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1. Femoral neck fractures: Key points to consider for fixation or replacement a narrative review of recent literature

Author: Manuel Giovanni Mazzoleni, Alfonso Liccardi, Giuseppe Basile, Martino Viganò, Alessandra Menon, Filippo Randelli, and Nicolo Cosmelli
Subjects: medicine.medical_specialty, Osteosynthesis, business.industry, medicine.medical_treatment, Implant failure, Avascular necrosis, medicine.disease, Femoral Neck Fractures, Prosthesis, Surgery, Femoral head, medicine.anatomical_structure, Hip replacement, medicine, General Earth and Planetary Sciences, Displacement (orthopedic surgery), business, General Environmental Science
Abstract: Introduction Femoral neck fractures (FNF) are frequent injuries and not rarely complicated by non-union, implant failure, and avascular necrosis. Some of these fractures represent a dilemma for trauma surgeons. Which fracture should be fixed? Which replaced with a prosthesis? How? The aim of this narrative review is to investigate the literature in order to provide the most updated and evidence-based knowledge about FNF’ treatment. Materials and methods A literature research has been performed to find the essential key points to consider when dealing with FNF and their treatment. The most representative papers and the new meta-analysis were matched with authors’ experience to give a concise but comprehensive view of the problem. Timing, age, comorbidities, vascularization of the femoral head, displacement, instability, comminution of the fracture, bone quality, and surgeon experience seem to be the major topics to consider in the decision making. We then focus on the optimal fixation or replacement as suggested by the literature. Results Age is the main independent factor to consider. Timing seems essential in the elderly population to reduce mortality and important in the younger patients to reduce complications. Vascular supply should be always considered. Displacement, instability, and comminution of the fracture are negative prognostic factors for fixation as well as, theoretically, bone quality. In the elderly hip replacement is mostly indicated. A stable and solid fixation is mandatory to allow early mobilization. Sliding Hip Screws (SHS) seem preferable to cannulated screws for displaced/unstable (Pauwels II-III, posterior comminution) and basicervical fracture patterns or in smokers. There is a tendency toward Total Hip Arthroplasty (THA) also in the elderly if the patient is an indipendent ambulator without severe comorbidities. Dual mobility cups are gaining popularity in THA for FNF. Conclusions FNF are frequent injuries and represent, in some cases, a dilemma for the trauma surgeon. Age, timing, comorbidities, bone quality, femoral head vascularization, fracture displacement, intrinsic instability, and comminution as surgeon experience should be carefully evaluated before surgery. A case-to-case analysis of the patient-related factors helps the surgeon to make the right choice and reduce the well-known complications.
Published: 2023
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2. Novelties in cardiac pacing. Left bundle branch pacing, a step-by-step guide

Author: Arif Al Nooryani, Tomasz Roleder, Balázs Berta, Juan F. Granada, Krzysztof Piotr Malinowski, Michael Magro, Enrico Fabris, Cyril Camaro, Javier Escaned, Floris Kauer, Holger Nef, Mark Kennedy, Hector Garcia Garcia, Sebastian Reith, Clemens von Birgelen, Fernando Rivero, Bruno Pereira, Renicus S Hermanides, Alexander Ijsselmuiden, Elvin Kedhi, Giuseppe De Luca, Wojciech Wojakowski, Fernando Alfonso, Health Technology & Services Research, Kedhi, E., Berta, B., Roleder, T., Hermanides, R. S., Fabris, E., Ijsselmuiden, A. J. J., Kauer, F., Alfonso, F., von Birgelen, C., Escaned, J., Camaro, C., Kennedy, M. W., Pereira, B., Magro, M., Nef, H., Reith, S., Al Nooryani, A., Rivero, F., Malinowski, K., De Luca, G., Garcia Garcia, H., Granada, J. F., and Wojakowski, W.
Subjects: Thin-cap fibroatheroma, Diabetes mellitu, medicine.medical_specialty, Population, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Predictive Value of Test, Coronary Artery Disease, Fractional flow reserve, Coronary Angiography, Coronary artery disease, Diabetes mellitus, Predictive Value of Tests, Internal medicine, Optical coherence tomography, Vulnerable plaque, Coronary Vessels, Humans, Prospective Studies, Tomography, Optical Coherence, Diabetes Mellitus, Fractional Flow Reserve, Myocardial, Plaque, Atherosclerotic, medicine, Clinical endpoint, Myocardial, Myocardial infarction, education, Tomography, Coronary Vessel, Atherosclerotic, Plaque, education.field_of_study, business.industry, Unstable angina, Hazard ratio, medicine.disease, n/a OA procedure, Prospective Studie, Optical Coherence, Cardiology, Cardiology and Cardiovascular Medicine, business, Mace, Human
Abstract: AimsThe aim of this study was to understand the impact of optical coherence tomography (OCT)-detected thin-cap fibroatheroma (TCFA) on clinical outcomes of diabetes mellitus (DM) patients with fractional flow reserve (FFR)-negative lesions.Methods and resultsCOMBINE OCT-FFR study was a prospective, double-blind, international, natural history study. After FFR assessment, and revascularization of FFR-positive lesions, patients with ≥1 FFR-negative lesions (target lesions) were classified in two groups based on the presence or absence of ≥1 TCFA lesion. The primary endpoint compared FFR-negative TCFA-positive patients with FFR-negative TCFA-negative patients for a composite of cardiac mortality, target vessel myocardial infarction, clinically driven target lesion revascularization or unstable angina requiring hospitalization at 18 months. Among 550 patients enrolled, 390 (81%) patients had ≥1 FFR-negative lesions. Among FFR-negative patients, 98 (25%) were TCFA positive and 292 (75%) were TCFA negative. The incidence of the primary endpoint was 13.3% and 3.1% in TCFA-positive vs. TCFA-negative groups, respectively (hazard ratio 4.65; 95% confidence interval, 1.99–10.89; P ConclusionsAmong DM patients with ≥1 FFR-negative lesions, TCFA-positive patients represented 25% of this population and were associated with a five-fold higher rate of MACE despite the absence of ischaemia. This discrepancy between the impact of vulnerable plaque and ischaemia on future adverse events may represent a paradigm shift for coronary artery disease risk stratification in DM patients.
Published: 2021
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3. Efficacy and safety of hydroxychloroquine in healthcare professionals with mild SARS-CoV-2 infection: Prospective, non-randomized trial

Author: Mª Queralt Gorgas, Benito Almirante, Alfonso Ayora, Andrés Antón, Juliana Esperalba, Xavier Vidal, Cristina Aguilera, Esteban Ribera, Manuel Alonso, Antònia Agustí, Elena Guillén, Meritxell Espuga, and Cristina Andrés
Subjects: 0301 basic medicine, Microbiology (medical), Adult, Male, medicine.medical_specialty, Health Personnel, 030106 microbiology, Loading dose, Article, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, hidroxicloroquina, pacientes externos, Internal medicine, Outpatients, Health care, medicine, Healthcare workers, Humans, 030212 general & internal medicine, Prospective Studies, Infección por SARS-CoV-2, business.industry, SARS-CoV-2, SARS-CoV-2 infection, COVID-19, Hydroxychloroquine, medicine.disease, Intensive care unit, COVID-19 Drug Treatment, Diarrhea, Pneumonia, trabajadores sanitarios, Female, medicine.symptom, business, Viral load, Delivery of Health Care, medicine.drug
Abstract: Objectives To assess the efficacy and safety of hydroxychloroquine (HCQ) compared with no treatment in healthcare workers with mild SARS-CoV-2 infection. Methods Prospective, non-randomized study. All health professionals with confirmed COVID-19 between April 7 and May 6, 2020, non-requiring initial hospitalization were asked to participate. Patients who accepted treatment were given HCQ for five days (loading dose of 400 mg q12 h the first day followed by200 mg q12 h). Control group included patients with contraindications for HCQ or who rejected treatment. Study outcomes were negative conversion and viral dynamics of SARS-CoV-2, symptoms duration and disease progression. Result Overall, 142 patients were enrolled: 87 in treatment group and 55 in control group. The median age was 37 years and 75% were female, with few comorbidities. There were no significant differences in time to negative conversion of PCR between both groups. The only significant difference in the probability of negative conversion of PCR was observed at day 21 (18.7%, 95%CI 2.0–35.4). The decrease of SARS-CoV-2 viral load during follow-up was similar in both groups. A non significant reduction in duration of some symptoms in HCQ group was observed. Two patients with HCQ and 4 without treatment developed pneumonia. No patients required admission to the Intensive Care Unit or died. About 50% of patients presented mild side effects of HCQ, mainly diarrhea. Conclusions Our study failed to show a substantial benefit of HCQ in viral dynamics and in resolution of clinical symptoms in health care workers with mild COVID-19.
Published: 2022
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4. Perfluorodecalin as Medium-Term Tamponade in the Case of Retinal Detachment Recurrence With an Inferior Retinal Break, Which Lies Posteriorly to an Encircling Band

Author: Gianni Virgili, Laura Cinelli, Alfonso Savastano, Tomaso Caporossi, Ruggero Tartaro, Fabrizio Giansanti, Ilaria Biagini, Lucia Finocchio, Stanislao Rizzo, and Francesco Barca
Subjects: Fluorocarbons, medicine.medical_specialty, business.industry, Retinal Detachment, Retinal detachment, Retinal, General Medicine, Retinal Perforations, medicine.disease, Medium term, Ophthalmology, chemistry.chemical_compound, Perfluorodecalin, chemistry, Recurrence, Vitrectomy, medicine, Humans, Tamponade, business
Published: 2022
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5. High plant-based diet and physical activity in women during menopausal transition

Author: Mauro Lombardo, Marco Alfonso Perrone, Alessandra Feraco, Chiara Bellia, Elvira Padua, Alfonso Bellia, Gianluca Rizzo, Massimiliano Caprio, Davide Lauro, Lombardo M., Rizzo G., Feraco A., Perrone M.A., Bellia C., Lauro D., Caprio M., Bellia A., and Padua E.
Subjects: Weight loss, Nutrition and Dietetics, Physical activity, business.industry, Physiology, Plant based, medicine.disease, Body composition, Plant-based diet, Menopause, medicine, medicine.symptom, business, Food Science
Abstract: Purpose The menopausal transition (MT) is a period when there may be an increase in visceral fat mass and a worsening of cardiometabolic risk factors. Few studies have evaluated the efficacy of plant-based low-calorie diets on groups of women at different stages of MT. The purpose of this study is to compare the effectiveness of a high plant-to-animal protein ratio diet in women of similar age but with different fertility statuses. Design/methodology/approach Subjects were divided into three groups according to their fertility status at the baseline: “premenopausal” (n = 11), “perimenopause” (n = 14) and “postmenopause” (n = 18). Body composition (BC) was measured at the beginning and after eight months of treatment. Individualised lifestyle treatment included a strong component of plant-based foods. Findings Forty-three overweight or obese Caucasian women (age 52.3 ± 4.5 years, body mass index 30.6 ± 5.4 kg/m2, fat mass 33.1 ± 9.3 kg data presented as means ± SD) were included in the study. Mean physical activity was 8.4 ± 7.6 metabolic equivalent of tasks/week. Subjects had an improvement in BC (fat mass −5.6 ± 4.0 kg, p < 0.001 protein −0.3 ± 0.5 kg, p < 0.001), HDL-C and systolic blood pressure values. Waist circumference and hip circumference decreased by 4.1 ± 3.1 cm and −6.0 ± 4.3 cm, respectively. Weight loss resulted in a significant improvement in some blood lipid values, such as total and high-density lipoprotein cholesterol. Adherence to a high plant protein diet helps adult women with different fertility statuses to improve BC and reduce cardiovascular risk factors. Long-term studies with larger sample sizes are needed to confirm these findings. Originality/value In pre-peri- and post-menopausal adult women, a diet high in plant proteins improves body composition and reduces cardiovascular risk factors.
Published: 2021
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6. Early INSURE Therapy Reduces CPAP Failure in Late Preterm Newborns with Respiratory Distress Syndrome

Author: Luis Alfonso Pérez-Vera, Maria Camila Alarcon Olave, Luis Alfonso Díaz-Martínez, Mario Augusto Rojas-Devia, Martha Lucía Africano-León, Sergio Alejandro Gómez-Ochoa, Paula Liseth Martínez-González, Diego Felipe Sarmiento-Villamizar, and Kihara Alejandra Jerez-Torra
Subjects: Pediatrics, medicine.medical_specialty, Respiratory distress, business.industry, medicine.medical_treatment, Gestational age, Retrospective cohort study, medicine.disease, Pulmonary hypertension, respiratory tract diseases, law.invention, Randomized controlled trial, law, Bubble CPAP, Pediatrics, Perinatology and Child Health, Cohort, Medicine, Intubation, business
Abstract: Background: INSURE (Intubation, Surfactant administration, and Extubation) therapy is controversial in managing respiratory distress syndrome (RDS) in late preterm newborns. This study aims to determine whether the use of the INSURE in late preterm infants with RDS is associated with improved outcomes compared to similar infants managed with CPAP alone. Methods: A retrospective cohort study compared two different neonatal care units with two different treatments of RDS in late preterm infants in Bucaramanga, Colombia. One cohort used selective bubble CPAP and rescue surfactant, the second cohort used selective bubble CPAP and INSURE within the first hour of life. We included all the newborns with gestational age between 33 - 366/7 weeks, born between 2012 to 2017, that developed early RDS and were treated with CPAP. Results: We recruited 208 patients (57 CPAP and rescue surfactant and 151 CPAP + INSURE). Early INSURE was reported in 117 patients (56.3 %). INSURE therapy was associated with a reduced risk of CPAP failure (RR = 0.50; 95 % CI 0.26 - 0.98); this effect was evident only when surfactant was administered within the first two hours of life (RR = 0.29; 95 % CI 0.12 - 0.69). Early INSURE was associated with a decreased risk of pneumothorax (RR = 0.07; 95 % CI 0.01 - 0.77) and pulmonary hypertension (RR = 0.34; 95 % CI 0.14 - 0.78). Conclusions: Early INSURE therapy was associated with a reduced incidence of CPAP failure, pneumothorax, and pulmonary hypertension in late preterm infants with moderate to severe RDS. Large, well-powered randomized controlled trials are needed to confirm these observations, but its use is supported by studies with similar results in more premature infants.
Published: 2021
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7. Trismus and TMJ disorders as first clinical manifestations in an intracranial acquired cholesteatoma

Author: Domenico Catapano, Alfonso Manfuso, Chiara Copelli, and Aurelio D'Ecclesia
Subjects: medicine.medical_specialty, TMJ disorders, Hearing loss, Chronic otitis, Case Report, Trismus, head and neck surgery, 03 medical and health sciences, otolaryngology / ENT, 0302 clinical medicine, otorhinolaryngologic diseases, medicine, Humans, Acquired cholesteatoma, neurosurgery, 030223 otorhinolaryngology, Cholesteatoma, Hearing Loss, Cholesteatoma, Middle Ear, business.industry, Middle Ear, General Medicine, Temporomandibular Joint Disorders, medicine.disease, Dermatology, Temporomandibular joint, Otitis Media, medicine.anatomical_structure, Neurosurgery, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Intracranial extension of acquired cholesteatoma is a rare occurrence that can develop secondary to trauma, chronic otitis media or acquired aural cholesteatoma. The most commonly observed symptoms are headache and hearing loss. The authors report on a rare case of intracranial cholesteatoma presenting with atypic symptoms: swelling and temporomandibular joint disorders.
Published: 2023

8. Risk of a syndemic between COVID-19 and dengue fever in southern Mexico

Author: Thelma Beatriz González-Castro, Carlos Alfonso Tovilla-Zárate, Diana L. González-Morales, and Juan Pablo Sánchez de la Cruz
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), COVID-19, Diagnostic test, General Medicine, medicine.disease, Risk Assessment, Syndemic, Timely diagnosis, Dengue fever, Dengue, Geography, Environmental health, Epidemiology, medicine, Humans, Risk assessment, Mexico, Healthcare system
Abstract: A syndemic is the convergence of two or more diseases in the same space and time. In Mexico, the dengue epidemic is active and predominates in areas of the Pacific and the Gulf of Mexico; in turn, the COVID-19 epidemic severely affects the same areas as dengue fever. Given that both these diseases share many clinical manifestations, in areas where tropical diseases are endemic, it is important to make careful evaluations of the patient who consults for fever in order to establish a timely diagnosis. Laboratory diagnostic tests are necessary to take the pertinent measures for each patient. In Mexico, the risk of a syndemic between COVID-19 and dengue fever is high, and thus it that can collapse health systems. The states of southeastern Mexico and the Pacific region require special attention, since they have geographic, environmental and climatic conditions that favor the rapid spread of dengue and COVID-19. Simultaneous infection will worsen the epidemiological situation, and complicate the diagnosis, control and treatment of both diseases.Una sindemia es la convergencia de dos o más enfermedades en un mismo espacio y tiempo. En México, la epidemia de dengue está activa y predomina en zonas del Pacífico y Golfo de México; por su parte, la epidemia de COVID-19 afecta severamente las mismas zonas que el dengue. Dado que estas enfermedades comparten numerosas manifestaciones clínicas, en zonas endémicas de enfermedades tropicales es importante la evaluación minuciosa del paciente que consulta por fiebre, para establecer oportunamente un diagnóstico correcto. Las pruebas de laboratorio son necesarias para llevar a cabo las medidas pertinentes en cada paciente. En México, el riesgo de sindemia de COVID-19 y dengue es alto, por lo que puede colapsar los sistemas de salud. Los estados del sureste y los colindantes con el Pacífico requieren especial atención ya que presentan condiciones geográficas, ambientales y climáticas que favorecen la rápida propagación del dengue y COVID-19. La infección simultánea empeorará la situación epidemiológica, complicará el diagnóstico, control y tratamiento de ambas enfermedades.
Published: 2023
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9. Patterns of Eating Associated with Sleep Characteristics: A Pilot Study among Individuals of Mexican Descent at the US-Mexico Border

Author: Karla Granados, Girardin Jean-Louis, Azizi Seixas, A Okuagu, Chloe Wills, Marcos Delgadillo, Sanjay R. Patel, John M. Ruiz, Orfeu M. Buxton, Sadia Ghani, Patricia L. Haynes, Michael A. Grandner, Pamela Alfonso-Miller, Patricia Molina, and Sairam Parthasarathy
Subjects: Adult, Male, Sleep Wake Disorders, Food intake, Adolescent, Neuroscience (miscellaneous), MEDLINE, Medicine (miscellaneous), Pilot Projects, Article, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Environmental health, Diabetes mellitus, Sleep Initiation and Maintenance Disorders, Surveys and Questionnaires, medicine, Humans, Mexico, business.industry, Middle Aged, medicine.disease, Sleep in non-human animals, Obesity, 030228 respiratory system, Female, Neurology (clinical), Psychology (miscellaneous), Descent (aeronautics), business, Sleep, 030217 neurology & neurosurgery
Abstract: INTRODUCTION: Previous studies have linked sleep to risk of diabetes and obesity, at least partially via alterations in food intake. Diabetes and obesity are common among Hispanics/Latinos, and studies are needed to better clarify the role of sleep in health among this group. Utilizing the revised TFEQ-R-18, this study will examine whether eating behaviors such as cognitive restraint, emotional eating and uncontrolled eating are related to self-reported sleep experiences. Specifically, we hypothesized that poor eating habits would be associated with (1) more insomnia symptoms, (2) overall worse sleep quality, (3) increased daytime sleepiness, and (4) shorter sleep duration. METHODS: Data were collected from N=100 adults (age 18–60, 47% female) of Mexican descent in the city of Nogales, AZ (34% not born in the US). Surveys were presented in English or Spanish. Eating Patterns were assessed with the Three-Factor Eating Questionnaire (TFEQ), which resulted in a total score and subscales for “cognitive restraint,” “uncontrolled eating, “and “emotional eating.” Insomnia was assessed with the use of the Insomnia Severity Index (ISI), Sleepiness with the use of the Epworth Sleepiness Scale (ESS), Sleep quality with the use of the Pittsburgh Sleep Quality Index (PSQI), and weekday and weekend sleep duration with the use of the Sleep Timing Questionnaire (STQ). Covariates included: age, sex, Body Mass Index (BMI), education and immigrant status. RESULTS: Overall TFEQ score (problematic eating) was positively associated with greater insomnia, poorer sleep quality, more sleepiness, and less weekend (but not weekday) sleep. Mean TFEQ score in the sample was 18.7 (range 0–51). In adjusted analyses, every point on the TFEQ was associated with 0.6 ISI points, 0.8 PSQI points, 0.5 ESS points, and 1.1 minutes of less weekend sleep duration. Regarding subscale scores, relationships were generally seen between sleep and emotional eating and unrestricted eating, and not cognitive restraint. CONCLUSIONS: Greater insomnia, poorer sleep quality, increased daytime sleepiness and decreased weekend sleep duration were associated with eating patterns at the US Mexico border, particularly in the area of unrestricted eating and emotional eating. This suggests possible mechanisms linking sleep and obesity in Hispanic/Latinos.
Published: 2023

10. Renal involvement in COVID-19: focus on kidney transplant sector

Author: Gabriella Iannuzzo, Caterina Sagnelli, Massimo Ciccozzi, Monica Gallo, Massimiliano Creta, Antonello Sica, Vincenzo d'Alessandro, Alfonso Fiorelli, Evangelista Sagnelli, Fabrizo Schonauer, Armando Calogero, Carlo Garofalo, Gaia Peluso, Michele Santangelo, Felice Crocetto, Filippo Varlese, Alfonso Reginelli, Sagnelli, Caterina, Sica, Antonello, Gallo, Monica, Peluso, Gaia, Varlese, Filippo, D'Alessandro, Vincenzo, Ciccozzi, Massimo, Crocetto, Felice, Garofalo, Carlo, Fiorelli, Alfonso, Iannuzzo, Gabriella, Reginelli, Alfonso, Schonauer, Fabrizio, Santangelo, Michele, Sagnelli, Evangelista, Creta, Massimiliano, Calogero, Armando, Sagnelli, C., Sica, A., Gallo, M., Peluso, G., Varlese, F., D'Alessandro, V., Ciccozzi, M., Crocetto, F., Garofalo, C., Fiorelli, A., Iannuzzo, G., Reginelli, A., Schonauer, F., Santangelo, M., Sagnelli, E., Creta, M., and Calogero, A.
Subjects: Microbiology (medical), medicine.medical_specialty, Transplant Recipient, Kidney transplantation, Diabetes mellitus, Pandemic, medicine, Humans, Intensive care medicine, Adverse effect, Pandemics, Asthma, Immunosuppressant, Kidney, Original Paper, business.industry, SARS-CoV-2, COVID-19, General Medicine, medicine.disease, Obesity, Transplant Recipients, Review article, Infectious Diseases, medicine.anatomical_structure, business, Human
Abstract: Introduction: Kidney transplant recipients and patients on the waiting list for kidney transplant who acquire SARS-CoV-2 infection are at serious risk of developing severe COVID-19, with an increased risk of mortality for the their immunosuppressive state; other risk factors for mortality have been identified in some comorbidities such as obesity, diabetes, asthma and chronic lung disease. Materials and methods: The COVID-19 pandemic has led to a sharp reduction in kidney transplants in most countries, mainly due to the concern of patients on the waiting list for their potential increased susceptibility to acquire SARS-CoV-2 infection in healthcare facilities and for the difficulties of transplant centers to ensure full activity as hospitals have had to focus most of their attention on COVID-19 patients. Indeed, while the infection curve continued its exponential rise, there was a vertical decline in kidney donation/transplant activity. Conclusion: This review article focuses on the damage induced by SARS-CoV-2 infection on kidney and on the adverse effect of this pandemic on the entire kidney transplant sector.
Published: 2021

11. Vascular Injury After Stenting ― Insights of Systemic Mechanisms of Vascular Repair ―

Author: Pilar Jiménez-Quevedo, Esther Bernardo, Iván J. Núñez-Gil, Luis Nombela-Franco, Antonio Fernández-Ortiz, Manel Sabaté, Shuji Otsuki, Pablo Salinas, Hernán Mejía-Rentería, Salvatore Brugaletta, Javier Escaned, Maria Del Trigo, Nieves Gonzalo, Cristina Fernández-Pérez, Raúl Herrera, Arancha Ortega-Pozi, Carlos Macaya, and Fernando Alfonso
Subjects: Male, medicine.medical_specialty, medicine.medical_treatment, Coronary Artery Disease, Coronary artery disease, Vascular healing, Percutaneous Coronary Intervention, Restenosis, Flow cytometry technique, Neointima, Internal medicine, Humans, Medicine, Stent implantation, Everolimus, Progenitor cell, Aged, Sirolimus, business.industry, Stent, Drug-Eluting Stents, General Medicine, Middle Aged, Vascular System Injuries, medicine.disease, Coronary Vessels, Treatment Outcome, Drug-eluting stent, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Tomography, Optical Coherence
Abstract: BACKGROUND The role of circulating progenitor cells (CPC) in vascular repair following everolimus-eluting stent (EES) implantation is largely unknown. The aim of the study was to investigate the relationship between temporal variation in CPC levels following EES implantation and the degree of peri-procedural vascular damage, and stent healing, as measured by optical coherence tomography (OCT).Methods and Results:CPC populations (CD133+/KDR+/CD45low) included patients with stable coronary artery disease undergoing stent implantation, and were evaluated using a flow cytometry technique both at baseline and at 1 week. OCT evaluation was performed immediately post-implantation to quantify the stent-related injury and at a 9-month follow up to assess the mid-term vascular response. Twenty patients (mean age 66±9 years; 80% male) with EES-treated stenoses (n=24) were included in this study. Vascular injury score was associated with the 1-week increase of CD133+/KDR+/CD45low (β 0.28 [95% CI 0.15; 0.41]; P
Published: 2022
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12. Hemodynamic alterations following a cerebellar arteriovenous malformation resection: Case report and densitometric quantitative analysis from CT imaging

Author: Luis Jiménez-Roldán, Daniel García-Pérez, Irene Panero, Pablo M. Munarriz, José A. Alén, and Alfonso Lagares
Subjects: Cerebellum, medicine.medical_specialty, business.industry, Hemodynamics, Context (language use), Arteriovenous malformation, General Medicine, Fourth ventricle, medicine.disease, Hydrocephalus, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Hounsfield scale, Edema, medicine, Surgery, Neurology (clinical), Radiology, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Background Cerebellar arteriovenous malformations (cAVMs) are rare and challenging lesions with an aggressive natural history. The mechanisms whereby a patient can worsen clinically after a supratentorial AVM resection include an acute alteration in cerebral hemodynamics, which is a known cause of postoperative hyperemia, edema and/or hemorrhage. These phenomena has not been described for cAVMS. Moreover, the underlying pathophysiology of edema and hemorrhage after AVM resection still remains controversial. Methods We report a patient that presented an abrupt neurological deterioration after cAVM surgical resection. Emergent external ventricular drainage to treat incipient hydrocephalus only partially reverted the patient's deterioration. Consecutive post-surgery CT images revealed fourth ventricle compression secondary to cerebellar swelling that concurred with a new neurological deterioration. Densitometric analysis was performed in these CT images to reveal the nature of these changes as well as their evolution over time. Results Importantly, we demonstrated a dynamic increase in the cerebellum mean density at the interval of Hounsfield values which correspond to hyperemia values. These changes were dynamic, and when hyperemia resolved and cerebellar density returned to basal levels, the fourth ventricle re-expanded and the patient neurologically recovered. Conclusions This study demonstrated the utility of quantitative CT image analysis in the context of hemodynamic alterations following cAVM resection. Densitometric CT analysis demonstrated that hyperemic changes, but not ischemic ones, were time-dependent and were responsible for swelling and hemorrhage that conditioned neurological status and patient's evolution.
Published: 2022
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13. Upfront primary tumour resection and survival in synchronous metastatic colorectal cancer according to primary tumour location and RAS status: Pooled analysis of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

Author: Antonieta Salud, Manuel Valladares-Ayerbes, Javier Sastre, Elena Asensio, Luis Robles, Eduardo Díaz-Rubio, Fernando Rivera, Enrique Aranda, Albert Abad, Auxiliadora Gómez-España, Vicente Alonso-Orduña, Alfredo Carrato, Clara Montagut, Maria Jose Safont, Cristina García González, Manuel Benavides, Encarnación González-Flores, Pilar García-Alfonso, and Jose María Vieitez
Subjects: Oncology, medicine.medical_specialty, Rectal Neoplasms, Colorectal cancer, business.industry, Tumor resection, Antibodies, Monoclonal, Angiogenesis Inhibitors, General Medicine, medicine.disease, Pooled analysis, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Colonic Neoplasms, medicine, Humans, Cooperative group, Surgery, Colorectal Neoplasms, business, Retrospective Studies
Abstract: Retrospective studies and meta-analyses suggest that upfront primary tumour resection (UPTR) confers a survival benefit in patients with asymptomatic unresectable metastatic colorectal cancer (mCRC) undergoing chemotherapy, however a consensus of its role in routine clinical practice in the current era of targeted therapies is lacking. This retrospective study aimed to analyse the survival benefit of UPTR in terms of tumour location and mutational status, in patients with synchronous mCRC receiving chemotherapy and targeted therapy.Survival was analysed in a pooled cohort of synchronous mCRC patients treated with a first-line anti-VEGF or anti-EGFR inhibitor in seven trials of the Spanish TTD group, according to UPTR, tumour-sidedness and mutational profiling.Of 1334 eligible patients, 642 (48%) had undergone UPTR. UPTR was associated with significantly longer overall survival (OS; 25.0 vs 20.3 months; HR 1.30, 95%CI 1.15-1.48; p 0.0001). UPTR was associated with significant OS benefit in both left-sided (HR 1.38, 95%CI 1.13-1.69; p = 0.002) and right-sided (HR 1.39, 95%CI 1.00-1.94; p = 0.049) tumours, RASwt (HR 1.29, 95%CI 1.05-1.60; p = 0.016) and BRAFwt (HR 1.49, 95%CI 1.21-1.84; p = 0.0002) tumours, and treatment with anti-EGFRs (HR 1.47, 95%CI 1.13-1.92; p = 0.004) and anti-VEGFs (HR 1.25, 95%CI 1.08-1.44; p = 0.003). Multivariate analysis identified number of metastatic sites, RAS status, primary tumour location and UPTR as independent prognostic factors for OS.Considering the selection bias inherent to this study, our results support UPTR before first-line anti-EGFR or anti-VEGF targeted therapy in right and left-sided asymptomatic unresectable synchronous mCRC patients. RAS/BRAF mutational status may also influence UPTR function.
Published: 2022
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14. Hamartoma pancreático: una causa benigna y poco frecuente de incidentaloma pancreático

Author: Alberto González Barranquero, Alfonso Sanjuanbenito Dehesa, José María Fernández Cebrián, José Manuel Molina Villar, and Ángela Santana Valenciano
Subjects: medicine.medical_specialty, business.industry, Incidentaloma, medicine, Hamartoma, Surgery, Radiology, medicine.disease, business
Published: 2022
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15. Optimal carbohydrate antigen 125 cutpoint for identifying low-risk patients after admission for acute heart failure

Author: Marco Metra, Eduardo Núñez, Gema Miñana, Pau Llàcer, Chim C. Lang, Juan Sanchis, Patricia Palau, Josep Lupón, Elena Revuelta-López, Enrique Santas, Rafael de la Espriella, Miguel Lorenzo, Julio Núñez, Vicent Bodí, Adriaan A. Voors, Antoni Bayes-Genis, Arturo Carratalá, Jozine M. ter Maaten, Alfonso Valle, Leong L. Ng, and Cardiovascular Centre (CVC)
Subjects: medicine.medical_specialty, Optimal cutoff, Antígeno carbohidrato 125, MONOCLONAL-ANTIBODY, endocrine system diseases, Carbohydrates, Aftercare, Insuficiencia cardiaca aguda, 030204 cardiovascular system & hematology, Worsening Heart Failure, CA125, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Cutoff, In patient, Outcome, Heart Failure, NATRIURETIC PEPTIDE, business.industry, MORTALITY, Pronóstico, General Medicine, Congestión, Prognosis, medicine.disease, Predictive value, Patient Discharge, female genital diseases and pregnancy complications, Carbohydrate antigen 125, Congestion, Acute Disease, CA-125 Antigen, Heart failure, Cohort, Risk stratification, business, Carbohydrate antigen
Abstract: Introduction and objectives: Carbohydrate antigen 125 (CA125) has been shown to be useful for risk stratification in patients admitted with acute heart failure (AHF). We sought to determine a CA125 cutpoint for identifying patients at low risk of 1-month death or the composite of death/HF readmission following admission for AHF.Methods: The derivation cohort included 3231 consecutive patients with AHF. CA125 cutoff values with 90% negative predictive value (NPV) and sensitivity up to 85% were identified. The adequacy of these cutpoints and the risk of 1-month death/HF readmission was then tested using the Royston-Parmar method. The best cutpoint was selected and externally validated in a cohort of patients hospitalized from BIOSTAT-CHF (n = 1583).Result: In the derivation cohort, the median [IQR] CA125 was 57 [25.3-157] U/mL. The optimal cutoff value was < 23 U/mL (21.5% of patients), with NPVs of 99.3% and 94.1% for death and the composite endpoint, respectively. On multivariate survival analyses, CA125 < 23 U/mL was independently associated with a lower risk of death (HR, 0.20; 95%Cl, 0.08-0.50; P < .001), and the combined endpoint (HR, 0.63; 95%Cl, 950.45-0.90; P = .009). The ability of this cutpoint to discriminate patients at a low 1-month risk was confirmed in the validation cohort (NPVs of 98.6% and 96.6% for death and the composite endpoint). The predicted ability of this cutoff remained significant at 6 months of follow-up.Conclusion: In patients admitted with AHF, CA125 < 23 U/mL identified a subgroup at low risk of short-term adverse events, a population that may not require intense postdischarge monitoring. (C) 2021 Sociedad Espanola de Cardiologia. Published by Elsevier Espafia, S.L.U. All rights reserved.
Published: 2022
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16. Clinical outcomes of everolimus-eluting bioresorbable scaffolds or everolimus-eluting stents in patients with acute myocardial infarction: two-year results of the randomised ISAR-Absorb MI trial

Author: Michael Maeng, Christian Bradaric, Michael Joner, Evgeny Kretov, Karl-Ludwig Laugwitz, Salvatore Cassese, Mira Heugl, Javier Cuesta, Robert A. Byrne, Fernando Alfonso, Evald Høj Christiansen, Constantin Kuna, Jens Wiebe, Adnan Kastrati, Heribert Schunkert, Tareq Ibrahim, and Fernando Rivero
Subjects: medicine.medical_specialty, Everolimus, business.industry, Everolimus eluting stent, Myocardial Infarction, Drug-Eluting Stents, Coronary Artery Disease, Prosthesis Design, medicine.disease, Percutaneous Coronary Intervention, Treatment Outcome, Research Correspondence, Internal medicine, Absorbable Implants, medicine, Cardiology, Humans, Stents, In patient, Myocardial infarction, Cardiology and Cardiovascular Medicine, business, Bioresorbable scaffold, medicine.drug
Published: 2022
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17. Severity of protein-energy wasting and obesity are independently related with poor quality of life in peritoneal dialysis patients

Author: Margarita Gutiérrez-Medina, Laura Cortés-Sanabria, Alfonso M. Cueto-Manzano, Erika F. Gómez-García, José Ramón Paniagua-Sierra, Roxana Michel Márquez-Herrera, Claudia N. Orozco-González, Fabiola Martin del Campo, and Enrique Rojas-Campos
Subjects: medicine.medical_specialty, medicine.medical_treatment, 030232 urology & nephrology, Protein-Energy Malnutrition, Peritoneal dialysis, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Internal medicine, medicine, Humans, Obesity, 030212 general & internal medicine, Hypoalbuminemia, Wasting, business.industry, Continuous ambulatory peritoneal dialysis, Anthropometry, medicine.disease, humanities, Cross-Sectional Studies, Nephrology, Quality of Life, Kidney Diseases, medicine.symptom, business, Peritoneal Dialysis, Kidney disease
Abstract: Protein-energy wasting (PEW) and poor health-related quality of life (HRQoL) are independently associated with morbi-mortality in continuous ambulatory peritoneal dialysis (CAPD). PEW may reduce HRQoL; however, we hypothesized HRQoL is affected differentially by PEW degrees or by individual criteria of nutritional status. AIM: To evaluate HRQoL according to PEW severity and nutritional status indicators in CAPD. This is a cross-sectional study in 151 patients. Subjective global assessment (SGA) was employed, and nutritional status classified as normal, mild-moderate PEW, and severe PEW. HRQoL was evaluated using Kidney Disease Quality of Life Short Form™, including physical (PCS), mental (MCS) and kidney disease (KDCS) components, and their subscales. Dietary intake, anthropometric and biochemical variables were measured. Forty-six percent of patients were well-nourished, 44% had mild-moderate PEW, and 10% severe PEW. Compared with well-nourished patients, those with mild-moderate (p=0.06) and severe (p=0.005) PEW had lower HRQoL score [68 (52-75), 55 (45-72), 46 (43-58), respectively]. PCS, MCS, and KDCS and their subscales had lower values as PEW was more severe. Patients with obesity and hypoalbuminemia had significantly lower HRQoL overall and component scores than their counterparts. Dietary intake was not associated with quality of life. In multivariate analysis obesity, PEW (by SGA), hypoalbuminemia, and low educational level predicted poor HRQoL (χ2 58.2, p
Published: 2022
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18. Androgen receptor splice variant-7 in breast cancer: clinical and pathologic correlations

Author: Kerry Mullaney, Donna C. Ferguson, Tiffany A. Traina, Marc Ladanyi, Timothy Ky. Tay, Ryma Benayed, Edi Brogi, Maria E. Arcila, Douglas A. Mata, Sarat Chandarlapaty, Ayca Gucalp, Timothy M. D'Alfonso, and Dara S. Ross
Subjects: Oncology, Pathology, medicine.medical_specialty, medicine.drug_class, business.industry, Apocrine, Context (language use), medicine.disease, Pathology and Forensic Medicine, Androgen receptor, Prostate cancer, Breast cancer, Estrogen, Internal medicine, medicine, Immunohistochemistry, business, Estrogen receptor alpha
Abstract: Androgen receptor (AR) inhibitor therapy is a developing treatment for AR-positive breast cancer (BC) with ongoing clinical trials. AR splice variant-7 (AR-V7) is a truncated variant of AR that leads to AR inhibitor therapy resistance in prostate cancer; recent studies have identified AR-V7 in BC and theorized that AR-V7 can have a similar impact. This study assessed the prevalence and clinicopathologic features associated with AR-V7 in a large BC cohort. BC samples were evaluated by MSK-Fusion targeted RNAseq for AR-V7 detection and MSK-IMPACT targeted DNAseq, including triple-negative tumors with no driver alteration and estrogen receptor-positive/ESR1 wildtype tumors progressing on therapy. Among 196 primary and metastatic/recurrent cases (196 RNAseq, 194DNAseq), 9.7% (19/196) were AR-V7 positive and 90.3% (177/196) AR-V7 negative. All AR-V7 positive BC were AR-positive by immunohistochemistry (19/19). The prevalence of AR-V7 by receptor subtype (N = 189) was: 18% (12/67) in ER-/PgR-/HER2-negative BC, 3.7% (4/109) in ER-positive/HER2-negative BC, and 15.4% (2/13) in HER2-positive BC; AR-V7 was detected in one ER-positive/HER2-unknown BC. Apocrine morphology was observed in 42.1% (8/19) of AR-V7 positive BC and 3.4% (6/177) AR-V7 negative BC (P
Published: 2022
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19. Long-Range Auditory Functional Connectivity in Hearing Loss and Rehabilitation

Author: Francesco Di Salle, Maria Teresa Pellecchia, Josef Pfeuffer, Donato Troisi, Ettore Cassandro, Sofia Cuoco, Renzo Manara, Alfonso Scarpa, Sara Ponticorvo, Arianna Cappiello, Fabrizio Esposito, Ponticorvo, Sara, Manara, Renzo, Pfeuffer, Josef, Cappiello, Arianna, Cuoco, Sofia, Pellecchia, Maria Teresa, Troisi, Donato, Scarpa, Alfonso, Cassandro, Ettore, Di Salle, Francesco, and Esposito, Fabrizio
Subjects: Hearing aid, medicine.medical_specialty, Hearing loss, medicine.medical_treatment, Altered brain connectivity, cerebral blood flow, Audiology, hearing aid, perfusion, 050105 experimental psychology, 03 medical and health sciences, functional connectivity, hearing loss, resting-state fMRI, Brain, Female, Gray Matter, Humans, Magnetic Resonance Imaging, Auditory Cortex, Hearing Loss, 0302 clinical medicine, otorhinolaryngologic diseases, Medicine, 0501 psychology and cognitive sciences, Neural plasticity, Rehabilitation, Resting state fMRI, business.industry, General Neuroscience, Functional connectivity, 05 social sciences, medicine.disease, Sensorineural hearing loss, medicine.symptom, business, Arterial spin labeling (ASL), 030217 neurology & neurosurgery
Abstract: Patients with age-related sensorineural hearing loss (HL) may benefit from auditory input amplification by using hearing aids (HA). However, the impact of both HL and HA-based rehabilitation on central auditory functional connectivity (FC) is not clear.
Published: 2021
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20. What Is the Correct Way to Manage Children Requiring Gastrostomy? Single Center Experience

Author: M. Romano, Alfonso Papparella, Edoardo Bindi, Carmine Noviello, Stefano Nobile, Giovanni Cobellis, Noviello, Carmine, Romano, Mercede, Bindi, Edoardo, Cobellis, Giovanni, Nobile, Stefano, and Papparella, Alfonso
Subjects: Pediatrics, medicine.medical_specialty, Nutritional Supplementation, Heart disease, medicine.medical_treatment, gastroesophageal reflux, RC799-869, Disease, Single Center, 03 medical and health sciences, 0302 clinical medicine, children, 030225 pediatrics, Medicine, Hepatology, business.industry, Gastroenterology, Reflux, Diseases of the digestive system. Gastroenterology, medicine.disease, Gastrostomy, neurological impairment patient, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, gastrostomy, GERD, 030211 gastroenterology & hepatology, medicine.symptom, business, Weight gain
Abstract: Children with complex medical issues often present different comorbidities that cause feeding difficulties. Gastrostomy is often helpful, and should be performed when nutritional supplementation is necessary for longer than 6 weeks. Recently, different techniques have been used for gastrostomy in children. The authors report on their experiences regarding the diagnostic and therapeutic management of children requiring gastrostomy. All patients managed in the last 10 years were reviewed, retrospectively. Everyone underwent investigation to exclude gastroesophageal reflux disease (GERD). A total of 148 patients: 111 cases (75%) were neurologically impaired patients, 18 (12%) had complex heart disease, 10 (6%) had metabolic diseases, 4 (3%) had fibrosis cystic, 4 (3%) had muscle disease, and one had chromosomopathy. After investigation, 49 patients had GERD. PEG was performed in 101 cases (68%), laparo-assisted gastrostomy was performed in 44 cases (29.7%), open gastrostomy was performed in three cases. At follow-up, all patients reported weight gain, but 13 cases had major complications. Currently, the surgeon has the possibility of choosing between several safe techniques for gastrostomy. In our experience, PEG is the most useful technique for patients without GERD, while a laparo-assisted technique is better for patients who require laparoscopic fundoplication.
Published: 2021
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21. Pulmonary Hamartoma Associated With Lung Cancer (PHALC Study): Results of a Multicenter Study

Author: Francesco Puma, Erino A. Rendina, Antonio D'Andrilli, Mark Ragusa, Alfonso Fiorelli, Nicoletta Pia Ardò, G. Bocchialini, Marco Anile, Paolo Carbognani, Simona Sobrero, Francesco Sollitto, Nicola Serra, Mario Santini, Luigi Ventura, Beatrice Trabalza Marinucci, Federico Venuta, Domenico Loizzi, Annalisa Carlucci, Giacomo Argento, Roberta Rapana, Giovanni Vicidomini, Francesco Ardissone, Valentina Tassi, Fiorelli, Alfonso, D'Andrilli, Antonio, Carlucci, Annalisa, Vicidomini, Giovanni, Argento, Giacomo, Trabalza Marinucci, Beatrice, Ardissone, Francesco, Rapanà, Roberta, Sobrero, Simona, Carbognani, Paolo, Ventura, Luigi, Bocchialini, Giovanni, Ragusa, Mark, Tassi, Valentina, Sollitto, Francesco, Loizzi, Domenico, Ardò, Nicoletta Pia, Anile, Marco, Puma, Francesco, Rendina, Erino Angelo, Venuta, Federico, Serra, Nicola, and Santini, Mario
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Lung Neoplasms, Hamartoma, Enucleation, Pulmonary Hamartoma, Benign tumor, 03 medical and health sciences, hamartoma, lung cancer, pulmonary, surgical resection, aged, humans, lung, retrospective studies, smokers, lung neoplasms, 0302 clinical medicine, medicine, Humans, 030212 general & internal medicine, Lung cancer, Lung, Aged, Retrospective Studies, Smokers, business.industry, Pulmonary, medicine.disease, Surgery, medicine.anatomical_structure, 030228 respiratory system, Multicenter study, Surgical resection, Population study, business, Wedge resection (lung)
Abstract: Purpose Pulmonary hamartoma is the most common benign tumor of the lung. We analyzed a 20-year historical series of patients with pulmonary hamartoma undergoing surgical resection, aiming to evaluate the characteristics, the outcomes, and the association between hamartoma and lung cancer. Methods It was a retrospective multicenter study including the data of all consecutive patients with pulmonary hamartoma undergoing surgical resection. The end-points were to evaluate: (i) the characteristics of hamartoma, (ii) outcomes, and (iii) whether hamartoma was a predictive factor for lung cancer development Results Our study population included 540 patients. Upfront surgical or endoscopic resection was performed in 385 (71%) cases while in the remaining 155 (29%) cases, the lesions were resected 20 ± 3.5 months later due to increase in size. In most cases, lung sparing resection was carried out including enucleation (n = 259; 48%) and wedge resection (n = 230; 43%) while 5 (1%) patients underwent endoscopic resection. Only two patients (0, 2%) had major complications. One patient (0.23%) had recurrence after endoscopic resection, while no cases of malignant degeneration were seen (mean follow-up:103.3 ± 93 months). Seventy-six patients (14%) had associated lung cancer, synchronous in 9 (12%) and metachronous in 67 (88%). Only age > 70-year-old (p = 0.0059) and smokers > 20 cigarettes/day (p Conclusion PH was a benign tumor, with no evidence of recurrence and/or of malignant degeneration after resection. The association between hamartoma and lung cancer was a spurious phenomenon due to common risk factors.
Published: 2021

22. Small fiber neuropathy in the cornea of Covid-19 patients associated with the generation of ocular surface disease

Author: Luis M. Quirós, Luis Fernández-Vega Cueto, Alberto Barros, Juan Queiruga-Piñeiro, José F. Alfonso, Javier Lozano-Sanroma, Jesus Merayo-Lloves, Juana Gallar, Ignacio Alcalde, Gallar, Juana [0000-0002-3559-3649], Fernández-Vega Cueto, Luis [0000-0001-9197-5847], Alfonso, José F. [0000-0002-0373-8209], Quirós, Luis M. [0000-0003-3505-3762], Gallar, Juana, Fernández-Vega Cueto, Luis, Alfonso, José F., and Quirós, Luis M.
Subjects: In vivo confocal microscopy, medicine.medical_specialty, Diabetic neuropathy, Small Fiber Neuropathy, Nerve fiber, Asymptomatic, Cornea, In vivo, Ophthalmology, medicine, Humans, Ocular Surface Disease Index, Dry eye disease, Retrospective Studies, High Impact Original Research, Plexus, Corneal neuropathy, Microscopy, Confocal, SARS-CoV-2, business.industry, COVID-19, Retrospective cohort study, medicine.disease, eye diseases, medicine.anatomical_structure, Dry Eye Syndromes, sense organs, medicine.symptom, business
Abstract: [Purpose]: To describe the association between Sars-CoV-2 infection and small fiber neuropathy in the cornea identified by in vivo corneal confocal microscopy., [Methods]: Twenty-three patients who had overcome COVID-19 were recruited to this observational retrospective study. Forty-six uninfected volunteers were also recruited and studied as a control group. All subjects were examined under in vivo confocal microscopy to obtain images of corneal subbasal nerve fibers in order to study the presence of neuroma-like structures, axonal beadings and dendritic cells. The Ocular Surface Disease Index (OSDI) questionnaire and Schirmer tear test were used as indicators of Dry Eye Disease (DED) and ocular surface pathology., [Results]: Twenty-one patients (91.31%) presented alterations of the corneal subbasal plexus and corneal tissue consistent with small fiber neuropathy. Images from healthy subjects did not indicate significant nerve fiber or corneal tissue damage. Eight patients reported increased sensations of ocular dryness after COVID-19 infection and had positive DED indicators. Beaded axons were found in 82.60% of cases, mainly in patients reporting ocular irritation symptoms. Neuroma-like images were found in 65.22% patients, more frequently in those with OSDI scores >13. Dendritic cells were found in 69.56% of patients and were more frequent in younger asymptomatic patients. The presence of morphological alterations in patients up to 10 months after recovering from Sars-CoV-2 infection points to the chronic nature of the neuropathy., [Conclusions]: Sars-CoV-2 infection may be inducing small fiber neuropathy in the ocular surface, sharing symptomatology and morphological landmarks with DED and diabetic neuropathy.
Published: 2022

23. Cancer- and Non-cancer Related Chronic Pain: From the Physiopathological Basics to Management

Author: Alessandro Spada, Elisabetta Saracco, Teresa Troiani, Mario Santagata, Maria Teresa Di Dato, Anna Maria Salzano, Fortunato Ciardiello, Antonello Sica, Dario Tammaro, Caterina Sagnelli, Pietro Buonavolontà, Armando Calogero, Erika Martinelli, Concetta Anna Dodaro, Alfonso Fiorelli, Beniamino Casale, Alfonso Papa, Sica, Antonello, Casale, Beniamino, Dato, Maria Teresa Di, Calogero, Armando, Spada, Alessandro, Sagnelli, Caterina, Santagata, Mario, Buonavolontà, Pietro, Fiorelli, Alfonso, Salzano, Anna, Dodaro, Concetta Anna, Martinelli, Erika, Saracco, Elisabetta, Troiani, Teresa, Tammaro, Dario, Ciardiello, Fortunato, Papa, Alfonso, Sica, A., Casale, B., Dato, M. T. D., Calogero, A., Spada, A., Sagnelli, C., Santagata, M., Buonavolonta, P., Fiorelli, A., Salzano, A., Dodaro, C. A., Martinelli, E., Saracco, E., Troiani, T., Tammaro, D. F., Ciardiello, F., and Papa, A.
Subjects: medicine.medical_specialty, Dose, Intrathecal therapy, Pain, Chronic pain, 03 medical and health sciences, 0302 clinical medicine, Refractory, Quality of life, Internal medicine, chronic pain therapy, Medicine, Intrathecal pump, 030212 general & internal medicine, Cancer pain, business.industry, Cancer, General Medicine, medicine.disease, Anxiety, medicine.symptom, business, 030217 neurology & neurosurgery, Research Article, Non-cancer pain
Abstract: The prevalence of chronic pain is between 33% to 64% and is due to cancer pain, but it has also been observed in non-cancer patients. Chronic pain is associated with lower quality of life and higher psychological distress and depressive/anxiety disorders in patients without a history of disorder. In this study we evaluated in clinical practice the effectiveness of the intrathecal pump in 140 patients who underwent pain therapy at our Center. These patients were consecutively enrolled from January 2010 to July 2018. Follow-up was carried out over these eight years regarding the infusion modalities. Pain relief was obtained in 71 (50,7%) patients out of the 140 that experienced satisfactory pain control globally. Intrathecal therapy is one of the best options for chronic severe refractory pain. The greatest advantage of this therapy is due to the possibility of treating the pain with minimal dosages of the drug, avoiding the appearance of troublesome side effects.
Published: 2019

24. Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author: Rheenen, Wouter van, Spek, Rick A. A. van der, Bakker, Mark K., Vugt, Joke J. F. A. van, Hop, Paul J., Zwamborn, Ramona A. J., Klein, Niek de, Westra, Harm Jan, Bakker, Olivier B., Deelen, Patrick, Shireby, Gemma, Needham, Merrilee, Ceroni, Mauro, Simoncini, Costanza, Gagliardi, Stella, Corrado, Lucia, Garton, Fleur C., Mazzini, Letizia, Westeneng, Henk Jan, Ross, Jay P., Valluzzi, Francesco, Aguggia, Marco, Raggi, Flavia, Rini, Augusto, Traynor, Bryan J., Singleton, Andrew B., Ngo, Shyuan T., Corcia, Philippe, Olsen, Catherine M., Hofman, Albert, Van Eijk, Kristel R., Pasterkamp, R. Jeroen, Tittmann, Lukas, Iacoangeli, Alfredo, Mitne Neto, Miguel, Sproviero, Daisy, Cauchi, Ruben J., Ophoff, Roel A., Wiedau Pazos, Martina, Lomen-Hoerth, Catherine, Deerlin, Vivianna M. van, Nicholson, Garth A., Brylev, Lev, Whiteman, David C., Grosskreutz, Julian, Fan, Dongsheng, Couratier, Philippe, Roediger, Annekathrin, Gaur, Nayana, D’alfonso, Sandra, Uitterlinden, André G., Pamphlett, Roger, Fominykh, Vera, Byrne, Ross P., Lieb, Wolfgang, Iazzolino, Barbara, Dekker, Annelot M., Slap Consortium, Demeshonok, Vera, Millecamps, Stéphanie, Ataulina, Anastasia, Rogelj, Boris, Koritnik, Blaž, Zidar, Janez, Ravnik-Glavač, Metka, Franke, Andre, Mcrae, Allan F., Rowe, Dominic B., Peotta, Laura, Cooper-Knock, Johnathan, Glavač, Damjan, Doherty, Mark, Rietschel, Marcella, Stević, Zorica, Drory, Vivian, Meininger, Vincent, Zarrelli, Michele, Povedano, Monica, Gaunt, Tom R., Steyn, Frederik J., Williams, Kelly L., Smith, Bradley N., Cugnasco, Paolo, Papurello, Diego Maria, Nozzoli, Cecilia, Sorarù, Gianni, Mather, Karen A., Ripke, Stephan, Nöthen, Markus M., Sachdev, Perminder S., Henders, Anjali K., Wallace, Leanne, Carvalho, Mamede de, Gromicho, Marta, Pinto, Susana, Marco, Giovanni de, Al Khleifat, Ahmad, Eberle, Michael A., Braun, Alice, Gusmaroli, Graziano, Siciliano, Gabriele, Petri, Susanne, Breen, Gerome, Weber, Markus, Rouleau, Guy A., Rojas García, Ricardo, Silani, Vincenzo, Amouyel, Philippe, Ghiglione, Paolo, Davey Smith, George, Curtis, Charles J., Shatunov, Aleksey, Mill, Jonathan, Mclaughlin, Russell L., Filosto, Massimiliano, Comi, Cristoforo, Gerfo, Annalisa lo, Ferlini, Alessandra, Riva, Nilo, Mora Pardina, Jesus S., Chiveri, Luca, Hardiman, Orla, Torrieri, Maria Claudia, Kenna, Kevin P., Wray, Naomi R., Tsai, Ellen, Runz, Heiko, Franke, Lude, Padovani, Alessandro, Chandran, Siddharthan, Al Chalabi, Ammar, Assialioui, Abdelilah, Labate, Carmelo, Damme, Philip van, Ticozzi, Nicola, Palumbo, Francesca, Inghilleri, Maurizio, Chiò, Adriano, Pal, Suvankar, Lunetta, Christian, Jörk, Alexander, Cichon, Sven, Kraft, Julia, Morrison, Karen E., Ruiz, Luigi, Shaw, Pamela J., Hardy, John, Orrell, Richard W., Sendtner, Michael, Meyer, Thomas, Dion, Patrick A., Calvo, Andrea, Kooyman, Maarten, Başak, Nazli, Gerardi, Francesca, Simone, Isabella L., Kooi, Anneke J. van der, Ratti, Antonia, Ferrandi, Delfina, Fogh, Isabella, Ludolph, Albert C., Moglia, Cristina, Brunetti, Maura, Diamanti, Luca, Barthel, Tabea, Blair, Ian P., Es, Michael A. van, Gallone, Salvatore, Canosa, Antonio, Guerra, Vito, Grassano, Maurizio, Beghi, Ettore, Pupillo, Elisabetta, Logroscino, Giancarlo, Ferrarese, Carlo, Nefussy, Beatrice, Theele, Erik, Rinaldi, Fabrizio, Weishaupt, Jochen H., Kiernan, Matthew C., Barberis, Marco, Osmanovic, Alma, Baloh, Robert H., Nordin, Angelica, Lerner, Yossef, Vito, Nicoletta di, Zabari, Michal, Zoccolella, Stefano, Heverin, Mark, Gotkine, Marc, Guaita, Maria Cristina, Brenner, David, Freischmidt, Axel, Sbaiz, Luca, Benyamin, Beben, Glass, Jonathan D., Landers, John E., Tazelaar, Gijs H. P., Rota, Eugenia, Bensimon, Gilbert, Ilse, Benjamin, Brice, Alexis, Durr, Alexandra, Payan, Christine A. M., Saker-Delye, Safa, Wood, Nicholas W., Gentile, Salvatore, Moisse, Matthieu, Topp, Simon, Henderson, Robert D., Rademakers, Rosa, Perrone, Patrizia, Stubendorff, Beatrice, Brown, Robert H., Restuadi, Restuadi, Tremolizzo, Lucio, Mundi, Ciro, Berg, Leonard H. van den, Passarella, Bruno, Delodovici, Maria Luisa, Furlong, Sarah, Bono, Giorgio, Manera, Umberto, Vasta, Rosario, Bombaci, Alessandro, Meineri, Piero, Mauro, Alessandro, Hannon, Eilis, Casale, Federico, Leone, Maurizio, Shaw, Christopher E., Fuda, Giuseppe, Salamone, Paolina, Mathers, Susan, Baird, Denis, Launaro, Nicola, Marchi, Fabiola de, Veldink, Jan H., Gellera, Cinzia, Salachas, François, Witte, Otto W., Andersen, Peter M., Bertolotto, Antonio, Gionco, Maurizio, Leotta, Daniela, Odddenino, Enrico, Slalom Consortium, Tamma, Filippo, Dotta, Michele, Lauria, Giuseppe, Steinbach, Robert, Imperiale, Daniele, Geda, Claudio, Dolzhenko, Egor, Cavallo, Roberto, Pignatta, Pietro, Groen, Ewout J. N., Cotelli, Maria Sofia, Mattei, Marco de, Calabrese, Gianluigi, Sapio, Alessia di, Giardini, Guido, Hübner, Christian A., Corti, Stefania, Bell, Shaughn, Comi, Giancarlo, Mccombe, Pamela A., Tiloca, Cinzia, Parals Consortium, Gawor, Klara, Peverelli, Silvia, Taroni, Franco, Pensato, Viviana, Castellotti, Barbara, Graff, Caroline, Comi, Giacomo P., Cereda, Cristina, Bo, Roberto del, Boero, Giovanni, Slagen Consortium, Vourc’h, Patrick, Stem Cell Aging Leukemia and Lymphoma (SALL), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), van Rheenen, Wouter, van der Spek, Rick AA, Bakker, Mark K, van Vugt, Joke JFA, Benyamin, Beben, Veldink, Jan H, SLALOM Consortium, PARALS Consortium, SLAGEN Consortium, SLAP Consortium, van Rheenen, W, van der Spek, R, Bakker, M, van Vugt, J, Hop, P, Zwamborn, R, de Klein, N, Westra, H, Bakker, O, Deelen, P, Shireby, G, Hannon, E, Moisse, M, Baird, D, Restuadi, R, Dolzhenko, E, Dekker, A, Gawor, K, Westeneng, H, Tazelaar, G, van Eijk, K, Kooyman, M, Byrne, R, Doherty, M, Heverin, M, Al Khleifat, A, Iacoangeli, A, Shatunov, A, Ticozzi, N, Cooper-Knock, J, Smith, B, Gromicho, M, Chandran, S, Pal, S, Morrison, K, Shaw, P, Hardy, J, Orrell, R, Sendtner, M, Meyer, T, Basak, N, van der Kooi, A, Ratti, A, Fogh, I, Gellera, C, Lauria, G, Corti, S, Cereda, C, Sproviero, D, D'Alfonso, S, Soraru, G, Siciliano, G, Filosto, M, Padovani, A, Chio, A, Calvo, A, Moglia, C, Brunetti, M, Canosa, A, Grassano, M, Beghi, E, Pupillo, E, Logroscino, G, Nefussy, B, Osmanovic, A, Nordin, A, Lerner, Y, Zabari, M, Gotkine, M, Baloh, R, Bell, S, Vourc'H, P, Corcia, P, Couratier, P, Millecamps, S, Meininger, V, Salachas, F, Mora Pardina, J, Assialioui, A, Rojas-Garcia, R, Dion, P, Ross, J, Ludolph, A, Weishaupt, J, Brenner, D, Freischmidt, A, Bensimon, G, Brice, A, Durr, A, Payan, C, Saker-Delye, S, Wood, N, Topp, S, Rademakers, R, Tittmann, L, Lieb, W, Franke, A, Ripke, S, Braun, A, Kraft, J, Whiteman, D, Olsen, C, Uitterlinden, A, Hofman, A, Rietschel, M, Cichon, S, Nothen, M, Amouyel, P, Traynor, B, Singleton, A, Mitne Neto, M, Cauchi, R, Ophoff, R, Wiedau-Pazos, M, Lomen-Hoerth, C, van Deerlin, V, Grosskreutz, J, Roediger, A, Gaur, N, Jork, A, Barthel, T, Theele, E, Ilse, B, Stubendorff, B, Witte, O, Steinbach, R, Hubner, C, Graff, C, Brylev, L, Fominykh, V, Demeshonok, V, Ataulina, A, Rogelj, B, Koritnik, B, Zidar, J, Ravnik-Glavac, M, Glavac, D, Stevic, Z, Drory, V, Povedano, M, Blair, I, Kiernan, M, Benyamin, B, Henderson, R, Furlong, S, Mathers, S, Mccombe, P, Needham, M, Ngo, S, Nicholson, G, Pamphlett, R, Rowe, D, Steyn, F, Williams, K, Mather, K, Sachdev, P, Henders, A, Wallace, L, de Carvalho, M, Pinto, S, Petri, S, Weber, M, Rouleau, G, Silani, V, Curtis, C, Breen, G, Glass, J, Brown, R, Landers, J, Shaw, C, Andersen, P, Groen, E, van Es, M, Pasterkamp, R, Fan, D, Garton, F, Mcrae, A, Davey Smith, G, Gaunt, T, Eberle, M, Mill, J, Mclaughlin, R, Hardiman, O, Kenna, K, Wray, N, Tsai, E, Runz, H, Franke, L, Al-Chalabi, A, Van Damme, P, van den Berg, L, Veldink, J, Ferrarese, C, Neurology, ANS - Neuroinfection & -inflammation, APH - Methodology, APH - Quality of Care, EURO-NMD, Internal Medicine, Epidemiology, Başak, Ayşe Nazlı (ORCID 0000-0001-9257-3540 & YÖK ID 1512), van Rheenen, W., Van der Spek, R.A.A., Bakker, M.K., van Vugt, J.J.F.A., Hop, P.J., Zwamborn, R.A.J., de Klein, N., Westra, H.J., Bakker, O.B., Deelen, P., Shireby, G., Hannon, E., Moisse, M., Baird, D., Restuadi, R., Dolzhenko, E., Dekker, A.M., Gawor, K., Westeneng, H.J., Tazelaar, G.H.P., van Eijk, K.R., Kooyman, M., Byrne, R.P., Doherty, M., Heverin, M., Al Khleifat, A., Iacoangeli, A., Shatunov, A., Ticozzi, N., Cooper-Knock, J., Smith, B.N., Gromicho, M., Chandran, S., Pal, S., Morrison, K.E., Shaw, P.J., Hardy, J., Orrell, R.W., Sendtner, M., Meyer, T., van der Kooi, A.J., Ratti, A., Fogh, I., Gellera, C., Lauria, G., Corti, S., Cereda, C., Sproviero, D., D'Alfonso, S., Sorarù, G., Siciliano, G., Filosto, M., Padovani, A., Chiò, A., Calvo, A., Moglia, C., Brunetti, M., Canosa, A., Grassano, M., Beghi, E., Pupillo, E., Logroscino, G., Nefussy, B., Osmanovic, A., Nordin, A., Lerner, Y., Zabari, M., Gotkine, M., Baloh, R.H., Bell, S., Vourc'h, P., Corcia, P., Couratier, P., Millecamps, S., Meininger, V., Salachas, F., Mora Pardina, J.S., Assialioui, A., Rojas-García, R., Dion, P.A., Ross, J.P., Ludolph, A.C., Weishaupt, J.H., Brenner, D., Freischmidt, A., Bensimon, G., Brice, A., Durr, A., Payan, C.A.M., Saker-Delye, S., Wood, N.W., Topp, S., Rademakers, R., Tittmann, L., Lieb, W., Franke, A., Ripke, S., Kraft, J.,Whiteman, David C., Olsen, Catherine M., Uitterlinden, A.G., Hofman, A., Rietschel, M., Cichon, S., Nothen, M.M., Amouyel, P., Comi, G., Riva, N., Lunetta, C., Gerardi, F., Cotelli, M.S., Rinaldi, F., Chiveri, L., Guaita, M.C., Perrone, P., Ceroni, M., Diamanti, L., Ferrarese, C., Tremolizzo, L., Delodovici, M.L., Bono, G., Manera, U., Vasta, R., Bombaci, A., Casale, F., Fuda, G., Salamone, P., Iazzolino, B., Peotta, L., Cugnasco, P., De Marco, G., Torrieri, M.C., Palumbo, F., Gallone, S., Barberis, M., Sbaiz, L., Gentile, S., Mauro, A., Mazzini, L., De Marchi, F., Corrado, L., Bertolotto, A., Gionco, M., Leotta, D., Odddenino, E., Imperiale, D., Cavallo, R., Pignatta, P., De Mattei, M., Geda, C., Papurello, D.M., Gusmaroli, G., Comi, C., Labate, C., Ruiz, L., Ferrandi, D., Rota, E., Aguggia, M., Di Vito, N., Meineri, P., Ghiglione, P., Launaro, N., Dotta, M., Di Sapio, A., Giardini, G., Tiloca, C., Peverelli, S., Taroni, F., Pensato, V., Castellotti, B., Comi, G.P., Del Bo, R., Gagliardi, S., Raggi, F., Simoncini, C., Lo Gerfo, A., Inghilleri, M., Ferlini, A., Simone, I.L., Passarella, B., Guerra, V., Zoccolella, S., Nozzoli, C., Mundi, C., Leone, M., Zarrelli, M., Tamma, F., Valluzzi, F., Calabrese, G., Boero, G., Rini, A., Traynor, B.J., Singleton, A.B., Neto, M.M., Cauchi, R.J., Ophoff, R.A., Wiedau-Pazos, M., Lomen-Hoerth, C., van Deerlin, V.M., Grosskreutz, J., Roediger, A., Gaur, N., Jork, A., Barthel, T., Theele, E., Ilse, B., Stubendorff, B., Witte, O.W., Steinbach, R., Hubner, C.A., Graff, C., Brylev, L., Fominykh, V., Demeshonok, V., Ataulina, A., Rogelj, B., Koritnik, B., Zidar, J., Ravnik-Glavac, M., Glavac, D., Stevic, Z., Drory, V., Povedano, M., Blair, I.P., Kiernan, M.C., Benyamin, B., Henderson, R.D., Furlong, S., Mathers, S., McCombe, P.A, Needham, M., Ngo, S.T., Nicholson, G.A., Pamphlett, R., Rowe, D.B., Steyn, F.J., Williams, K.L., Mather, K.A., Sachdev, P.S., Henders, A.K., Wallace, L., de Carvalho, M., Pinto, S., Petri, S., Weber, M., Rouleau, G.A., Silani, V., Curtis, C.J., Breen, G., Glass, J.D., Brown, R.H., Landers, J.E., Shaw, C.E., Andersen, P.M., Groen, E.J.N, van Es, M.A., Pasterkamp, R.J., Fan, D.S., Garton, F.C., McRae, A.F., Smith, G.D., Gaunt, T.R., Eberle, M.A., Mill, J., McLaughlin, R.L., Hardiman, O., Kenna, K.P., Wray, N.R., Tsai, E.L., Runz, H., Franke, L., Al-Chalabi, A., Van Damme, P., van den Berg, L.H., Veldink, J.H., Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), and School of Medicine
Subjects: Male, Genetics and heredity, amyotrophic lateral sclerosis, Neurologi, Glutamine, Medizin, Genome-wide association study, Disease, SUSCEPTIBILITY, Genome-wide association studies, DISEASE, Genètica mèdica, 0302 clinical medicine, neurodegenerative disease, genome-wide association study, ALS, gene, autophagy, Risk Factors, amyotrophic lateral sclerosi, RNA-Seq, Amyotrophic lateral sclerosis, disease-modifying therapies, blood [Cholesterol], Genetics, Genetics & Heredity, Neurons, 0303 health sciences, Medical genetics, Neurodegenerative diseases, Genome-wide association, Mendelian randomization, Frontotemporal dementia, Hexanucleotide repeat, Mutant SOD1, Metaanalysis, ALS, Susceptibility, Identification, Brain, Amyotrophic Lateral Sclerosis, Cholesterol, Disease Progression, Female, Humans, Mendelian Randomization Analysis, Microsatellite Repeats, Neurodegenerative Diseases, Quantitative Trait Loci, Genome-Wide Association Study, Mutation, MUTANT SOD1, genetics [Amyotrophic Lateral Sclerosis], medicine.anatomical_structure, Neurology, risk factor, metabolism [Neurons], MENDELIAN RANDOMIZATION, nerve cell, Life Sciences & Biomedicine, quantitative trait locu, Biology, 03 medical and health sciences, Amyotrophic lateral sclerosis -- Diagnosis, blood, ddc:570, medicine, degenerative disease, Motor neuron disease, human, Genomes, GENOME-WIDE ASSOCIATION, gene, Gene, metabolism [Glutamine], METAANALYSIS, 030304 developmental biology, Mendelian randomization analysi, Science & Technology, HEXANUCLEOTIDE REPEAT, meta analysi, IDENTIFICATION, metabolism [Amyotrophic Lateral Sclerosis], FRONTOTEMPORAL DEMENTIA, medicine.disease, metabolism [Brain], genetics [Neurodegenerative Diseases], Expression quantitative trait loci, disease exacerbation, Neuron, gemone, genetic, Vesicle-mediated transport, metabolism, Nervous system -- Degeneration, Esclerosi lateral amiotròfica, 030217 neurology & neurosurgery
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons., Dutch Research Council (NWO); VENI Scheme Grant; VIDI Grant; Prinses Beatrix Spierfonds; Neuromuscular Fellowship Grant; Medical Research Council (MRC); Clinical Infrastructure Award; Epidemiology Unit; Integrative Epidemiology Unit; Canadian Institutes of Health Research; IWT; National Institute on Aging; National Health and Medical Research Council (NHMRC); Enabling Grant; NHMRC/Australian Research Council Strategic Award; NHMRC; NHMRC Centre of Research Excellence Grant; National Health and Medical Research Council of Australia (NHMRC) Research Fellowship; United Kingdom, Medical Research Council; Economic and Social Research Council; European Union (EU); Horizon 2020; European Community's Health Seventh Framework Programme; EuroMOTOR; European Research Council (ERC); Research and Innovation Programme; EScORIAL; ALS Foundation Netherlands; Alzheimer’s Society PhD Studentship; ARSla Funding; Biogen; University of Bristol; Motor Neurone Disease Association (MNDA); NIHR Maudsley Biomedical Research Centre; Dutch Ministry of Education, Culture, and Science; Netherlands Organization for Scientific Research (NWO; BRAINSCAPES); Gravitation Program; ALS Liga België; National Lottery of Belgium; KU Leuven Opening the Future Fund; KU Leuven Funds, “Een Hart voor ALS”, “Laeversfonds voor ALS Onderzoek” and the “Valéry Perrier Race against ALS Fund”; E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders; ALS Liga België; “Live now” Charity Foundation; Moscow ALS palliative Care Service; Canadian Institutes of Health; Research Australia; Ice Bucket Challenge Grant; NIH Intramural Research Programs; FightMND Mid-Career Fellowship; NIHR Senior Investigator; Sheffield NIHR Biomedical Research Centre; Motor Neurone Disease Association; National Institute for Health Research (NIHR) Biomedical Research Centre; Maudsley NHS Foundation Trust; King’s College London; NIHR Senior Investigator Award; Netherlands Organization for Health Research and Development; Vici Scheme; Netherlands Organization for Health Research and Development STRENGTH Project; PPP Allowance
Published: 2021
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25. Beta-Blocker Exposure and Survival in Patients With Transthyretin Amyloid Cardiomyopathy

Author: Inés Gómez-Otero, Raquel Bilbao-Quesada, Carlos González-Juanatey, Eduardo Barge-Caballero, María G. Crespo-Leiro, Eva González-Babarro, Andrea López-López, Alfonso Varela-Román, Mario Gutiérrez-Feijoo, Óscar Díaz-Castro, Manuel López-Pérez, and Gonzalo Barge-Caballero
Subjects: Male, medicine.medical_specialty, medicine.drug_class, Adrenergic beta-Antagonists, Gastroenterology, Interquartile range, Internal medicine, medicine, Humans, Prealbumin, Adverse effect, Beta blocker, Proportional Hazards Models, Heart Failure, Amyloid Neuropathies, Familial, biology, Proportional hazards model, business.industry, Hazard ratio, General Medicine, Middle Aged, medicine.disease, Survival Analysis, Transthyretin, Treatment Outcome, Spain, Case-Control Studies, Heart failure, Disease Progression, Quality of Life, biology.protein, Female, Amyloid cardiomyopathy, business
Abstract: To investigate a potential association between beta-blocker exposure and survival in patients with transthyretin amyloid cardiomyopathy (ATTR-CM).In this real-world prospective registry of 128 consecutive patients with ATTR-CM recruited in 7 institutions in Galicia (Spain), survival of 65 patients who received beta blockers on registry enrollment was compared with that of 63 untreated controls by means of both unweighted Cox regression and Cox regression with inverse probability of treatment weighting. Tolerance to and adverse effects of beta blockers were recorded. Median study follow-up was 520 days.Patients with ATTR-CM who received beta blockers showed statistically significant lower all-cause mortality than untreated controls as evaluated by either unweighted Cox regression (hazard ratio, 0.31; 95% CI, 0.12 to 0.79) or Cox regression with inverse probability of treatment weighting (hazard ratio, 0.18; 95% CI, 0.08 to 0.41; P.001). Several sensitivity analyses confirmed the internal validity of these results. The overall frequency of beta-blocker suspension due to adverse effects was 25% (95% CI, 15.5% to 34.5%).In this real-world, prospective, multi-institutional registry, patients with ATTR-CM who received beta blockers had lower all-cause mortality than untreated controls.
Published: 2022
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26. Heart Rate and Mortality in Patients With Acute Symptomatic Pulmonary Embolism

Author: G. Pellejero, Jose Gutierrez, R. Malý, M. Basaglia, L. Chasco, P. Suchon, R. Le Mao, Laurent Bertoletti, F. Martins, J. Caprini, A. Braester, F. Galeano-Valle, Hanh My Bui, J. Alonso, Y. Sato, G. Vidal, Y. Nishimoto, C. Tolosa, E. Nofuentes-Pérez, A.M. Díaz-Brasero, N. Ait Abdallah, M.D. Adarraga, R. Sánchez-Martínez, L. Font, Raquel López-Reyes, Inna Tzoran, Karine Lacut, J. del Toro, Andris Skride, Ana Jaureguizar, Joseph A. Caprini, C. Amado, R. García de la Garza, A.M. Camon, S. Merla, Luciano López-Jiménez, G. Salgueiro, Sebastian Schellong, Alfonso Muriel, F. Bilora, S. Lainez-Justo, B. Suárez-Rodríguez, Carme Font, F. Beddar Chaib, I. Francisco, C. Jiménez-Alfaro, P. Azcarate-Agüero, Maurizio Ciammaichella, J.A. Porras, N. Vo Hong, F. Martín-Martos, Dominique Farge-Bancel, D. Farge-Bancel, José Luis Lobo, M. Giménez-Suau, E. Grau, F. García-Bragado, Ángeles Blanco-Molina, Carmen Fernández-Capitán, María del Carmen Díaz-Pedroche, C. Grange, Adriana Visonà, L. Guirado, P. Villares, P. López-Miguel, José María Pedrajas, S. Accassat, Beatriz Valero, B. Crichi, Juan J. López-Núñez, Luis Jara-Palomares, G. Sarlon-Bartoli, J. Lima, C. Bortoluzzi, Alicia Lorenzo, C. de Ancos, M.A. Fidalgo, Philippe Debourdeau, Pablo Javier Marchena, C. Rodríguez-Matute, A.I. Farfán-Sedano, José Luis Fernández-Reyes, J.C. Escribano, Juan I. Arcelus, M. Barrón, I. Quere, Remedios Otero, A. De Angelis, P. Morange, Peter Verhamme, G. Kenet, P. Prandoni, Pedro Ruiz-Artacho, C. Siniscalchi, A. Zaicenko, M. Olid-Velilla, C. García-Díaz, B. Barrón-Andrés, T. Sancho, Fernando Uresandi, Javier Trujillo-Santos, A. Muñoz-Blanco, A. Villalobos, A. Dubois-Silva, J. Moisés, J. Osorio, M.I. Mercado, J.M. Suriñach, M.A. Aibar, M.D. Joya, Cihan Ay, J.A. Díaz-Peromingo, H. Bounameaux, Diego Martínez-Urbistondo, Thomas Vanassche, L. Bertoletti, Marijan Bosevski, Farès Moustafa, M. Martín del Pozo, J.F. Sánchez-Muñoz-Torrero, H.M. Bui, Ingrid Pabinger, M.C. Olivares, M. García de Herreros, M.J. Núñez-Fernández, B. Zalunardo, J.F. Varona, Stephan Nopp, Behnood Bikdeli, B. Brandolin, B. Bikdeli, Olga Madridano, Manuel Monreal, M.J. Jaras, Alessandra Bura-Rivière, Abílio Reis, J. Portillo, O. Espitia, J. Catella, Aitor Ballaz, F. Esposito, R. Barba, R. Valle, H. Helfer, I. Tzoran, J.B. López-Sáez, P. Ruiz-Artacho, M.A. García, J. Aibar, C. Gómez-Cuervo, C. Gabara, A. Latorre, J. Ruiz-Ruiz, Benjamin Brenner, S. Fonseca, S. Schellong, Raffaele Pesavento, Barry M. Brenner, Silvia Soler, Paolo Prandoni, Victor F. Tapson, Ana Maestre, Pierpaolo Di Micco, M. Muñoz, J. Criado, D. Jiménez, Antonella Tufano, G. Krstevski, B. Valero, Henri Bounameaux, M.I. Torres, G. Poenou, Isabelle Mahé, Aída Gil-Díaz, A. Asuero, S. Otalora, V. Rosa, L. Vela, E. Imbalzano, C. Vandenbriele, C. Barbagelata, Jana Hirmerova, J. Meireles, David Jiménez, Lucia Mazzolai, L. Hernández-Blasco, M. Bosevski, Gili Kenet, C. Mella, M. Monreal, J.R. Vela, P. Di Micco, Carlos Zamora, K. Flores, P. Demelo-Rodríguez, Radovan Malý, J. Birzulis, J.A. Nieto, J. Castro, M.V. Di Campli, Francis Couturaud, Raquel Barba, Jaureguizar, A., Jimenez, D., Bikdeli, B., Ruiz-Artacho, P., Muriel, A., Tapson, V., Lopez-Reyes, R., Valero, B., Kenet, G., Monreal, M., Prandoni, P., Brenner, B., Farge-Bancel, D., Barba, R., Di Micco, P., Bertoletti, L., Schellong, S., Tzoran, I., Reis, A., Bosevski, M., Bounameaux, H., Maly, R., Verhamme, P., Caprini, J. A., Bui, H. M., Adarraga, M. D., Aibar, J., Aibar, M. A., Alonso, J., Amado, C., Arcelus, J. I., Asuero, A., Azcarate-Aguero, P., Ballaz, A., Barbagelata, C., Barron, M., Barron-Andres, B., Blanco-Molina, A., Beddar Chaib, F., Camon, A. M., Castro, J., Chasco, L., Criado, J., de Ancos, C., del Toro, J., Demelo-Rodriguez, P., Diaz-Brasero, A. M., Diaz-Pedroche, M. C., Diaz-Peromingo, J. A., Di Campli, M. V., Dubois-Silva, A., Escribano, J. C., Esposito, F., Farfan-Sedano, A. I., Fernandez-Capitan, C., Fernandez-Reyes, J. L., Fidalgo, M. A., Flores, K., Font, C., Font, L., Francisco, I., Gabara, C., Galeano-Valle, F., Garcia, M. A., Garcia-Bragado, F., Garcia de Herreros, M., Garcia de la Garza, R., Garcia-Diaz, C., Gil-Diaz, A., Gomez-Cuervo, C., Gimenez-Suau, M., Grau, E., Guirado, L., Gutierrez, J., Hernandez-Blasco, L., Jara-Palomares, L., Jaras, M. J., Jimenez-Alfaro, C., Joya, M. D., Lainez-Justo, S., Latorre, A., Lima, J., Lobo, J. L., Lopez-Jimenez, L., Lopez-Miguel, P., Lopez-Nunez, J. J., Lopez-Saez, J. B., Lorenzo, A., Madridano, O., Maestre, A., Marchena, P. J., Martin del Pozo, M., Martin-Martos, F., Martinez-Urbistondo, D., Mella, C., Mercado, M. I., Moises, J., Munoz, M., Munoz-Blanco, A., Nieto, J. A., Nofuentes-Perez, E., Nunez-Fernandez, M. J., Olid-Velilla, M., Olivares, M. C., Osorio, J., Otalora, S., Otero, R., Pedrajas, J. M., Pellejero, G., Porras, J. A., Portillo, J., Rodriguez-Matute, C., Rosa, V., Ruiz-Ruiz, J., Salgueiro, G., Sanchez-Martinez, R., Sanchez-Munoz-Torrero, J. F., Sancho, T., Soler, S., Suarez-Rodriguez, B., Surinach, J. M., Torres, M. I., Tolosa, C., Trujillo-Santos, J., Uresandi, F., Valle, R., Varona, J. F., Vela, L., Vela, J. R., Vidal, G., Villalobos, A., Villares, P., Zamora, C., Ay, C., Nopp, S., Pabinger, I., Vanassche, T., Vandenbriele, C., Hirmerova, J., Accassat, S., Ait Abdallah, N., Bura-Riviere, A., Catella, J., Couturaud, F., Crichi, B., Debourdeau, P., Espitia, O., Grange, C., Helfer, H., Lacut, K., Le Mao, R., Mahe, I., Morange, P., Moustafa, F., Poenou, G., Sarlon-Bartoli, G., Suchon, P., Quere, I., Braester, A., Basaglia, M., Bilora, F., Bortoluzzi, C., Brandolin, B., Ciammaichella, M., De Angelis, A., Imbalzano, E., Merla, S., Pesavento, R., Siniscalchi, C., Tufano, A., Visona, A., Vo Hong, N., Zalunardo, B., Nishimoto, Y., Sato, Y., Birzulis, J., Skride, A., Zaicenko, A., Fonseca, S., Martins, F., Meireles, J., Krstevski, G., and Mazzolai, L.
Subjects: Male, Registrie, Pulmonary and Respiratory Medicine, medicine.medical_specialty, pulmonary embolism, Critical Care and Intensive Care Medicine, Logistic regression, Heart Rate, Internal medicine, Heart rate, medicine, In patient, Aged, Aged, 80 and over, business.industry, medicine.disease, mortality, Pulmonary embolism, Prospective Studie, Increased risk, Spain, Cardiology, Positive relationship, Female, Cardiology and Cardiovascular Medicine, business, Human
Abstract: Background: The association between heart rate (HR) and pulmonary embolism (PE) outcomes has not been well studied. Furthermore, optimal cutoffs to identify low-risk and intermediate- to high-risk patients are not well known. Research Question: Does an association exist between baseline HR and PE outcome across the continuum of HR values? Study Design and Methods: The current study included 44,331 consecutive nonhypotensive patients with symptomatic PE from the Registro Informatizado de la Enfermedad TromboEmbólica registry between 2001 and 2021. Outcomes included 30-day all-cause and PE-specific mortality. We used hierarchical logistic regression to assess the association between admission HR and outcomes. Results: A positive relationship was found between admission HR and 30-day all-cause and PE-related mortality. Considering an HR of 80 to 99 beats/min as a reference, patients in the higher HR strata showed higher rates of all-cause death (adjusted OR, 1.5 for HR of 100-109 beats/min; adjusted OR, 1.7 for HR of 110-119 beats/min; adjusted OR, 1.9 for HR of 120-139 beats/min; and adjusted OR, 2.4 for HR of ≥ 140 beats/min). Patients in the lower strata of HR showed significantly lower rates of 30-day all-cause mortality compared with the same reference group (adjusted OR, 0.6 for HR of 60-79 beats/min; and adjusted OR, 0.5 for HR of < 60 beats/min). The findings for 30-day PE-related mortality were similar. For identification of low-risk patients, a cutoff value of 80 beats/min (vs 110 beats/min) increased the sensitivity of the simplified Pulmonary Embolism Severity Index (sPESI) from 93.4% to 98.8%. For identification of intermediate- to high-risk patients, a cutoff value of 140 beats/min (vs 110 beats/min) increased the specificity of the Bova score from 93.2% to 98.0%. Interpretation: In nonhypotensive patients with acute symptomatic PE, a high HR portends an increased risk of all-cause and PE-related mortality. Modifying the HR cutoff in the sPESI and the Bova score improves prognostication of patients with PE.
Published: 2022
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27. Polymer-Free Biolimus-Eluting Stents or Polymer-Based Zotarolimus-Eluting Stents for Coronary Bifurcation Lesions

Author: Mauro Chiarito, Federico Landra, Arnaldo Poli, Guglielmo Gallone, Vincenzo Infantino, Grzegorz Smolka, Davide Capodanno, Andrea Rognoni, Franco Fabbiocchi, Fabrizio D'Ascenzo, Alfonso Ielasi, Alaide Chieffo, Gennaro Sardella, Maurizio D'Urbano, Giacomo Boccuzzi, Gaetano M. De Ferrari, Massimo Mancone, Fabrizio Tomai, Giulio G. Stefanini, Arturo Giordano, Maurizio Di Biasi, Carlo Briguori, Maurizio Tespili, and Javier Escaned
Subjects: Male, medicine.medical_specialty, Acute coronary syndrome, Polymers, medicine.medical_treatment, Coronary Artery Disease, 030204 cardiovascular system & hematology, Prosthesis Design, Coronary artery disease, 03 medical and health sciences, Percutaneous Coronary Intervention, 0302 clinical medicine, Internal medicine, medicine, Humans, Zotarolimus, cardiovascular diseases, 030212 general & internal medicine, Myocardial infarction, Sirolimus, business.industry, Infant, Percutaneous coronary intervention, Stent, Drug-Eluting Stents, General Medicine, medicine.disease, Treatment Outcome, Conventional PCI, Cardiology, Female, Stents, Cardiology and Cardiovascular Medicine, business, Mace, medicine.drug
Abstract: Background A polymer-free biolimus-eluting stent (PF-BES) and a zotarolimus-eluting stent (ZES) recently showed similar clinical profiles and appear to be competing options in specific clinical settings of patients undergoing percutaneous coronary intervention (PCI). Whether they perform similarly also in complex procedural settings as coronary bifurcation lesions remains unaddressed. Methods All consecutive patients undergoing coronary bifurcation PCI with PF-BES or the new iteration of the ZES from three large multicenter real-world registries were included. The primary outcome was major adverse cardiovascular events (MACE), a composite of all-cause death, myocardial infarction (MI), target lesion revascularization (TLR) and stent thrombosis (ST). Multiple analyses to adjust for baseline differences were carried out including propensity-score matching, propensity-score stratification and inverse-probability-weighting. Outcomes are reported according to Cox proportional hazard models censored at 400-day follow-up. Results 1169 patients treated with PF-BES (n = 440) or ZES (n = 729) on the main branch of a coronary bifurcation lesion were included (mean age 69 ± 11 years, 75.4% male, 53.8% acute coronary syndrome at presentation, 26.6% left main bifurcation, median dual antiplatelet therapy duration 12 [range 12–12] months). MACE, all-cause death, TLR and ST tended towards non-statistically higher rates with the PF-BES as compared to the ZES. Higher MI and target vessel revascularization occurrence was observed with PF-BES. Conclusions In this large contemporary cohort of patients undergoing coronary bifurcation PCI, the occurrence of MACE was non-statistically different with the use of PF-BES and ZES devices. However, differences favoring the ZES device that may entail clinical relevance were observed. Further studies are needed to confirm these findings and explore whether they remain valid when a short dual antiplatelet therapy is adopted.
Published: 2022
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28. Local Field Potential-Based Programming: A Proof-of-Concept Pilot Study

Author: Han Yan, Sara Breitbart, Darcia Paul, Alfonso Fasano, Andres M. Lozano, Jürgen Germann, Suneil K. Kalia, Carolina Gorodetsky, Peter L. Carlen, Aaron Loh, and George M. Ibrahim
Subjects: Adult, medicine.medical_specialty, Deep brain stimulation, Deep Brain Stimulation, medicine.medical_treatment, Pilot Projects, Local field potential, Globus Pallidus, Physical medicine and rehabilitation, Seizure control, Humans, Medicine, Prospective Studies, Child, Prospective cohort study, Dystonia, business.industry, Parkinson Disease, General Medicine, medicine.disease, Neuromodulation (medicine), Absence seizure, Anesthesiology and Pain Medicine, Neurology, Proof of concept, Neurology (clinical), business
Abstract: Objectives Programming deep brain stimulation (DBS) is still based on a trial-and-error approach, often becoming a time-consuming process for both treating physicians and patients. Several strategies have been proposed to streamline DBS programming, most of which are preliminary and mainly address Parkinson's disease, a condition readily responsive to DBS adjustments. In the present proof-of-principle pilot study, we successfully demonstrate that local field potentials (LFP)-based programming can be an effective approach when used for DBS indications that have a delayed temporal onset of benefit. Materials and methods A recently commercialized implantable pulse generator (IPG) with the capability to non-invasively and chronically stream live and/or record LFPs from DBS electrode after implantation was used to program one pediatric patient with generalized dystonia and an adult with seizures refractory to multiple medications and vagal nerve stimulation. Results The IPG survey function detected a peak in the delta range (1.95 Hz) in the left globus pallidus of first patient. This LFP was detected when recording in the brain area adjacent to contacts 9 and 10 and absent when recording from other areas. The chronic recording of the 1.95 Hz LFP with two sets of stimulation showed a greater power increase with the settings associated with a worsening of dystonia. Broadband LFP home recording of "absence seizure" and "focal/partial seizure" was used in the second patient and reviewer with the IPG "timeline" and "event" functions. The chronic recording of the 2.93 Hz and 8.79 Hz (spit sensing) showed a reduced power with the stimulation setting associated with seizure control. Conclusions The approach presented in this pilot proof-of-concept study may inform and streamline the DBS programming for conditions requiring clinicians and patients to wait weeks before appreciating any clinical benefit. Prospective studies on larger samples of patients are warranted.
Published: 2022
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29. Depression and Pain: Use of Antidepressants

Author: José Luis Cortes-Altamirano, Herlinda Bonilla-Jaime, Tania Molina-Jiménez, Maribel Maetizi Estevez Cabrera, Alfonso Alfaro-Rodríguez, and José Armando Sánchez-Salcedo
Subjects: medicine.medical_specialty, Serotonergic, medicine, Humans, Pharmacology (medical), Serotonin and Noradrenaline Reuptake Inhibitors, Psychiatry, Depression (differential diagnoses), Pharmacology, Depression, business.industry, Chronic pain, General Medicine, medicine.disease, Comorbidity, Antidepressive Agents, Psychiatry and Mental health, Mood, Neurology, Neuropathic pain, Antidepressant, Neurology (clinical), Chronic Pain, business, Reuptake inhibitor, Selective Serotonin Reuptake Inhibitors
Abstract: Background:Emotional disorders are common comorbid affectations that exacerbate the severity and persistence of chronic pain. Specifically, depressive symptoms can lead to an excessive duration and intensity of pain. Clinical and preclinical studies have been focused on the underlying mechanisms of chronic pain and depression comorbidity and the use of antidepressants to reduce pain.Aim:This review provides an overview of the comorbid relationship of chronic pain and depression, the clinical and pre-clinical studies performed on the neurobiological aspects of pain and depression, and the use of antidepressants as analgesics.Method:A systematic search of literature databases was conducted according to pre-defined criteria. The authors independently conducted a focused analysis of the full-text articles.Results:Studies suggest that pain and depression are highly intertwined and may co-exacerbate physical and psychological symptoms. One important biochemical basis for pain and depression focuses on the serotonergic and norepinephrine system, which have been shown to play an important role in this comorbidity. Brain structures that codify pain are also involved in mood. It is evident that using serotonergic and norepinephrine antidepressants are strategies commonly employed to mitigate painConclusion:Literature indicates that pain and depression impact each other and play a prominent role in the development and maintenance of other chronic symptoms. Antidepressants continue to be a major therapeutic tool for managing chronic pain. Tricyclic antidepressants (TCAs) are more effective in reducing pain than Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin- Noradrenaline Reuptake Inhibitors (SNRIs).
Published: 2022
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30. Axial Impairment Following Deep Brain Stimulation in Parkinson’s Disease: A Surgicogenomic Approach

Author: Rajasumi Rajalingam, Ziv Gan-Or, Erfan Ghani Kakhki, Melanie Cohn, Mahdi Ghani, Maryam Naghibzadeh, Ekaterina Rogaeva, Yu-Yan Poon, Taline Naranian, Renato P. Munhoz, Jürgen Germann, Eric Yu, Marta Statucka, Suneil K. Kalia, Maryam Abdollahi, Anthony E. Lang, Alexandre Boutet, Mojgan Hodaie, Gavin J B Elias, Alfonso Fasano, Christine Sato, Naomi P. Visanji, Danielle Moreno, and Andres M. Lozano
Subjects: Oncology, medicine.medical_specialty, Linkage disequilibrium, Levodopa, Deep brain stimulation, Parkinson's disease, Deep Brain Stimulation, medicine.medical_treatment, Disease, Cellular and Molecular Neuroscience, Internal medicine, Humans, Medicine, Trypsin, Genotyping, Allele frequency, Retrospective Studies, business.industry, Parkinson Disease, medicine.disease, Subthalamic nucleus, Treatment Outcome, Neurology (clinical), business, medicine.drug
Abstract: Background: Postoperative outcome following deep brain stimulation (DBS) of the subthalamic nucleus is variable, particularly with respect to axial motor improvement. We hypothesized a genetic underpinning to the response to surgical intervention, termed “surgicogenomics”. Objective: We aimed to identify genetic variants associated with clinical heterogeneity in DBS outcome of Parkinson’s disease (PD) patients that could then be applied clinically to target selection leading to improved surgical outcome. Methods: Retrospective clinical data was extracted from 150 patient’s charts. Each individual was genotyped using the genome-wide NeuroX array tailored to study neurologic diseases. Genetic data were clustered based on surgical outcome assessed by comparing pre- and post-operative scores of levodopa equivalent daily dose and axial impairment at one and five years post-surgery. Allele frequencies were compared between patients with excellent vs. moderate/poor outcomes grouped using a priori defined cut-offs. We analyzed common variants, burden of rare coding variants, and PD polygenic risk score. Results: NeuroX identified 2,917 polymorphic markers at 113 genes mapped to known PD loci. The gene-burden analyses of 202 rare nonsynonymous variants suggested a nominal association of axial impairment with 14 genes (most consistent with CRHR1, IP6K2, and PRSS3). The strongest association with surgical outcome was detected between a reduction in levodopa equivalent daily dose and common variations tagging two linkage disequilibrium blocks with SH3GL2. Conclusion: Once validated in independent populations, our findings may be implemented to improve patient selection for DBS in PD.
Published: 2022
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31. Morphologic and Genomic Characteristics of Breast Cancers Occurring in Individuals with Lynch Syndrome

Author: Jorge S. Reis-Filho, Pamela Drullinsky, Maksym Misyura, Liying Zhang, Vikas Rai, Edaise M da Silva, Britta Weigelt, Jinru Shia, Hong Zhang, Edi Brogi, Joshua Z. Drago, Mark E. Robson, Antonio Marra, Christopher J Schwartz, Pedram Razavi, Hannah Y Wen, Andrea Gazzo, Diana Mandelker, Pier Selenica, Timothy M. D'Alfonso, and Fresia Pareja
Subjects: Oncology, congenital, hereditary, and neonatal diseases and abnormalities, Cancer Research, medicine.medical_specialty, Oncology and Carcinogenesis, Breast Neoplasms, MLH1, DNA Mismatch Repair, Rare Diseases, Breast cancer, Clinical Research, Internal medicine, Breast Cancer, Genetics, medicine, PMS2, Humans, 2.1 Biological and endogenous factors, Genetic Testing, Oncology & Carcinogenesis, Aetiology, Germ-Line Mutation, Retrospective Studies, Cancer, business.industry, Microsatellite instability, medicine.disease, digestive system diseases, Lynch syndrome, Colo-Rectal Cancer, Hereditary Nonpolyposis, MSH6, Good Health and Well Being, MSH2, Female, Microsatellite Instability, Colorectal Neoplasms, MutL Protein Homolog 1, Digestive Diseases, business
Abstract: Purpose: Lynch syndrome is defined by germline pathogenic mutations involving DNA mismatch repair (MMR) genes and linked with the development of MMR-deficient colon and endometrial cancers. Whether breast cancers developing in the context of Lynch syndrome are causally related to MMR deficiency (MMRd), remains controversial. Thus, we explored the morphologic and genomic characteristics of breast cancers occurring in Lynch syndrome individuals. Experimental Design: A retrospective analysis of 20,110 patients with cancer who underwent multigene panel genetic testing was performed to identify individuals with a likely pathogenic/pathogenic germline variant in MLH1, MSH2, MSH6, or PMS2 who developed breast cancers. The histologic characteristics and IHC assessment of breast cancers for MMR proteins and programmed death-ligand 1 (PD-L1) expression were assessed on cases with available materials. DNA samples from paired tumors and blood were sequenced with Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets (≥468 key cancer genes). Microsatellite instability (MSI) status was assessed utilizing MSISensor. Mutational signatures were defined using SigMA. Results: A total of 272 individuals with Lynch syndrome were identified, 13 (5%) of whom had primary breast cancers. The majority of breast cancers (92%) were hormone receptor–positive tumors. Five (42%) of 12 breast cancers displayed loss of MMR proteins by IHC. Four (36%) of 11 breast cancers subjected to tumor-normal sequencing showed dominant MSI mutational signatures, high tumor mutational burden, and indeterminate (27%) or high MSISensor scores (9%). One patient with metastatic MMRd breast cancer received anti-PD1 therapy and achieved a robust and durable response. Conclusions: A subset of breast cancers developing in individuals with Lynch syndrome are etiologically linked to MMRd and may benefit from anti-PD1/PD-L1 immunotherapy.
Published: 2022
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32. Quantifying the Impact of Atrial Fibrillation on Heart Failure–Related Patient-Reported Outcomes in the Utah mEVAL Program

Author: Jason Bensch, Rachel Hess, Benjamin A. Steinberg, James C. Fang, Ann Lyons, Mingyuan Zhang, Peter Wohlfahrt, John A. Spertus, Alfonso Siu, T. Jared Bunch, Jonathan P. Piccini, Tom Greene, and Josef Stehlik
Subjects: medicine.medical_specialty, Article, Primary outcome, Quality of life, Utah, Atrial Fibrillation, medicine, Humans, Sinus rhythm, Patient Reported Outcome Measures, Aged, Heart Failure, business.industry, Stroke Volume, Valine, Atrial fibrillation, Mean age, Middle Aged, medicine.disease, Clinical Practice, Kansas City Cardiomyopathy Questionnaire, Heart failure, Emergency medicine, Quality of Life, Cardiology and Cardiovascular Medicine, business
Abstract: Atrial fibrillation (AF) frequently complicates heart failure (HF), and each is associated with lower overall health-related quality of life. We aimed to quantify the incremental burden of AF on the health-related quality of life of patients with HF in clinical practice.We used data from the Utah mEVAL program to analyze patient-reported outcomes (PROs) among patients with HF with and without AF. The primary outcome was the HF-specific Kansas City Cardiomyopathy Questionnaire, with generic PROs as secondary outcomes. Among 1707 patients with HF, 36% had AF (n = 616). Those with HF and AF were older (mean age 69 years vs 58 years, P.001), more likely to have prior stroke (29% vs 17%, P.001) and ischemic cardiomyopathy (28% vs 23%, P = .01), but had similar ejection fractions (mean 44% each, P = .6). After adjustment, and compared with HF alone, HF with AF was associated with worse Kansas City Cardiomyopathy Questionnaire scores (adjusted mean difference -3.45, 95% confidence interval [CI] -6.24 to -0.65), and worse Patient-Reported Outcomes Measurement Information System physical function scores (adjusted mean difference -1.63, 95% CI -2.59 to -0.67). The difference in visual analog scale general health was borderline (adjusted mean difference -2.01, 95% CI -4.51 to 0.49), and Patient-Reported Outcomes Measurement Information System depression scores were similar (adjusted mean difference 0.54, 95% CI -0.48 to 1.57).AF complicates nearly one-third of HF cases, and patients with HF and AF are substantially older and sicker. After adjustment, AF was independently associated with worse disease-specific and overall health-related quality of life than HF alone. Whether maintaining sinus rhythm can improve the HF-related health status of patients with HF in clinical practice should be explored further.
Published: 2022
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33. Does capsule endoscopy impact clinical management in established Crohn's disease?

Author: Saioa Rubio, Susana Oquiñena, María Rullán, Óscar Nantes, Ignacio Fernandez-Urien, Alfonso Elosua, Elena Macías, Ana Borda, and Cristina Rodríguez
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Patency capsule, Clinical Decision-Making, Disease, Single Center, Capsule Endoscopy, Severity of Illness Index, Gastroenterology, law.invention, Young Adult, Crohn Disease, Capsule endoscopy, law, Internal medicine, Active disease, Humans, Medicine, Mild disease, Aged, Retrospective Studies, Aged, 80 and over, Crohn's disease, Hepatology, business.industry, Disease Management, Middle Aged, medicine.disease, Cohort, Female, business
Abstract: Background Capsule endoscopy (SBCE) has developed a relevant role in patients with established Crohn's Disease (CD). However, evaluation of the impact in clinical management has been scarce. Aims To evaluate therapeutic impact of SBCE in an 11-year real-life cohort of known CD patients. Methods Retrospective single center study including all patients with established CD submitted to SBCE procedure from 01/01/2008 to 31/12/2019. Patency capsule was used in selected patients. Small bowel mucosal inflammation was quantified using Lewis score. Therapeutic impact was defined as a change in CD-related treatment recommended based on SBCE results. Patients were assigned to four groups regarding SBCE indication: staging, flare, post-op and remission. Results From the 432 SBCE performed 87.5% were conclusive. Active disease was present in 63.7 of patients; 41.6% mild inflammation and 21.9% moderate-to-severe activity. A change of management was guided by SBCE in 51.3% of procedures: 199 (46.1%) escalation and 23 (5.3%) de-escalation, with significant changes in all groups. Escalation increased with disease activity: 57.8% in mild and 89.5% in moderate-to-severe disease. De-escalation was conducted in 13.9% procedures with mucosal healing and 1.1% with mild disease. Conclusion SBCE is a useful tool for guiding therapeutic management in CD patients both for treatment escalation and de-escalation.
Published: 2022
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34. Tasas de colectomía en colitis ulcerosa 15 años después del diagnóstico. Datos de la cohorte Navarra 2001-2003

Author: Ana Campillo, Saioa Rubio, Rebeca Irisarri, Ernesto Pérez, Óscar Nantes, Ramón Angós, Alfonso Elosua, Cristina Rodríguez, José Manuel Zozaya, and Carlos Prieto
Subjects: 0301 basic medicine, medicine.medical_specialty, Colectomies, Univariate analysis, Hepatology, Megacolon, business.industry, medicine.medical_treatment, Gastroenterology, Retrospective cohort study, medicine.disease, Ulcerative colitis, 03 medical and health sciences, Ileostomy, 030104 developmental biology, 0302 clinical medicine, Internal medicine, Cohort, medicine, 030211 gastroenterology & hepatology, business, Colectomy
Abstract: INTRODUCTION Knowing the natural history of ulcerative colitis (UC) is essential to understand the course of the disease, assess the impact of different treatment strategies and identify poor prognostic factors. One of the most significant matters in this regard is the need for surgery. OBJECTIVES To analyse the Colectomy Incidence Rate (CIR) from diagnosis to end of follow-up (31/12/2017) and identify predictive factors for colectomy. MATERIAL AND METHODS A retrospective study enrolling patients with a definitive diagnosis (DD) of UC or Unclassified Colitis (UnC) in the 2001-03 Navarra cohort. RESULTS We enrolled 174 patients with a DD of UC (E2 42.8%; E3 26.6%) and 5 patients with a DD of UnC: 44.1% women, median age 39.2 years (range 7-88) and median follow-up 15.7 years. A total of 8 patients underwent surgery (CIR 3 colectomies/103 patient-years: 3 at initial diagnosis (
Published: 2022
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35. MR1-dependent immune surveillance of the skin contributes to pathogenesis and is a photobiological target of UV light therapy in a mouse model of atopic dermatitis

Author: Karmella Naidoo, Aurélie Gestin, Yanyan Li, Ian F. Hermans, Katie Gell, Gavin F. Painter, Andrew J. Marshall, Elizabeth A. Jacobsen, David O’Sullivan, Alfonso J Schmidt, Olivier Gasser, Alissa Cait, Christophe Pellefigues, Katherine Woods, Regan J. Anderson, Johannes U Mayer, and Kef K Prasit
Subjects: UV Light Therapy, biology, business.industry, Histocompatibility Antigens Class I, Immunology, Endogeny, Atopic dermatitis, Inhibitory postsynaptic potential, medicine.disease, Major histocompatibility complex, Mucosal-Associated Invariant T Cells, Dermatitis, Atopic, Blockade, Minor Histocompatibility Antigens, Pathogenesis, Disease Models, Animal, Mice, Eosinophil activation, biology.protein, Animals, Immunology and Allergy, Medicine, Ultraviolet Therapy, business
Abstract: Background: Mucosal-associated invariant T (MAIT) cells are unconventional T cells which recognize microbial metabolites presented by the major histocompatibility complex class I-related molecule MR1. Although MAIT cells have been shown to reside in human and murine skin, their contribution to atopic dermatitis (AD), an inflammatory skin disease associated with barrier dysfunction and microbial translocation, has not yet been determined. Methods: Genetic deletion of MR1 and topical treatment with inhibitory MR1 ligands, which result in the absence and functional inhibition of MAIT cells, respectively, were used to investigate the role of MR1-dependent immune surveillance in a MC903-driven murine model of AD. Results: The absence or inhibition of MR1 arrested AD disease progression through the blockade of both eosinophil activation and recruitment of IL-4- and IL-13-producing cells. In addition, the therapeutic efficacy of phototherapy against MC903-driven AD could be increased with prior application of folate, which photodegrades into the inhibitory MR1 ligand 6-formylpterin. Conclusion: We identified MAIT cells as sentinels and mediators of cutaneous type 2 immunity. Their pathogenic activity can be inhibited by topical application or endogenous generation, via phototherapy, of inhibitory MR1 ligands.
Published: 2023
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36. Inequality of weight status in urban Cuba: 2001–2010

Author: Liang Wang, Peng Jia, Alina Alfonso León, Lanlin Ding, Youfa Wang, Alfonso Sousa-Poza, Peng Nie, and Hong Xue
Subjects: Adult, medicine.medical_specialty, Waist, Inequality, Epidemiology, media_common.quotation_subject, Computer applications to medicine. Medical informatics, R858-859.7, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, 0502 economics and business, medicine, Urban Cuba, Humans, 030212 general & internal medicine, Obesity, 050207 economics, Body mass index, media_common, Decomposition, Gini coefficient, business.industry, Public health, Research, 05 social sciences, Public Health, Environmental and Occupational Health, Cuba, medicine.disease, Confidence interval, Obesity, Abdominal, Waist circumference, Public aspects of medicine, RA1-1270, business, Demography
Abstract: Background Although understanding changes in the body weight distribution and trends in obesity inequality plays a key role in assessing the causes and persistence of obesity, limited research on this topic is available for Cuba. This study thus analyzed changes in body mass index (BMI) and waist circumference (WC) distributions and obesity inequality over a 9-year period among urban Cuban adults. Methods Kolmogorov-Smirnov tests were first applied to the data from the 2001 and 2010 National Survey on Risk Factors and Chronic Diseases to identify a rightward shift in both the BMI and WC distributions over the 2001–2010 period. A Shapley technique decomposed the increase in obesity prevalence into a mean-growth effect and a (re)distributional component. A univariate assessment of obesity inequality was then derived by calculating both the Gini and generalized entropy (GE) measures. Lastly, a GE-based decomposition partitioned overall obesity inequality into within-group and between-group values. Results Despite some relatively pronounced left-skewing, both the BMI and WC distributions exhibited a clear rightward shift to which the increases in general and central obesity can be mostly attributed. According to the Gini coefficients, both general and central obesity inequality increased over the 2001–2010 period, from 0.105 [95% confidence interval (CI) = 0.103–0.106] to 0.110 [95% CI = 0.107–0.112] and from 0.083 [95% CI = 0.082–0.084] to 0.085 [95% CI = 0.084–0.087], respectively. The GE-based decomposition further revealed that both types of inequality were accounted for primarily by within-group inequality (93.3%/89.6% and 87.5%/84.8% in 2001/2010 for general/central obesity, respectively). Conclusions Obesity inequality in urban Cuba worsened over the 2001–2010 time period, with within-group inequality in overall obesity dominant over between-group inequality. In general, the results also imply that the rise in obesity inequality is immune to health care system characteristics.
Published: 2021

37. Handling benign interlobar lymphadenopathy during thoracoscopic lobectomy

Author: Alfonso Fiorelli, Stefano Forte, Giovanni Natale, Wentao Fang, Mario Santini, Fiorelli, Alfonso, Forte, Stefano, Natale, Giovanni, Santini, Mario, and Fang, Wentao
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, lobectomy, Lung Neoplasms, thoracoscopy, Dissection (medical), 03 medical and health sciences, 0302 clinical medicine, Suture (anatomy), medicine.artery, lymphadenopathy, Massive bleeding, Technical Note, medicine, Thoracoscopy, Humans, RC254-282, Aged, Bronchus, medicine.diagnostic_test, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, General Medicine, medicine.disease, Anterior Temporal Lobectomy, Surgery, Lung Neoplasm, Interlobar, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Pulmonary artery, Female, Lymph, business, Human
Abstract: The presence of calcified or inflammatory lymph nodes between the target bronchus and pulmonary artery is a huge challenge when performing thoracoscopic lobectomy as it may frequently result in tearing of the vessel, and massive bleeding. Herein, we describe a simple strategy in which thoracoscopic lobectomy was safely completed in similar cases. After fissure dissection, the target pulmonary artery was exposed by more than two‐thirds of its circumference. A needle was passed across the nodes and the target vessel was closed with a proximal and distal suture. After dissection of lymphadenopathies, the target bronchus was exposed, and stapled. This strategy was applied with success to complete right lower lobectomies for cancer in three patients. No complications occurred during the operation. Only one patient had persistent air leaks that spontaneously ceased 11 days later. Final pathology showed pN0 disease in all cases., Calcified or inflammatory lymph nodes between the target bronchus and pulmonary artery is a huge challenge when performing thoracoscopic lobectomy. Here, we report a strategy to handle this clinical situation. A needle was passed across the nodes and the target vessel was closed with a proximal and distal suture, and then gradually transected with scissors. After dissection of adenopathies, the target bronchus was stapled.
Published: 2021

38. MicroRNAs in amniotic fluid and maternal blood plasma associated with sex determination and early gonad differentiation in cattle

Author: Alfonso Gutiérrez-Adán, Patrick Lonergan, Isabel Gómez-Redondo, Benjamín Planells, José María Sánchez, John A. Browne, Science Foundation Ireland, Ministerio de Ciencia e Innovación (España), European Commission, Fernández Sánchez, José María (0000-0003-3889-2342), Gómez-Redondo, Isabel (0000-0002-9319-7580), Planells, Benjamín (0000-0002-5910-1039), Gutiérrez-Adán, Alfonso (0000-0001-9893-9179), and Lonergan, Pat (0000-0001-9500-057X)
Subjects: Male, 0301 basic medicine, Sex Differentiation, Amniotic fluid, Gonad, Biology, Andrology, Plasma, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, microRNA, medicine, Animals, Amnion, Gonads, Embryo, Cell Biology, General Medicine, AcademicSubjects/SCI01070, Amniotic Fluid, medicine.disease, Sexual dimorphism, MicroRNAs, 030104 developmental biology, Testis determining factor, medicine.anatomical_structure, Reproductive Medicine, AcademicSubjects/MED00773, Female, Cattle, Circulating miRNAs, 030217 neurology & neurosurgery, Research Article
Abstract: We hypothesized that sexually dimorphic differences exist in the expression of miRNAs in amniotic fluid (AF) and maternal blood plasma (MP) in association with the process of sex determination and gonad differentiation in cattle. Amniotic fluid and MP were collected from six pregnant heifers (three carrying a single male and three a single female embryo) following slaughter on Day 39 postinsemination, coinciding with the peak of SRY expression. Samples (six AF and six MP) were profiled using an miRNA Serum/Plasma Focus PCR Panel. Differentially expressed (DE) miRNAs were identified in AF (n = 5) and associated MP (n = 56) of male vs. female embryos (P, Grant Support. Supported by Science Foundation Ireland (13/IA/1983) and grant RTI2018–093548-BI00 from the Spanish Ministry of Science and Innovation. IG-R was supported by a predoctoral fellowship from the Spanish Ministry of Science and Innovation (BES-2016-077794), and BP was supported by a Marie Sklodowska-Curie ITN European Joint Doctorate in Biology and Technology of Reproductive Health (REP-BIOTECH 675526).
Published: 2021
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39. Risk Factors for Intracerebral Hemorrhage in Patients With Atrial Fibrillation on Non–Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention

Author: Panagiotis Halvatsiotis, Giuseppe Reale, Jennifer A. Frontera, Giuseppe Martini, S. Pegoraro, Leonardo Pantoni, Aristeidis H. Katsanos, Piergiorgio Lochner, Daniel Strbian, Giorgia Zepponi, Valentina Saia, Karen L. Furie, Giancarlo Agnelli, Elisa Giorli, Erica Scher, Lina Palaiodimou, Valentina Arnao, Giorgio Silvestrelli, Simona Marcheselli, Letizia Riva, Andrea Zini, Angela Risitano, Tiziana Tassinari, Carlo Emanuele Saggese, Francesco Palmerini, Erika Schirinzi, Michael E. Reznik, Marina Mannino, Jukka Putaala, Maria Kosmidou, Michela Giustozzi, Cesare Porta, Maurizio Paciaroni, Marina Padroni, Loris Poli, Maria Cristina Vedovati, Danilo Toni, Manuel Cappellari, Alessandro Rocco, Alessandro Pezzini, Ashkan Shoamanesh, Stefano Forlivesi, Serena Monaco, Raffaele Ornello, Simona Sacco, Silvia Rosa, Shadi Yaghi, Valeria Terruso, Andrea Alberti, Francesco Corea, Elena Ferrari, Christoph Stretz, Marialuisa Zedde, Monica Acciarresi, Cataldo D'Amore, Kateryna Antonenko, Nemanja Popovic, Francesca Guideri, Evangelos Ntais, Boris Doronin, Luca Masotti, Filippo Angelini, Giovanni Orlandi, Licia Denti, Nicola Mumoli, Sotirios Giannopoulos, Elisabetta Toso, Maria Giulia Mosconi, Paolo Aridon, Aurelia Zauli, Giuseppe Micieli, Azmil H. Abdul-Rahim, Laura Brancaleoni, Marina Diomedi, Elisa Grifoni, Georgios Tsivgoulis, Maurizio Acampa, Michele Venti, Walter Ageno, Pietro Caliandro, Alfonso Ciccone, Isabella Canavero, Laura Franco, George Ntaios, Fabio Bandini, Vera Volodina, Pierluigi Bertora, Dimitrios Sagris, Antonio Baldi, Michele Romoli, Hanne Sallinen, Michelangelo Mancuso, Yuriy Flomin, Rossana Tassi, Valeria Caso, Massimo Del Sette, Enrico Maria Lotti, Antonio Gasparro, Alberto Chiti, Jesse Dawson, Brian Mac Grory, Alberto Rigatelli, Paciaroni, Maurizio, Agnelli, Giancarlo, Giustozzi, Michela, Caso, Valeria, Toso, Elisabetta, Angelini, Filippo, Canavero, Isabella, Micieli, Giuseppe, Antonenko, Kateryna, Rocco, Alessandro, Diomedi, Marina, Katsanos, Aristeidis H, Shoamanesh, Ashkan, Giannopoulos, Sotirio, Ageno, Walter, Pegoraro, Samuela, Putaala, Jukka, Strbian, Daniel, Sallinen, Hanne, Mac Grory, Brian C, Furie, Karen L, Stretz, Christoph, Reznik, Michael E, Alberti, Andrea, Venti, Michele, Mosconi, Maria Giulia, Vedovati, Maria Cristina, Franco, Laura, Zepponi, Giorgia, Romoli, Michele, Zini, Andrea, Brancaleoni, Laura, Riva, Letizia, Silvestrelli, Giorgio, Ciccone, Alfonso, Zedde, Maria Luisa, Giorli, Elisa, Kosmidou, Maria, Ntais, Evangelo, Palaiodimou, Lina, Halvatsiotis, Panagioti, Tassinari, Tiziana, Saia, Valentina, Ornello, Raffaele, Sacco, Simona, Bandini, Fabio, Mancuso, Michelangelo, Orlandi, Giovanni, Ferrari, Elena, Pezzini, Alessandro, Poli, Lori, Cappellari, Manuel, Forlivesi, Stefano, Rigatelli, Alberto, Yaghi, Shadi, Scher, Erica, Frontera, Jennifer A, Masotti, Luca, Grifoni, Elisa, Caliandro, Pietro, Zauli, Aurelia, Reale, Giuseppe, Marcheselli, Simona, Gasparro, Antonio, Terruso, Valeria, Arnao, Valentina, Aridon, Paolo, Abdul-Rahim, Azmil H, Dawson, Jesse, Saggese, Carlo Emanuele, Palmerini, Francesco, Doronin, Bori, Volodina, Vera, Toni, Danilo, Risitano, Angela, Schirinzi, Erika, Del Sette, Massimo, Lochner, Piergiorgio, Monaco, Serena, Mannino, Marina, Tassi, Rossana, Guideri, Francesca, Acampa, Maurizio, Martini, Giuseppe, Lotti, Enrico Maria, Padroni, Marina, Pantoni, Leonardo, Rosa, Silvia, Bertora, Pierluigi, Ntaios, George, Sagris, Dimitrio, Baldi, Antonio, D'Amore, Cataldo, Mumoli, Nicola, Porta, Cesare, Denti, Licia, Chiti, Alberto, Corea, Francesco, Acciarresi, Monica, Flomin, Yuriy, Popovic, Nemanja, and Tsivgoulis, Georgios
Subjects: Male, Administration, Oral, 030204 cardiovascular system & hematology, Settore MED/11, 0302 clinical medicine, 80 and over, risk factors, Medicine, atrial fibrillation, Prospective Studies, Aged, 80 and over, cerebral hemorrhage, logistic models, white matter, Aged, Antithrombins, Atrial Fibrillation, Case-Control Studies, Cerebral Hemorrhage, Female, Humans, Middle Aged, Risk Factors, Stroke, Atrial fibrillation, Vitamin K antagonist, 3. Good health, Administration, Settore MED/26 - Neurologia, Cardiology and Cardiovascular Medicine, medicine.drug, Oral, medicine.medical_specialty, medicine.drug_class, Settore MED/26, Lower risk, 03 medical and health sciences, Internal medicine, cardiovascular diseases, logistic model, Advanced and Specialized Nursing, Intracerebral hemorrhage, business.industry, Warfarin, medicine.disease, Clinical trial, Concomitant, Heart failure, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Background and Purpose: Clinical trials on stroke prevention in patients with atrial fibrillation have consistently shown clinical benefit from either warfarin or non–vitamin K antagonist oral anticoagulants (NOACs). NOAC-treated patients have consistently reported to be at lower risk for intracerebral hemorrhage (ICH) than warfarin-treated patients. The aims of this prospective, multicenter, multinational, unmatched, case-control study were (1) to investigate for risk factors that could predict ICH occurring in patients with atrial fibrillation during NOAC treatment and (2) to evaluate the role of CHA 2 DS 2 -VASc and HAS-BLED scores in the same setting. Methods: Cases were consecutive patients with atrial fibrillation who had ICH during NOAC treatment. Controls were consecutive patients with atrial fibrillation who did not have ICH during NOAC treatment. As within the CHA 2 DS 2 -VASc and HAS-BLED scores there are some risk factors in common, several multivariable logistic regression models were performed to identify independent prespecified predictors for ICH events. Results: Four hundred nineteen cases (mean age, 78.8±8.1 years) and 1526 controls (mean age, 76.0±10.3 years) were included in the study. From the different models performed, independent predictors of ICH were increasing age, concomitant use of antiplatelet agents, active malignancy, high risk of fall, hyperlipidemia, low clearance of creatinine, peripheral artery disease, and white matter changes. Low doses of NOACs (given according to label or not) and congestive heart failure were inversely associated with the risk of ICH. HAS-BLED and CHA 2 DS 2 -VASc scores performed poorly in predicting ICH with areas under the curves of 0.496 (95% CI, 0.468–0.525) and 0.530 (95% CI, 0.500–0.560), respectively. Conclusions: Several risk factors were associated to ICH in patients treated with NOACs for stroke prevention but not HAS-BLED and CHA 2 DS 2 -VASc scores.
Published: 2021
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40. Intermittent BRAF inhibition in advanced BRAF mutated melanoma results of a phase II randomized trial

Author: Clara Mayo de las Casas, Maria Gonzalez-Cao, Sebastian Ochenduszko, Juana Oramas, Miguel Angel Molina, Eva Muñoz-Couselo, Ana Arance, Roberto Diaz Beveridge, Miguel A Berciano-Guerrero, Enrique Espinosa, Luis de la Cruz, Delvys Rodriguez, Pablo Cerezuela, Ana Drozdowskyj, L. Bellido, Clara Montagut, Teresa Puertolas, Laura Basterretxea, Jose A. Lopez-Martin, Alfonso Berrocal, Maria-Jose Villanueva, and Begoña Campos
Subjects: Proto-Oncogene Proteins B-raf, Oncology, medicine.medical_specialty, Cancer therapy, Pyridones, Science, General Physics and Astronomy, Antineoplastic Agents, Pyrimidinones, VEMURAFENIB, Article, General Biochemistry, Genetics and Molecular Biology, DOUBLE-BLIND, chemistry.chemical_compound, Piperidines, Internal medicine, Oximes, medicine, Clinical endpoint, Humans, Progression-free survival, MEK INHIBITION, Càncer, Vemurafenib, Melanoma, Protein Kinase Inhibitors, Aged, Cobimetinib, Trametinib, Multidisciplinary, business.industry, Imidazoles, Dabrafenib, General Chemistry, EFFICACY, medicine.disease, Clinical trial, chemistry, Mutation, Azetidines, Melanoma -- Tractament, business, medicine.drug
Abstract: Combination treatment with BRAF (BRAFi) plus MEK inhibitors (MEKi) has demonstrated survival benefit in patients with advanced melanoma harboring activating BRAF mutations. Previous preclinical studies suggested that an intermittent dosing of these drugs could delay the emergence of resistance. Contrary to expectations, the first published phase 2 randomized study comparing continuous versus intermittent schedule of dabrafenib (BRAFi) plus trametinib (MEKi) demonstrated a detrimental effect of the “on−off” schedule. Here we report confirmatory data from the Phase II randomized open-label clinical trial comparing the antitumoral activity of the standard schedule versus an intermittent combination of vemurafenib (BRAFi) plus cobimetinib (MEKi) in advanced BRAF mutant melanoma patients (NCT02583516). The trial did not meet its primary endpoint of progression free survival (PFS) improvement. Our results show that the antitumor activity of the experimental intermittent schedule of vemurafenib plus cobimetinib is not superior to the standard continuous schedule. Detection of BRAF mutation in cell free tumor DNA has prognostic value for survival and its dynamics has an excellent correlation with clinical response, but not with progression. NGS analysis demonstrated de novo mutations in resistant cases., Whether intermittent strategies of delivering drugs can improve cancer patients survival is still unclear. Here, the authors reports the results of a randomized phase II clinical trial aimed to compare the efficacy and safety of two dosing regimens (continuous and intermittent) of vemurafenib and cobimetinib combination as first-line treatment of patients with unresectable or metastatic advanced melanoma with BRAFV600 mutation
Published: 2021

41. The effect of bariatric surgery on ischemic stroke risk

Author: Michael D. Williams, Marc A. Sarran, Philip Omotosho, Syed I. Khalid, Seungjun Kim, Adan Z. Becerra, and Alfonso Torquati
Subjects: medicine.medical_specialty, animal structures, business.industry, Cardiovascular health, Bariatric Surgery, medicine.disease, Logistic regression, Obesity, Obesity, Morbid, Surgery, Sample size determination, Diabetes mellitus, Ischemic stroke, Humans, Medicine, business, Body mass index, Stroke, Ischemic Stroke, Retrospective Studies
Abstract: Background Metabolic and bariatric surgery (MBS) has demonstrated improvements in diabetes and cardiovascular health. The effect of MBS on the risk of ischemic stroke remains unclear. Objectives The goal of this study was to determine the risk of stroke following MBS compared with patients with obesity who qualified for but did not undergo MBS. Setting The Mariner Database, a national claims database. Methods We identified patients with body mass index (BMI) ≥40 or those with a BMI and a qualifying co-morbidity, who underwent MBS between 2010 to 2019. Similar patients who did not undergo MBS served as controls. Coarsened exact matching was performed followed by logistic regression analysis to determine the effect of BMS on stroke risk. Results A total of 70 622 BMS patients and 1 320 182 MBS-eligible controls were identified. After matching, the 1-year stroke risk among MBS patients (n = 56 514) versus controls (n = 56 514) was .6% versus 1.2% (OR .54, 95% CI .47–.61). The 5-year stroke risk for MBS (n = 27619) versus control (n = 27619) was 2.8% versus 3.6% (OR .78, 95% CI .65–.90). Conclusion MBS appears to reduce the risk of stroke following surgery. To our knowledge, this is the largest sample size in a study of ischemic cerebrovascular disease in bariatric surgery.
Published: 2021
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42. Self-expandable transcatheter heart valves for aortic stenosis. Short-term outcome and matched hemodynamic performance

Author: Itziar Gómez Salvador, Hipólito Gutiérrez, Manuel Carrasco-Moraleja, Sandra Santos-Martínez, Silvio Vera, Ignacio J. Amat-Santos, Roman Arnold, Guillermo Galeote, Victor Alfonso Jimenez-Diaz, Carlos Baladrón, José Antonio Baz, J. Alberto San Román, Pablo Catalá, Alfredo Redondo, Luis Nombela-Franco, Raúl Moreno, Tania Rodriguez-Gabella, Mario García-Gómez, Alex F Castro-Mejía, Ana Serrador, and Pilar Jiménez-Quevedo
Subjects: medicine.medical_specialty, medicine.medical_treatment, Population, Hemodynamics, Regurgitation (circulation), 030204 cardiovascular system & hematology, Prosthesis Design, Ventricular Function, Left, Transcatheter Aortic Valve Replacement, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Cardiac skeleton, Embolization, education, Body surface area, education.field_of_study, Ejection fraction, business.industry, Stroke Volume, Aortic Valve Stenosis, General Medicine, medicine.disease, Stenosis, Treatment Outcome, Aortic Valve, Heart Valve Prosthesis, Cardiology, business
Abstract: Introduction and objectives Aortic self-expandable (SE) transcatheter aortic valve implantation (TAVI) devices are particularly useful for patients with aortic stenosis and small/tortuous vessels, small aortic annuli, or low coronary ostia. However, it is unclear whether the growing range of SE devices shows comparable hemodynamic and clinical outcomes. We aimed to determine the differential hemodynamic (residual valve area and regurgitation) and clinical outcomes of these devices in comparable scenarios. Methods All patients were enrolled from 4 institutions and were managed with 4 different SE TAVI devices. Baseline and follow-up clinical data were collected and echocardiographic tests blindly and centrally analyzed. Patients were compared according to valve type and a 1:1 matched comparison was performed according to degree of calcification, aortic annulus dimensions, left ventricular ejection fraction, and body surface area. Results In total, 514 patients were included (Evolut R/PRO, 217; ACURATE neo, 107; ALLEGRA, 102; Portico, 88). Surgical risk scores were comparable in the unmatched population. No differences were observed in the post-TAVI regurgitation rate and in in-hospital mortality (2.7%). The rate of pacemaker implantation at discharge was significantly different among devices (P=.049), with Portico showing the highest rate (23%) and ACURATE neo the lowest (9.5%); Evolut R/PRO and ALLEGRA had rates of 15.9% and 21.2%, respectively. The adjusted comparison showed worse residual TAVI gradients and aortic valve area with ACURATE neo vs ALLEGRA (P=.001) but the latter had higher risk of valve embolization and a tendency for more cerebrovascular events. Conclusions A matched comparison of 4 SE TAVI devices showed no differences regarding residual aortic regurgitation and in-hospital mortality.
Published: 2021
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43. Factors associated with poor prognosis in patients with atrial fibrillation: An emergency department perspective the EMERG-AF study

Author: Amparo Fernández-Simón, Blanca Coll-Vinent, José Ormaetxe, José Ríos, Emerg-Af investigators, Juan Tamargo, Coral Suero, Alfonso Martín, Juan M Sanchez, Carmen Del Arco, Susana Sánchez, Manuel Cancio, Mercedes Varona, and José Carbajosa
Subjects: Male, Poor prognosis, medicine.medical_specialty, Hemorrhage, Risk Factors, Cause of Death, Internal medicine, Atrial Fibrillation, medicine, Humans, In patient, Prospective Studies, Stroke, Aged, Aged, 80 and over, business.industry, Atrial fibrillation, General Medicine, Emergency department, Prognosis, medicine.disease, Cohort, Emergency Medicine, Female, Observational study, Emergency Service, Hospital, business, Major bleeding
Abstract: Objective We sought to identify the factors associated with a worse prognosis in Emergency Department (ED) patients with atrial fibrillation (AF), crucial information to guide management decisions. Methods This is a secondary analysis of a prospective, multicenter, observational cohort of consecutive AF patients attended in 62 EDs in Spain. Clinical variables were collected on enrollment. Follow-up was performed at 30 days and one year. The primary composite outcome was all-cause mortality, major bleeding and/or stroke at one year. Secondary outcomes were each of these components considered separately, plus one-year cardiovascular mortality and the composite outcome at 30 days. Results We analyzed 1107 patients. The primary outcome occurred in 209 patients (18.9%), one-year all-cause mortality in 151 (13.6%), major bleeding in 47 (4.2%), and stroke in 31 (2.8%). Disability (HR 2.064, 95% CI 1.478–2.882), previous known AF (HR 1.829, 95% CI 1.096–3.051), long duration of the AF episode (HR 1.849, 95% CI 1.052–3.252) and renal failure (HR 2.073, 95% CI 1.433–2.999) were independently associated with the primary outcome, whereas anticoagulation at discharge was inversely associated (HR 0.576, 95% CI 0.415–0.801). Disability was associated with mortality, cardiovascular mortality, and the composite at 30 days, and renal failure with mortality and major bleeding. Conclusions Comorbidities like renal failure, long AF duration and disability were related to adverse outcomes and should be decisive to guide management decisions in ED patients with AF. Anticoagulation had a positive impact on prognosis and should be the mainstay of therapy in AF patients attended in ED.
Published: 2021
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44. Uso de la cápsula endoscópica en enfermedad inflamatoria intestinal en práctica clínica en España. Resultados de una encuesta nacional

Author: Yamile Zabana, Alicia López-García, Óscar Nantes Castillejo, Óscar Murcia Pomares, Ignacio Fernández-Urién Sainz, and Alfonso Elosua González
Subjects: Gynecology, medicine.medical_specialty, Hepatology, business.industry, Gastroenterology, medicine.disease, Inflammatory bowel disease, law.invention, Clinical Practice, 03 medical and health sciences, 0302 clinical medicine, Capsule endoscopy, law, 030220 oncology & carcinogenesis, medicine, 030211 gastroenterology & hepatology, business
Abstract: Resumen Introduccion La capsula endoscopica de intestino delgado (CEID) es una tecnica diagnostica poco invasiva cuyo empleo en la enfermedad inflamatoria intestinal (EII) se ha extendido. Se ha desarrollado recientemente una capsula panenterica, PillCamCrohn's (PCC). Carecemos de informacion sobre la disponibilidad y el uso de la CEID y la PCC en nuestro medio. Metodos Realizamos una encuesta electronica y anonima entre los miembros del Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa y la Asociacion Espanola de Gastroenterologia consistente en 37 preguntas de respuesta multiple. Resultados Participaron 150 miembros, la mayoria con dedicacion especial a la EII (69,3%). El 72,8% trabajaban en centros con unidad de EII. El 79% tenian la CEID disponible en su hospital, y el 14% la derivaban a otro centro. El 22% tenian disponible la PCC, y el 9% la derivaban a otro centro. El 79,3% de encuestados con CEID disponible la utilizaban en un pequeno porcentaje de pacientes con EII y el 15,6% en la mayoria. Los escenarios mas frecuentes fueron la sospecha de enfermedad de Crohn (76,3%), la valoracion de actividad inflamatoria (54,7%) y la evaluacion de la extension de la enfermedad (54,7%). Mas de la mitad (59,7%) utilizaban preferentemente la capsula Patency® para valoracion de la permeabilidad intestinal. Casi todos los encuestados (99,3%) consideraban que se deberian implementar recursos formativos en esta tecnica. Conclusiones La CEID cuenta con una amplia disponibilidad en los hospitales espanoles para el manejo de la EII, si bien su uso es todavia limitado. Existe una oportunidad para aumentar la formacion en esta tecnica, y, con ella, su empleo.
Published: 2021
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45. Beneficio del empleo precoz de la oxigenoterapia nasal de alto flujo (ONAF) en pacientes con neumonía por SARS-CoV-2

Author: Alfonso Lluna Carrascosa, Laura García-Pereña, Sara Velasco Fuentes, Violeta Ramos Sesma, María Lucía Tornero Divieso, and Jorge Parra-Ruiz
Subjects: Mechanical ventilation, índice de Kirby, Coronavirus disease 2019 (COVID-19), business.industry, medicine.medical_treatment, COVID-19, neumonía, Retrospective cohort study, General Medicine, medicine.disease, medicine.disease_cause, Article, Pneumonia, Anesthesia, medicine, pneumonia, Intubation, In patient, ONAF, High flow, business, Nasal cannula, Kirby index, HNFC
Abstract: Introducción: La COVID-19 grave se asocia con una neumonía bilateral hipoxemiante que desemboca en la necesidad de ventilación mecánica en un considerable número de pacientes. Hasta la fecha no existen recomendaciones acerca del momento óptimo para el inicio de la ONAF. Pacientes y Métodos: Estudio retrospectivo de todos los pacientes ingresados por neumonía por COVID-19 y que precisaron ONAF entre marzo de 2020 y febrero de 2021. Se agruparon los pacientes en función del momento de inicio de la ONAF de acuerdo con la PaFi modificada. Resultados: Se incluyeron 53 pacientes, en 44 se inició la ONAF precozmente y en 9 de ellos se inició tardíamente. No existieron diferencias clínico-epidemiológicas significativas. La utilización precoz de la ONAF se asoció con una disminución de la necesidad de intubación (29,5% vs 66,6%, p=0,044), de la estancia hospitalaria (18,8 d vs 36 d, p=0,022) y de la mortalidad (22,7% vs 55,5%, p=0,061). Conclusiones: El empleo precoz de la ONAF se asocia con una disminución de la necesidad de intubación, de la mortalidad y de la estancia hospitalaria global.
Published: 2022
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46. Evolution Over Time of Ventilatory Management and Outcome of Patients With Neurologic Disease

Author: Tejerina E. E., Pelosi P., Robba C., Penuelas O., Muriel A., Barrios D., Frutos-Vivar F., Raymondos K., Du B., Thille A. W., Rios F., Gonzalez M., Del-Sorbo L., Marin M. D. C., Valle Pinheiro B., Soares M. A., Nin N., Maggiore S. M., Bersten A., Amin P., Cakar N., Young Suh G., Abroug F., Jibaja M., Matamis D., Ali Zeggwagh A., Sutherasan Y., Anzueto A., Esteban A, Fernando Ríos, Damian Violi, Marisol Rodríguez-Goñi, Roger Lamoglie, Fernando Villarejo, Norberto Tiribelli, Santiago Ilutovich, Matías Brizuela, Mariana Monllau, Fernando Saldarini, Silvina Borello, Alberto Marino, Mauricio Vinzio, Karina Bonasegla, Julián Hernández, María Belén Yapur, María Eugenia González, Sebastián E Mare, Judith Sagardía, Marco Bezzi, Cecilia Pereyra, Julian Strati, Daniel Vargas, Claudia Diaz, Pablo Gómez, Marcelo Palavecino, Graciela Elizabeth, Aguilera García, M Eugenia, Luis Pablo Cardonnet, Lisandro Betttini, Hernán Nuñez, Lucas Vallejo, Fernando Fernández, Jorge Arroyo, Daniel Duarte, Gerardo Filippa, Cayetano Galetti, Hernan Nunia, Fernando Lambert, Elisa Estenssoro, Marina Busico, Javier Horacio Álvarez, Alejandro Raimondi, Gustavo Badariotti, Martín Lugaro, Fernando Lipovestky, Alan Javier Zazu, Hugo Capponcelli, Patricia Vogl, Cristina Orlandi, Alejandro Gómez, Gustavo Jannello, Alejandro Risso, Leticia Rapetti, Guillermo Chiappero, Juan Domingo Fernández, Rodrigo E Gómez-Paz, Marcos Juan Zec, Pascual Valdez, Jorgelina Guyon, Ariel Chena, Sergio Lasdica, Martin Deheza, Schimdt Alejandra, Francisco Criado, Norma Beatriz Márquez, Pablo Desmery, José Luis Scapellato, Gonzalo Javier Ríos, Cristian Casabella, Jasmin Board, Andrew Davies, Andrew Bersten, Elisha Matheson, Amy Waters, John Santamaria, Jennifer Holmes, Cartan Costello, Manoj K Saxena, John Myburgh, Ellen Kinkel, Forbes McGain, Claire Cattigan, Allison Bone, Ian Seppelt, Leonie Weisbrodt, Cheryl Cuzner, Christopher MacIsaac, Deborah Barge, Tania Caf, Cameron Knott, Graeme Duke, Imogen Mitchell, Helen Rodgers, Rachel Whyte, Elisha Fulton, Alistair Nichol, Hergen Buscher, Priya Nair, Claire Reynolds, Simon J G Hockley, Ian Moore, Katherine Davidson, David Milliss, Raju Pusapati, Helen Wong, Jason Fletcher, Julie Smith, Paul Goldrick, Dianne Stephens, Jane Thomas, Anders Aneman, Sutrisno Gunawan, Tom Cowlam, George Lukas, Rick McAllister, Minka Springham, Joanne Sutton, Jeff Presneill, Tony Sutherland, Dianne Hill, Howard Connor, Jenny Dennett, Tim Coles, Freddy Sandy, Sando Chavarria, Marcelo Choque, Ronald Pairumani, Juan Guerra, Marco Antônio Soares Reis, José Carlos Versiani, Eduardo Fonseca Sad, Maria Aparecida Braga, Dinalva Aparecida Gomes, Fernando Antônio Botoni, Maurício Meireles Góes, Frederico Costa Val Barros, Rogério de Castro Pereira, Hugo Urbano, Valéria de Carvalho Magela, Aline Camile Yehia, Bruno Bonaccorsi Fernandino, Marco Antônio Ribeiro Leão, Rovílson Lara, Rubens Altair Amaral de Pádua, Janine Dias Alves, Aloísio Marques do Nascimento, Bruno do Valle Pinheiro, Carlos Alberto Studart Gomes, Marcelo Alcântara Holanda, Frederico Rodrigues Anselmo, Niall Ferguson, Neill Adhikari, Robert Fowler, Cheromi Sittambalam, Mehar-Un-Nisa Raja, Nicole Marinoff, Lauralyn McIntryre, Shawna Reddie, Laura Jones, Irene Watpool, Jeffrey Singh, Madison Dennis, Andrea Matte, Marc Lipkus, Ryan Albert, Andrew Steel, Emily Stern, Michael Miletin, Antonio Raso, Robyn Klages, Jan Friedrich, Orla Smith, Laura Wilson, Deborah Cook, Mark Bailey, Sangeeta Mehta, Stephen Lapinsky, Hannah Mathers, Cheryl Ethier, Stephanie Lubchansky, Samer Haj-Bakri, Dietrich Henzler, Lisa Julien, Luis Soto-Román, Juan Carlos Maurelia, César Antonio Maquilon, Luis Soto-Germani, Bin Du, Yan Kang, Bo Wang, Fachun Zhou, Fang Xu, Haibo Qiu, Yi Yang, Qingyuan Zhan, Bing Sun, Zhenjie Hu, Bin Yu, Xi Zhu, Yu Bai, Gang Li, Yi Li, Geng Zhang, Jianbiao Meng, Xiaobo Huang, Hong Pu, Daxing Yu, Chuanyun Qian, Wei Zhang, Yongjie Yin, Debiao Song, Yunxuan Yue, Zhengxuan Lv, Chengmin Yu, Qunmei Yao, Xue Wang, Yuan Xu, Wei He, Mian Chen, Zhihua Hu, Dongpo Jiang, Jian Huang, Wei Yu, Juanxian Gu, Yangong Chao, Zhixiang Li, Zhicheng Zhang, Wanxia Li, Zhenyang He, Jianguo Li, Chang Liu, Tiehe Qin, Shouhong Wang, Feng Li, Jun Jin, Jianhong Fu, Hongyang Xu, Hongyuan Lin, Jianying Guo, Yalin Liu, Jinghua Wang, Maoqin Li, Jiaqiong Li, Lei Chen, Qing Song, Liang Pan, Xianyao Wan, Jiuzhi Zhang, Weihai Yao, Yuhong Guo, Pang Wing Yan, Kelly Choy, Kwan Ming Chit, Patricia Leung, Chau Chin Man, Marco González, Ricardo Buitrago, Marcela Granados, Guillermo Ortiz, Cesar Enciso, Mario Gómez, Bladimir Alejandro Gil, Juan Pablo Sedano, Luis Fernando Castro Castro, Carlo Alberto Acosta, Marco Gonzalez, Francisco Molina, Camilo Pizarro, Mario Villabon, Carmelo Dueñas, Carlos Andrés Díaz, Nelson Fonseca, Rubén Camargo, Juan David Uribe, Hans-Henrik Bülow, Simona Beniczky, Jens Brushoj, Mikkel Præst, Birgitte Viebaek, Sine Wichman, Anette Mortensen, Susanne Andi Iversen, Bo Broberg, Edgard Luna, Manuel Jibaja, Leonardo Pazmiño, Katty Trelles, Fabricio Picoita, Gustavo Paredes, Vanesa Ramírez, Guillermo Falconí, Cristian Cevallos, Boris Villamagua, Marco Escobar, Freddy Sánchez, Miguel Llano, Miguel Lazcano, Ramiro Puetate, José Miguel Guerrero, Mijail Játiva, Myriam Montalvo, Franklin Villegas, Luis González Zambrano, Ronnie Mantilla, Gina Quinde, Andrea Gimenez, Luis Gonzalez Mosquera, Henry Caballero, María Fernanda García, Marcelo Ochoa, Soraya Puertas, Jackeline Coello, Mario Acosta, Medhat Soliman, Arnaud W Thille, Achille Kouatchet, Alain Mercat, Laurent Brochard, François Collet, Guillaume Marcotte, Pascal Beuret, Jean-Christophe M Richard, Gaëtan Bedunaeu, Pierre-Gildas Guitard, Fabien Soulis, Frédéric Bellec, Philippe Berger, Dorothée Carpentier, Benoit Veber, Salem Ould Zein, Géraldine Dessertaine, C Canevet, Fabien Grelon, Konstantinos Raymondos, Rolf Dembinski, Rolf Rossaint, Steffen Weber-Carstens, Christian Putensen, Maximillian Ragaller, Michael Quintel, Winfried Schubert, Thomas Bein, Heinrich Paulus, Walter Brandt, Lutz Pfeiffer, Silke Frenzel, Thoralf Kerner, P Kruska, Leila Eckholt, Joachim Hartung, Harald Fritz, Monika Holler, Johannes Busch, Andreas Viehöfer, Jens Buettner, Jörn Schlechtweg, Achim Lunkeit, Roland Schneider, Maria Wussow, Nils Marquardt, Christian Frenkel, Falk Hildebrandt, Tumbass Volker, Thomas Lipp, Cezar Mihailescu, Thomas Moellhoff, Thomas Steinke, Oliver Franke, Marcus Ruecker, Markus Schappacher, Steffen Appel, Heinz Kerger, Andreas Schwartz, Jan Dittmann, Jörg Haberkorn, Wolfgang Baier, Walter Seyde, Dimitros Matamis, Eleni Antoniadou, Pertsas Evangelos, Maria Giannakou, Zoltan Szentkereszty, Zsolt Molnar, Pravin Amin, Farhad N Kapadia, Nagarajan Ramakrishnan, Deepak Govil, Anitha Shenoy, Umesh G, Samir Sahu, Sheila Nainan Myatra, Subhash Kumar Todi, Sanjay Dhanuka, Mayur Patel, P Samaddar, Dhruva Chaudhry, Vivek Joshi, Srinivas Samavedam, Ankur Devendra Bhavsar, Prachee Sathe, Sujoy Mukherjee, Salvatore Maurizio Maggiore, Francesco Idone, Federica Antonicelli, Paolo Navalesi, Rosanna Vaschetto, Arianna Boggero, Rosalba Tufano, Michele Iannuzzi, Edoardo De Robertis, Romano Tetamo, Andrea Neville Cracchiolo, Antonio Braschi, Francesco Mojoli, Ilaria 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Jose Angel Baltazar Torres, Gustavo Morales Muñoz, Antonio Villa Delgado, Javier Ladape Martinez, Amine Ali Zeggwagh, Tarek Dendane, Abderrahim Azzouzi, Ahmed Sbihi, Wajdi Maazouzi, Mourad Amor, Charki Haimeur, Michael A Kuiper, Matty Koopmans, Uli Strauch, Dennis Bergmans, Serge Heines, Sylvia den Boer, Bas M Kors, Peter van der Voort, Paul J Dennesen, Bert Beishuizen, Ingrid van den Hul, Erna Alberts, Harry P P M Gelissen, Eduard Bootsma, Auke Reidinga, Kim Heus, Diane Mackle, Paul Young, Rachael Parke, Eileen Gilder, Jodi Brown, Lynette Newby, Catherine Simmonds, Jan Mehrtens, Seton Henderson, Tony Williams, Judi Tai, Chantal Hogan, Mary La Pine, John Durning, Sheree Gare, Troy Browne, Shirley Nelson, Jennifer Goodson, Julio Osorio, Chabu Coronado, Rollin Roldán Mori, Rosa Luz López Martínez, Adam Mikstacki, Barbara Tamowicz, Rui Moreno, Eduardo Almeida, Joana Silvestre, Heloisa Castro, Irene Aragão, Susana Alves Ferreira, Nelson Barros, Filomena Faria, Carlos André Correia Casado, Fausto Fialho Moura, Paulo Marcal, Ricardo Matos, Edward Nicolayenko, Mikhail Kirov, Andrey Yaroshetskiy, Andrei Piontek, Valery Subbotin, Yaseen Arabi, Olivia Dulfo, Chafrina Marie Olay, Edgardo E Tabhan, Nicolas Nin, Alfonso Muñoz, César Aragón, Ana Villagrá, Ainhoa Rosselló, Joan Maria Raurich, María Garitacelaya, Miguel Ángel González-Gallego, Francisco Ortuño, Miguel Fernández-Vivas, David Freire, Francisco Guerrero, Francisco Manzano, Juan Carlos, Alfredo Padrón, Pedro Rosa, Rafael Morales, Liliana Caipe, Maurizio Bottiroli, José María Nicolás, Marta Ugalde, Javier Ruiz, Lucia Capilla, Guillermo Muñiz, Jesús Sánchez-Ruiz, Javier Cebrián, Begoña Balerdi, Elena Parreño, Alvaro van Bommel, César Pérez-Calvo, Irene Dot, Javier Blanco, Raquel Manzanedo, José J Blanco, Daniel Fontaneda, Raúl González, Javier Díaz Domínguez, Alfonso Moreno, Antonio Reyes, Ian Carrasco, Itziar Mintegui, Rosa Sebastián, Javier García-Alonso, Carolina Lorencio, Josep Maria Sirvent, Patricia Jimeno, Miguel León, Pedro Galdos, Nuria Alonso, Julia López-Díaz, María Victoria de la Torre, Jorge Vidal Hernández, Nicolás Zamboschi, Francisco Lucena, Gemma Rialp, Raquel Montoiro, Victoria Goñi, María Ángeles Pena, Antonio Maestre, Marc Fabra, Jacinto Baena, Eva Benveniste, Susana Temprano, Jesús Sánchez, Carmen Campos, Sara Cabañes, María Elena Pérez-Losada, José Claudio Leo, Enrique Piacentini, María Del Carmen de la Torre, Laura Álvarez-Montero, Fernando Sánchez, Antonio Viñuales, Bernabé Álvarez, Javier Castañeda, Ángela Alonso, María Isabel Ruiz, Pedro Jesús Domínguez, Marcos Delgado, Eugenio Palazón, Antonio García-Jiménez, Rosa Álvaro, Clara Laplaza Eva Regidor, Enrique Maraví, José María Quiroga, Amalia Martínez de la Gandara, Cecilia Carbayo, María Luisa Navarrete, Manuel Valledor, Raquel Yano, José María Gutiérrez, Javier González-Robledo, Amparo Ferrandiz, Alberto Belenguer, Lidón Mateu, Laura Sayagues, María José Tolón, Nieves Franco, Elena Gallego, Félix Lacoma, Patricia Albert, 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Yao, Yuhong Guo, Pang Wing Yan, Kelly Choy, Kwan Ming Chit, Patricia Leung, Chau Chin Man, Marco González, Ricardo Buitrago, Marcela Granados, Guillermo Ortiz, Cesar Enciso, Mario Gómez, Bladimir Alejandro Gil, Juan Pablo Sedano, Luis Fernando Castro Castro, Carlo Alberto Acosta, Marco Gonzalez, Francisco Molina, Camilo Pizarro, Mario Villabon, Carmelo Dueñas, Carlos Andrés Díaz, Nelson Fonseca, Rubén Camargo, Juan David Uribe, Hans-Henrik Bülow, Simona Beniczky, Jens Brushoj, Mikkel Præst, Birgitte Viebaek, Sine Wichman, Anette Mortensen, Susanne Andi Iversen, Bo Broberg, Edgard Luna, Manuel Jibaja, Leonardo Pazmiño, Katty Trelles, Fabricio Picoita, Gustavo Paredes, Vanesa Ramírez, Guillermo Falconí, Cristian Cevallos, Boris Villamagua, Marco Escobar, Freddy Sánchez, Miguel Llano, Miguel Lazcano, Ramiro Puetate, José Miguel Guerrero, Mijail Játiva, Myriam Montalvo, Franklin Villegas, Luis González Zambrano, Ronnie Mantilla, Gina Quinde, Andrea Gimenez, Luis Gonzalez Mosquera, Henry Caballero, María Fernanda García, Marcelo Ochoa, Soraya Puertas, Jackeline Coello, Mario Acosta, Medhat Soliman, Arnaud W Thille, Achille Kouatchet, Alain Mercat, Laurent Brochard, François Collet, Guillaume Marcotte, Pascal Beuret, Jean-Christophe M Richard, Gaëtan Bedunaeu, Pierre-Gildas Guitard, Fabien Soulis, Frédéric Bellec, Philippe Berger, Dorothée Carpentier, Benoit Veber, Salem Ould Zein, Géraldine Dessertaine, C Canevet, Fabien Grelon, Konstantinos Raymondos, Rolf Dembinski, Rolf Rossaint, Steffen Weber-Carstens, Christian Putensen, Maximillian Ragaller, Michael Quintel, Winfried Schubert, Thomas Bein, Heinrich Paulus, Walter Brandt, Lutz Pfeiffer, Silke Frenzel, Thoralf Kerner, P Kruska, Leila Eckholt, Joachim Hartung, Harald Fritz, Monika Holler, Johannes Busch, Andreas Viehöfer, Jens Buettner, Jörn Schlechtweg, Achim Lunkeit, Roland Schneider, Maria Wussow, Nils Marquardt, Christian Frenkel, Falk Hildebrandt, Tumbass Volker, Thomas Lipp, Cezar Mihailescu, Thomas Moellhoff, Thomas Steinke, Oliver Franke, Marcus Ruecker, Markus Schappacher, Steffen Appel, Heinz Kerger, Andreas Schwartz, Jan Dittmann, Jörg Haberkorn, Wolfgang Baier, Walter Seyde, Dimitros Matamis, Eleni Antoniadou, Pertsas Evangelos, Maria Giannakou, Zoltan Szentkereszty, Zsolt Molnar, Pravin Amin, Farhad N Kapadia, Nagarajan Ramakrishnan, Deepak Govil, Anitha Shenoy, Umesh G, Samir Sahu, Sheila Nainan Myatra, Subhash Kumar Todi, Sanjay Dhanuka, Mayur Patel, P Samaddar, Dhruva Chaudhry, Vivek Joshi, Srinivas Samavedam, Ankur Devendra Bhavsar, Prachee Sathe, Sujoy Mukherjee, Salvatore Maurizio Maggiore, Francesco Idone, Federica Antonicelli, Paolo Navalesi, Rosanna Vaschetto, Arianna Boggero, Rosalba Tufano, Michele Iannuzzi, Edoardo De Robertis, Romano Tetamo, Andrea Neville Cracchiolo, Antonio Braschi, Francesco Mojoli, Ilaria Curro', Mirko Belliato, Chiara Verga, Marta Ferrari, Erika Mannelli, Valerio Mangani, Giorgio Tulli, Francesca Frigieri, Armando Pedulla', Monica Rocco, Giorgia Citterio, Di Russo, Gaetano Perchiazzi, Loredana Pitagora, Antonio Pesenti, Michela Bombino, Davide Chiumello, Federica Tallarini, Serena Azzari, Antonina Pigna, Ivano Aprile, Marco Adversi, Antonio Corcione, Marianna Esposito, Annunziata Mattei, Vito Marco Ranieri, Rosario Urbino, Ilaria Maria Mastromauro, Antonino Giarratano, Maurizio Raineri Santi, Ambrogio Sansone, Younsuck Koh, Moo Suk Park, Je Hyeong Kim, Kyung Chan Kim, Hye Sook Choi, Yun Seong Kim, Jin Hwa Lee, Myung-Goo Lee, Won-Yeon Lee, Jin Young An, Gee Young Suh, Ki-Suck Jung, Asisclo J Villagómez Ortiz, César Cruz Lozano, Zalatiel Maycotte Luna, José Francisco López Baca, José Elizalde, Guillermo Cueto Robledo, Mario Alonso Treviño Salinas, Ricardo Martinez Zubieta, Claudia Olvera-Guzman, Marco Montes De Oca, Silvio A Ñamendys-Silva, José Salvador Martínez Cano, Jose Angel Baltazar Torres, Gustavo Morales Muñoz, Antonio Villa Delgado, Javier Ladape Martinez, Amine Ali Zeggwagh, Tarek Dendane, Abderrahim Azzouzi, Ahmed Sbihi, Wajdi Maazouzi, Mourad Amor, Charki Haimeur, Michael A Kuiper, Matty Koopmans, Uli Strauch, Dennis Bergmans, Serge Heines, Sylvia den Boer, Bas M Kors, Peter van der Voort, Paul J Dennesen, Bert Beishuizen, Ingrid van den Hul, Erna Alberts, Harry P P M Gelissen, Eduard Bootsma, Auke Reidinga, Jasmin Board, Andrew Davies, Kim Heus, Diane Mackle, Paul Young, Rachael Parke, Eileen Gilder, Jodi Brown, Lynette Newby, Catherine Simmonds, Jan Mehrtens, Seton Henderson, Tony Williams, Judi Tai, Chantal Hogan, Mary La Pine, John Durning, Sheree Gare, Troy Browne, Shirley Nelson, Jennifer Goodson, Julio Osorio, Chabu Coronado, Rollin Roldán Mori, Rosa Luz López Martínez, Adam Mikstacki, Barbara Tamowicz, Rui Moreno, Eduardo Almeida, Joana Silvestre, Heloisa Castro, Irene Aragão, Susana Alves Ferreira, Nelson Barros, Filomena Faria, Carlos André Correia Casado, Fausto Fialho Moura, Paulo Marcal, Ricardo Matos, Edward Nicolayenko, Mikhail Kirov, Andrey Yaroshetskiy, Andrei Piontek, Valery Subbotin, Yaseen Arabi, Olivia Dulfo, Chafrina Marie Olay, Edgardo E Tabhan, Nicolas Nin, Alfonso Muñoz, César Aragón, Ana Villagrá, Ainhoa Rosselló, Joan Maria Raurich, María Garitacelaya, Miguel Ángel González-Gallego, Francisco Ortuño, Miguel Fernández-Vivas, David Freire, Francisco Guerrero, Francisco Manzano, Juan Carlos, Alfredo Padrón, Pedro Rosa, Rafael Morales, Liliana Caipe, Maurizio Bottiroli, José María Nicolás, Marta Ugalde, Javier Ruiz, Lucia Capilla, Guillermo Muñiz, Jesús Sánchez-Ruiz, Javier Cebrián, Begoña Balerdi, Elena Parreño, Alvaro van Bommel, César Pérez-Calvo, Irene Dot, Javier Blanco, Raquel Manzanedo, José J Blanco, Daniel Fontaneda, Raúl González, Javier Díaz Domínguez, Alfonso Moreno, Antonio Reyes, Ian Carrasco, Itziar Mintegui, Rosa Sebastián, Javier García-Alonso, Carolina Lorencio, Josep Maria Sirvent, Patricia Jimeno, Miguel León, Pedro Galdos, Nuria Alonso, Julia López-Díaz, María Victoria de la Torre, Jorge Vidal Hernández, Nicolás Zamboschi, Francisco Lucena, Gemma Rialp, Raquel Montoiro, Victoria Goñi, María Ángeles Pena, Antonio Maestre, Marc Fabra, Jacinto Baena, Eva Benveniste, Susana Temprano, Jesús Sánchez, Carmen Campos, Sara Cabañes, María Elena Pérez-Losada, José Claudio Leo, Enrique Piacentini, María Del Carmen de la Torre, Laura Álvarez-Montero, Fernando Sánchez, Antonio Viñuales, Bernabé Álvarez, Javier Castañeda, Ángela Alonso, María Isabel Ruiz, Pedro Jesús Domínguez, Marcos Delgado, Eugenio Palazón, Antonio García-Jiménez, Rosa Álvaro, Clara Laplaza Eva Regidor, Enrique Maraví, José María Quiroga, Amalia Martínez de la Gandara, Cecilia Carbayo, María Luisa Navarrete, Manuel Valledor, Raquel Yano, José María Gutiérrez, Javier González-Robledo, Amparo Ferrandiz, Alberto Belenguer, Lidón Mateu, Laura Sayagues, María José Tolón, Nieves Franco, Elena Gallego, Félix Lacoma, Patricia Albert, Vicente Arraez, Mar Gobernado, Susana Moradillo, Carolina Gímenez-Esparza, Teresa Sánchez de Dios, Carlos Marian Crespo, Cecilia Hermosa, Federico Gordo, Genis Carrasco, María Ángeles Alonso, Alejandro Algora, Raúl de Pablo, Sofía García, Ana Carolina Caballero, José María Montón, Teresa Mut, Eva Manteiga, Alejandro de la Serna, Ana Esther Trujillo, Rafael Blancas, Inmaculada Vallverdú, José Manuel Serrano, Miquel Ferrer, Juan Diego Jiménez, Carlos Gallego, Dolores Vila, Luis Marina, Valentín Parra, Juan Ramón Cortés, Chen Chin-Ming, Ai-Chin Cheng, Fekri Abroug, Besbes Mohamed, Imed Chouchene, Mounir Bouaziz, Stambouli Neji, Islem Ouanes, Ayed Samia, Nahit Cakar, Ismail Kati, Ali Aydım Altunkan, Remzi Iscimen, Zafer Dogan, Bilge Çetin, Tayfun Adanir, Sabriye Guvenc, Unase Büyükkoçak, Antonio Anzueto, Ashley Ellis, Gary Kinasewitz, Allan Walkey, Phil Alkana, Gregory A Schmidt, Susan Gillen, Kathleen Lilli, Jennifer Twombley, Denice Wells, Larry Welder, Alejandro Arroliga, Alfredo Vasquez-Sandoval, Vincent John Scott, Craig Cernosek, Christopher Spradley, Dimple Tejwani, Sindhaghatta Venkatram, Gilda Diaz-Fuentes, Amber Monson, Anthony Saleh, Madhav Gudi, George Liziamma, Mohamed A Saad, Crissie De Spirito, Bryan Beatty, Samir Vermani, Crissie Despirito, Zaza Cohen, Amee Patrawalla, Samir Abdelhadi, Rupesh Vakil, Steven Y Chang, Brian Sherman, Rosanna Del Giudice, John Oropell, Timothy D Girard, Cayce Strength, Joyce Okahashi, Leanne Boehm, Matthew Kirchner, Ashley Ellis, Gary Kinasewitz, Erwin J Oei, Sebastian Circo, Nelson Medina, Mohammed Al-Jagbeer, V J Cardenas Jr, Smyth Smith, Shelby Sutton, Marcela Canola-Mazo, Tim Houlihan, Yogeet Kaur, Travis Parry, Craig A Piquette, Kerry Canady, Rahul Nanchal, Dana K Soetaert, Maria Del Mar Torres-Perez, Carlos Robles-Arias, William Rodriguez-Cintron, Mark Tidswell, Jennifer Germain, Lori-Ann Kozikowski, Erin Braden, Geneva Tatem, Javier Hurtado, Alberto Deicas, Daniel Weiss, Marta Beron, Román Garrido, Cristina Santos, Mario Cancela, Raúl Lombardi, Pedro Alzugaray, Jorge Gerez, Silvia Mareque, Graciela Franca, Oscar Cluzet, Edgardo Nuñez, Julio Pontet, Sergio Cáceres, Elias Caragna, Alberto Soler, Frank Torres, Gastón Pittini, Gabriel D Empaire, Stevens Salva, Fernando Pérez, Clara Pacheco, Zoraida Parra, Ingrid Von der Osten, Luis Williams, José Salinas, Do Danh Quynh, Pham Thi Van Anh, Nguyen Huu Hoang, Nghuyen Ba Tuan
Subjects: Male, medicine.medical_treatment, pulmonary complications, RESPIRATORY-DISTRESS-SYNDROME, Critical Care and Intensive Care Medicine, CASE-FATALITY, 0302 clinical medicine, Risk Factors, Brain Injuries, Traumatic, Multicenter Studies as Topic, Hospital Mortality, Prospective Studies, Simplified Acute Physiology Score, Stroke, POPULATION, Age Factors, ANEURYSMAL SUBARACHNOID HEMORRHAGE, Middle Aged, Hemorrhagic Stroke, Intensive Care Units, Observational Studies as Topic, Anesthesia, Breathing, Female, medicine.symptom, Ventilator Weaning, Cohort study, Adult, TRAUMATIC BRAIN-INJURY, Pressure support ventilation, mechanical ventilation, prognosis factors, ACUTE LUNG INJURY, 03 medical and health sciences, medicine, Humans, Aged, Ischemic Stroke, Mechanical ventilation, Noninvasive Ventilation, business.industry, MORTALITY, neurologic patients, Organ dysfunction, 030208 emergency & critical care medicine, Length of Stay, medicine.disease, TRENDS, Respiration, Artificial, 030228 respiratory system, Etiology, NEUROCRITICAL CARE, Nervous System Diseases, Tracheotomy, business
Abstract: OBJECTIVES: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality. DESIGN: Secondary analysis of three prospective, observational, multicenter studies. SETTING: Cohort studies conducted in 2004, 2010, and 2016. PATIENTS: Adult patients who received mechanical ventilation for more than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p < 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p < 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p < 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma. CONCLUSIONS: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease.
Published: 2021
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47. Outcome of acute hypoxaemic respiratory failure: insights from the LUNG SAFE Study

Author: Pham, Tài, Pesenti, Antonio, Bellani, Giacomo, Rubenfeld, Gordon, Fan, Eddy, Bugedo, Guillermo, Lorente, José Angel, Fernandes, Antero do Vale, Van Haren, Frank, Bruhn, Alejandro, Rios, Fernando, Esteban, Andres, Gattinoni, Luciano, Larsson, Anders, McAuley, Daniel F., Ranieri, Marco, Thompson, B. Taylor, Wrigge, Hermann, Brochard, Laurent J., Laffey, John G, Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, Giacomo Bellani, Tài Pham, Eddy Fan, Fernando Rios, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Lise Piquilloud, Fekri Abroug, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E McKenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Joris Vermassen, Philippe Meersseman, Helga Ceunen, Jonas I Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, Marlus M Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Ahmad Yazid Bin Hj Abul Wahab, Maizatul Ismail, Suresh Shindhe, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, Shou H Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E SolisQuesada, Christian M Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Boris G Villamagua, Iguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Siu-Ming Au, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, Francesco L Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, PierreLouis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, Daniele M Combaux, Fabien Grelon, Charlene Le Moal, Elise P Sauvadet, Adrien 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Silvio A Ñamendys-Silva, Yves D Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, Asisclo J Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Alejandro Rojas, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama, Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra Rinia, Monique Raaijmakers, Hellen M van Wezel, Serge J Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin McArthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, Danielle J Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas 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Jovanovic, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, Juan C Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, Guillermo M Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, Antonio L RuizAguilar, Luis M Claraco-Vega, Juan Alfonso Soler, Maria Del Carmen Lorente, Cecilia Hermosa, Federico Gordo, Miryam PrietoGonzález, Juan B López-Messa, Manuel P Perez, Cesar P Perez, Raquel Montoiro Allue, Ferran RocheCampo, Marcos Ibañez-Santacruz, Susana TempranoSusana, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel González, Dácil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, Antonio G Jimenez, Francisco P Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, Corcoles G Virgilio, Noelia N Recio, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin 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Angel, Fernandes, Antero do Vale, Van Haren, Frank, Bruhn, Alejandro, Rios, Fernando, Esteban, Andre, Gattinoni, Luciano, Larsson, Ander, McAuley, Daniel F., Ranieri, Marco, Thompson, B. Taylor, Wrigge, Hermann, Brochard, Laurent J., Laffey, John G, Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, John G Laffey, Giacomo Bellani, Tài Pham, Eddy Fan, Fernando Rios, Frank van Haren, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Eddy Fan, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Tài Pham, Hermann Wrigge, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Giacomo Bellani, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Anders Larsson, Lise Piquilloud, Fekri Abroug, Daniel F McAuley, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E McKenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Pieter Depuydt, Joris Vermassen, Philippe Meersseman, Helga Ceunen, Jonas I Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, Marlus M Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Ahmad Yazid Bin Hj Abul Wahab, Maizatul Ismail, Suresh Shindhe, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Haibo Qiu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, Shou H Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E SolisQuesada, Christian M Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Jonas Nielsen, Boris G 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C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Lise Piquilloud, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Lia McNamee, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R Jha, Matthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla Oneill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Javier Hurtado, Nicolás Nin, Javier Hurtado, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz MesarJarone Lee, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Daniel R Crouch, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Dina Gomaa, Rebecca M Baro, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, Intensive Care Medicine, ACS - Diabetes & metabolism, ACS - Pulmonary hypertension & thrombosis, ACS - Microcirculation, Pham, T, Pesenti, A, Bellani, G, Rubenfeld, G, Fan, E, Bugedo, G, Lorente, J, Fernandes, A, Van Haren, F, Bruhn, A, Rios, F, Esteban, A, Gattinoni, L, Larsson, A, Mcauley, D, Ranieri, M, Thompson, B, Wrigge, H, Brochard, L, Laffey, J, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), St. Michael's Hospital, University of Toronto, Groupe de recherche clinique CARMAS, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano [Milano] (UNIMI), University of Milan, San Gerardo Hospital, Sunnybrook Health Sciences Center, Mount Sinai Hospital [Toronto, Canada] (MSH), Pontificia Universidad Católica de Chile (UC), University Hospital of Getafe, CIBER Enfermedades Respiratorias (CIBERES), Universidad Europea de Madrid, Hospital Garcia de Orta (EPE), Canberra Hospital, Medical School [Australian National University - ANU], Australian National University (ANU), University of Canberra, Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), University of Göttingen - Georg-August-Universität Göttingen, Uppsala University, Queen's University [Belfast] (QUB), Royal Victoria Hospital, McGill University Health Center [Montreal] (MUHC), Università degli Studi di Bologna, Massachusetts General Hospital [Boston], University Hospital Leipzig, Department of Anaesthesiology, Intensive Care and Emergency Medicine, Pain Therapy, Bergmannstrost Hospital Halle, 06112, Halle, National University of Ireland [Galway] (NUI Galway), Bayer GlaxoSmithKline, GSK Baxter International Boehringer Ingelheim Wellcome Trust, WT National Institute for Health Research, NIHR Queen's University Belfast, QUB Medical Research Council Canada, MRC European Society of Intensive Care Medicine, ESICM, Support statement: This work was supported by the European Society of Intensive Care Medicine. Funding information for this article has been deposited with the Crossref Funder Registry., Conflict of interest: T. Pham has nothing to disclose. A. Pesenti reports personal fees from Maquet, Novalung/Xenios, Baxter, Gilead and Boehringer Ingelheim, outside the submitted work. G. Bellani reports grants and personal fees from Draeger Medical, personal fees from Getinge, Hamilton, GE Healthcare, Dimar SRL, Intersurgical and Flowmeter SPA, outside the submitted work. G. Rubenfeld has nothing to disclose. E. Fan reports personal fees from ALung Technologies, Getinge and MC3 Cardiopulmonary, grants, personal fees and non-financial support from Fresenius Medical Care, outside the submitted work. G. Bugedo has nothing to disclose. J.A. Lorente has nothing to disclose. A.D. V. Fernandes has nothing to disclose. F. Van Haren has nothing to disclose. A. Bruhn has nothing to disclose. F. Rios has nothing to disclose. A. Esteban has nothing to disclose. L. Gattinoni has nothing to disclose. A. Larsson reports grants from the Swedish Heart and Lung Foundation, during the conduct of the study. D.F. McAuley reports personal fees from consultancy for GlaxoSmithKline, Boehringer Ingelheim and Bayer, outside the submitted work, in addition, his institution has received funds from grants from the UK NIHR, Wellcome Trust, Innovate UK, NI HSC R&D Division, NI Chest Heart and Stroke, and MRC, is one of four named inventors on a patent US8962032 covering the use of sialic acid-bearing nanoparticles as anti-inflammatory agents issued to his institution, The Queen’s University of Belfast (http://www.google.com/patents/US8962032), and is a Director of Research for the Intensive Care Society and NIHR EME Programme Director. M. Ranieri has nothing to disclose. B.T. Thompson reports personal fees from Bayer, Thetis and Novartis, outside the submitted work. H. Wrigge reports personal fees for consultancy from Dräger Medical, personal fees for advisory board work from Liberate Medical, grants and personal fees for lectures from InfectoPharm, personal fees for lectures from MSD and GE, outside the submitted work. L.J. Brochard reports grants from Medtronic Covidien, grants and non-financial support from Fisher Paykel, non-financial support from Air Liquide, Sentec and Philips, other (patent) from General Electric, outside the submitted work. J.G. Laffey reports grants and personal fees from Baxter, grants and non-financial support from Aerogen and Factor Biosciences, outside the submitted work., LUNG SAFE Investigators and the European Society of Intensive Care Medicine Trials Group: Antonio Pesenti, John G Laffey, Laurent Brochard, Andres Esteban, Luciano Gattinoni, Frank van Haren, Anders Larsson, Daniel F McAuley, Marco Ranieri, Gordon Rubenfeld, B Taylor Thompson, Hermann Wrigge, Arthur S Slutsky, John G Laffey, Giacomo Bellani, Tài Pham, Eddy Fan, Fernando Rios, Frank van Haren, Thierry Sottiaux, Pieter Depuydt, Fredy S Lora, Luciano Cesar Azevedo, Eddy Fan, Guillermo Bugedo, Haibo Qiu, Marcos Gonzalez, Juan Silesky, Vladimir Cerny, Jonas Nielsen, Manuel Jibaja, Tài Pham, Hermann Wrigge, Dimitrios Matamis, Jorge Luis Ranero, Pravin Amin, S M Hashemian, Kevin Clarkson, Giacomo Bellani, Kiyoyasu Kurahashi, Asisclo Villagomez, Amine Ali Zeggwagh, Leo M Heunks, Jon Henrik Laake, Jose Emmanuel Palo, Antero do Vale Fernandes, Dorel Sandesc, Yaasen Arabi, Vesna Bumbasierevic, Nicolas Nin, Jose A Lorente, Anders Larsson, Lise Piquilloud, Fekri Abroug, Daniel F McAuley, Lia McNamee, Javier Hurtado, Ed Bajwa, Gabriel Démpaire, Hektor Sula, Lordian Nunci, Alma Cani, Alan Zazu, Christian Dellera, Carolina S Insaurralde, Risso V Alejandro, Julio Daldin, Mauricio Vinzio, Ruben O Fernandez, Luis P Cardonnet, Lisandro R Bettini, Mariano Carboni Bisso, Emilio M Osman, Mariano G Setten, Pablo Lovazzano, Javier Alvarez, Veronica Villar, Norberto C Pozo, Nicolas Grubissich, Gustavo A Plotnikow, Daniela N Vasquez, Santiago Ilutovich, Norberto Tiribelli, Ariel Chena, Carlos A Pellegrini, María G Saenz, Elisa Estenssoro, Matias Brizuela, Hernan Gianinetto, Pablo E Gomez, Valeria I Cerrato, Marco G Bezzi, Silvina A Borello, Flavia A Loiacono, Adriana M Fernandez, Serena Knowles, Claire Reynolds, Deborah M Inskip, Jennene J Miller, Jing Kong, Christina Whitehead, Shailesh Bihari, Aylin Seven, Amanda Krstevski, Helen J Rodgers, Rebecca T Millar, Toni E McKenna, Irene M Bailey, Gabrielle C Hanlon, Anders Aneman, Joan M Lynch, Raman Azad, John Neal, Paul W Woods, Brigit L Roberts, Mark R Kol, Helen S Wong, Katharina C Riss, Thomas Staudinger, Xavier Wittebole, Caroline Berghe, Pierre A Bulpa, Alain M Dive, Rik Verstraete, Herve Lebbinck, Pieter Depuydt, Joris Vermassen, Philippe Meersseman, Helga Ceunen, Jonas I Rosa, Daniel O Beraldo, Claudio Piras, Adenilton M Rampinelli, Antonio P Nassar Jr, Sergio Mataloun, Marcelo Moock, Marlus M Thompson, Claudio H Gonçalves, Ana Carolina P Antônio, Aline Ascoli, Rodrigo S Biondi, Danielle C Fontenele, Danielle Nobrega, Vanessa M Sales, Ahmad Yazid Bin Hj Abul Wahab, Maizatul Ismail, Suresh Shindhe, John Laffey, Francois Beloncle, Kyle G Davies, Rob Cirone, Venika Manoharan, Mehvish Ismail, Ewan C Goligher, Mandeep Jassal, Erin Nishikawa, Areej Javeed, Gerard Curley, Nuttapol Rittayamai, Matteo Parotto, Niall D Ferguson, Sangeeta Mehta, Jenny Knoll, Antoine Pronovost, Sergio Canestrini, Alejandro R Bruhn, Patricio H Garcia, Felipe A Aliaga, Pamela A Farías, Jacob S Yumha, Claudia A Ortiz, Javier E Salas, Alejandro A Saez, Luis D Vega, Eduardo F Labarca, Felipe T Martinez, Nicolás G Carreño, Pilar Lora, Haitao Liu, Haibo Qiu, Ling Liu, Rui Tang, Xiaoming Luo, Youzhong An, Huiying Zhao, Yan Gao, Zhe Zhai, Zheng L Ye, Wei Wang, Wenwen Li, Qingdong Li, Ruiqiang Zheng, Wenkui Yu, Juanhong Shen, Xinyu Li, Tao Yu, Weihua Lu, Ya Q Wu, Xiao B Huang, Zhenyang He, Yuanhua Lu, Hui Han, Fan Zhang, Renhua Sun, Hua X Wang, Shu H Qin, Bao H Zhu, Jun Zhao, Jian Liu, Bin Li, Jing L Liu, Fa C Zhou, Qiong J Li, Xing Y Zhang, Zhou Li-Xin, Qiang Xin-Hua, Liangyan Jiang, Yuan N Gao, Xian Y Zhao, Yuan Y Li, Xiao L Li, Chunting Wang, Qingchun Yao, Rongguo Yu, Kai Chen, Huanzhang Shao, Bingyu Qin, Qing Q Huang, Wei H Zhu, Ai Y Hang, Ma X Hua, Yimin Li, Yonghao Xu, Yu D Di, Long L Ling, Tie H Qin, Shou H Wang, Junping Qin, Yi Han, Suming Zhou, Monica P Vargas, Juan I Silesky Jimenez, Manuel A González Rojas, Jaime E SolisQuesada, Christian M Ramirez-Alfaro, Jan Máca, Peter Sklienka, Jakob Gjedsted, Aage Christiansen, Jonas Nielsen, Boris G Villamagua, Iguel Llano, Philippe Burtin, Gautier Buzancais, Pascal Beuret, Nicolas Pelletier, Satar Mortaza, Alain Mercat, Jonathan Chelly, Sébastien Jochmans, Nicolas Terzi, Cédric Daubin, Guillaume Carteaux, Nicolas de Prost, Jean-Daniel Chiche, Fabrice Daviaud, Tài Pham, Muriel Fartoukh, Guillaume Barberet, Jerome Biehler, Jean Dellamonica, Denis Doyen, Jean-Michel Arnal, Anais Briquet, Sami Hraiech, Laurent Papazian, Arnaud Follin, Damien Roux, Jonathan Messika, Evangelos Kalaitzis, Laurence Dangers, Alain Combes, Siu-Ming Au, Gaetan Béduneau, Dorothée Carpentier, Elie H Zogheib, Herve Dupont, Sylvie Ricome, Francesco L Santoli, Sebastien L Besset, Philippe Michel, Bruno Gelée, Pierre-Eric Danin, Bernard Goubaux, Philippe J Crova, Nga T Phan, Frantz Berkelmans, Julio C Badie, Romain Tapponnier, Josette Gally, Samy Khebbeb, Jean-Etienne Herbrecht, Francis Schneider, PierreLouis M Declercq, Jean-Philippe Rigaud, Jacques Duranteau, Anatole Harrois, Russell Chabanne, Julien Marin, Charlene Bigot, Sandrine Thibault, Mohammed Ghazi, Messabi Boukhazna, Salem Ould Zein, Jack R Richecoeur, Daniele M Combaux, Fabien Grelon, Charlene Le Moal, Elise P Sauvadet, Adrien Robine, Virginie Lemiale, Danielle Reuter, Martin Dres, Alexandre Demoule, Dany Goldgran-Toledano, Loredana Baboi, Claude Guérin, Ralph Lohner, Jens Kraßler, Susanne Schäfer, Kai D Zacharowski, Patrick Meybohm, Andreas W Reske, Philipp Simon, HansBernd F Hopf, Michael Schuetz, Thomas Baltus, Metaxia N Papanikolaou, Theonymfi G Papavasilopoulou, Giannis A Zacharas, Vasilis Ourailogloy, Eleni K Mouloudi, Eleni V Massa, Eva O Nagy, Electra E Stamou, Ellada V Kiourtzieva, Marina A Oikonomou, Luis E Avila, Cesar A Cortez, Johanna E Citalán, Sameer A Jog, Safal D Sable, Bhagyesh Shah, Mohan Gurjar, Arvind K Baronia, Mohammedfaruk Memon, Radhakrishnan Muthuchellappan, Venkatapura J Ramesh, Anitha Shenoy, Ramesh Unnikrishnan, Subhal B Dixit, Rachana V Rhayakar, Nagarajan Ramakrishnan, Vallish K Bhardwaj, Heera L Mahto, Sudha V Sagar, Vijayanand Palaniswamy, Deeban Ganesan, Seyed Mohammadreza Hashemian, Hamidreza Jamaati, Farshad Heidari, Edel A Meaney, Alistair Nichol, Karl M Knapman, Donall O'Croinin, Eimhin S Dunne, Dorothy M Breen, Kevin P Clarkson, Rola F Jaafar, Rory Dwyer, Fahd Amir, Olaitan O Ajetunmobi, Aogan C O'Muircheartaigh, Colin S Black, Nuala Treanor, Daniel V Collins, Wahid Altaf, Gianluca Zani, Maurizio Fusari, Savino Spadaro, Carlo A Volta, Romano Graziani, Barbara Brunettini, Salvatore Palmese, Paolo Formenti, Michele Umbrello, Andrea Lombardo, Elisabetta Pecci, Marco Botteri, Monica Savioli, Alessandro Protti, Alessia Mattei, Lorenzo Schiavoni, Andrea Tinnirello, Manuel Todeschini, Antonino Giarratano, Andrea Cortegiani, Antonino Giarratano, Andrea Cortegiani, Massimo M Antonelli, Luca M Montini, Paolo Casalena, Sergio Scafetti, Giovanna Panarello, Giovanna Occhipinti, Nicolò Patroniti, Matteo Pozzi, Roberto R Biscione, Michela M Poli, Ferdinando Raimondi, Daniela Albiero, Giulia Crapelli, Eduardo Beck, Vincenzo Pota, Vincenzo Schiavone, Alexandre Molin, Fabio Tarantino, Giacomo Monti, Elena Frati, Lucia Mirabella, Gilda Cinnella, Tommaso Fossali, Riccardo Colombo, Pierpaolo Terragni, Ilaria Pattarino, Francesco Mojoli, Antonio Braschi, Erika E Borotto, Andrea N Cracchiolo, Daniela M Palma, Francesco Raponi, Giuseppe Foti, Ettore R Vascotto, Andrea Coppadoro, Luca Brazzi, Leda Floris, Giorgio A Iotti, Aaron Venti, Osamu Yamaguchi, Shunsuke Takagi, Hiroki N Maeyama, Eizo Watanabe, Yoshihiro Yamaji, Kazuyoshi Shimizu, Kyoko Shiozaki, Satoru Futami, Sekine Ryosuke, Koji Saito, Yoshinobu Kameyama, Keiko Ueno, Masayo Izawa, Nao Okuda, Hiroyuki Suzuki, Tomofumi Harasawa, Michitaka Nasu, Tadaaki Takada, Fumihito Ito, Shin Nunomiya, Kansuke Koyama, Toshikazu Abe, Kohkichi Andoh, Kohei Kusumoto, Akira Hirata, Akihiro Takaba, Hiroyasu Kimura, Shuhei Matsumoto, Ushio Higashijima, Hiroyuki Honda, Nobumasa Aoki, Hiroshi Imai, Yasuaki Ogino, Ichiko Mizuguchi, Kazuya Ichikado, Kenichi Nitta, Katsunori Mochizuki, Tomoaki Hashida, Hiroyuki Tanaka, Tomoyuki Nakamura, Daisuke Niimi, Takeshi Ueda, Yozo Kashiwa, Akinori Uchiyama, Olegs Sabelnikovs, Peteris Oss, Youssef Haddad, Kong Y Liew, Silvio A Ñamendys-Silva, Yves D Jarquin-Badiola, Luis A Sanchez-Hurtado, Saira S Gomez-Flores, Maria C Marin, Asisclo J Villagomez, Jordana S Lemus, Jonathan M Fierro, Mavy Ramirez Cervantes, Francisco Javier Flores Mejia, Dulce Dector, Alejandro Rojas, Daniel R Gonzalez, Claudia R Estrella, Jorge R Sanchez-Medina, Alvaro Ramirez-Gutierrez, Fernando G George, Janet S Aguirre, Juan A Buensuseso, Manuel Poblano, Juan A Buensuseso, Manuel Poblano, Tarek Dendane, Amine Ali Zeggwagh, Hicham Balkhi, Mina Elkhayari, Nacer Samkaoui, Hanane Ezzouine, Abdellatif Benslama, Mourad Amor, Wajdi Maazouzi, Nedim Cimic, Oliver Beck, Monique M Bruns, Jeroen A Schouten, Myra Rinia, Monique Raaijmakers, Leo M Heunks, Hellen M van Wezel, Serge J Heines, Ulrich Strauch, Marc P Buise, Fabienne D Simonis, Marcus J Schultz, Jennifer C Goodson, Troy S Browne, Leanlove Navarra, Anna Hunt, Robyn A Hutchison, Mathew B Bailey, Lynette Newby, Colin McArthur, Michael Kalkoff, Alex Mcleod, Jonathan Casement, Danielle J Hacking, Finn H Andersen, Merete S Dolva, Jon H Laake, Andreas Barratt-Due, Kim Andre L Noremark, Eldar Søreide, Brit Å Sjøbø, Anne B Guttormsen, Hector H Leon Yoshido, Ronald Zumaran Aguilar, Fredy A Montes Oscanoa, Alain U Alisasis, Joanne B Robles, Rossini Abbie B Pasanting-Lim, Beatriz C Tan, Pawel Andruszkiewicz, Karina Jakubowska, Cristina M Coxo, António M Alvarez, Bruno S Oliveira, Gustavo M Montanha, Nelson C Barros, Carlos S Pereira, António M Messias, Jorge M Monteiro, Ana M Araujo, Nuno T Catorze, Susan M Marum, Maria J Bouw, Rui M Gomes, Vania A Brito, Silvia Castro, Joana M Estilita, Filipa M Barros, Isabel M Serra, Aurelia M Martinho, Dana R Tomescu, Alexandra Marcu, Ovidiu H Bedreag, Marius Papurica, Dan E Corneci, Silvius Ioan Negoita, Evgeny Grigoriev, Alexey I Gritsan, Andrey A Gazenkampf, Ghaleb Almekhlafi, Mohamad M Albarrak, Ghanem M Mustafa, Khalid A Maghrabi, Nawal Salahuddin, Tharwat M Aisa, Ahmed S Al Jabbary, Edgardo Tabhan, Yaseen M Arabi, Yaseen M Arabi, Olivia A Trinidad, Hasan M Al Dorzi, Edgardo E Tabhan, Vesna Bumbasirevic, Bojan Jovanovic, Stefan Bolon, Oliver Smith, Jordi Mancebo, Hernan Aguirre-Bermeo, Juan C Lopez-Delgado, Francisco Esteve, Gemma Rialp, Catalina Forteza, Candelaria De Haro, Antonio Artigas, Guillermo M Albaiceta, Sara De Cima-Iglesias, Leticia Seoane-Quiroga, Alexandra Ceniceros-Barros, Antonio L RuizAguilar, Luis M Claraco-Vega, Juan Alfonso Soler, Maria Del Carmen Lorente, Cecilia Hermosa, Federico Gordo, Miryam PrietoGonzález, Juan B López-Messa, Manuel P Perez, Cesar P Perez, Raquel Montoiro Allue, Ferran RocheCampo, Marcos Ibañez-Santacruz, Susana TempranoSusana, Maria C Pintado, Raul De Pablo, Pilar Ricart Aroa Gómez, Silvia Rodriguez Ruiz, Silvia Iglesias Moles, Mª Teresa Jurado, Alfons Arizmendi, Enrique A Piacentini, Nieves Franco, Teresa Honrubia, Meisy Perez Cheng, Elena Perez Losada, Javier Blanco, Luis J Yuste, Cecilia Carbayo-Gorriz, Francisca G Cazorla-Barranquero, Javier G Alonso, Rosa S Alda, Ángela Algaba, Gonzalo Navarro, Enrique Cereijo, Esther Diaz-Rodriguez, Diego Pastor Marcos, Laura Alvarez Montero, Luis Herrera Para, Roberto Jimenez Sanchez, Miguel Angel Blasco Navalpotro, Ricardo Diaz Abad, Raquel Montiel González, Dácil Parrilla Toribio, Alejandro G Castro, Maria Jose D Artiga, Oscar Penuelas, Tomas P Roser, Moreno F Olga, Elena Gallego Curto, Rocío Manzano Sánchez, Vallverdu P Imma, Garcia M Elisabet, Laura Claverias, Monica Magret, Ana M Pellicer, Lucia L Rodriguez, Jesús Sánchez-Ballesteros, Ángela González-Salamanca, Antonio G Jimenez, Francisco P Huerta, Juan Carlos J Sotillo Diaz, Esther Bermejo Lopez, David D Llinares Moya, Alec A Tallet Alfonso, Palazon Sanchez Eugenio Luis, Palazon Sanchez Cesar, Sánchez I Rafael, Corcoles G Virgilio, Noelia N Recio, Christian C Rylander, Bernhard Holzgraefe, Lars M Broman, Joanna Wessbergh, Linnea Persson, Fredrik Schiöler, Hans Kedelv, Anna Oscarsson Tibblin, Henrik Appelberg, Lars Hedlund, Johan Helleberg, Karin E Eriksson, Rita Glietsch, Niklas Larsson, Ingela Nygren, Silvia L Nunes, Anna-Karin Morin, Thomas Kander, Anne Adolfsson, Lise Piquilloud, Hervé O Zender, Corinne Leemann-Refondini, Souheil Elatrous, Slaheddine Bouchoucha, Imed Chouchene, Islem Ouanes, Asma Ben Souissi, Salma Kamoun, Oktay Demirkiran, Mustafa Aker, Emre Erbabacan, Ilkay Ceylan, Nermin Kelebek Girgin, Menekse Ozcelik, Necmettin Ünal, Basak Ceyda Meco, Onat O Akyol, Suleyman S Derman, Barry Kennedy, Ken Parhar, Latha Srinivasa, Lia McNamee, Danny McAuley, Phil Hopkins, Clare Mellis, Vivek Kakar, Dan Hadfield, Andre Vercueil, Kaushik Bhowmick, Sally K Humphreys, Andrew Ferguson, Raymond Mckee, Ashok S Raj, Danielle A Fawkes, Philip Watt, Linda Twohey, Rajeev R Jha, Matthew Thomas, Alex Morton, Varsha Kadaba, Mark J Smith, Anil P Hormis, Santhana G Kannan, Miriam Namih, Henrik Reschreiter, Julie Camsooksai, Alek Kumar, Szabolcs Rugonfalvi, Christopher Nutt, Orla Oneill, Colette Seasman, Ged Dempsey, Christopher J Scott, Helen E Ellis, Stuart Mckechnie, Paula J Hutton, Nora N Di Tomasso, Michela N Vitale, Ruth O Griffin, Michael N Dean, Julius H Cranshaw, Emma L Willett, Nicholas Ioannou, Sarah Gillis, Peter Csabi, Rosaleen Macfadyen, Heidi Dawson, Pieter D Preez, Alexandra J Williams, Owen Boyd, Laura Ortiz-Ruiz de Gordoa, Jon Bramall, Sophie Symmonds, Simon K Chau, Tim Wenham, Tamas Szakmany, Piroska Toth-Tarsoly, Katie H McCalman, Peter Alexander, Lorraine Stephenson, Thomas Collyer, Rhiannon Chapman, Raphael Cooper, Russell M Allan, Malcolm Sim, David W Wrathall, Donald A Irvine, Kim S Zantua, John C Adams, Andrew J Burtenshaw, Gareth P Sellors, Ingeborg D Welters, Karen E Williams, Robert J Hessell, Matthew G Oldroyd, Ceri E Battle, Suresh Pillai, Istvan Kajtor, Mageswaran Sivashanmugavel, Sinead C Okane, Adrian Donnelly, Aniko D Frigyik, Jon P Careless, Martin M May, Richard Stewart, T John Trinder, Samantha J Hagan, Jade M Cole, Caroline C MacFie, Anna T Dowling, Javier Hurtado, Nicolás Nin, Javier Hurtado, Edgardo Nuñez, Gustavo Pittini, Ruben Rodriguez, María C Imperio, Cristina Santos, Ana G França, Alejandro Ebeid, Alberto Deicas, Carolina Serra, Aditya Uppalapati, Ghassan Kamel, Valerie M Banner-Goodspeed, Jeremy R Beitler, Satyanarayana Reddy Mukkera, Shreedhar Kulkarni, John O Shinn Iii, Dina Gomaa, Christopher Tainter, Jarone Lee, Tomaz MesarJarone Lee, Dale J Yeatts, Jessica Warren, Michael J Lanspa, Russel R Miller, Colin K Grissom, Samuel M Brown, Philippe R Bauer, Ryan J Gosselin, Barrett T Kitch, Jason E Cohen, Scott H Beegle, Shazia Choudry, Renaud M Gueret, Aiman Tulaimat, William Stigler, Hitesh Batra, Nidhi G Huff, Keith D Lamb, Trevor W Oetting, Nicholas M Mohr, Claine Judy, Shigeki Saito, Fayez M Kheir, Fayez Kheir, Adam B Schlichting, Angela Delsing, Daniel R Crouch, Mary Elmasri, Daniel R Crouch, Dina Ismail, Kyle R Dreyer, Thomas C Blakeman, Dina Gomaa, Rebecca M Baro, Carolina Quintana Grijalba, Peter C Hou, Raghu Seethala, Imo Aisiku, Galen Henderson, Gyorgy Frendl, Sen-Kuang Hou, Robert L Owens, Ashley Schomer, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - (MGD) Services des soins intensifs, and UCL - (SLuc) Service de soins intensifs
Subjects: Pulmonary and Respiratory Medicine, ARDS, Unidades de cuidados intensivos, [SDV]Life Sciences [q-bio], medicine.medical_treatment, mechanical ventilation, NO, law.invention, 03 medical and health sciences, Tratamiento médico, 0302 clinical medicine, law, Settore MED/41 - ANESTESIOLOGIA, Insuficiencia respiratoria, Medicine, Humans, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Lung, Mechanical ventilation, Respiratory Distress Syndrome, business.industry, Respiration, Incidence (epidemiology), medicine.disease, Intensive care unit, Respiration, Artificial, 3. Good health, Intensive Care Units, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], medicine.anatomical_structure, 030228 respiratory system, Respiratory failure, Heart failure, Anesthesia, Artificial, ards, business, Respiratory Insufficiency, Enfermedad
Abstract: BackgroundCurrent incidence and outcome of patients with acute hypoxaemic respiratory failure requiring mechanical ventilation in the intensive care unit (ICU) are unknown, especially for patients not meeting criteria for acute respiratory distress syndrome (ARDS).MethodsAn international, multicentre, prospective cohort study of patients presenting with hypoxaemia early in the course of mechanical ventilation, conducted during four consecutive weeks in the winter of 2014 in 459 ICUs from 50 countries (LUNG SAFE). Patients were enrolled with arterial oxygen tension/inspiratory oxygen fraction ratio ≤300 mmHg, new pulmonary infiltrates and need for mechanical ventilation with a positive end-expiratory pressure of ≥5 cmH2O. ICU prevalence, causes of hypoxaemia, hospital survival and factors associated with hospital mortality were measured. Patients with unilateral versus bilateral opacities were compared.Findings12 906 critically ill patients received mechanical ventilation and 34.9% with hypoxaemia and new infiltrates were enrolled, separated into ARDS (69.0%), unilateral infiltrate (22.7%) and congestive heart failure (CHF; 8.2%). The global hospital mortality was 38.6%. CHF patients had a mortality comparable to ARDS (44.1% versus 40.4%). Patients with unilateral-infiltrate had lower unadjusted mortality, but similar adjusted mortality compared to those with ARDS. The number of quadrants on chest imaging was associated with an increased risk of death. There was no difference in mortality comparing patients with unilateral-infiltrate and ARDS with only two quadrants involved.InterpretationMore than one-third of patients receiving mechanical ventilation have hypoxaemia and new infiltrates with a hospital mortality of 38.6%. Survival is dependent on the degree of pulmonary involvement whether or not ARDS criteria are reached.
Published: 2021
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48. Nivolumab Plus Ipilimumab for Treatment-Naïve Metastatic Uveal Melanoma: An Open-Label, Multicenter, Phase II Trial by the Spanish Multidisciplinary Melanoma Group (GEM-1402)

Author: Teresa Curiel, J.M. Piulats, Salvador Martín-Algarra, Montserrat Gomà, Miriam Redrado, Luis Merino, Alfonso Berrocal-Jaime, Mar Varela, Rafael López Castro, Lorenzo Alonso Carrión, Alfonso Calvo González, Enrique Espinosa, Delvys Rodriguez-Abreu, and Antonio Rullan
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, business.industry, Melanoma, Ipilimumab, medicine.disease, Therapy naive, Clinical trial, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, In patient, Open label, Nivolumab, business, Survival analysis, medicine.drug
Abstract: PURPOSE This study aimed to assess the efficacy of the combination of nivolumab (nivo) plus ipilimumab (ipi) as a first-line therapy with respect to the 12-month overall survival (OS) in patients with metastatic uveal melanoma (MUM) who are not eligible for liver resection. METHODS This was a single-arm, phase II trial led by the Spanish Multidisciplinary Melanoma Group (GEM) on nivo plus ipi for systemic treatment-naïve patients of age > 18 years, with histologically confirmed MUM, Eastern Cooperative Oncology Group-PS 0/1, and confirmed progressive metastatic disease (M1). Nivo (1 mg/kg once every 3 weeks) and ipi (3 mg/kg once every 3 weeks) were administered during four inductions, followed by nivo (3 mg/kg once every 2 weeks) until progressive disease, toxicity, or withdrawal. The primary end point was 12-month OS. OS, progression-free survival (PFS), and overall response rate were evaluated every 6 weeks using RECIST (v1.1). Safety was also evaluated. Logistic regression and Cox proportional hazard models comprising relevant clinical factors were used to evaluate the potential association with response to treatment and survival. Cytokines were quantified in serum samples for their putative role in immune modulation/angiogenesis and/or earlier evidence of involvement in immunotherapy. RESULTS A total of 52 patients with a median age of 59 years (range, 26-84 years) were enrolled. Overall, 78.8%, 56%, and 32% of patients had liver M1, extra-liver M1, and elevated lactate dehydrogenase. Stable disease was the most common outcome (51.9%). The primary end point was 12-month OS, which was 51.9% (95% CI, 38.3 to 65.5). The median OS and PFS were 12.7 months and 3.0 months, respectively. PFS was influenced by higher LDH values. CONCLUSIONS Nivo plus ipi in the first-line setting for MUM showed a modest improvement in OS over historical benchmarks of chemotherapy, with a manageable toxicity profile.
Published: 2021
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49. Effects of Bisphosphonate Treatment on Circulating Lipid and Glucose Levels in Patients with Metabolic Bone Disorders

Author: Gabriella Iannuzzo, M. Evangelista, Alfonso Giaquinto, Domenico Rendina, V. Abate, Gianpaolo De Filippo, Luigi Gennari, Tommaso Picchioni, Alessio Buonaiuto, Matteo Nicola Dario Di Minno, Marco Gentile, Pasquale Strazzullo, Daniela Merlotti, Iannuzzo, Gabriella, De Filippo, Gianpaolo, Merlotti, Daniela, Abate, Veronica, Buonaiuto, Alessio, Evangelista, Marco, Gentile, Marco, Giaquinto, Alfonso, Picchioni, Tommaso, Di Minno, Matteo Nicola Dario, Strazzullo, Pasquale, Gennari, Luigi, and Rendina, Domenico
Subjects: 0301 basic medicine, medicine.medical_specialty, Statin, medicine.drug_class, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Osteoporosis, 030209 endocrinology & metabolism, Zoledronic Acid, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, medicine, Humans, Bisphosphonate, Glucose homeostasis, Orthopedics and Sports Medicine, Triglycerides, Original Research, Retrospective Studies, Bone Density Conservation Agents, Diphosphonates, business.industry, Osteoporosi, Paget’s disease of bone, Osteitis Deformans, medicine.disease, Lipids, Metabolic Bone Disorder, Cholesterol, Glucose, 030104 developmental biology, Paget's disease of bone, Zoledronic acid, Clodronic acid, lipids (amino acids, peptides, and proteins), business, medicine.drug
Abstract: Bisphosphonates are the first-choice treatment of osteoporosis and Paget’s disease of bone. Among the bisphosphonates, the non-amino-bisphosphonates, such as clodronic acid, are intracellular converted into toxic analogues of ATP and induce cellular apoptosis whereas the amino-bisphosphonates, such as zoledronic acid, inhibit the farnesyl-diphosphate-synthase, an enzyme of the mevalonate pathway. This pathway regulates cholesterol and glucose homeostasis and is a target for statins. In this retrospective cohort study, we evaluated the effects of an intravenous infusion of zoledronic acid (5 mg) or clodronic acid (1500 mg) on blood lipid (i.e. total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and triglycerides) and glucose levels in patients with osteoporosis and Paget’s disease of bone. All patients were evaluated before, 1 and 6 months after bisphosphonate treatment. Pagetic and osteoporotic patients treated with zoledronic acid showed a significant reduction in glucose and atherogenic lipids during follow-up whereas these phenomena were not observed after clodronic treatment. The effect on circulating lipid levels was similar in naïve and re-treated Pagetic patients. Zoledronic acid treatment was associated with a reduction in blood glucose and atherogenic lipids in patients with metabolic bone disorders. The extent of change was similar to that obtained with the regular assumption of a low-intensity statin. Further studies are warranted to better evaluate the clinical implications of these observations. Supplementary Information The online version of this article (10.1007/s00223-021-00811-w) contains supplementary material, which is available to authorized users.
Published: 2021
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50. Unplanned Percutaneous Coronary Revascularization After TAVR

Author: Victor Alfonso Jimenez Diaz, Diego López Otero, Philippe Garot, Marco Pavani, José M. de la Torre Hernández, Jorn Brouwer, Maria Luisa Salido Tahoces, Carlo Andrea Pivato, Giulio G. Stefanini, Revival Investigators, Ferdinando Varbella, Michael Joner, Enrico Cerrato, Bernhard Reimers, Luigi Biasco, Marco Barbanti, Tobias Rheude, Alfonso Ielasi, Alaide Chieffo, Luis Nombela-Franco, Luca Testa, Erika Munoz Garcia, Massimo Leoncini, Darren Mylotte, and Thomas Pilgrim
Subjects: Acute coronary syndrome, medicine.medical_specialty, business.industry, Unstable angina, medicine.medical_treatment, Percutaneous coronary intervention, 030204 cardiovascular system & hematology, Revascularization, medicine.disease, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Valve replacement, Internal medicine, Conventional PCI, Cardiology, Medicine, cardiovascular diseases, 030212 general & internal medicine, Myocardial infarction, Cardiology and Cardiovascular Medicine, business
Abstract: Objectives This study sought to evaluate the incidence and causes of percutaneous coronary intervention (PCI) at different time periods following transcatheter aortic valve replacement (TAVR). Background Coronary artery disease (CAD) and aortic stenosis frequently coexist, but the optimal management of CAD following TAVR remains incompletely elucidated. Methods Patients undergoing unplanned PCI after TAVR were retrospectively included in an international multicenter registry. Results Between July 2008 and March 2019, a total of 133 patients (0.9%; from a total cohort of 15,325) underwent unplanned PCI after TAVR (36.1% after balloon-expandable bioprosthesis, 63.9% after self-expandable bioprosthesis). The median time to PCI was 191 days (interquartile range: 59 to 480 days). The daily incidence of PCI was highest during the first week after TAVR and then declined over time. Overall, the majority of patients underwent PCI due to an acute coronary syndrome, and specifically 32.3% had non–ST-segment elevation myocardial infarction, 15.4% had unstable angina, 9.8% had ST-segment elevation myocardial infarction, and 2.2% had cardiac arrest. However, chronic coronary syndromes are the main indication beyond 2 years. PCI success was reported in almost all cases (96.6%), with no significant differences between patients treated with balloon-expandable and self-expandable bioprostheses (100% vs. 94.9%; p = 0.150). Conclusions Unplanned PCI after TAVR is rare, with an incidence declining over time after TAVR. The main indication to PCI is acute coronary syndrome in the first 2 years after TAVR, and thereafter chronic coronary syndromes become prevalent. Unplanned PCIs are frequently successfully performed after TAVR, with no apparent differences between balloon-expandable and self-expandable bioprostheses. (Revascularization After Transcatheter Aortic Valve Implantation [REVIVAL]; NCT03283501 )
Published: 2021
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