea, A, H Gómez Facundo, P Troncoso Pereira, V Pérez Guarinos, C, Blaser, B, Piazza, G, Gagliardi, B, Serin, H, S Yurdaor, S, Arslan, E, Kopac, O, Uyanik, A, B Ozmen, B, Tiftik, E, Aksoy, B, Yalcinkaya, A, Ozoglu, F, D Kocer, M, Bilicen, G, N Cinar, E, Uslu, Ö, Kaya, Y, Demirci, K, Wong, J, Mmh, Farhan-Alanie, Suresh, G, Asif, A, J Finch, B, Bhahirathan, Y, Herron, J, Z Yi Tew, Obukofe, R, Russell, C, Suchett-Kay, I, Netke, T, Williams, L, Kisiel, A, Y Liu, F, Claireaux, H, James, P, Mondal, A, Kalderon, R, H Nadama, H, Al-Saraff, Z, Jph, Tam, Powell-Chandler, A, Wood, F, Rebecca, Gorgievska, Ragavoodoo, A, Thakrar, C, Rojoa, D, Palmer, C, Davidson, K, Giacci, L, Hale, J, W Gan, F, Makin-Taylor, R, Y Hey, C, Toh, C, M Findlay, J, Griffiths, N, Ganesananthan, S, Jasionowska, S, Poustie, M, Wong, C, Turner, T, Pyc, W, Sloper, W, Warner, C, Coey, J, Mason, D, Sait, S, Kowal, M, Owen, M, Saiyed, A, Ashworth, I, Akbari, K, Curran, M, Martin, P, Parker, D, Kwok, K, Lye, C, Ghaly, M, Sammour, T, Lewis, D, Mundasad, R, Wilkes, A, Ctercteko, G, Maslyankov, S, Dimov, R, Iliev, S, Dimitrov, D, Marek, F, Örhalmi, J, Skalický, P, Skalický, T, Chrz, K, Christensen, P, Worsøe, J, S Kristensen, E, J Emmertsen, K, S Loeve, U, L Mihaljevic, A, Herrle, F, M Konstantinidis, K, Korkolis, D, Karanikas, I, Vincenti, L, Anania, G, Borghi, F, Agresta, F, Maretto, I, Parisi, A, Bucci, L, G De Palma, Guglielmi, A, Cucinotta, E, F La Torre, Cianchi, F, Guerrieri, M, Trompetto, M, Persiani, R, Micheletto, G, Delrio, P, Cantafio, S, Ronconi, M, Pag, Bisagni, M De Prizio, Franceschi, A, Galleano, R, Cavallini, M, Brescia, A, D'Ambra, L, Benevento, A, Niolu, P, Calgaro, M, Colangelo, E, Grottola, T, F Altomare, D, Puleo, S, Salamone, G, Pietrabissa, A, Poggioli, G, Erdas, E, Ottonello, R, Tonini, V, Selvaggi, F, Sammarco, G, Ceccarelli, G, C De Nisco, Surgo, D, Taglietti, L, Ozolins, A, Sivinš, A, Poskus, T, Psaila, J, A Bemelman, W, J Graat, L, Langenhoff, B, Bpl, Wijnhoven, Ahw van de Ven, Poelman, M, Lps, Stassen, Slooter, G, Yiz, Acherman, Hoff, C, F Gerhards, M, Mwj, Stommel, J Hazebroek, E, Aaw van Geloven, A Schasfoort, R, L van Leeuwen, B, B Tuynman, J, Mwa van Tilburg, G Boerma, E, Sharma, P, Jenkins, B, P Bissett, I, Herd, A, Gordon, A, Vernon, D, Omundsen, M, J, Ly, Reddy, A, Bonnet, G, Harmston, C, Morales, M, Francisco, V, Costa, S, Manso, A, Amorim, E, Pereira, J, Cardoso, J, Ourô, S, Caratão, M, Nascimento, C, B Ribeiro da Silva, Taranu, V, Dias, R, Mendes, J, Allen, M, Silva, A, Carlos, S, Barbosa, E, Carneiro, C, Ramos, L, Lencastre, L, Martins, R, Silva-Vaz, P, F Ridgway, P, A McNamara, D, Cahill, R, Hogan, A, Larkin, J, R O'Connell, P, Negoi, I, Abelevich, A, M Ćuk, V, Vician, M, Ede, C, Sardiwalla, I, Mulira, S, Montwedi, D, Oyomno, M, Sabia, D, V Portugal Porras, Vigorita, V, G Sanz Ortega, García, J, A Espí Macías, F Blanco Antona, A Luján Mompeán, J, S Salvans Ruiz, Villarejo-Campos, P, M Romero Simó, Sánchez-Guillén, L, M Jiménez-Gómez, L, A Sánchez López, Golda, T, D Julià Bergkvist, Nevado, C, F Noguera Aguilar, J, B Ricardo Felipe, Septiem, J, A Rodríguez Sánchez, Cañete-Gómez, J, I Ruiz Montesinos, Millán-Scheiding, M, Prieto-Nieto, I, Frasson, M, D García Olmo, Hübner, M, Petermann, D, O Sauvain, M, Ozben, V, E Geçim, I, Disçi, E, Rencuzogullari, A, Kurt, A, Bisgin, T, Pehlivan, M, Isik, A, Onur, E, Leventoglu, S, C Haksal, M, S Erturk, M, Keskin, M, Guner, A, S Tutcu Sahin, S Ozbalci, G, Pergel, A, Albayrak, D, Bruce, D, Fearnhead, N, Arthur, J, Harron, M, Beattie, G, Titu, L, Saunders, M, Phillips, J, Dindyal, S, Cresswell, B, Gercek, Y, Lee, J, Linn, T, Faulkner, G, Lockwood, S, Rees, J, Charalabopoulos, A, Campbell, B, Kontovounisios, C, Amarnath, T, Johnson, M, Epanomeritakis, E, Vigs, S, Nastro, P, Gilliam, A, Smolarek, S, Wilson, T, Orbell, J, Mcintyre, R, Agarwal, T, Hainsworth, P, Patel, P, Vijay, J, Liu, B, P Dhruva Rao, Roxburgh, C, Vipond, M, Youssef, H, Thorn, C, Schizas, A, Denley, S, Bowley, D, Das, K, Cuming, T, Saha, A, Chung, L, Pitt, J, Davis, P, Jones, O, Taylor, M, Bhargava, A, Haji, A, Watson, N, Bloom, I, Singh, B, Norwood, M, Gurjar, S, Stylianides, N, Mirza, S, Evans, M, Williams, G, Patil, P, Hernon, J, Finch, G, Green, S, Chapple, K, Fafemi, O, Warusavitarne, J, Samee, A, Carden, C, Ong, L, Verma, K, Joseph, A, Rawat, N, Pinkney, T, Oke, O, Glen, P, Maxwell-Armstrong, C, Oliphant, R, Garner, J, J Moug, S, Middleton, S, N Lund, J, J Smart, N, Osborn, G, Moore, T, Raymond, T, H Knowles, C, S Hany, T, Clarke, R, Khera, G, Brady, R, Sellahewa, C, Mason, C, Torrance, A, Lasithiotakis, K, Knight, J, Pullybank, A, Ainsworth, P, Reid, F, Ramwell, A, Maslekar, S, George, R, Skull, A, Holtham, S, Muhammad, K, Lal, R, Varcada, M, M Smith, F, Howlader, M, Defriend, D, Kirk, S, Richards, T, Evans, C, M Borg, C, Telford, K, Sarfraz, N, Busby, K, Hollingshead, J, Speake, D, Pawa, N, West, D, Chadwick, M, Komolafe, O, Richardson, S, Thornton, M, Goede, A, Osborne, C, Bandyopadhyay, D, 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Yuksek A., Mazlum S.S., Yelkenci C., Baran T., Satilmisoglu M., Sahin A.Z., Kilinc A., Isik K., Yumurtaci O., Emin A., Girit C., Yildirak M.K., Senyigit E., Guldag A., Soyleyici B., Aytin Y.E., Akay F.E., Iskan N.G., Mutlu B., Sunay A.O., Tie-Gill T., Ramsay G., De Paola L., McGuckin S., Alshakhs A., Ahmeidat A., Goergen N., Ali Z., Mullarkey L., Walshe R., Lewis E., Berry B., Moneim J., Mookerjee S., Christy S., Ojofeitimi O., Carroll L., Hylands A., Delaugere L.P., Reveendran D., Coulter C., Ralston C., Laverty L., Gallagher P., Ahmed A., Yeo Y.Q., Elliott D., Bennett J., Mcnamara M., Sivarajah S., Dunmore C., Aitken G., Nair M., Aly M.H., Buari M., Ahmed K., Sheikh Z., Monks M., Lehmann J., Rotimi O., Bell T., Limnatitou D., Gormley S., Taleongpong P., Patel V., Macgregor L., Amini S., Turner C., Dwyer-Hemmings L., Busuttil A., Powell J., Hensher C., Vivian F., Wcislo K., Millar Z., Hirosue S., Ogunmwonyi I., Nakakande D., Gaze H., Pillai S., Khoury G., Powell T., Maleyko I., 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J., Ayyar S., Polson R., Mackenzie E., Doyle N., Habib Z., Zardab M., Sartaj F., Farooq H., Tabibi M., Drury D.J., James S.J., Barnett R., Cahya E., Lou G., Coyle M., Homyer K., Zhu L.Y., Woods M., Chang J., O'Callaghan H., Suchett-Kaye I., Mihailidis T.H., Alawattegama H., Seite E., Barrett A., Riordan E., Lam W., Dowdeswell M., Mulvenna C., Awokoya O., Gurowich L., Dhera K., Hayat S., Tincknell L., Spazzapan M., Teeling F., Sysum K., Latter J., Latter M., Khan S., Woodmass M., Hayden H., Ali Y., Husain S., Arnold A., Pedersen A.C., Cunha P., Ahmed M., Al Zawawi S., Kudva V., Theodoropoulou K., Miscampbell M., Robinson A.V., Johnston J., Dharni A., Lamb S., Westerman T., Evans E., Campbell L., Gillespie M., Cheong C.M., Kulathevanayagam K., Varghese A., Ike S.I., Chu T.S.M., Baljer B., Mogg J.A.W., Rai P., Claireaux H.A., Williams M., Smillie R., Goetz J., Appleby E., Fadipe T., Vaughan-Burleigh S., Jovaisaite A., Shah S.M., Khalid N., Gutmann D., Davison S., Alame Y.J., Syed L., Owen W.J., Ahsan S.D., Anthony-Uzoeto U., Hall C.M., Zheng S., Wynter K., James C., Sapre D., Ghosh R., Baird J., Cockburn L., Blackwood O., Simpson W., Jeong S., Bishop S., Bate R., Hobson C., Adam A.H., Redclift C., Do J., Adeleye O., Poli F., Batterham A., Brown S., Parekh J.N., Clay W., Pieri K., Jackson A., Saxena A., Gurung B., Oyebola T., O'Brien F., Djeugam B., Gardezi S., Ul-Hasan S., Martin-Hernandez M.P., Sisley M., Modi S., Antakia R., Elbayouk A., Soh Y.J., Mather J., Yusuf Z., Al-Sarraf Z., Naja M., Rassool S.B., Convill J., Nikookam Y., Warsame A., Pace C., Kiandee M., Ridwan R., Carey C., Hirri F., McMillan M.J.A., Ling J.J., Pendelbury L., Kerimzade K., Tang A., Howard E.O., Humayun S., Wadsworth O.J., Tan K., Abdelhameed F., Haglund C., Radnaeva I., Hu N., Rambhatla S., Waldron D., Madahar P., Malik S., Meney L.C., Ibrahim I., Kang C.K., Chiu J.Z.J., Livie V., Ibrahim B., Khalil M., Pooley G., Shishkin B., Docherty J., Southgate A., Coomes A., McGee F., Flanagan S., Tan Q.J., Anwar H., Clough R., Chrisp B., Cassels J., Cross G.W.V., Mercer L., Mercer C., Refalo A., Hadley R., McTighe A., Farrow F., Brodie A., Davis G., Shah D.R., Bowers C., Patel S., Morice O., Burzic A., Cheung J., Shashidhara A., Theodoraki G., Birk J., Ong A., Ng M.P.E., Wong R.T.W., Maese S., Yeap B., Iqbal Z., Melaugh T., Perchard W., Scurr T., Campbell E., Kelk L., Ghosh A., Gibbins A., Mala D., Loizidou A., Hall O., Mecia L., Hew C., Varathan K., Tong L., Chandrasekar B., Buchanan E., O'Connell M., Kwak S.Y., Ong E.H., Gardner S., Lim J., Maden C., Illahi M., Tan Z.X., Edwards S., Stahl R., Stahl J., Hickman A., Collett D., Goolam-Mahomed Z., Allen B., Atiyah A., Ahmad H., Jones J., McGregor O., Ogundiya E., Boulbadaoui A., Kirnon-Jackman O., Lim Q.X., Peckham H., Yeoh T., Yong S.Q., Chen J.Y., Siva S., Sam Z.H., Gilani M., Goh Y.N., Muthukumar M.G., Phillips S., Tjoakarfa J., Giri A., Suresan S., Thomas P., Johnson T.A., Williams R.I., Rashid A., Kushairi A., Rais A., James A., Bugelli M., Chechelnitskaya Y., Sandhu N., Tandon R., Gray M., Kumar A., Ciurleo C., Nyamali I., Hiremath S., Sinha S., Chowdhary M., Bradley E., McTiernan M., Macdonald S., Sharkey S., McLaughlin N., Amey C., Kraria L., Skan O., Kind C., Tupper P., Van Rhee C., Honeyman S.I., Menon G., Jegatheeswaran L., Madhavan A., Warne M., Malcolm F.L., Lessware T., Wilkerson H.T., Chatterjee-Woolman S., Yoong A., Ahmed W.U.R., Longshaw A., Flannery O., Green R., Leaning M., Cragg J., Sharriff H., Doherty C., Kwan K.W.L., Sanders-Crook L., Bhatia S., Eames S., Lewis F., Kirupananthan P., Boh Z.Y., Dass S., Soma A., Newton A., Hill M., Shafiq Y., Brkljac M., Boyce L., English W.J., Lam S., Chipeta C., Jain C., Garofalidou T., Novotny S.A., Locke S., Bowman C., Begaj A., Murphy C., Radcliffe K., Chong J.T., Jeffrey E., Chaudhury N., Rajendran K., Akbar Z., Walters B., Kulendrarajah B., Tran N., Shrestha S., Parmar S., Gallagher C., Hennessy L., Pentti E., Badhrinarayanan S., Fung A., Mansoor M., Kenny R., Kan P., Lee D.E., Khosla S., Samake M., Shaban F., Aftab R., Gough M., Woodburn B., Vayalapra S., McMurrugh K., Jimulia D., Deol S., Pike S., Embury-Young Y., Patel M., Kilgallon E., Keating R., Walsh A., Khan H., Logue G., Orekoya M., Alasmar M., Charalambides M., Llavall A.C., Williamson E., Bharwada Y., Zearmal S., Evans H., Panikkar M., de la Cruz G., Caplan J., Ruparelia A., Tanvir T., Soare C., Pang Y.L., Trotter J., Zaidi A., Thakrar V., Pulickal P., Ahmed H., Parnell J., Lennock S., Ford V., Brignall R., O'Neill D., Hanna R., Kane R., Nicola M., Rajput K., Xiao Y., Michael S., Wright E., Juniper S., Thompson E., Hoskyns L., Kanitkar A., Ross C., Unsworth A., Rshaidat H., Demarre K., Chiang A., Bareh A., van Dellen J., Faqihinejad C., Gadhvi A., Grant R., Lewsey J., Morris A., Martin H., McClarty C., Sanyal S., Alsaif A., Palkhi A., Bhopal S., Burford C., Huq T., Irwin E., Matthews L., Ngu W.S., Hosfield T., Muneeb F., Page O., Zeb E., Al-Azzawi A., McIntosh J., Vucicevic A., Hughes M., Brooks L., Fanibi B., Dixon M., Njoku P., Morris D., Jobson J., Chowdhury H., Joseph N., Zulkefley N., Hunt G., Christodoulou T., Wright O., Soman S., Jamal M., Beqiri S., Borgas P., Christie S., Pereira F., Browne S., Yiu J., Dworkin A., Brayley J., Palmer A., Charalambos M., Jones C.S., Toner S., Cowden R., Lee L., Nicol P., Holman O., Imtiaz M., Albert V., Leung S.P., Erotocritou M., Stroud R., Wilkin R., Thomson W., Mackee L., Kler A., Reynolds L., Mohamed S.H., Majeed Y., Fakim B., Jones A., Liversedge G., Carrington Z., Windebank J., Izzarina A., Akbani U., Craven J., Aldarragi A., Harding S., Millward A., Bedford M., Gopalan V., Midgen A., Khadka P., Cheng O., Taneja S., Manobharath N., Kok J.Y., Lim D.W.E., Buick T., Boland M., Piya S., Devlin R., Fairfield C.J., George R.J., Rahi M., Zaman S., Hajiev S., Ross T., Crisp E., Thompson C., Charalambous A., Hollywood J.L., Hammond R.F.L., Matthews J., Mendonca V., Spinty J., Khan K., Cheng J., Glynn N., Muhammad U., Khan M., Anderson L., Mccormack K., Mak J., Patrawala S., Milinkovic N., Schofield R., Chauhan M., Hartley L., Hind J., Nelson L., Ratnasingham D., Whitehead T., Dimitriadis S., Marshall K., Flint E.J., Horner C., Heybourne A., Morgan H., Wickstone C., Panagiotou D., O'Connell E., Dean K., Iqbal R., Walsh L., Yu N., Rana N., Massie E., Ng J., Jung M., Lee Y.D., Harris M., White S., Boev B., Tonchev P., Prochazka V., Risko J., Skalicky A., Ravn S., Ojakaar A., Dorr-Harim C., Koutserimpas C., Giraudo G., Armellini A., Ruzzenente A., Mazzeo C., De Padua C., Luc A.R., Maroli A., Vitali M., Gusai G.P., Quattromani R., Virgilio E., Berti S., Di Mola F.F., Papagni V., Tuminello F., Vittori L., Longheu A., Loche G.A., Braccio B., De Luca E., Resta G., Ancans G., Tamosiunas A., Petrulionis M., Abdulrahman N., van de Pas K.G.H., Thomas G., Brandsma A.M., Davids J., Rottier S.J., de Roy van Zuidewijn D., Hawkins R., Ong H.I., Li Y., Desmond B., Winstanley J., Martins M., Americano M., Frade S., Senhorinho R., Peixoto R., Alves-Vale C., Lamas M., O'Connor D.B., Hoo M., Gopaul A., Scanlon K., O'Dwyer N., Jovanovic M., Panyko A., Van Vuuren S., Centeno A., Bernado I.R., Senorans M.P.G., Amor L.G., Ramirez A.C., Abrisqueta J., Gomez M.E., Arroyo A., Cerdan C., Romeu N.G., Enriquez-Navascues J.M., Collado-Roura F., Curchod P., Gaspar S., Imadalou L., Mutlu D., Akyol C., Uygur F.A., Eray I.C., Biyiklioglu O., Cetin M.F., Isik A.E., Karip B., Dogan H., Sarigul L., Tunc E., Aydin T., Bodur S., Karabulut K., Francis A.A., Al-hadithi A., Lau I.S.F., Smith E., Mahapatra S., McAuliffe O., Imam L., Akram B., Hossaini S., Davies R., Ko M., Collins J., Pandya A., Reilly S., Archer J., Livie J., Chaudhry F.A., Ntakomyti E., Diallo R., Bylinski T., Wright J., Masiha E., Tung J., Shirazi B., Neilson A., Epton S., Patel N., Trussell S., Couldrey A., Donnelly C., Eftychiou S., Salman M., Skejo, Licari L., Men, Chapman, S. J., Blanco-Colino, R., Perez-Ajates, S., Bautista, O. A., Hodson, J., Glasbey, J. C., Pata, F., Pellino, G., Soares, A. S. A., van Elst, T., Van Straten, S., Nepogodiev, D., Borakati, A., Bath, M. F., Yasin, I. H., Mclean, K., Arthur, T., Kovacevic, M., Delibegovic, S., Karamanliev, M., Swamad, M., Zebrak, R., Paramasivam, R., Martensen, A., Larsen, H. M., Radeker, L., Frey, P. E., Kechagias, A., Venara, A., Duchalais, E., Ioannidis, A., Pasquali, S., Simioni, A. S. A., Farina, V., Podda, M., Lorenzon, L., Jakubauskas, M., Schaeff, V., Otto, A., Fagan, P. V. B., Wells, C. I., Joao, A. A., Soares, A., Juloski, J., El Kasmi, Y. E. K., Espin-Basany, E., Clerc, D., Ciubotaru, C., Popescu, S., Yanishev, A., Lee, S., Ozkan, B. B., Sen, A. Y., Aktas, M. K., Baki, B. E., Yuksek, B., Kamarajah, S., Khaw, R. A., Mills, E., Goodson, R., Thakral, N., Ablett, A. D., Adra, M., Kwek, I., Khan, S. M., Quinn, P., Manley, L. R., Badran, A., Ramjeeawon, A., Campbell, A., Tan, H. L., Rye, D. 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Z., Abdulrahman, Z., Pruijssers, S. R., Geneta, V. P., Chu, M., Wilton, S., Kandelaki, H., Peng, S. L., Campbell, S., Lim, Y. K., Yassaie, S. S., Murray, M., Haran, C., Tan, J., Castro, J., Laranjeira, A., Catarino, S., Neves-Marques, C., Correia, J. G., Vieira, B. N., Quintela, A. C., Serra, M. L., Maciel, J., Cunha, M., Aparicio, D. J., Neves, J., Azevedo, J., Romano, M., Eiro, F., Romano, J., Monteiro, C., Claro, M., Capote, H., Ferreira, M., Sousa, X., Peyroteo, M., Machado, N. D., Guerreiro, I., Costa, M., Rosete, M., Salman, M., English, C., Mohammed, N., Litvin, A., Cuk, V. V., Meszarosova, K., Jaich, R., De Lima, H., Brooks, S., Marx, M., Salvation, M. N., Cardo, J. G., Mora-Guzman, I., Muriel, J. S., de Andres Olabarria, U., Muriel, P., Vinas, C. J., Alconchel, F., Sinovas, O. E., Oro, C. F., Otero, M. L., Jimenez, S. F., Bellmunt, O. C., Caballero, J. M., Rubio-Perez, I., Aguilar-Martinez, M. M., Segura-Sampedro, J. J., Moreno, C. O., Parra, D. N., Diz, A. M. 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M., Zheng, S., Wynter, K., James, C., Sapre, D., Ghosh, R., Baird, J., Cockburn, L., Blackwood, O., Simpson, W., Jeong, S., Bishop, S., Bate, R., Hobson, C., Adam, A. H., Redclift, C., Do, J., Adeleye, O., Poli, F., Batterham, A., Brown, S., Parekh, J. N., Clay, W., Pieri, K., Jackson, A., Saxena, A., Gurung, B., Oyebola, T., O'Brien, F., Djeugam, B., Gardezi, S., Ul-Hasan, S., Martin-Hernandez, M. P., Sisley, M., Modi, S., Antakia, R., Elbayouk, A., Soh, Y. J., Mather, J., Yusuf, Z., Al-Sarraf, Z., Naja, M., Rassool, S. B., Convill, J., Nikookam, Y., Warsame, A., Pace, C., Kiandee, M., Ridwan, R., Carey, C., Hirri, F., Mcmillan, M. J. A., Ling, J. J., Pendelbury, L., Kerimzade, K., Tang, A., Howard, E. O., Humayun, S., Wadsworth, O. J., Tan, K., Abdelhameed, F., Haglund, C., Radnaeva, I., Hu, N., Rambhatla, S., Waldron, D., Madahar, P., Malik, S., Meney, L. C., Ibrahim, I., Kang, C. K., Chiu, J. Z. J., Livie, V., Ibrahim, B., Khalil, M., Pooley, G., Shishkin, B., Docherty, J., Southgate, A., Coomes, A., Mcgee, F., Flanagan, S., Tan, Q. J., Anwar, H., Clough, R., Chrisp, B., Cassels, J., Cross, G. W. V., Mercer, L., Mercer, C., Refalo, A., Hadley, R., Mctighe, A., Farrow, F., Brodie, A., Davis, G., Shah, D. R., Bowers, C., Patel, S., Morice, O., Burzic, A., Cheung, J., Shashidhara, A., Theodoraki, G., Birk, J., Ong, A., Ng, M. P. E., Wong, R. T. W., Maese, S., Yeap, B., Iqbal, Z., Melaugh, T., Perchard, W., Scurr, T., Campbell, E., Kelk, L., Ghosh, A., Gibbins, A., Mala, D., Loizidou, A., Hall, O., Mecia, L., Hew, C., Varathan, K., Tong, L., Chandrasekar, B., Buchanan, E., O'Connell, M., Kwak, S. Y., Ong, E. H., Gardner, S., Lim, J., Maden, C., Illahi, M., Tan, Z. X., Edwards, S., Stahl, R., Stahl, J., Hickman, A., Collett, D., Goolam-Mahomed, Z., Allen, B., Atiyah, A., Ahmad, H., Jones, J., Mcgregor, O., Ogundiya, E., Boulbadaoui, A., Kirnon-Jackman, O., Lim, Q. X., Peckham, H., Yeoh, T., Yong, S. Q., Chen, J. Y., Siva, S., Sam, Z. H., Gilani, M., Goh, Y. N., Muthukumar, M. G., Phillips, S., Tjoakarfa, J., Giri, A., Suresan, S., Thomas, P., Johnson, T. A., Williams, R. I., Rashid, A., Kushairi, A., Rais, A., James, A., Bugelli, M., Chechelnitskaya, Y., Sandhu, N., Tandon, R., Gray, M., Kumar, A., Ciurleo, C., Nyamali, I., Hiremath, S., Sinha, S., Chowdhary, M., Bradley, E., Mctiernan, M., Macdonald, S., Sharkey, S., Mclaughlin, N., Amey, C., Kraria, L., Skan, O., Kind, C., Tupper, P., Van Rhee, C., Honeyman, S. I., Menon, G., Jegatheeswaran, L., Madhavan, A., Warne, M., Malcolm, F. L., Lessware, T., Wilkerson, H. T., Chatterjee-Woolman, S., Yoong, A., Ahmed, W. U. R., Longshaw, A., Flannery, O., Green, R., Leaning, M., Cragg, J., Sharriff, H., Doherty, C., Kwan, K. W. L., Sanders-Crook, L., Bhatia, S., Eames, S., Lewis, F., Kirupananthan, P., Boh, Z. Y., Dass, S., Soma, A., Newton, A., Hill, M., Shafiq, Y., Brkljac, M., Boyce, L., English, W. J., Lam, S., Chipeta, C., Jain, C., Garofalidou, T., Novotny, S. A., Locke, S., Bowman, C., Begaj, A., Murphy, C., Radcliffe, K., Chong, J. T., Jeffrey, E., Chaudhury, N., Rajendran, K., Akbar, Z., Walters, B., Kulendrarajah, B., Tran, N., Shrestha, S., Parmar, S., Gallagher, C., Hennessy, L., Pentti, E., Badhrinarayanan, S., Fung, A., Mansoor, M., Kenny, R., Kan, P., Lee, D. E., Khosla, S., Samake, M., Shaban, F., Aftab, R., Gough, M., Woodburn, B., Vayalapra, S., Mcmurrugh, K., Jimulia, D., Deol, S., Pike, S., Embury-Young, Y., Patel, M., Kilgallon, E., Keating, R., Walsh, A., Khan, H., Logue, G., Orekoya, M., Alasmar, M., Charalambides, M., Llavall, A. C., Williamson, E., Bharwada, Y., Zearmal, S., Evans, H., Panikkar, M., de la Cruz, G., Caplan, J., Ruparelia, A., Tanvir, T., Soare, C., Pang, Y. L., Trotter, J., Zaidi, A., Thakrar, V., Pulickal, P., Ahmed, H., Parnell, J., Lennock, S., Ford, V., Brignall, R., O'Neill, D., Hanna, R., Kane, R., Nicola, M., Rajput, K., Xiao, Y., Michael, S., Wright, E., Juniper, S., Thompson, E., Hoskyns, L., Kanitkar, A., Ross, C., Unsworth, A., Rshaidat, H., Demarre, K., Chiang, A., Bareh, A., van Dellen, J., Faqihinejad, C., Gadhvi, A., Grant, R., Lewsey, J., Morris, A., Martin, H., Mcclarty, C., Sanyal, S., Alsaif, A., Palkhi, A., Bhopal, S., Burford, C., Huq, T., Irwin, E., Matthews, L., Ngu, W. S., Hosfield, T., Muneeb, F., Page, O., Zeb, E., Al-Azzawi, A., Mcintosh, J., Vucicevic, A., Hughes, M., Brooks, L., Fanibi, B., Dixon, M., Njoku, P., Morris, D., Jobson, J., Chowdhury, H., Joseph, N., Zulkefley, N., Hunt, G., Christodoulou, T., Wright, O., Soman, S., Jamal, M., Beqiri, S., Borgas, P., Christie, S., Pereira, F., Browne, S., Yiu, J., Dworkin, A., Brayley, J., Palmer, A., Charalambos, M., Jones, C. 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J., Horner, C., Heybourne, A., Morgan, H., Wickstone, C., Panagiotou, D., O'Connell, E., Dean, K., Iqbal, R., Walsh, L., Yu, N., Rana, N., Massie, E., Ng, J., Jung, M., Lee, Y. D., Harris, M., White, S., Boev, B., Tonchev, P., Prochazka, V., Risko, J., Skalicky, A., Ravn, S., Ojakaar, A., Dorr-Harim, C., Koutserimpas, C., Giraudo, G., Armellini, A., Ruzzenente, A., Mazzeo, C., De Padua, C., Luc, A. R., Maroli, A., Vitali, M., Gusai, G. P., Quattromani, R., Virgilio, E., Berti, S., Di Mola, F. F., Papagni, V., Tuminello, F., Vittori, L., Longheu, A., Loche, G. A., Braccio, B., De Luca, E., Resta, G., Ancans, G., Tamosiunas, A., Petrulionis, M., Abdulrahman, N., van de Pas, K. G. H., Thomas, G., Brandsma, A. M., Davids, J., Rottier, S. J., de Roy van Zuidewijn, D., Hawkins, R., Ong, H. I., Li, Y., Desmond, B., Winstanley, J., Martins, M., Americano, M., Frade, S., Senhorinho, R., Peixoto, R., Alves-Vale, C., Lamas, M., O'Connor, D. B., Hoo, M., Gopaul, A., Scanlon, K., O'Dwyer, N., Jovanovic, M., Panyko, A., Van Vuuren, S., Centeno, A., Bernado, I. R., Senorans, M. P. G., Amor, L. G., Ramirez, A. C., Abrisqueta, J., Gomez, M. E., Arroyo, A., Cerdan, C., Romeu, N. G., Enriquez-Navascues, J. M., Collado-Roura, F., Curchod, P., Gaspar, S., Imadalou, L., Mutlu, D., Akyol, C., Uygur, F. A., Eray, I. C., Biyiklioglu, O., Cetin, M. F., Isik, A. E., Karip, B., Dogan, H., Sarigul, L., Tunc, E., Aydin, T., Bodur, S., Karabulut, K., Francis, A. A., Al-hadithi, A., Lau, I. S. F., Smith, E., Mahapatra, S., Mcauliffe, O., Imam, L., Akram, B., Hossaini, S., Davies, R., Ko, M., Collins, J., Pandya, A., Reilly, S., Archer, J., Livie, J., Chaudhry, F. A., Ntakomyti, E., Diallo, R., Bylinski, T., Wright, J., Masiha, E., Tung, J., Shirazi, B., Neilson, A., Epton, S., Patel, N., Trussell, S., Couldrey, A., and Donnelly, C.
Subjects: operative, Male, postoperative discharge, Postoperative Complications, 0302 clinical medicine, Colostomy, CRITERIA, Prospective Studies, Bowel function, Colectomy, IMAGINE, stoma, intestines, Proctectomy, Ileostomy, digestive, oral, and skin physiology, patient discharge, colorectal surgery, hospital discharge, bowel function, RECOVERY, Middle Aged, adult, colostomy, elective surgical procedures, female, follow-up studies, humans, ileostomy, ileus, male, middle aged, multivariate analysis, patient readmission, patient safety, postoperative complications, prospective studies, recovery of function, colectomy, proctectomy, Patient Discharge, Colorectal surgery, ileus - - discharge - bowel function - elective - colorectal surgery, Elective Surgical Procedures, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Patient Safety, Cohort study, safety, Adult, medicine.medical_specialty, Ileus, Patient Readmission, defecation, 03 medical and health sciences, medicine, Hospital discharge, Humans, colorectal surgery, colorectal resection, Colorectal resection, defecation, postoperative complications, colorectal surgery, intestines, patient discharge, patient readmission, safety, surgical procedures, operative, colorectal resection, ileus, business.industry, Recovery of Function, Odds ratio, medicine.disease, digestive system diseases, surgical procedures, Surgery, Multivariate Analysis, Defecation, business, Follow-Up Studies
Abstract: Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function.A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien-Dindo classification system.A total of 3288 patients were included in the analysis, of whom 301 (9·2 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4-7) and 7 (6-8) days respectively (P 0·001). There were no significant differences in rates of readmission between these groups (6·6 versus 8·0 per cent; P = 0·499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0·90, 95 per cent c.i. 0·55 to 1·46; P = 0·659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34·7 versus 39·5 per cent; major 3·3 versus 3·4 per cent; P = 0·110).Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients.El íleo es frecuente tras la cirugía colorrectal y se asocia con un aumento del riesgo de las complicaciones postoperatorias. Identificar las características de una recuperación normal del tránsito y la idoneidad para el alta hospitalaria es una tarea difícil. Este estudio examinó la seguridad del alta hospitalaria antes del restablecimiento de la función intestinal. MÉTODOS: Se llevó a cabo un estudio de cohortes prospectivo y multicéntrico a través de una red de colaboración internacional. Se incluyeron pacientes adultos sometidos a resección electiva colorrectal entre enero y abril 2018. El objetivo principal fue el reingreso hospitalario durante los 30 primeros días tras la intervención. Se utilizó un análisis de regresión multivariable para evaluar el impacto del momento del alta en función del restablecimiento de la función intestinal. El objetivo secundario fue las complicaciones postoperatorias en los primeros 30 días después de la cirugía, valoradas mediante el sistema de clasificación de Clavien-Dindo.Se incluyeron en el análisis 3.288 pacientes, de los cuales 301 (9,2%) fueron dados de alta antes del restablecimiento de la función intestinal. La mediana de la estancia hospitalaria de los pacientes dados de alta antes y después del restablecimiento de la función intestinal fue 5 (rango intercuartílico: 4-7) y 7 (6-8) días, respectivamente (P 0,001). No hubo diferencias significativas en las tasas de reingreso entre estos grupos (6,6% versus 8,0%; P = 0,499), y este resultado se mantuvo en el análisis multivariable tras el ajuste por diferencias basales (razón de opotunidades, odds ratio, OR 0,90; i.c. del 95% 0,55-1,46, P = 0,659). Las tasas de complicaciones postoperarorias fueron similares en aquellos dados de alta antes o después del restablecimiento de la función intestinal (complicaciones menores: 34,7% versus 39,5%; complicaciones mayores 3,3% versus 3,4%; P = 0,110). CONCLUSIÓN: Dar de alta antes del restablecimiento de la función intestinal tras cirugía colorrectal electiva parece ser seguro en pacientes debidamente seleccionados.
Published: 2020
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31. Intubation Practices and Adverse Peri-intubation Events in Critically Ill Patients From 29 Countries

Author: Russotto V., Myatra S. N., Laffey J. G., Tassistro E., Antolini L., Bauer P., Lascarrou J. B., Szuldrzynski K., Camporota L., Pelosi P., Sorbello M., Higgs A., Greif R., Putensen C., Agvald-Ohman C., Chalkias A., Bokums K., Brewster D., Rossi E., Fumagalli R., Pesenti A., Foti G., Bellani G., Hazem Abdelkarem Ahmed, Neill K J Adhikari, Kehari Agrawal, Nipun Agrawal, Hernan Aguirre-Bermeo, Christina Agvald-Öhman, Meraj Ahmad, Samareh Ajami, Shazia N Akhtar, Adnan Alghamdi, Abdulmueti Alhadi, Syed M Ali, Mohd N Ali, Anita Alias, Ghaleb Almekhlafi, Julio Alonso, Diana Alvarez Montenegro, Rubina Aman, Matthew Anstey, Irene Aragão, Eleni Arnaoutoglou, Elie Azoulay, Laura Baccari, Nishanth Baliga, Ramya Ballekatte Manjunath, Shrirang Bamane, Anna Bandert, Roland Bartholdy, Marta Basto, Vera Baturova, Philippe R Bauer, Agrippino Bellissima, Vladislav Belsky, Prashant Bendre, Annalisa Benini, Sebastien Besset, Mahuya Bhattacharyya, Piotr Bielanski, Luca Bigatello, Florence Boissier, Kristaps Bokums, Elisa Boni, Iwona Bonney, David Bowen, Alexandre Boyer, Luca Brazzi, David Brewster, Lina Broman, Alexander Browne, Cedric Bruel, Yannick Brunin, Guillermo Bugedo, Italo Calamai, Patricia Campos, Federico G Canavosio, Iacopo Cappellini, Marco Cascella, Nuno Catorze, Athanasios Chalkias, Benoit Champigneulle, Juhi Chandwani, Anne Chao, Satish Chaurasia, Rajesh Chawla, Aakanksha Chawla, Olivia Cheetham, Frank Chemouni, Lee Chew Kiok, Jung-Yien Chien, Timothy Chimunda, Ching-Tang Chiu, Fernando Chiumiento, Nai-Kuan Chou, Nicolas Chudeau, Sandra Colica, Gwenhael Colin, Jean-Michel Constantin, Damien Contou, Andrea Cortegiani, Paulo F Costa, Vasco Costa, Andrea Costamagna, Antonella Cotoia, Andrea N Cracchiolo, Petra Crone, Rui P Cunha, Renata Curić Radivojević, Amit Das, Sampat Dash, Gennaro De Pascale, Silvia De Rosa, Lorenzo Del Sorbo, Valentina Della Torre, Barbara Di Caprio, Raffaele Di Fenza, Ida Di Giacinto, Aikaterini Dimitropoulou, Marcel Dudda, Christopher Edmunds, Stefan F Ehrentraut, Nadia El-Fellah, Muhammed Elhadi, Ahmed Elhadi, Patricia Escudero-Acha, Missael Espinoza, Clelia Esposito, Fabrizio Fabretti, Daniel G Fein, Massimo Ferluga, Marco Fernandes, Alexis Ferre, Janet Ferrier, Marek Flaksa, Fernando Flores, Jesus Flores Gonzalez, Xavier E Fonseca Fuentes, Roland Francis, Daniela G Franco, Pawel Franczyk, Jean-Pierre Frat, Mikhail Furman, Maurizio Fusari, Piotr Galkin, Alice Gallo de Moraes, Renato Gammaldi, Maria F García Aguilera, Eugenio Garofalo, Tomasz Gaszynski, Jonathan Gatward, Mohamed Ghula, Angelo Giacomucci, Ilaria Giovannini, Kingsly Gnanadurai, Thomas Godet, Alberto Goffi, Gemma Goma Fernandez, Maria Gonzalez, Daira González, Alejandro González-Castro, Kadarapura N Gopalakrishna, Eric Gottesman, Alexandre Gros, Christophe Guervilly, Christophe Guitton, Manish Gupta, Kulbhusahn Gupta, Tarikul Hamid, Olfa Hamzaoui, Katrin Hannesdottir, Shahnaz Hasan, Mozaffer Hossain, Sazzad Hossein, Sami Hraiech, Chun-Kai Huang, Cameron Hypes, Soad Imhmed Alkhumsi, Motiul Islam, Muhamad A Ismail, Višnja Ivančan, Sophie Jacquier, Bharat Jagiasi, Nikhilesh Jain, Muhamad Fadhil Hadi Jamaluddin, Milosz Jankowski, Deepak Jeswani, Deepti Jeswani, Simant Jha, Laura Jones, Benjamin Jones, Mathieu Jozwiak, Aleksandra Jumić, Oliver Kamp, Ilias Karametos, Alexey Karelov, Panagiotis Katsoulis, David A Kaufman, Shuchi Kaushik, Callum T Kaye, Subba R Kesavarapu, Ala Khaled, Hapiz Khalidah, Akram Khan, Sudhir Khunteta, Detlef Kindgen-Milles, Sara V Korula, Amol Kothekar, Salman S Koul, Ditte Krog, Shih-Chi Ku, Mira Kuellmar, Lu-Cheng Kuo, Swarna D Kuragayala, Aikaterini Kyparissi, Gonzalo Labarca, John G Laffey, Jaya Lalwani, Antonio Landaverde, Jean-Baptiste Lascarrou, Andres Laserna, Chien-Chang Lee, Stephane Legriel, Andrew Lehr, Tiago Leonor, Yongxing Li, Anna Lisa Licciardi, Edward Litton, Vladimir Lomivorotov, Federico Longhini, Claudia L Lopez Nava, Luis R Loza Gallardo, Ramona Lungu, Annalisa Luzi, Wuhua Ma, Marat Magomedov, Alexandros Makris, Harish Mallapura Maheshwarappa, Tommaso Maraffi, Maria E Marcelli, Karim Mariano, Nathalie Marin, Nadezhda Marova, Maelle Martin, Mayra Martinez Gonzalez, Emilio Maseda, Fiore Mastroianni, Marijana Matas, Dubier Matos, Jessica G Maugeri, Mohd Z Mazlan, Melanie Meersch, Ranjan Meher, Tasneem H Mehesry, Maria Meirik, Armand Mekontso Dessap, Kwabena Mensah, Emmanuelle Mercier, Pavel Michalek, Abhirup Midya, Slobodan Mihaljević, Adrien Mirouse, Prasanna Mishra, Ravi Mistry, Mate Moguš, Norbaniza Mohd Nordin, Noryani Mohd Samat, Luca Montini, Giorgia Montrucchio, Valeria Moro, Diego Morocho Tutillo, Jarrod Mosier, Sircar Mrinal, Wojciech Mudyna, Grégoire Muller, Kartik Munta, Satheesh Munusamy, Stefania Musso, Stefano Muttini, Ismail Nahla Irtiza, Evi Nakou, Amit Narkhede, Joseph Nates, Moana R Nespoli, Francesca Nespoli, Artem Nikitenko, Carla Nogueira, Ross O'Grady, Yewande E Odeyemi, Annika Ohlsson, Alberto Orsello, Vijayanand Palaniswamy, Daniela M Palma, Salvatore Palmese, Jesus N Pantoja Leal, Eleni Papandreou, Metaxia Papanikolaou, Matteo Parotto, Mayur Patel, Mario Pavlek, Niccolò Pedrotti, Ngu Pei Hwa, Lorella Pelagalli, Miryam Pérez Ruiz, Elin Persson, Athanasia Petsiou, Angelo Pezzi, Sam Philip, Francois Philippard, Mariusz Piegat, Sébastien Pili-Floury, Riccardo Pinciroli, Marcia Pinto, Gael Piton, Gaetan Plantefeve, Caroline Pouplet, Sofia Pouriki, Andrea Pradella, Kumar Prashant, Christian Putensen, Alice Quayle, Lua Rahmani, Ian Randall, Banambar Ray, Adrian Regli, Syed T Reza, Jean Damien Ricard, Ivano Riva, Oriol Roca, Roberto Rona, Jon Rosell, Rebecca Rowley, Sheng-Yuan Ruan, Kay Rumschuessel, Annalisa Rundo, Pierpaolo Russo, Vincenzo Russotto, Samir Sahu, Gabriele Sales, Charlotte Salmon-Gandonnière, Nandyelly San Juan Roman, Luis Sánchez-Hurtado, Benjamin J Sandefur, Manel Santafe, Lida Santoro, Rhik Sanyal, Lakshmikanthcharan Saravanabavan, Bhagyesh Shah, Mehul Shah, Ming-Hann Shin, Monica Silva, Shannon Simpson, Ayush Sinah, Atul K Singh, Dinesh K Singh, Nitesh Singh, Lalit Singh, Lukasz Skowronski, Miguel A Sosa, Savino Spadaro, Martin Spangfors, Jesper Sperber, Rosario Spina, Anand Srivastava, Andrew Steel, Alejandro Suarez de la Rica, Singh Sujeet Kumar, Omprakash Sundrani, Nilu Sunil, Bharadwaj Suparna, Manimala R Surath, Yadullah Syed, Tamas Szakmany, Benjamin Sztrymf, Alexis Tabah, Stefano Tarantino, Maria Tileli, Hugo Tirape-Castro, Otoniel Toledo-Salinas, Jacopo Tramarin, Dimitrios Tsiftsis, Iva Tucić, Jose A Tutillo León, Lorenzo Tutino, Vijay N Tyagi, Kyriaki Vagdatli, Sneha Varkey, Maria M Vera, Magnus Von Seth, Carl Wahlstrom, Wan Mohd N Wan Hassan, Wan N Wan Ismail, Kuo-Chuan Wang, Hadrien Winiszewski, Jiayan Wu, Lun Wu, Yu-Chang Yeh, Paul Young, Gianluca Zani, Jonathan Zarka, Dawn Zhao, Diane Zlotnik, Russotto, V, Myatra, S, Laffey, J, Tassistro, E, Antolini, L, Bauer, P, Lascarrou, J, Szuldrzynski, K, Camporota, L, Pelosi, P, Sorbello, M, Higgs, A, Greif, R, Putensen, C, Agvald-Öhman, C, Chalkias, A, Bokums, K, Brewster, D, Rossi, E, Fumagalli, R, Pesenti, A, Foti, G, Bellani, G, Russotto V., Myatra S.N., Laffey J.G., Tassistro E., Antolini L., Bauer P., Lascarrou J.B., Szuldrzynski K., Camporota L., Pelosi P., Sorbello M., Higgs A., Greif R., Putensen C., Agvald-Ohman C., Chalkias A., Bokums K., Brewster D., Rossi E., Fumagalli R., Pesenti A., Foti G., Bellani G., and Hazem Abdelkarem Ahmed, Neill K J Adhikari, Kehari Agrawal, Nipun Agrawal, Hernan Aguirre-Bermeo, Christina Agvald-Öhman, Meraj Ahmad, Samareh Ajami, Shazia N Akhtar, Adnan Alghamdi, Abdulmueti Alhadi, Syed M Ali, Mohd N Ali, Anita Alias, Ghaleb Almekhlafi, Julio Alonso, Diana Alvarez Montenegro, Rubina Aman, Matthew Anstey, Irene Aragão, Eleni Arnaoutoglou, Elie Azoulay, Laura Baccari, Nishanth Baliga, Ramya Ballekatte Manjunath, Shrirang Bamane, Anna Bandert, Roland Bartholdy, Marta Basto, Vera Baturova, Philippe R Bauer, Agrippino Bellissima, Vladislav Belsky, Prashant Bendre, Annalisa Benini, Sebastien Besset, Mahuya Bhattacharyya, Piotr Bielanski, Luca Bigatello, Florence Boissier, Kristaps Bokums, Elisa Boni, Iwona Bonney, David Bowen, Alexandre Boyer, Luca Brazzi, David Brewster, Lina Broman, Alexander Browne, Cedric Bruel, Yannick Brunin, Guillermo Bugedo, Italo Calamai, Patricia Campos, Federico G Canavosio, Iacopo Cappellini, Marco Cascella, Nuno Catorze, Athanasios Chalkias, Benoit Champigneulle, Juhi Chandwani, Anne Chao, Satish Chaurasia, Rajesh Chawla, Aakanksha Chawla, Olivia Cheetham, Frank Chemouni, Lee Chew Kiok, Jung-Yien Chien, Timothy Chimunda, Ching-Tang Chiu, Fernando Chiumiento, Nai-Kuan Chou, Nicolas Chudeau, Sandra Colica, Gwenhael Colin, Jean-Michel Constantin, Damien Contou, Andrea Cortegiani, Paulo F Costa, Vasco Costa, Andrea Costamagna, Antonella Cotoia, Andrea N Cracchiolo, Petra Crone, Rui P Cunha, Renata Curić Radivojević, Amit Das, Sampat Dash, Gennaro De Pascale, Silvia De Rosa, Lorenzo Del Sorbo, Valentina Della Torre, Barbara Di Caprio, Raffaele Di Fenza, Ida Di Giacinto, Aikaterini Dimitropoulou, Marcel Dudda, Christopher Edmunds, Stefan F Ehrentraut, Nadia El-Fellah, Muhammed Elhadi, Ahmed Elhadi, Patricia Escudero-Acha, Missael Espinoza, Clelia Esposito, Fabrizio Fabretti, Daniel G Fein, Massimo Ferluga, Marco Fernandes, Alexis Ferre, Janet Ferrier, Marek Flaksa, Fernando Flores, Jesus Flores Gonzalez, Xavier E Fonseca Fuentes, Roland Francis, Daniela G Franco, Pawel Franczyk, Jean-Pierre Frat, Mikhail Furman, Maurizio Fusari, Piotr Galkin, Alice Gallo de Moraes, Renato Gammaldi, Maria F García Aguilera, Eugenio Garofalo, Tomasz Gaszynski, Jonathan Gatward, Mohamed Ghula, Angelo Giacomucci, Ilaria Giovannini, Kingsly Gnanadurai, Thomas Godet, Alberto Goffi, Gemma Goma Fernandez, Maria Gonzalez, Daira González, Alejandro González-Castro, Kadarapura N Gopalakrishna, Eric Gottesman, Alexandre Gros, Christophe Guervilly, Christophe Guitton, Manish Gupta, Kulbhusahn Gupta, Tarikul Hamid, Olfa Hamzaoui, Katrin Hannesdottir, Shahnaz Hasan, Mozaffer Hossain, Sazzad Hossein, Sami Hraiech, Chun-Kai Huang, Cameron Hypes, Soad Imhmed Alkhumsi, Motiul Islam, Muhamad A Ismail, Višnja Ivančan, Sophie Jacquier, Bharat Jagiasi, Nikhilesh Jain, Muhamad Fadhil Hadi Jamaluddin, Milosz Jankowski, Deepak Jeswani, Deepti Jeswani, Simant Jha, Laura Jones, Benjamin Jones, Mathieu Jozwiak, Aleksandra Jumić, Oliver Kamp, Ilias Karametos, Alexey Karelov, Panagiotis Katsoulis, David A Kaufman, Shuchi Kaushik, Callum T Kaye, Subba R Kesavarapu, Ala Khaled, Hapiz Khalidah, Akram Khan, Sudhir Khunteta, Detlef Kindgen-Milles, Sara V Korula, Amol Kothekar, Salman S Koul, Ditte Krog, Shih-Chi Ku, Mira Kuellmar, Lu-Cheng Kuo, Swarna D Kuragayala, Aikaterini Kyparissi, Gonzalo Labarca, John G Laffey, Jaya Lalwani, Antonio Landaverde, Jean-Baptiste Lascarrou, Andres Laserna, Chien-Chang Lee, Stephane Legriel, Andrew Lehr, Tiago Leonor, Yongxing Li, Anna Lisa Licciardi, Edward Litton, Vladimir Lomivorotov, Federico Longhini, Claudia L Lopez Nava, Luis R Loza Gallardo, Ramona Lungu, Annalisa Luzi, Wuhua Ma, Marat Magomedov, Alexandros Makris, Harish Mallapura Maheshwarappa, Tommaso Maraffi, Maria E Marcelli, Karim Mariano, Nathalie Marin, Nadezhda Marova, Maelle Martin, Mayra Martinez Gonzalez, Emilio Maseda, Fiore Mastroianni, Marijana Matas, Dubier Matos, Jessica G Maugeri, Mohd Z Mazlan, Melanie Meersch, Ranjan Meher, Tasneem H Mehesry, Maria Meirik, Armand Mekontso Dessap, Kwabena Mensah, Emmanuelle Mercier, Pavel Michalek, Abhirup Midya, Slobodan Mihaljević, Adrien Mirouse, Prasanna Mishra, Ravi Mistry, Mate Moguš, Norbaniza Mohd Nordin, Noryani Mohd Samat, Luca Montini, Giorgia Montrucchio, Valeria Moro, Diego Morocho Tutillo, Jarrod Mosier, Sircar Mrinal, Wojciech Mudyna, Grégoire Muller, Kartik Munta, Satheesh Munusamy, Stefania Musso, Stefano Muttini, Ismail Nahla Irtiza, Evi Nakou, Amit Narkhede, Joseph Nates, Moana R Nespoli, Francesca Nespoli, Artem Nikitenko, Carla Nogueira, Ross O'Grady, Yewande E Odeyemi, Annika Ohlsson, Alberto Orsello, Vijayanand Palaniswamy, Daniela M Palma, Salvatore Palmese, Jesus N Pantoja Leal, Eleni Papandreou, Metaxia Papanikolaou, Matteo Parotto, Mayur Patel, Mario Pavlek, Niccolò Pedrotti, Ngu Pei Hwa, Lorella Pelagalli, Miryam Pérez Ruiz, Elin Persson, Athanasia Petsiou, Angelo Pezzi, Sam Philip, Francois Philippard, Mariusz Piegat, Sébastien Pili-Floury, Riccardo Pinciroli, Marcia Pinto, Gael Piton, Gaetan Plantefeve, Caroline Pouplet, Sofia Pouriki, Andrea Pradella, Kumar Prashant, Christian Putensen, Alice Quayle, Lua Rahmani, Ian Randall, Banambar Ray, Adrian Regli, Syed T Reza, Jean Damien Ricard, Ivano Riva, Oriol Roca, Roberto Rona, Jon Rosell, Rebecca Rowley, Sheng-Yuan Ruan, Kay Rumschuessel, Annalisa Rundo, Pierpaolo Russo, Vincenzo Russotto, Samir Sahu, Gabriele Sales, Charlotte Salmon-Gandonnière, Nandyelly San Juan Roman, Luis Sánchez-Hurtado, Benjamin J Sandefur, Manel Santafe, Lida Santoro, Rhik Sanyal, Lakshmikanthcharan Saravanabavan, Bhagyesh Shah, Mehul Shah, Ming-Hann Shin, Monica Silva, Shannon Simpson, Ayush Sinah, Atul K Singh, Dinesh K Singh, Nitesh Singh, Lalit Singh, Lukasz Skowronski, Miguel A Sosa, Savino Spadaro, Martin Spangfors, Jesper Sperber, Rosario Spina, Anand Srivastava, Andrew Steel, Alejandro Suarez de la Rica, Singh Sujeet Kumar, Omprakash Sundrani, Nilu Sunil, Bharadwaj Suparna, Manimala R Surath, Yadullah Syed, Tamas Szakmany, Benjamin Sztrymf, Alexis Tabah, Stefano Tarantino, Maria Tileli, Hugo Tirape-Castro, Otoniel Toledo-Salinas, Jacopo Tramarin, Dimitrios Tsiftsis, Iva Tucić, Jose A Tutillo León, Lorenzo Tutino, Vijay N Tyagi, Kyriaki Vagdatli, Sneha Varkey, Maria M Vera, Magnus Von Seth, Carl Wahlstrom, Wan Mohd N Wan Hassan, Wan N Wan Ismail, Kuo-Chuan Wang, Hadrien Winiszewski, Jiayan Wu, Lun Wu, Yu-Chang Yeh, Paul Young, Gianluca Zani, Jonathan Zarka, Dawn Zhao, Diane Zlotnik
Subjects: Male, medicine.medical_specialty, Critical Illness, medicine.medical_treatment, Aged, Female, Heart Arrest, Humans, Hypotension, Hypoxia, Intensive Care Units, Intubation, Intratracheal, Logistic Models, Medical Errors, Middle Aged, Prospective Studies, Respiration, Artificial, Respiratory Insufficiency, Vasoconstrictor Agents, 01 natural sciences, NO, tracheal intubation, adverse peri-intubation events, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Intensive care, Settore MED/41 - ANESTESIOLOGIA, Medicine, Intubation, Intubation, Critical Care, 030212 general & internal medicine, 0101 mathematics, 610 Medicine & health, Prospective cohort study, business.industry, Respiration, 010102 general mathematics, Tracheal intubation, General Medicine, Intratracheal, Intubation procedure, Respiratory failure, Artificial, Emergency medicine, Airway management, business
Abstract: Importance: Tracheal intubation is one of the most commonly performed and high-risk interventions in critically ill patients. Limited information is available on adverse peri-intubation events. Objective: To evaluate the incidence and nature of adverse peri-intubation events and to assess current practice of intubation in critically ill patients. Design, Setting, and Participants: The International Observational Study to Understand the Impact and Best Practices of Airway Management in Critically Ill Patients (INTUBE) study was an international, multicenter, prospective cohort study involving consecutive critically ill patients undergoing tracheal intubation in the intensive care units (ICUs), emergency departments, and wards, from October 1, 2018, to July 31, 2019 (August 28, 2019, was the final follow-up) in a convenience sample of 197 sites from 29 countries across 5 continents. Exposures: Tracheal intubation. Main Outcomes and Measures: The primary outcome was the incidence of major adverse peri-intubation events defined as at least 1 of the following events occurring within 30 minutes from the start of the intubation procedure: cardiovascular instability (either: systolic pressure 30 minutes, new or increase need of vasopressors or fluid bolus >15 mL/kg), severe hypoxemia (peripheral oxygen saturation
Published: 2021

32. Changes in gut microbiota in the acute phase after spinal cord injury correlate with severity of the lesion

Author: Angelica Bava, Valentina Cagnetta, Tiziana Giovannini, Sauro Biscotto, Sonia Cremascoli, Marco Candela, Laura Terenghi, Lucia Rapisarda, Maurizio Cazzaniga, Ernesto Losavio, Maria Chiara Bulzamini, Maria Cristina Pagliacci, Gabriele Bazzocchi, Federica D’Amico, Luisa De Palma, Maria Pia Onesta, Beatrice Aiachini, Patrizia Brigidi, Carlotte Kiekens, Antonino Massone, Michele Scarazzato, Mirco Castiglioni, Giuseppina Frasca, Mimosa Balloni, Claudia Oggerino, Silvia Turroni, Bazzocchi G., Turroni S., Bulzamini M.C., D'Amico F., Bava A., Castiglioni M., Cagnetta V., Losavio E., Cazzaniga M., Terenghi L., De Palma L., Frasca G., Aiachini B., Cremascoli S., Massone A., Oggerino C., Onesta M.P., Rapisarda L., Pagliacci M.C., Biscotto S., Scarazzato M., Giovannini T., Balloni M., Candela M., Brigidi P., and Kiekens C.
Subjects: 0301 basic medicine, Male, Disease, Gut flora, Severity of Illness Index, Feces, 0302 clinical medicine, RNA, Ribosomal, 16S, Defecation, Spinal cord injury, education.field_of_study, Multidisciplinary, Spinal Cord Injurie, biology, Middle Aged, Traumatic injury, Italy, Acute Disease, Medicine, 030211 gastroenterology & hepatology, Female, medicine.symptom, Case-Control Studie, Human, Adult, Science, Population, Spinal cord diseases, Article, Lesion, 03 medical and health sciences, Young Adult, medicine, Humans, Microbiome, education, Spinal Cord Injuries, Aged, business.industry, biology.organism_classification, medicine.disease, Gastrointestinal Microbiome, 030104 developmental biology, Case-Control Studies, Immunology, Dysbiosis, Fece, business
Abstract: After spinal cord injury (SCI), patients face many physical and psychological issues including intestinal dysfunction and comorbidities, strongly affecting quality of life. The gut microbiota has recently been suggested to influence the course of the disease in these patients. However, to date only two studies have profiled the gut microbiota in SCI patients, months after a traumatic injury. Here we characterized the gut microbiota in a large Italian SCI population, within a short time from a not only traumatic injury. Feces were collected within the first week at the rehabilitation center (no later than 60 days after SCI), and profiled by 16S rRNA gene-based next-generation sequencing. Microbial profiles were compared to those publicly available of healthy age- and gender-matched Italians, and correlated to patient metadata, including type of SCI, spinal unit location, nutrition and concomitant antibiotic therapies. The gut microbiota of SCI patients shows distinct dysbiotic signatures, i.e. increase in potentially pathogenic, pro-inflammatory and mucus-degrading bacteria, and depletion of short-chain fatty acid producers. While robust to most host variables, such dysbiosis varies by lesion level and completeness, with the most neurologically impaired patients showing an even more unbalanced microbial profile. The SCI-related gut microbiome dysbiosis is very likely secondary to injury and closely related to the degree of completeness and severity of the lesion, regardless of etiology and time interval. This microbial layout could variously contribute to increased gut permeability and inflammation, potentially predisposing patients to the onset of severe comorbidities.
Published: 2021

33. Differences in hub and spoke vascular units practice during the novel Coronavirus-19 (COVID-19) outbreak in Lombardy, Italy

Author: Bellosta, Raffaello, Bissacco, Daniele, Rossi, Giovanni, Pirrelli, Stefano, Lanza, Gaetano, Frigerio, Dalmazio, Chiesa, Roberto, Castelli, Patrizio, Bonardelli, Stefano, Trimarchi, Santi, Stefano Aiello, Aldo Arzini, Luca Attisani, Vittorio Baratta, Luca Bassi, Giovanni Bonalumi, Antonio Bozzani, Franco Briolini, Cristina Busoni, Gianluca Canu, Michele Carmo, Roberto Caronno, Claudio Carugati, Pietro Cefali, Efrem Civilini, Emidio Costantini, Matteo Crippa, Ruggiero Curci, Raffaello Dallatana, Gaetano Deleo, Domenico Diaco, Matteo Ferraris, Davide Foresti, Marco Franchin, Francesca Giovannini, Viviana Grassi, Andrea Kahlberg, Jessica Lanza, Davide Logaldo, Chiara Lomazzi, Sergio Losa, Alfredo Lista, Gianluca Lussardi, Luca Luzzani, Clara Magri, Enrico M Marone, Daniele Mascia, Daniela Mazzaccaro, Roberto Mezzetti, Alessandro C Molinari, Giovanni Nano, Matteo A Pegorer, Gabriele Piffaretti, Tiziano Porretta, Franco Ragni, Andrea Rignano, Federico Romani, Piergiorgio Sala, Vittorio Segramora, Marco Setti, Antonino Silvestro, Giovanna Simonetti, Anna M Socrate, Silvia Stegher, Valerio Tolva, Matteo Tozzi, Piero Trabattoni, Pierluigi Vandone, Monica Vescovi, Marco Viani, Stefano Zoli, Bellosta, Raffaello, Bissacco, Daniele, Rossi, Giovanni, Pirrelli, Stefano, Lanza, Gaetano, Frigerio, Dalmazio, Chiesa, Roberto, Castelli, Patrizio, Bonardelli, Stefano, Trimarchi, Santi, Stefano, Aiello, Aldo, Arzini, Luca, Attisani, Vittorio, Baratta, Luca, Bassi, Giovanni, Bonalumi, Antonio, Bozzani, Franco, Briolini, Cristina, Busoni, Gianluca, Canu, Michele, Carmo, Roberto, Caronno, Claudio, Carugati, Pietro, Cefali, Efrem, Civilini, Emidio, Costantini, Matteo, Crippa, Ruggiero, Curci, Raffaello, Dallatana, Gaetano, Deleo, Domenico, Diaco, Matteo, Ferrari, Davide, Foresti, Marco, Franchin, Francesca, Giovannini, Viviana, Grassi, Kahlberg, ANDREA LUITZ, Jessica, Lanza, Davide, Logaldo, Chiara, Lomazzi, Sergio, Losa, Alfredo, Lista, Gianluca, Lussardi, Luca, Luzzani, Clara, Magri, Enrico, M Marone, Daniele, Mascia, Daniela, Mazzaccaro, Roberto, Mezzetti, Alessandro, C Molinari, Giovanni, Nano, Matteo, A Pegorer, Gabriele, Piffaretti, Tiziano, Porretta, Franco, Ragni, Andrea, Rignano, Federico, Romani, Piergiorgio, Sala, Vittorio, Segramora, Marco, Setti, Antonino, Silvestro, Giovanna, Simonetti, Anna, M Socrate, Silvia, Stegher, Valerio, Tolva, Matteo, Tozzi, Piero, Trabattoni, Pierluigi, Vandone, Monica, Vescovi, Marco, Viani, and Stefano, Zoli
Subjects: Adult, Male, medicine.medical_specialty, Multivariate analysis, medicine.medical_treatment, Pneumonia, Viral, COVID-19, Vascular surgical procedures, Multicenter registry, Emergencies, Disease, Vascular surgery, Vascular emergencies, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Clinical endpoint, Humans, Registries, Vascular Diseases, Pandemics, Referral and Consultation, Aged, Retrospective Studies, business.industry, Vascular disease, SARS-CoV-2, Mortality rate, General Medicine, Middle Aged, medicine.disease, Hospitalization, Pneumonia, 030228 respiratory system, Amputation, Italy, Surgery, Female, Cardiology and Cardiovascular Medicine, business
Abstract: BACKGROUND: To highlight clinical practice among referral (Hub, HH) or satellite (Spoke, SH) hospitals Vascular Surgery Units (VSUs) in Lombardy, during the COVID-19 pandemic "phase 1" period (March 8 - May 3, 2020). METHODS: The Vascular Surgery Group of Regione Lombardia Register, a real-word, multicenter, retrospective register was interrogated. All patients admitted with vascular disease were included. Patients' data on demographics, COVID-19 positivity, comorbidities and outcomes were extrapolated. Two cohorts were obtained: patients admitted to HH or SH. Primary endpoint was 30- day mortality rate. Secondary outcomes were 30-day complications and amputation (in case of peripheral artery disease [PAD]) rates. Univariate and multivariate analysis were used to compare HH and SH groups and predictors of poor outcomes. RESULTS: During the study period, 659 vascular patients in 4 HH and 27 SH were analyzed. Among these, 321 (48.7%) were admitted to a HH. No difference in COVID-19 positive patients was described (21.7% in HH vs 15.9% in SH; p=.058). After 30 days from intervention, HH and SH experienced similar mortality and no-intervention-related complication rate (12.1% vs 10.0%; p=.427 and 10.3% vs 8.3%; p=.377, respectively). Conversely, in HH postoperative complications were higher (23.4% vs 16.9%, p=.038) and amputations in patients treated for PAD were lower (10.8% vs 26.8%; p
Published: 2020

34. Optimizing Lipid Pattern by Adding a Combined Nutraceutical or Pravastatin to Fenofibrate Treatment in Hypertriglyceridemic Subjects: Single Site, Randomized, Open-Label, Post-Market Clinical Investigation

Author: Arrigo F G Cicero, Marilisa Bove, Marina Giovannini, Fulvio Ventura, Federica Fogacci, Claudio Borghi, Cicero, Arrigo F G, Fogacci, Federica, Bove, Marilisa, Ventura, Fulvio, Giovannini, Marina, and Borghi, Claudio
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Time Factors, Down-Regulation, Type 2 diabetes, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Fenofibrate, Internal medicine, Product Surveillance, Postmarketing, Internal Medicine, medicine, Humans, Prospective Studies, Adverse effect, Triglycerides, Pravastatin, Hypertriglyceridemia, business.industry, nutritional and metabolic diseases, medicine.disease, Clinical trial, Treatment Outcome, 030104 developmental biology, Italy, Tolerability, Dietary Supplements, Drug Therapy, Combination, Female, lipids (amino acids, peptides, and proteins), Nutraceutical, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine, business, Biomarkers, Dyslipidemia, medicine.drug
Abstract: INTRODUCTION: Fenofibrate is an effective and safe treatment for hypertriglyceridemia. However, after TG reduction a residual dyslipidemia could appear and require further treatment. AIM: To comparatively evaluate the short-term tolerability and efficacy of a combined lipid-lowering nutraceutical and pravastatin 40 mg in fenofibrate treated patients. METHOD: We prospectively enrolled 40 patients well-tolerating treatment with micronized fenofibrate 145 mg/day and with residual dyslipidemia (LDL-C > 115 mg/dL and TG > 150 mg/dL). Exclusion criteria have been type 2 diabetes, Familial Hypercholesterolemia, previous cardiovascular diseases and severe chronic kidney disease. Then, we have randomly assigned the patients to treatment with pravastatin 40 mg or a combined lipid-lowering nutraceutical (Armolipid Plus®, containing monacolin 3 mg and berberine 500 mg). RESULTS: After 8 weeks of treatment, 80% of pravastatin treated patients (N. 16/20) and 75% of those treated with Armolipid Plus® (N. 15/20) reached the desired LDL-C target, while 50% of pravastatin treated patients (N. 10/20) and 80% of the Armolipid Plus® treated ones reached the desired TG target (N. 16/20). No one adverse event has been registered during Armolipid Plus®, while 1 patient claimed myalgia and 1 reported significant increase of CPK (> 3 ULN) during pravastatin treatment. Both patients were then treated with Armolipid Plus® with resolution of symptoms and CPK increase, respectively. CONCLUSION: In hypertriglyceridemic patients treated with fenofibrate, the association with a combined lipid lowering nutraceutical seem to be more effective in optimizing residual hypertriglyceridemia than pravastatin 40 mg, while being more tolerable and having similar effect on LDL-C plasma level.
Published: 2018
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35. Serum uric acid predicts incident metabolic syndrome in the elderly in an analysis of the Brisighella Heart Study

Author: Elisa Grandi, Marina Giovannini, Sergio D'Addato, Martina Rosticci, Claudio Borghi, Federica Fogacci, Arrigo F G Cicero, Cicero, Arrigo Francesco Giuseppe, Fogacci, Federica, Giovannini, Marina, Grandi, Elisa, Rosticci, Martina, D’Addato, Sergio, and Borghi, Claudio
Subjects: Male, Serum, medicine.medical_specialty, Science, Population, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Internal medicine, Epidemiology, medicine, Humans, Prospective Studies, Hyperuricemia, education, Aged, Aged, 80 and over, Metabolic Syndrome, education.field_of_study, Multidisciplinary, business.industry, Incidence, Incidence (epidemiology), Serum uric acid, Middle Aged, medicine.disease, Uric Acid, ROC Curve, Cohort, Medicine, Female, Metabolic syndrome, business, Historical Cohort
Abstract: Several epidemiological studies report a positive correlation between hyperuricemia and metabolic syndrome (MetS) in adults, which hyperuricemic subjects seem to more easily develop. We aimed to verify if serum uric acid (SUA) concentrations were positively associated with MetS prevalence and middle-term (4-year) incidence in older overall healthy subjects. We also purposed to identify which SUA cut-off values could be functional in MetS diagnosis in addition to the traditionally used parameters. For this reason, we selected from the historical cohort of the Brisighella Heart Study 923 older healthy subjects repeatedly visited during the 2008 and 2012 population surveys. In our sample, MetS was more frequent for higher SUA concentrations rather than the population’s mean in both men [OR = 2.12, 95%C.I.(1.55, 2.90)] and women [OR = 2.69,95%C.I.(1.91, 3.78)]. ROC analysis showed SUA was predictive of MetS in the whole population [AUC = 0.647, 95%C.I.(0.609, 0.686), P = 0.000001] and in both sex subgroups [men: AUC = 0.592, 95%C.I.(0.529, 654); P = 0.004; women: AUC = 0.758, 95%C.I.(0.711, 0.806), P 0.05). In conclusion, in our cohort, SUA is a frequent component of MetS, other than a middle-term predictor of newly diagnosed MetS in older women.
Published: 2018

36. Management of diabetic macular edema with intravitreal dexamethasone implants: Expert recommendations using a Delphi-based approach

Author: Alfonso Giovannini, Federico Ricci, Mariacristina Parravano, Francesco Bandello, Giovannini, A., Parravano, M., Ricci, F., and Bandello, F.
Subjects: Male, Vascular Endothelial Growth Factor A, medicine.medical_specialty, Delphi Technique, Diabetic macular edema, Visual Acuity, Angiogenesis Inhibitors, Dexamethasone, Macular Edema, 03 medical and health sciences, 0302 clinical medicine, Settore MED/30, Ophthalmology, Humans, Medicine, Glucocorticoids, Aged, Drug Implants, Anti vegf, Diabetic Retinopathy, treatment, business.industry, General Medicine, Delphi consensus, intravitreal dexamethasone implant, Intravitreal Injections, 030221 ophthalmology & optometry, anti–vascular endothelial growth factor, Female, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Objectives: Despite being approved and effective, steroids, and especially dexamethasone intravitreal implants, still have a poorly-defined role in management of diabetic macular edema. In order to overcome some of the limitations in current recommendations, a group of experts met to define consensus on some of the most controversial issues on the use of dexamethasone intravitreal implants in daily management of diabetic macular edema. Methods: A Delphi-based approach was utilized to develop clinically relevant statements applicable to routine treatment settings. A Steering Committee composed of four experts formulated 30 relevant statements, which were voted upon by a panel of 40 ophthalmologists/retinal specialists from across Italy. Results: Dexamethasone intravitreal implants were considered to be a valid first-line alternative to treatment with an anti–vascular endothelial growth factor agent and should be the first choice in pseudophakic and vitrectomized patients. A Pro Re Nata regimen was felt to be appropriate for retreatment with dexamethasone intravitreal implants while a 6-month waiting period was not considered suitable. Among steroid treatments, dexamethasone intravitreal implants were considered to have the best ocular tolerability. In patients with persistent macular edema after the loading-phase treatment with an anti–vascular endothelial growth factor, consensus was reached that clinicians should consider switching therapy to dexamethasone intravitreal implants. Moreover, dexamethasone intravitreal implants can reduce the treatment burden for individuals who are not able to cope with the more intensive treatment regimen required by anti–vascular endothelial growth factor therapy. Conclusions: While further studies are needed, this survey provides some key recommendations for clinicians treating diabetic macular edema that may be useful when choosing dexamethasone intravitreal implants in daily practice.
Published: 2018
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37. Combined therapy with intravitreal aflibercept and subtenon corticosteroids in eyes with severe diabetic papillopathy: two case reports

Author: Alfonso Giovannini, Piergiorgio Neri, Ilir Arapi, and Arjeta Grezda
Subjects: Male, medicine.medical_specialty, Visual acuity, Triamcinolone acetonide, genetic structures, Recombinant Fusion Proteins, Case Report, Diabetic papillopathy, Ophthalmology, Edema, medicine, Humans, Subtenon triamcinolone acetonide, Macular edema, Glucocorticoids, Aflibercept, business.industry, General Medicine, Middle Aged, medicine.disease, Diagnosis of exclusion, eye diseases, Vitreous Body, Receptors, Vascular Endothelial Growth Factor, Diabetes Mellitus, Type 2, Medicine, Combined therapy, Female, medicine.symptom, business, medicine.drug, Papilledema
Abstract: Background Diabetic papillopathy is a rare diagnosis of exclusion characterized by unilateral or bilateral optic disc edema with variable degrees of visual loss. Although the visual prognosis has been generally reported as favorable, the presence of severe disc edema associated with macular edema prompts the need for treatment. We present a specific and unreported therapeutic approach consisting of intravitreal aflibercept and subtenon triamcinolone acetonide injections in two patients with evidence of diabetic papillopathy and macular edema. Case presentation In the first case, a 60-year-old Caucasian woman affected by type II diabetes mellitus presented with fundoscopic evidence of sequential bilateral optic disc edema associated with acute severe visual loss in both eyes. The second patient, a diabetic 57-year-old Caucasian male, presented with sudden painless visual loss in his left eye. Multimodal imaging and systemic findings correlated towards an infrequent diagnosis of diabetic papillopathy. In a period of 5–7 weeks after treatment, both patients experienced almost full visual and anatomical recovery. A steady situation was observed at 12 months of follow-up. Conclusions Both our cases displayed a severe grade of optic disc edema, which was optimally reversed with intravitreal aflibercept and subtenon triamcinolone acetonide leading to a relatively rapid and safe improvement in visual acuity.
Published: 2021

38. Neonatal Early Onset Sepsis: Impact of Kaiser Calculator in an Italian Tertiary Perinatal Center

Author: Eleonora Pontello, Francesca Tormena, Nicoletta Mainini, Paola Lago, Valentina Favero, Anna Chiara Frigo, Beatrice Galeazzo, and Michela Giovannini
Subjects: Microbiology (medical), Male, Pediatrics, medicine.medical_specialty, newborns, medicine.drug_class, Antibiotics, Population, antibiotics, early onset sepsis, infection, sepsis calculator, Sepsis, Risk Factors, medicine, Humans, Blood culture, education, Retrospective Studies, education.field_of_study, medicine.diagnostic_test, Neonatal sepsis, business.industry, Incidence (epidemiology), Infant, Newborn, Gestational age, medicine.disease, Decision Support Systems, Clinical, Anti-Bacterial Agents, Infectious Diseases, Pediatrics, Perinatology and Child Health, Gestation, Female, Neonatal Sepsis, business
Abstract: BACKGROUND Suspected early-onset sepsis (EOS) results in antibiotic treatment and blood withdraw of a substantial number of neonates who are uninfected. We evaluated if the EOS calculator can reduce antibiotic exposure and invasive procedures for suspected EOS in term and late preterm neonates, without any significant increase in adverse outcomes. METHODS The proportion of EOS risk in neonates ≥35 weeks gestation exposed to antibiotics, intensive monitoring and blood withdrawal was compared between a baseline period (January 2018-May 2018), when Centers for Disease Control guidelines approach was used, and a post-EOS calculator-implementation period (June 2018-December 2019). RESULTS We included 4363 newborn infants with gestational age ≥35 weeks, respectively 824 in baseline period and 3539 in the EOS calculator period. Among them, 1021 (23.4%) infants presented risk factors for neonatal sepsis. There was a halving in empirical antibiotics exposure: 3% in the baseline and 1.4% in the post-EOS-implementation period, P < 0.05. Blood culture and laboratory evaluations had fallen from 30.6% to 15.4% (P < 0.05). Close monitoring of vital parameters decreased from 25.4% to 4.8% (P < 0.05). The number of antibiotic days per 100 live births decreased from 15.05 to 6.36 days (P
Published: 2021

39. Acute Delta Hepatitis in Italy spanning three decades (1991-2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Author: Tommaso, Stroffolini, Filomena, Morisco, Luigina, Ferrigno, Giuseppina, Pontillo, Giuseppina, Iantosca, Valentina, Cossiga, Simonetta, Crateri, Maria Elena Tosti, Valeria, Alfonsi, Franca, D'Angelo, Zotti, Carla Maria, Rainero, Erika, Marengo, Noemi, Silvana, Malaspina, Angela, Gallone, Annalisa, Castella, Maria Teresa Galati, Annamaria, Scala, Paolo, Castagna, Virginia, Silano, Sebastiano, D'Agosta, Maria Grazia Tacca, Silvia, Iodice, Vilma, Corvi, Maurizio, Oddone, Daniela, Rivetti, Paola, Ravaschietto, Franco, Giovanetti, Teresa, Cappello, Alessandro, Smaniotto, Mario, Ruffier, Marina, Verardo, Maria, Gramegna, Sabrina, Senatore, Danilo, Cereda, Annalisa, Donadini, Carla, Nespoli, Livia, Trezzi, Giorgio, Gennati, Angelo, Monteverdi, Liana, Boldori, Franco Paolo Tortorella, Paola Elvira Merlini, Davide Di Caterina, Marino, Faccini, Anna, Lamberti, Eva, Rossetti, Rita, Brugnoli, Giulia, Mainardi, Alessandra, Vezzoli, Daniela, Caso, Milena, Testa, Alice, Erba, Paola, Senegaglia, Annamaria, Spagna, Silvia, Lodola, Marcello, Tirani, Enza, Giompapa, Luigi Guido Roveri, Gabriele, Guardigli, Vanna, Scalvinoni, Silvia, Spertini, Sabine, Gamper, Andrea, Grünfelder, Barbara, Ploner, Verena, Runggatscher, Silvia, Molinaro, Maria Grazia Zuccali, Silvia, Franchini, Francesca, Russo, Francesca, Zanella, Donatella, Rizzato, Graziella, Carpene, Nadia, Lamonato, Emanuela, Destefani, Alessandra Dal Zotto, Rita Dal Zotto, Paola, Casagrande, Felice, Foglia, Gemma, Zorzi, Ester, Chermaz, Liana, Gava, Luigi, Nicolardi, Lorena, Pavanetto, Cecilia, Battiston, Francesco De Grandi, Laura, Rizzato, Michele, Tonon, Elisabetta, Cannizzo, Maurizio, Foroni, Laura, Colucci, Monica, Barbieri, Rosanna, Ledri, Tolinda, Gallo, Giulio, Rocco, Rossana, Stacul, Ariella, Breda, Andrea, Iob, Simonetta, Micossi, Oriana, Feltrin, Giuseppina, Caernelos, Marco, Mela, Virna, Frumento, Anna, Opisso, Alessandro, Cuccu, Giorgio, Zoppi, Patrizia, Torracca, Armanda, Capellini, Francesco, Maddalo, Giovanna, Mattei, Claudio, Gualanduzzi, Erika, Massimiliani, Anna Rita Sacchi, Laura, Gardenghi, Anna Rosa Gianninoni, Elena Dalle Donne, Roberto, Rangoni, Annalisa, Califano, Chiara, Reali, Emilia, Biguzzi, Barbara, Bondi, Anna, Pecci, Bianca Maria Borrini, Lucia, Pecori, Emanuela, Balocchini, Costanza, Pierozzi, Rosa, Luzzoli, Paola, Marchini, Lara, Lucchesi, Alberto, Tomasi, Elisabetta, Raso, Nadia, Olimpi, Cristiana, Berti, Francesca, Matarazzo, Nicoletta, Galletti, Laura, Puppa, Marinella, Frasca, Alessandro, Barbieri, Chiara, Cinughi, Maria, Bandini, Iorio, Lezzi, Fabrizia, Verdelli, Renzo, Paradisi, Rita, Bindi, Cinzia Monica Sansone, Maria, Rosati, Federica, Zacchini, Simonetta, Baretti, Rossella, Cecconi, Chiara, Staderini, Poalo, Filidei, Elisabetta, Alfaroli, Franco, Barghini, Marina, Cadoni, Anna, Tosti, Giovannini, G, Giovanni, Piattellini, Alessandra, Buscosi, Anna, Pasquale, Carla, Ciani, Maria Claudia Paoloni, Franco, Santocchia, Maria Laura Proietti, Daniel, Fiacchini, Dzenana, Hazurovic, Maria Sole Giamprini, Katia, Gatti, Jacqueline Van Will, Alfredo, Vaccaro, Maria Margherita Sbarbati, Alessandra, Amelio, Daniela, Cimini, Vania, Moroni, Daniela, Francoletti, Federica, Scaccia, Elisabetta, Branchesi, Selena, Saracino, Catia, Mezzanotte, Susanna, Cimica, Vita, Vitale, Franca, Laici, Irene, Petrelli, Barbara, Airini, Gabriella, Passarini, Lucia, Ruffini, Anna Maria Lambertucci, Annarita, Mogetta, Francesca, Cioccoloni, Giuseppe, Ciarrocchi, Marina, Pistolesi, Erika, Fratello, Francesca, Picciotti, Claudio, Angelini, Paola, Scognamiglio, Francesco, Vairo, Andreina, Ercole, Antonio Salvatore Maglietta, Fabrizio, Magrelli, Fabrizio, Perrelli, Carlo, Cerocchi, Paolo, Grillo, Cristina, Vazzoler, Maria Rosaria Loffredo, Alessio, Pendenza, Maria Rosaria Nappi, Paola, Bueti, Luigi, Santucci, Franca, Mangiagli, Donatella, Varrenti, Silvia, Aquilani, Pietro, Dionette, Daniela, Corpolongo, Giuseppe Di Luzio, Manuela Di Giacomo, Enrico, Giansanti, Cristiana, Mancini, Claudio, Turchi, Carla, Granchelli, Graziella, Soldato, Felesina, D'Eugenio, Ida, Albanesi, Maria Antonietta Ferrara, Annarita, Citarella, Elena, Fossi, Rosa, Alfieri, Milena, Scotto, Anna Luisa Caiazzo, Rosa, Prato, Maria, Chironna, Domenico, Martinelli, Francesca, Fortunato, Maria Giovanna Cappelli, Daniela, Loconsole, Anna, Morea, Giulia Del Matto, Raffaele, Angelillis, Marcello, Antonazzo, Valerio, Aprile, Grazia Maria Avella, Roberta, Cambria, Giovanni, Caputi, Rosati, Cipriani, Carlo De Santis, Francesco, Desiante, Marisa, Ferraro, Vera, Laforgia, Antonino, Madaro, Maria Giuseppina Maluccio, Anna Maria Matera, Stefania, Menolascina, Giuseppina, Moffa, Maria, Nesta, Rita, Olivieri, Onofrio, Pagone, Pasquale, Pedote, Rosella, Squicciarini, Stefano, Termite, Viviana, Vitale, Francesco, Negrone, Manuela, Maldini, Giovanni, Laugello, Teresa, Russo, Anna Domenica Mignuoli, Giuseppe, Afflitto, Benedetto, Caroleo, Maria, Montesanti, Vincenzo De Giorgio, Antonio, Maradei, Rocco Cataldo Romeo, Francesca, Scrivano, Elisa, Lazzarino, Vittoria, Surace, Antonella, Giordano, Alessandro, Bisbano, Anita, Arcuri, Ida, Valentini, Rossana, Mangione, Valentina, Meli, Mario, Cuccia, Elena, Longhitano, Fiorenzo, Delogu, Donatella, Fracasso, Maria Vittoria Marceddu, Antonina, Puggioni, Maria Valentina Eugenua Marras, Rita, Serpi, Simonetta, Santus, Valentina, Marras, Stroffolini, Tommaso, Morisco, Filomena, Ferrigno, Luigina, Pontillo, Giuseppina, Iantosca, Giuseppina, Cossiga, Valentina, Crateri, Simonetta, and Tosti, Maria Elena
Subjects: Adult, Male, medicine.medical_specialty, HBsAg, Hepatitis B virus, viruses, Population, hepatitis delta, medicine.disease_cause, Virology, Internal medicine, Epidemiology, medicine, Humans, hepatitis B vaccination, education, Hepatitis, education.field_of_study, Hepatitis B Surface Antigens, Hepatology, business.industry, Immunization Programs, Incidence (epidemiology), virus diseases, biochemical phenomena, metabolism, and nutrition, medicine.disease, Hepatitis B, Hepatitis D, Vaccination, Infectious Diseases, surveillance, epidemiology, Female, Hepatitis Delta Virus, business, Viral hepatitis
Abstract: Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p
Published: 2021

40. Novel dominant distal titinopathy phenotype associated with copy number variation

Author: Nicolas Leboucq, Martial Mallaret, Raul Juntas Morales, Mireille Cossée, K. Gaudon, Emmanuelle Uro-Coste, Delphine Lacourt, Henri Pegeot, C. Thèze, Emmeline Lagrange, Aurélien Perrin, Pascale Richard, Corinne Metay, Valérie Rigau, Michel Koenig, Diane Giovannini, Françoise Chapon, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire [Grenoble] (CHU), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Biochimie Métabolique et Centre de Génétique moléculaire et chromosomique [CHU Pitié Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), MORNET, Dominique, CHU Montpellier, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), CHU Grenoble, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), AFM 21384 grant (The French Muscular Dystrophy Association (AFM-Téléthon)), the Délégation à la Recherche Clinique et à l'Innovation du Groupement de Coopération Sanitaire de la Mission d'Enseignement, de Recherche, de Référence et d'Innovation (DRCI-GCS-MERRI) de Montpellier-Nîmes., Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and CHU Toulouse [Toulouse]
Subjects: Male, DNA Copy Number Variations, [SDV]Life Sciences [q-bio], Neurosciences. Biological psychiatry. Neuropsychiatry, Brief Communication, Muscular Dystrophies, Frameshift mutation, 03 medical and health sciences, 0302 clinical medicine, Medicine, Humans, In patient, Connectin, Copy-number variation, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Aberrant splicing, RC346-429, Gene, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Aged, Genetics, Aged, 80 and over, 0303 health sciences, business.industry, General Neuroscience, Middle Aged, Phenotype, Pedigree, [SDV] Life Sciences [q-bio], Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology. Diseases of the nervous system, Neurology (clinical), business, Haploinsufficiency, 030217 neurology & neurosurgery, RC321-571
Abstract: International audience; The aim of this study was to analyze patients from two distinct families with a novel distal titinopathy phenotype associated with exactly the same CNV in the TTN gene. We used an integrated strategy combining deep phenotyping and complete molecular analyses in patients. The CNV is the most proximal out-of-frame TTN variant reported and leads to aberrant splicing transcripts leading to a frameshift. In this case, the dominant effect would be due to dominant-negative and/or haploinsufficiency. Few CNV in TTN have been reported to date. Our data represent a novel phenotype-genotype association and provides hypotheses for its dominant effects.
Published: 2021
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41. Polypharmacy is a determinant of hospitalization in Parkinson's disease

Author: S, Giovannini, A, Laudisio, L, Navarini, M R, Lo Monaco, M, Ciaburri, E, Serafini, C, Loreti, D, Coraci, P, Caliandro, L, Padua, R, Bernabei, L, Biscotti, and G, Zuccalà
Subjects: Cohort Studies, Hospitalization, Male, Logistic Models, Neuroprotective Agents, Risk Factors, Polypharmacy, Humans, Female, Parkinson Disease, Length of Stay, Aged, Retrospective Studies
Abstract: Patients with Parkinson's disease (PD) are at a higher risk of hospitalization and recurrent hospitalizations, with consequent complications. Polypharmacy is associated with several adverse outcomes, including hospitalization, increased length of hospital stay, and mortality. The aim of this study was to evaluate among patients with PD the association between the number of medications and incident hospitalizations.We analysed the data of 165 patients with Parkinson's disease attending a geriatric Day Hospital who were enrolled in a cohort study and followed for a median of two years.Over the follow-up, 46 participants (46%) were hospitalized at least one time; multiple admissions were observed in 12 subjects (7%). The median number of agents was 5 (4-7). In Cox regression, the number of drugs was associated with increased hospitalization rates (HR=1.23; 95% CI=1.06-1.43), also after excluding non-neurological medications (HR=1.18; 95% CI=1.01-1.38). Using Poisson regression, polypharmacy (i.e., use of5 drugs) predicted the number of repeated hospitalizations (IRR=2.62; 95% CI=1.28-5.36; p=.008).Among patients with PD, the number of daily medications is associated with increased risk of hospitalization; an increasing number of drugs is associated with increasing number of hospitalizations.
Published: 2021

42. Outcomes of duodenal stenting: Experience in a French tertiary center with 220 cases

Author: Christophe Zemmour, Marc Giovannini, Valentin Lestelle, Géraldine Capodano, S Hoibian, Sébastien Godat, Jean-Philippe Ratone, Christian Pesenti, Erwan Bories, Aurélien Proux, Fabrice Caillol, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Dupuis, Christine
Subjects: Male, Malignant gastroduodenal stricture, [SDV]Life Sciences [q-bio], Digestive System Neoplasms, Endoscopy, Gastrointestinal, MESH: Aged, 80 and over, 0302 clinical medicine, Cumulative incidence, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, medicine.diagnostic_test, Palliative Care, Gastroenterology, Gastric outlet obstruction, Middle Aged, Duodenal stenting, MESH: Endoscopy, Gastrointestinal, [SDV] Life Sciences [q-bio], Oncology, 030220 oncology & carcinogenesis, Female, MESH: Palliative Care, 030211 gastroenterology & hepatology, France, MESH: Pancreatic Neoplasms, Adult, medicine.medical_specialty, Self Expandable Metallic Stents, 03 medical and health sciences, MESH: Gastric Outlet Obstruction, Pancreatic cancer, medicine, Overall survival, Humans, Endoscopic stenting, Aged, Retrospective Studies, MESH: Humans, Hepatology, Gastric Outlet Obstruction, MESH: Digestive System Neoplasms, business.industry, Endoscopy, MESH: Adult, MESH: Retrospective Studies, Retrospective cohort study, Gastroduodenal self-expandable metal stents, medicine.disease, MESH: Male, MESH: Self Expandable Metallic Stents, Surgery, Pancreatic Neoplasms, MESH: France, business, MESH: Female
Abstract: International audience; Introduction: Endoscopic stenting for malignant gastroduodenal outlet obstruction (MGOO) is described as ineffective and not long-lasting despite a few favorable studies. This study aimed to evaluate the clinical outcomes of a large series of patients in a tertiary center. Methods: A single-center retrospective study was performed using data collected from all patients who received palliative duodenal self-expandable metal stents between January 2011 and December 2016. The primary endpoints were patient diet after the first duodenal procedure (Gastric Outlet Obstruction Scoring System, GOOSS) and clinical success. The secondary endpoints were the median patency duration (calculated according to the Kaplan-Meier method) and the cumulative incidence of reintervention. Results: Two-hundred twenty patients were included. The increase in the GOOSS score was significant (p < 0.001), and the clinical success rate was 86.3%. The median estimated patency duration was 9.0 months [6.5-29.1]. Patients with pancreatic adenocarcinoma had significantly longer patency durations (p = 0.02). The estimated cumulative probability of a second duodenal procedure after 4 months was 13%. Conclusions: In this large series of patients who underwent duodenal stenting for MGOO, we observed significant changes in GOOSS scores, a relatively long patency duration compared to findings in previous series, and a low probability of subsequent duodenal procedures, primarily due to a low median overall survival time (4 months).
Published: 2020
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43. The effect of delayed umbilical cord clamping on cord blood gas analysis in vaginal and caesarean‐delivered term newborns without fetal distress: a prospective observational study

Author: Enrico Ferrazzi, Giulia Emily Cetera, Eugenio Denaro, Fabio Mosca, Dario Consonni, Fabio Parazzini, Genny Raffaeli, Beatrice Letizia Crippa, Stefano Ghirardello, Valeria Cortesi, and Niccolò Giovannini
Subjects: Male, pCO2, Time-to-Treatment, Umbilical Cord, 03 medical and health sciences, 0302 clinical medicine, Venous Cord Blood, Pregnancy, Fetal distress, Humans, Medicine, Acidosis, 030219 obstetrics & reproductive medicine, Cesarean Section, business.industry, Vaginal delivery, Infant, Newborn, Pregnancy Outcome, Obstetrics and Gynecology, Metabolic acidosis, Delivery, Obstetric, Fetal Blood, medicine.disease, Constriction, Obstetric Labor Complications, Italy, Anesthesia, Cord blood, Female, Base excess, Blood Gas Analysis, medicine.symptom, business
Abstract: OBJECTIVE To determine variations in cord blood gas (CBG) parameters after 3-minute delayed cord clamping (DCC) in vaginal deliveries (VDs) and caesarean deliveries (CDs) at term without fetal distress. DESIGN Prospective observational study. SETTING University hospital. SAMPLE CBG from 97 VDs and 124 CDs without fetal distress. METHODS Comparison of paired arterial-venous CBG parameters drawn at birth from the unclamped cord and after 3-minutes DCC for VDs and CDs. MAIN OUTCOME MEASURES Base excess, bicarbonate, haematocrit and haemoglobin from both arterial and venous cord blood, lactate, neonatal outcomes, partial pressure of oxygen (pO2 ), partial pressure of carbon dioxide (pCO2 ), pH, and postpartum haemorrhage. RESULTS Arterial cord blood pH, bicarbonate ( HCO3- , mmol/l), and base excess (BE, mmol/l) decreased significantly after 3-minute DCC both in VDs (pH = 7.23 versus 7.27; P
Published: 2019
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44. Early Prediction of Graft Outcomes After Kidney Transplantation From Donors After Circulatory Death: Biomarkers and Transplantation Characteristics

Author: Paolo Malvezzi, Rachel Tetaz, Candice Trocme, Diane Giovannini, Xavier Moreau-Gaudry, Bénédicte Janbon, Lionel Rostaing, Anne-Sophie Truche, Sabrina Vergnaud, Service de néphrologie, dialyse, aphérèses et transplantation, and Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble
Subjects: Adult, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Urinary system, Population, 030232 urology & nephrology, Urology, Delayed Graft Function, Renal function, 030230 surgery, 03 medical and health sciences, 0302 clinical medicine, Lipocalin-2, Risk Factors, Acetylglucosaminidase, medicine, Clinical endpoint, Humans, education, Kidney transplantation, Transplantation, education.field_of_study, Kidney, L-Lactate Dehydrogenase, business.industry, Middle Aged, Prognosis, medicine.disease, Kidney Transplantation, Tissue Donors, Confidence interval, 3. Good health, Perfusion, medicine.anatomical_structure, ROC Curve, Creatinine, Female, Surgery, business, Biomarkers
Abstract: Background This study aimed to identify transplantation characteristics and biomarkers that predict outcomes for kidney transplant (KT) patients from donors after circulatory death (DCDs). Methods Consecutive patients receiving a KT from a DCD in our center between 2014 and 2016 were included; the reference population was recipients with a living donor KT. The urinary tubular injury biomarker-to-creatinine ratio and serum lactate dehydrogenase (LDH) were measured at post-transplant days 1 and 3. The primary outcome was the occurrence of delayed graft function (DGF). Descriptive and receiver operating characteristic analyses were performed. Results Forty-one patients were included in the analysis: 15 (36.59%) DCD KTs (9 of which suffered from DGF) and 26 (63.41%) living donor KTs. For the primary endpoint, neutrophil gelatinase-associated lipocalin, N-acetyl-beta-D-glucosaminidase, urinary tubular injury biomarker-to-creatinine ratio, and LDH areas under the curve were 1 and 0.96 (95% confidence interval: 0.84-1.0), 1 and 0.92 (95% confidence interval: 0.73-1.0), respectively. Among the transplant characteristics, only the 30-minute resistive index on the perfusion machine was significantly higher in DCD KTs with DGF vs those without DGF (0.26 mm Hg/mL/min [0.20; 0.32] vs 0.14 mm Hg/mL/min [0.12; 0.16], P = .05). Median 3-month creatinine clearance among DGF DCD KTs was 49 mL/min/1.73 m2 [IQR: 42; 65] and 65 mL/min/1.73 m2 [IQR: 62; 66] among DCD KTs without DGF (P = .22). Conclusion In the DCD KT population, clinical and biological markers were identified that provided predictive tools for DGF. Thus, systematic measurement of these biomarkers, particularly LDH, could improve the management of kidney graft recipients’ immunosuppressive therapy.
Published: 2019
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45. Impact of needle-based confocal laser endomicroscopy on the therapeutic management of single pancreatic cystic lesions

Author: Louis Buscail, Bertrand Napoleon, Alain Sauvanet, Alain Aubert, Raphael Bourdariat, Laurent Palazzo, Goeffroy Vanbiervliet, Rodica Gincul, Sébastien Marque, Anne-Isabelle Lemaistre, Frédérique Maire, Fabrice Caillol, Maxime Palazzo, Marc Giovannini, Ivan Borbath, Bertrand Pujol, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, and UCL - (SLuc) Service de gastro-entérologie
Subjects: Adult, Male, Endoscopic ultrasound, medicine.medical_specialty, Pancreatic disease, Databases, Factual, 030230 surgery, Article, 03 medical and health sciences, Cystic lesion, 0302 clinical medicine, Internal medicine, Clinical information, Humans, Medicine, Prospective Studies, Endoscopic Ultrasound-Guided Fine Needle Aspiration, Pancreas, Retrospective Studies, Observer Variation, Confocal laser endomicroscopy, Microscopy, Confocal, medicine.diagnostic_test, business.industry, Reproducibility of Results, Endoscopy, Middle Aged, Hepatology, medicine.disease, EUS-FNA, Pancreatic cysts, Needle-based confocal laser endomicroscopy, Female, 030211 gastroenterology & hepatology, Surgery, Radiology, Pancreatic Cyst, business, Abdominal surgery
Abstract: Background and aim The diagnosis and therapeutic management of large single pancreatic cystic lesions (PCLs) represent major issues for clinicians and essentially rely on endoscopic ultrasound fine-needle aspiration (EUS-FNA) findings. Needle-based confocal laser endomicroscopy (nCLE) has high diagnostic performance for PCLs. This study aimed to evaluate the impact of nCLE on the therapeutic management of patients with single PCLs. Methods Retrospective and comparative study. Five independent pancreatic disease experts from tertiary hospitals independently reviewed data from a prospective database of 206 patients with single PCL, larger than 2 cm and who underwent EUS-FNA and nCLE. Two evaluations were performed. The first one included the sequential review of clinical information, EUS report and FNA results. The second one included the same data + nCLE report. Participants had to propose a therapeutic management for each case. Results The addition of nCLE to EUS-FNA led to significant changes in therapeutic management for 28% of the patients (p p p Conclusion The addition of nCLE to EUS-FNA significantly improves reliability of PCL diagnosis and could impact the therapeutic management of patients with single PCLs. ClinicalTrials.gov number, NCT01563133.
Published: 2019
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46. Longitudinal cognitive decline in mild cognitive impairment subjects with early amyloid-β neocortical deposition

Author: Mattia Riondato, A Tartaglione, Andrea Ciarmiello, Valerio Duce, Antonio Mannironi, M De Biasi, G Giovacchini, Elena Carabelli, Chiara Passera, Luigi Mansi, O. Ferrando, and Elisabetta Giovannini
Subjects: Male, Amyloid, Longitudinal study, medicine.medical_specialty, Neocortex, Standardized uptake value, Internal medicine, Stilbenes, mental disorders, Humans, Medicine, Cognitive Dysfunction, Radiology, Nuclear Medicine and imaging, Cognitive decline, Cognitive impairment, Florbetaben, Aged, Aged, 80 and over, Aniline Compounds, business.industry, Neuropsychology, General Medicine, Middle Aged, Mental Status and Dementia Tests, Early Diagnosis, Positron-Emission Tomography, Female, Analysis of variance, Radiopharmaceuticals, business
Abstract: The rate of clinical progression of cognitive impairment in subjects with early amyloid deposition is unknown. The primary aim of the study was to follow the rate of cognitive decline over 1 year in patients with amnestic mild cognitive impairment (aMCI) by determining amyloid retention levels in terms of standardized uptake value ratios (SUVr) that ranged from 0.85 to 1.57. The secondary objective was to compare the rate of cognitive decline between subjects with and without early amyloid positivity. Of 66 aMCI subjects evaluated with [18F]florbetaben PET imaging and neuropsychological tests at baseline, 41 completed the 1-year follow-up. Amyloid status was determined with SUVr cut-off values generated from baseline images by visual assessment by three independent certified readers. Repeated-measures ANOVA with amyloid load and neuropsychological scores as the main effects was use to test group, time and group-by-time interactions. The Tukey post-hoc test was used to analyse all significant interactions. Of the 41 aMCI subjects, 38 completed the assessment according to the study protocol. Amyloid-positive (Aβ+ ) subjects (N = 18, age 75.6 ± 5.8 years, six men, 12 women) showed greater clinical deterioration according to the Mattis Dementia Rating Scale (MDRS) score (p = 0.006). Amyloid-negative (Aβ−) subjects (N = 20, age 72.4 ± 5.8 years, 11 men, 6 women) showed no significant changes in MDRS score over 1 year. MDRS score significantly decreased (MDRS+) in 37% of the aMCI subjects, and remained stable (MDRS−) in the remaining 63%. Among subjects with cognitive deterioration, 86% were Aβ+ and 14% were Aβ−, while 25% of the MDRS− subjects were Aβ+ and 75% were Aβ− (χ2 = 13, P = 0.0003). SUVr above 1.21 identified individuals who would show significant progression over 1 year, with a sensitivity of 67% and a specificity of 90%, as compared to Aβ− subjects. The positive predictive value, negative predictive value, and likelihood ratio were 86% (95% CI 70–94%), 75% (95% CI 58–87%), 7 (95% CI 5–10). This study demonstrated that early amyloid deposition predicts cognitive decline in subjects with aMCI, with a higher rate of decline in those with SUVr above a threshold of 1.21. Detection of early amyloid positivity may help in selecting the target population for preventive therapeutic interventions and in designing treatment trials (Trial number, EudraCT 2015-001184-39).
Published: 2019
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47. Farm productive contexts and the dynamics of bovine viral diarrhea (BVD) transmission

Author: Vittoria Colizza, Bryan Iotti, Armando Giovannini, Sergio Rosati, Mario Giacobini, Lara Savini, Eugenio Valdano, Luca Candeloro, University of Turin, Departament d'Enginyeria Informàtica i Matemàtiques, Universitat Rovira i Virgili, Istituto Zooprofilattico Sperimentale dell'Umbria e delle Marche (IZSUM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, BVD, Cattle trade movements, Metapopulation model, Productive classes, Targeted intervention, Animals, Bovine Virus Diarrhea-Mucosal Disease, Cattle, Dairying, Female, Italy, Models, Statistical, Animal Husbandry, Diarrhea Viruses, Bovine Viral, 040301 veterinary sciences, [SDV]Life Sciences [q-bio], 030231 tropical medicine, Metapopulation, Disease, Biology, law.invention, 0403 veterinary science, 03 medical and health sciences, 0302 clinical medicine, Food Animals, Models, law, Diarrhea Viruses, Seroprevalence, Socioeconomics, Viral diarrhea, 2. Zero hunger, 04 agricultural and veterinary sciences, Statistical, Transmission (mechanics), Scale (social sciences), Herd, Bovine Viral, Animal Science and Zoology, Viral disease
Abstract: Bovine viral diarrhea (BVD) is a viral disease that affects cattle and that is endemic to many European countries. It has a markedly negative impact on the economy, through reduced milk production, abortions, and a shorter lifespan of the infected animals. Cows becoming infected during gestation may give birth to Persistently Infected (PI) calves, which remain highly infective throughout their life, due to the lack of immune response to the virus. As a result, they are the key driver of the persistence of the disease both at herd scale, and at the national level. In the latter case, the trade-driven movements of PIs, or gestating cows carrying PIs, are responsible for the spatial dispersion of BVD. Past modeling approaches to BVD transmission have either focused on within-herd or between-herd transmission. A comprehensive portrayal, however, targeting both the generation of PIs within a herd, and their displacement throughout the country due to trade transactions, is still missing. We overcome this by designing a multiscale metapopulation model of the spatial transmission of BVD, accounting for both within-herd infection dynamics, and its spatial dispersion. We focus on Italy, a country where BVD is endemic and seroprevalence is very high. By integrating simple within-herd dynamics of PI generation, and the highly-resolved cattle movement dataset available, our model requires minimal arbitrary assumptions on its parameterization. We use our model to study the role of the different productive contexts of the Italian market, and test possible intervention strategies aimed at prevalence reduction. We find that dairy farms are the main drivers of BVD persistence in Italy, and any control strategy targeting these farms would lead to significantly higher prevalence reduction, with respect to targeting other production compartments. Our multiscale metapopulation model is a simple yet effective tool for studying BVD dispersion and persistence at country level, and is a good instrument for testing targeted strategies aimed at the containment or elimination of this disease. Furthermore, it can readily be applied to any national market for which cattle movement data is available.
Published: 2019
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48. Palliative endoscopic drainage of malignant stenosis of biliary confluence: Efficiency of multiple drainage approach to drain a maximum of liver segments

Author: Marc Giovannini, Jean Philippe Ratone, Marine Gilabert, Christian Pesenti, Christophe Zemmour, Simon Launay, Fabrice Caillol, Erwan Bories, Dupuis, Christine, Unité d’échoendoscopie et d’endoscopie d’oncologie digestive [Institut Paoli-Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Unité de Biostatistiques [Institut Paoli-Calmettes] (Département de la Recherche clinique et de l'Innovation), and Département d’Oncologie Chirurgicale [Institut Paoli-Calmettes, Marseille]
Subjects: Male, medicine.medical_specialty, Constriction, Pathologic, ERCP, 03 medical and health sciences, Endoscopic drainage, 0302 clinical medicine, Cause of Death, Humans, Medicine, Endoscopy, Digestive System, Mortality, Drainage, hilar stenosis, Aged, Proportional Hazards Models, Aged, 80 and over, palliative biliary drainage, business.industry, Palliative Care, Gastroenterology, Original Articles, Middle Aged, biliary hilum stenting, medicine.disease, Surgery, Stenosis, ROC Curve, Oncology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030220 oncology & carcinogenesis, Confluence, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 030211 gastroenterology & hepatology, Bile Ducts, EUS-guided biliary drainage of the liver hilum, business
Abstract: International audience; Background and aim:More than 50% of the liver should be drained in case of unresectable hilar liver stenosis; however, it remains unclear if the use of several types of drainage (endoscopic retrograde cholangiography and pancreatography, percutaneous-biliary drainage, endoscopic ultrasound biliary drainage (EUS-BD)), allowing better drainage, has an impact on survival. The aim of our study was to evaluate the percentage of liver drained and its correlation on survival whatever the drainage technique used.Patients and methods:This study was a retrospective analysis of a prospective registry of patients with malignant drainage stenosis of the hilum. The quality of drainage was evaluated based on the percentage of liver segments drained, which was calculated by dividing the number of liver segments drained by the total number of liver segments. Drainage could be achieved via an endoscopic, EUS-guided or percutaneous route not associated with the procedure.Results:Sixty patients (38 men) were included from January 2015 to July 2016. The mean patient age was 69.84 years. Stenosis was classified as type II for 17 (29%) patients, type III for 20 (34%) patients, and type IV for 22 (37%) patients. Histology revealed cholangiocarcinoma for 26 (43%) patients, metastatic disease from colorectal cancer for 15 (25%) patients and another cancer for 19 (32%) patients. The median survival time was five (2.3-12.3) months.The percentage of liver segments drained had a significant prognostic impact on overall survival regardless of the technique used to drain the liver. The percentage of liver segments drained was dichotomized based on a threshold value of 80%, resulting in two groups (
Published: 2019
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49. Case Report and Review of the Literature: Bullous Skin Eruption After the Booster-Dose of Influenza Vaccine in a Pediatric Patient With Polymorphic Maculopapular Cutaneous Mastocytosis

Author: Fausto Andrea Pedaci, Silvia Ricci, Clementina Canessa, Cesare Filippeschi, Lorenzo Lodi, Lucrezia Sarti, Francesca Mori, Mattia Giovannini, Teresa Oranges, Simona Barni, Chiara Azzari, Davide Sarcina, and Giulia Liccioli
Subjects: Ketotifen, Pediatrics, medicine.medical_specialty, pediatrics, Adolescent, Influenza vaccine, premedication, Immunology, adverse reaction, Immunization, Secondary, Case Report, Booster dose, Histamine Release, Cell Degranulation, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, prevention, Adrenal Cortex Hormones, Risk Factors, Urticaria Pigmentosa, medicine, Immunology and Allergy, Humans, cutaneous mastocytosis, Mast Cells, Vaccines, Combined, Adverse effect, Immunization Schedule, Skin Diseases, Vesiculobullous, business.industry, Cutaneous Mastocytosis, RC581-607, vaccination, Vaccination, Treatment Outcome, Influenza Vaccines, 030220 oncology & carcinogenesis, Histamine H1 Antagonists, Betamethasone, Female, Oxatomide, Immunologic diseases. Allergy, business, medicine.drug
Abstract: Vaccination is a well-known trigger for mast cell degranulation in subjects affected by mastocytosis. Nevertheless, there is no exact standardized protocol to prevent a possible reaction after a vaccine injection, especially for patients who have already presented a previous vaccine-related adverse event, considering that these patients frequently tolerate future vaccine doses. For this reason, we aim to share our experience at Meyer Children’s University Hospital in Florence to raise awareness on the potential risk for future vaccinations and to discuss the valuable therapeutic strategies intended to prevent them, taking into account what is proposed by experts in literature. We describe the case of an 18-month-old female affected by a polymorphic variant of maculopapular cutaneous mastocytosis that presented an extensive bullous cutaneous reaction 24 hours after the second dose (booster dose) of inactivated-tetravalent influenza vaccine, treated with a single dose of oral corticosteroid therapy with betamethasone (0.1 mg/kg) and an oral antihistamine therapy with oxatomide (1 mg/kg/daily) for a week, until resolution. To the best of our knowledge, in the literature, no documented case of reaction to influenza vaccine in maculopapular cutaneous mastocytosis is described. Subsequently, the patient started a background therapy with ketotifen daily (0.05 mg/kg twice daily), a non-competitive H1-antihistamine, and a mast cell stabilizer (dual activity). A non-standardized pharmacological premedication protocol with an H1-receptor antagonist (oxatomide, 0.5 mg/kg) administered 12 hours before the immunizations, and a single dose of betamethasone (0.05 mg/kg) together with another dose of oxatomide (0.5 mg/kg) administered 2 hours before the injections was followed to make it possible for the patient to continue with the scheduled vaccinations. Indeed, no reactions were subsequently reported. Thus, in our experience, a background therapy with ketotifen associated with a premedication protocol made by two doses of oxatomide and a single dose of betamethasone was helpful to make possible the execution of the other vaccines. We suggest how in these children, it could be considered the idea of taking precaution when vaccination is planned, regardless of the kind of vaccine and if a dose of the same vaccine was previously received. However, international consensus needs to be reached to manage vaccinations in children with mastocytosis and previous adverse reactions to vaccines.
Published: 2021

50. MYNd&CO (Mindfulness, Yoga, Nutrition, development & Coaching, and Osteopathy) randomized controlled trial for a positive psychophysical experience in pregnancy and after birth: a study protocol

Author: Giovannini, Niccolò, Cetera, Giulia Emily, Ercolino, Carolina, Miozzo, Monica Rosa, Parazzini, Fabio, Ferrazzi, Enrico Maria, Manzotti, Andrea, and Colaceci, Sofia
Subjects: Osteopathy, Pregnancy Complications, Pregnancy, Yoga, Parturition, Humans, Mentoring, Female, Original Article: New Approaches for Nursing Care, Mindfulness, Prenatal education, Randomized Controlled Trials as Topic
Abstract: Background and aim of the study: The medicalisation of birth pathway may negatively impact on women’s empowerment, enhancing distress even in cases of healthy pregnancies. We have built a program which is comprised of Mindfulness, Yoga, Nutrition, development & Counselling, Coaching, antenatal classes, and Osteopathic treatment (MYNd&CO). Methods: This study is a randomized controlled trial involving low-risk pregnant women. They will be randomized to the experimental (MYNd&CO intervention plus standard care) or control group (standard care). The primary (general health and wellbeing, maternal distress) and secondary outcome measures (urinary incontinence, sexual problems, and physical wellbeing) will be assessed via questionnaires at baseline and 6 months after childbirth. The independent-samples t-test and Chi-square will be used to detect changes in the outcomes between intervention and control group. Discussion: The trial is expected to increase knowledge about the effectiveness of a holistic approach in low-risk pregnant women, in terms of obstetrical and psychophysiological outcomes.
Published: 2021

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