Author: "Yonathan" / Topic: internal medicine - Searchworks@Jio Institute Digital Library Search Results

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1. Pulmonary embolism in patients with COVID-19: incidence, risk factors, clinical characteristics, and outcome

Author: Fahd Beddar Chaib, Maria Adroher Muñoz, Juan González del Castillo, Anna Palau-Vendrell, Eric Jorge García-Lamberechts, Sònia Jiménez, Pere Llorens, Carlos Cardozo, Nieves López-Laguna, Josep Maria Mòdol Deltell, Alexandre Mebazaa, Alfons Aguirre Tejedo, Víctor Gil, Aitor Alquézar-Arbé, Òscar Miró, Guillermo Burillo-Putze, Matilde González Tejera, Josep Tost, Yonathan Freund, Carmen Del Arco Galán, Josep Maria Guardiola, Alfonso Martín, Pascual Piñera, Teresa Agudo Villa, Francisco Javier Martín-Sánchez, Lluís LLauger García, María Carmen Ponce, Javier Jacob, María Pilar López Díez, and Eva Quero Motto
Subjects: medicine.medical_specialty, Population, 030204 cardiovascular system & hematology, Chest pain, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, 030212 general & internal medicine, education, Outcome, education.field_of_study, Clinical characteristics, SARS-CoV-2, business.industry, Incidence, Incidence (epidemiology), Pulmonary embolism, COVID-19, Retrospective cohort study, Odds ratio, medicine.disease, Confidence interval, Risk factors, Heart failure, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract: Aims We investigated the incidence, risk factors, clinical characteristics, and outcomes of pulmonary embolism (PE) in patients with COVID-19 attending emergency departments (EDs), before hospitalization. Methods and Results We retrospectively reviewed all COVID-19 patients diagnosed with PE in 62 Spanish EDs (20% of Spanish EDs, case group) during the first COVID-19 outbreak. COVID-19 patients without PE and non-COVID-19 patients with PE were included as control groups. Adjusted comparisons for baseline characteristics, acute episode characteristics, and outcomes were made between cases and randomly selected controls (1:1 ratio). We identified 368 PE in 74 814 patients with COVID-19 attending EDs (4.92‰). The standardized incidence of PE in the COVID-19 population resulted in 310 per 100 000 person-years, significantly higher than that observed in the non-COVID-19 population [35 per 100 000 person-years; odds ratio (OR) 8.95 for PE in the COVID-19 population, 95% confidence interval (CI) 8.51–9.41]. Several characteristics in COVID-19 patients were independently associated with PE, the strongest being D-dimer >1000 ng/mL, and chest pain (direct association) and chronic heart failure (inverse association). COVID-19 patients with PE differed from non-COVID-19 patients with PE in 16 characteristics, most directly related to COVID-19 infection; remarkably, D-dimer >1000 ng/mL, leg swelling/pain, and PE risk factors were significantly less present. PE in COVID-19 patients affected smaller pulmonary arteries than in non-COVID-19 patients, although right ventricular dysfunction was similar in both groups. In-hospital mortality in cases (16.0%) was similar to COVID-19 patients without PE (16.6%; OR 0.96, 95% CI 0.65–1.42; and 11.4% in a subgroup of COVID-19 patients with PE ruled out by scanner, OR 1.48, 95% CI 0.97–2.27), but higher than in non-COVID-19 patients with PE (6.5%; OR 2.74, 95% CI 1.66–4.51). Adjustment for differences in baseline and acute episode characteristics and sensitivity analysis reported very similar associations. Conclusions PE in COVID-19 patients at ED presentation is unusual (about 0.5%), but incidence is approximately ninefold higher than in the general (non-COVID-19) population. Moreover, risk factors and leg symptoms are less frequent, D-dimer increase is lower and emboli involve smaller pulmonary arteries. While PE probably does not increase the mortality of COVID-19 patients, mortality is higher in COVID-19 than in non-COVID-19 patients with PE.
Published: 2021
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2. Electrolyte imbalance in COVID-19 patients admitted to the Emergency Department: a case–control study

Author: Quentin Le Bastard, Marie Caroline Richard, Lucile Figueres, Antoine Kratz, Tahar Chouihed, Damien Masson, Yonathan Freund, Marine Dubroux, Nicolas Goffinet, Hugo De Carvalho, and Emmanuel Montassier
Subjects: Adult, Male, medicine.medical_specialty, Hypochloremia, Water-Electrolyte Imbalance, Hypokalemia, Reference range, Acid-Base Imbalance, EM - Original, 030204 cardiovascular system & hematology, Logistic regression, Severity of Illness Index, Electrolytes, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Internal Medicine, Humans, Medicine, 030212 general & internal medicine, Aged, Electrolyte imbalance, business.industry, Case-control study, COVID-19, nutritional and metabolic diseases, Emergency department, Odds ratio, Middle Aged, medicine.disease, Case-Control Studies, Emergency Medicine, Female, medicine.symptom, Emergency Service, Hospital, business, Hyponatremia
Abstract: In patients visiting the emergency department (ED), a potential association between electrolytes disturbance and coronavirus disease 2019 (COVID-19) has not been well studied. We aim to describe electrolyte disturbance and explore risk factors for COVID-19 infection in patients visiting the ED. We carried out a case–control study in three hospitals in France, including adult ED inpatients (≥ 18 years old). A total of 594 ED case patients in whom infection with COVID-19 was confirmed, were matched to 594 non-COVID-19 ED patients (controls) from the same period, according to sex and age. Hyponatremia was defined by a sodium of less than 135 mmol/L (reference range 135–145 mmol/L), hypokalemia by a potassium of less than 3.5 mmol/L (reference range 3.5–5.0 mmol/L), and hypochloremia by a chloride of less than 95 mmol/L (reference range 98–108 mmol/L). Among both case patients and controls, the median (IQR) age was 65 years (IQR 51–76), and 44% were women. Hyponatremia was more common among case patients than among controls, as was hypokalemia and hypochloremia. Based on the results of the multivariate logistic regression, hyponatremia, and hypokalemia were associated with COVID-19 among case patients overall, with an adjusted odds ratio of 1.89 [95% CI 1.24–2.89] for hyponatremia and 1.76 [95% CI 1.20–2.60] for hypokalemia. Hyponatremia and hypokalemia are independently associated with COVID-19 infection in adults visiting the ED, and could act as surrogate biomarkers for the emergency physician in suspected COVID-19 patients.
Published: 2021
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3. Concerns regarding result analysis and the corresponding risk of pulmonary embolism severity and in-hospital mortality. Author's reply

Author: Sònia Jiménez, Yonathan Freund, and Òscar Miró
Subjects: Postoperative Complications, Internal Medicine, Humans, Hospital Mortality, Pulmonary Embolism
Published: 2022

4. Genetic Determinants of Lung Cancer Prognosis in Never Smokers: A Pooled Analysis in the International Lung Cancer Consortium

Author: David C. Christiani, Sanjay Shete, Paul Brennan, Ping Yang, Yonathan Brhane, Keitaro Matsuo, Christopher I. Amos, Rayjean J. Hung, Yohan Bossé, John K. Field, John R. McLaughlin, Geoffrey Liu, Takashi Kohno, Adonina Tardón, and Kouya Shiraishi
Subjects: Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Lung Neoplasms, Epidemiology, Locus (genetics), Article, 03 medical and health sciences, 0302 clinical medicine, Statistical significance, Internal medicine, medicine, Humans, Allele, Lung cancer, Lung, business.industry, Middle Aged, Prognosis, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Tumor progression, 030220 oncology & carcinogenesis, Expression quantitative trait loci, Adenocarcinoma, Female, business
Abstract: Background: Lung cancer remains the leading cause of cancer death worldwide, with 15% to 20% occurring in never smokers. To assess genetic determinants for prognosis among never smokers, we conducted a genome-wide investigation in the International Lung Cancer Consortium (ILCCO). Methods: Genomic and clinical data from 1,569 never-smoking patients with lung cancer of European ancestry from 10 ILCCO studies were included. HRs and 95% confidence intervals of overall survival were estimated. We assessed whether the associations were mediated through mRNA expression–based 1,553 normal lung tissues from the lung expression quantitative trait loci (eQTL) dataset and Genotype-Tissue Expression (GTEx). For cross-ethnicity generalization, we assessed the associations in a Japanese study (N = 887). Results: One locus at 13q22.2 was associated with lung adenocarcinoma survival at genome-wide level, with carriers of rs12875562-T allele exhibiting poor prognosis [HR = 1.71 (1.41–2.07), P = 3.60 × 10−8], and altered mRNA expression of LMO7DN in lung tissue (GTEx, P = 9.40 × 10−7; Lung eQTL dataset, P = 0.003). Furthermore, 2 of 11 independent loci that reached the suggestive significance level (P < 10−6) were significant eQTL affecting mRNA expression of nearby genes in lung tissues, including CAPZB at 1p36.13 and UBAC1 at 9q34.3. One locus encoding NWD2/KIAA1239 at 4p14 showed associations in both European [HR = 0.50 (0.38–0.66), P = 6.92 × 10−7] and Japanese populations [HR = 0.79 (0.67–0.94), P = 0.007]. Conclusions: Based on the largest genomic investigation on the lung cancer prognosis of never smokers to date, we observed that lung cancer prognosis is affected by inherited genetic variants. Impact: We identified one locus near LMO7DN at genome-wide level and several potential prognostic genes with cis-effect on mRNA expression. Further functional genomics work is required to understand their role in tumor progression.
Published: 2020
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5. Utility of 6-Minute Walk Test to Predict Response to Cardiac Resynchronization Therapy in Patients With Mild Heart Failure

Author: Natalia Hernandez, Scott McNitt, Valentina Kutyifa, Wojciech Zareba, Scott D. Solomon, Spencer Rosero, Ilan Goldenberg, Yonathan Buber, and Bronislava Plonsky
Subjects: Male, medicine.medical_specialty, Multivariate analysis, medicine.medical_treatment, Cardiac resynchronization therapy, Walk Test, 030204 cardiovascular system & hematology, Ventricular Function, Left, law.invention, Cardiac Resynchronization Therapy, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Humans, Medicine, In patient, 6-minute walk test, 030212 general & internal medicine, Heart Failure, business.industry, Left bundle branch block, Stroke Volume, Middle Aged, medicine.disease, Treatment Outcome, Echocardiography, Heart failure, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Multicenter Automatic Defibrillator Implantation Trial
Abstract: Clinical studies of heart failure (HF) generally utilize the 6-minute walk test (6MWT) for functional capacity (FC) assessment. However, data on the impact of cardiac resynchronization therapy (CRT) on 6MWT and its role to predict long-term outcomes in mild HF patients with CRT are lacking. We studied 1,381 subjects with mild HF enrolled in Multicenter Automatic Defibrillator Implantation Trial - Cardiac Resynchronization Therapy with 6MWT data at baseline and 1 year. We assessed the effects of CRT-D on percent change in 6MWT at 1 year by left bundle branch block (LBBB) status, identified independent predictors of 6MWT at 1 year, and evaluated the association between changes in 6MWT and risk for HF or death. Treatment with CRT-D versus implantable cardiac defibrillator (ICD) was not associated with a significant improvement in 6MWT at 1-year in LBBB subjects (2.2 % vs 0.0%, p = 0.428, but it was associated with a deterioration in 6MWT in non-LBBB subjects (4.1% vs 0.0%, p = 0.308). Multivariate analysis showed that each 5% reduction in 6MWT was independently associated with a corresponding 3% increase in the risk of subsequent HF or death (p = 0.014). In conclusion, our findings suggest that 6MWT has limited utility to identify CRT response in mild HF subjects with LBBB. However, 6MWT showed a signal toward deterioration in mild HF subjects with non-LBBB, and this was predictive of subsequent increased risk of HF or death.
Published: 2020
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6. Association Between Pulmonary Embolism and COVID‐19 in Emergency Department Patients Undergoing Computed Tomography Pulmonary Angiogram: The PEPCOV International Retrospective Study

Author: Anne Laure Feral-Pierssens, Judith Gorlicki, Pierre Géraud Claret, Ben Bloom, Mélanie Roussel, Florent Femy, A Penaloza, Alfons Aguirre, Fabien Brigant, Òscar Miró, Pierrick Le Borgne, Alessio Marra, Said Laribi, Yonathan Freund, Sébastien Beaune, Olivier Lucidarme, Emmanuel Montassier, Tahar Chouihed, Céline Occelli, Anthony Chauvin, Bárbara Lara Hernández, Jennifer Truchot, Barbara Pena, Prabakar Vaittinada Ayar, Sami Ellouze, Marine Cachanado, Nicolas Javaud, Tabassome Simon, Marie Drogrey, Service des Urgences [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Hospital Clínic de Barcelona [Catalonia, Spain], ASST Papa Giovanni XXIII [Bergamo, Italy], Université de Sherbrooke (UdeS), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Cliniques Universitaires Saint-Luc [Bruxelles], Université Catholique de Louvain = Catholic University of Louvain (UCL), Pontificia Universidad Católica de Chile (UC), Hôpital Ambroise Paré [AP-HP], Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), SAMU 93 [Bobigny], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine d'urgence [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Universidad de Alicante, IMIM-Hospital del Mar, Generalitat de Catalunya, Hôpital Louis Mourier - AP-HP [Colombes], Hôpital Lariboisière-Fernand-Widal [APHP], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des Urgences [CHU Nantes], Hôtel-Dieu de Nantes, Microbiotes, Hôtes, Antibiotiques et Résistances bactériennes (MiHAR) (MiHAR), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital Pasteur [Nice] (CHU), Services des urgences [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service des Urgences [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Hopital Saint-Louis [AP-HP] (AP-HP), Les Hôpitaux Universitaires de Strasbourg (HUS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Nanomédecine Régénérative (NanoRegMed), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Radiologie [CHU Pitié-Salpétrière], Barts Health NHS Trust [London, UK], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Gestionnaire, Hal Sorbonne Université, Service d'Accueil des Urgences [CHU Pitié-Salpêtrière] (SAU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, and Service d'Urgences Adultes [CHU Saint-Antoine]
Subjects: medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Pulmonary angiogram, Tomografia, [SDV]Life Sciences [q-bio], Computed tomography, Logistic regression, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Clinical endpoint, Pandèmia de COVID-19, 2020, Embòlia pulmonar, medicine.diagnostic_test, business.industry, 030208 emergency & critical care medicine, Retrospective cohort study, General Medicine, Emergency department, medicine.disease, 3. Good health, Pulmonary embolism, [SDV] Life Sciences [q-bio], Emergency Medicine, business
Abstract: International audience; Background: There have been reports of procoagulant activity in patients with COVID-19. Whether there is an association between pulmonary embolism (PE) and COVID-19 in the emergency department (ED) is unknown. The aim of this study was to assess whether COVID-19 is associated with PE in ED patients who underwent a computed tomographic pulmonary angiogram (CTPA).Methods: A retrospective study in 26 EDs from six countries. ED patients in whom a CTPA was performed for suspected PE during a 2-month period covering the pandemic peak. The primary endpoint was the occurrence of a PE on CTPA. COVID-19 was diagnosed in the ED either on CT or reverse transcriptase-polymerase chain reaction. A multivariable binary logistic regression was built to adjust with other variables known to be associated with PE. A sensitivity analysis was performed in patients included during the pandemic period.Results: A total of 3,358 patients were included, of whom 105 were excluded because COVID-19 status was unknown, leaving 3,253 for analysis. Among them, 974 (30%) were diagnosed with COVID-19. Mean (±SD) age was 61 (±19) years and 52% were women. A PE was diagnosed on CTPA in 500 patients (15%). The risk of PE was similar between COVID-19 patients and others (15% in both groups). In the multivariable binary logistic regression model, COVID-19 was not associated with higher risk of PE (adjusted odds ratio = 0.98, 95% confidence interval = 0.76 to 1.26). There was no association when limited to patients in the pandemic period.Conclusion: In ED patients who underwent CTPA for suspected PE, COVID-19 was not associated with an increased probability of PE diagnosis. These results were also valid when limited to the pandemic period. However, these results may not apply to patients with suspected COVID-19 in general.
Published: 2020
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7. Validation of the Bacterial Meningitis Score in adults consulting at an emergency department: a retrospective multicentric study

Author: Gauthier Pean-de-Ponfilly, Celine Mesnil, Jérôme Robert, Yonathan Freund, Quentin Delannoy, Constance Severin, Emmanuelle Cambau, Patrick Plaisance, Hervé Jacquier, Pierre Hausfater, and Anthony Chauvin
Subjects: Adult, medicine.medical_specialty, 030204 cardiovascular system & hematology, Sensitivity and Specificity, Procalcitonin, Meningitis, Bacterial, law.invention, Leukocyte Count, 03 medical and health sciences, 0302 clinical medicine, CSF pleocytosis, Predictive Value of Tests, law, Internal medicine, medicine, Humans, Child, CSF albumin, Retrospective Studies, medicine.diagnostic_test, Lumbar puncture, business.industry, digestive, oral, and skin physiology, Infant, 030208 emergency & critical care medicine, Retrospective cohort study, medicine.disease, 3. Good health, stomatognathic diseases, Gram staining, Emergency Medicine, Absolute neutrophil count, Emergency Service, Hospital, business, Meningitis
Abstract: OBJECTIVE The Bacterial Meningitis Score (BMS) is recommended by pediatric academic societies to rule out the diagnosis of bacterial meningitis. The aim of this study was to evaluate the performance of the BMS to identify adults at no risk for bacterial meningitis. METHODS We conducted a multicentric retrospective study including adults who consulted the emergency department (ED) for meningitis [cerebrospinal fluid (CSF) white blood cells ≥5/mm with a ratio of white blood cells/red blood cells
Published: 2020
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8. Circulating neutrophil subsets in advanced lung cancer patients exhibit unique immune signature and relate to prognosis

Author: Ester Forkosh, Mark D. Robinson, Carsten Krieg, Hovav Nechushtan, Alon Pomerantz, Liran Levy, Evgeniy Eruslanov, Asaf Zlotnik, Lukas M. Weber, Ophir Eyal, Yonathan Levin, Pazzit Aloni, Sunil Singhal, Silvia Guglietta, Zvi G. Fridlender, and Merav E. Shaul
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Lung Neoplasms, Neutrophils, GPI-Linked Proteins, Biochemistry, CXCR4, Gastroenterology, Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antigens, CD, Internal medicine, Genetics, medicine, Humans, Clinical significance, Lymphocytes, Stage (cooking), Lung cancer, Molecular Biology, Aged, Aged, 80 and over, COPD, business.industry, Cancer, Middle Aged, Flow Cytometry, Prognosis, medicine.disease, 030104 developmental biology, Tumor progression, Female, business, Cell Adhesion Molecules, 030217 neurology & neurosurgery, Biotechnology
Abstract: The accumulation of circulating low-density neutrophils (LDN) has been described in cancer patients and associated with tumor-supportive properties, as opposed to the high-density neutrophils (HDN). Here we aimed to evaluate the clinical significance of circulating LDN in lung cancer patients, and further assessed its diagnostic vs prognostic value. Using mass cytometry (CyTOF), we identified major subpopulations within the circulating LDN/HDN subsets and determined phenotypic modulations of these subsets along tumor progression. LDN were highly enriched in the low-density (LD) fraction of advanced lung cancer patients (median 7.0%; range 0.2%-80%, n = 64), but not in early stage patients (0.7%; 0.05%-6%; n = 35), healthy individuals (0.8%; 0%-3.5%; n = 15), or stable chronic obstructive pulmonary disease (COPD) patients (1.2%; 0.3%-7.4%, n = 13). Elevated LDN (>10%) remarkably related with poorer prognosis in late stage patients. We identified three main neutrophil subsets which proportions are markedly modified in cancer patients, with CD66b+ /CD10low /CXCR4+ /PDL1inter subset almost exclusively found in advanced lung cancer patients. We found substantial variability in subsets between patients, and demonstrated that HDN and LDN retain a degree of inherent spontaneous plasticity. Deep phenotypic characterization of cancer-related circulating neutrophils and their modulation along tumor progression is an important advancement in understanding the role of myeloid cells in lung cancer.
Published: 2020
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9. Comparison of Patients Infected With Delta Versus Omicron COVID-19 Variants Presenting to Paris Emergency Departments : A Retrospective Cohort Study

Author: Donia, Bouzid, Benoit, Visseaux, Christian, Kassasseya, Asma, Daoud, Florent, Fémy, Christelle, Hermand, Jennifer, Truchot, Sebastien, Beaune, Nicolas, Javaud, Olivier, Peyrony, Anthony, Chauvin, Prabakar, Vaittinada Ayar, Arthur, Bourg, Bruno, Riou, Stephane, Marot, Ben, Bloom, Marine, Cachanado, Tabassome, Simon, Yonathan, Freund, and Melkir, Saib
Subjects: Adult, Male, Paris, SARS-CoV-2, Internal Medicine, COVID-19, Humans, Female, General Medicine, Middle Aged, Emergency Service, Hospital, Retrospective Studies
Abstract: At the end of 2021, the B.1.1.529 SARS-CoV-2 variant (Omicron) wave superseded the B.1.617.2 variant (Delta) wave.To compare baseline characteristics and in-hospital outcomes of patients with SARS-CoV-2 infection with the Delta variant versus the Omicron variant in the emergency department (ED).Retrospective chart reviews.13 adult EDs in academic hospitals in the Paris area from 29 November 2021 to 10 January 2022.Patients with a positive reverse transcriptase polymerase chain reaction (RT-PCR) test result for SARS-CoV-2 and variant identification.Main outcome measures were baseline clinical and biological characteristics at ED presentation, intensive care unit (ICU) admission, mechanical ventilation, and in-hospital mortality.A total of 3728 patients had a positive RT-PCR test result for SARS-CoV-2 during the study period; 1716 patients who had a variant determination (818 Delta and 898 Omicron) were included. Median age was 58 years, and 49% were women. Patients infected with the Omicron variant were younger (54 vs. 62 years; difference, 8.0 years [95% CI, 4.6 to 11.4 years]), had a lower rate of obesity (8.0% vs. 12.5%; difference, 4.5 percentage points [CI, 1.5 to 7.5 percentage points]), were more vaccinated (65% vs. 39% for 1 dose and 22% vs. 11% for 3 doses), had a lower rate of dyspnea (26% vs. 50%; difference, 23.6 percentage points [CI, 19.0 to 28.2 percentage points]), and had a higher rate of discharge home from the ED (59% vs. 37%; difference, 21.9 percentage points [-26.5 to -17.1 percentage points]). Compared with Delta, Omicron infection was independently associated with a lower risk for ICU admission (adjusted difference, 11.4 percentage points [CI, 8.4 to 14.4 percentage points]), mechanical ventilation (adjusted difference, 3.6 percentage points [CI, 1.7 to 5.6 percentage points]), and in-hospital mortality (adjusted difference, 4.2 percentage points [CI, 2.0 to 6.5 percentage points]).Patients with COVID-19 illness and no SARS-CoV-2 variant determination in the ED were excluded.Compared with the Delta variant, infection with the Omicron variant in patients in the ED had different clinical and biological patterns and was associated with better in-hospital outcomes, including higher survival.None.
Published: 2022

10. Pulmonary embolism severity and in-hospital mortality: An international comparative study between COVID-19 and non-COVID patients

Author: Òscar Miró, Sònia Jiménez, Pere Llorens, Melanie Roussel, Judith Gorlicki, Eric Jorge García-Lamberechts, Pierrick Le Borgne, Javier Jacob, Anthony Chauvin, Olivier Lucidarme, Guillermo Burillo-Putze, Alfons Aguirre, Fabien Brigant, Laura Lozano, Juan González del Castillo, and Yonathan Freund
Subjects: Risk factors, PESI, Pulmonary embolism, Internal Medicine, Mortality, Article, Severity, COVID
Abstract: Objective: To compare the severity of pulmonary embolism (PE) between patients with and without COVID, and to assess the association between severity and in-hospital-mortality. Methods: We performed an analysis of 549 COVID (71.3% PCR-confirmed) and 439 non-COVID patients with PE consecutively included by 62 Spanish and 16 French emergency departments. PE-severity was assessed by size, the presence of right ventricular dysfunction (RVD), and the sPESI. The association of PE-severity and in-hospital-mortality was assessed both in COVID and non-COVID patients, and the interaction of COVID status and PE severity/outcome associations was also evaluated. Results: COVID patients had PEs of smaller size (43% vs 56% lobar or larger, 42% vs. 35% segmental and 13% vs. 9% subsegmental, respectively; p = 0.01 for trend), less RVD (22% vs. 16%, p=0.02) and lower sPESI (p=0.03 for trend). Risk of in-hospital death was higher in COVID patients (12.8% vs. 5.3%, p < 0.001). PE-severity assessed by RVD and sPESI was independently associated with in-hospital-mortality in COVID patients, while PE size and sPESI were significantly associated with in-hospital-mortality in non-COVID. COVID status showed a significant interaction in the association of PE size and outcome (p=0.01), with OR for in-hospital mortality in COVID and non-COVID patients with lobar or larger PE of 0.92 (95%CI=0.19-4.47) and 4.47 (95% CI=1.60-12.5), respectively. Sensitivity analyses using only PCR-confirmed COVID cases confirmed these results. Conclusion: COVID patients present a differential clinical picture, with PE of less severity than in non-COVID patients. An increased sPESI was associated with the risk of mortality in both groups but, PE size did not seem to be associated with in-hospital mortality in COVID patients.
Published: 2022

11. A half century of fish gonadotropin‐releasing hormones: Breaking paradigms

Author: Vance L. Trudeau, José Antonio Muñoz-Cueto, Matan Golan, Yonathan Zohar, and Nilli Zmora
Subjects: 0106 biological sciences, medicine.medical_specialty, medicine.drug_class, Endocrinology, Diabetes and Metabolism, media_common.quotation_subject, Zoology, Biology, 010603 evolutionary biology, 01 natural sciences, Gonadotropin-Releasing Hormone, 03 medical and health sciences, Cellular and Molecular Neuroscience, Endocrinology, Internal medicine, Gene duplication, medicine, Animals, 030304 developmental biology, media_common, Mammals, 0303 health sciences, Endocrine and Autonomic Systems, Neuroendocrinology, Neurosecretory Systems, %22">Fish , Reproduction, Gonadotropin, Gonadotropins, Hormone
Abstract: The field of fish gonadotropin-releasing hormones (GnRHs) is also celebrating its 50th anniversary this year. This review provides a chronological history of fish GnRH biology over the past five decades. It demonstrates how discoveries in fish regarding GnRH and GnRH receptor multiplicity, dynamic interactions between GnRH neurons, and additional neuroendocrine factors acting alongside GnRH, amongst others, have driven a paradigm shift in our understanding of GnRH systems and functions in vertebrates, including mammals. The role of technological innovations in enabling scientific discoveries is portrayed, as well as how fundamental research in fish GnRH led to translational outcomes in aquaculture. The interchange between fish and mammalian GnRH research is discussed, as is the value and utility of using fish models for advancing GnRH biology. Current challenges and future perspectives are presented, with the hope of expanding the dialogue and collaborations within the neuroendocrinology scientific community at large, capitalizing on diversifying model animals and the use of comparative strategies.
Published: 2021
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12. Safety and Efficiency of Diagnostic Strategies for Ruling Out Pulmonary Embolism in Clinically Relevant Patient Subgroups : A Systematic Review and Individual-Patient Data Meta-analysis

Author: Milou A.M. Stals, Toshihiko Takada, Noémie Kraaijpoel, Nick van Es, Harry R. Büller, D. Mark Courtney, Yonathan Freund, Javier Galipienzo, Grégoire Le Gal, Waleed Ghanima, Menno V. Huisman, Jeffrey A. Kline, Karel G.M. Moons, Sameer Parpia, Arnaud Perrier, Marc Righini, Helia Robert-Ebadi, Pierre-Marie Roy, Maarten van Smeden, Phil S. Wells, Kerstin de Wit, Geert-Jan Geersing, and Frederikus A. Klok
Subjects: Fibrin Fibrinogen Degradation Products, Neoplasms, Internal Medicine, Humans, General Medicine, Venous Thromboembolism, Pulmonary Embolism, Probability
Abstract: Background: How diagnostic strategies for suspected pulmonary embolism (PE) perform in relevant patient subgroups defined by sex, age, cancer, and previous venous thromboembolism (VTE) is unknown. Purpose: To evaluate the safety and efficiency of the Wells and revised Geneva scores combined with fixed and adapted D-dimer thresholds, as well as the YEARS algorithm, for ruling out acute PE in these subgroups. Data Sources: MEDLINE from 1 January 1995 until 1 January 2021. Study Selection: 16 studies assessing at least 1 diagnostic strategy. Data Extraction: Individual-patient data from 20553 patients. Data Synthesis: Safety was defined as the diagnostic failure rate (the predicted 3-month VTE incidence after exclusion of PE without imaging at baseline). Efficiency was defined as the proportion of individuals classified by the strategy as "PE con -sidered excluded" without imaging tests. Across all strategies, efficiency was highest in patients younger than 40 years (47% to 68%) and lowest in patients aged 80 years or older (6.0% to 23%) or patients with cancer (9.6% to 26%). However, efficiency improved considerably in these subgroups when pretest probabil-ity-dependent D-dimer thresholds were applied. Predicted failure rates were highest for strategies with adapted D-dimer thresh-olds, with failure rates varying between 2% and 4% in the pre-defined patient subgroups. Limitations: Between-study differences in scoring predictor items and D-dimer assays, as well as the presence of differential verifica-tion bias, in particular for classifying fatal events and subsegmental PE cases, all of which may have led to an overestimation of the predicted failure rates of adapted D-dimer thresholds. Conclusion: Overall, all strategies showed acceptable safety, with pretest probability-dependent D-dimer thresholds having not only the highest efficiency but also the highest predicted failure rate. From an efficiency perspective, this individual-patient data meta-analysis supports application of adapted D-dimer thresholds. Primary Funding Source: Dutch Research Council. (PROSPERO: CRD42018089366)
Published: 2021

13. Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol

Author: Gregory G. Schwartz, Michael Szarek, Vera A. Bittner, Rafael Diaz, Shaun G. Goodman, J. Wouter Jukema, Ulf Landmesser, Patricio López-Jaramillo, Garen Manvelian, Robert Pordy, Michel Scemama, Peter R. Sinnaeve, Harvey D. White, Ph Gabriel Steg, P.h. Gabriel Steg, Deepak L. Bhatt, Robert A. Harrington, Andreas M. Zeiher, Pierluigi Tricoci, Matthew T. Roe, Kenneth W. Mahaffey, Jay M. Edelberg, Corinne Hanotin, Guillaume Lecorps, Angèle Moryusef, William J. Sasiela, Jean-François Tamby, Philip E. Aylward, Heinz Drexel, Peter Sinnaeve, Mirza Dilic, Renato D. Lopes, Nina N. Gotcheva, Juan-Carlos Prieto, Huo Yong, Ivan Pećin, Zeljko Reiner, Petr Ostadal, Steen Hvitfeldt Poulsen, Margus Viigimaa, Markku S. Nieminen, Nicolas Danchin, Vakhtang Chumburidze, Nikolaus Marx, Evangelos Liberopoulos, Pablo Carlos Montenegro Valdovinos, Hung-Fat Tse, Robert Gabor Kiss, Denis Xavier, Doron Zahger, Marco Valgimigli, Takeshi Kimura, Hyo Soo Kim, Sang-Hyun Kim, Andrejs Erglis, Aleksandras Laucevicius, Sasko Kedev, Khalid Yusoff, Gabriel Arturo Ramos López, Marco Alings, Sigrun Halvorsen, Roger M. Correa Flores, Rody G. Sy, Andrzej Budaj, Joao Morais, Maria Dorobantu, Yuri Karpov, Arsen D. Ristic, Terrance Chua, Jan Murin, Zlatko Fras, Anthony J. Dalby, José Tuñón, H. Asita de Silva, Emil Hagström, Christian Müller, Chern-En Chiang, Piyamitr Sritara, Sema Guneri, Alexander Parkhomenko, Kausik K. Ray, Patrick M. Moriarty, Robert Vogel, Bernard Chaitman, Sheryl F. Kelsey, Anders G. Olsson, Jean-Lucien Rouleau, Maarten L. Simoons, Karen Alexander, Chiara Meloni, Robert Rosenson, Eric J.G. Sijbrands, John H. Alexander, Luciana Armaganijan, Akshay Bagai, Maria Cecilia Bahit, J. Matthew Brennan, Shaun Clifton, Adam D. DeVore, Shalonda Deloatch, Sheila Dickey, Keith Dombrowski, Grégory Ducrocq, Zubin Eapen, Patricia Endsley, Arleen Eppinger, Robert W. Harrison, Connie Ng Hess, Mark A. Hlatky, Joseph Dedrick Jordan, Joshua W. Knowles, Bradley J. Kolls, David F. Kong, Sergio Leonardi, Linda Lillis, David J. Maron, Jill Marcus, Robin Mathews, Rajendra H. Mehta, Robert J. Mentz, Humberto Graner Moreira, Chetan B. Patel, Sabrina Bernardez Pereira, Lynn Perkins, Thomas J. Povsic, Etienne Puymirat, William Schuyler Jones, Bimal R. Shah, Matthew W. Sherwood, Kenya Stringfellow, Darin Sujjavanich, Mustafa Toma, Charlene Trotter, Sean F.P. van Diepen, Matthew D. Wilson, Andrew Tze-Kay Yan, Lilia B. Schiavi, Marcelo Garrido, Andrés F. Alvarisqueta, Sonia A. Sassone, Anselmo P. Bordonava, Alberto E. Alves De Lima, Jorge M. Schmidberg, Ernesto A. Duronto, Orlando C. Caruso, Leonardo P. Novaretto, Miguel Angel Hominal, Oscar R. Montaña, Alberto Caccavo, Oscar A. Gomez Vilamajo, Alberto J. Lorenzatti, Luis R. Cartasegna, Gustavo A. Paterlini, Ignacio J. Mackinnon, Guillermo D. Caime, Marcos Amuchastegui, Oscar Salomone, Oscar R. Codutti, Horacio O. Jure, Julio O.E. Bono, Adrian D. Hrabar, Julio A. Vallejos, Rodolfo A. Ahuad Guerrero, Federico Novoa, Cristian A. Patocchi, Cesar J. Zaidman, Maria E. Giuliano, Ricardo D. Dran, Marisa L. Vico, Gabriela S. Carnero, Pablo N. Guzman, Juan C. Medrano Allende, Daniela F. Garcia Brasca, Miguel H. Bustamante Labarta, Sebastian Nani, Eduardo D.S. Blumberg, Hugo R. Colombo, Alberto Liberman, Victorino Fuentealba, Hector L. Luciardi, Gabriel D. Waisman, Mario A. Berli, Ruben O. Garcia Duran, Horacio G. Cestari, Hugo A. Luquez, Jorge A. Giordano, Silvia S. Saavedra, Gerardo Zapata, Osvaldo Costamagna, Susana Llois, Jonathon H. Waites, Nicholas Collins, Allan Soward, Chris L.S. Hii, James Shaw, Margaret A. Arstall, John Horowitz, Daniel Ninio, James F. Rogers, David Colquhoun, Romulo E. Oqueli Flores, Philip Roberts-Thomson, Owen Raffel, Sam J. Lehman, Constantine Aroney, Steven G.M. Coverdale, Paul J. Garrahy, Gregory Starmer, Mark Sader, Patrick A. Carroll, Ronald Dick, Robert Zweiker, Uta Hoppe, Kurt Huber, Rudolf Berger, Georg Delle-Karth, Bernhard Frey, Dirk Faes, Kurt Hermans, Bruno Pirenne, Attilio Leone, Etienne Hoffer, Mathias C.M. Vrolix, Luc De Wolf, Bart Wollaert, Marc Castadot, Karl Dujardin, Christophe Beauloye, Geert Vervoort, Harry Striekwold, Carl Convens, John Roosen, Emanuele Barbato, Marc Claeys, Frank Cools, Ibrahim Terzic, Fahir Barakovic, Zlatko Midzic, Belma Pojskic, Emir Fazlibegovic, Azra Durak-Nalbantic, Mehmed Kulić, Dusko Vulic, Adis Muslibegovic, Boris Goronja, Gilmar Reis, Luciano Sousa, Jose C. Nicolau, Flavio E. Giorgeto, Ricardo P. Silva, Lilia Nigro Maia, Rafael Rech, Paulo R.F. Rossi, Maria José A.G. Cerqueira, Norberto Duda, Renato Kalil, Adrian Kormann, José Antonio M. Abrantes, Pedro Pimentel Filho, Ana Priscila Soggia, Mayler O.N. de Santos, Fernando Neuenschwander, Luiz C. Bodanese, Yorghos L. Michalaros, Freddy G. Eliaschewitz, Maria H. Vidotti, Paulo E. Leaes, Roberto V. Botelho, Sergio Kaiser, Euler Roberto F. Fernandes Manenti, Dalton B. Precoma, Jose C. Moura Jorge, Pedro Silva, Jose A. Silveira, Wladmir Saporito, Jose A. Marin Neto, Gilson S. Feitosa, Luiz Eduardo F. Ritt, Juliana A. de Souza, Fernando Costa, Weimar K.S.B. Souza, Helder J.L. Reis, Leandro Machado, José Carlos Aidar Ayoub, Georgi V. Todorov, Fedya P. Nikolov, Elena S. Velcheva, Maria L. Tzekova, Haralambi O. Benov, Stanislav L. Petranov, Haralin S. Tumbev, Nina S. Shehova-Yankova, Dimitar T. Markov, Dimitar H. Raev, Mihail N. Mollov, Kostadin N. Kichukov, Katya A. Ilieva-Pandeva, Raya Ivanova, Maryana Gospodinov, Valentina M. Mincheva, Petar V. Lazov, Bojidar I. Dimov, Manohara Senaratne, James Stone, Jan Kornder, Stephen Pearce, Danielle Dion, Daniel Savard, Yves Pesant, Amritanshu Pandey, Simon Robinson, Gilbert Gosselin, Saul Vizel, Gordon Hoag, Ronald Bourgeois, Anne Morisset, Eric Sabbah, Bruce Sussex, Simon Kouz, Paul MacDonald, Ariel Diaz, Nicolas Michaud, David Fell, Raymond Leung, Tycho Vuurmans, Christopher Lai, Frank Nigro, Richard Davies, Gustavo Nogareda, Ram Vijayaraghavan, John Ducas, Serge Lepage, Shamir Mehta, James Cha, Robert Dupuis, Peter Fong, Sohrab Lutchmedial, Josep Rodes-Cabau, Hussein Fadlallah, David Cleveland, Thao Huynh, Iqbal Bata, Adnan Hameed, Cristian Pincetti, Sergio Potthoff, Juan C. Prieto, Monica Acevedo, Arnoldo Aguirre, Margarita Vejar, Mario Yañez, Guillermo Araneda, Mauricio Fernandez, Luis Perez, Paola Varleta, Fernando Florenzano, Laura Huidobro, Carlos A. Raffo, Claudia Olivares, Leonardo Nahuelpan, Humberto Montecinos, Jiyan Chen, Yugang Dong, Weijian Huang, Jianzhong Wang, Shi'An Huang, Zhuhua Yao, Xiang Li, Lan Cui, Wenhua Lin, Yuemin Sun, Jingfeng Wang, Jianping Li, Xuelian Zhang, Hong Zhu, Dandan Chen, Lan Huang, Shaohong Dong, Guohai Su, Biao Xu, Xi Su, Xiaoshu Cheng, Jinxiu Lin, Wenxia Zong, Huanming Li, Yi Feng, Dingli Xu, Xinchun Yang, Yuannan Ke, Xuefeng Lin, Zheng Zhang, Zeqi Zheng, Zhurong Luo, Yundai Chen, Chunhua Ding, Yi Zhong, Yang Zheng, Xiaodong Li, Daoquan Peng, Shuiping Zhao, Ying Li, Xuebo Liu, Meng Wei, Shaowen Liu, Yihua Yu, Baiming Qu, Weihong Jiang, Yujie Zhou, Xingsheng Zhao, Zuyi Yuan, Ying Guo, Xiping Xu, Xubo Shi, Junbo Ge, Guosheng Fu, Feng Bai, Weiyi Fang, Xiling Shou, Xiangjun Yang, Jian'An Wang, Meixiang Xiang, Yingxian Sun, Qinghua Lu, Ruiyan Zhang, Jianhua Zhu, Yizhou Xu, Zhongcai Fan, Tianchang Li, Chun Wu, Nicolas Jaramillo, Gregorio Sanchez Vallejo, Diana C. Luna Botia, Rodrigo Botero Lopez, Dora I. Molina De Salazar, Alberto J. Cadena Bonfanti, Carlos Cotes Aroca, Juan Diego Higuera, Marco Blanquicett, Sandra I. Barrera Silva, Henry J. Garcia Lozada, Julian A. Coronel Arroyo, Jose L. Accini Mendoza, Ricardo L. Fernandez Ruiz, Alvaro M. Quintero Ossa, Fernando G. Manzur Jatin, Aristides Sotomayor Herazo, Jeffrey Castellanos Parada, Rafael Suarez Arambula, Miguel A. Urina Triana, Angela M. Fernandez Trujillo, Maja Strozzi, Siniša Car, Melita Jerić, Davor Miličić, Martina Lovrić Benčić, Hrvoje Pintarić, Đeiti Prvulović, Jozica Šikić, Viktor Peršić, Dean Mileta, Kresimir Štambuk, Zdravko Babić, Vjekoslav Tomulic, Josip Lukenda, Stanka Mejic-Krstulovic, Boris Starcevic, Jindrich Spinar, David Horak, Zdenek Velicka, Josef Stasek, David Alan, Vilma Machova, Ales Linhart, Vojtech Novotny, Vladimir Kaucak, Richard Rokyta, Robert Naplava, Zdenek Coufal, Vera Adamkova, Ivo Podpera, Jiri Zizka, Zuzana Motovska, Ivana Marusincova, Premysl Svab, Petr Heinc, Jiri Kuchar, Petr Povolny, Jiri Matuska, Steen H. Poulsen, Bent Raungaard, Peter Clemmensen, Lia E. Bang, Ole May, Morten Bøttcher, Jens D. Hove, Lars Frost, Gunnar Gislason, John Larsen, Peter Betton Johansen, Flemming Hald, Peter Johansen, Jørgen Jeppesen, Tonny Nielsen, Kjeld S. Kristensen, Piotr Maria Walichiewicz, Jens D. Lomholdt, Ib C. Klausen, Peter Kaiser Nielsen, Flemming Davidsen, Lars Videbaek, Mai Soots, Veiko Vahula, Anu Hedman, Üllar Soopõld, Kaja Märtsin, Tiina Jurgenson, Arved Kristjan, Heikki Huikuri, Juhani Airaksinen Pierre Coste, Emile Ferrari, Olivier Morel, Gilles Montalescot, Jacques Machecourt, Gilles Barone-Rochette, Jacques Mansourati, Yves Cottin, Florence Leclercq, Abdelkader Belhassane, Nicolas Delarche, Franck Boccara, Franck Paganelli, Jérôme Clerc, Francois Schiele, Victor Aboyans, Vincent Probst, Jacques Berland, Thierry Lefèvre, Bernard Citron, Irakli Khintibidze, Tamaz Shaburishvili, Zurab Pagava, Ramaz Ghlonti, Zaza Lominadze, George Khabeishvili, Rayyan Hemetsberger, Kemala Edward, Ursula Rauch-Kröhnert, Matthias Stratmann, Karl-Friedrich Appel, Ekkehard Schmidt, Heyder Omran, Christoph Stellbrink, Thomas Dorsel, Emmanouil Lianopoulos, Hans Friedrich Vöhringer, Roger Marx, Andreas Zirlik, Detlev Schellenberg, Thomas Heitzer, Ulrich Laufs, Christian Werner, Stephan Gielen, Sebastian Nuding, Bernhard Winkelmann, Steffen Behrens, Karsten Sydow, Mahir Karakas, Gregor Simonis, Thomas Muenzel, Nikos Werner, Stefan Leggewie, Dirk Böcker, Rüdiger Braun-Dullaeus, Nicole Toursarkissian, Michael Jeserich, Matthias Weißbrodt, Tim Schaeufele, Joachim Weil, Heinz Völler, Johannes Waltenberger, Mohammed Natour, Susanne Schmitt, Dirk Müller-Wieland, Stephan Steiner, Lothar Heidenreich, Elmar Offers, Uwe Gremmler, Holger Killat, Werner Rieker, Sotiris Patsilinakos, Athanasios Kartalis, Athanassios Manolis, Dimitrios Sionis, Geargios Chachalis, Ioannis Skoumas, Vasilios Athyros, Panagiotis Vardas, Frangkiskos Parthenakis, John Lekakis, Apostolos Hatzitolios, Sergio R. Fausto Ovando, Juan L. Arango Benecke, Edgar R. Rodriguez De Leon, Bryan P.Y. Yan, David C.W. Siu, Tibor Turi, Bela Merkely, Imre Ungi, Geza Lupkovics, Lajos Nagy, András Katona, István Édes, Gábor Müller, Iván Horvath, Tibor Kapin, Zsolt Szigeti, József Faluközy, Mukund Kumbla, Manjinder Sandhu, Sharath Annam, Naveen Reddy Proddutur, Reddy Regella, Rajendra K. Premchand, Ajaykumar Mahajan, Sudhir Pawar, Atul D. Abhyanakar, Prafulla Kerkar, Ravishankar A. Govinda, Abraham Oomman, Dhurjati Sinha, Sachin N. Patil, Dhiman Kahali, Jitendra Sawhney, Abhijeet B. Joshi, Sanjeev Chaudhary, Pankaj Harkut, Santanu Guha, Sanjay Porwal, Srimannarayana Jujjuru, Ramesh B. Pothineni, Minguel R. Monteiro, Aziz Khan, Shamanna S. Iyengar, Jasprakash Singh Grewal, Manoj Chopda, Mahesh C. Fulwani, Aparna Patange, Patil Sachin, Vijay K. Chopra, Naresh K. Goyal, Rituparna Shinde, Gajendra V. Manakshe, Nitin Patki, Sumeet Sethi, Vengatesh Munusamy, Sunil Karnaand Sunil Thanvi, Srilakshmi Adhyapak, Chandrakant Patil, Ulhas Pandurangi, Rishabh Mathur, Jugal Gupta, Suhas Kalashetti, Ajit Bhagwat, Bagirath Raghuraman, Shiv Kumar Yerra, Prasant Bhansali, Rohidas Borse, Patil Rahul, Srihari Das, Vinay Kumar, Jabir Abdullakutty, Shireesh Saathe, Priya Palimkar, Jabir Abdullkutty, Shireesh Sathe, Shaul Atar, Michael Shechter, Morris Mosseri, Yaron Arbel, Chorin Ehud, Havakuk Ofer, Chaim Lotan, Uri Rosenschein, Amos Katz, Yaakov Henkin, Adi Francis, Marc Klutstein, Eugenia Nikolsky, Robert Zukermann, Yoav Turgeman, Majdi Halabi, Alon Marmor, Ran Kornowski, Michael Jonas, Offer Amir, Yonathan Hasin, Yoseph Rozenman, Shmuel Fuchs, Vered Zvi, Osamah Hussein, Dov Gavish, Zvi Vered, Yoseph Caraco, Mazen Elias, Naveh Tov, Efrat Wolfovitz, Michael Lishner, Nizar Elias, Giancarlo Piovaccari, Annamaria De Pellegrin, Raffaella Garbelotto, Gabriele Guardigli, Valgimigli Marco, Giovanni Licciardello, Carla Auguadro, Filippo Scalise, Claudio Cuccia, Alessandro Salvioni, Giuseppe Musumeci, Michelle Senni, Paolo Calabrò, Salvatore Novo, Pompilio Faggiano, Marco Metra, Nicoletta B. De Cesare, Sergio Berti, Claudio Cavallini, Enrico Puccioni, Marcello Galvani, Maurizio Tespili, Piermarco Piatti, Michela Palvarini, Giuseppe De Luca, Roberto Violini, Alessandro De Leo, Zoran Olivari, Pasquale Perrone Filardi, Maurizio Ferratini, Vittorio Racca, Kazuoki Dai, Yuji Shimatani, Haruo Kamiya, Kenji Ando, Yoshihiro Takeda, Yoshihiro Morino, Yoshiki Hata, Kazuo Kimura, Koichi Kishi, Ichiro Michishita, Hiroki Uehara, Toshinori Higashikata, Atsushi Hirayama, Keiji Hirooka, Yasuji Doi, Satoru Sakagami, Shuichi Taguchi, Akihiro Koike, Hiroyuki Fujinaga, Shinji Koba, Ken Kozuma, Tomohiro Kawasaki, Yujiro Ono, Masatoshi Shimizu, Yousuke Katsuda, Atsuyuki Wada, Toshiro Shinke, Junya Ako, Kenshi Fujii, Toshiyuki Takahashi, Tomohiro Sakamoto, Koichi Nakao, Yutaka Furukawa, Hiroshi Sugino, Ritsu Tamura, Toshiaki Mano, Masaaki Uematsu, Noriaki Utsu, Kashima Ito, Takuya Haraguchi, Katsuhiko Sato, Yasunori Ueda, Akira Nishibe, Kazuteru Fujimoto, Motomaru Masutani, Jung Han Yoon, Hack-Lyoung Kim, Hun Sik Park, In-Ho Chae, Moo Hyun Kim, Myung Ho Jeong, Seungwoon Rha, Chongjin Kim, Hae Young Kim, Taekjong Hong, Seung-Jea Tahk, Youngkwon Kim, Arija Busmane, Natalija Pontaga, Aldis Strelnieks, Iveta Mintale, Iveta Sime, Zaneta Petrulioniene, Roma Kavaliauskiene, Ruta Jurgaitiene, Gintare Sakalyte, Rimvydas Slapikas, Sigute Norkiene, Nerijus Misonis, Aleksandras Kibarskis, Raimondas Kubilius, Stojko Bojovski, Nensi Lozance, Aleksandar Kjovkaroski, Snezana Doncovska, Tiong Kiam Ong, Sazzli Kasim, Oteh Maskon, Balachandran Kandasamy, Houng B. Liew, Wan Mohd Izani Wan Mohamed, Armando García Castillo, Jorge Carrillo Calvillo, Pedro Fajardo Campos, Juan Carlos Núñez Fragoso, Edmundo Alfredo Bayram Llamas, Marco Antonio Alcocer Gamba, Jaime Carranza Madrigal, Luis Gerardo González Salas, Enrique López Rosas, Belinda González Díaz, Eduardo Salcido Vázquez, Alfredo Nacoud Ackar, Guillermo Antonio Llamas Esperón, Carlos Rodolfo Martínez Sánchez, María Guerrero De Leon, Rodrigo Suarez Otero, Guillermo Fanghänel Salmón, Jesús Antonio Pérez Ríos, José Angel Garza Ruíz, Robert W. Breedveld, Margriet Feenema-Aardema, Alida Borger-Van Der Burg, Pieter A.M. Hoogslag, Harry Suryapranata, Antonius Oomen, Paulus Van Haelst, Margriet Feenema-Aradema, Jacobijne J. Wiersma, Dirk Basart, Ruud M.A. Van Der Wal, Peter Zwart, Pascalle Monraats, Henricus Van Kesteren, Ioannis Karalis, Johan Jukema, Gerardus J.E. Verdel, Bart R.G. Brueren, Roland PTh Troquay, Eric P. Viergever, Nadea Y.Y. Al-Windy, Gerard L. Bartels, Jan H. Cornel, Walter R.M. Hermans, Johannes P.R. Herrman, Robert J. Bos, Reginald G.E.J. Groutars, Coenraad C. Van Der Zwaan, Refik Kaplan, Raymond Lionarons, Eelko Ronner, Bjorn E. Groenemeijer, Patrick N.A. Bronzwaer, Anho A.H. Liem, Bernard J.W.M. Rensing, Marcel J.J.A. Bokern, Remco Nijmeijer, Ferry M.R.J. Hersbach, Frank F. Willems, Antonius T.M. Gosselink, Saman Rasoul, John Elliott, Gerard Wilkins, Raewyn Fisher, Douglas Scott, Hamish Hart, Ralph Stewart, Scott Harding, Ian Ternouth, Nicholas Fisher, Samuel Wilson, Denise Aitken, Russell Anscombe, Laura Davidson, Tadeusz Tomala, Ottar Nygård, Jon Arne Sparby, Kjell Andersen, Lars Gullestad, Jarle Jortveit, Peter S. Munk, Erlend gyllensten Singsaas, Ulf Hurtig, Jorge R. Calderon Ticona, Julio R. Durand Velasquez, Sandra A. Negron Miguel, Enrique S. Sanabria Perez, Jesus M. Carrion Chambilla, Carlos A. Chavez Ayala, Reynaldo P. Castillo Leon, Rolando J. Vargas Gonzales, Jose D. Hernandez Zuniga, Luis A. Camacho Cosavalente, Jorge E. Bravo Mannucci, Javier Heredia Landeo, Nassip C. Llerena Navarro, Yudy M. Roldan Concha, Víctor E. Rodriguez Chavez, Henry A. Anchante Hernandez, Carlos A. Zea Nunez, Walter Mogrovejo Ramos, Arthur Ferrolino, Rosa Allyn G. Sy, Louie Tirador, Generoso Matiga, Raul Martin Coching, Alisa Bernan, Gregorio Rogelio, Dante D. Morales, Edgar Tan, Dennis Jose Sulit, Adrian Wlodarczak, Krystyna Jaworska, Grzegorz Skonieczny, Lidia Pawlowicz, Pawel Wojewoda, Benita Busz-Papiez, Janusz Bednarski, Aleksander Goch, Pawel Staneta, Elzbieta Dulak, Krzysztof Saminski, Wlodzimierz Krasowski, Wanda Sudnik, Aleksander Zurakowski, Marcin Skorski, Roman Lysek, Beata Miklaszewicz, Jacek Kubica, Jan Andrzej Lipko, Edyta Kostarska-Srokosz, Marek Piepiorka, Anna Drzewiecka, Ryszard Sciborski, Arkadiusz Stasiewski, Tomasz Blicharski, Leszek Bystryk, Michal Szpajer, Marek Korol, Tomasz Czerski, Ewa Mirek-Bryniarska, Jacek Gniot, Andrzej Lubinski, Jerzy Gorny, Edward Franek, Grzegorz Raczak, Hanna Szwed, Pedro Monteiro, Jose Mesquita Bastos, Helder H. Pereira, Dinis Martins, Filipe Seixo, Carlos Mendonça, Ana Botelho, Francisca Caetano, Bogdan Minescu, Octavian Istratoaie, Dan N. Tesloianu, Gabriel Cristian, Silviu Dumitrescu, Cristian G.C. Podoleanu, Mircea C.A. Constantinescu, Cristina M. Bengus, Constantin Militaru, Doina Rosu, Irinel R. Parepa, Adrian V. Matei, Tom M. Alexandru, Mihaela Malis, Ioan Coman, Rodica Stanescu-Cioranu, Doina Dimulescu, Yury Shvarts, Olga Orlikova, Zhanna Kobalava, Olga L. Barbarash, Valentin Markov, Nadezhda Lyamina, Alexander Gordienko, Konstantin Zrazhevsky, Alexander Y. Vishnevsky, Victor Gurevich, Raisa Stryuk, Nikita V. Lomakin, Igor Bokarev, Tatiana Khlevchuk, Sergey Shalaev, Larisa Khaisheva, Petr Chizhov, Inna Viktorova, Natalya Osokina, Vladimir Shchekotov, Evgenia Akatova, Galina Chumakova, Igor Libov, Mikhail I. Voevoda, Tatyana V. Tretyakova, Evgeny Baranov, Sergey Shustov, Sergey Yakushin, Ivan Gordeev, Niiaz Khasanov, Olga Reshetko, Tatiana Sotnikova, Olga Molchanova, Konstantin Nikolaev, Liudmila Gapon, Elena Baranova, Zaur Shogenov, Elena Kosmachova, Yuriy Karpov, Anton Povzun, Liudmila Egorova, Vadim V. Tyrenko, Igor G. Ivanov, Masterov Ilya, Sergey Kanorsky, Dragan Simic, Nikola Ivanovic, Goran Davidovic, Nebojsa Tasic, Milika R. Asanin, Stevo Stojic, Svetlana R. Apostolovic, Stevan Ilic, Biljana Putnikovic Tosic, Aleksandar Stankovic, Aleksandra Arandjelovic, Slavica Radovanovic, Branislava Todic, Jovan Balinovac, Dragan V. Dincic, Petar Seferovic, Ana Karadzic, Slobodan Dodic, Sinisa Dimkovic, Tamara Jakimov, Kian-Keong Poh, Hean Yee Ong, Justin Tang I-Shing, Karol Micko, Jan Nociar, Daniel Pella, Peter Fulop, Marian Hranai, Juraj Palka, Juraj Mazur, Ivan Majercák, Andrej Dzupina, František Fazekas, Jozef Gonsorcik, Viliam Bugan, Juraj Selecky, Gabriel Kamensky, Jaroslava Strbova, Rudolf Smik, Andrej Dukat, Peter Olexa, Ivan Žuran, Janez Poklukar, Nataša Černič Šuligoj, Matija Cevc, Henry P. Cyster, Naresh Ranjith, Clive Corbett, Junaid Bayat, Ellen Makoali Makotoko, Hendrik du Toit Theron, Ilse E. Kapp, Matthys M. de V Basson, Hanlie Lottering, Dina Van Aswegen, Louis J. Van Zyl, Peter J. Sebastian, Thayabran Pillay, Jan A. Saaiman, Patrick J. Commerford, Soraya Cassimjee, Garda Riaz, Iftikhar O. Ebrahim, Mahomed Sarvan, Joseph H. Mynhardt, Helmuth Reuter, Rajendran Moodley, Manuel Vida, Angel R. Cequier Fillat, Vicente Bodí Peris, Francisco Fuentes Jimenez, Francisco Marín, Jose M. Cruz Fernández, Rafael Jesus Hidalgo Urbano, Blas Gil-Extremera, Pablo Toledo, Fernando Worner Diz, David Garcia-Dorado, Andres Iñiguez, José Tuñón Fernández, Jose R. Gonzalez-Juanatey, Javier Fernandez Portales, Fernando Civeira Murillo, Laia Matas Pericas, Jose Luis Zamorano, Manuel De Mora Martin, Jordi Bruguera Cortada, Joaquin J. Alonso Martin, Jose Maria Serrano Antolin, José R. De Berrazueta Fernández, José Antonio Vázquez de Prada, Jose Francisco Díaz Fernández, José Alberto García Lledó, Juan Cosín Sales, Javier Botas Rodriguez, Gabriel Gusi Tragant, Amparo Benedicto, Carlos Gonzalez-Juanatey, Mercedes Camprubí Potau, Ignacio Plaza Perez, César Morís De La Tassa, Pablo Loma-Osorio Rincon, Javier Balaguer Recena, Juan M. Escudier, Antonio Coca Payeras, Norberto Alonso Orcajo, Pedro Valdivielso, Godwin Constantine, Ruvaiz Haniffa, Nirmali Tissera, Stanley Amarasekera, Chandrike Ponnamperuma, Nimali Fernando, Kaputella Fernando, Jayanthimala Jayawardena, Santharaj Wijeyasingam, Gotabhaya Ranasinghe, Ruvan Ekanayaka, Sepalika Mendis, Vajira Senaratne, Gnanamoorthy Mayurathan, Ajantha Rajapaksha, Thilak Sirisena, Jagath I. Herath, Naomali Amarasena, Stefan Berglund, Gundars Rasmanis, Ola Vedin, Nils Witt, Georgios Mourtzinis, Peter Nicol, Ole Hansen, Stefano Romeo, Steen Agergaard Jensen, Ingemar Torstensson, Ulf Ahremark, Torbjörn Sundelin, Tiziano Moccetti, Francois Mach, Ronald Binde, Oliver Gämperli, Wei-Chuan Tsai, Kwo-Chang Ueng, Wen-Ter Lai, Ming-En Liu, Juey-Jen Hwang, Wei-Hsian Yin, I-Chang Hsieh, Ming-Jer Hsieh, Wei Hsiang Lin, Jen-Yuan Kuo, Tsuei-Yuan Huang, Chih-Yuan Fang, Pinij Kaewsuwanna, Wasant Soonfuang, Woravut Jintapakorn, Apichard Sukonthasarn, Nattawut Wongpraparut, Krisada Sastravaha, Nakarin Sansanayudh, Wirash Kehasukcharoen, Dilok Piyayotai, Paiboon Chotnoparatpat, Ahmet Camsari, Hakan Kultursay, Bulent Mutlu, Murat Ersanli, Mustafa Demirtas, Cevat Kirma, Ertan Ural, Lale Koldas, Oleksandr Karpenko, Alexander Prokhorov, Ihor Vakaluyk, Halyna Myshanych, Dmytro Reshotko, Valeriy Batushkin, Leonid Rudenko, Ihor Kovalskyi, Mykola Kushnir, Vira Tseluyko, Yuriy Mostovoy, Mykola Stanislavchuk, Yulian Kyiak, Yuriy Karpenko, Yaroslav Malynovsky, Andriy Klantsa, Oles Kutniy, Ekaterina Amosova, Viktor Tashchuk, Oleh Leshchuk, Mykola Rishko, Mykola Kopytsya, Andriy Yagensky, Mykola Vatutin, Andriy Bagriy, Olga M. Barna, Olexiy Ushakov, Georgiy Dzyak, Borys Goloborodko, Anatolii Rudenko, Volodymyr Zheleznyy, Jasper Trevelyan, Azfar Zaman, Kaeng Lee, Andrew Moriarty, Rajesh K. Aggarwal, Piers Clifford, Yuk-Ki Wong, Syed M.R. Iqbal, Eduardas Subkovas, Denise Braganza, David Sarkar, Robert Storey, Huw Griffiths, Sam Mcclure, Rangasamy Muthusamy, Simon Smith, John Kurian, Terry Levy, Craig Barr, Honer Kadr, Robert Gerber, Audrius Simaitis, Handrean Soran, Anthony Mathur, Adrian Brodison, Mohammad Ayaz, Muhammad Cheema, Richard Oliver, Simon Thackray, Telal Mudawi, Gohar Rahman, Ayyaz Sultan, Timothy Reynolds, David Sharman, null david Sprigings, Rob Butler, Peter Wilkinson, Gregory Y.H. Lip, Julian Halcox, Sean Gallagher, Nicholas Ossei-Gerning, Gil Vardi, Duccio Baldari, David Brabham, Charles Treasure, Charles Dahl, Bruce Palmer, Alan Wiseman, Abul Khan, Sanjeev Puri, Ann Elizabeth Mohart, Carlos Ince, Enrique Flores, Scott Wright, Shi-Chi Cheng, Michael Rosenberg, William Rogers, Edward Kosinski, Les Forgosh, Jonathan Waltman, Misal Khan, Mohammad Shoukfeh, Georges Dagher, Patrick Cambier, Ira Lieber, Priya Kumar, Cara East, Perry Krichmar, Mian Hasan, Lindsey White, Thomas Knickelbine, Thomas Haldis, Eve Gillespie, Thomas Amidon, David Suh, Imran Arif, Mouhamad Abdallah, Faiq Akhter, Eric Carlson, Michael D'Urso, Fadi El-Ahdab, William Nelson, Katie Moriarty, Barry Harris, Steven Cohen, Luther Carter, Daniel Doty, Kenneth Sabatino, Tariq Haddad, Amir Malik, Sunder Rao, Angel Mulkay, Ion Jovin, Kim Klancke, Vinay Malhotra, Sai K. Devarapalli, Michael Koren, Harish Chandna, George Dodds, Tauqir Goraya, James Bengston, Matthew Janik, Joseph Moran, Andrew Sumner, John Kobayashi, William Davis, Shahram Yazdani, John Pasquini, Maitreya Thakkar, Amarnath Vedere, Wayne Leimbach, James Rider, Sarah fenton, Narendra Singh, Anil V. Shah, Denise Janosik, Carl Pepine, Brett Berman, Joseph Gelormini, Christopher Daniels, Kerensky Richard, Friederike Keating, Nicholas I. Kondo, Sanjay Shetty, Howard Levite, Winfried Waider, Theodore Takata, Mazen Abu-Fadel, Vipul Shah, Rahul Aggarwal, Mark Izzo, Anil Kumar, Brack Hattler, Rose Do, Chad Link, Anna Bortnick, George Kinzfogl, Arnold Ghitis, John Larry, Edward Teufel, Peter Kuhlman, Brent Mclaurin, Wenwu Zhang, Stephen Thew, Jalal Abbas, Matthew White, Othman Islam, Sumeet Subherwal, Nandkishore Ranadive, Babak Vakili, Christian Gring, David Henderson, Timothy Schuchard, Naim Farhat, Geoffrey Kline, Sharan Mahal, Jack Whitaker, Shawn Speirs, Rolf Andersen, Nizar Daboul, Phillip Horwitz, Firas Zahr, George Ponce, Zubair Jafar, Joseph Mcgarvey, Vipul Panchal, Stephen Voyce, Thomas Blok, William Sheldon, Masoud M. Azizad, Carsten Schmalfuss, Mark Picone, Robert Pederson, William Herzog, Keith Friedman, Jason Lindsey, Rosemary Nowins, Eichenlaub Timothy, Parilak Leonard, Norman Lepor, Mahfouz El Shahawy, Howard Weintraub, Anand Irimpen, Alvaro Alonso, Wade May, Daniels Christopher, Thomas Galski, Alan Chu, Freny Mody, Ebrahimi Ramin, Zachary Hodes, Joseph Rossi, Gregory Rose, James Fairlamb, Charles Lambert, Ajit Raisinghani, Antonio Abbate, George Vetrovec, Marilyn King, Charles Carey, Jaime Gerber, Liwa Younis, Hyeun Park, Mladen Vidovich, Thomas Knutson, Dennis Friedman, Fred Chaleff, Arthur Loussararian, Phillip Rozeman, Carey Kimmelstiel, Jeffrey Kuvin, Kevin Silver, Malcolm Foster, Glen Tonnessen, Andrey Espinoza, Mohamadali Amlani, Andreas Wali, Christopher Malozzi, Geert T. Jong, Clara Massey, Keattiyoat Wattanakit, Philip J. O'Donnell, Dinesh Singal, Naseem Jaffrani, Sridhar Banuru, Daniel Fisher, Mark Xenakis, Neal Perlmutter, Ravi Bhagwat, James Strader, Ronald Blonder, Ayim Akyea-Djamson, Ajay Labroo, Kwan Lee, H. John Marais, Edmund Claxton, Robert Weiss, Rohr Kathryn, Martin Berk, Peter Rossi, Parag Joshi, Amit Khera, Ajit S. Khaira, Greg Kumkumian, Steven Lupovitch, Joshua Purow, Stephen Welka, David Hoffman, Stuart Fischer, Eugene Soroka, Donald Eagerton, Samir Pancholy, Michael Ray, Norman Erenrich, Michael Farrar, Stewart Pollock, William J. French, Steve Diamantis, Douglas Guy, Lawrence Gimple, Mark Neustel, Steven Schwartz, Edward Pereira, Seals Albert, Douglas Spriggs, Janet Strain, Suneet Mittal, Anthony Vo, Majed Chane, Jason Hall, Nampalli Vijay, Kapildeo Lotun, F. Martin Lester, Ahed Nahhas, Theodore Pope, Paul Nager, Rakesh Vohra, Mukesh Sharma, Riyaz Bashir, Hinan Ahmed, Michael Berlowitz, Robert Fishberg, Robert Barrucco, Eric Yang, Michael Radin, Daniel Sporn, Dwight Stapleton, Steven Eisenberg, Joel Landzberg, Martin Mcgough, Samir Turk, Michael Schwartz, P. Sandy Sundram, Diwakar Jain, Mark Zainea, Carlos Bayron, Ronald Karlsberg, Suhail Dohad, Henry Lui, William Keen, Donald Westerhausen, Sandeep Khurana, Himanshu Agarwal, Jessica Birchem, William Penny, Mark Chang, Sherrill Murphy, John Henry, Branislav Schifferdecker, John M Gilbert, Gopal Chalavarya, Charles Eaton, John F. Schmedtje, Stuart Christenson, Imran Dotani, Douglas Denham, Alexander Macdonell, Paul Gibson, Aref Rahman, Tammam Al Joundi, Nizar Assi, Gary Conrad, Purushotham Kotha, Michael Love, Gregory Giesler, Howard Rubenstein, Dawood Gamil, Laura Akright, Justine Krawczyk, Joanne Cobler, Terry Wells, James Welker, Robert Foster, Richard Gilmore, Jay Anderson, Douglas Jacoby, Bill Harris, Geraldine Gardner, Ramprasad Dandillaya, Kishor Vora, John Kostis, John Hunter, David Laxson, Eric Ball, Flavia Egydio, Anelise Kawakami, Janaina Oliveira, Julianna Wozniak, Alexander Matthews, Caroline Ratky, Janine Valiris, Lisa Berdan, Anita Hepditch, Kirby Quintero, Tyrus Rorick, Melissa Westbrook, Andrea Pascual, Carla Rovito, Madeleine Bezault, Elodie Drouet, Tabassome Simon, Caroline Alsweiler, Anne Luyten, Julie Butters, Liddy Griffith, Michelle Shaw, Lena Grunberg, Shahidul Islam, Marie-France Brégeault, Nathalie Bougon, Douglas Faustino, Sylvie Fontecave, Judith Murphy, Melanie Verrier, null Veronique Agnetti, Dorthe Andersen, Emmy Badreddine, Mhamed Bekkouche, Cecile Bouancheau, Imane Brigui, Maddy Brocklehurst, Joseph Cianciarulo, Dawn Devaul, Szilvia Domokos, Cecile Gache, Caroline Gobillot, Severine Guillou, Jan Healy, Megan Heath, Gayatri Jaiwal, Carine Javierre, Julien Labeirie, Myriam Monier, Ulises Morales, Asmaa Mrabti, Bicky Mthombeni, Betim Okan, Lucile Smith, Jennifer Sheller, Sebastien Sopena, Valerie Pellan, Fadela Benbernou, Nafissa Bengrait, Maud Lamoureux, Katarina Kralova, Raphael Bejuit, Anthony Coulange, Christelle Berthou, Jérôme Repincay, Christelle Lorenzato, Alexis Etienne, Valerie Gouet, Virginie Loizeau, Mickael Normand, Anne Ourliac, Christelle Rondel, Antony Adamo, Pascale Beltran, Pauline Barraud, Helene Dubois-Gache, Benjamin Halle, Lamia Metwally, Maxime Mourgues, Marc Sotty, Marion Vincendet, Raluca Cotruta, Zhu Chengyue, Dominique Fournie-Lloret, Christine Morrello, Aurelie Perthuis, Patrick Picault, Isabelle Zobouyan, Helen M. Colhoun, Michael A. Dempsey, Mark A. McClanahan, Masira, and Laucevičius, Aleksandras
Subjects: Male, Acute coronary syndrome, medicine.medical_specialty, Cardiac & Cardiovascular Systems, Randomization, PCSK9 inhibitor, LOW-DENSITY-LIPOPROTEIN, Antibodies, Monoclonal, Humanized, acute coronary syndrom, Placebo, Gastroenterology, lipoprotein(a), Internal medicine, medicine, Humans, Low-density lipoprotein cholesterol, Aged, Alirocumab, RISK, low-density lipoprotein cholesterol, Science & Technology, biology, business.industry, PCSK9, PCSK9 Inhibitors, Hazard ratio, ALIROCUMAB, acute coronary syndrome, Cholesterol, LDL, Lipoprotein(a), Middle Aged, EFFICACY, medicine.disease, Cardiovascular Diseases, CARDIOVASCULAR-DISEASE, SAFETY, Cardiovascular System & Cardiology, biology.protein, Female, lipids (amino acids, peptides, and proteins), STATIN, low-density lipoprotein, cholesterol PCSK9 inhibitor, CORONARY, Cardiology and Cardiovascular Medicine, business, Life Sciences & Biomedicine, Mace
Abstract: Digital, Background Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. Objectives In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. Methods ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was 13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with Pinteraction = 0.43. Conclusions In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402), Ciencias Médicas y de la Salud
Published: 2021
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14. Pro-inflammatory cytokine profile is present in the serum of Mexican patients with different stages of diabetic retinopathy secondary to type 2 diabetes

Author: Jonathan Uriel Quevedo-Martínez, Diana Venegas, Victor Manuel Bautista-de Lucio, Joanna Jimenez, Osvaldo Garcia, and Yonathan Garfias
Subjects: 0301 basic medicine, medicine.medical_specialty, medicine.medical_treatment, Type 2 diabetes, Gastroenterology, Retina, Proinflammatory cytokine, immunology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Blood serum, Internal medicine, Diabetes mellitus, medicine, Creatinine, business.industry, Interleukin, Diabetic retinopathy, RE1-994, medicine.disease, diagnostic tests/investigation, Ophthalmology, 030104 developmental biology, Cytokine, chemistry, inflammation, 030221 ophthalmology & optometry, business
Abstract: AimIt’s been reported that pro-inflammatory cytokines are elevated in patients with diabetic retinopathy (DR); this may contribute to the pathophysiology of the disease. The aim of this study is to measure the concentration of various inflammatory cytokines from the main CD4+ T helper inflammatory responses in blood serum from Mexican patients with DR in different stages using cytometric bead array (CBA) technology and correlate them with the presence and severity of DR in order to find possible DR biomarkers that serve as diagnostic or therapeutic predictors.Methods64 subjects were included in the study, 16 in the control group, 16 in the type 2 diabetes mellitus no DR (NDR) group, 16 in the non-proliferative DR (NPDR) group and 16 in the proliferative DR (PDR) group. Cytokine concentrations of interleukin (IL) 1ß, IL‐2, IL‐4, IL‐6, IL‐8, IL‐10, IL‐12, IL‐17A, tumour necrosis factor alpha (TNFα) and interferon-gamma in serum samples were measured using Human Inflammatory and TH1/TH2/TH17 CBA Kit.ResultsIL-6, IL-12, IL-17a and TNFα were significantly higher in the patients with DR compared with the control group. The PDR group showed a slightly lower concentration of serum cytokines IL-6, IL-12 and IL-17a. TNFα showed a higher concentration compared with healthy controls, NDR and NPDR subjects. We also found a positive statistical correlation between the presence and severity of DR with the clinical parameters haemoglobin A1c, body mass index and serum creatinine and the concentration of serum cytokines IL-6 and TNFα.ConclusionOur findings suggest that patients with diabetes and DR have a stronger chronic inflammatory profile compared with non-diabetic subjects.
Published: 2021

15. Medical Therapy of Heart Failure with Reduced Ejection Fraction—A Call for Comparative Research

Author: Maria Novosadova, Alexandre Mebazaa, Alain Cohen-Solal, Koji Takagi, B. Davison, Gad Cotter, Yonathan Freund, Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Service des Urgences [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Momentum Research Inc. [Durham, NC, USA] (MRI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and dilanian, gilles
Subjects: blockers of rennin angiotensin system, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Renal function, heart failure, Review, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, heart failure reduced ejection fraction, Renin–angiotensin system, Heart rate, medicine, 030212 general & internal medicine, Adverse effect, Ejection fraction, beta blockers, treatment, business.industry, General Medicine, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Blood pressure, Heart failure, Cardiology, Medicine, business, Ivabradine, medicine.drug
Abstract: International audience; The armamentarium of therapies for patients with heart failure and reduced ejection fraction (HFREF) has increase substantially with the introduction of Angiotensin Receptor Neprilysin Inhibitor (ARNi), sodium glucose cotransport inhibitors (SGLTis), ivabradine, and Vericinguat, bringing to seven the number of potential therapies for HFREF. In the current review we highlight available data on the different classes of medications. Renin angiotensin blockers (RAASbs) and beta blockers (BBs) were shown to have very substantial effects in patients with HFREF. These medications are generic and hence relatively inexpensive. They have a 30-year track record of relatively benign short- and long-term safety profiles and should remain the cornerstone of therapy for patients with HFREF. ARNis are effective in further reducing adverse effects and should replace RAASbs in symptomatic HFREF patients, despite their relatively high prices. The addition of SGLTis (congested patients), Ivabradine (tachycardic patients), and Vericinguat (hypertensive patients) should be considered in patients who remain symptomatic despite optimal doses of RAASbs/ARNis, MRAs, and BBs. Comparative studies examining the efficacy of these medications, and strategies and prioritizing some over others should be considered as, given their similar side effects on heart rate, blood pressure, and renal function, it is highly unlikely that all can be given to the same patient.
Published: 2021
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16. Gnrh2 maintains reproduction in fasting zebrafish through dynamic neuronal projection changes and regulation of gonadotropin synthesis, oogenesis, and reproductive behaviors

Author: Nilli Zmora, Ten-Tsao Wong, Yonathan Zohar, Miranda Marvel, and Berta Levavi-Sivan
Subjects: 0301 basic medicine, medicine.medical_specialty, medicine.drug_class, Science, media_common.quotation_subject, Neuropeptide, Sexual behaviour, Gonadotropic cell, Oogenesis, Article, Animals, Genetically Modified, Gonadotropin-Releasing Hormone, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Neurites, medicine, Animals, Zebrafish, Gametogenesis, media_common, Neurons, Multidisciplinary, biology, Reproduction, Endocrine system and metabolic diseases, Fasting, biology.organism_classification, 030104 developmental biology, Endocrinology, Mutagenesis, Pituitary Gland, Medicine, Gonadotropin, Gonadotropins, 030217 neurology & neurosurgery, Hormone
Abstract: Restricted food intake, either from lack of food sources or endogenous fasting, during reproductive periods is a widespread phenomenon across the animal kingdom. Considering previous studies show the canonical upstream regulator of reproduction in vertebrates, the hypothalamic Gonadotropin-releasing hormone (Gnrh), is inhibited in some fasting animals, we sought to understand the neuroendocrine control of reproduction in fasted states. Here, we explore the roles of the midbrain neuropeptide, Gnrh2, in inducing reproduction via its pituitary prevalence, gonadotropin synthesis, gametogenesis, and reproductive outputs in the zebrafish model undergoing different feeding regimes. We discovered a fasting-induced four-fold increase in length and abundance of Gnrh2 neuronal projections to the pituitary and in close proximity to gonadotropes, whereas the hypothalamic Gnrh3 neurons are reduced by six-fold in length. Subsequently, we analyzed the functional roles of Gnrh2 by comparing reproductive parameters of a Gnrh2-depleted model, gnrh2−/−, to wild-type zebrafish undergoing different feeding conditions. We found that Gnrh2 depletion in fasted states compromises spawning success, with associated decreases in gonadotropin production, oogenesis, fecundity, and male courting behavior. Gnrh2 neurons do not compensate in other circumstances by which Gnrh3 is depleted, such as in gnrh3−/− zebrafish, implying that Gnrh2 acts to induce reproduction specifically in fasted zebrafish.
Published: 2021
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17. Association between benzodiazepine outpatient treatment and risk of early seizure recurrence in emergency patients with seizure: A multicenter retrospective study

Author: Laura Luhmann, Ulysse Hatabian, Valentin Belaud, Christian Kassasseya, Mélanie Roussel, Ben Bloom, Vincent Navarro, Olivier Peyrony, Emmanuel Montassier, Pierrick Le Borgne, Xavier Eyer, Marie Drogrey, Anthony Chauvin, Christophe Choquet, and Yonathan Freund
Subjects: Adult, Male, medicine.medical_specialty, medicine.drug_class, Logistic regression, Seizure recurrence, 03 medical and health sciences, Benzodiazepines, 0302 clinical medicine, Recurrence, Seizures, Internal medicine, Outpatients, medicine, Clinical endpoint, Humans, Retrospective Studies, Benzodiazepine, business.industry, 030208 emergency & critical care medicine, Retrospective cohort study, General Medicine, Odds ratio, Emergency department, Confidence interval, Emergency Medicine, business, Emergency Service, Hospital
Abstract: Introduction Seizures are one of the most common neurological reasons for emergency department (ED) visits. The benefit of ED-initiated, short-course outpatient benzodiazepine (BZD) treatment to prevent early recurrent seizure is unknown. This study assesses the risk of early seizure recurrence in patients who were or were not started with outpatient BZD in the ED. Methods This was a multicenter retrospective study conducted in eight French EDs between January 1 and December 31, 2019. All patients admitted for seizure were retrospectively screened and those discharged home from the ED were included. Patients with a history of chronic alcohol intoxication or chronic BZD therapy were excluded. Baseline characteristics, type of seizure, and 30-day outcome were retrospectively collected from the electronic health records. The primary endpoint was a return visit for seizure recurrence within 30 days. Independent factors associated with a seizure recurrence were identified using a multivariable binary logistic regression. Results A total of 2,218 patients were included and 1,820 were analyzed. The median age was 39 years and 60% were men. Among them 82% of patients had a generalized tonic-clonic seizure and 47% of seizures were idiopathic. BZD treatment was started in 773 (42%) patients. A total of 154 (8%) patients had an early recurrence at 30 days: 68 (9%) in patients who were treated with BZD versus 86 (8%) in patients who were not (odds ratio [OR] = 1.07, 95% confidence interval [CI] = 0.71 to 1.43). In multivariable analysis, two factors were independently associated with the primary endpoint: chronic epileptic treatment (adjusted OR = 2.58, 95% CI = 1.55 to 4.37) and having had a focal seizure (adjusted OR = 2.16, 95% CI = 1.56 to 4.37). Conclusion BZD therapy was started in 42% of patients who were discharged home after ED visit for a seizure. This treatment was not an independent factor associated with the risk of return visit for seizure recurrence at 30 days.
Published: 2021

18. Trajectories of depression symptoms over time differ by APOE4 genotype in older adults with type 2 diabetes

Author: Michal Schnaider Beeri, Laili Soleimani, Anthony Heymann, Ramit Ravona-Springer, Yuval Berman, Inbar Lavie, and Yonathan Schwartz
Subjects: Apolipoprotein E, Male, medicine.medical_specialty, Genotype, Apolipoprotein E4, Type 2 diabetes, Neuropsychological Tests, Article, Cognition, Internal medicine, Diabetes mellitus, medicine, Humans, Cognitive Dysfunction, Cognitive decline, Depression (differential diagnoses), Aged, business.industry, Depression, medicine.disease, Psychiatry and Mental health, Diabetes Mellitus, Type 2, Geriatric Depression Scale, Female, Geriatrics and Gerontology, business
Abstract: Objectives The APOE-e4 genotype has been associated with old-age depression, but this relationship has been rarely investigated in type 2 diabetes (T2D) older adults, who are at significantly increased risk for depression, a major contributor to T2D complications. We examined whether trajectories of depression symptoms over time differ by APOE-e4 genotype in older adults with T2D. Methods Participants [n=754 (13.1% APOE-e4 carriers)] were from the longitudinal Israel Diabetes and Cognitive Decline (IDCD) study. They were initially cognitively normal and underwent evaluations of depression approximately every 18 months using the 15-item version of the Geriatric Depression Scale (GDS) and the depression subscale of the Neuropsychiatric Inventory (NPI). APOE was defined as a dichotomy of e4 carriers and non-carriers. We used Hierarchical Linear Mixed Models (HLMM) that modeled the effects of APOE status on repeated GDS and NPI-depression scores in an unadjusted model (Model 1), adjusting for demographic factors (Model 2) and additionally adjusting for cardiovascular factors and global cognition (Model 3). Results Participants' mean age was 71.37 (SD=4.5); 38.2% female. In comparison to non-carriers, APOE-e4 carriers had lower mean GDS scores (β=-0.46, p=0.018) and lower NPI-depression scores (β=-0.170, p=0.038) throughout all study follow period. The groups did not differ in the slope of change over time in GDS (β=-0.005, p=0.252) or NPI-depression (β=-0.001, p=0.994) scores. Additional adjustment for cardiovascular factors and global cognition did not alter these results. Conclusions In older adults with T2D, APOE-e4 carriers have less depressive symptoms in successive measurements suggesting they may be less susceptible to depression. This article is protected by copyright. All rights reserved.
Published: 2021

19. Abdominal ultrasound in the diagnostic work-up of visceral leishmaniasis and for detection of complications of spleen aspiration

Author: Florian Vogt, Tadele Mulaw, Helina Fikre, Rezika Mohammed, Yonathan Gebrewold, Ermias Diro, Angela Schuster, Tigist Mekonnen, Tadfe Bogale, and Johan van Griensven
Subjects: Male, Physiology, RC955-962, 030218 nuclear medicine & medical imaging, Geographical Locations, 0302 clinical medicine, Medical Conditions, Postoperative Complications, Arctic medicine. Tropical medicine, Zoonoses, Immune Physiology, Ascites, Abdomen, Medicine and Health Sciences, Prospective Studies, Prospective cohort study, Leishmaniasis, Subclinical infection, Ultrasonography, Incidence (epidemiology), Biopsy, Needle, HIV diagnosis and management, Work-up, Infectious Diseases, Leishmaniasis, Visceral, Female, medicine.symptom, Public aspects of medicine, RA1-1270, Research Article, Neglected Tropical Diseases, Adult, medicine.medical_specialty, Visual analogue scale, 030231 tropical medicine, Pain, Gastroenterology and Hepatology, 03 medical and health sciences, Kala-Azar, Signs and Symptoms, Diagnostic Medicine, Internal medicine, medicine, Parasitic Diseases, Humans, Protozoan Infections, business.industry, Public Health, Environmental and Occupational Health, Biology and Life Sciences, medicine.disease, Tropical Diseases, Visceral leishmaniasis, Cross-Sectional Studies, Splenomegaly, People and Places, Africa, Ethiopia, Clinical Medicine, business, Spleen
Abstract: Introduction Abdominal ultrasound (US) is increasingly used in the diagnostic work-up of infectious diseases, but studies on its diagnostic value in visceral leishmaniasis (VL) are lacking. US could help to identify complications of spleen aspiration (SA). We aimed to assess the diagnostic value of US and the evolution of findings after VL treatment; the incidence and degree of splenic injury; and the pain perceived during SA. Methodology/result We conducted a cross-sectional prospective study at the Leishmaniasis Research and Treatment Center, Gondar, Ethiopia between Oct 2017 and Dec 2018. We enrolled VL suspects undergoing tissue aspiration; US were conducted before and after SA, and at the end of VL treatment. Splenic injury was graded using the American association of surgery trauma injury scale (grade 1–4). The pain perceived during SA was graded using a visual analogue scale. Out of 392 VL suspects, 192 (49%) were confirmed VL cases. The median age was 25 years (IQR 21–30). Massive splenomegaly and hepatomegaly were the most common US findings. Splenic nodules were seen in 3.7% of the 190 VL cases and 1.5% of the 197 non-VL cases. Ascites was more common in VL (16.4%) than in non-VL cases (9.1%). The frequency of US abnormalities decreased with treatment. None of the US findings had sufficient sensitivity and specificity to justify its use as a diagnostic test. US detected splenic injury in four of the 318 patients who had post-SA US. All four patients remained clinically stable. Pain was perceived as moderate or severe in 51% of patients. Conclusion The diagnostic value of abdominal US for VL was low but found useful to detect subclinical splenic injury. SA caries a risk of splenic injury and was perceived painful by most. Further research on less invasive diagnostic tools is needed., Author summary Diagnostic value of abdominal US for visceral leishmaniasis in Ethiopian setting is limited. US finding of patients decreased in frequency with VL treatment. US detects iatrogenic subclinical splenic injury trough splenic aspiration in VL suspects. Iatrogenic splenic injury occurred in 1.3%of all blinded splenic aspirations done in VL suspected patients. 51% of VL suspects described moderate to severe pain (score ≥ 5 on visual analogue scale) after splenic aspiration.
Published: 2021

20. Assessing Lung Cancer Absolute Risk Trajectory Based on a Polygenic Risk Model

Author: Maria Teresa Landi, Loic Le Marchand, Lambertus A. Kiemeney, Christopher I. Amos, Melinda C. Aldrich, Adonina Tardón, Angeline S. Andrew, Chu Chen, Paul Brennan, Philip Lazarus, Mattias Johansson, Nilanjan Chatterjee, Shanbeth Zienolddiny, Matthew T. Warkentin, Stig E. Bojesen, Matthew B. Schabath, S. M. Arnold, Demetrius Albanes, Geoffrey Liu, Heike Bickeböller, Angela Risch, Rayjean J. Hung, Yonathan Brhane, Neil E. Caporaso, Gad Rennert, Stephen Lam, David C. Christiani, John K. Field, and James McKay
Subjects: 0301 basic medicine, Oncology, Male, Cancer Research, Multifactorial Inheritance, Lung Neoplasms, Decile, Machine Learning, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Risk Factors, Mass Screening, Family history, Medical History Taking, Lung, Early Detection of Cancer, Oligonucleotide Array Sequence Analysis, Incidence (epidemiology), Incidence, Smoking, Absolute risk reduction, Age Factors, Middle Aged, 3. Good health, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], 030220 oncology & carcinogenesis, Practice Guidelines as Topic, Female, Adult, medicine.medical_specialty, Context (language use), Risk Assessment, Article, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Internal medicine, medicine, Biomarkers, Tumor, Humans, Genetic Predisposition to Disease, Lung cancer, Aged, Models, Genetic, business.industry, medicine.disease, Confidence interval, United Kingdom, 030104 developmental biology, Case-Control Studies, National Lung Screening Trial, business, Tomography, X-Ray Computed, Genome-Wide Association Study
Abstract: Lung cancer is the leading cause of cancer-related death globally. An improved risk stratification strategy can increase efficiency of low-dose CT (LDCT) screening. Here we assessed whether individual's genetic background has clinical utility for risk stratification in the context of LDCT screening. On the basis of 13,119 patients with lung cancer and 10,008 controls with European ancestry in the International Lung Cancer Consortium, we constructed a polygenic risk score (PRS) via 10-fold cross-validation with regularized penalized regression. The performance of risk model integrating PRS, including calibration and ability to discriminate, was assessed using UK Biobank data (N = 335,931). Absolute risk was estimated on the basis of age-specific lung cancer incidence and all-cause mortality as competing risk. To evaluate its potential clinical utility, the PRS distribution was simulated in the National Lung Screening Trial (N = 50,772 participants). The lung cancer ORs for individuals at the top decile of the PRS distribution versus those at bottom 10% was 2.39 [95% confidence interval (CI) = 1.92–3.00; P = 1.80 × 10−14] in the validation set (Ptrend = 5.26 × 10−20). The OR per SD of PRS increase was 1.26 (95% CI = 1.20–1.32; P = 9.69 × 10−23) for overall lung cancer risk in the validation set. When considering absolute risks, individuals at different PRS deciles showed differential trajectories of 5-year and cumulative absolute risk. The age reaching the LDCT screening recommendation threshold can vary by 4 to 8 years, depending on the individual's genetic background, smoking status, and family history. Collectively, these results suggest that individual's genetic background may inform the optimal lung cancer LDCT screening strategy. Significance: Three large-scale datasets reveal that, after accounting for risk factors, an individual's genetics can affect their lung cancer risk trajectory, thus may inform the optimal timing for LDCT screening.
Published: 2021

21. Proportion of TLR-9 Gene Polymorphisms at rs352139 (G1174A) in HIV/AIDS Patients in West Java, Indonesia

Author: Agnes Rengga Indrati, Edhyana Sahiratmadja, and Yehezkiel Yonathan
Subjects: medicine.medical_specialty, lcsh:R5-920, cd4+, hiv/aids, polymorphisms, rapid progression, tlr-9, west java, business.industry, lcsh:R, Wild type, lcsh:Medicine, General Medicine, West java, medicine.disease, Immunodeficiency Syndrome, Acquired immunodeficiency syndrome (AIDS), Internal medicine, Genotype, medicine, business, lcsh:Medicine (General), Gene, Mass screening, Cohort study
Abstract: Background: Human immunodeficiency virus (HIV) infection is the main cause of the immunodeficiency syndrome (AIDS). TLR-9 gene encodes a toll-like receptor-9 that plays a key role in innate immunity. This study aimed to describe the proportion of TLR-9 polymorphisms at rs352139 in patients with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) in Bandung, West Java, Indonesia. Methods: This was a descriptive study involving a total of 96 patients with HIV/AIDS treated in a tertiary hospital in Bandung, West Java, Indonesia in 2013. TLR-9 gene polymorphisms at rs 352139 were examined using a mass screening platform and the genotypes proportion was presented in percentage and compared with other populations. Results: The average age of the HIV/AIDS patients recruited was 30 years (SD + 6.1) and the baseline mean of CD4+ count was 318.02 mm 3 (Normal was 1,500 mm 3 ) (SD + 273.1). The proportion of polymorphisms at rs352139or G1174A presented a wild type genotype GG (42.7%), GA (44.9%), and AA (12.4%), resulting in a total proportion nucleotide change of 57.3%. Conclusion: A total proportion of nucleotide change or polymorphisms is higher than the wild type. A further cohort study is of great interest to associate the rs352139 polymorphisms with a decrease in CD4+cells in HIV/AIDS patients, confirming a rapid disease progression.
Published: 2020

22. Effect of an Emergency Department Care Bundle on 30-Day Hospital Discharge and Survival Among Elderly Patients With Acute Heart Failure: The ELISABETH Randomized Clinical Trial

Author: Sébastien Beaune, Said Laribi, Céline Occelli, Jerome Bokobza, Tahar Chouihed, Frederic Balen, Marine Cachanado, Youri Yordanov, Tabassome Simon, Jennifer Truchot, Alexandre Mebazaa, Quentin Delannoy, Thibaut Desmettre, Anne-Laure Feral-Pierssens, Yonathan Freund, Xavier Bobbia, Judith Gorlicki, Ben Bloom, Olivier Ganansia, and Mehdi Khellaf
Subjects: Geriatrics, Acute coronary syndrome, medicine.medical_specialty, business.industry, 010102 general mathematics, Atrial fibrillation, General Medicine, Emergency department, medicine.disease, 01 natural sciences, 3. Good health, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Interquartile range, Internal medicine, Heart failure, medicine, Clinical endpoint, 030212 general & internal medicine, 0101 mathematics, business, Original Investigation
Abstract: Key Points Question Does an intervention aimed at improving guideline adherence for the management of acute heart failure, including intensive intravenous nitrate therapy and management of precipitating factors, improve hospital discharge and survival at 30 days? Findings In this stepped-wedge cluster randomized trial that included 503 patients 75 years and older who presented to the emergency department with acute heart failure, implementation of an early and comprehensive care bundle compared with usual care improved guideline adherence, but had no significant effect on number of days alive and out of hospital at 30 days (median of 19 d in both groups). Meanings This emergency department care bundle did not improve 30-day outcomes among older patients with acute heart failure. Abstract Importance Clinical guidelines for the early management of acute heart failure in the emergency department (ED) setting are based on only moderate levels of evidence, with subsequent low adherence to these guidelines. Objective To test the effect of an early guideline-recommended care bundle on short-term prognosis in older patients with acute heart failure in the ED. Design, Setting, and Participants Stepped-wedge cluster randomized trial in 15 EDs in France of 503 patients 75 years and older with a diagnosis of acute heart failure in the ED from December 2018 to September 2019 and followed up for 30 days until October 2019. Interventions A care bundle that included early intravenous nitrate boluses; management of precipitating factors, such as acute coronary syndrome, infection, or atrial fibrillation; and moderate dose of intravenous diuretics (n = 200). In the control group, patient care was left to the discretion of the treating emergency physician (n = 303). Each center was randomized to the order in which they switched to the “intervention period.” After the initial 4-week control period for all centers, 1 center entered in the intervention period every 2 weeks. Main Outcomes and Measures The primary end point was the number of days alive and out of hospital at 30 days. Secondary outcomes included 30-day all-cause mortality, 30-day cardiovascular mortality, unscheduled readmission, length of hospital stay, and kidney impairment. Results Among 503 patients who were randomized (median age, 87 years; 298 [59%] women), 502 were analyzed. In the intervention group, patients received a median (interquartile range) of 27.0 (9-54) mg of intravenous nitrates in the first 4 hours vs 4.0 (2.0-6.0) mg in the control group (adjusted difference, 23.8 [95% CI, 13.5-34.1]). There was a significantly higher percentage of patients in the intervention group treated for their precipitating factors than in the control group (58.8% vs 31.9%; adjusted difference, 31.1% [95% CI, 14.3%-47.9%]). There was no statistically significant difference in the primary end point of the number of days alive and out of hospital at 30 days (median [interquartile range], 19 [0- 24] d in both groups; adjusted difference, −1.9 [95% CI, −6.6 to 2.8]; adjusted ratio, 0.88 [95% CI, 0.64-1.21]). At 30 days, there was no significant difference between the intervention and control groups in mortality (8.0% vs 9.7%; adjusted difference, 4.1% [95% CI, −17.2% to 25.3%]), cardiovascular mortality (5.0% vs 7.4%; adjusted difference, 2.1% [95% CI, −15.5% to 19.8%]), unscheduled readmission (14.3% vs 15.7%; adjusted difference, −1.3% [95% CI, −26.3% to 23.7%]), median length of hospital stay (8 d in both groups; adjusted difference, 2.5 [95% CI, −0.9 to 5.8]), and kidney impairment (1% in both groups). Conclusions and Relevance Among older patients with acute heart failure, use of a guideline-based comprehensive care bundle in the ED compared with usual care did not result in a statistically significant difference in the number of days alive and out of the hospital at 30 days. Further research is needed to identify effective treatments for acute heart failure in older patients. Trial Registration ClinicalTrials.gov Identifier: NCT03683212
Published: 2020

23. Assessment of the efficacy of hemodialysis on uric acid clearance in a sub-Saharan African population at the end stage kidney disease

Author: Marie Solange Doualla, Marie Patrice Halle, Mickael Essouma, Félicité Kamdem, Gloria Ashuntantang, Aude Ingrid Agouak, Jan René Nkeck, and Yonathan Batchama Lobe
Subjects: Nephrology, Adult, Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, 030232 urology & nephrology, hyperuricemia, 030204 cardiovascular system & hematology, lcsh:RC870-923, 03 medical and health sciences, chemistry.chemical_compound, Young Adult, 0302 clinical medicine, Renal Dialysis, Internal medicine, Chronic Kidney Disease, medicine, Humans, Renal replacement therapy, Hyperuricemia, Cameroon, Dialysis, Aged, hemodialysis, business.industry, Odds ratio, Middle Aged, lcsh:Diseases of the genitourinary system. Urology, medicine.disease, Uric Acid, Treatment Outcome, chemistry, Uric acid, Kidney Failure, Chronic, Female, Hemodialysis, business, Kidney disease, Research Article
Abstract: Background Uricemia dramatically rises with the stage of chronic kidney disease (CKD) and correlates with its mortality. Hemodialysis (HD) being the most used treatment at the end stage in sub-Saharan Africa, we sought to evaluate its efficacy on the clearance of uric acid (UAc) when used alone and twice per week. Methods A cross-sectional study of all consenting patients with CKD stage 5 recruited at random during HD sessions in a reference Centre in Cameroon from January to April 2017. We collected socio-demographic data, relevant clinical information, HD related variables, and measured serum uric acid (SUA) levels before and after the dialysis to assess the uric acid clearance. A clearance between 65 and 80% and above 80% was considered as low and good efficacy of HD respectively. Statistical analysis was performed using SPSS version 21.0. Factors associated with HD efficacy were assessed using Fisher’s exact test and are presented with their odds ratios (OR) and 95% confidence levels. Results One hundred four patients (53 females) were included. The mean age was 49.9 ± 13.3 years. Hypertension (25%) and chronic glomerulonephritis (16%) were the main suspected etiologies of CKD. The median time on renal replacement therapy by HD was 3 years [1; 6]. The prevalence of hyperuricemia was 81.9%. The means of SUA levels were 78.8 ± 13.8 mg/L and 26.4 ± 6.6 mg/L respectively before and after dialysis. Mean SUA clearance was 66% ± 10%. The efficacy of HD on UAc was moderate in 92 (63.9%) and good in 2 (1.4%) patients. Excess weight (OR 0.4 [0.2; 0.9]) and Kt/Vurea Conclusion HD used alone for 2 sessions per week has a moderate efficacy on uric acid clearance in CKD. Therefore, we should improve the Kt/V (> 1.2), and combine HD to uric acid lowering drugs and diet modifications to increase its efficacy.
Published: 2020

24. High-dose intravenous nitrates in acute heart failure: Level of evidence and adherence

Author: Yonathan Freund and Judith Gorlicki
Subjects: Heart Failure, medicine.medical_specialty, Nitrates, business.industry, General Medicine, Evidence-based medicine, medicine.disease, Heart failure, Internal medicine, Hypertension, Emergency Medicine, medicine, Cardiology, Humans, business
Published: 2020

25. Community-Based Hemoglobin A(1C) Testing in Barbershops to Identify Black Men With Undiagnosed Diabetes

Author: Joseph Ravenell, Yonathan Ararso, David C. Lee, Marcela Osorio, Ta’Loria Young, Stephen P. Wall, and Mary Ann Sevick
Subjects: Adult, Male, medicine.medical_specialty, MEDLINE, Timely diagnosis, Barbering, Prediabetic State, Diabetes mellitus, Internal Medicine, Research Letter, Medicine, Humans, Mass Screening, Aged, Community based, Glycated Hemoglobin, Extramural, business.industry, Middle Aged, medicine.disease, United States, Black or African American, Hemoglobin A, Diabetes Mellitus, Type 2, Family medicine, New York City, Hemoglobin, Undiagnosed diabetes, business
Abstract: This cross-sectional study evaluates the use of hemoglobin A(1c) testing at barbershops owned by black individuals for timely diagnosis of diabetes among black men and suggests appropriate methods for care.
Published: 2020

26. Immune-mediated genetic pathways resulting in pulmonary function impairment increase lung cancer susceptibility

Author: Yohan Bossé, Christopher I. Amos, Paul Brennan, Iona Cheng, Melinda C. Aldrich, John S. Witte, John K. Field, George Davey Smith, Neil E. Caporaso, Maria Teresa Landi, Gad Rennert, Matthew T. Warkentin, Michael P.A. Davies, Mattias Johansson, Lambertus A. Kiemeney, Paolo Vineis, Ghislaine Scelo, Demetrius Albanes, James D. McKay, Rebecca E. Graff, Adonina Tardón, David C. Christiani, Matthew B. Schabath, Caroline L Relton, Richard M. Martin, Sanjay Shete, Chu Chen, Philip C Haycock, Aage Haugen, Sara R. Rashkin, Eric J. Duell, M. Dawn Teare, Loic Le Marchand, Shanbeh Zienolddiny, Jennifer A. Doherty, Jonas Manjer, Susanne M. Arnold, Angeline S. Andrew, Yonathan Brhane, David Zaridze, Philip Lazarus, Ma'en Obeidat, Geoffrey Liu, Gary E. Goodman, Nima C. Emami, Heike Bickeböller, Stig E. Bojesen, Rayjean J. Hung, Stephen Lam, Linda Kachuri, and Venkata S. K. Manem
Subjects: Male, 0301 basic medicine, Oncology, Vital capacity, Lung Neoplasms, Carcinogenesis, Vital Capacity, General Physics and Astronomy, Pulmonary function testing, 0302 clinical medicine, Hàbit de fumar, Forced Expiratory Volume, Genetics research, Epidemiology of cancer, 2.1 Biological and endogenous factors, Carcinogènesi, Prospective Studies, Aetiology, lcsh:Science, Lung, Cancer, 0303 health sciences, Multidisciplinary, Smoking, Single Nucleotide, Middle Aged, respiratory system, Respiratory Function Tests, 3. Good health, Phenotype, medicine.anatomical_structure, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], 030220 oncology & carcinogenesis, Respiratory, Adenocarcinoma, Female, ICEP, Lung cancer, Bristol Population Health Science Institute, Adult, medicine.medical_specialty, Lung Neoplasms/genetics, Science, Polymorphism, Single Nucleotide, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, FEV1/FVC ratio, Rare Diseases, Cancer epidemiology, All institutes and research themes of the Radboud University Medical Center, Internal medicine, Tobacco, Mendelian randomization, Genetics, medicine, Humans, Genetic Predisposition to Disease, Polymorphism, Aged, 030304 developmental biology, Tobacco Smoke and Health, business.industry, Prevention, Human Genome, Lung/physiopathology, General Chemistry, Mendelian Randomization Analysis, medicine.disease, Lung cancer susceptibility, respiratory tract diseases, 030104 developmental biology, Càncer de pulmó, lcsh:Q, business
Abstract: This research was supported by funding from the National Institutes of Health (US NCI R25T CA112355 and R01 CA201358; PI: Witte) and the Canadian Institute for Health Research (Foundation grant FDN 167273, PI: Hung; Canada Research Chair, PI: Hung). The OncoArray project was supported by NIH U19 CA203654 (MPI: Hung, Amos, Brennan, Lin). The Boston Lung Cancer Study was funded by NIH (NCI) U01CA209414 (PI: Christiani). The lung eQTL study at Laval University was supported by the Fondation de l’Institut universitaire de cardiologie et de pneumologie de Québec and the Canadian Institutes of Health Research (MOP − 123369). Y.B. holds a Canada Research Chair in Genomics of Heart and Lung Diseases. The EAGLE study was supported by the Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS. The Multiethnic Cohort Study is supported by National Institutes of Health (CA164973). The CARET study was supported by the National Institutes of Health/National Cancer Institute: UM1 CA167462 (PI: Goodman), U01 CA6367307 (PIs: Omen, Goodman); R01 CA111703 (PI: Chen), 5R01 CA151989-01A1 (PI: Doherty) and U01 CA167462 (PI: Chen). M.B.S. was supported in part by a Cancer Center Support Grant (P30 CA076292) and by NIH P50 CA119997. R.M.M. is supported by a CRUK programme grant, the Integrative Cancer Epidemiology Programme (C18281/A19169), and by the National Institute for Health Research (NIHR) Bristol Biomedical Research Centre based at University Hospitals Bristol NHS Foundation Trust and the University of Bristol., Kachuri, L., Johansson, M., Rashkin, S.R., Graff, R.E., Bossé, Y., Manem, V., Caporaso, N.E., Landi, M.T., Christiani, D.C., Vineis, P., Liu, G., Scelo, G., Zaridze, D., Shete, S.S., Albanes, D., Aldrich, M.C., Tardón, A., Rennert, G., Chen, C., Goodman, G.E., Doherty, J.A., Bickeböller, H., Field, J.K., Davies, M.P., Dawn Teare, M., Kiemeney, L.A., Bojesen, S.E., Haugen, A., Zienolddiny, S., Lam, S., Le Marchand, L., Cheng, I., Schabath, M.B., Duell, E.J., Andrew, A.S., Manjer, J., Lazarus, P., Arnold, S., McKay, J.D., Emami, N.C., Warkentin, M.T., Brhane, Y., Obeidat, M., Martin, R.M., Relton, C., Davey Smith, G., Haycock, P.C., Amos, C.I., Brennan, P., Witte, J.S., Hung, R.J.
Published: 2020
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27. Time-pattern of adverse outcomes after an infection-triggered acute heart failure decompensation and the influence of early antibiotic administration and hospitalisation: results of the PAPRICA-3 study

Author: Alberto Dominguez-Rodriguez, Pere Llorens, José Manuel Garrido, Javier Jacob, Lissete Travería Bécquer, Marta Fuentes, Koji Takagi, Miguel Alberto Rizzi, Amparo Valero, Joan Padrosa, Pablo Herrero-Puente, Víctor Gil, Eva Salvo, Gemma Martínez, Alfons Aguirre, María Pilar López-Díez, Òscar Miró, Etienne Gayat, Mattia Arrigo, Francisco Javier Martín-Sánchez, Yonathan Freund, Alexandre Mebazaa, and Rosa Escoda
Subjects: Male, medicine.medical_specialty, Time Factors, Adverse outcomes, medicine.drug_class, Antibiotics, Outcomes, 030204 cardiovascular system & hematology, Infections, Patient Readmission, 03 medical and health sciences, Time pattern, 0302 clinical medicine, Patient disposition, Infeccion, Internal medicine, medicine, Humans, Decompensation, Registries, 030212 general & internal medicine, Mortality, Aged, Aged, 80 and over, Heart Failure, Framingham Risk Score, business.industry, Hazard ratio, Acute heart failure, General Medicine, medicine.disease, Patient Discharge, Anti-Bacterial Agents, Hospitalization, Trigger, Heart failure, Acute Disease, Cardiology, Acute heart failure, Infeccion, Mortality, Outcomes, Trigger, Female, Infection, Cardiology and Cardiovascular Medicine, business
Abstract: Objective: To investigate whether patients with an acute heart failure (AHF) episode triggered by infection present different outcomes compared to patients with no trigger and the effects of early antibiotic administration (EAA) and hospitalisation. Methods: Two groups were made according to the AHF trigger: infection (G1) or none identified (G2). The primary outcome was 13-week (91-days) all-cause mortality, and secondary outcomes were 13-week post-discharge mortality, readmission or combined endpoint. Comparisons are presented as unadjusted and adjusted (MEESSI risk score) hazard ratios (uHR/aHR) for G1 compared to G2 patients, also estimated by weeks. Stratified analysis by EAA (provided/not provided) and patient disposition (discharged/hospitalised) was performed. Results: We included 6727 patients (G1 = 3973; G2 = 2754). The 13-week mortality uHR was 1.11 (0.99-1.25; p = 0.06; with significant increases in the first 3 weeks), and the aHR was 0.91 (0.81-1.02; p = 0.11). There were no differences in unadjusted secondary post-discharge outcomes; however, G1 outcomes significantly improved after adjustment: aHR 0.83 (0.71-0.96; p = 0.01) for mortality, 0.92 (0.84-0.99; p = 0.04) for readmission, and 0.92 (0.85-0.99; p = 0.04) for the combined endpoint. We found a differentiated effect of hospitalisation (p < 0.05 for interaction; better post-discharge readmission and combined outcomes in G1), and a trend (p = 0.06) to lower mortality in G1 patients with EAA. Additionally, there were some differences between groups in baseline and acute episode characteristics. Conclusion: AHF triggered by infection is not associated with a higher mid-term mortality and has better post-discharge outcomes; however, the first 3 weeks are an extremely vulnerable period. Since hospitalisation could have a role in limiting adverse post-discharge events, and EAA in reducing mortality, these relationships should be prospectively explored in further studies.
Published: 2020

28. Islet-Like Structures Generated In Vitro from Adult Human Liver Stem Cells Revert Hyperglycemia in Diabetic SCID Mice

Author: Giovanni Camussi, Victor Navarro-Tableros, Maria Chiara Deregibus, Sara Giunti, Marta Tapparo, Adriana Pitino, Yonathan Gomez, Ciro Tetta, Maria Felice Brizzi, Chiara Pasquino, Camillo Ricordi, and Chiara Gai
Subjects: 0301 basic medicine, Male, Cancer Research, medicine.medical_treatment, Cellular differentiation, Liver Stem Cell, Mice, SCID, 0302 clinical medicine, Insulin-Secreting Cells, Protamines, Liver stem cells, C-Peptide, Stem Cells, Diabetes, Cell Differentiation, medicine.anatomical_structure, Phenotype, Liver, 030220 oncology & carcinogenesis, Stem cell, Pancreas, 3D culture, Adult, medicine.medical_specialty, Pancreatic islets, Diabetete Tipo 1, Biology, Article, Pancreatic β cells, Diabetes Mellitus, Experimental, 03 medical and health sciences, Islets of Langerhans, In vivo, Internal medicine, Spheroids, Cellular, medicine, Animals, Humans, Insulin-producing stem cells, Insulin, cellule staminali, Cell Biology, Transplantation, 030104 developmental biology, Endocrinology, Glucose, Gene Expression Regulation, Diabetete Tipo 1, cellule staminali, Hyperglycemia, Biomarkers
Abstract: A potential therapeutic strategy for diabetes is the transplantation of induced-insulin secreting cells. Based on the common embryonic origin of liver and pancreas, we studied the potential of adult human liver stem-like cells (HLSC) to generate in vitro insulin-producing 3D spheroid structures (HLSC-ILS). HLSC-ILS were generated by a one-step protocol based on charge dependent aggregation of HLSC induced by protamine. 3D aggregation promoted the spontaneous differentiation into cells expressing insulin and several key markers of pancreatic β cells. HLSC-ILS showed endocrine granules similar to those seen in human β cells. In static and dynamic in vitro conditions, such structures produced C-peptide after stimulation with high glucose. HLSC-ILS significantly reduced hyperglycemia and restored a normo-glycemic profile when implanted in streptozotocin-diabetic SCID mice. Diabetic mice expressed human C-peptide and very low or undetectable levels of murine C-peptide. Hyperglycemia and a diabetic profile were restored after HLSC-ISL explant. The gene expression profile of in vitro generated HLSC-ILS showed a differentiation from HLSC profile and an endocrine commitment with the enhanced expression of several markers of β cell differentiation. The comparative analysis of gene expression profiles after 2 and 4 weeks of in vivo implantation showed a further β-cell differentiation, with a genetic profile still immature but closer to that of human islets. In conclusion, protamine-induced spheroid aggregation of HLSC triggers a spontaneous differentiation to an endocrine phenotype. Although the in vitro differentiated HLSC-ILS were immature, they responded to high glucose with insulin secretion and in vivo reversed hyperglycemia in diabetic SCID mice. Electronic supplementary material The online version of this article (10.1007/s12015-018-9845-6) contains supplementary material, which is available to authorized users.
Published: 2018

29. TwoBRMpromoter polymorphisms predict poor survival in patients with hepatocellular carcinoma

Author: Roxana Bucur, Devalben Patel, Zhuo Chen, Kit Man Wong, Sean P. Cleary, Dangxiao Cheng, Osvaldo Espin-Garcia, Jonghun J. Lee, Rayjean J. Hung, Jennifer J. Knox, Catherine Brown, David Reisman, Ivan Pasic, Geoffrey Liu, Yonathan Brhane, and Wei Xu
Subjects: Adult, Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, Adolescent, Genotype, Kaplan-Meier Estimate, Biology, Bioinformatics, Logistic regression, Polymorphism, Single Nucleotide, Risk Assessment, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Epigenetics, Allele, Promoter Regions, Genetic, Molecular Biology, Gene, Aged, Proportional Hazards Models, Aged, 80 and over, Liver Neoplasms, Hazard ratio, Wild type, Middle Aged, Prognosis, medicine.disease, Confidence interval, Logistic Models, 030104 developmental biology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Female, Transcription Factors
Abstract: BACKGROUND: Polymorphisms in the promoter of the BRM gene, a critical subunit of the chromatin remodeling SWI/SNF complex, have previously been implicated in risk and prognosis in Caucasian-predominant lung, head and neck, esophageal, and pancreatic cancers, and in hepatocellular cancers in Asians. We investigated the role of these polymorphisms in hepatocellular carcinoma (HCC) risk and prognosis. METHODS: HCC cases were recruited in a comprehensive cancer centre while the matched controls were recruited from family practice units from the same catchment area. For risk analyses, unconditional logistic regression analyses were performed in HCC patients and matched healthy controls. Overall survival analyses were performed using Cox proportional hazard models, Kaplan-Meier curves, and log-rank tests. RESULTS: In 266 HCC cases and 536 controls, no association between either BRM promoter polymorphism (BRM-741 or BRM-1321) and risk of HCC was identified (p>0.10 for all comparisons). There was significant worsening of overall survival as the number of variant alleles increased: BRM-741 per variant allele adjusted hazards ratio (aHR) 5.77, 95% confidence interval (CI) 2.89–11.54 and BRM-1321 per variant allele aHR 4.09, 95% CI 2.22–7.51. The effects of these two polymorphisms were at least additive, where individuals who were double homozygotes for the variant alleles had a 45-fold increase in risk of death when compared to those who were double wildtype for the two polymorphisms. CONCLUSION: Two BRM promoter polymorphisms were strongly associated with HCC prognosis but were not associated with increased HCC susceptibility. The association was strongest in double homozygotes for the allele variants. This article is protected by copyright. All rights reserved
Published: 2017
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30. The effect of G-CSF and AMD3100 on mice treated with streptozotocin: Expansion of alpha-cells and partial islet protection

Author: Teresa Gledhill, Olga Wittig, Yonathan Gomez, Dylana Diaz-Solano, and Jose E. Cardier
Subjects: Blood Glucose, Male, 0301 basic medicine, Benzylamines, medicine.medical_specialty, endocrine system diseases, medicine.medical_treatment, Immunology, Cyclams, Biochemistry, Streptozocin, Diabetes Mellitus, Experimental, Islets of Langerhans, Mice, 03 medical and health sciences, 0302 clinical medicine, Heterocyclic Compounds, Insulin-Secreting Cells, Internal medicine, Diabetes mellitus, Granulocyte Colony-Stimulating Factor, medicine, Animals, Insulin, Immunology and Allergy, Progenitor cell, Molecular Biology, geography, geography.geographical_feature_category, business.industry, Pancreatic islets, nutritional and metabolic diseases, Hematology, Streptozotocin, Islet, medicine.disease, Haematopoiesis, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Glucagon-Secreting Cells, Hyperglycemia, 030220 oncology & carcinogenesis, Bone marrow, business, medicine.drug
Abstract: Administration of streptozotocin (STZ) is one of the most used experimental models of diabetes (STZ-DT). STZ induces beta-cell damage in pancreatic islets. It is known that hematopoietic stem progenitor cells (HSPCs) are mobilized from bone marrow to damaged tissues. In this work, we evaluated the effects of the hematopoietic mobilizers G-CSF (250μg/kg; for five consecutive days) and AMD3100 (5mg/kg; single s.c injection) in mice treated with STZ (175mg/kg). Mice injected with STZ showed a significant reduction in the number and area of islets and in the number of beta- and alpha-cells. Concurrently, they had hyperglycemia (blood glucose over 300mg/dl) associated with very low levels of insulin in plasma. The number and area of islets from STZ-DT mice treated with G-CSF and/or AMD3100 were similar to the controls. However, these mice had neither a reduction of hyperglycemia nor an improvement in the insulin levels. Analysis of islet cellularity showed a large reduction in beta-cells with a significant expansion of alpha-cells. These results indicate that G-CSF and AMD3100 induce partial protection of islet tissues and expansion of alpha-cells in mice treated with STZ but do not protect beta-cells from the damage induced by this compound.
Published: 2017
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31. Seasonal expression of arginine vasotocin mRNA and its correlations to gonadal steroidogenic enzymes and sexually dimorphic coloration during sex reversal in the gilthead seabream (Sparus aurata)

Author: Ten-Tsao Wong, Yonathan Zohar, and José J. Reyes-Tomassini
Subjects: Male, 0301 basic medicine, endocrine system, medicine.medical_specialty, Gonad, Physiology, Aquatic Science, Biochemistry, 03 medical and health sciences, Vasotocin, Hermaphrodite, Internal medicine, medicine, Animals, Amino Acid Sequence, RNA, Messenger, Aromatase, Gonads, Sex Characteristics, Base Sequence, biology, urogenital system, Pigments, Biological, General Medicine, Sex reversal, Sea Bream, Sexual dimorphism, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Gene Expression Regulation, Hypothalamus, biology.protein, Female, Seasons, Development of the gonads, Hormone
Abstract: Arginine vasotocin is a hormone produced in the hypothalamus of teleost fish that has been shown to regulate gonad development and sexual behavior. To study the role of arginine vasotocin in the gonadal cycle of the hermaphrodite gilthead seabream, Sparus aurata, we cloned the seabream arginine vasotocin (avt) complementary DNA (cDNA). We investigated the expression of brain avt throughout the gonad cycle using real-time quantitative PCR and compared its expression levels to the expression levels of two key gonadal steroidogenic enzymes, cyp19a1a and cyp11b2. In July, when the process of sex reversal is thought to begin, avt expression was elevated over the previous 2 months. Avt in the brain remained at or above the level of July until November then peaked again in December. There was no difference between males and females in the expression levels of brain avt throughout the year. However, only in ambisexual fish was the expression of the cyp19a1a gonadal aromatase correlated to the expression of avt in the brain. Cyp11b2 did not show any correlation to brain avt expression. We also found that females had more intense body coloration than males and that this intensity peaked prior to spawning. Avt expression and female coloration were positively correlated. The fact that brain avt expression was lowest during gonad quiescence, together with the observation of a correlation between brain avt with gonadal cyp19a1a and body coloration during that time suggests that avt may play a role during the process of sex reversal and spawning of the gilthead seabream.
Published: 2017
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32. Prevalence of pulmonary embolism in patients with isolated syncope in the emergency department: the PEEPS multicenter prospective cohort study

Author: Anne Laure Philippon, Clara Damas Perrichet, Yonathan Freund, Samia Boussouar, Marine Cachanado, Anne Laure Feral-Pierssens, Pierre Alexis Raynal, and Victoria Donciu
Subjects: medicine.medical_specialty, biology, business.industry, Syncope (genus), Emergency department, biology.organism_classification, Chest pain, medicine.disease, Work-up, Confidence interval, Pulmonary embolism, Internal medicine, medicine, In patient, medicine.symptom, Prospective cohort study, business
Abstract: Introduction: The prevalence of pulmonary embolism (PE) in patients that present to the Emergency Department (ED) with isolated syncope is unclear. Conflicting results were recently reported with a prevalence ranging from less than 1% to up to 17%. However, these studies included patients that may also have had other symptoms suggestive of PE (chest pain or dyspnea), or patients that had no systematic assessment for the presence of PE. Since a low prevalence ( Aims: to evaluate the prevalence of PE in ED patients with isolated syncope. Methods: Multicenter prospective cohort study in seven EDs in France. Adult patients who presented to the ED with syncope (transient loss of consciousness) were included. Patients with chest pain or dyspnea were excluded. Included patients underwent formal work-up for PE, including D-dimer testing and further imaging if positive. Cases of PE were adjudicated by two independent expert radiologists with the review of imaging studies. Results: 411 patients were recruited and tested with D-dimer, in whom 137 (33%) underwent a computed tomographic pulmonary angiogram or a ventilation-perfusion scan. A PE was confirmed in nine patients (prevalence of 2.2%, 95% confidence interval 1.1% to 4.3%), including one sub-segmental PE. Conclusion: In our sample of patients with isolated syncope, the prevalence of PE was 2.2%. This value is not sufficiently low to negate the requirement for a formal work up in the ED, even in the absence of chest pain or dyspnea.
Published: 2019
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33. Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial

Author: Kausik K Ray, Helen M Colhoun, Michael Szarek, Marie Baccara-Dinet, Deepak L Bhatt, Vera A Bittner, Andrzej J Budaj, Rafael Diaz, Shaun G Goodman, Corinne Hanotin, Robert A Harrington, J Wouter Jukema, Virginie Loizeau, Renato D Lopes, Angèle Moryusef, Jan Murin, Robert Pordy, Arsen D Ristic, Matthew T Roe, José Tuñón, Harvey D White, Andreas M Zeiher, Gregory G Schwartz, Philippe Gabriel Steg, Gregory G. Schwartz, Ph. Gabriel Steg, Deepak L. Bhatt, Vera A. Bittner, Shaun G. Goodman, Robert A. Harrington, J. Wouter Jukema, Harvey D. White, Andreas M. Zeiher, Pierluigi Tricoci, Matthew T. Roe, Kenneth W. Mahaffey, Jay M. Edelberg, Guillaume Lecorps, William J. Sasiela, Jean-François Tamby, Philip E. Aylward, Heinz Drexel, Peter Sinnaeve, Mirza Dilic, Renato D. Lopes, Nina N. Gotcheva, Juan-Carlos Prieto, Huo Yong, Patricio López-Jaramillo, Ivan Pećin, Zeljko Reiner, Petr Ostadal, Margus Viigimaa, Markku S. Nieminen, Vakhtang Chumburidze, Nikolaus Marx, Nicolas Danchin, Evangelos Liberopoulos, Pablo Carlos Montenegro Valdovinos, Hung-Fat Tse, Robert Gabor Kiss, Denis Xavier, Doron Zahger, Marco Valgimigli, Takeshi Kimura, Hyo Soo Kim, Sang-Hyun Kim, Andrejs Erglis, Aleksandras Laucevicius, Sasko Kedev, Khalid Yusoff, Gabriel Arturo Ramos López, Marco Alings, Sigrun Halvorsen, Roger M. Correa Flores, Andrzej Budaj, Joao Morais, Maria Dorobantu, Yuri Karpov, Arsen D. Ristic, Terrance Chua, Zlatko Fras, Anthony J. Dalby, H. Asita de Silva, Emil Hagström, Ulf Landmesser, Chern-En Chiang, Piyamitr Sritara, Sema Guneri, Alexander Parkhomenko, Kausik K. Ray, Patrick M. Moriarty, Robert Vogel, Bernard Chaitman, Sheryl F. Kelsey, Anders G. Olsson, Jean-Lucien Rouleau, Maarten L. Simoons, Karen Alexander, Chiara Meloni, Robert Rosenson, Eric J.G. Sijbrands, John H. Alexander, Luciana Armaganijan, Akshay Bagai, Maria Cecilia Bahit, J. Matthew Brennan, Shaun Clifton, Adam D. DeVore, Shalonda Deloatch, Sheila Dickey, Keith Dombrowski, Grégory Ducrocq, Zubin Eapen, Patricia Endsley, Arleen Eppinger, Robert W. Harrison, Connie Ng Hess, Mark A. Hlatky, Joseph Dedrick Jordan, Joshua W. Knowles, Bradley J. Kolls, David F. Kong, Sergio Leonardi, Linda Lillis, David J. Maron, Jill Marcus, Robin Mathews, Rajendra H. Mehta, Robert J. Mentz, Humberto Graner Moreira, Chetan B. Patel, Sabrina Bernardez-Pereira, Lynn Perkins, Thomas J. Povsic, Etienne Puymirat, William Schuyler Jones, Bimal R. Shah, Matthew W. Sherwood, Kenya Stringfellow, Darin Sujjavanich, Mustafa Toma, Charlene Trotter, Sean Van Diepen, Matthew D. Wilson, Andrew T. Yan, Lilia B. Schiavi, Marcelo Garrido, Andrés F. Alvarisqueta, Sonia A. Sassone, Anselmo P. Bordonava, Alberto E. Alves De Lima, Jorge M. Schmidberg, Ernesto A. Duronto, Orlando C. Caruso, Leonardo P. Novaretto, Miguel Angel Hominal, Oscar R. Montaña, Alberto Caccavo, Oscar A. Gomez Vilamajo, Alberto J. Lorenzatti, Luis R. Cartasegna, Gustavo A. Paterlini, Ignacio J. Mackinnon, Guillermo D. Caime, Marcos Amuchastegui, Oscar Salomone, Oscar R. Codutti, Horacio O. Jure, Julio OE Bono, Adrian D. Hrabar, Julio A. Vallejos, Rodolfo A. Ahuad Guerrero, Federico Novoa, Cristian A. Patocchi, Cesar J. Zaidman, Maria E. Giuliano, Ricardo D. Dran, Marisa L. Vico, Gabriela S. Carnero, Pablo N. Guzman, Juan C. Medrano Allende, Daniela F. Garcia Brasca, Miguel H Bustamante Labarta, Sebastian Nani, Eduardo DS Blumberg, Hugo R Colombo, Alberto Liberman, Victorino Fuentealba, Hector L Luciardi, Gabriel D Waisman, Mario A Berli, Ruben O Garcia Duran, Horacio G Cestari, Hugo A Luquez, Jorge A Giordano, Silvia S Saavedra, Gerardo Zapata, Osvaldo Costamagna, Susana Llois, Jonathon H Waites, Nicholas Collins, Allan Soward, Chris LS Hii, James Shaw, Margaret A Arstall, John Horowitz, Daniel Ninio, James F Rogers, David Colquhoun, Romulo E Oqueli Flores, Philip Roberts-Thomson, Owen Raffel, Sam J Lehman, Constantine Aroney, Steven GM Coverdale, Paul J Garrahy, Gregory Starmer, Mark Sader, Patrick A Carroll, Ronald Dick, Robert Zweiker, Uta Hoppe, Kurt Huber, Rudolf Berger, Georg Delle-Karth, Bernhard Frey, Franz Weidinger, Dirk Faes, Kurt Hermans, Bruno Pirenne, Attilio Leone, Etienne Hoffer, Mathias CM Vrolix, Luc De Wolf, Bart Wollaert, Marc Castadot, Karl Dujardin, Christophe Beauloye, Geert Vervoort, Harry Striekwold, Carl Convens, John Roosen, Emanuele Barbato, Marc Claeys, Frank Cools, Ibrahim Terzic, Fahir Barakovic, Zlatko Midzic, Belma Pojskic, Emir Fazlibegovic, Mehmed Kulić, Azra Durak-Nalbantic, Dusko Vulic, Adis Muslibegovic, Boris Goronja, Gilmar Reis, Luciano Sousa, Jose C Nicolau, Flavio E Giorgeto, Ricardo P Silva, Lilia Nigro Maia, Rafael Rech, Paulo RF Rossi, Maria José AG Cerqueira, Norberto Duda, Renato Kalil, Adrian Kormann, José Antonio M Abrantes, Pedro Pimentel Filho, Ana Priscila Soggia, Mayler ON de Santos, Fernando Neuenschwander, Luiz C Bodanese, Yorghos L Michalaros, Freddy G Eliaschewitz, Maria H Vidotti, Paulo E Leaes, Roberto V Botelho, Sergio Kaiser, Euler Roberto Fernandes Manenti, Dalton B Precoma, Jose C Moura Jorge, Pedro G de B Silva, Jose A Silveira, Wladmir Saporito, Jose A Marin-Neto, Gilson S Feitosa, Luiz Eduardo F Ritt, Juliana A de Souza, Fernando Costa, Weimar KSB Souza, Helder JL Reis, Leandro Machado, José Carlos Aidar Ayoub, Georgi V Todorov, Fedya P Nikolov, Elena S Velcheva, Maria L Tzekova, Haralambi O Benov, Stanislav L Petranov, Haralin S Tumbev, Nina S Shehova-Yankova, Dimitar T Markov, Dimitar H Raev, Mihail N Mollov, Kostadin N Kichukov, Katya A Ilieva-Pandeva, Raya Ivanova, Maryana Gospodinov, Valentina M Mincheva, Petar V Lazov, Bojidar I Dimov, Manohara Senaratne, James Stone, Jan Kornder, Stephen Pearce, Danielle Dion, Daniel Savard, Yves Pesant, Amritanshu Pandey, Simon Robinson, Gilbert Gosselin, Saul Vizel, Gordon Hoag, Ronald Bourgeois, Anne Morisset, Eric Sabbah, Bruce Sussex, Simon Kouz, Paul MacDonald, Ariel Diaz, Nicolas Michaud, David Fell, Raymond Leung, Tycho Vuurmans, Christopher Lai, Frank Nigro, Richard Davies, Gustavo Nogareda, Ram Vijayaraghavan, John Ducas, Serge Lepage, Shamir Mehta, James Cha, Robert Dupuis, Peter Fong, Sohrab Lutchmedial, Josep Rodes-Cabau, Hussein Fadlallah, David Cleveland, Thao Huynh, Iqbal Bata, Adnan Hameed, Cristian Pincetti, Sergio Potthoff, Juan C Prieto, Monica Acevedo, Arnoldo Aguirre, Margarita Vejar, Mario Yañez, Guillermo Araneda, Mauricio Fernandez, Luis Perez, Paola Varleta, Fernando Florenzano, Laura Huidobro, Carlos A Raffo, Claudia Olivares, Leonardo Nahuelpan, Humberto Montecinos, Jiyan Chen, Yugang Dong, Weijian Huang, Jianzhong Wang, Shi'An Huang, Zhuhua Yao, Xiang Li, Lan Cui, Wenhua Lin, Yuemin Sun, Jingfeng Wang, Jianping Li, Xuelian Zhang, Hong Zhu, Dandan Chen, Lan Huang, Shaohong Dong, Guohai Su, Biao Xu, Xi Su, Xiaoshu Cheng, Jinxiu Lin, Wenxia Zong, Huanming Li, Yi Feng, Dingli Xu, Xinchun Yang, Yuannan Ke, Xuefeng Lin, Zheng Zhang, Zeqi Zheng, Zhurong Luo, Yundai Chen, Chunhua Ding, Yi Zhong, Yang Zheng, Xiaodong Li, Daoquan Peng, Shuiping Zhao, Ying Li, Xuebo Liu, Meng Wei, Shaowen Liu, Yihua Yu, Baiming Qu, Weihong Jiang, Yujie Zhou, Xingsheng Zhao, Zuyi Yuan, Ying Guo, Xiping Xu, Xubo Shi, Junbo Ge, Guosheng Fu, Feng Bai, Weiyi Fang, Xiling Shou, Xiangjun Yang, Jian'An Wang, Meixiang Xiang, Yingxian Sun, Qinghua Lu, Ruiyan Zhang, Jianhua Zhu, Yizhou Xu, Zhongcai Fan, Tianchang Li, Chun Wu, Nicolas Jaramillo, Gregorio Sanchez Vallejo, Diana C Luna Botia, Rodrigo Botero Lopez, Dora I Molina De Salazar, Alberto J Cadena Bonfanti, Carlos Cotes Aroca, Juan Diego Higuera, Marco Blanquicett, Sandra I Barrera Silva, Henry J Garcia Lozada, Julian A Coronel Arroyo, Jose L Accini Mendoza, Ricardo L Fernandez Ruiz, Alvaro M. Quintero Ossa, Fernando G Manzur Jatin, Aristides Sotomayor Herazo, Jeffrey Castellanos Parada, Rafael Suarez Arambula, Miguel A Urina Triana, Angela M Fernandez Trujillo, Maja Strozzi, Siniša Car, Melita Jerić, Davor Miličić, Martina Lovrić Benčić, Hrvoje Pintarić, Đeiti Prvulović, Jozica Šikić, Viktor Peršić, Dean Mileta, Kresimir Štambuk, Zdravko Babić, Vjekoslav Tomulic, Josip Lukenda, Stanka Mejic-Krstulovic, Boris Starcevic, Jindrich Spinar, David Horak, Zdenek Velicka, Josef Stasek, David Alan, Vilma Machova, Ales Linhart, Vojtech Novotny, Vladimir Kaucak, Richard Rokyta, Robert Naplava, Zdenek Coufal, Vera Adamkova, Ivo Podpera, Jiri Zizka, Zuzana Motovska, Ivana Marusincova, Premysl Svab, Petr Heinc, Jiri Kuchar, Petr Povolny, Jiri Matuska, Steen H Poulsen, Bent Raungaard, Peter Clemmensen, Lia E Bang, Ole May, Morten Bøttcher, Jens D Hove, Lars Frost, Gunnar Gislason, John Larsen, Peter Betton Johansen, Flemming Hald, Peter Johansen, Jørgen Jeppesen, Tonny Nielsen, Kjeld S Kristensen, Piotr Maria Walichiewicz, Jens D Lomholdt, Ib C Klausen, Peter Kaiser Nielsen, Flemming Davidsen, Lars Videbaek, Mai Soots, Veiko Vahula, Anu Hedman, Üllar Soopõld, Kaja Märtsin, Tiina Jurgenson, Arved Kristjan, Juhani K Helsinki, Saila Vikman, Heikki Huikuri, Juhani Airaksinen, Pierre Coste, Emile Ferrari, Olivier Morel, Gilles Montalescot, Jacques Machecourt, Gilles Barone-Rochette, Jacques Mansourati, Yves Cottin, Florence Leclercq, Abdelkader Belhassane, Nicolas Delarche, Franck Boccara, Franck Paganelli, Jérôme Clerc, Francois Schiele, Victor Aboyans, Vincent Probst, Jacques Berland, Thierry Lefèvre, Bernard Citron, Irakli Khintibidze, Tamaz Shaburishvili, Zurab Pagava, Ramaz Ghlonti, Zaza Lominadze, George Khabeishvili, Rayyan Hemetsberger, Kemala Edward, Ursula Rauch-Kröhnert, Matthias Stratmann, Karl-Friedrich Appel, Ekkehard Schmidt, Heyder Omran, Christoph Stellbrink, Thomas Dorsel, Emmanouil Lianopoulos, Hans Friedrich Vöhringer, Roger Marx, Andreas Zirlik, Detlev Schellenberg, Thomas Heitzer, Ulrich Laufs, Christian Werner, Stephan Gielen, Sebastian Nuding, Bernhard Winkelmann, Steffen Behrens, Karsten Sydow, Mahir Karakas, Gregor Simonis, Thomas Muenzel, Nikos Werner, Stefan Leggewie, Dirk Böcker, Rüdiger Braun-Dullaeus, Nicole Toursarkissian, Michael Jeserich, Matthias Weißbrodt, Tim Schaeufele, Joachim Weil, Heinz Völler, Johannes Waltenberger, Mohammed Natour, Susanne Schmitt, Dirk Müller-Wieland, Stephan Steiner, Lothar Heidenreich, Elmar Offers, Uwe Gremmler, Holger Killat, Werner Rieker, Sotiris Patsilinakos, Athanasios Kartalis, Athanassios Manolis, Dimitrios Sionis, Geargios Chachalis, Ioannis Skoumas, Vasilios Athyros, Panagiotis Vardas, Frangkiskos Parthenakis, Dimitrios Alexopoulos, Georgios Hahalis, John Lekakis, Apostolos Hatzitolios, Sergio R Fausto Ovando, Juan L Arango Benecke, Edgar R Rodriguez De Leon, Bryan PY Yan, David CW Siu, Tibor Turi, Bela Merkely, Imre Ungi, Geza Lupkovics, Lajos Nagy, András Katona, István Édes, Gábor Müller, Iván Horvath, Tibor Kapin, Zsolt Szigeti, József Faluközy, Mukund Kumbla, Manjinder Sandhu, Sharath Annam, Naveen Reddy Proddutur, Reddy Regella, Rajendra K Premchand, Ajaykumar Mahajan, Sudhir Pawar, Atul D Abhyanakar, Prafulla Kerkar, Ravishankar A Govinda, Abraham Oomman, Dhurjati Sinha, Sachin N Patil, Dhiman Kahali, Jitendra Sawhney, Abhijeet B Joshi, Sanjeev Chaudhary, Pankaj Harkut, Santanu Guha, Sanjay Porwal, Srimannarayana Jujjuru, Ramesh B Pothineni, Minguel R Monteiro, Aziz Khan, Shamanna S Iyengar, Jasprakash Singh Grewal, Manoj Chopda, Mahesh C Fulwani, Aparna Patange, Patil Sachin, Vijay K Chopra, Naresh K Goyal, Rituparna Shinde, Gajendra V Manakshe, Nitin Patki, Sumeet Sethi, Vengatesh Munusamy, Sunil Karna, Sunil Thanvi, Srilakshmi Adhyapak, Chandrakant Patil, Ulhas Pandurangi, Rishabh Mathur, Jugal Gupta, Suhas Kalashetti, Ajit Bhagwat, Bagirath Raghuraman, Shiv Kumar Yerra, Prasant Bhansali, Rohidas Borse, Patil Rahul, Srihari Das, Vinay Kumar, Jabir Abdullakutty, Shireesh Saathe, Priya Palimkar, Shireesh Sathe, Shaul Atar, Michael Shechter, Morris Mosseri, Yaron Arbel, Chorin Ehud, Havakuk Ofer, Chaim Lotan, Uri Rosenschein, Amos Katz, Yaakov Henkin, Adi Francis, Marc Klutstein, Eugenia Nikolsky, Robert Zukermann, Yoav Turgeman, Majdi Halabi, Alon Marmor, Ran Kornowski, Michael Jonas, Offer Amir, Yonathan Hasin, Yoseph Rozenman, Shmuel Fuchs, Vered Zvi, Osamah Hussein, Dov Gavish, Zvi Vered, Yoseph Caraco, Mazen Elias, Naveh Tov, Efrat Wolfovitz, Michael Lishner, Nizar Elias, Giancarlo Piovaccari, Annamaria De Pellegrin, Raffaella Garbelotto, Gabriele Guardigli, Valgimigli Marco, Giovanni Licciardello, Carla Auguadro, Filippo Scalise, Claudio Cuccia, Alessandro Salvioni, Giuseppe Musumeci, Michelle Senni, Paolo Calabrò, Salvatore Novo, Pompilio Faggiano, Marco Metra, Nicoletta B De Cesare, Sergio Berti, Claudio Cavallini, Enrico Puccioni, Marcello Galvani, Maurizio Tespili, Piermarco Piatti, Michela Palvarini, Giuseppe De Luca, Roberto Violini, Alessandro De Leo, Zoran Olivari, Pasquale Perrone Filardi, Maurizio Ferratini, Vittorio Racca, Kazuoki Dai, Yuji Shimatani, Haruo Kamiya, Kenji Ando, Yoshihiro Takeda, Yoshihiro Morino, Yoshiki Hata, Kazuo Kimura, Koichi Kishi, Ichiro Michishita, Hiroki Uehara, Toshinori Higashikata, Atsushi Hirayama, Keiji Hirooka, Yasuji Doi, Satoru Sakagami, Shuichi Taguchi, Akihiro Koike, Hiroyuki Fujinaga, Shinji Koba, Ken Kozuma, Tomohiro Kawasaki, Yujiro Ono, Masatoshi Shimizu, Yousuke Katsuda, Atsuyuki Wada, Toshiro Shinke, Junya Ako, Kenshi Fujii, Toshiyuki Takahashi, Tomohiro Sakamoto, Koichi Nakao, Yutaka Furukawa, Hiroshi Sugino, Ritsu Tamura, Toshiaki Mano, Masaaki Uematsu, Noriaki Utsu, Kashima Ito, Takuya Haraguchi, Katsuhiko Sato, Yasunori Ueda, Akira Nishibe, Kazuteru Fujimoto, Motomaru Masutani, Jung Han Yoon, Hack-Lyoung Kim, Hun Sik Park, In-Ho Chae, Moo Hyun Kim, Myung Ho Jeong, Seungwoon Rha, Chongjin Kim, Hyo-Soo Kim, Hae Young Kim, Taekjong Hong, Seung-Jea Tahk, Youngkwon Kim, Arija Busmane, Natalija Pontaga, Aldis Strelnieks, Iveta Mintale, Iveta Sime, Zaneta Petrulioniene, Roma Kavaliauskiene, Ruta Jurgaitiene, Gintare Sakalyte, Rimvydas Slapikas, Sigute Norkiene, Nerijus Misonis, Aleksandras Kibarskis, Raimondas Kubilius, Stojko Bojovski, Nensi Lozance, Aleksandar Kjovkaroski, Snezana Doncovska, Tiong Kiam Ong, Sazzli Kasim, Oteh Maskon, Balachandran Kandasamy, Houng B Liew, Wan Mohd Izani Wan Mohamed, Armando García Castillo, Jorge Carrillo Calvillo, Pedro Fajardo Campos, Juan Carlos Núñez Fragoso, Edmundo Alfredo Bayram Llamas, Marco Antonio Alcocer Gamba, Jaime Carranza Madrigal, Luis Gerardo González Salas, Enrique López Rosas, Belinda González Díaz, Eduardo Salcido Vázquez, Alfredo Nacoud Ackar, Guillermo Antonio Llamas Esperón, Carlos Rodolfo Martínez Sánchez, María Guerrero De Leon, Rodrigo Suarez Otero, Guillermo Fanghänel Salmón, Jesús Antonio Pérez Ríos, José Angel Garza Ruíz, Robert W Breedveld, Margriet Feenema-Aardema, Alida Borger-Van Der Burg, Pieter AM Hoogslag, Harry Suryapranata, Antonius Oomen, Paulus Van Haelst, Jacobijne J Wiersma, Dirk Basart, Ruud MA Van Der Wal, Peter Zwart, Pascalle Monraats, Henricus Van Kesteren, Ioannis Karalis, Johan Jukema, Gerardus JE Verdel, Bart RG Brueren, Roland PTh Troquay, Eric P Viergever, Nadea YY Al-Windy, Gerard L Bartels, Jan H Cornel, Walter RM Hermans, Johannes PR Herrman, Robert J Bos, Reginald GEJ Groutars, Coenraad C Van Der Zwaan, Refik Kaplan, Raymond Lionarons, Eelko Ronner, Bjorn E Groenemeijer, Patrick NA Bronzwaer, Anho AH Liem, Bernard JWM Rensing, Marcel JJA Bokern, Remco Nijmeijer, Ferry MRJ Hersbach, Frank F Willems, Antonius TM Gosselink, Saman Rasoul, John Elliott, Gerard Wilkins, Raewyn Fisher, Douglas Scott, Hamish Hart, Ralph Stewart, Scott Harding, Ian Ternouth, Nicholas Fisher, Samuel Wilson, Denise Aitken, Russell Anscombe, Laura Davidson, Tadeusz Tomala, Ottar Nygård, Jon Arne Sparby, Kjell Andersen, Lars 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Fernandez, J, Garcia Lledo, J, Cosin Sales, J, Botas Rodriguez, J, Gusi Tragant, G, Benedicto, A, Gonzalez-Juanatey, C, Camprubi Potau, M, Plaza Perez, I, De La Tassa, C, Loma-Osorio Rincon, P, Balaguer Recena, J, Escudier, J, Payeras, A, Alonso Orcajo, N, Valdivielso, P, Constantine, G, Haniffa, R, Tissera, N, Amarasekera, S, Ponnamperuma, C, Fernando, N, Fernando, K, Jayawardena, J, Wijeyasingam, S, Ranasinghe, G, Ekanayaka, R, Mendis, S, Senaratne, V, Mayurathan, G, Sirisena, T, Rajapaksha, A, Herath, J, Amarasena, N, Berglund, S, Rasmanis, G, Vedin, O, Witt, N, Mourtzinis, G, Nicol, P, Hansen, O, Romeo, S, Agergaard Jensen, S, Torstensson, I, Ahremark, U, Sundelin, T, Moccetti, T, Muller, C, Mach, F, Binde, R, Tsai, W, Ueng, K, Lai, W, Liu, M, Hwang, J, Yin, W, Hsieh, I, Hsieh, M, Kuo, J, Huang, T, Fang, C, Kaewsuwanna, P, Soonfuang, W, Jintapakorn, W, Sukonthasarn, A, Wongpraparut, N, Sastravaha, K, Sansanayudh, N, Kehasukcharoen, W, Piyayotai, D, Chotnoparatpat, P, Camsari, A, Kultursay, H, Mutlu, B, Ersanli, M, Demirtas, M, Kirma, C, Ural, E, Koldas, L, Karpenko, O, Prokhorov, A, Vakaluyk, I, Myshanych, H, Reshotko, D, Batushkin, V, Rudenko, L, Kovalskyi, I, Kushnir, M, Tseluyko, V, Mostovoy, Y, Stanislavchuk, M, Kyiak, Y, Karpenko, Y, Malynovsky, Y, Klantsa, A, Kutniy, O, Amosova, E, Tashchuk, V, Leshchuk, O, Rishko, M, Kopytsya, M, Yagensky, A, Vatutin, M, Bagriy, A, Barna, O, Ushakov, O, Dzyak, G, Goloborodko, B, Rudenko, A, Zheleznyy, V, Trevelyan, J, Zaman, A, Lee, K, Moriarty, A, Aggarwal, R, Clifford, P, Wong, Y, Iqbal, S, Subkovas, E, Braganza, D, Sarkar, D, Storey, R, Griffiths, H, Mcclure, S, Muthusamy, R, Smith, S, Kurian, J, Levy, T, Barr, C, Kadr, H, Gerber, R, Simaitis, A, Soran, H, Mathur, A, Brodison, A, Ayaz, M, Cheema, M, Oliver, R, Thackray, S, Mudawi, T, Rahman, G, Sultan, A, Sharman, D, Sprigings, D, Butler, R, Wilkinson, P, Lip, G, Halcox, J, Gallagher, S, Ossei-Gerning, N, Vardi, G, Baldari, D, Brabham, D, Treasure II, C, Dahl, C, Palmer, B, Wiseman, A, Puri, S, Mohart, A, Ince, C, Flores, E, Wright, S, Cheng, S, Rosenberg, M, Rogers, W, Kosinski, E, Forgosh, L, Waltman, J, Khan, M, Shoukfeh, M, Dagher, G, Cambier, P, Lieber, I, Kumar, P, East, C, Krichmar, P, Hasan, M, White, L, Knickelbine, T, Haldis, T, Gillespie, E, Amidon, T, Suh, D, Arif, I, Abdallah, M, Akhter, F, Carlson, E, D'Urso, M, El-Ahdab, F, Nelson, W, Moriarty, K, Harris, B, Cohen, S, Carter, L, Doty, D, Sabatino, K, Haddad, T, Malik, A, Rao, S, Mulkay, A, Jovin, I, Klancke, K, Malhotra, V, Devarapalli, S, Koren, M, Chandna, H, Dodds III, G, Goraya, T, Bengston, J, Janik, M, Moran, J, Sumner, A, Kobayashi, J, Davis, W, Yazdani, S, Pasquini, J, Thakkar, M, Vedere, A, Leimbach, W, Rider, J, Fenton, S, Singh, N, Shah, A, Janosik, D, Pepine, C, Berman, B, Gelormini, J, Daniels, C, Richard, K, Keating, F, Kondo, N, Shetty, S, Levite, H, Waider, W, Takata, T, Abu-Fadel, M, Shah, V, Izzo, M, Kumar, A, Hattler, B, Do, R, Link, C, Bortnick, A, Kinzfogl III, G, Ghitis, A, Larry, J, Teufel, E, Kuhlman, P, Mclaurin, B, Zhang, W, Thew, S, Abbas, J, White, M, Islam, O, Subherwal, S, Ranadive, N, Vakili, B, Gring, C, Henderson, D, Schuchard, T, Farhat, N, Kline, G, Mahal, S, Whitaker, J, Speirs, S, Andersen, R, Daboul, N, Horwitz, P, Zahr, F, Ponce, G, Jafar, Z, Mcgarvey, J, Panchal, V, Voyce, S, Blok, T, Sheldon, W, Azizad, M, Schmalfuss, C, Picone, M, Pederson, R, Herzog, W, Friedman, K, Lindsey, J, Nowins, R, Timothy, E, Leonard, P, Lepor, N, El Shahawy, M, Weintraub, H, Irimpen, A, Alonso, A, May, W, Christopher, D, Galski, T, Chu, A, Mody, F, Ramin, E, Hodes, Z, Rossi, J, Rose, G, Fairlamb, J, Lambert, C, Raisinghani, A, Abbate, A, Vetrovec, G, King, M, Carey, C, Gerber, J, Younis, L, Vidovich, M, Knutson, T, Friedman, D, Chaleff, F, Loussararian, A, Rozeman, P, Kimmelstiel, C, Kuvin, J, Silver, K, Foster, M, Tonnessen, G, Espinoza, A, Amlani, M, Wali, A, Malozzi, C, Jong, G, Massey, C, Wattanakit, K, O'Donnell, P, Singal, D, Jaffrani, N, Banuru, S, Fisher, D, Xenakis, M, Perlmutter, N, Bhagwat, R, Strader, J, Blonder, R, Akyea-Djamson, A, Labroo, A, Marais, H, Claxton, E, Weiss, R, Kathryn, R, Berk, M, Joshi, P, Khera, A, Khaira, A, Kumkumian, G, Lupovitch, S, Purow, J, Welka, S, Hoffman, D, Fischer, S, Soroka, E, Eagerton, D, Pancholy, S, Ray, M, Erenrich, N, Farrar, M, Pollock, S, French, W, Diamantis, S, Guy, D, Gimple, L, Neustel, M, Schwartz, S, Pereira, E, Albert, S, Spriggs, D, Strain, J, Mittal, S, Vo, A, Chane, M, Hall, J, Vijay, N, Lotun, K, Lester, F, Nahhas, A, Pope, T, Nager, P, Vohra, R, Sharma, M, Bashir, R, Ahmed, H, Berlowitz, M, Fishberg, R, Barrucco, R, Yang, E, Radin, M, Sporn, D, Stapleton, D, Eisenberg, S, Landzberg, J, Mcgough, M, Turk, S, Schwartz, M, Sundram, P, Jain, D, Zainea, M, Bayron, C, Karlsberg, R, Dohad, S, Lui, H, Keen, W, Westerhausen, D, Khurana, S, Agarwal, H, Birchem, J, Penny, W, Chang, M, Murphy, S, Henry, J, Schifferdecker, B, Gilbert, J, Chalavarya, G, Eaton, C, Schmedtje, J, Christenson, S, Dotani, I, Denham, D, Macdonell, A, Gibson, P, Rahman, A, Al Joundi, T, Assi, N, Conrad, G, Kotha, P, Love, M, Giesler, G, Rubenstein, H, Gamil, D, Akright, L, Krawczyk, J, Cobler, J, Wells, T, Welker, J, Foster, R, Gilmore, R, Anderson, J, Jacoby, D, Gardner, G, Dandillaya, R, Vora, K, Kostis, J, Hunter, J, Laxson, D, Ball, E, Egydio, F, Kawakami, A, Oliveira, J, Wozniak, J, Matthews, A, Ratky, C, Valiris, J, Berdan, L, Hepditch, A, Quintero, K, Rorick, T, Westbrook, M, Pascual, A, Rovito, C, Bezault, M, Drouet, E, Simon, T, Alsweiler, C, Luyten, A, Butters, J, Griffith, L, Shaw, M, Grunberg, L, Islam, S, Bregeault, M, Bougon, N, Faustino, D, Fontecave, S, Murphy, J, Verrier, M, Agnetti, V, Andersen, D, Badreddine, E, Bekkouche, M, Bouancheau, C, Brigui, I, Brocklehurst, M, Cianciarulo, J, Devaul, D, Domokos, S, Gache, C, Gobillot, C, Guillou, S, Healy, J, Heath, M, Jaiwal, G, Javierre, C, Labeirie, J, Monier, M, Morales, U, Mrabti, A, Mthombeni, B, Okan, B, Smith, L, Sheller, J, Sopena, S, Pellan, V, Benbernou, F, Bengrait, N, Lamoureux, M, Kralova, K, Scemama, M, Bejuit, R, Coulange, A, Berthou, C, Repincay, J, Lorenzato, C, Etienne, A, Gouet, V, Normand, M, Ourliac, A, Rondel, C, Adamo, A, Beltran, P, Barraud, P, Dubois-Gache, H, Halle, B, Metwally, L, Mourgues, M, Sotty, M, Vincendet, M, Cotruta, R, Chengyue, Z, Fournie-Lloret, D, Morrello, C, Perthuis, A, Picault, P, Zobouyan, I, Dempsey, M, Mcclanahan, M, ODYSSEY OUTCOMES Comm Investigato, and Ege Üniversitesi
Subjects: Male, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences, STATIN THERAPY, blood-glucose, Endocrinology, Diabetes and Metabolism, GUIDELINES, PCSK9, 0302 clinical medicine, Endocrinology, GENETIC-VARIANTS, Cardiovascular Disease, Diabetes Complication, Aged Antibodies, Monoclonal, Humanized / therapeutic use* Cardiovascular Diseases / blood Cardiovascular Diseases / prevention & control* Diabetes Complications / blood Diabetes Complications / prevention & control* Female Humans Male Middle Aged Substances, Clinical endpoint, Medicine, guidelines, 030212 general & internal medicine, Prediabetes, Myocardial infarction, myocardial-infarction, genetic-variants, statin therapy, risk, pcsk9, association, liraglutide, evolocumab, RISK, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti, BLOOD-GLUCOSE, ASSOCIATION, Middle Aged, Cardiovascular Diseases, Female, Life Sciences & Biomedicine, Human, medicine.medical_specialty, Acute coronary syndrome, PCSK9 inhibitor, acute coronary syndrome, lipoprotein(a), low-density lipoprotein cholesterol, 030209 endocrinology & metabolism, Antibodies, Monoclonal, Humanized, Diabetes Complications, Endocrinology & Metabolism, 03 medical and health sciences, Diabetes mellitus, Internal medicine, Internal Medicine, Humans, Aged, Alirocumab, diabetes, PCSK9, hyperlipidemia, Science & Technology, ODYSSEY OUTCOMES Committees and Investigators, business.industry, Unstable angina, EVOLOCUMAB, medicine.disease, MYOCARDIAL-INFARCTION, LIRAGLUTIDE, Human medicine, business
Abstract: Doi, Yasuji/0000-0002-8368-0827; galvani, marcello/0000-0001-5897-667X; Gislason, Gunnar H/0000-0002-0548-402X; Taskinen, Marja-Riitta/0000-0002-6229-3588; Sherwood, Matthew/0000-0002-4305-5883; Malynovsky, Yaroslav V/0000-0002-9118-1104; Viktorova, vic-inna@mail.ru I.A./0000-0001-8728-2722; bastos, jose/0000-0002-9526-3123; Yang, Eric H/0000-0003-4889-7454; Rudenko, Anatoliy Viktorovich/0000-0003-1099-1613; Novotny, Vojtech/0000-0003-3521-9945; Nikolaev, Konstantin/0000-0003-4601-6203; Reshetko, Olga/0000-0003-3107-7636; Leonardi, Sergio/0000-0002-4800-6132; Muenzel, Thomas/0000-0001-5503-4150; Ushakov, Alexei V/0000-0002-7020-4442; Tse, Hung Fat/0000-0002-9578-7808; Podoleanu, Cristian/0000-0001-9987-2519; Raffel, Owen C/0000-0001-5470-7050; Khasanov, Niiaz/0000-0002-7760-0763; Chumakova, Galina A/0000-0002-2810-6531; Ersanli, Murat/0000-0003-1847-3087; cornel, jan hein/0000-0002-1006-2112; Abbate, Antonio/0000-0002-1930-785X; Racca, Vittorio/0000-0002-4465-3789; Urina-Triana, Miguel A/0000-0001-6003-4622; Rasputina, Lesia/0000-0003-1230-4039; Racca, Vittorio/0000-0002-4465-3789; Reis, Gilmar/0000-0002-4847-1034; Sandhu, Manjinder/0000-0003-2538-2079; Keskin, Kudret/0000-0002-9049-1530; PAREPA, IRINEL/0000-0002-7571-9015; Manakshe, Gajendra/0000-0002-4983-4271; Nicolau, Jose C/0000-0002-9680-3689; Strelnieks, Aldis/0000-0003-3493-2562; Budaj, Andrzej/0000-0002-6395-2098; Marin, Francisco/0000-0001-7246-7708; Wongpraparut, Nattawut/0000-0002-1541-3313; Yuan, Zuyi/0000-0002-4141-0298; Jeong, Myung Ho/0000-0003-2424-810X; Mostovoy, Yuriy/0000-0002-7041-1230; Pepine, Carl/0000-0002-6011-681X; Lopez-Jaramillo, Patricio/0000-0002-9122-8742; Garcia-Lledo, Alberto/0000-0002-8986-2584; Tesloianu, Nicolae-Dan/0000-0002-1007-3022; Kosmacheva, Elena/0000-0001-8600-0199; Kunz Sebba Barroso Souza, Weimar/0000-0002-1265-1930; Katz, Amos/0000-0003-0422-934X; Tunon, Jose/0000-0002-1373-0999; Acevedo, Monica/0000-0002-7989-6633; Hove, Jens/0000-0002-5600-5623; Yakushin, Sergey/0000-0001-7202-742X; Gonzalez Juanatey, Jose Ramon/0000-0001-9681-3388; Lyamina, Nadezhda/0000-0001-6939-3234; Aylward, Philip/0000-0002-5358-8552; Apostolovic, Svetlana/0000-0001-9015-297X; Airaksinen, Juhani/0000-0002-0193-568X; Nahhas, Prof. Dr. Ahmed/0000-0002-2887-8187; Barbarash, Olga/0000-0002-4642-3610, WOS: 000475553300016, PubMed: 31272931, Background After acute coronary syndrome, diabetes conveys an excess risk of ischaemic cardiovascular events. A reduction in mean LDL cholesterol to 1.4-1.8 mmol/L with ezetimibe or statins reduces cardiovascular events in patients with an acute coronary syndrome and diabetes. However, the efficacy and safety of further reduction in LDL cholesterol with an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) after acute coronary syndrome is unknown. We aimed to explore this issue in a prespecified analysis of the ODYSSEY OUTCOMES trial of the PCSK9 inhibitor alirocumab, assessing its effects on cardiovascular outcomes by baseline glycaemic status, while also assessing its effects on glycaemic measures including risk of new-onset diabetes. Methods ODYSSEY OUTCOMES was a randomised, double-blind, placebo-controlled trial, done at 1315 sites in 57 countries, that compared alirocumab with placebo in patients who had been admitted to hospital with an acute coronary syndrome (myocardial infarction or unstable angina) 1-12 months before randomisation and who had raised concentrations of atherogenic lipoproteins despite use of high-intensity statins. Patients were randomly assigned (1: 1) to receive alirocumab or placebo every 2 weeks; randomisation was stratified by country and was done centrally with an interactive voice-response or web-response system. Alirocumab was titrated to target LDL cholesterol concentrations of 0.65-1.30 mmol/L. in this prespecified analysis, we investigated the effect of alirocumab on cardiovascular events by glycaemic status at baseline (diabetes, prediabetes, or normoglycaemia)-defined on the basis of patient history, review of medical records, or baseline HbA(1c) or fasting serum glucose-and risk of new-onset diabetes among those without diabetes at baseline. the primary endpoint was a composite of death from coronary heart disease, non-fatal myocardial infarction, fatal or non-fatal ischaemic stroke, or unstable angina requiring hospital admission. ODYSSEY OUTCOMES is registered with ClinicalTrials. gov, number NCT01663402. Findings At study baseline, 5444 patients (28.8%) had diabetes, 8246 (43.6%) had prediabetes, and 5234 (27.7%) had normoglycaemia. There were no significant differences across glycaemic categories in median LDL cholesterol at baseline (2.20-2.28 mmol/L), after 4 months' treatment with alirocumab (0.80 mmol/L), or after 4 months' treatment with placebo (2.25-2.28 mmol/L). in the placebo group, the incidence of the primary endpoint over a median of 2.8 years was greater in patients with diabetes (16.4%) than in those with prediabetes (9.2%) or normoglycaemia (8.5%); hazard ratio (HR) for diabetes versus normoglycaemia 2.09 (95% CI 1.78-2.46, p, Sanofi; Regeneron Pharmaceuticals, Sanofi and Regeneron Pharmaceuticals.
Published: 2019
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34. Lung cancer risk in never-smokers of European descent is associated with genetic variation in the 5(p)15.33 TERT-CLPTM1Ll region

Author: Melinda C. Aldrich, Mónica Pérez-Ríos, Ping Yang, Walid Saliba, Neil E. Caporaso, Ann G. Schwartz, Donatella Ugolini, Jun Ying, Zuo-Feng Zhang, Thomas Muley, David C. Christiani, Xuemei Ji, Mariza de Andrade, Matthew B. Schabath, Kjell Grankvist, Rayjean J. Hung, Olle Melander, Yonathan Brhane, Alberto Ruano-Ravina, Monica Neri, Irene Orlow, Aage Haugen, M. Dawn Teare, Olga Y. Gorlova, Ivan P. Gorlov, Hedy S. Rennert, Hermann Brenner, Susanne M. Arnold, Jie Na, Erik H.F.M. van der Heijden, H-Erich Wichmann, Hal Morgenstern, Shanbeh Zienolddiny, Angela Risch, Maria Timofeeva, Adonina Tardón, Curtis C. Harris, Margaret R. Spitz, Geoffrey Liu, John K. Field, Lambertus A. Kiemeney, Gadi Rennert, Loic Le Marchand, Christopher I. Amos, Vidar Skaug, Triantafillos Liloglou, Angeline S. Andrew, Paul Brennan, Philip Lazarus, Elise D. Bowman, Younghun Han, Nancy Diao, Bríd M. Ryan, Wei V. Chen, Jose I. Mayordomo, Heike Bickeböller, Richard S. Houlston, Xifeng Wu, Stig E. Bojesen, Yafang Li, Maria Teresa Landi, Michael P.A. Davies, Juan-Miguel Barros-Dios, Stefano Bonassi, Angela S. Wenzlaff, and Mattias Johansson
Subjects: 0301 basic medicine, Oncology, Lung Neoplasms, Genotyping Techniques, Genome-wide association study, Lung Cancer, Never Smokers, Genome-wide Association Study, Genetic Susceptibility, Disease, Cardiorespiratory Medicine and Haematology, 0302 clinical medicine, Risk Factors, 2.1 Biological and endogenous factors, Medicine, Aetiology, Telomerase, Lung, Cancer, Single Nucleotide, Middle Aged, 3. Good health, Europe, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], 030220 oncology & carcinogenesis, Genetic susceptibility, Lung cancer, Never smokers, Chromosomes, Human, Pair 5, Female, Pair 5, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], Human, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Clinical Sciences, Oncology and Carcinogenesis, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Article, Chromosomes, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Clinical Research, Internal medicine, Tobacco, Genetics, Genetic predisposition, Humans, Genetic Predisposition to Disease, Oncology & Carcinogenesis, Polymorphism, Cancer och onkologi, Tobacco Smoke and Health, business.industry, Prevention, Human Genome, Membrane Proteins, Genetic Variation, Odds ratio, medicine.disease, Confidence interval, respiratory tract diseases, Good Health and Well Being, 030104 developmental biology, Case-Control Studies, Cancer and Oncology, Etiology, business, Genome-Wide Association Study
Abstract: Introduction: Inherited susceptibility to lung cancer risk in never-smokers is poorly understood. The major reason for this gap in knowledge is that this disease is relatively uncommon (except in Asians), making it difficult to assemble an adequate study sample. In this study we conducted a genome-wide association study on the largest, to date, set of European-descent never-smokers with lung cancer. Methods: We conducted a two-phase (discovery and replication) genome-wide association study in never-smokers of European descent. We further augmented the sample by performing a meta-analysis with never-smokers from the recent OncoArray study, which resulted in a total of 3636 cases and 6295 controls. We also compare our findings with those in smokers with lung cancer. Results: We detected three genome-wide statistically significant single nucleotide polymorphisms rs31490 (odds ratio [OR]: 0.769, 95% confidence interval [CI]: 0.722-0.820; p value 5.31 x 10(-16)), rs380286 (OR: 0.770, 95% CI: 0.723-0.820; p value 4.32 x 10(-16)), and rs4975616 OR: 0.778, 95% CI: 0.730-0.829; p value 1.04 x 10(-14)). All three mapped to Chromosome 5 CLPTM1L-TERT region, previously shown to be associated with lung cancer risk in smokers and in never-smoker Asian women, and risk of other cancers including breast, ovarian, colorectal, and prostate. Conclusions: We found that genetic susceptibility to lung cancer in never-smokers is associated to genetic variants with pan-cancer risk effects. The comparison with smokers shows that top variants previously shown to be associated with lung cancer risk only confer risk in the presence of tobacco exposure, underscoring the importance of gene-environment interactions in the etiology of this disease. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Published: 2019
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35. ABCC2 polymorphisms and survival in the Princess Margaret cohort study and the NCIC clinical trials group BR.24 trial of platinum-treated advanced stage non-small cell lung cancer patients

Author: Bingshu E. Chen, Qin Kuang, Sharon Marsh, Zhuo Chen, Ming-Sound Tsao, Sevtap Savas, Abul Kalam Azad, Yonathan Brhane, Sinead Cuffe, Dangxiao Cheng, Xin Qiu, Scott A. Laurie, Penelope A. Bradbury, Geoffrey Liu, Xiaoping Qiu, Glenwood D. Goss, Wei Xu, Natasha B. Leighl, Lesley Seymour, and Frances A. Shepherd
Subjects: Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Prognostic variable, Lung Neoplasms, Genotype, Epidemiology, Bioinformatics, Polymorphism, Single Nucleotide, 030226 pharmacology & pharmacy, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Internal medicine, Humans, Medicine, Allele, Lung cancer, Aged, Proportional Hazards Models, Aged, 80 and over, business.industry, Hazard ratio, Middle Aged, Prognosis, medicine.disease, Multidrug Resistance-Associated Protein 2, Confidence interval, Clinical trial, Treatment Outcome, 030220 oncology & carcinogenesis, Cohort, Female, Multidrug Resistance-Associated Proteins, business, Cohort study
Abstract: Background The drug transporter ABCC2 is upregulated in non-small cell lung cancer (NSCLC) and implicated in platinum resistance. We evaluated the association between germline polymorphisms in the ABCC2 gene and survival outcomes of platinum-treated advanced NSCLC patients. Material and methods Ten candidate and tagging germline polymorphisms in the ABCC2 gene were genotyped in a discovery cohort of 170 platinum-treated stage IV NSCLC patients from the Princess Margaret Cancer Centre. Associations with overall survival were assessed using multivariate Cox proportional hazard models adjusted for prognostic variables. To validate our results, we analyzed the association of the two top polymorphisms in the ABCC2 gene on survival outcomes of 219 stage IIIB-IV NSCLC patients enrolled on the NCIC Clinical Trials Group BR.24 clinical trial. Results Only one polymorphism was validated across both cohorts for an association with overall survival: the A allele of the ABCC2 polymorphism, rs8187710 (4544G>A), was associated with adverse overall survival (adjusted hazard ratio [aHR] 2.22; 95% CI: 1.2–4.0; p =0.009) among our stage IV NSCLC patients. A significant association with overall survival (aHR 1.73; 95% CI: 1.0–2.9; p =0.036) was observed for the same ABCC2 polymorphism in the BR.24 validation cohort. No other ABCC2 polymorphisms were associated with outcome. Conclusion The ABCC2 polymorphism, rs8187710 (4544G>A), is associated with overall survival in platinum-treated advanced NSCLC patients. Additional studies are needed to evaluate the predictive versus prognostic nature of this relationship, and to explore the functional effect of this polymorphism on the pharmacokinetics of platinum drugs.
Published: 2016
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36. Hépatite auto-immune induite par la nitrofurantoïne : une complication rare à connaître

Author: Frédéric Charlotte, Bénédicte Lebrun-Vignes, Zahir Amoura, F. Cohen Aubart, Yonathan Freund, M. Pineton De Chambrun, Julien Haroche, B. Sorin, and Makoto Miyara
Subjects: Gynecology, 03 medical and health sciences, Drug induced toxicity, medicine.medical_specialty, 0302 clinical medicine, business.industry, Gastroenterology, Internal Medicine, Medicine, 030211 gastroenterology & hepatology, 030212 general & internal medicine, business
Abstract: Resume Introduction La nitrofurantoine peut entrainer des effets indesirables hepatiques et pulmonaires. Parmi les atteintes hepatiques, l’hepatite auto-immune induite par la nitrofurantoine est une complication rare a ne pas confondre avec l’hepatite toxique. Observation Vingt ans apres un premier episode d’hepatite aigue lors d’un traitement par nitrofurantoine, une patiente de 86 ans presentait une hepatite aigue apres reintroduction de cet antibiotique. Le diagnostic d’hepatite auto-immune declenchee par la nitrofurantoine a pu etre porte sur l’anamnese, la biologie (hypergammaglobulinemie polyclonale importante, presence d’anticorps anti-nucleaires, et d’anticorps anti-muscle lisse) et l’histologie hepatique (infiltrat lymphocytaire et activite necrotico-inflammatoire importante). L’evolution de l’hepatite auto-immune etait favorable sous corticoides et azathioprine associes a l’arret de la nitrofurantoine. Apres 2 mois de traitement, la patiente decedait d’un episode d’insuffisance cardiaque globale refractaire. Conclusion L’hepatite auto-immune induite par la nitrofurantoine est une complication grave qu’il faut evoquer systematiquement lors d’une hepatite aigue chez un patient prenant de la nitrofurantoine. La presence d’une hypergammaglobulinemie polyclonale oriente le diagnostic. Il faut alors rechercher les auto-anticorps (anti-nucleaires et anti-muscle lisse) et proposer une biopsie hepatique. Le traitement est celui des hepatites auto-immunes, avec habituellement une evolution favorable et peu de rechutes apres arret de la nitrofurantoine.
Published: 2016
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37. Efficacy and Safety of BRAF Inhibitors With or Without MEK Inhibitors in BRAF-Mutant Advanced Non-Small-Cell Lung Cancer: Findings From a Real-Life Cohort

Author: Elizabeth Dudnik, Mira Wollner, Noa Popovits-Hadar, Abed Agbarya, Teodor Kuznetsov, Shoshana Keren, Damien Urban, Ronen Brenner, Aharon Yonathan Cohen, Alona Zer, Jair Bar, Ofer Rotem, Amir Onn, Moshe Mishaeli, Nir Peled, Hovav Nechushtan, Mor Moskovitz, Tzippy Shochat, Laila C. Roisman, Natalie Maimon Rabinovich, and Elias Bshara
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, Oncology, Adult, Male, Proto-Oncogene Proteins B-raf, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Pyridones, Pyrimidinones, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Carcinoma, Non-Small-Cell Lung, Antineoplastic Combined Chemotherapy Protocols, Oximes, medicine, Humans, Lung cancer, Vemurafenib, Aged, Trametinib, Aged, 80 and over, business.industry, Imidazoles, Dabrafenib, Middle Aged, medicine.disease, MAP Kinase Kinase Kinases, Survival Analysis, Confidence interval, Discontinuation, Clinical trial, 030104 developmental biology, 030220 oncology & carcinogenesis, Mutation, Female, business, V600E, medicine.drug
Abstract: Background Real-life comparative data on BRAF inhibitors (BRAFi) and BRAFi + MEK inhibitors (MEKi) combination in BRAF-mutant (BRAFm) non–small-cell lung cancer (NSCLC) is lacking. Patients and Methods Consecutive BRAFm advanced NSCLC patients (n = 58) treated in 9 Israeli centers in 2009-2018 were identified. These were divided according to mutation subtype and treatment into groups A1 (V600E, BRAFi; n = 5), A2 (V600E, BRAFi + MEKi; n = 15), A3 (V600E, no BRAFi; n = 7), B1 (non-V600E, BRAFi ± MEKi; n = 7), and B2 (non-V600E, no BRAFi; n = 23); one patient received both BRAFi and BRAFi + MEKi. Safety, objective response rate, progression-free survival with BRAFi ± MEKi, and overall survival were assessed. Results Objective response rate was 40%, 67%, and 33% in groups A1, A2, and B1, respectively (P = .5 for comparison between groups A1 and A2). In group B1, G469A and L597R mutations were associated with response to BRAFi + MEKi. Median progression-free survival was 1.2 months (95% confidence interval [CI], 0.5-5.3), 5.5 months (95% CI, 0.7-9.3), and 3.6 months (95% CI, 1.5-6.7) for groups A1, A2, and B1, respectively (log-rank for comparison between groups A1 and A2, P = .04). Median overall survival with BRAFi ± MEKi was 1.7 months (95% CI, 0.5-NR), 9.5 months (95% CI, 0.2-14.9), and 7.1 months (95% CI, 1.8-NR) in groups A1, A2, and B1, respectively (log-rank for comparison between groups A1 and A2, P = .6). Safety profiles differed slightly, and similar treatment discontinuation rates were observed with BRAFi and BRAFi + MEKi. Conclusion In the real-life setting, activity and safety of BRAFi + MEKi in V600E BRAFm NSCLC are comparable to those observed in prospective clinical trials; the combination of BRAFi + MEKi is superior to monotherapy with a BRAFi. Further research should be done to explore the impact of BRAFi + MEKi treatment on the natural history of BRAFm NSCLC.
Published: 2018

38. Safety of the Combination of<scp>PERC</scp>and<scp>YEARS</scp>Rules in Patients With Low Clinical Probability of Pulmonary Embolism: A Retrospective Analysis of Two Large European Cohorts

Author: Charlotte Steinier, Delphine Douillet, Ben Bloom, Boris Germeau, Anne-Laure Philippon, Judith Gorlicki, Caroline Soulie, Andrea Penaloza, Thomas Moumneh, Jennifer Truchot, Pierre-Marie Roy, Yonathan Freund, Marine Cachanado, Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service des Urgences [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Barts Health NHS Trust [London, UK], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, UCL - SSS/IREC/EPID - Pôle d'épidémiologie et biostatistique, and UCL - (SLuc) Service des urgences
Subjects: Adult, Male, medicine.medical_specialty, Computed Tomography Angiography, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Risk Assessment, Decision Support Techniques, 03 medical and health sciences, 0302 clinical medicine, Thromboembolism, Internal medicine, medicine, Clinical endpoint, Retrospective analysis, Humans, 030212 general & internal medicine, Aged, Retrospective Studies, Computed tomography angiography, medicine.diagnostic_test, business.industry, Retrospective cohort study, General Medicine, Emergency department, Middle Aged, medicine.disease, Confidence interval, 3. Good health, Pulmonary embolism, Emergency Medicine, Female, Emergency Service, Hospital, Pulmonary Embolism, Risk assessment, business
Abstract: International audience; BACKGROUND: This study aimed to determine the failure rate of a combination of the PERC and the YEARS rules for the diagnosis of pulmonary embolism (PE) in the emergency department (ED).METHODS: We performed a retrospective analysis of two European cohorts of emergency patients with low gestalt clinical probability of PE (PROPER and PERCEPIC). All patients we included were managed using a conventional strategy (D-dimer test, followed, if positive, by computed tomographic pulmonary angiogram (CTPA). We tested a diagnostic strategy that combined PERC and YEARS to rule out PE. The primary endpoint was a thromboembolic event diagnosed in the ED or at 3-months follow-up. Secondary endpoints included a thromboembolic event at baseline in the ED and a CTPA in the ED. Ninety-five percent confidence intervals (CIs) of proportions were calculated with the use of Wilson's continuity correction.RESULTS: We analyzed 1,951 patients (mean±SD age= 47±18years, 56% women) with an overall proportion of patients with PE of 3.5%. Both PERC and YEARS strategies were associated with 11 missed PE in the ED: failure rate 0.57 (95% CI= 0.32-1.02). At 3-month follow-up, the overall failure rate was 0.83% (95% CI= 0.51-1.35). Among the 503 patients who underwent a CTPA (26%), the use of the PERC-YEARS combination would have ruled out PE without CTPA in 249 patients (50% [95%CI= 45%-54%], absolute reduction13% (95% CI= 11%-14%]).CONCLUSION: The combination of PERC then YEARS was associated with a low risk of PE diagnostic failure and would have resulted in a relative reduction of almost half of CTPA.
Published: 2018
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39. Genome-wide association study of familial lung cancer

Author: Ann G. Schwartz, Elena Kupert, Neil E. Caporaso, Paul Brennan, James McKay, Sarah C. Nelson, David C. Qian, Ping Yang, Diptasri Mandal, Christine M. Lusk, John R. McLaughlin, Yonathan Brhane, Younghun Han, Ming You, Yohan Bossé, Valerie Gaborieau, Susan M. Pinney, Wenying Zheng, Yafang Li, Adrienne M. Stilp, Mariza de Andrade, Rayjean J. Hung, Colette Gaba, Joan E. Bailey-Wilson, Marshall W. Anderson, Christopher I. Amos, Cathy C. Laurie, Angela S. Wenzlaff, Maria Teresa Landi, Jinyoung Byun, and Xifeng Wu
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Genome-wide association study, Single-nucleotide polymorphism, Biology, Adenocarcinoma, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, CDKN2A, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, 1000 Genomes Project, Lung cancer, Medical History Taking, Lung, Cancer Biomarkers and Molecular Epidemiology, Chromosomes, Human, Pair 15, General Medicine, medicine.disease, Squamous carcinoma, 030104 developmental biology, 030220 oncology & carcinogenesis, Case-Control Studies, Carcinoma, Squamous Cell, Chromosomes, Human, Pair 4, Chromosomes, Human, Pair 9, Imputation (genetics), Genome-Wide Association Study
Abstract: To identify genetic variation associated with lung cancer risk, we performed a genome-wide association analysis of 685 lung cancer cases that had a family history of two or more first or second degree relatives compared with 744 controls without lung cancer that were genotyped on an Illumina Human OmniExpressExome-8v1 array. To ensure robust results, we further evaluated these findings using data from six additional studies that were assembled through the Transdisciplinary Research on Cancer of the Lung Consortium comprising 1993 familial cases and 33 690 controls. We performed a meta-analysis after imputation of all variants using the 1000 Genomes Project Phase 1 (version 3 release date September 2013). Analyses were conducted for 9 327 222 SNPs integrating data from the two sources. A novel variant on chromosome 4p15.31 near the LCORL gene and an imputed rare variant intergenic between CDKN2A and IFNA8 on chromosome 9p21.3 were identified at a genome-wide level of significance for squamous cell carcinomas. Additionally, associations of CHRNA3 and CHRNA5 on chromosome 15q25.1 in sporadic lung cancer were confirmed at a genome-wide level of significance in familial lung cancer. Previously identified variants in or near CHRNA2, BRCA2, CYP2A6 for overall lung cancer, TERT, SECISPB2L and RTEL1 for adenocarcinoma and RAD52 and MHC for squamous carcinoma were significantly associated with lung cancer.
Published: 2018

40. Prevalence and characteristics of metabolic syndrome in gout patients in a hospital setting in sub-Saharan Africa

Author: Yonathan Lobe Batchama, Félicité Kamdem, Henry Luma Namme, Fernando Kemta Lekpa, Jude Moutchia-Suh, Marie Doualla-Bija, and Vicky Joceline Ama Moor
Subjects: musculoskeletal diseases, Adult, medicine.medical_specialty, Gout, Cross-sectional study, Endocrinology, Diabetes and Metabolism, Population, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Internal Medicine, Prevalence, Medicine, Humans, Hyperuricemia, Cameroon, education, Aged, 030203 arthritis & rheumatology, Metabolic Syndrome, education.field_of_study, business.industry, nutritional and metabolic diseases, General Medicine, Middle Aged, medicine.disease, Cross-Sectional Studies, Metabolic syndrome, business, Body mass index, Cohort study
Abstract: Background Evidence from epidemiological studies suggests an important association between gout and the metabolic syndrome (MetS). However, to the best of our knowledge, prevalence of metabolic syndrome in gout has not been reported in sub-Saharan African (SSA) settings. Objectives The aim of this study was to determine the prevalence and characteristics of MetS in gout in a SSA population. Method After prior ethical clearance, we carried out a cross-sectional study involving gout patients in a referral hospital in Douala-Cameroon. Metabolic syndrome was defined using International Diabetes Foundation criteria. Associations between variables were assessed using logistic regression.p Results On 174 gout patients (48.3% females) who consented to participate in the study, the median (IQR) age was 55.00 (14.25) years, and the median (IQR) duration of gout was 7.5 (10.0) years. Prevalence of metabolic syndrome was 54.6% (95% CI: 47.9%–62.8%). One hundred and forty-seven (84.5%) participants had central obesity, 62 (35.6%) raised triglycerides, 79 (45.4%) reduced HDL-C, 129 (74.1%) raised blood pressure, and 85 (48.9%) had raised fasting plasma glucose. On logistic regression analyses, gout patients with metabolic syndrome significantly had a higher body mass index (OR: 1.09, 95% CI: 1.02–1.17), and higher levels of serum uric acid (OR: 1.02, 95% CI: 1.01–1.04). Conclusions About 1 out of every 2 gout patients in this population have metabolic syndrome. These gout patients with metabolic syndrome significantly have a higher body mass index, and higher levels of serum uric acid. Cohort studies are required to clearly establish the direction of the relationship between gout and metabolic syndrome.
Published: 2018

41. Early variation of quick sequential organ failure assessment score to predict in-hospital mortality in emergency department patients with suspected infection

Author: Florence Dumas, E. Krastinova, Bruno Riou, Andrea Penaloza, Sébastien Beaune, Andrianjafy H, Anne-Laure Feral-Pierssens, Yonathan Freund, Le Borgne P, Youri Yordanov, Ben Bloom, N. Lemachatti, Pierre-Géraud Claret, Mar Ortega, Pierre Hausfater, Jennifer Truchot, and Céline Occelli
Subjects: Adult, Male, medicine.medical_specialty, Internationality, Databases, Factual, Organ Dysfunction Scores, Multiple Organ Failure, Bacteremia, Kaplan-Meier Estimate, Risk Assessment, Severity of Illness Index, Cohort Studies, Sex Factors, Belgium, Predictive Value of Tests, Internal medicine, Cause of Death, medicine, Clinical endpoint, Hospital discharge, Prevalence, Humans, Hospital Mortality, Prospective Studies, Prospective cohort study, Aged, Proportional Hazards Models, Aged, 80 and over, In hospital mortality, Sequential organ failure assessment, business.industry, Hazard ratio, Age Factors, Emergency department, Middle Aged, Confidence interval, Spain, Multivariate Analysis, Emergency Medicine, Disease Progression, Female, France, business, Emergency Service, Hospital
Abstract: BACKGROUND The quick sequential organ failure assessment (qSOFA) score showed good prognostic performance in patients with suspicion of infection in the emergency department (ED). However, previous studies only assessed the performance of individual values of qSOFA during the ED stay. As this score may vary over short timeframes, the optimal time of measurement, and the prognostic value of its variation are unclear. The objective of the present study was to prospectively assess the prognostic value of the change in qSOFA over the first 3 h (ΔqSOFA = qSOFA at 3 h-qSOFA at inclusion). PATIENTS AND METHODS This is an international prospective cohort study conducted in 17 EDs in France, Belgium, and Spain. From November 2016 to March 2017, patients with a suspected infection and a qSOFA score of 2 or higher were included and followed up until death or hospital discharge. qSOFA was measured at inclusion, 1 h and 3 h. Primary end point was in-hospital mortality, truncated at 28 days. RESULTS Of 534 recruited patients, 512 were included in the analysis. The qSOFA was improved at 3 h (ΔqSOFA < 0) in 287 (55%) patients. Overall in-hospital mortality was 27%: 44% when ΔqSOFA greater than 0, 36% when ΔqSOFA = 0, and 18% when ΔqSOFA less than 0. A positive ΔqSOFA was independently associated with reduced in-hospital mortality (adjusted hazard ratio of 0.48, 95% confidence interval: 0.34-0.68). After modeling qSOFA kinetics in the first 3 h, there was a significant difference in adjusted slopes between patients who died and those who survived (0.15, 95% confidence interval: 0.09-0.22, P < 0.001). CONCLUSION In patients with suspected infection presenting to the ED with a qSOFA of 2 or higher, the early change in qSOFA is a strong independent predictor of mortality.
Published: 2018

42. Elevated Platelet Count Appears to Be Causally Associated with Increased Risk of Lung Cancer: A Mendelian Randomization Analysis

Author: Xuesi Dong, Loic Le Marchand, Thomas Muley, Matthew J. Barnett, Shanbeh Zienolddiny, Jennifer A. Doherty, Adonina Tardón, John McLaughlin, Gad Rennert, Demetrius Albanes, Chu Chen, Geoffrey Liu, Heike Bickeboeller, Philip Lazarus, Rayjean J. Hung, Christopher I. Amos, Younghun Han, Yongyue Wei, Stephen J. Chanock, Angela Cox, Ming-Sound Tsao, Penella J. Woll, H. E. Wichmann, Fangyi Gu, Dawn Teare, Lambertus A. Kiemeney, Bin Zhu, James D. McKay, Jianling Bai, Neil E. Caporaso, Richard S. Houlston, Gary E. Goodman, Stephen Lam, Erik H.F.M. van der Heijden, Mattias Johansson, Jonas Manjer, Angela Risch, Ying Zhu, Maria Teresa Landi, Ruyang Zhang, Yuanqing Ye, Michael P.A. Davies, Stig E. Bojesen, Angeline S. Andrew, Linda Kachuri, Dakai Zhu, Hans Brunnström, Feng Chen, Melinda C. Aldrich, Eric J. Duell, Vidar Skaug, Walid Saliba, Olle Melander, Robert Carreras-Torres, Mikael Johansson, Yang Zhao, John K. Field, Hongbing Shen, Michael W. Marcus, Juncheng Dai, Ana Fernández-Somoano, Guillermo Fernández-Tardón, Paul Brennan, David C. Christiani, Fiona Taylor, Aage Haugen, Sipeng Shen, Frances A. Shepherd, Zhibin Hu, Lynne R. Wilkens, Yonathan Brhane, Victoria L. Stevens, Matthew B. Schabath, Xifeng Wu, Susanne M. Arnold, Kjell Grankvist, and Albert Rosenberger
Subjects: 0301 basic medicine, Oncology, Blood Platelets, medicine.medical_specialty, Lung Neoplasms, Epidemiology, Single-nucleotide polymorphism, Adenocarcinoma of Lung, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Carcinoma, Non-Small-Cell Lung, Mendelian randomization, Biomarkers, Tumor, Medicine, Humans, Genetic Predisposition to Disease, Platelet activation, Lung cancer, Lung, business.industry, Platelet Count, Cancer, Mendelian Randomization Analysis, medicine.disease, Prognosis, Small Cell Lung Carcinoma, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], 030220 oncology & carcinogenesis, Case-Control Studies, Carcinoma, Squamous Cell, Medical genetics, business, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
Abstract: The CAPUA study was supported by FIS-FEDER/Spain grants FIS-01/310, FIS-PI03-0365, and FIS-07-BI060604; FICYT/Asturias grants FICYT PB02-67 and FICYT IB09-133; and the University Institute of Oncology (IUOPA) of the University of Oviedo and the Ciber de Epidemiologiay Salud Pública (CIBERESP), Spain. (...), Zhu, Y., Wei, Y., Zhang, R., Dong, X., Shen, S., Zhao, Y., Bai, J., Albanes, D., Caporaso, N.E., Landi, M.T., Zhu, B., Chanock, S.J., Gu, F., Lam, S., Tsao, M.-S., Shepherd, F.A., Tardon, A., Fernandez-Somoano, A., Fernandez-Tardon, G., Chen, C., Barnett, M.J., Doherty, J., Bojesen, S.E., Johansson, M., Brennan, P., McKay, J.D., Carreras-Torres, R., Muley, T., Risch, A., Wichmann, H.-E., Bickeboeller, H., Rosenberger, A., Rennert, G., Saliba, W., Arnold, S.M., Field, J.K., Davies, M.P.A., Marcus, M.W., Wu, X., Ye, Y., Le Marchand, L., Wilkens, L.R., Melander, O., Manjer, J., Brunnstrom, H., Hung, R.J., Liu, G., Brhane, Y., Kachuri, L., Andrew, A.S., Duell, E.J., Kiemeney, L.A., Van der Heijden, E.H.F.M., Haugen, A., Zienolddiny, S., Skaug, V., Grankvist, K., Johansson, M., Woll, P.J., Cox, A., Taylor, F., Teare, D.M., Lazarus, P., Schabath, M.B., Aldrich, M.C., Houlston, R.S., McLaughlin, J., Stevens, V.L., Shen, H., Hu, Z., Dai, J., Amos, C.I., Han, Y., Zhu, D., Goodman, G.E., Chen, F., Christiani, D.C.
Published: 2018

43. Effect of the Pulmonary Embolism Rule-Out Criteria on Subsequent Thromboembolic Events Among Low-Risk Emergency Department Patients: The PROPER Randomized Clinical Trial

Author: A. Aubry, Thibaut Desmettre, Sébastien Beaune, Marine Cachanado, Karim Tazarourte, Tabassome Simon, Alexandra Rousseau, Ben Bloom, Mehdi Khellaf, Charlotte Orsini, Nacera Baarir, Jennifer Truchot, Anne-Laure Feral-Pierssens, Agathe Leleu, Yonathan Freund, Sandrine Charpentier, Pierre-Alexis Raynal, Bruno Riou, Florence Dumas, and Mathias Wargon
Subjects: Adult, Male, Risk, medicine.medical_specialty, Randomization, 030204 cardiovascular system & hematology, law.invention, Decision Support Techniques, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Clinical Protocols, law, Internal medicine, Thromboembolism, Clinical endpoint, medicine, Pulmonary angiography, Humans, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Cross-Over Studies, business.industry, General Medicine, Emergency department, Middle Aged, medicine.disease, Crossover study, Pulmonary embolism, Female, business, Emergency Service, Hospital, Pulmonary Embolism
Abstract: The safety of the pulmonary embolism rule-out criteria (PERC), an 8-item block of clinical criteria aimed at ruling out pulmonary embolism (PE), has not been assessed in a randomized clinical trial.To prospectively validate the safety of a PERC-based strategy to rule out PE.A crossover cluster-randomized clinical noninferiority trial in 14 emergency departments in France. Patients with a low gestalt clinical probability of PE were included from August 2015 to September 2016, and followed up until December 2016.Each center was randomized for the sequence of intervention periods. In the PERC period, the diagnosis of PE was excluded with no further testing if all 8 items of the PERC rule were negative.The primary end point was the occurrence of a thromboembolic event during the 3-month follow-up period that was not initially diagnosed. The noninferiority margin was set at 1.5%. Secondary end points included the rate of computed tomographic pulmonary angiography (CTPA), median length of stay in the emergency department, and rate of hospital admission.Among 1916 patients who were cluster-randomized (mean age 44 years, 980 [51%] women), 962 were assigned to the PERC group and 954 were assigned to the control group. A total of 1749 patients completed the trial. A PE was diagnosed at initial presentation in 26 patients in the control group (2.7%) vs 14 (1.5%) in the PERC group (difference, 1.3% [95% CI, -0.1% to 2.7%]; P = .052). One PE (0.1%) was diagnosed during follow-up in the PERC group vs none in the control group (difference, 0.1% [95% CI, -∞ to 0.8%]). The proportion of patients undergoing CTPA in the PERC group vs control group was 13% vs 23% (difference, -10% [95% CI, -13% to -6%]; P .001). In the PERC group, rates were significantly reduced for the median length of emergency department stay (mean reduction, 36 minutes [95% CI, 4 to 68]) and hospital admission (difference, 3.3% [95% CI, 0.1% to 6.6%]).Among very low-risk patients with suspected PE, randomization to a PERC strategy vs conventional strategy did not result in an inferior rate of thromboembolic events over 3 months. These findings support the safety of PERC for very low-risk patients presenting to the emergency department.clinicaltrials.gov Identifier: NCT02375919.
Published: 2018

44. SPECT myocardial perfusion imaging findings in a patient with hypereosinophilic myocarditis

Author: John N. Makaryus, Nicholas Chan, Yonathan Litwok, and Loukas Boutis
Subjects: Myocardial perfusion imaging, medicine.medical_specialty, Myocarditis, Text mining, medicine.diagnostic_test, business.industry, Internal medicine, Cardiology, Medicine, Radiology, Nuclear Medicine and imaging, Cardiology and Cardiovascular Medicine, business, medicine.disease
Published: 2019
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45. Architecture of GnRH-Gonadotrope-Vasculature Reveals a Dual Mode of Gonadotropin Regulation in Fish

Author: Matan Golan, Einat Zelinger, Berta Levavi-Sivan, and Yonathan Zohar
Subjects: medicine.medical_specialty, Pituitary gland, medicine.drug_class, Enteroendocrine cell, Gonadotrophs, Gonadotropic cell, Animals, Genetically Modified, Gonadotropin-Releasing Hormone, Endocrinology, Internal medicine, medicine, Animals, Axon, Zebrafish, Neurons, biology, Luteinizing Hormone, biology.organism_classification, Delivery mode, medicine.anatomical_structure, Pituitary Gland, Follicle Stimulating Hormone, Gonadotropin, Luteinizing hormone
Abstract: The function and components of the hypothalamic-pituitary axis are conserved among vertebrates; however, in fish, a neuroglandular mode of delivery (direct contact between axons and endocrine cells) was considered dominant, whereas in tetrapods hypothalamic signals are relayed to their targets via the hypophysial portal blood system (neurovascular delivery mode). By using a transgenic zebrafish model we studied the functional and anatomical aspects of gonadotrope regulation thus revisiting the existing model. FSH cells were found to be situated close to the vasculature whereas the compact organization of LH cells prevented direct contact of all cells with the circulation. GnRH3 fibers formed multiple boutons upon reaching the pituitary, but most of these structures were located in the neurohypophysis rather than adjacent to gonadotropes. A close association was observed between FSH cells and GnRH3 boutons, but only a fifth of the LH cells were in direct contact with GnRH3 axons, suggesting that FSH cells are more directly regulated than LH cells. GnRH3 fibers closely followed the vasculature in the neurohypophysis and formed numerous boutons along these tracts. These vessels were found to be permeable to relatively large molecules, suggesting the uptake of GnRH3 peptides. Our findings have important implications regarding the differential regulation of LH and FSH and contradict the accepted notion that fish pituitary cells are mostly regulated directly by hypothalamic fibers. Instead, we provide evidence that zebrafish apply a dual mode of gonadotrope regulation by GnRH3 that combines both neuroglandular and neurovascular components.
Published: 2015
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46. A 54-Year-Old Woman With a Single Coronary Artery and Watershed Ischemia Treated With Nitrates

Author: Yonathan F. Melman, Saumya Das, and Donald E. Cutlip
Subjects: Chest pressure, medicine.medical_specialty, Coronary Vessel Anomalies, Vasodilator Agents, Myocardial Ischemia, Ischemia, Exertional dyspnea, Coronary Angiography, Coronary Circulation, Internal medicine, Single coronary artery, medicine, Humans, Medical history, Nitrates, business.industry, Myocardial Perfusion Imaging, Middle Aged, medicine.disease, Surgery, Treatment Outcome, Cardiology, Female, Tomography, X-Ray Computed, Cardiology and Cardiovascular Medicine, business
Abstract: A 54-year-old woman with a medical history notable for obesity and hypertension was referred to our institution after a positive nuclear stress test. She had reported several weeks of gradually worsening chest pressure and exertional dyspnea with recent difficulty performing even activities of daily
Published: 2015
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47. Heat Acclimatization Protects the Left Ventricle from Increased Diastolic Chamber Stiffness Immediately after Coronary Artery Bypass Surgery: A Lesson from 30 Years of Studies on Heat Acclimation Mediated Cross Tolerance

Author: Mara Shochina, Michal Horowitz, Arthur Pollak, Dan Gilon, Yonathan Hasin, and G. Merin
Subjects: medicine.medical_specialty, Physiology, Diastole, 030204 cardiovascular system & hematology, lcsh:Physiology, law.invention, Coronary artery disease, 03 medical and health sciences, Coronary artery bypass surgery, 0302 clinical medicine, Heat acclimation, law, Physiology (medical), Internal medicine, medicine, Cardiopulmonary bypass, heat acclimatization, diastolic stiffness, Original Research, lcsh:QP1-981, business.industry, coronary bypass, medicine.disease, Cross-tolerance, medicine.anatomical_structure, cross-tolerance, Ventricle, Cardiology, heat acclimation, business, 030217 neurology & neurosurgery, Artery
Abstract: During the period of 1986–1997 the first 4 publications on the mechanical and metabolic properties of heat acclimated rat's heart were published. The outcome of these studies implied that heat acclimation, sedentary as well as combined with exercise training, confers long lasting protection against ischemic/reperfusion insult. These results promoted a clinical study on patients with coronary artery disease scheduled for elective coronary artery bypass operations aiming to elucidate whether exploitation of environmental stress can be translated into human benefits by improving physiological recovery. During the 1998 study, immediate-post operative chamber stiffness was assessed in patients acclimatized to heat and low intensity training in the desert (spring in the Dead Sea, 17–33°C) vs. patients in colder weather (spring in non-desert areas, 6–19°C) via echocardiogram acquisition simultaneous with left atrial pressure measurement during fast intravascular fluid bolus administration. We showed that patients undergoing “heat acclimatization combined with exercise training” were less susceptible to ischemic injury, therefore expressing less diastolic dysfunction after cardiopulmonary bypass compared to non-acclimatized patients. This was the first clinical translational study on cardiac patients, while exploiting environmental harsh conditions for human benefits. The original experimental data are described and discussed in view of the past as well as the present knowledge of the protective mechanisms induced by Heat Acclimation Mediated Cross-tolerance.
Published: 2017
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48. Effects of the intensity of prehospital treatment on short-term outcomes in patients with acute heart failure: the SEMICA-2 study

Author: Mirã³, Ã’Scar, Hazlitt, Melissa, Escalada, Xavier, Llorens, Pere, Gil, Vãctor, MartÃn-SÃ¡nchez, Francisco Javier, Harjola, Pia, Rico, Verã³nica, Herrero-Puente, Pablo, Jacob, Javier, Cone, David C., Mã¶ckel, Martin, Christ, Michael, Freund, Yonathan, Di Somma, Salvatore, Laribi, Said, Mebazaa, Alexandre, Harjola, Veli-Pekka, Fuentes, Marta, Gil, Cristina, Alonso, Hã©ctor, Garmila, Pablo, Adrada, Esther RodrÃguez, Escoda, Rosa, Xipell, Carolina, Sã¡nchez, Carolina, Gaytan, Josep MÂª, Salvo, Eva, PÃ©rez-DurÃ¡, MarÃa JosÃ©, Noval, Antonio, Torres, JosÃ© M., Juan-GÃ³mez, Maria Ãngeles, LÃ³pez-Grima, MarÃa Luisa, Valero, Amparo, Aguirre, Alfons, Pedragosa, Maria Ã€ngels, Alonso, Maria Isabel, Ruiz, Francisco, Franco, JosÃ© Miguel, DIAZ DELGADO, ELENA LOPEZ, Mecina, Ana BelÃ©n, Tost, Josep, Sã¡nchez, Susana, Piã±era, Pascual, Torres-Garate, Raquel, Alquezar, Aitor, Rizzi, Miguel Alberto, Herrera, Sergio, Cabello, Irene, Ãlvarez-PÃ©rez, JosÃ© MarÃa, LÃ³pez-Diez, Maria Pilar, VÃ¡zquez-Alvarez, Joaquin, SÃ¡nchez-Gonzalez, Marta, Gil-RomÃ¡n, Jose Juan, Carratalã¡, JosÃ© Manuel, Brouzet, Benjamin, Marquina, Vãctor, Jimã©nez, Inmaculada, Hernã¡ndez, Nã©stor, Romã¡n, Francisco, Antonio Andueza, Juan, Romero, Rodolfo, Calvache, Roberto, Lorca, Maria Teresa, Calderã³n, Luis, Arriaga, Beatriz Amores, Sierra, Beatriz, MartÃn-Mojarro, Enrique, TraverÃa-BÃ©cquer, Lisette, Llauger-Garcia, Lluãs, Corominas-LaSalle, Gerard, AgÃ¼era-Urbano, Carmen, Soy-Ferrer, Ester, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Université Pierre et Marie Curie - Paris 6 (UPMC), Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'Anesthésie Réanimation SMUR [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and University of Helsinki
Subjects: Male, Emergency Medical Services, Time Factors, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, 0302 clinical medicine, Risk Factors, Positive airway pressure, Clinical endpoint, Odds Ratio, 030212 general & internal medicine, Hospital Mortality, Registries, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, Furosemide, General Medicine, Combined Modality Therapy, 3. Good health, prehospital care, Treatment Outcome, Acute Disease, advanced life support, outcome, Cardiology, Breathing, Female, Cardiology and Cardiovascular Medicine, medicine.drug, medicine.medical_specialty, acute heart failure, mortality, cardiology and cardiovascular medicine, Advanced Cardiac Life Support, 03 medical and health sciences, Internal medicine, Statistical significance, medicine, Humans, Aged, Heart Failure, Chi-Square Distribution, business.industry, Odds ratio, Length of Stay, medicine.disease, Advanced life support, Logistic Models, Spain, Heart failure, Emergency medicine, business
Abstract: Little is known about treatments provided by advanced life support (ALS) ambulance teams to patients with acute heart failure (AHF) during the prehospital phase, and their influence on short-term outcome. We evaluated the effect of prehospital care in consecutive patients diagnosed with AHF in Spanish emergency departments (EDs). We selected patients from the EAHFE registry arriving at the ED by ALS ambulances with available follow-up data. We recorded specific prehospital ALS treatments (supplemental oxygen, diuretics, nitroglycerin, non-invasive ventilation) and patients were grouped according to whether they received low- (LIPHT; 0/1 treatments) or high-intensity prehospital therapy (HIPHT; > 1 treatment) for AHF. We also recorded 46 covariates. The primary endpoint was all-cause 7-day mortality, and secondary endpoints were prolonged hospitalisation (> 10 days) and in-hospital and 30-day mortality. Unadjusted and adjusted odds ratios were calculated to compare the groups. We included 1493 patients [mean age 80.7 (10) years; women 54.8%]. Prehospital treatment included supplemental oxygen in 71.2%, diuretics in 27.9%, nitroglycerin in 13.5%, and non-invasive ventilation in 5.3%. The LIPHT group included 1041 patients (70.0%) with an unadjusted OR for 7-day mortality of 1.770 (95% CI 1.115–2.811; p = 0.016), and 1.939 (95% CI 1.114–3.287, p = 0.014) after adjustment for 16 discordant covariables. The adjusted ORs for all secondary endpoints were always > 1 in the LIPHT group, but none reached statistical significance. Patients finally diagnosed with AHF at then ED that have received LIPHT by the ALS ambulance teams have a poorer short-term outcome, especially during the first 7 days.
Published: 2017
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49. Rapid Rule-out of Acute Myocardial Infarction With a Single High-Sensitivity Cardiac Troponin T Measurement Below the Limit of Detection: A Collaborative Meta-analysis

Author: Steve Goodacre, Lukas P. Staub, W. Frank Peacock, Joanna M. Young, A. Mark Richards, Peter M. George, Ulf Ekelund, Andrew W. Munro, Chris J. Pemberton, Arash Mokhtari, Anne Marie Dupuy, Louise Cullen, Karin Wildi, Martin Than, Kai M. Eggers, Richard Body, Paul Collinson, John W. Pickering, Christopher M. Florkowski, Allan S. Jaffe, Ewoud ter Avest, Richard W. Troughton, Raphael Twerenbold, Sally Aldous, Yonathan Freund, Christian Mueller, Jaimi H. Greenslade, William A. Parsonage, Edward Carlton, Sarah J. Lord, Juan Sanchis, Sebbane Mustapha, and Faculteit Medische Wetenschappen/UMCG
Subjects: Male, Chest Pain, medicine.medical_specialty, Acute coronary syndrome, Myocardial Infarction, 030204 cardiovascular system & hematology, Chest pain, 03 medical and health sciences, Hospital, Electrocardiography, 0302 clinical medicine, Troponin T, Limit of Detection, Internal medicine, Journal Article, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Myocardial infarction, cardiovascular diseases, Aged, Troponin T/blood, Emergency Service, biology, business.industry, Chest Pain/etiology, General Medicine, Emergency department, Middle Aged, medicine.disease, Troponin, biology.protein, Cardiology, Female, medicine.symptom, business, Emergency Service, Hospital, Myocardial Infarction/blood, Mace, Meta-Analysis, Cohort study
Abstract: Background: High-sensitivity assays for cardiac troponin T (hs-cTnT) are sometimes used to rapidly rule out acute myocardial infarction (AMI).Purpose: To estimate the ability of a single hs-cTnT concentration below the limit of detection (Data Sources: EMBASE and MEDLINE without language restrictions (1 January 2008 to 14 December 2016).Study Selection: Cohort studies involving adults presenting to the ED with possible acute coronary syndrome in whom an ECG and hs-cTnT measurements were obtained and AMI outcomes adjudicated during initial hospitalization.Data Extraction: Investigators of studies provided data on the number of low-risk patients (no new ischemia on ECG and hs-cTnT measurements Data Synthesis: Of 9241 patients in 11 cohort studies, 2825 (30.6%) were classified as low risk. Fourteen (0.5%) low-risk patients had AMI. Sensitivity of the risk classification for AMI ranged from 87.5% to 100% in individual studies. Pooled estimated sensitivity was 98.7% (95% CI, 96.6% to 99.5%). Sensitivity for 30-day MACEs ranged from 87.9% to 100%; pooled sensitivity was 98.0% (CI, 94.7% to 99.3%). No low-risk patients died.Limitation: Few studies, variation in timing and methods of reference standard troponin tests, and heterogeneity of risk and prevalence of AMI across studies.Conclusion: A single hs-cTnT concentration below the limit of detection in combination with a nonischemic ECG may successfully rule out AMI in patients presenting to EDs with possible emergency acute coronary syndrome.Primary Funding Source: Emergency Care Foundation.
Published: 2017
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50. Neurokinin B regulates reproduction via inhibition of kisspeptin in a teleost, the striped bass

Author: Nilli Zmora, Yonathan Zohar, Ten-Tsao Wong, John Stubblefield, and Berta Levavi-Sivan
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, DNA, Complementary, Neurokinin B, Endocrinology, Diabetes and Metabolism, Neuropeptide, Biology, Gonadotropic cell, FSHB, 03 medical and health sciences, chemistry.chemical_compound, Endocrinology, Kisspeptin, Internal medicine, medicine, Animals, Cloning, Molecular, Receptor, Kisspeptins, Reproduction, Preoptic area, 030104 developmental biology, chemistry, Gene Expression Regulation, Hypothalamus, Pituitary Gland, Bass
Abstract: Kisspeptin and neurokinin B (NKB) are neuropeptides co-expressed in the mammalian hypothalamus and coordinately control GnRH signaling. We have found that Nkb and kisspeptin neurons are distinct in the teleost, striped bass (STB) and capitalized on this phenomenon to study the mode of action of Nkb and its related neuropeptide-F (Nkf), both of which are encoded by the tac3 gene. In vitro brain slices and in vivo administration studies revealed that Nkb/f consistently downregulated kiss2, whereas antagonist (AntD) administration restored this effect. Overall, a minor effect was noted on gnrh1 expression, whereas Gnrh1 content in the pituitaries was reduced after Nkb/f treatment and increased with AntD. Concomitantly, immunostaining demonstrated that hypothalamic Nkb neurons border and densely innervate the largest kiss2 neuronal population in the hypothalamus, which also coexpresses Nkb receptor. No expression of Nkb receptor or Nkb neuronal projections was detected near/in Gnrh1 soma in the preoptic area. At the level of the pituitary, however, the picture was more complex: both Nkb/f and AntD upregulated lhb and fshb expression and Lh secretion in vivo. Together with the stimulatory effect of Nkb/f on Lh/Fsh secretion from pituitary cells, in vitro, this may indicate an additional independent action of Nkb/f within the pituitary, in which the hypothalamic pathway is more dominant. The current study demonstrates that Nkb/f utilizes multiple pathways to regulate reproduction in the STB and that in the brain, Nkb mainly acts as a negative modulator of kiss2 to regulate the release of Gnrh1.
Published: 2017

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