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64. Memory in low-grade glioma patients treated with radiotherapy or temozolomide: a correlative analysis of EORTC study 22033-26033

Author

Vasilis Golfinopoulos, Roger Stupp, Mohamed Ben Hassel, Jaap C. Reijneveld, Martin J B Taphoorn, A Josephine Drijver, Andreas F. Hottinger, Thierry Gorlia, Elodie Vauleon, Khê Hoang-Xuan, Daniëlle B.P. Eekers, Salvador Villà Freixa, Brigitta G. Baumert, Martin J. van den Bent, Tzahala Tzuk-Shina, Jacolien E.C. Bromberg, A. Lucas, Martin Klein, Neurology, Vrije Universiteit Amsterdam [Amsterdam] (VU), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Service d'Oncologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Leiden University Medical Center (LUMC), Medical Center Haaglanden, CRLCC Eugène Marquis (CRLCC), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Rambam Health Care Campus [Haifa, Israel], Hospital Universitari de Bellvitge, l'Hospitalet de Llobregat, European Organisation for Research and Treatment of Cancer [Bruxelles] (EORTC), European Cancer Organisation [Bruxelles] (ECCO), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), University of Illinois [Chicago] (UIC), University of Illinois System, Radiotherapie, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Medical psychology, and CCA - Cancer Treatment and quality of life

Subjects
Oncology, Cancer Research, medicine.medical_treatment, memory functioning, temozolomide, radiation therapy, Antineoplastic Agents, Alkylating/therapeutic use, Brain Neoplasms/drug therapy, Brain Neoplasms/radiotherapy, Glioma/drug therapy, Glioma/radiotherapy, Humans, Progression-Free Survival, Temozolomide/therapeutic use, chemotherapy, low-grade glioma, radiotherapy, TOXICITY, memory, 0302 clinical medicine, Gliomas, Medicine, Neuropsychological assessment, PLUS PROCARBAZINE, NEUROCOGNITIVE FUNCTION, medicine.diagnostic_test, Brain Neoplasms, Glioma, Impaired memory, CHEMOTHERAPY, OPEN-LABEL, Chemotherapy regimen, 030220 oncology & carcinogenesis, COGNITIVE SEQUELAE, medicine.drug, medicine.medical_specialty, Radioteràpia, Verbal learning, BRAIN RADIATION, chemotherapy regimen, 03 medical and health sciences, european organization for research and treatment of cancer, SDG 3 - Good Health and Well-being, Internal medicine, VINCRISTINE, Antineoplastic Agents, Alkylating, Temozolomide, Radiotherapy, Recall, business.industry, Editorials, ADULTS, OLIGODENDROGLIOMA, medicine.disease, Radiation therapy, mental recall, Neurology (clinical), low grade glioma, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract

Background EORTC study 22033–26033 showed no difference in progression-free survival between high-risk low-grade glioma receiving either radiotherapy (RT) or temozolomide (TMZ) chemotherapy alone as primary treatment. Considering the potential long-term deleterious impact of RT on memory functioning, this study aims to determine whether TMZ is associated with less impaired memory functioning. Methods Using the Visual Verbal Learning Test (VVLT), memory functioning was evaluated at baseline and subsequently every 6 months. Minimal compliance for statistical analyses was set at 60%. Conventional indices of memory performance (VVLT Immediate Recall, Total Recall, Learning Capacity, and Delayed Recall) were used as outcome measures. Using a mixed linear model, memory functioning was compared between treatment arms and over time. Results Neuropsychological assessment was performed in 98 patients (53 RT, 46 TMZ). At 12 months, compliance had dropped to 66%, restricting analyses to baseline, 6 months, and 12 months. At baseline, patients in either treatment arm did not differ in memory functioning, sex, age, or educational level. Over time, patients in both arms showed improvement in Immediate Recall (P = 0.017) and total number of words recalled (Total Recall; P < 0.001, albeit with delayed improvement in RT patients (group by time; P = 0.011). Memory functioning was not associated with RT gross, clinical, or planned target volumes. Conclusion In patients with high-risk low-grade glioma there is no indication that in the first year after treatment, RT has a deleterious effect on memory function compared with TMZ chemotherapy.

Published
2021

65. Lumasiran for Advanced Primary Hyperoxaluria Type 1: Phase 3 ILLUMINATE-C Trial

Author

Michael, M., Groothoff, J. W., Shasha-Lavsky, H., Lieske, J. C., Frishberg, Y., Simkova, E., Sellier-Leclerc, A. L., Devresse, A., Guebre-Egziabher, F., Bakkaloglu, S. A., Mourani, C., Saqan, R., Singer, R., Willey, R., Habtemariam, B., Gansner, J. M., Bhan, I., Mcgregor, T., Magen, D., Paediatric Nephrology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ARD - Amsterdam Reproduction and Development, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, CarMeN, laboratoire, Texas Children's Hospital [Houston, USA], Baylor College of Medicine (BCM), Baylor University, Emma Children’s Hospital, Amsterdam UMC - Amsterdam University Medical Center, Galilee Medical Center [Nahariya, Israel], Bar-Ilan University [Israël], Mayo Clinic [Rochester], Shaare Zedek Medical Center [Jerusalem, Israel], Al Jalila Children's Specialty Hospital, Filières Maladies Rares ORKID et ERK-Net, Centre d'Investigation Clinique [Bron] (CIC1407), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupement Hospitalier Est [Bron], Cliniques Universitaires Saint-Luc [Bruxelles], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Gazi University, Hôpital Hôtel Dieu de France [Beirut, Lebanon] (2HDF), Jordan University of Science and Technology [Irbid, Jordan] (JUST), Canberra Health Services [Garran, ACT, Australia] (CHS), Alnylam Pharmaceuticals [Cambridge, MA, USA], and Rambam Health Care Campus [Haifa, Israel]

Subjects
Adult, Male, RNA interference (RNAi), safety, Lumasiran, urinary oxalate (UOx), Adolescent, [SDV]Life Sciences [q-bio], kidney disease, efficacy, Young Adult, nephrocalcinosis, glycolate, pharmacodynamics, Humans, Child, Hyperoxaluria, Oxalates, systemic oxalosis, hemodialysis, cardiac dysfunction, phase 3 clinical trial, Infant, Newborn, Infant, Middle Aged, adverse events, primary hyperoxaluria type 1 (PH1), [SDV] Life Sciences [q-bio], plasma oxalate (POx), anti-drug antibodies, pediatric, Nephrology, Child, Preschool, Hyperoxaluria, Primary, Female, Kidney Diseases, pharmacokinetics
Abstract

Rationale & Objective: Lumasiran reduces urinary and plasma oxalate (POx) in patients with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function. ILLUMINATE-C evaluates the efficacy, safety, pharmacokinetics, and pharmacodynamics of lumasiran in patients with PH1 and advanced kidney disease. Study Design: Phase 3, open-label, single-arm trial. Setting & Participants: Multinational study; enrolled patients with PH1 of all ages, estimated glomerular filtration rate ≤45 mL/min/1.73 m2 (if age ≥12 months) or increased serum creatinine level (if age

Published
2023

66. Highlights from ASCO-GI 2021 from EORTC Gastrointestinal tract cancer group

Author

Elisa Fontana, Maria Alsina, Manfred P Lutz, Anna Dorothea Wagner, Lucjan Wyrwicz, Francesco Sclafani, Elizabeth C Smyth, Thibaud Koessler, Irit Ben-Aharon, Radka Obermannova, Mark Peeters, Markus Moehler, Dirk Arnold, Juan W. Valle, Koessler, Thibaud [0000-0001-9196-9076], Smyth, Elizabeth [0000-0001-6427-229X], Valle, Juan W [0000-0002-1999-0863], Apollo - University of Cambridge Repository, Institut Català de la Salut, [Koessler T] Department of Oncology, Geneva University Hospital, Geneva, Switzerland. Swiss Cancer Center Leman (SCCL), University of Geneva, Lausanne, Switzerland. European Organisation for Research and Treatment of Cancer, Brussel, Belgium. [Alsina M] European Organisation for Research and Treatment of Cancer, Brussel, Belgium. Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Arnold D] European Organisation for Research and Treatment of Cancer, Brussel, Belgium. Department of Oncology, Haematology and Palliative Care, Asklepios Klinik Altona, Asklepios Tumorzentrum Hamburg, Hamburg, Germany. [Ben-Aharon I] European Organisation for Research and Treatment of Cancer, Brussel, Belgium. Division of Oncology, Rambam Health Care Campus, Rappaport Faculty of Medicine, Technion, Haifa, Israel. [Lutz MP] European Organisation for Research and Treatment of Cancer, Brussel, Belgium. Caritasklinikum, Saarbrucken, Germany. [Obermannova R] European Organisation for Research and Treatment of Cancer, Brussel, Belgium. Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute and Faculty of Medicine, Masaryk University, Brno, Czech Republic. Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czech Republic, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Immunoteràpia, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Cancer immunotherapy, Drug development, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms [DISEASES], Internal medicine, neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales [ENFERMEDADES], medicine, Humans, Routine clinical practice, Molecular Targeted Therapy, Aparell digestiu - Càncer - Tractament, Gastrointestinal Neoplasms, Gastrointestinal tract, Clinical Trials as Topic, business.industry, Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], terapéutica::terapia biológica::inmunomodulación::inmunoterapia [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Cancer, diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Congresses as Topic, medicine.disease, Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Colorectal cancer, Survival Analysis, Clinical Practice, Treatment Outcome, Hepatocellular carcinoma, Perspective, Avaluació de resultats (Assistència sanitària), Biliary tract cancer, Human medicine, Immunotherapy, Gastric cancer, business, Early phase
Abstract

Biliary tract cancer; Colorectal cancer; Drug development Cáncer del tracto biliar; Cáncer colorrectal; Desarrollo de fármacos Càncer del tracte biliar; Càncer colorectal; Desenvolupament de fàrmacs Last year the field of immunotherapy was finally introduced to GI oncology, with several changes in clinical practice such as advanced hepatocellular carcinoma or metastatic colorectal MSI-H. At the virtual ASCO-GI symposium 2021, several large trial results have been reported, some leading to a change of practice. Furthermore, during ASCO-GI 2021, results from early phase trials have been presented, some with potential important implications for future treatments. We provide here an overview of these important results and their integration into routine clinical practice. Open Access funding provided by Université de Genève.

Published
2021
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67. The COVID-19 Pandemic and the Need for an Integrated and Equitable Approach: An International Expert Consensus Paper

Author

Sergio Pillon, Mariella Catalano, Benjamin Brenner, Zsolt Pecsvarady, Ismail Elalamy, Joseph Lewis, Jean-Claude Wautrecht, D. Olinic, Vincent Maréchal, Mouna Sassi, Isabelle Mahé, Anna Falanga, Nusrat Jabeen, Charles A. Carter, Mary-Paula Colgan, Alexander Makatsariya, Alfonso Tafur, Kasse Aa, Tazi Mezalek Zoubida, Meletios-Athanasios Dimopoulos, Michèle Sabbah, Darko Antic, Yiannis Theodorou, Alex C. Spyropoulos, Vladimir Chekhonin, Meganathan Kannan, Katalin Farkas, Peter Klein-Wegel, Job Harenberg, P Massamba Mbaye, Joseph Gligorov, Manuel Monreal Bosch, Grigoris T. Gerotziafas, Pier Luigi Antignani, Hikmat Abdel-Razeq, James D. Douketis, Gerit Schernthaner, Petros Agathaggelou, Ali T. Taher, Jawed Fareed, Essam Abo Elnazar, Irina Panovska-Stavridis, Patrick Van Dreden, Fabio Leivano, Gerry Fowkes, Fakiha Siddiqui, Mark A. Ligocki, Tishya Indran, Kostantinos Konstantinidis, Bulent Kantarcioglu, Jin Shiomura, Bahare Fazeli, Chryssa Papageorgiou, Yongquan Gu, Anny Slama-Schwok, Eduardo Ramacciotti, Zenguo Zhai, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli Studi di Milano = University of Milan (UNIMI), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sechenov First Moscow State Medical University, Campbell University [Buies Creek, NC, USA] (CU), University of Karachi, Heidelberg University, Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Loyola University [Chicago], Cyprus Institute (CyI), University of Belgrade [Belgrade], Nuova Villa Claudia [Rome, Italy] (NVC), Universidad Católica San Antonio de Murcia (UCAM), Rambam Health Care Campus [Haifa, Israel], Technion - Israel Institute of Technology [Haifa], Ministry of Health of the Russian Federation (MHRF), St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Trinity College Dublin, National and Kapodistrian University of Athens (NKUA), McMaster University [Hamilton, Ontario], Firestone Institute for Respiratory Health [Hamilton, ON, Canada] (FIRH), Ministry of Health [Saudi Arabia], Szent Imre Hospital [Budapest, Hungary] (SIH), Mashhad University of Medical Sciences, University of Edinburgh, Capital University of Medical Sciences [Beijing] (CUMS), Hôpitaux Universitaires de l'Est Parisien [Paris] (HUEP), Monash Medical Centre [Clayton, Australia], Central University of Tamil Nadu [Thiruvarur, India] (CUTN), Central University of Tamil Nadu (CUTN), Okmeydani Training and Research Hospital [Istanbul, Turkey] (OTRH), Centre International de Cancérologie de Dakar [Dakar, Senegal] (CICD), Aristotle University of Thessaloniki, University Hospital Southampton NHS Foundation Trust, Université Virtuelle du Sénégal [Dakar, Senegal] (UVS), Innovations thérapeutiques en hémostase (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University Clinic of Hematology [Skopje, Republic of North Macedonia] (UCH), University of Medicine and Pharmacy [Cluj-Napoca, Romania] (UMP), Service d'Anesthésie réanimation [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Flor Ferenc Teaching Hospital [Kistarcsa, Hungary] (2FTH), San Camillo Forlanini Hospital [Rome], Loyola University Medical Center (LUMC), Science Valley Research Institute [São Paulo, Brazil] (SVRI), King Hussein Cancer Center [Amman, Jordan] (KH2C), CHU Fattouma Bourguiba [Monastir] (HFB), Medizinische Universität Wien = Medical University of Vienna, Nobelpharma Co. Ltd. [Tokyo, Japan], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), North Shore University Cardiologists [Skokie, Illinois, USA] (NSUC), American University of Beirut Faculty of Medicine and Medical Center (AUB), Klinikum Ernst von Bergmann [Potsdam, Germany] (KEVB), Peking University [Beijing], Chinese Academy of Medical Sciences [Beijing, China] (CAMS), Peking Union Medical College [Beijing, China], Université Mohammed V de Rabat [Agdal] (UM5), Scientific Reviewer Committee: Gregory Y H Lip, Michael Makris, Sam Schulman, Wolfgang Siess, Christian Weber, Sabbah, Michèle, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Milan, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and University of Mohammed V

Subjects
medicine.medical_specialty, Telemedicine, Economic growth, COVID-19 Vaccines, Population, Psychological intervention, Disease, 030204 cardiovascular system & hematology, Risk Assessment, Herd immunity, 03 medical and health sciences, COVID-19 Testing, 0302 clinical medicine, Consensus Paper, Pandemic, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030212 general & internal medicine, Disease management (health), education, Pandemics, thrombosis, education.field_of_study, SARS-CoV-2, Immunization Programs, pandemic, Public health, COVID-19, Disease Management, health care systems, Hematology, 3. Good health, Public Health, Business
Abstract

Background One year after the declaration of the coronavirus disease 2019 (COVID-19) pandemic by the World Health Organization (WHO) and despite the implementation of mandatory physical barriers and social distancing, humanity remains challenged by a long-lasting and devastating public health crisis. Management Non-pharmacological interventions (NPIs) are efficient mitigation strategies. The success of these NPIs is dependent on the approval and commitment of the population. The launch of a mass vaccination program in many countries in late December 2020 with mRNA vaccines, adenovirus-based vaccines, and inactivated virus vaccines has generated hope for the end of the pandemic. Current Issues The continuous appearance of new pathogenic viral strains and the ability of vaccines to prevent infection and transmission raise important concerns as we try to achieve community immunity against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and its variants. The need of a second and even third generation of vaccines has already been acknowledged by the WHO and governments. Perspectives There is a critical and urgent need for a balanced and integrated strategy for the management of the COVID-19 outbreaks organized on three axes: (1) Prevention of the SARS-CoV-2 infection, (2) Detection and early diagnosis of patients at risk of disease worsening, and (3) Anticipation of medical care (PDA). Conclusion The “PDA strategy” integrated into state policy for the support and expansion of health systems and introduction of digital organizations (i.e., telemedicine, e-Health, artificial intelligence, and machine-learning technology) is of major importance for the preservation of citizens' health and life world-wide.

Published
2021

68. Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic

Author

Ajit S. Puri, Allan Taylor, Huynh Le Vu, Tatemi Todaka, Teddy Y. Wu, Octavio M. Pontes-Neto, Eytan Raz, Pedro Lylyk, Jasmine Johann, Roberta Novakovic, Hormuzdiyar H. Dasenbrock, Francisco Mont’Alverne, Nobuyuki Sakai, Melanie Walker, Hugh Stephen Winters, Ossama Mansour, Yohei Takenobu, Gregory Walker, Miki Fujimura, Saif Bushnaq, Odysseas Kargiotis, Nabeel Herial, Markus A Möhlenbruch, Malveeka Sharma, Hiroshi Tokimura, Maxim Mokin, Jean Raymond, Michael D. Hill, Amal Abou-Hamden, Leonardo Renieri, Serdar Geyik, Yuri Sugiura, Luisa Fonseca, Roberto Crosa, Fabricio O Lima, Ameer E Hassan, Viet Quy Nguyen, Jane G. Morris, Steven W. Hetts, Jawad F. Kirmani, Matthew S. Tenser, Muhammad M. Qureshi, Gianmarco Bernava, Mahmoud H Mohammaden, Verónica V. Olavarría, Jun Deguchi, André Beer-Furlan, Steve M. Cordina, Hiroshi Yamagami, Mohamad Abdalkader, Toshiyuki Fujinaka, Clifford J. Eskey, Rotem Sivan-Hoffmann, Hao Zhang, Anirudh Kulkarni, Brendan Steinfort, Özlem Aykaç, Barbara Voetsch, Alex Brehm, Italo Linfante, Wenguo Huang, Omer Eker, M. Luis Silva, Pascal Jabbour, Lissa Peeling, Mollie McDermott, Pascale Lavoie, Kazutaka Sonoda, Thomas Devlin, Alicia C. Castonguay, Jin Soo Lee, Diogo C Haussen, Dileep R. Yavagal, Thanh N. Nguyen, Umair Rashid, Vasu Saini, Raghid Kikano, Hiroyuki Hashimoto, Masaaki Uno, Saima Ahmad, Artem Kaliaev, Eiji Hagashi, Ajay K. Wakhloo, Romain Bourcier, Ryoo Yamamoto, Jesse M. Thon, Georgios Tsivgoulis, Dorothea Altschul, Achmad Fidaus Sani, Satoshi Yamada, Varsha Singh, David S Liebeskind, Tatsuo Amano, Anchalee Churojana, Juan F. Arenillas, Junichi Iida, Charles C. Matouk, Nobuyuki Ohara, Osama O. Zaidat, Mario Martínez-Galdámez, Chandril Chugh, Don Frei, Vanessa Chalumeau, Brijesh P Mehta, Marios Psychogios, Anna Luisa Kühn, Leticia C Rebello, Xianjin Shang, Hosam Al-Jehani, Hiroki Fukuda, Hong Gee Roh, Gisele Sampaio Silva, Rakesh Khatri, Kenichi Todo, Amal Al Hashmi, Alex Bou Chebl, Sunil A Sheth, Zhongming Qiu, Oriana Cornett, Zhengzhou Yuan, Wazim Izzath, Hesham Masoud, Rodrigo Rivera, Michel Piotin, Vikram Huded, Mamoru Murakami, Mohamed Teleb, Viktor Szeder, Ruchir Shah, Dheeraj Gandhi, John Thornton, Michael Chen, Vitor Mendes Pereira, Nadia Hammami, Alice Ma, Anna M. Cervantes-Arslanian, James E. Siegler, Seby John, Carlos Ynigo Lopez, Mudassir Farooqui, David Ozretić, Takuya Kanamaru, Romain Guile, Daisuke Watanabe, Kosuke Miyake, Alejandro Rodriguez Vasquez, Patrick Nicholson, Yuki Yamamoto, William J. Mack, Naoto Kimura, Simon Mathew John, Robert Fahed, Yuji Matsumaru, David Y. Chung, Rishi Gupta, Ryuhei Kono, Michael Frankel, Victor S. Lopez Rivera, Johanna T. Fifi, Raul G Nogueira, Paolo Machi, Tudor G. Jovin, Jordi Blasco, Emma Griffin, Salvatore Mangiafico, Masafumi Morimoto, Jun Luo, Santiago Ortega-Gutierrez, Monika Killer-Oberpfalzer, Daniel Giansante Abud, Syed I. Hussain, Fawaz Al-Mufti, Yusuke Sugimura, Atilla Özcan Özdemir, Stephan A. Mayer, Sumeet Multani, Adel Alhazzani, Alhamza R Al-Bayati, Michael Kelly, Lee A Birnbaum, Shadi Yaghi, Jeyaraj D Pandian, Ji Man Hong, Junsuke Shimbo, Johnny Ho-Yin Wong, Elena A. Cora, Laura Mechtouff, Pedro S.C. Magalhães, Pablo M. Lavados, Yuichi Murayama, Dong Hun Shin, Simon Nagel, Ken Wong, Jose Antonio Fiorot, Jeremy Payne, Randall C. Edgell, Adrienne Weeks, CarMeN, laboratoire, Department of Neurology [Boston], Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Emory University School of Medicine, Emory University [Atlanta, GA], Boston University School of Medicine (BUSM), Boston University [Boston] (BU), National Hospital Organization Osaka National Hospital [Japon] (NHO Osaka National Hospital), Alexandria University [Alexandrie], Boston Medical Center [Boston, MA, USA] (BMC), Xinqiao Hospital [Chongqing, China] (XH), University of Cape Town, La Sagrada Familia Clinic/Clínica La Sagrada Familia [Buenos Aires, Argentina] (LSFC), Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Hospital General de Fortaleza [Fortaleza, Brazil] (HGF), Nottingham University Hospitals NHS Trust [UK], Kobe City Medical Center General Hospital [Kobe, Hyogo, Japan] (KCMCGH), Azienda Ospedaliero-Universitaria Careggi [Firenze, Toscana, Italy] (AOUC), University Hospital Centre Zagreb, Partenaires INRAE, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de Neuroradiologie [CHU de Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cleveland Clinic Abu Dhabi [Abou Dabi, Émirats arabes unis], Hôpital de Beaumont [Dublin, Ireland] (HB), Hospital-Estadual Central [Vitoria, Brazil] (HEC), Instituto de NeuroCirugía Asenjo, Institut national de neurologie Mongi-Ben Hamida [Tunis], Hue Central Hospital [Thua Thien Hue, Vietnam] (HCH), University of California [San Francisco] (UC San Francisco), University of California (UC), Centre hospitalier universitaire de Nantes (CHU Nantes), Washington University School of Medicine (WUSM), University of Washington [Seattle], Englewood Hospital and Medical Center [Englewood], Jefferson (Philadelphia University + Thomas Jefferson University), Westchester Medical Center [Valhalla, New York, USA] (WMC), Eskisehir Osmangazi University, University of Maryland School of Medicine, University of Maryland System, MAX Superspecialty Hospital [Saket, New Delhi, India] (MSH), Yale School of Medicine [New Haven, Connecticut] (YSM), Université Laval [Québec] (ULaval), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Rush University Medical Center [Chicago], Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), University of Toronto, NH Mazumdar Shah Medical Center [Bangalore, India] (NHMSMC), IMS Tokyo-Katsushika General Hospital [Tokyo, Japan], Gachon University [Seongnam, Korea] (GU), Hospital Municipal Sao Jose [Joinville, Santa Catarina, Brazil] (HMSJ), Lau Medical Center [Beirut, Lebanon] (LMC), University of Iowa [Iowa City], Royal Adelaide Hospital [Adelaide Australia], Kyorin University [Tokyo, Japan], Yokohama Brain and Spine Center [Yokohama, Japan] (YBSC), Dalhousie University [Halifax], Rambam Health Care Campus [Haifa, Israel], Centro Endovascular Neurologico Medica Uruguaya [Montevideo, Uruguay] (CENMU), Heidelberg University Hospital [Heidelberg], Imam Abdulrahman bin Faisal University [Alkhobar, Saudi Arabia] (IAFU), McGovern Medical School [Houston, TX, USA] (McGMS), The University of Texas Health Science Center at Houston (UTHealth), Cooper Medical School of Rowan University [Camden] (CMSRU), Airlangga University [Jawa Timur, Indonesia] (AU), University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS), Geneva University Hospitals and Geneva University, Universidade de São Paulo = University of São Paulo (USP), Beth Israel Lahey Health [Burlington, MA, USA] (BILH), New York University School of Medicine (NYU Grossman School of Medicine), Memorial Neuroscience Institute [Pembroke Pines, FL, USA] (MNI), Iwate Prefectural Central Hospital [Morioka, Iwate, Japan] (IPCH), Japanese Red Cross Musashino Hospital [Tokyo], Ajou University, University of Ottawa [Ottawa], Saga-ken Medical Centre Koseikan [Saga, Japan] (SMCK), University of South Alabama, Konkuk University [Seoul], Royal Free Hospital [London, UK], Hospital Clinico Universitario de Valladolid [Castilla y León, Spain] (HCUV), Universidad de Valladolid [Valladolid] (UVa), Instituto de Ciencia de Materiales de Aragón [Saragoza, España] (ICMA-CSIC), University of Zaragoza - Universidad de Zaragoza [Zaragoza], Hospital Clínic de Barcelona [Catalonia, Spain], Centro Hospitalar Universitário de São João [Porto], Christchurch Hospital [Christchurch, New Zealand] (CH), University Hospital Basel [Basel], University of Southern California (USC), Kohnan Hospital - Sendai [Miyagi, Japan], University of Texas Southwestern Medical Center [Dallas], Nara City Hospital [Nara, Japan] (NCH), Toyonaka Municipal Hospital [Osaka, Japan] (TMH), Kagoshima City Hospita [Kagoshima, Japan] (KCH), Texas Tech University System [Lubbock, TX, USA] (TTUS), University of Saskatchewan [Saskatoon] (U of S), National Institute of Information and Communications Technology [Tokyo, Japan] (NICT), Royal Prince Alfred Hospital [Camperdown, Australia] (RPAH), Banner Desert Medical Center [Mesa, AZ, USA] (BDMC), Japanese Red Cross Matsue Hospital [Shimane, Japan] (JRCMH), Shiroyama Hospital [Osaka, Japan] (SH), Niigata City General Hospital [Niigata, Japan] (NCGH), Sugimura Hospital [Kumamoto, Japan] (SH), Kawasaki Medical School [Kurashiki, Japan] (KMS), Osaka Red Cross Hospital [Osaka, Japan] (ORCH), Université de Tsukuba = University of Tsukuba, Saiseikai Central Hospital [Tokyo, Japan] (SCH), Kinikyo Chuo Hospital - Sapporo [Hokkaido, Japan] (KCHS), NTT Medical Center Tokyo [Tokyo, Japan] (NTTMCT), Yokohama Shintoshi Neurosurgical Hospital [Yokohama, Japan]. (YSNH), Osaka General Medical Center [Osaka, Japan] (OGMC), University of Miami Leonard M. Miller School of Medicine (UMMSM), Bon Secours Mercy Health System [Toledo, OH, USA] (BSMHS), Maoming City Hospital [Guandong, China] (MCH), Miami Cardiac & Vascular Institute [Miami, FL, USA] (MC&VI), Hackensack University Medical Center [Hackensack], David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), University of Tennessee [Chattanooga] (UTC), The University of Texas at San Antonio (UTSA), Mianyang 404 Hospital [Sichuan, China] (M404H), Siriraj Hosital - Mahidol University [Bangkok, Thailand] (SHMU), SUNY Upstate Medical University, State University of New York (SUNY), Royal North Shore Hospital (RNSH), The University of Texas Rio Grande Valley [Harlingen, TX, USA] (UTRGV), Khoula Hospital [Muscat, Oman] (Ministry of Health - KH), University of Michigan [Ann Arbor], University of Michigan System, University of South Florida [Tampa] (USF), Henry Ford Health System [Detroit, MI, USA] (HFHS), Metropolitan Hospital [Piraeus, Greece] (MH), National and Kapodistrian University of Athens (NKUA), Maine Medical Center, Dartmouth Hitchcock Medical Center [Lebanon, NH, USA] (DHMC), Centro Universitário Feevale (BRAZIL), The Valley Hospital [Ridgewood, NJ, USA] (TVH), St Joseph's University Medical Center [Paterson, NJ, USA] (StJUMC), Christian Medical College and Hospital Ludhiana [Punjab, India] (CMCHL), Universidad del Desarrollo, University Graduate School of Medicine [Osaka, Japan], Tokushima University, Universidade Federal de São Paulo, Istanbul Aydin University [İstanbul, Turkey] (IAU), Swedish Medical Center [Englewood, CO, USA] (SMC), Bayhealth Medical Center [Dover, DE, USA] (BMC), Saiseikai Fukuoka General Hospital [Fukuoka, Japan] (SFGH), Osaka Rosai Hospital - Sakai [Osaka, Japan] (ORHS), King Saud University [Riyadh] (KSU), Mount Sinai Health System, University of Calgary, Huzhou University [Zhejiang], The Affiliated Hospital of Southwest Medical University - Luzhou [Sichuan, China] (TAHSMUL), Yijishan Hospital of Wannan Medical College [Wuhu, Anhui, China] (YHWMC), University of Toledo, WellStar Health System [Marietta, GA, USA] (WHS), Institut National de la Recherche Scientifique [Québec] (INRS), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), SVIN COVID-19 Registry, the Middle East North Africa Stroke and Interventional Neurotherapies Organization (MENA-SINO), Japanese Society of Vascular and Interventional Neurology Society (JVIN), University of California [San Francisco] (UCSF), University of California, Yale University School of Medicine, University of São Paulo (USP), and University of California-University of California

Subjects
[SDV]Life Sciences [q-bio], COVID-19, Subarachnoid Hemorrhage* / diagnostic imaging, 030204 cardiovascular system & hematology, Intracranial Aneurysm* / therapy, lcsh:RC346-429, 0302 clinical medicine, Pandemic, Myocardial infarction, Prospective Studies, Stroke, Original Research, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Intracranial Aneurysm* / diagnostic imaging, Cardiology, Subarachnoid haemorrhage, haemorrhage, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Subgroup analysis, subarachnoid, Intracranial Aneurysm* / epidemiology, 03 medical and health sciences, Aneurysm, Internal medicine, medicine, Humans, coil, cardiovascular diseases, Pandemics, lcsh:Neurology. Diseases of the nervous system, Retrospective Studies, business.industry, SARS-CoV-2, Intracranial Aneurysm, Subarachnoid Hemorrhage, medicine.disease, infection, nervous system diseases, Mechanical thrombectomy, Cross-Sectional Studies, aneurysm, Neurology (clinical), Subarachnoid Hemorrhage* / epidemiology, business, 030217 neurology & neurosurgery
Abstract

BackgroundDuring the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study’s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines.MethodsWe conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March–31 May 2020. The prior 1-year control period (1 March–31 May 2019) was obtained to account for seasonal variation.FindingsThere was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI −24.3% to −20.7%, pInterpretationThere was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction.

Published
2021

69. ESMO Congress 2021: highlights from the EORTC gastrointestinal tract cancer group’s perspective

Author

T, Koessler, M, Alsina, D, Arnold, I, Ben-Aharon, M, Collienne, M P, Lutz, C, Neuzillet, R, Obermannova, M, Peeters, F, Sclafani, E, Smyth, J W, Valle, A D, Wagner, L, Wyrwicz, E, Fontana, M, Moehler, Institut Català de la Salut, [Koessler T] Department of Oncology, Geneva University Hospital, Geneva, Switzerland. Swiss Cancer Center Leman (SCCL), University of Geneva, Lausanne, Switzerland. [Alsina M] Hospital Universitario de Navarra (HUN), Medical Oncology Department, Pamplona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Arnold D] Department of Oncology, Haematology and Palliative Care, Asklepios Klinik Altona, Asklepios Tumorzentrum Hamburg, Hamburg, Germany. [Ben-Aharon I] Division of Oncology, Rambam Health Care Campus, Rappaport Faculty of Medicine, Technion, Haifa, Israel. [Collienne M] Department of Oncology, Haematology and Palliative Care, Asklepios Klinik Altona, Asklepios Tumorzentrum Hamburg, Hamburg, Germany. European Organisation for Research and Treatment of Cancer, Brussels, Belgium. [Lutz MP] Caritasklinikum, Saarbrucken, Germany, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Cancer Research, Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], terapéutica::terapia biológica::inmunomodulación::inmunoterapia [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Immunoteràpia, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Medical Oncology, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Estómac - Càncer - Tractament, Oncology, Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms [DISEASES], neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales [ENFERMEDADES], Humans, Immunotherapy, Human medicine, Gastrointestinal Neoplasms, Aparell digestiu - Càncer - Tractament
Abstract

Neuroendocrine tumours; Pancreatic cancer; Stomach cancer Tumores neuroendocrinos; Cáncer de páncreas; Cáncer de estómago Tumors neuroendocrins; Càncer de pàncrees; Càncer d'estómac There has been no major change of practice in gastrointestinal oncology at the European Society for Medical Oncology (ESMO) symposium 2021, but confirmation that immunotherapy in combination with chemotherapy has become standard of care in several indications. The European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Track Cancer Group has selected important phase II and III trials presented during the symposium across all gastrointestinal cancers as well as early reports on new drugs or new combinations that may change practice in the future. This work was supported by a donation from the Swiss Cancer Research Foundation from Switzerland. MC was supported by a grant by EORTC Cancer Research Fund (ECRF) and the Gastrointestinal Tract Cancer Group.

Published
2022

71. Ceftazidime, carbapenems, or piperacillin-tazobactam as single definitive therapy for Pseudomonas aeruginosa bloodstream infection: a multi-site retrospective study

Author

Céline Pulcini, Sofia Maraki, Christian G. Giske, V. Vitrat, Bojana Beović, Alba Rivera, Maria Zacharioudaki, Michal Landes, Lior Nesher, Michael Buhl, Mical Paul, Julie Gibbs, Alasdair P. MacGowan, Manal Abdel Fattah, Isabel Machuca, Justine Haquin, Adi Zaidman-Shimshovitz, Leonard Leibovici, Iris Gomez Alfaro, Yulia Weissman, Andreja Saje, Pontus Naucler, John Karlsson Valik, Monica Gozalo-Marguello, Susanna Mauer, Leonardo Pagani, Antonio Oliver, Bibiana Chazan, Luis Martinez Martinez, Yaakov Dickstein, Natividad Benito, Diamantis P. Kofteridis, Isabel Fernández Morales, Anna Yanovskay, K.L. McCarthy, Dafna Yahav, Tanya Babich, Angela Cano, Ronen Ben Ami, Sally Grier, Enrique Ruiz de Gopegui, Manica Mueller-Premru, Eva María González-Barberá, Ruben Cardona, Miguel Salavert, Jesús Rodríguez-Baño, David L. Paterson, Evelina Tacconelli, Stockholm County Council, Tel Aviv University [Tel Aviv], Karolinska University Hospital [Stockholm], Universitat Autònoma de Barcelona (UAB), Hospital de la Santa Creu i Sant Pau, Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Southmead Hospital, Emek Medical Center, Tel Aviv Sourasky Medical Center [Te Aviv], Soroka University Medical Center [Beer Sheva, Israel], University of Queensland [Brisbane], University Hospital Tuebingen, University Hospital Virgen Macarena, Hospital Universitario Son Espases, University of Córdoba [Córdoba], Marqués de Valdecilla University Hospital, La Fe University Hospital, Hospital Universitario y Politécnico La Fe, University of Ljubljana, Central Hospital of Bolzano, Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], University Hospital of Heraklion, Rambam Health Care Campus, and Rabin Medical Center - Beilinson and Hasharon Hospitals [Petach-Tikva, Israel]

Subjects
0301 basic medicine, systolic blood pressure, Carbapenem, all cause mortality, antibiotic resistance, drug safety, retrospective study, Antibiotics, diarrhea, clinical outcome, Ceftazidime, Bacteremia, rash, functional status, medicine.disease_cause, intensive care unit, assisted ventilation, 0302 clinical medicine, meropenem, piperacillin, antibiotic therapy, heart rate, polycyclic compounds, Medicine, 030212 general & internal medicine, ceftazidime, adult, carbapenem derivative, Anti-Bacterial Agents, 3. Good health, antiinfective agent, microbial sensitivity test, aged, hospital patient, female, Infectious Diseases, priority journal, risk factor, Pseudomonas aeruginosa, Piperacillin/tazobactam, Pseudomonas infection, albumin blood level, hospital infection, Charlson Comorbidity Index, geographic locations, hospitalization, immobility, medicine.drug, Microbiology (medical), bacteremia, beta-lactam, monotherapy, pseudomonas, medicine.medical_specialty, medicine.drug_class, seizure, Beta-lactam, 030106 microbiology, education, bloodstream infection, tracheostomy, piperacillin plus tazobactam, Article, 03 medical and health sciences, male, acute kidney failure, Clostridium difficile infection, Internal medicine, Pseudomonas, bacterium isolation, parasitic diseases, metastasis, Sequential Organ Failure Assessment Score, human, Adverse effect, albumin, nonhuman, business.industry, Cefta, Odds ratio, biochemical phenomena, metabolism, and nutrition, bacterial strain, medicine.disease, bacterial infections and mycoses, Monotherapy, major clinical study, drug efficacy, multicenter study, Carbapenems, bacteria, septic shock, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, penicillanic acid, imipenem
Abstract

This study was presented as poster presentation at the European Society of Clinical Microbiology and Infectious Diseases annual conference, Madrid, Spain, 21–24 April 2018., [Background] The optimal antibiotic regimen for Pseudomonas aeruginosa bacteremia is controversial. Although β-lactam monotherapy is common, data to guide the choice between antibiotics are scarce. We aimed to compare ceftazidime, carbapenems, and piperacillin-tazobactam as definitive monotherapy. [Methods] A multinational retrospective study (9 countries, 25 centers) including 767 hospitalized patients with P. aeruginosa bacteremia treated with β-lactam monotherapy during 2009–2015. The primary outcome was 30-day all-cause mortality. Univariate and multivariate, including propensity-adjusted, analyses were conducted introducing monotherapy type as an independent variable. [Results] Thirty-day mortality was 37/213 (17.4%), 42/210 (20%), and 55/344 (16%) in the ceftazidime, carbapenem, and piperacillin-tazobactam groups, respectively. Type of monotherapy was not significantly associated with mortality in either univariate, multivariate, or propensity-adjusted analyses (odds ratio [OR], 1.14; 95% confidence interval [CI], 0.52–2.46, for ceftazidime; OR, 1.3; 95% CI, 0.67–2.51, for piperacillin-tazobactam, with carbapenems as reference in propensity adjusted multivariate analysis; 542 patients). No significant difference between antibiotics was demonstrated for clinical failure, microbiological failure, or adverse events. Isolation of P. aeruginosa with new resistance to antipseudomonal drugs was significantly more frequent with carbapenems (36/206 [17.5%]) versus ceftazidime (25/201 [12.4%]) and piperacillin-tazobactam (28/332 [8.4%] (P = .007). [Conclusions] No significant difference in mortality, clinical, and microbiological outcomes or adverse events was demonstrated between ceftazidime, carbapenems, and piperacillin-tazobactam as definitive treatment of P. aeruginosa bacteremia. Higher rates of resistant P. aeruginosa after patients were treated with carbapenems, along with the general preference for carbapenem-sparing regimens, suggests using ceftazidime or piperacillin-tazobactam for treating susceptible infection., This study was conducted with no external funding. In Sweden only, the research was funded by grants from the Stockholm County Council and Emil and Wera Cornell Foundation.

Published
2020

72. Risk factors for mortality among patients with Pseudomonas aeruginosa bacteraemia: a retrospective multicentre study

Author

Alba Rivera, Justine Haquin, Michael Buhl, Evelina Tacconelli, Yaakov Dickstein, Antonio Oliver, Natividad Benito, Eva María González-Barberá, Tanya Babich, Luis Martínez-Martínez, Adi Zaidman-Shimshovitz, Anna Yanovskay, Dafna Yahav, Isabel Machuca, Manal Abdel Fattah, Manica Mueller-Premru, Ruben Cardona, Sally Grier, Angela Cano, Miguel Salavert, Enrique Ruiz de Gopegui, Diamantis P. Kofteridis, Yulia Weissman, John Karlsson Valik, Bibiana Chazan, Lior Nesher, Michal Landes, Susanna Maurer, Andreja Saje, Monica Gozalo-Marguello, Alasdair P. MacGowan, Leonardo Pagani, Maria Zacharioudaki, Ronen Ben Ami, Leonard Leibovici, Mical Paul, Isabel Fernández Morales, K.L. McCarthy, Jesús Rodríguez-Baño, David L. Paterson, Pontus Naucler, Iris Gomez Alfaro, Céline Pulcini, Sofia Maraki, Christian G. Giske, V. Vitrat, Bojana Beović, Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], Karolinska Institutet [Stockholm], Instituto de Investigaciones Biomédicas Sant Pau [Barcelona, Spain], Hospital de la Santa Creu i Sant Pau, Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Southmead Hospital [Bristol, UK], Rappaport faculty of Medicine, Technion - Israel Institute of Technology [Haifa], Tel Aviv Sourasky Medical Center [Te Aviv], Soroka University Medical Center [Beer Sheva, Israel], University of Queensland [Brisbane], Tübingen University Hospital [Germany], University Hospital Virgen Macarena, Hospital Son Dureta, Hospital Universitario Son Espases, Reina Sofía University Hospital, Marqués de Valdecilla University Hospital, La Fe University Hospital, University of Ljubljana, Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], University General Hospital of Heraklion, Rambam Health Care Campus, and Rabin Medical Center - Beilinson and Hasharon Hospitals [Petach-Tikva, Israel]

Subjects
Male, 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, Bacteremia, medicine.disease_cause, 03 medical and health sciences, Bacteraemia, Mortality, Pseudomonas, Risk factors, 0302 clinical medicine, Internal medicine, Pseudomonas, medicine, Humans, Pseudomonas Infections, Pharmacology (medical), 030212 general & internal medicine, Mortality, Aged, Retrospective Studies, Pseudomonas aeruginosa, business.industry, Retrospective cohort study, General Medicine, Odds ratio, Middle Aged, Confidence interval, Anti-Bacterial Agents, 3. Good health, Icu admission, Infectious Diseases, Risk factors, Concomitant, Cohort, Propensity score matching, Bacteraemia, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract

This study aimed to evaluate risk factors for 30-day mortality among hospitalised patients with Pseudomonas aeruginosa bacteraemia, a highly fatal condition. A retrospective study was conducted between 1 January 2009 and 31 October 2015 in 25 centres (9 countries) including 2396 patients. Univariable and multivariable analyses of risk factors were conducted for the entire cohort and for patients surviving >= 48 h. A propensity score for predictors of appropriate empirical therapy was introduced into the analysis. Of the 2396 patients, 636 (26.5%) died within 30 days. Significant predictors (odds ratio and 95% confidence interval) of mortality in the multivariable analysis included patient-related factors: age (1.02, 1.01-1.03); female sex (1.34, 1.03-1.77); bedridden functional capacity (1.99, 1.24-3.21); recent hospitalisation (1.43, 1.07-1.92); concomitant corticosteroids (1.33, 1.02-1.73); and Charlson comorbidity index (1.05, 1.01-1.93). Infection-related factors were multidrug-resistant Pseudomonas (1.52, 1.15-2.1), nonurinary source (2.44, 1.54-3.85) and Sequential Organ Failure Assessment (SOFA) score (1.27, 1.18-1.36). Inappropriate empirical therapy was not associated with increased mortality (0.81, 0.49-1.33). Among 2135 patients surviving >= 48 h, hospital-acquired infection (1.59, 1.21-2.09), baseline endotracheal tube (1.63, 1.13-2.36) and ICU admission (1.53, 1.02-2.28) were additional risk factors. Risk factors for mortality among patients with P. aeruginosa were mostly irreversible. Early appropriate empirical therapy was not associated with reduced mortality. Further research should be conducted to explore subgroups that may not benefit from broad-spectrum antipseudomonal empirical therapy. Efforts should focus on prevention of infection, mainly hospital-acquired infection and multidrug-resistant pseudomonal infection. (C) 2019 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Published
2020

74. A Dominant Mutation in Nuclear Receptor Interacting Protein 1 Causes Urinary Tract Malformations via Dysregulation of Retinoic Acid Signaling

Author

Soeren S. Lienkamp, Richard P. Lifton, Benjamin Dekel, Anna Carina Weiss, Friedhelm Hildebrandt, Vincent Cavaillès, Michael M. Kaminski, Amelie T. van der Ven, Tobias Bohnenpoll, Johanna Magdalena Schmidt, Rachel Shukrun, Hadas Ityel, Ali G. Gharavi, Eugen Widmeier, Weining Lu, Hagith Yonath, Jing Chen, Yair Anikster, Andreas Kispert, Nina Mann, Stuart B. Bauer, Daniella Magen, Asaf Vivante, Robert Kleta, Velibor Tasic, Shirlee Shril, Maike Getwan, Catherine Teyssier, Horia Stanescu, Simone Sanna-Cherchi, Sheba Medical Center, Medizinische Hochschule Hannover (MHH), Department of Neurology, Children's Hospital [Boston], Boston Children's Hospital, Columbia University, New York, NY, United States, Rambam Health Care Campus, Tel Aviv University [Tel Aviv], Yale University School of Medicine, Department of Pediatric Nephrology, University Children’s Hospital, Centre for Nephrology [London, UK], University College of London [London] (UCL), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre for Biological Signaling Studies [Freiburg] (BIOSS), University of Freiburg [Freiburg], Pediatrics, University of Michigan [Ann Arbor], and University of Michigan System-University of Michigan System

Subjects
0301 basic medicine, Retinoic acid, Tretinoin, [SDV.CAN]Life Sciences [q-bio]/Cancer, Retinoic acid receptor beta, 030105 genetics & heredity, Biology, Retinoic acid-inducible orphan G protein-coupled receptor, Mice, 03 medical and health sciences, chemistry.chemical_compound, retinoic acid, Animals, Urinary Tract, ComputingMilieux_MISCELLANEOUS, CAKUT, Adaptor Proteins, Signal Transducing, NRIP1, Nuclear Proteins, General Medicine, Retinoic acid receptor gamma, Retinoid X receptor gamma, Molecular biology, Nuclear Receptor Interacting Protein 1, 3. Good health, Retinoic acid receptor, Basic Research, 030104 developmental biology, Nuclear receptor, chemistry, Nephrology, Retinoic acid receptor alpha, Mutation, Signal Transduction
Abstract

Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of CKD in the first three decades of life. However, for most patients with CAKUT, the causative mutation remains unknown. We identified a kindred with an autosomal dominant form of CAKUT. By whole-exome sequencing, we identified a heterozygous truncating mutation (c.279delG, p.Trp93fs*) of the nuclear receptor interacting protein 1 gene (NRIP1) in all seven affected members. NRIP1 encodes a nuclear receptor transcriptional cofactor that directly interacts with the retinoic acid receptors (RARs) to modulate retinoic acid transcriptional activity. Unlike wild-type NRIP1, the altered NRIP1 protein did not translocate to the nucleus, did not interact with RARα, and failed to inhibit retinoic acid–dependent transcriptional activity upon expression in HEK293 cells. Notably, we also showed that treatment with retinoic acid enhanced NRIP1 binding to RARα. RNA in situ hybridization confirmed Nrip1 expression in the developing urogenital system of the mouse. In explant cultures of embryonic kidney rudiments, retinoic acid stimulated Nrip1 expression, whereas a pan-RAR antagonist strongly reduced it. Furthermore, mice heterozygous for a null allele of Nrip1 showed a CAKUT-spectrum phenotype. Finally, expression and knockdown experiments in Xenopus laevis confirmed an evolutionarily conserved role for NRIP1 in renal development. These data indicate that dominant NRIP1 mutations can cause CAKUT by interference with retinoic acid transcriptional signaling, shedding light on the well documented association between abnormal vitamin A levels and renal malformations in humans, and suggest a possible gene-environment pathomechanism in this disease.

Published
2017

75. Defects in t6A tRNA modification due to GON7 and YRDC mutations lead to Galloway-Mowat syndrome

Author

Arrondel, Christelle, Missoury, Sophia, Snoek, Rozemarijn, Patat, Julie, Menara, Giulia, Collinet, Bruno, Liger, Dominique, Durand, Dominique, Gribouval, Olivier, Boyer, Olivia, Buscara, Laurine, Martin, Gaëlle, Machuca, Eduardo, Nevo, Fabien, Lescop, Ewen, Braun, Daniela A., Boschat, Anne-Claire, Sanquer, Sylvia, Guerrera, Ida Chiara, Revy, Patrick, Parisot, Mélanie, Masson, Cécile, Boddaert, Nathalie, Charbit, Marina, Decramer, Stéphane, Novo, Robert, Macher, Marie-Alice, Ranchin, Bruno, Bacchetta, Justine, Laurent, Audrey, Collardeau-Frachon, Sophie, van Eerde, Albertien M., Hildebrandt, Friedhelm, Magen, Daniella, Antignac, Corinne, van Tilbeurgh, Herman, Mollet, Géraldine, Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Molecular bases of hereditary kidney diseases: nephronophthisis and hypodysplasia (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Molecular medicine [Utrecht], University Medical Center [Utrecht], Department of Genetics [Utrecht, the Netherlands], Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Institut de recherche pour le développement [IRD] : UR206-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de néphrologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Department of Medicine [Boston, MA, USA], Harvard Medical School [Boston] (HMS)-Boston Children's Hospital, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biochimie métabolique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme Protéomique Necker [SFR Necker] (PPN - 3P5), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Genome dynamics in the immune system (Equipe Inserm U1163), Plateforme de génomique [SFR Necker], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Neuroimagerie en psychiatrie (U1000), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Service de Pédiatrie - Néphrologie, Médecine interne, Hypertension, CHU Toulouse [Toulouse]-Hôpital des Enfants, CHU Toulouse [Toulouse], Unité Néphrologie Pédiatrique [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Néphrologie pédiatrique [Hôpital Robert Debré, Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Service de néphrologie, rhumatologie et dermatologie pédiatriques [Hôpital Femme Mère Enfant, HCL], Hospices Civils de Lyon (HCL)-Hôpital Mère Enfant, Service de Pathologie [Hôpital Femme-Mère-Enfant, HCL], Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Division of Nephrology [Boston, MA, USA] (Department of Medicine), Boston Children's Hospital, Pediatric Nephrology Institute [Haifa, Israel], Rambam Health Care Campus [Haifa, Israel]-Technion Faculty of Medicine [Haifa, Israel], Service de Génétique Médicale [CHU Necker], This work was supported by the Fondation pour le Recherche Médicale (project DEQ2015031682) (to C. Antignac), the European Union’s Seventh Framework Programme (FP7/2012, grant 305608 EURenOmics) (to C. Antignac), the Investments for the Future Program (grant ANR-10-IAHY-01) (to C. Antignac), ANR KeoGamo (ANR-18-CE11-0008-01) (to G. Mollet and H.v.T.). This work was supported by the French Infrastructure for Integrated Structural Biology (FRISBI) (ANR-10-INSB-05–01) (to H.v.T.) and the Dutch Kidney Foundation (grant 15OP14) (to A.M.v.E.). S.M. is supported by a Ph.D. grant of the Fondation pour le Recherche Médicale (FRM). P.R. is a scientist from Centre National de la Recherche Scientifique (CNRS)., ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-18-CE11-0008,KeoGamo,Caractérisation fonctionnelle du complexe KEOPS et son implication dans le syndrome de Galloway-Mowat(2018), ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), European Project: 305608,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,EURENOMICS(2012), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Gribouval, Olivier, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Caractérisation fonctionnelle du complexe KEOPS et son implication dans le syndrome de Galloway-Mowat - - KeoGamo2018 - ANR-18-CE11-0008 - AAPG2018 - VALID, Infrastructure Française pour la Biologie Structurale Intégrée - - FRISBI2010 - ANR-10-INBS-0005 - INBS - VALID, and European Consortium for High-Throughput Research in Rare Kidney Diseases - EURENOMICS - - EC:FP7:HEALTH2012-10-01 - 2017-09-30 - 305608 - VALID

Subjects
Male, Adenosine, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.GEN] Life Sciences [q-bio]/Genetics, Nephrosis/genetics, Microcephaly/genetics, RNA, Transfer, MESH: Child, lcsh:Science, Child, MESH: Intrinsically Disordered Proteins, Research Support, Non-U.S. Gov't, Medical genetics, Nuclear Proteins, RNA-Binding Proteins, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, MESH: Nephrosis, Microcephaly, Nephrosis, Intrinsically Disordered Proteins/genetics, Female, Multiprotein Complexes/chemistry, RNA, Transfer/genetics, RNA-Binding Proteins/chemistry, MESH: Mutation, MESH: GTP-Binding Proteins, Science, Nuclear Proteins/chemistry, MESH: Microcephaly, Article, MESH: Hernia, Hiatal, GTP-Binding Proteins, Hernia, Hiatal/genetics, GTP-Binding Proteins/chemistry, Journal Article, Humans, X-ray crystallography, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Multiprotein Complexes, MESH: Adenosine, MESH: RNA, Transfer, RNA modification, MESH: Male, tRNAs, Intrinsically Disordered Proteins, MESH: RNA-Binding Proteins, Hernia, Hiatal, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Multiprotein Complexes, Mutation, lcsh:Q, Adenosine/analogs & derivatives, MESH: Nuclear Proteins, MESH: Female
Abstract

N6-threonyl-carbamoylation of adenosine 37 of ANN-type tRNAs (t6A) is a universal modification essential for translational accuracy and efficiency. The t6A pathway uses two sequentially acting enzymes, YRDC and OSGEP, the latter being a subunit of the multiprotein KEOPS complex. We recently identified mutations in genes encoding four out of the five KEOPS subunits in children with Galloway-Mowat syndrome (GAMOS), a clinically heterogeneous autosomal recessive disease characterized by early-onset steroid-resistant nephrotic syndrome and microcephaly. Here we show that mutations in YRDC cause an extremely severe form of GAMOS whereas mutations in GON7, encoding the fifth KEOPS subunit, lead to a milder form of the disease. The crystal structure of the GON7/LAGE3/OSGEP subcomplex shows that the intrinsically disordered GON7 protein becomes partially structured upon binding to LAGE3. The structure and cellular characterization of GON7 suggest its involvement in the cellular stability and quaternary arrangement of the KEOPS complex., The biosynthesis of N6-threonylcarbamoylated adenosine 37 in tRNA (t6A) involves the YRDC enzyme and the KEOPS complex. Here, the authors report mutations in YRDC and the KEOPS component GON7 in Galloway-Mowat syndrome and determine the crystal structure of a GON7-containg subcomplex that suggests a role in KEOPS complex stability.

Published
2019

76. Polysensitivity in delayed cutaneous adverse drug reactions to macrolides, clindamycin and pristinamycin: clinical history and patch testing

Author

M. Paul, C. Haddad, M. El Khoury, Pierre Wolkenstein, Saskia Ingen-Housz-Oro, Haudrey Assier, O. Chosidow, G. Gener, Service de dermatologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Rambam Health Care Campus

Subjects
Adult, Male, medicine.medical_specialty, Time Factors, Dermatology, Cross Reactions, Patch testing, 030207 dermatology & venereal diseases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Clinical history, medicine, Humans, Drug reaction, ComputingMilieux_MISCELLANEOUS, Pristinamycin, Aged, Retrospective Studies, Skin, 030203 arthritis & rheumatology, Aged, 80 and over, business.industry, Clindamycin, Retrospective cohort study, Middle Aged, Patch Tests, Anti-Bacterial Agents, chemistry, Female, Drug Eruptions, Macrolides, business, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, medicine.drug
Abstract

International audience

Published
2018

77. Antibiotic treatment of infections caused by carbapenem-resistant Gram-negative bacilli: an international ESCMID cross-sectional survey among infectious diseases specialists practicing in large hospitals

Author

Papst, Lea, Beović, Bojana, Pulcini, Céline, Durante-Mangoni, Emanuele, Rodríguez-Baño, Jesús, Kaye, Keith S, Daikos, George L, Raka, Lul, Paul, Mical, Esgap, Esgbis, ESGIE and the CRGNB treatment survey study group collaborators: Abbo, L, Abgueguen, P, Almirante, B, Azzini, Am, Bani-Sadr, F, Bassetti, M, Ben-Ami, R, Beović, B, Béraud, G, Botelho-Nevers, E, Bou, G, Boutoille, D, Cabié, A, Cacopardo, B, Cascio, A, Cassir, N, Castelli, F, Cecala, M, Charmillon, A, Chirouze, C, Cisneros, Jm, Colmenero, Jd, Coppola, N, Corcione, S, Daikos, Gl, Dalla Gasperina, D, De la Calle Cabrera, C, Delobel, P, Di Caprio, D, Durante Mangoni, E, Dupon, M, Ettahar, N, Falagas, Me, Falcone, M, Fariñas, Mc, Faure, E, Forestier, E, Foti, G, Gallagher, J, Gattuso, G, Gendrin, V, Gentile, I, Giacobbe, Dr, Gogos, Ca, Grandiere Perez, L, Hansmann, Y, Horcajada, Jp, Iacobello, C, Jacob, Jt, Justo, Ja, Kernéis, S, Komnos, A, Kotnik Kevorkijan, B, Lebeaux, D, Le Berre, R, Lechiche, C, Le Moing, V, Lescure, Fx, Libanore, M, Martinot, M, Merino de Lucas, E, Mondain, V, Mondello, P, Montejo, M, Mootien, J, Muñoz, P, Nir-Paz, R, Pan, A, Paño-Pardo, Jr, Patel, G, Paul, M, Pérez Rodríguez MT, Piroth, L, Pogue, J, Potoski, Ba, Pourcher, V, Pyrpasopoulou, A, Rahav, G, Rizzi, M, Rodríguez-Baño, J, Salavert, M, Scheetz, M, Sims, M, Spahija, G, Stefani, S, Stefos, A, Tamma, Pd, Tattevin, P, Tedesco, A, Torre-Cisneros, J, Tripolitsioti, P, Tsiodras, S, Uomo, G, Verdon, R, Viale, P, Vitrat, V, Weinberger, M, Wiener-Well, Y, Papst L., Beovic B., Pulcini C., Durante-Mangoni E., Rodriguez-Bano J., Kaye K.S., Daikos G.L., Raka L., Paul M., Abbo L., Abgueguen P., Almirante B., Azzini A.M., Bani-Sadr F., Bassetti M., Ben-Ami R., Beraud G., Botelho-Nevers E., Bou G., Boutoille D., Cabie A., Cacopardo B., Cascio A., Cassir N., Castelli F., Cecala M., Charmillon A., Chirouze C., Cisneros J.M., Colmenero J.D., Coppola N., Corcione S., Dalla Gasperina D., De la Calle Cabrera C., Delobel P., Di Caprio D., Durante Mangoni E., Dupon M., Ettahar N., Falagas M.E., Falcone M., Farinas M.C., Faure E., Forestier E., Foti G., Gallagher J., Gattuso G., Gendrin V., Gentile I., Giacobbe D.R., Gogos C.A., Grandiere Perez L., Hansmann Y., Horcajada J.P., Iacobello C., Jacob J.T., Justo J.A., Kerneis S., Komnos A., Kotnik Kevorkijan B., Lebeaux D., Le Berre R., Lechiche C., Le Moxing V., Lescure F.X., Libanore M., Martinot M., Merino de Lucas E., Mondain V., Mondello P., Montejo M., Mootien J., Munoz P., Nir-Paz R., Pan A., Pano-Pardo J.R., Patel G., Perez Rodriguez M.T., Piroth L., Pogue J., Potoski B.A., Pourcher V., Pyrpasopoulou A., Rahav G., Rizzi M., Salavert M., Scheetz M., Sims M., Spahija G., Stefani S., Stefos A., Tamma P.D., Tattevin P., Tedesco A., Torre-Cisneros J., Tripolitsioti P., Tsiodras S., Uomo G., Verdon R., Viale P., Vitrat V., Weinberger M., Wiener-Well Y., University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Monaldi Hospital, Hospital Virgen Macarena, University of Michigan Medical School [Ann Arbor], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, National and Kapodistrian University of Athens (NKUA), University Clinical Center of Kosova, Rambam Health Care Campus, Jackson Memorial Hospital, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Vall d'Hebron University Hospital [Barcelona], University of Verona (UNIVR), Centre Hospitalier Universitaire de Reims (CHU Reims), Ospedale 'Santa Maria della Misericordia' = University Hospital 'Santa Maria della Misericordia', Tel Aviv Sourasky Medical Centre, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Hospital Universitario, A Coruña, Centre hospitalier universitaire de Nantes (CHU Nantes), CHU de la Martinique [Fort de France], ARNAS 'Garibaldi, S. Luigi-Currò, Ascoli-Tomaselli', Università degli studi di Palermo - University of Palermo, Assistance Publique-Hôpitaux de Marseille (AP-HM), ASST Spedali Civili of Brescia, ARNAS Civico Palermo, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hospital Universitario Virgen del Rocío [Sevilla], Hospital Regional Universitario de Málaga [Spain], Università degli studi della Campania 'Luigi Vanvitelli', University of Turin, University of Insubria, Varese, Hospital Clínic de Barcelona, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], AO San Sebastiano, CHU Bordeaux [Bordeaux], CH Valenciennes, Henry Dunant Hospital, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Hospital Marques de Valdecillas, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Métropole Savoie [Chambéry], Ospedale di Reggio Calabria, Children’s Hospital of Philadelphia (CHOP ), Carlo Poma Hospital Mantova (ASST Mantova ), CH Belfort-Montbéliard, University of Naples Federico II, AUO San Martino IST Ist Nazl Ric Canc, I-16132 Genoa, Italy, University of Patras [Patras], Centre Hospitalier Le Mans (CH Le Mans), CHU Strasbourg, IMIM-Hospital del Mar, Generalitat de Catalunya, Cannizzaro Hospital, Emory University School of Medicine, Emory University [Atlanta, GA], University of South Carolina [Columbia], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), General Hospital of Larissa, University medical centre Maribor (UKC Maribor), 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), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), AP-HP - Hôpital Bichat - Claude Bernard [Paris], University of Ferrara at St. Anna Hospital, CH Colmar, Hospital General Universitario de Alicante, CHU Nice [Cimiez], Hôpital Cimiez [Nice] (CHU), AOU Policlinico 'G. Martino', Messina, Italy, Hospital Universitario Cruces = Cruces University Hospital, Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Hospital General Universitario 'Gregorio Marañón' [Madrid], Hadassah Hebrew University Medical Center [Jerusalem], Azienda Istituti Ospitalieri di Cremona, Lozano Blesa Clinical Hospital [Zaragoza, Spain], Mount Sinai Hospital [Toronto, Canada] (MSH), Complejo Hospitalario de Vigo, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Detroit Medical Center, University of Pittsburgh Medical Center [Pittsburgh, PA, États-Unis] (UPMC), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hippokration General Hospital, Sheba Medical Centre, Ramat Gan, Israel, ASST Papa Giovanni XXIII [Bergamo, Italy], Hospital Universitario La Fe, Valencia, Northwestern Hospital Chicago, Beaumont Hospital, Lagjia e Universitetit, Rruga 1, nr.32, 10000 Prishtina, Kosovo, parent, Università degli studi di Catania [Catania], Larissa University Hospital, Johns Hopkins University School of Medicine [Baltimore], CHU Pontchaillou [Rennes], Ospedale Fracastoro San Bonifacio [Verona], Hospital Reina Sofia, Cordoba, Agioi Anargiroi Hospital, Attikon University Hospital, Ospedale Cardarelli, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), CH Annecy Genevois, Assah Harofeh Medical Centre, Zerifin, Israel, Shaare Zedek Medical Centre, Jerusalem, Israel, National Institutes of Health (US), Instituto de Salud Carlos III, Ministerio de Economía, Industria y Competitividad (España), Red Española de Investigación en Patología Infecciosa, European Commission, Papst, Lea, Beović, Bojana, Pulcini, Céline, Durante-Mangoni, Emanuele, Rodríguez-Baño, Jesú, Kaye, Keith S, Daikos, George L, Raka, Lul, Paul, Mical, Papst, L., Beovic, B., Pulcini, C., Durante-Mangoni, E., Rodriguez-Bano, J., Kaye, K. S., Daikos, G. L., Raka, L., Paul, M., Abbo, L., Abgueguen, P., Almirante, B., Azzini, A. M., Bani-Sadr, F., Bassetti, M., Ben-Ami, R., Beraud, G., Botelho-Nevers, E., Bou, G., Boutoille, D., Cabie, A., Cacopardo, B., Cascio, A., Cassir, N., Castelli, F., Cecala, M., Charmillon, A., Chirouze, C., Cisneros, J. M., Colmenero, J. D., Coppola, N., Corcione, S., Dalla Gasperina, D., De la Calle Cabrera, C., Delobel, P., Di Caprio, D., Dupon, M., Ettahar, N., Falagas, M. E., Falcone, M., Farinas, M. C., Faure, E., Forestier, E., Foti, G., Gallagher, J., Gattuso, G., Gendrin, V., Gentile, I., Giacobbe, D. R., Gogos, C. A., Grandiere Perez, L., Hansmann, Y., Horcajada, J. P., Iacobello, C., Jacob, J. T., Justo, J. A., Kerneis, S., Komnos, A., Kotnik Kevorkijan, B., Lebeaux, D., Le Berre, R., Lechiche, C., Le Moxing, V., Lescure, F. X., Libanore, M., Martinot, M., Merino de Lucas, E., Mondain, V., Mondello, P., Montejo, M., Mootien, J., Munoz, P., Nir-Paz, R., Pan, A., Pano-Pardo, J. R., Patel, G., Perez Rodriguez, M. T., Piroth, L., Pogue, J., Potoski, B. A., Pourcher, V., Pyrpasopoulou, A., Rahav, G., Rizzi, M., Salavert, M., Scheetz, M., Sims, M., Spahija, G., Stefani, S., Stefos, A., Tamma, P. D., Tattevin, P., Tedesco, A., Torre-Cisneros, J., Tripolitsioti, P., Tsiodras, S., Uomo, G., Verdon, R., Viale, P., Vitrat, V., Weinberger, M., Wiener-Well, Y., Università degli studi di Verona = University of Verona (UNIVR), Assistance Publique - Hôpitaux de Marseille (APHM), Hospital Regional Universitario de Málaga = Regional University Hospital of Malaga [Spain], and Università degli studi di Torino = University of Turin (UNITO)

Subjects
0301 basic medicine, Acinetobacter baumannii, Carbapenem, Antibiotics, Drug Resistance, Drug resistance, Tigecycline, Carbapenem-resistant Gram-negative bacilli, Combination therapy, Enterobacteriaceae, Polymyxin, Pseudomonas aeruginosa, Survey, 0302 clinical medicine, Surveys and Questionnaires, polycyclic compounds, 030212 general & internal medicine, Anti-Bacterial Agents, Carbapenems, Cross Infection, Cross-Sectional Studies, Drug Resistance, Bacterial, Gram-Negative Bacteria, Gram-Negative Bacterial Infections, Hospitals, Humans, Microbial Sensitivity Tests, Microbiology (medical), Infectious Diseases, biology, Microbial Sensitivity Test, Bacterial, antibiotic management, carbapenem-resistant Gram-negative bacteria, General Medicine, 3. Good health, medicine.drug, Human, medicine.medical_specialty, medicine.drug_class, 030106 microbiology, Fosfomycin, carbapenem-resistant Gram-negative bacteria, 03 medical and health sciences, Hospital, Internal medicine, Anti-Bacterial Agent, medicine, Gram-Negative Bacterial Infection, Cross-Sectional Studie, business.industry, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, bacterial infections and mycoses, Infectious disease (medical specialty), Carbapenem-resistant gram-negative bacilli, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, antibiotic management, business, Rifampicin
Abstract

ESGAP, ESGBIS, ESGIE and the CRGNB treatment survey study group., [Objectives] To explore contemporary antibiotic management of infections caused by carbapenem-resistant Gram-negative bacteria in hospitals., [Methods] Cross-sectional, internet-based questionnaire survey. We contacted representatives of all hospitals with more than 800 acute-care hospital beds in France, Greece, Israel, Italy, Kosovo, Slovenia, Spain and selected hospitals in the USA. We asked respondents to describe the most common actual practice at their hospital regarding management of carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa through close-ended questions., [Results] Between January and June 2017, 115 of 141 eligible hospitals participated (overall response rate 81.6%, country-specific rates 66.7%–100%). Most were tertiary-care (99/114, 86.8%), university-affiliated (110/115, 89.1%) hospitals and most representatives were infectious disease specialists (99/115, 86.1%). Combination therapy was prescribed in 114/115 (99.1%) hospitals at least occasionally. Respondents were more likely to consider combination therapy when treating bacteraemia, pneumonia and central nervous system infections and for Enterobacteriaceae, P. aeruginosa and A. baumannii similarly. Combination of a polymyxin with a carbapenem was used in most cases, whereas combinations of a polymyxin with tigecycline, an aminoglycoside, fosfomycin or rifampicin were also common. Monotherapy was used for treatment of complicated urinary tract infections, usually with an aminoglycoside or a polymyxin. The intended goal of combination therapy was to improve the effectiveness of the treatment and to prevent development of resistance. In general, respondents shared the misconception that combination therapy is supported by strong scientific evidence., [Conclusions] Combination therapy was the preferred treatment strategy for infections caused by carbapenem-resistant Gram-negative bacteria among hospital representatives, even though high-quality evidence for carbapenem-based combination therapy is lacking., EDM received funding by NIH for project HHSN272201000039C. JRB received funding for research from Plan Nacional de I + D + i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001)—co-financed by European Development Regional Fund A way to achieve Europe, Operative Programme Intelligent Growth 2014–2020.

Published
2018

78. A direct aspiration first pass technique for acute stroke therapy: a systematic review and meta-analysis

Author

Benjamin Gory, Michel Piotin, Raphaël Blanc, R. Sivan‐Hoffmann, Xavier Armoiry, Bertrand Lapergue, F. Turjman, M. Mazighi, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Matériaux, ingénierie et science [Villeurbanne] (MATEIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Warwick Medical School, University of Warwick [Coventry], Rambam Health Care Campus [Haifa, Israel], Hôpital Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Foch [Suresnes], Département de Neuroradiologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 ( CNC ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Matériaux, ingénierie et science [Villeurbanne] ( MATEIS ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ) -Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ), Department of Interventional Neuroradiology, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), and Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
medicine.medical_specialty, Mechanical Thrombolysis, medicine.medical_treatment, [ SPI.MAT ] Engineering Sciences [physics]/Materials, 030218 nuclear medicine & medical imaging, law.invention, [SPI.MAT]Engineering Sciences [physics]/Materials, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, systematic review, law, Modified Rankin Scale, medicine, Humans, Stroke, a direct aspiration first pass technique, business.industry, endovascular procedure, Retrospective cohort study, Thrombolysis, medicine.disease, stroke, Confidence interval, 3. Good health, Surgery, stent retriever, meta-analysis, Outcome and Process Assessment, Health Care, Neurology, thrombectomy, Meta-analysis, Neurology (clinical), business, Complication, 030217 neurology & neurosurgery
Abstract

International audience; Background and purposeA direct aspiration first pass technique (ADAPT), involving the first-line use of a large-bore distal aspiration catheter, is a new strategy in the mechanical thrombectomy of acute ischemic stroke caused by large-vessel occlusion. However, its impact on reperfusion rates, clinical outcomes and complication rates has not been fully examined. MethodsWe conducted a systematic review of the literature searching multiple databases for reports on thrombectomy of acute stroke with ADAPT and performed meta-analyses of clinical and radiographic outcomes. ResultsWe selected 16 articles that included a total of 1378 patients treated with ADAPT. The mean admission National Institutes of Health Stroke Scale score was 17 and pre-treatment intravenous thrombolysis was used in 51% of cases. The successful recanalization (thrombolysis in cerebral ischemia 2b-3) rate was 66% [95% confidence interval (CI), 59-72%] with ADAPT and a rescue stent retriever was used in 31% of cases (95% CI, 24-37%) yielding an overall thrombolysis in cerebral ischemia 2b-3 rate of 89% (95% CI, 85-92%). We found a pooled estimate of 50% (95% CI, 45-54%) for functional independence (modified Rankin Scale score 0-2) at 90days, 15% (95% CI, 10-21%) for mortality within 90days and 5% (95% CI, 3-7%) for symptomatic intracranial hemorrhage. ConclusionsADAPT therapy is associated with similar reperfusion rates, clinical outcomes and complication rates compared with thrombectomy with stent retrievers. However, the major limitations of current evidence (i.e. retrospective studies and selection bias) indicate a need for adequately powered, multicenter randomized controlled trials to determine the best strategy.

Published
2018

79. The management of iron deficiency in inflammatory bowel disease – an online tool developed by the RAND/UCLA appropriateness method

Author

O. Haagen Nielsen, Milan Lukas, Gerassimos J. Mantzaris, Axel Dignass, Yehuda Chowers, Peter L. Lakatos, Silvio Danese, H. Stoevelaar, Bjørn Moum, Murat Törüner, Pierre Michetti, Günter Weiss, Fernando Gomollón, Walter Reinisch, Stefan Lindgren, J. van der Woude, Laurent Peyrin-Biroulet, Charlie W. Lees, Department Internal Medicine III [Medizinische Universität Wien], Medizinische Universität Wien = Medical University of Vienna, Rambam Health Care Campus, Department of Gastroenterology [Humanitas Research Hospital], Humanitas Research Hospital, Department of Gastroenterology, Oncology, Infectious Diseases and Metabolism [Agaplesion Markus Hospital], Agaplesion Markus Krankenhaus = Agaplesion Markus Hospital [Frankfurt], Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, Herlev and Gentofte Hospital, Semmelweis University [Budapest], Western General Hospital, Edinburgh, Skane University Hospital [Lund], Charles University in Prague, First Faculty of Medicine, Department of Gastroenterology [Evangelismos Athens General Hospital], Evangelismos Athens General Hospital, Division of Gastroenterology and Hepatology [CHU Vaudois], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Oslo University Hospital [Oslo], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ankara University School of Medicine [Turkey], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Internal Medicine III (Dep Med Int - INNSBRUCK), Innsbruck Medical University [Austria] (IMU), Ismar Healthcare NV, Charles University [Prague] (CU), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), UL, NGERE, Reinisch, W, Chowers, Y, Danese, S, Dignass, A, Gomollon, F, Nielsen, Oh, Lakatos, Pl, Lees, Cw, Lindgren, S, Lukas, M, Mantzaris, Gj, Michetti, P, Moum, B, Peyrin-Biroulet, L, Toruner, M, van der Woude, J, Weiss, G, and Stoevelaar, H

Subjects
medicine.medical_specialty, Blood transfusion, Anemia, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Iron, Alternative medicine, MEDLINE, Inflammatory bowel disease, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, Internal medicine, medicine, Humans, Pharmacology (medical), Blood Transfusion, Hematinic, Practice Patterns, Physicians', Internet, Hepatology, Anemia, Iron-Deficiency, Dose-Response Relationship, Drug, business.industry, Gastroenterology, Iron deficiency, Iron Deficiencies, medicine.disease, Decision Support Systems, Clinical, Inflammatory Bowel Diseases, 3. Good health, Surgery, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Practice Guidelines as Topic, Hematinics, 030211 gastroenterology & hepatology, Administration, Intravenous, Drug Therapy, Combination, Iron Deficiency Anaemia and Ibd, business
Abstract

BackgroundIron deficiency is a common and undertreated problem in inflammatory bowel disease (IBD).AimTo develop an online tool to support treatment choice at the patient-specific level.MethodsUsing the RAND/UCLA Appropriateness Method (RUAM), a European expert panel assessed the appropriateness of treatment regimens for a variety of clinical scenarios in patients with non-anaemic iron deficiency (NAID) and iron deficiency anaemia (IDA). Treatment options included adjustment of IBD medication only, oral iron supplementation, high-/low-dose intravenous (IV) regimens, IV iron plus erythropoietin-stimulating agent (ESA), and blood transfusion. The panel process consisted of two individual rating rounds (1148 treatment indications; 9-point scale) and three plenary discussion meetings.ResultsThe panel reached agreement on 71% of treatment indications. ‘No treatment’ was never considered appropriate, and repeat treatment after previous failure was generally discouraged. For 98% of scenarios, at least one treatment was appropriate. Adjustment of IBD medication was deemed appropriate in all patients with active disease. Use of oral iron was mainly considered an option in NAID and mildly anaemic patients without disease activity. IV regimens were often judged appropriate, with high-dose IV iron being the preferred option in 77% of IDA scenarios. Blood transfusion and IV+ESA were indicated in exceptional cases only.ConclusionsThe RUAM revealed high agreement amongst experts on the management of iron deficiency in patients with IBD. High-dose IV iron was more often considered appropriate than other options. To facilitate dissemination of the recommendations, panel outcomes were embedded in an online tool, accessible via http://ferroscope.com/.

Published
2013

80. Is there a terrible issue with bacterial resistance: pro-con

Author

Didier Raoult, Mical Paul, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Rambam Health Care Campus, and INSB-INSB-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Microbiology (medical), medicine.drug_class, 030106 microbiology, Antibiotics, Context (language use), Drug resistance, medicine.disease_cause, Article, Microbiology, 03 medical and health sciences, Antibiotic resistance, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Streptococcus pneumoniae, Drug Resistance, Bacterial, medicine, Prevalence, Humans, Treatment Failure, ComputingMilieux_MISCELLANEOUS, biology, business.industry, General Medicine, Bacterial Infections, biology.organism_classification, medicine.disease, 3. Good health, Acinetobacter baumannii, Anti-Bacterial Agents, Infectious Diseases, Staphylococcus aureus, Middle East respiratory syndrome, business
Abstract

We are observing a major increase in antibiotic resistance of many bacterial species, Klebsiella pneumoniae and Acinetobacter baumannii in particular [1]. This triggers an alarmist response in major journals in the world, the WHO and the CDC [2]. It is clear that the response of the media and governments to ongoing events is not always rational and often leads to overreactions. Hence, very few of the virus or prion alerts in last 30 years have been confirmed, including bioterrorism, avian flu, ‘Mad cow’ disease, severe acute respiratory syndrome, Middle East respiratory syndrome, coronavirus and the globalized threat of Ebola which has been predicted since 1976 [3]. In this context, wemust carefully appraise alerts on antibiotic resistance to avoid overreacting. Indeed, in the 1970s, the end of the antibiotic era had already been predicted at the time of the emergence of resistance in Serratia marcescens [4]. It is important to balance correctly the burden of disease, because this impacts drug development, drug agencies’ approval thresholds for new drugs, allocation of research funds and more. The medical literature draws attention to bacteria becoming resistant but neglects bacteria becoming susceptible. For example Staphylococcus aureus, which is perhaps the biggest bacterial killer in developed countries, is less resistant now than 10 years ago in most of the countries worldwide [5], and in Marseille there is three times less methicillin-resistant S. aureus now as there was 10 years ago [6]. The sum of bacteria that became less resistant and bacteria that became more resistant in the last 15 years in Marseille does not suggest that the problem of resistance has worsened [6]. Susceptibilities to old antibiotics such as trimethoprim-sulfamethoxazole in S. aureus and chloramphenicol or aminoglycosides in Gram-negative bacteria in hospitals is increasing with time in many hospitals. Moreover, community-acquired bacteria such as Streptococcus pyogenes, Streptococcus pneumoniae and Haemophilus influenzae

Published
2016

81. Mutations in GTPBP3 cause a mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis, and encephalopathy

Author

Rosalba Carrozzo, Abraham Lorber, Kei Murayama, Michal Minczuk, Tom Sante, Björn Menten, Joél Smet, Massimo Zeviani, Dominique Chretien, Marlène Rio, Sarah F. Pearce, Joanna Rorbach, Yoshimi Tokuzawa, Thomas Schwarzmayr, Daniele Ghezzi, Agnès Rötig, Patrick F. Chinnery, Asaad Khoury, Yoshihito Kishita, Ellen Crushell, François Feillet, Enrico Bertini, Peter Freisinger, Robert W. Taylor, Ewen W. Sommerville, Thomas Meitinger, Luc Régal, Arnold Munnich, Thomas Wieland, Thomas Klopstock, Robert Kopajtich, Johannes A. Mayr, Holger Prokisch, Bénédict Mousson de Camaret, Rudy Van Coster, Tim M. Strom, Hanna Mandel, Yasushi Okazaki, Zahra Assouline, Angela Pyle, Arnaud Vanlander, Tobias B. Haack, Masakazu Kohda, Metodi D. Metodiev, Thomas J. Nicholls, Christopher A. Powell, Akira Ohtake, Federica Invernizzi, Klaus Marquard, Eleonora Lamantea, Ann Saada, Helmholtz-Zentrum München (HZM), MRC Mitochondrial Biology Unit, University of Cambridge [UK] (CAM), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Reutlingen University, Rambam Health Care Campus, Department of Pediatric Neurology and Metabolism [Ghent], Ghent University Hospital, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Dipartimento di Neuroscienze [IRCCS Gesù Roma], IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Wellcome Trust Centre for Mitochondrial Research, Newcastle University [Newcastle]-International Centre for Life-Institute of Genetic Medicine, Klinikum Stuttgart, Department of Metabolism [Chiba], Children's Hospital Chiba, Institute of Human Genetics, Technische Universität München [München] (TUM)-Helmholtz-Zentrum München (HZM)-German Research Center for Environmental Health, Paracelsus Medical University and Universitätsklinikum Salzburg, Department of Genetics and Metabolic Diseases and the Monique and Jacques Roboh Department of Genetic Research, Hadassah Hebrew University Medical Center [Jerusalem], Saitama Medical University, National Centre for Inherited Metabolic Disorders [Dublin], Temple Street Children's University Hospital [Dublin], Saitama University, Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Médecine Infantile I [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service des Maladies Héréditaires du Métabolisme, Hospices Civils de Lyon (HCL)-Centre de Biologie et de pathologie Est, Center for Medical Genetics [Ghent], Hôpitaux universitaires de Louvain, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Munich Heart Alliance, Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität München [München] (TUM)-Ludwig-Maximilians-Universität München (LMU), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Friedrich-Baur Institute, Ludwig-Maximilians-Universität München (LMU), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz-Zentrum München (HZM)-German Research Center for Environmental Health, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre de Biologie et de pathologie Est-Hospices Civils de Lyon (HCL), and Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU)

Subjects
Male, Mitochondrial translation, [SDV]Life Sciences [q-bio], Respiratory chain, medicine.disease_cause, Consanguinity, RNA, Transfer, pathology [Brain], Genetics(clinical), Child, metabolism [GTP-Binding Proteins], metabolism [RNA, Transfer], Genetics (clinical), Genetics, Mutation, physiopathology [Acidosis, Lactic], Brain Diseases, genetics [Cardiomyopathy, Hypertrophic], Lactic, Respiratory chain complex, genetics [Brain Diseases], Brain, 3. Good health, Pedigree, genetics [Acidosis, Lactic], Lactic acidosis, Child, Preschool, genetics [RNA, Transfer], Acidosis, Lactic, Female, RNA Interference, GTPBP3, Acidosis, GTPBP3 protein, human, Mitochondrial DNA, genetics [GTP-Binding Proteins], Cardiomyopathy, Molecular Sequence Data, Biology, Human mitochondrial genetics, Cell Line, GTP-Binding Proteins, ddc:570, Report, medicine, Humans, Amino Acid Sequence, Preschool, Protein Processing, physiopathology [Cardiomyopathy, Hypertrophic], Post-Translational, Infant, Newborn, Infant, Cardiomyopathy, Hypertrophic, Fibroblasts, medicine.disease, Newborn, Transfer, Protein Biosynthesis, Sequence Alignment, Protein Processing, Post-Translational, Hypertrophic, physiopathology [Brain Diseases], RNA
Abstract

International audience; Respiratory chain deficiencies exhibit a wide variety of clinical phenotypes resulting from defective mitochondrial energy production through oxidative phosphorylation. These defects can be caused by either mutations in the mtDNA or mutations in nuclear genes coding for mitochondrial proteins. The underlying pathomechanisms can affect numerous pathways involved in mitochondrial physiology. By whole-exome and candidate gene sequencing, we identified 11 individuals from 9 families carrying compound heterozygous or homozygous mutations in GTPBP3, encoding the mitochondrial GTP-binding protein 3. Affected individuals from eight out of nine families presented with combined respiratory chain complex deficiencies in skeletal muscle. Mutations in GTPBP3 are associated with a severe mitochondrial translation defect, consistent with the predicted function of the protein in catalyzing the formation of 5-taurinomethyluridine (τm(5)U) in the anticodon wobble position of five mitochondrial tRNAs. All case subjects presented with lactic acidosis and nine developed hypertrophic cardiomyopathy. In contrast to individuals with mutations in MTO1, the protein product of which is predicted to participate in the generation of the same modification, most individuals with GTPBP3 mutations developed neurological symptoms and MRI involvement of thalamus, putamen, and brainstem resembling Leigh syndrome. Our study of a mitochondrial translation disorder points toward the importance of posttranscriptional modification of mitochondrial tRNAs for proper mitochondrial function.

Published
2014

82. The phylogenetic and geographic structure of Y-chromosome haplogroup R1a

Author

Doron M. Behar, Elza Khusnutdinova, Shirin Farjadian, Gyaneshwer Chaubey, Ardeshir Bahmanimehr, Oleg Balanovsky, Tena Šarić, Roy J. King, Peter A. Underhill, Jianbin Wang, Toomas Kivisild, Rene J. Herrera, Hovhannes Sahakyan, Jelena Šarac, Viola Grugni, Levon Yepiskoposyan, G. David Poznik, Natalie M. Myres, Stephen R. Quake, Ben Passarelli, Ornella Semino, Julie Di Cristofaro, Siiri Rootsi, Pavao Rudan, Ajai Kumar Pathak, Richard Villems, Mari Järve, Jad Kanbar, Carlos Bustamante, Jacques Chiaroni, Alena Kushniarevich, Alice A. Lin, UMR 6578 : Anthropologie Bio-Culturelle (UAABC), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Molecular Medicine Laboratory, Rambam Health Care Campus, Dipartimento di Genetica e Microbiologia, Università degli Studi di Pavia, Russian Academy of Medical Sciences, Leverhulme Centre for Human Evolutionary Studies University of Cambridge, University of Cambridge [UK] (CAM), and Università degli Studi di Pavia = University of Pavia (UNIPV)

Subjects
Male, Asia, Genetic Linkage, Y chromosome, Polymorphism, Single Nucleotide, Article, Haplogroup, Evolution, Molecular, Gene Frequency, Phylogenetics, Ethnicity, Genetics, Humans, Clade, Alleles, Phylogeny, Genetics (clinical), Spatial Analysis, R1a, phylogeography, Chromosomes, Human, Y, Phylogenetic tree, Haplotype, Haplogroup L3, Europe, Phylogeography, Geography, Haplotypes, Evolutionary biology, Microsatellite Repeats
Abstract

International audience; : R1a-M420 is one of the most widely spread Y-chromosome haplogroups; however, its substructure within Europe and Asia has remained poorly characterized. Using a panel of 16 244 male subjects from 126 populations sampled across Eurasia, we identified 2923 R1a-M420 Y-chromosomes and analyzed them to a highly granular phylogeographic resolution. Whole Y-chromosome sequence analysis of eight R1a and five R1b individuals suggests a divergence time of ∼25 000 (95% CI: 21 300-29 000) years ago and a coalescence time within R1a-M417 of ∼5800 (95% CI: 4800-6800) years. The spatial frequency distributions of R1a sub-haplogroups conclusively indicate two major groups, one found primarily in Europe and the other confined to Central and South Asia. Beyond the major European versus Asian dichotomy, we describe several younger sub-haplogroups. Based on spatial distributions and diversity patterns within the R1a-M420 clade, particularly rare basal branches detected primarily within Iran and eastern Turkey, we conclude that the initial episodes of haplogroup R1a diversification likely occurred in the vicinity of present-day Iran.European Journal of Human Genetics advance online publication, 26 March 2014; doi:10.1038/ejhg.2014.50.

Published
2014

83. Complicated intra-abdominal infections worldwide : the definitive data of the CIAOW Study

Author

Sartelli, Massimo, Catena, Fausto, Ansaloni, Luca, Coccolini, Frederico, Corbella, Davide, Moore, Ernest, Malangoni, Mark, Velmahos, George, Coimbra, Raul, Koike, Kaoru, Leppaniemi, Ari, Biffl, Walter, Balogh, Zsolt, Bendinelli, Cino, Gupta, Sanjay, Kluger, Yoram, Agresta, Ferdinando, Di Saverio, Salmone, Tugnoli, Gregorio, Jovine, Elio, Ordonez, Carlos, Whelan, James, Fraga, Gustavo, Carlos, Gomes, Augusto, Pereira, Gerson, Yuan, Kuo-Ching, Bala, Miklosh, Peev, Miroslav, Ben-Ishay, Offir, Cui, Yunfeng, Marwah, Sanjay, Zachariah, Sanoop, Wani Imtiaz, Rangarajan, Muthukumaran, Sakakushev, Boris, Kong, Victor, Ahmed, Adamu, Abbas, Ashraf, Gonsaga, Ricardo, Guercioni, Gianluca, Vettoretto, Nereo, Poiasina, Elia, Díaz-Nieto, Rafael, Massalou, Damien, Skrovina, Matej, Gerych, Ihor, Augustin, Goran, Kenig, Jakub, Khokha, Vladimir, Tranà, Cristian, Kok, Kenneth, Mefire, Alain, Lee, Jae, Hong, Suk-Kyung, Lohse, Helmut, Ghnnam, Wagih, Verni, Alfredo, Lohsiriwat, Varut, Siribumrungwong, Boonying, El Zalabany, Tamer, Tavares, Alberto, Baiocchi, Gianluca, Das, Koray, Jarry, Julien, Zida, Maurice, Sato, Norio, Murata, Kiyoshi, Shoko, Tomohisa, Irahara, Takayuki, Hamedelneel, Ahmed, Naidoo, Noel, Adesunkanmi, Abdul, Kobe, Yoshiro, Ishii, Wataru, Oka, Kazuyuki, Izawa, Yoshimitsu, Hamid, Hytham, Khan, Iqbal, Attri, AK, Sharma, Rajeev, Sanjuan, Juan, Badiel, Marisol, Barnabé, Rita, II kirurgian klinikka, [Sartelli, M] Department of Surgery, Macerata Hospital, Macerata, Italy. [Catena, F] Emergency Surgery, Maggiore Parma Hospital, Parma, Italy. [Ansaloni, L, Coccolini, F, Poiasina, E] Department of General Surgery, Ospedali Riuniti, Bergamo, Italy. [Corbella, D] Department of Anestesiology, Ospedali Riuniti, Bergamo, Italy. [Moore, EE, Biffl, W] Department of Surgery, Denver Health Medical Center, Denver, USA. [Malangoni, M] American Board of Surgery, Philadelphia, USA. [Velmahos, G, Peev, MP] Division of Trauma, Emergency Surgery and Surgical Critical Care, Harvard Medical School, Massachusetts General Hospital, Massachusetts, USA. [Coimbra, R] Department of Surgery, UC San Diego Health System, San Diego, USA. [Koike, K] Department of Primary Care & Emergency Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan. [Leppaniemi, A] Department of Abdominal Surgery, University Hospital Meilahti, Helsinki, Finland. [Balogh, Z, Bendinelli, C] Department of Surgery, University of Newcastle, Newcastle, NSW, Australia. [Gupta, S] Department of Surgery, Govt Medical College and Hospital, Chandigarh, India. [Kluger, Y, Ben-Ishay, O, Attri, A, Sharma, R] Department of General Surgery, Rambam Health Care Campus, Haifa, Israel. [Agresta, F] Department of Surgery, Adria Hospital Adria, Adria, Italy. [Di Saverio, S, Tugnoli, G] Trauma Surgery Unit, Maggiore Hospital, Bologna, Italy. [Jovine, E, Bananbé, R] Department of Surgery, Maggiore Hospital, Bologna, Italy. [Ordoñez, CA, Sanjuán, J, Badiel, M] Department of Surgery, Fundación Valle del Lilí, Cali, Colombia. [Whelan, JF] Division of Trauma/Critical Care Department of Surgery Virginia Commonwealth University, Richmond, VA, USA. [Fraga, GP] Division of Trauma Surgery, Campinas University, Campinas, Brazil. [Gomes, CA] Department of Surgery, Monte Sinai Hospital, Juiz de Fora, Brazil. [Pereira, CA] Department of Surgery, Emergency Unit, Ribeirão Preto, Brazil. [Yuan, KC]Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan. [Bala, M] Department of General Surgery, Hadassah Medical Center, Jerusalem, Israel. [Cui, Y] Department of Surgery, Tianjin Nankai Hospital, Nankai Clinical School of Medicine, Tianjin Medical University, Tianjin, China. [Marwah, S] Department of Surgery, Pt BDS Post-graduate Institute of Medical Sciences, Rohtak, India. [Zachariah, S] Department of Surgery, MOSC Medical College, Cochin, India. [Wani, I] Department of Surgery, SKIMS, Srinagar, India. [Rangarajan, M] Department of Surgery, Kovai Medical Center, Coimbatore, India. [Shakakusev, B] First Clinic of General Surgery, University Hospital/UMBAL/St George Plovdiv, Plovdiv, Bulgaria. [Kong, V] Department of Surgery, Edendale Surgery, Pietermaritzburg, Republic of South Africa. [Ahmed, A] Department of Surgery, Ahmadu Bello University Teaching Hospital Zaria, Kaduna, Nigeria. [Abbas, A, Ghnnam, W] Department of Surgery, Mansoura University Hospital, Mansoura, Egypt. [Gonsaga, RA] Department of Surgery, Faculdades Integradas Padre Albino, Catanduva, Brazil. [Guercioni, G] Department of Surgery, Mazzoni Hospital, Ascoli Piceno, Italy. [Vettoretto, N] Department of Surgery, Mellini Hospital, Chiari, BS, Italy. [Díaz-Nieto, R] Department of General and Digestive Surgery, Virgen de la Victoria, University Hospital, Málaga, Spain. [Massalou, D] Department of General Surgery and Surgical Oncology, Université de Nice Sophia-Antipolis, Universitary Hospital of Nice, Nice, France. [Skrovina, M] Department of Surgery, Hospital and Oncological Centre, Novy Jicin, Czech Republic. [Gerych, I] Department of General Surgery, Lviv Emergency Hospital, Lviv, Ukraine. [Augustin, G] Department of Surgery, University Hospital Center Zagreb, Zagreb, Croatia. [Kenig, J] 3rd Department of General Surger Jagiellonian Univeristy, Narutowicz Hospital, Krakow, Poland. [Khokha, V] Department of Surgery, Mozyr City Hospital, Mozyr, Belarus. [Tranà, C] Department of Surgery, Ancona University, Ancona, Italy. [Kok, KY] Department of Surgery, Ripas Hospital, Bandar Seri Begawan, Brunei. [Mefire, AC] Clinical Sciences, Regional Hospitals Limbe and Buea, Limbe, Cameroon. [Lee, JG] Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. [Hong, SK] Division of Trauma and Surgical Critical Care, Department of Surgery, University of Ulsan, Seoul, Republic of Korea. [Lohse, HA] II Cátedra de Clínica Quirúrgica, Hospital de Clínicas, Asuncion, Paraguay. [Verni, A] Department of Surgery, Cutral Có Clinic, Cutral Có, Argentina. [Lohsiriwat, V] Department of Surgery, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand. [Siribumrungwong, B] Department of Surgery, Thammasat University Hospital, Pathumthani, Thailand. [El Zalabany, T] Department of Surgery, Bahrain Defence Force Hospital, Manama, Bahrain. [Tavares, A] Department of Surgery, Hospital Regional de Alta Especialidad del Bajio, Leon, Mexico. [Baiocchi, G] Clinical and Experimental Sciences, Brescia Ospedali Civili, Brescia, Italy. [Das, K] General Surgery, Adana Numune Training and Research Hospital, Adana, Turkey. [Jarry, J] Visceral Surgery, Military Hospital Desgenettes, Lyon, France. [Zida, M] Visceral Surgery, Teaching Hospital Yalgado Ouedraogo, Ouedraogo, Burkina Faso. [Murata, K] Department of Acute and Critical care medicine, Tokyo Medical and Dental University, Tokyo, Japan. [Shoko, T] he Shock Trauma and Emergency Medical Center, Matsudo City Hospital, Chiba, Japan. [Irahara, T] Emergency and Critical Care Center of Nippon Medical School, Tama-Nagayama Hospital, Tokyo, Japan. [Hamedelneel, AO] Department of Surgery, Our Lady of Lourdes Hospital, Drogheda, Ireland. [Naidoo, N] Department of Surgery, Port Shepstone Hospital, Port Shepstone, South Africa. [Adesunkanmi, AR] Department of Surgery, Obafemi Awolowo UNiversity Hospital, Ile-Ife, Nigeria. [Kobe, Y] Department of Emergency and Critical Care Medicine, Chiba University Hospital, Chiba, Japan. [Ishii, W] Department of Emergency and Critical Care Medicine, Chiba University Hospital, Chiba, Japan, and Depatment of Emergency Medicine, Kyoto Second Red Cross Hospital, Kyoto, Japan. [Oka, K] Tajima emergency & Critical Care Medical Center, Toyooka Public Hospital, Toyooka, Hyogo, Japan. [Izawa, Y] Emergency and Critical Care Medicine, Jichi Medical University, Shimotsuke, Japan. [Hamid, H] Department of Surgery, Mayo General Hospital Castlebar Co. Mayo, Castlebar, Ireland.

Subjects
Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Digestive System Surgical Procedures [Medical Subject Headings], APPENDICEAL ABSCESS, medicine.medical_treatment, Diseases::Bacterial Infections and Mycoses::Infection::Cross Infection [Medical Subject Headings], Phenomena and Processes::Microbiological Phenomena::Drug Resistance, Microbial [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drainage [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Reoperation [Medical Subject Headings], Study Protocol, Infección hospitalaria, Procedimientos quirúrgicos del sistema digestivo, Diseases::Bacterial Infections and Mycoses::Infection::Sepsis [Medical Subject Headings], Publication Characteristics::Study Characteristics::Multicenter Study [Medical Subject Headings], Enfermedad crítica, Adulto, Mortality rate, Farmacoresistencia microbiana, Immunosuppression, Diverticulitis, Humanos, 3. Good health, Emergency Medicine, Diseases::Digestive System Diseases::Peritoneal Diseases::Peritonitis [Medical Subject Headings], KLEBSIELLA-PNEUMONIAE, Reoperación, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Critical Illness [Medical Subject Headings], medicine.medical_specialty, CHOLECYSTECTOMY, education, Peritonitis, RELAPAROTOMY, Diseases::Bacterial Infections and Mycoses::Infection::Suppuration::Abscess::Abdominal Abscess [Medical Subject Headings], SECONDARY PERITONITIS, Internal medicine, complicated intra-abdomina infections, appendicitis, cholecystitis, postoperative, colonic perforation, gastroduodenal perforation, diverticulitis, small bowel perforation, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], medicine, MANAGEMENT, METAANALYSIS, Estudio multicéntrico, Diseases::Bacterial Infections and Mycoses::Infection::Intraabdominal Infections [Medical Subject Headings], SEPSIS, business.industry, Abdominal Infection, Absceso abdominal, ACUTE CHOLECYSTITIS, medicine.disease, 3126 Surgery, anesthesiology, intensive care, radiology, Infecciones intraabdominales, Appendicitis, Surgery, Cholecystitis, Drenaje, Cholecystectomy, business, DIVERTICULITIS
Abstract

Journal Article; The CIAOW study (Complicated intra-abdominal infections worldwide observational study) is a multicenter observational study underwent in 68 medical institutions worldwide during a six-month study period (October 2012-March 2013). The study included patients older than 18 years undergoing surgery or interventional drainage to address complicated intra-abdominal infections (IAIs). 1898 patients with a mean age of 51.6 years (range 18-99) were enrolled in the study. 777 patients (41%) were women and 1,121 (59%) were men. Among these patients, 1,645 (86.7%) were affected by community-acquired IAIs while the remaining 253 (13.3%) suffered from healthcare-associated infections. Intraperitoneal specimens were collected from 1,190 (62.7%) of the enrolled patients. 827 patients (43.6%) were affected by generalized peritonitis while 1071 (56.4%) suffered from localized peritonitis or abscesses. The overall mortality rate was 10.5% (199/1898). According to stepwise multivariate analysis (PR = 0.005 and PE = 0.001), several criteria were found to be independent variables predictive of mortality, including patient age (OR = 1.1; 95%CI = 1.0-1.1; p

Published
2014

84. Letter: European Medicines Agency recommendations for allergic reactions to intravenous iron-containing medicines

Author

Axel Dignass, O. Haagen Nielsen, Milan Lukas, Günter Weiss, H. Stoevelaar, Bjørn Moum, Laurent Peyrin-Biroulet, Gerassimos J. Mantzaris, Silvio Danese, Yehuda Chowers, Peter L. Lakatos, Murat Törüner, Pierre Michetti, Fernando Gomollón, Walter Reinisch, Stefan Lindgren, J. van der Woude, Charlie W. Lees, Gomollon, F, Chowers, Y, Danese, S, Dignass, A, Nielsen, Oh, Lakatos, Pl, Lees, Cw, Lindgren, S, Lukas, M, Mantzaris, Gj, Michetti, P, Moum, B, Peyrin-Biroulet, L, Toruner, M, van der Woude, J, Weiss, G, Stoevelaar, H, Reinisch, W, Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, Rambam Health Care Campus, Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Agaplesion Markus Krankenhaus = Agaplesion Markus Hospital [Frankfurt], Herlev and Gentofte Hospital, Semmelweis University [Budapest], Western General Hospital, Edinburgh, Skane University Hospital [Lund], Charles University in Prague, First Faculty of Medicine, ISCARE, Evangelismos Athens General Hospital, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Oslo University Hospital [Oslo], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ankara University School of Medicine [Turkey], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Clinical Immunology and Infectious Diseases [IMU], Innsbruck Medical University [Austria] (IMU), Ismar Healthcare NV, Department Internal Medicine III [Medizinische Universität Wien], Medizinische Universität Wien = Medical University of Vienna, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)

Subjects
medicine.medical_specialty, [SDV]Life Sciences [q-bio], Iron, Intravenous iron, Federal Government, Drug Hypersensitivity, Irritable Bowel Syndrome, 03 medical and health sciences, 0302 clinical medicine, Health care, Agency (sociology), medicine, Humans, Pharmacology (medical), University medical, General hospital, Erasmus+, ComputingMilieux_MISCELLANEOUS, Hepatology, Traditional medicine, Anemia, Iron-Deficiency, business.industry, Gastroenterology, University hospital, 3. Good health, Europe, 030220 oncology & carcinogenesis, Family medicine, 030211 gastroenterology & hepatology, Administration, Intravenous, business, Research center
Abstract

*CIBEREHD, Hospital Cl inico Universitario Lozano Blesa, Zaragoza, Spain. Rambam Health Care Campus, Haifa, Israel. Humanitas Clinical and Research Center, Milan, Italy. Agaplesion Markus Hospital, Frankfurt, Germany. Herlev Hospital, University of Copenhagen, Copenhagen, Denmark. **Semmelweis University, Budapest, Hungary. Western General Hospital, Edinburgh, UK. University Hospital Skane, University of Lund, Malm€o, Sweden. ISCARE Lighthouse and 1st Medical Faculty, Charles University, Prague, Czech Republic. Evangelismos Hospital, Athens, Greece. ***Lausanne University Medical Center, Lausanne, Switzerland. Oslo University Hospital, University of Oslo, Oslo, Norway. University Hospital of Nancy, Universit e Henri Poincar e 1, Vandoeuvre-l es-Nancy, France. Ankara University School of Medicine, Ankara, Turkey. Erasmus University Medical Center, Rotterdam, The Netherlands. ****Clinical Immunology and Infectious Diseases, Medical University of Innsbruck, Innsbruck, Austria. Ismar Healthcare, Lier, Belgium. Department Internal Medicine III, Medical University of Vienna, Vienna, Austria. E-mails: fgomollon@gmail.com, fgomollon@me.com

Published
2014

85. Complicated intra-abdominal infections in a worldwide context: an observational prospective study (CIAOW Study)

Author

Ashraf Abbas, Cristian Tranà, Offir Ben-Ishay, Sanjay Gupta, Kenneth Y.Y. Kok, Kuo Ching Yuan, Khalid Al Khalifa, Kaoru Koike, Alberto Tavares, Tomohisa Shoko, Zsolt J. Balogh, Maurice Zida, Gian Luca Baiocchi, Alain Chichom Mefire, Sanoop K. Zachariah, Rafael Díaz-Nieto, Mark A. Malangoni, Rita Barnabé, Walter L. Biffl, Abdul Rashid K. Adesunkanmi, Ari Leppäniemi, Goran Augustin, Luca Ansaloni, Boris Sakakushev, Noel Naidoo, Federico Coccolini, Wataru Ishii, Rajeev Sharma, Nereo Vettoretto, Miroslav P. Peev, Carlos A. Ordoñez, Miklosh Bala, Suk-Kyung Hong, Ashok K. Attri, Massimo Sartelli, Ferdinando Agresta, Yoshiro Kobe, Koray Das, Norio Sato, Carlos Augusto Gomes, Ricardo Alessandro Teixeira Gonsaga, Tamer El Zalabany, Cino Bendinelli, Helmut Alfredo Segovia Lohse, Alfredo Verni, Ahmed O. Hamedelneel, Takayuki Irahara, Adamu Ahmed, Gregorio Tugnoli, Yoram Kluger, Damien Massalou, Julien Jarry, Matej Skrovina, Jae Gil Lee, Ernest E. Moore, Yunfeng Cui, Elia Poiasina, Varut Lohsiriwat, Raul Coimbra, Sanjay Marwah, Vladimir Khokha, Jakub Kenig, Wagih Ghnnam, Juan Sanjuan, Ihor Gerych, Kiyoshi Murata, Gianluca Guercioni, Victor Y. Kong, George C. Velmahos, Fausto Catena, Salomone Di Saverio, Boonying Siribumrungwong, Elio Jovine, Gerson Alves Pereira Júnior, [Sartelli,M] Department of Surgery, Macerata Hospital, Macerata, Italy. [Catena,F] Emergency Surgery, Maggiore Parma Hospital, Parma, Italy. [Ansaloni,L, Poiasina,E, Coccolini,F] Department of General Surgery, Ospedali Riuniti, Bergamo, Italy. [Moore,E, Biffl,W] Department of Surgery, Denver Health Medical Center, Denver, CO, USA. [Malangoni,M] American Board of Surgery, Philadelphia, PA, USA. [Velmahos,G, Peev,MP] Harvard Medical School, Division of Trauma, Emergency Surgery and Surgical Critical Care Massachusetts General Hospital, Boston, MA, USA. [Coimbra,R] Department of Surgery, UC San Diego Health System, San Diego, CA, USA. [Koike,K, Sato,N] Department of Primary Care & Emergency Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan. [Leppaniemi,A] Department of Abdominal Surgery, University Hospital Meilahti, Helsinki, Finland. [Balogh,Z, Bendinelli,C] Department of Surgery, University of Newcastle, Newcastle, NSW, Australia. [Gupta,S, Attri,AK, Sharma,R] Department of Surgery, Govt Medical College and Hospital, Chandigarh, India. [Kluger,Y, Ben-Ishay,O] Department of General Surgery, Rambam Health Care Campus, Haifa, Israel. [Agresta,F] Department of Surgery, Adria Hospital, Adria, Italy. [Saverio,S di, Tugnoli,G] Trauma Surgery Unit, Maggiore Hospital, Bologna, Italy. [Jovine,E, Barnabé,R] Department of Surgery, Maggiore Hospital, Bologna, Italy. [Ordonez,C, Sanjuán,J] Department of Surgery, Universidad del Valle, Fundación Valle del Lili, Cali, Colombia. [Gomes,A] Department of Surgery, Monte Sinai Hospital, Juiz de Fora, Brazil. [Pereira Junior,GA] Emergency Unit, Department of Surgery, Ribeirão Preto, Brazil . [Yuan,K-CH] Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan. [Bala,M] Department of General Surgery, Hadassah Medical Center, Jerusalem, Israel. [Cui,Y] Department of Surgery, Tianjin Nankai Hospital, Nankai Clinical School of Medicine, Tianjin Medical University, Tianjin, China. [Marwah,S] Department of Surgery, Pt BDS Post-graduate Institute of Medical Sciences, Rohtak, India. [Zachariah,S] Department of Surgery, MOSC medical college, Cochin, India. [Sakakushev,B] First Clinic of General Surgery, University Hospital /UMBAL/ St George Plovdiv, Plovdiv, Bulgaria. [Sakakushev,B] General Surgery Clinic, Medical University/University Hospital St.George, Plovdiv, Bulgaria. [Kong,V] Department of Surgery, Edendale Hospital, Pietermaritzburg, Republic of South Africa. [Ahmed,A] Department of Surgery, Ahmadu Bello University Teaching Hospital Zaria, Kaduna, Nigeria. [Abbas,A] Department of Surgery, Mansoura University Hospital, Mansoura, Egypt . [Teixeira Gonsaga,RA] Department of Surgery, Faculdades Integradas Padre Albino, Catanduva, Brazil. [Guercioni,G] Department of Surgery, Mazzoni Hospital, Ascoli Piceno, Italy. [Vettoretto,N] Department of Surgery, Mellini Hospital, Chiari (BS), Italy. [Díaz Nieto,R] Department of General and Digestive Surgery, Hospital Universitario Virgen de la Victoria, Málaga, Spain. [Massalou,D] Department of General Surgery and Surgical Oncology, Université de Nice Sophia-Antipolis, Universitary Hospital of Nice, France. [Skrovina,M] Department of Surgery, Hospital and Oncological Centre, Novy Jicin, Czech Republic. [Gerych,I] Department of General Surgery, Lviv Emergency Hospital, Lviv, Ukraine. [Agustin,G] Department of Surgery, University Hospital Center Zagreb, Zagreb, Croatia. [Kenig,J] 3rd Department of General Surger Jagiellonian Univeristy, Narutowicz Hospital, Krakow, Poland. [Khokha,V] Department of Surgery, Mozyr City Hospital, Mozyr, Belarus. [Tranà,C] Department of Surgery, Ancona University, Ancona, Italy. [Yen Kok,KY] Department of Surgery, Ripas Hospital, Bandar Seri Begawan, Brunei. [Mefire,ACH] Clinical Sciences, Regional Hospitals Limbe and Buea, Limbe, Cameroon. [Lee,JG] Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. [Hong,S-K] Division of Trauma and Surgical Critical Care, Department of Surgery, University of Ulsan, Seoul, Republic of Korea . [Segovia Lohse,HA] II Cátedra de Clínica Quirúrgica, Hospital de Clínicas, Asunción, Paraguay. [Ghnnam,W] Department of Surgery, Khamis Mushayt General Hospital, Khamis Mushayt, Saudi Arabia. [Verni,A] Department of Surgery, Cutral Co Clinic, Neuquen, Argentina. [Lohsiriwat,W] Department of Surgery, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand. [Siribumrungwong,B] Department of Surgery, Thammasat University Hospital, Pathumthani, Thailand. [Tavares,A] Department of Surgery, Hospital Regional de Alta Especialidad del Bajio, León, México. [Baiocchi,G] Department of Clinical and Experimental Sciences, Brescia University, Brescia, Italy. [Das,K] General Surgery, Adana Numune Training and Research Hospital, Adana, Turkey. [Jarry,J] Visceral Surgery, Military Hospital Desgenettes, Lyon, France. [Zida,M] Visceral Surgery, Teaching Hospital Yalgado Ouedraogo, Ouagadougou, Burkina Faso. [Murata,K] Department of Acute and Critical care medicine, Tokyo Medical and Dental University, Tokyo, Japan. [Shoko,T] The Shock Trauma and Emergency Medical Center, Matsudo City Hospital, Chiba, Japan. [Irahara,T] Emergency and Critical Care Center of Nippon Medical School, Tama-Nagayama Hospital, Tokyo, Japan. [Hamedelneel,AO] Department of Surgery, Our Lady of Lourdes Hospital, Drogheda, Ireland. [Naidoo,N] Department of Surgery, Port Shepstone Hospital, Port Shepstone, South Africa. [Kayode Adesunkanmi,AR] Department of Surgery, College of Health Sciences, Obafemi Awolowo University Hospital, Ile-Ife, Nigeria. [Kobe,Y] Department of Emergency and Critical Care Medicine, Chiba University Hospital, Chiba, Japan. [El Zalabany,T, and Khalifa,K Al] Department of Surgery, Bahrain Defence Force Hospital, Manama, Bahrain. [Ishii,W] Department of Emergency Medicine, Kyoto Second Red Cross Hospital, Kyoto, Japan.

Subjects
Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Drainage [Medical Subject Headings], Pediatrics, medicine.medical_specialty, Infecciones Intraabdominales, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Digestive System Surgical Procedures [Medical Subject Headings], Infección Hospitalaria, Diseases::Bacterial Infections and Mycoses::Infection::Cross Infection [Medical Subject Headings], MEDLINE, Peritonitis, Context (language use), Absceso Abdominal, Phenomena and Processes::Microbiological Phenomena::Drug Resistance, Microbial [Medical Subject Headings], Review, 030230 surgery, Enfermedad Crítica, Diseases::Bacterial Infections and Mycoses::Infection::Suppuration::Abscess::Abdominal Abscess [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Reoperation [Medical Subject Headings], 03 medical and health sciences, 0302 clinical medicine, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], Medicine, intra-abdominal infections, Prospective cohort study, Diseases::Bacterial Infections and Mycoses::Infection::Sepsis [Medical Subject Headings], Estudio Multicéntrico, Publication Characteristics::Study Characteristics::Multicenter Study [Medical Subject Headings], Diseases::Bacterial Infections and Mycoses::Infection::Intraabdominal Infections [Medical Subject Headings], business.industry, Adulto, Mortality rate, Abdominal Infection, Mean age, Farmacoresistencia microbiana, medicine.disease, 3. Good health, Humanos, Procedimientos Quirúrgicos del Sistema Digestivo, 030220 oncology & carcinogenesis, Emergency Medicine, DOENÇAS INFECCIOSAS, Observational study, Surgery, Drenaje, Diseases::Digestive System Diseases::Peritoneal Diseases::Peritonitis [Medical Subject Headings], business, Reoperación, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Critical Illness [Medical Subject Headings]
Abstract

Despite advances in diagnosis, surgery, and antimicrobial therapy, mortality rates associated with complicated intra-abdominal infections remain exceedingly high. The World Society of Emergency Surgery (WSES) has designed the CIAOW study in order to describe the clinical, microbiological, and management-related profiles of both community- and healthcare-acquired complicated intra-abdominal infections in a worldwide context. The CIAOW study (Complicated Intra-Abdominal infection Observational Worldwide Study) is a multicenter observational study currently underway in 57 medical institutions worldwide. The study includes patients undergoing surgery or interventional drainage to address complicated intra-abdominal infections. This preliminary report includes all data from almost the first two months of the six-month study period. Patients who met inclusion criteria with either community-acquired or healthcare-associated complicated intra-abdominal infections (IAIs) were included in the study. 702 patients with a mean age of 49.2 years (range 18–98) were enrolled in the study. 272 patients (38.7%) were women and 430 (62.3%) were men. Among these patients, 615 (87.6%) were affected by community-acquired IAIs while the remaining 87 (12.4%) suffered from healthcare-associated infections. Generalized peritonitis was observed in 304 patients (43.3%), whereas localized peritonitis or abscesses was registered in 398 (57.7%) patients. The overall mortality rate was 10.1% (71/702). The final results of the CIAOW Study will be published following the conclusion of the study period in March 2013.

Published
2013

86. The Basque Paradigm: Genetic Evidence of a Maternal Continuity in the Franco-Cantabrian Region since Pre-Neolithic Times

Author

Lluis Quintana-Murci, Christine Harmant, Doron M. Behar, Wolfgang Haak, Mannis van Oven, Begoña Martínez-Cruz, David Comas, Bernard Oyharçabal, Jasone Salaberria, Frédéric Bauduer, Jeremy Manry, Institut Pasteur, National Geographic Society, Conseil régional d'Aquitaine, Conseil Général des Pyrénées-Atlantiques, Conseil des Elus du Pays-Basque, Centre National de la Recherche Scientifique (France), Centre Hospitalier de la Côte Basque, Netherlands Forensic Institute, Netherlands Genomics Initiative, Netherlands Organization for Scientific Research, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Rambam Health Care Campus [Haifa, Israel], Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Adelaide, Universitat Pompeu Fabra [Barcelona] (UPF), Centre de recherche sur la langue et les textes basques (IKER), Université de Pau et des Pays de l'Adour (UPPA)-Université Bordeaux Montaigne (UBM)-Centre National de la Recherche Scientifique (CNRS), Maladies Rares - Génétique et Métabolisme (MRGM), Université Bordeaux Segalen - Bordeaux 2-Hôpital Pellegrin-Service de Génétique Médicale du CHU de Bordeaux, This work was supported by the Institut Pasteur, National Geographic, and the Histoire des populations et variation linguistique dans les Pyrénées de l'Ouest project, which received funding from the Conseil Régional d'Aquitaine, the Conseil Général des Pyrénées-Atlantiques, the Conseil des Elus du Pays-Basque, and the Centre National de la Recherche Scientifique interdisciplinary program Origine de l'Homme, des Langues et du Langage. This study also benefited from the support of Department of Hematology, Centre Hospitalier de la Côte Basque, in Bayonne, and Association Sang 64., and Genographic Consortium Members: Syama Adhikarla (Madurai Kamaraj University, Madurai, Tamil Nadu, India), Christina J. Adler (University of Adelaide, South Australia, Australia), Elena Balanovska (Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow, Russia), Oleg Balanovsky (Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow, Russia), Jaume Bertranpetit (Universitat Pompeu Fabra, Barcelona, Spain), Andrew C. Clarke (University of Otago, Dunedin, New Zealand), Alan Cooper (University of Adelaide, South Australia, Australia), Clio S. I. Der Sarkissian (University of Adelaide, South Australia, Australia), Matthew C. Dulik (University of Pennsylvania, Philadelphia, Pennsylvania, United States), Jill B. Gaieski (University of Pennsylvania, Philadelphia, Pennsylvania, United States), ArunKumar GaneshPrasad (Madurai Kamaraj University, Madurai, Tamil Nadu, India), Angela Hobbs (National Health Laboratory Service, Johannesburg, South Africa), Asif Javed (IBM, Yorktown Heights, New York, United States), Li Jin (Fudan University, Shanghai, China), Matthew E. Kaplan (University of Arizona, Tucson, Arizona, United States), Shilin Li (Fudan University, Shanghai, China), Elizabeth A. Matisoo-Smith (University of Otago, Dunedin, New Zealand), Marta Melé (Universitat Pompeu Fabra, Barcelona, Spain), Nirav C. Merchant (University of Arizona, Tucson, Arizona, United States), R. John Mitchell (La Trobe University, Melbourne, Victoria, Australia), Amanda C. Owings (University of Pennsylvania, Philadelphia, Pennsylvania, United States), Laxmi Parida (IBM, Yorktown Heights, New York, United States), Ramasamy Pitchappan (Madurai Kamaraj University, Madurai, Tamil Nadu, India), Daniel E. Platt (IBM, Yorktown Heights, New York, United States), Colin Renfrew (University of Cambridge, Cambridge, United Kingdom), Daniela R. Lacerda (Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil), Ajay K. Royyuru (IBM, Yorktown Heights, New York, United States), Fabrício R. Santos (Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil), Theodore G. Schurr (University of Pennsylvania, Philadelphia, Pennsylvania, United States), Himla Soodyall (National Health Laboratory Service, Johannesburg, South Africa), David F. Soria Hernanz (National Geographic Society, Washington, District of Columbia, United States), Pandikumar Swamikrishnan (IBM, Somers, New York, United States), Chris Tyler-Smith (The Wellcome Trust Sanger Institute, Hinxton, United Kingdom), Arun Varatharajan Santhakumari (Madurai Kamaraj University, Madurai, Tamil Nadu, India), Pedro Paulo Vieira (Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil), Miguel G. Vilar (University of Pennsylvania, Philadelphia, Pennsylvania, United States), R. Spencer Wells (National Geographic Society, Washington, District of Columbia, United States), Janet S. Ziegle (Applied Biosystems, Foster City, California, United States)

Subjects
Haplogroup H, Population, Molecular Sequence Data, Context (language use), Biology, DNA, Mitochondrial, Haplogroup, White People, Prehistory, Gene Frequency, Report, Ethnicity, Genetics, Humans, Genetics(clinical), education, Genetics (clinical), Mesolithic, Phylogeny, [SDV.GEN]Life Sciences [q-bio]/Genetics, education.field_of_study, Genètica humana, Genètica de poblacions, Base Sequence, País Basc, Genetic Variation, Before Present, Addendum, Genetics, Population, Haplotypes, Evolutionary biology, Human mitochondrial DNA haplogroup
Abstract

Behar, Doron M. et al.-- The Genographic Consortium, Different lines of evidence point to the resettlement of much of western and central Europe by populations from the Franco-Cantabrian region during the Late Glacial and Postglacial periods. In this context, the study of the genetic diversity of contemporary Basques, a population located at the epicenter of the Franco-Cantabrian region, is particularly useful because they speak a non-Indo-European language that is considered to be a linguistic isolate. In contrast with genome-wide analysis and Y chromosome data, where the problem of poor time estimates remains, a new timescale has been established for the human mtDNA and makes this genome the most informative marker for studying European prehistory. Here, we aim to increase knowledge of the origins of the Basque people and, more generally, of the role of the Franco-Cantabrian refuge in the postglacial repopulation of Europe. We thus characterize the maternal ancestry of 908 Basque and non-Basque individuals from the Basque Country and immediate adjacent regions and, by sequencing 420 complete mtDNA genomes, we focused on haplogroup H. We identified six mtDNA haplogroups, H1j1, H1t1, H2a5a1, H1av1, H3c2a, and H1e1a1, which are autochthonous to the Franco-Cantabrian region and, more specifically, to Basque-speaking populations. We detected signals of the expansion of these haplogroups at ∼4,000 years before present (YBP) and estimated their separation from the pan-European gene pool at ∼8,000 YBP, antedating the Indo-European arrival to the region. Our results clearly support the hypothesis of a partial genetic continuity of contemporary Basques with the preceding Paleolithic/Mesolithic settlers of their homeland., This work was supported by the Institut Pasteur, National Geographic, and the Histoire des populations et variation linguistique dans les Pyrénées de l'Ouest project, which received funding from the Conseil Régional d'Aquitaine, the Conseil Général des Pyrénées-Atlantiques, the Conseil des Elus du Pays-Basque, and the Centre National de la Recherche Scientifique interdisciplinary program Origine de l'Homme, des Langues et du Langage. This study also benefited from the support of Department of Hematology, Centre Hospitalier de la Côte Basque, in Bayonne, and Association Sang 64.

Published
2012

87. Is there a role for TNF-? antagonists in the treatment of SSc? EUSTAR expert consensus development using the Delphi technique

Author

Distler J.H.W., Jordan S., Airò P., Alegre-Sancho J.J., Allanore Y., Balbir Gurman A., Caporali R., Caramaschi P., Carreira P.E., Chizzolini C., Cutolo M., Tuncay Duruöz M., Farge-Bancel D., Hesselstrand R., Iannone F., De Keyser F., Kucharz E.J., Launay D., García De La Peña Lefebvre P., Lukacova O., Marasini B., Martinovic D., Marques Neto J.F., Radic M., Rednic S., Riemekasten G., Rovensky J., Seidel M.F., Senel S., Smith V., Sunderkötter C., Ton E., Van Laar J.M., Matucci-Cerinic M., Müller-Ladner U., Distler O., and Distler, J.H.W., Department of Rheumatology, University of Erlangen-Nuremberg, Germany -- Jordan, S., Department of Rheumatology, University Hospital Zurich, Gloriastr. 25, 8091 Zürich, Switzerland -- Airò, P., Unit of Rheumatology and Clinical Immunology, Spedali Civili, Brescia, Italy -- Alegre-Sancho, J.J., Hospital Universitario Dr. Peset Valencia, Spain -- Allanore, Y., Université Paris Descartes, Service de Rhumatologie A, Hôpital Cochin, Paris, France -- Balbir Gurman, A., B. Shine Rheumatology Unit, Rambam Health Care Campus, Haifa, Israel -- Caporali, R., Division of Rheumatology, University of Pavia, Matteo Foundation, Pavia, Italy -- Caramaschi, P., Rheumatology Unit, Verona, Italy -- Carreira, P.E., Servicio de Reumatologia, Hospital Universitario 12 de Octubre, Madrid, Spain -- Chizzolini, C., Immunology and Allergy, University Hospital, Geneva, Switzerland -- Cutolo, M., Research Laboratory and Academic Unit of Clinical Rheumatology, Dept. Internal Medicine, University of Genova, Italy -- Tuncay Duruöz, M., Celal Bayar University Medical School, PM and R Department, Rheumatology Division, Manisa, Turkey -- Farge-Bancel, D., Service de Médecine Interne et Pathologie Vasculaire, Inserm U976, Hopital Saint-Louis, Paris, France -- Hesselstrand, R., Department of Rheumatology, Lund University Hospital, Lund, Sweden -- Iannone, F., DiMIMP - Rheumatology Unit, University of Bari, Italy -- De Keyser, F., Department of Rheumatology, Ghent University Hospital, Belgium -- Kucharz, E.J., Department of Internal Medicine and Rheumatology, Medical University of Silesia, Katowice, Poland -- Launay, D., Department of Internal Medicine, Lille 2 University, Lille, France -- García De La Peña Lefebvre, P., Hospital Universitario Madrid Norte Sanchinarro, Spain -- Lukacova, O., National Institute for Rheumatic Diseases, Piešt' any, Slovakia -- Marasini, B., Istituto Clinico Humanitas, University of Milan, Italy -- Martinovic, D., Department of Rheumatology, University Hospital Split, Split, Croatia -- Marques Neto, J.F., FCM-UNICAMP, Campinas, SP, Brazil -- Radic, M., Department of Rheumatology, University Hospital Split, Split, Croatia -- Rednic, S., Clinica Reumatologie, University of Medicine and Pharmacy, Iuliu Hatieganu Cluj, Cluj-Napoca, Romania -- Riemekasten, G., Charité- Universitätsmedizin Berlin, Medizinische Klinik Mit Schwerpunkt Rheumatologie und Klinische Immunologie, Berlin, Germany -- Rovensky, J., National Institute for Rheumatic Diseases, Piešt' any, Slovakia -- Seidel, M.F., Medizinische Klinik und Poliklinik 1, Rheumatology, Bonn, Germany -- Senel, S., Cumhuriyet University, School of Medicine, Division of Rheumatology, Sivas, Turkey -- Smith, V., Department of Rheumatology, Ghent University Hospital, Belgium -- Sunderkötter, C., Department of Dermatology, University Hospital Münster, Münster, Germany -- Ton, E., Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, Netherlands -- Van Laar, J.M., Musculoskeletal Research Group, Institute of Cellular Medicine, Medical School, Newcastle upon Tyne, United Kingdom -- Matucci-Cerinic, M., Department of Biomedicine, Division of Rheumatology AOUC, University of Florence, Florence, Italy -- Müller-Ladner, U., Justus-Liebig University Giessen, Department of Rheumatology and Clinical Immunology, Kerckhoff Clinic Bad Nauheim, Bad Nauheim, Germany -- Distler, O., Department of Rheumatology, University Hospital Zurich, Gloriastr. 25, 8091 Zürich, Switzerland

Subjects
TNF-?, skin and connective tissue diseases, Fibrosis, Scleroderma
Abstract

Objective: To obtain experiences and expert opinion on treatment of SSc patients with TNF-? antagonists. Methods: An investigation was carried out among the EUSTAR centres into their expertise on use of TNF-? antagonists. Assessment forms on the frequency of TNF-? inhibitor use were distributed to EULAR Scleroderma Trials and Research Group (EUSTAR) centres. Afterwards, a three round Delphi exercise was performed to obtain expert consensus on the use of TNF-? inhibitors in SSc. Results: Seventy-nine centres returned information on use of TNF-? antagonists in SSc patients. A total of 65 patients were treated with TNF-a inhibitors in 14 different centres. Forty-eight of the 65 patients treated with TNF-? inhibitors improved. Improvement was mainly seen in patients with arthritis, whereas the effects on fibrosis varied. In the first round of the subsequent Delphi approach, 71 out of 79 experts stated that they would use TNF-? antagonists in SSc. Arthritis was suggested as an indication for TNFa antagonists by 75% of the experts. However, after the third stage of the Delphi exercise, the acceptance for the off-label use of TNF-a antagonists decreased and 59% recommended that TNF-? antagonists should not be used or only used in clinical trials in SSc patients, while 38% of the experts suggested the use of TNF-a antagonists for arthritis associated with SSc. Conclusions: Most of the experts do not recommend the routine use of TNF-a antagonists in systemic sclerosis. Arthritis might be a potential indication in SSc, although controlled clinical trials with TNF-? antagonists are needed before general recommendations can be given. © Copyright Clinical and Experimental Rheumatology 2011., Distler, O.; Department of Rheumatology, University Hospital Zurich, Gloriastr. 25, 8091 Zürich, Switzerland; email: oliver.distler@usz.ch

Published
2011

88. Strong Maternal Khoisan Contribution to the South African Coloured Population: A Case of Gender-Biased Admixture

Author

Lluis Quintana-Murci, Doron M. Behar, Oleg Balanovsky, Connie Bormans, Valery Zaporozhchenko, Paul D. van Helden, Eileen G. Hoal, Christine Harmant, Hélène Quach, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Russian Academy of Medical Sciences, Family Tree DNA [Houston, TX], Stellenbosch University, Rambam Health Care Campus [Haifa, Israel], and This work was supported by Institut Pasteur and by the Centre National de la Recherche Scientifique (CNRS). Mitochondrial DNA and Y chromosome databases used for comparative analyses were partly supported by the Russian Fund of Humanities (grant 07-01-12114) and created with the help of Andrey Pshenichnov, Roman Sychev, and Elena Balanovska. P.D.V.H. and E.G.H. are supported by the Department of Science and Technology (DST) and the National Research Foundation (NRF) Centre of Excellence for Biomedical Tuberculosis Research.

Subjects
Male, Genetic Linkage, Population, Genetic admixture, Black People, Mothers, Biology, DNA, Mitochondrial, Polymorphism, Single Nucleotide, Sex Factors, Sex factors, Cape, Report, Genetics, Humans, Genetics(clinical), education, Historical record, Genetics (clinical), education.field_of_study, [SDV.GEN]Life Sciences [q-bio]/Genetics, Chromosomes, Human, Y, Correction, Large sample, Phylogeography, Genetics, Population, Ethnology, Female
Abstract

International audience; The study of recently admixed populations provides unique tools for understanding recent population dynamics, socio-cultural factors associated with the founding of emerging populations, and the genetic basis of disease by means of admixture mapping. Historical records and recent autosomal data indicate that the South African Coloured population forms a unique highly admixed population, resulting from the encounter of different peoples from Africa, Europe, and Asia. However, little is known about the mode by which this admixed population was recently founded. Here we show, through detailed phylogeographic analyses of mitochondrial DNA and Y-chromosome variation in a large sample of South African Coloured individuals, that this population derives from at least five different parental populations (Khoisan, Bantus, Europeans, Indians, and Southeast Asians), who have differently contributed to the foundation of the South African Coloured. In addition, our analyses reveal extraordinarily unbalanced gender-specific contributions of the various population genetic components, the most striking being the massive maternal contribution of Khoisan peoples (more than 60%) and the almost negligible maternal contribution of Europeans with respect to their paternal counterparts. The overall picture of gender-biased admixture depicted in this study indicates that the modern South African Coloured population results mainly from the early encounter of European and African males with autochthonous Khoisan females of the Cape of Good Hope around 350 years ago.

Published
2010

89. Maternal traces of deep common ancestry and asymmetric gene flow between Pygmy hunter-gatherers and Bantu-speaking farmers

Author

Judith R. Kidd, Patrick Mouguiama-Daouda, Hélène Quach, Paul Verdu, Lluis Quintana-Murci, Christine Harmant, Etienne Patin, Kenneth K. Kidd, Jean Dausset, Serge Bahuchet, Lucas Sica, Doron M. Behar, Francesca Luca, Alain Froment, Jean-Marie Hombert, Shay Tzur, Lolke van der Veen, David Comas, Blandine Massonnet, Evelyne Heyer, Antonio Salas, Oleg Balanovsky, Antoine Gessain, Prévention et Thérapie Moléculaires des Maladies Infectieuses Humaines, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherches Médicales de Franceville (CIRMF), Dynamique Du Langage (DDL), Université Lumière - Lyon 2 (UL2)-Centre National de la Recherche Scientifique (CNRS), Unitat de Biologia Evolutiva, Universitat Pompeu Fabra [Barcelona] (UPF), Molecular Medicine Laboratory, Rambam Health Care Campus, Russian Academy of Medical Sciences, Department of Genetics, Yale School of Medicine [New Haven, Connecticut] (YSM), Epidémiologie et Physiopathologie des Virus Oncogènes, Eco-Anthropologie et Ethnobiologie (EAE), Muséum national d'Histoire naturelle (MNHN)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Adaptations humaines aux environnements tropicaux durant l'Holocène (ADENTHRO), Service de Recherche en Hémato-Immunologie (SRHI - UMR_E 05), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7), Unidade de Xenetica (UX), Universidade de Santiago de Compostela [Spain] (USC ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Yale University School of Medicine, Université Paris Diderot - Paris 7 (UPD7)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Universidad de Santiago de Compostela [Spain] (USC), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Muséum national d'Histoire naturelle (MNHN)

Subjects
Male, 0106 biological sciences, MESH: Sequence Analysis, DNA, [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, Population genetics, Haploidy, MESH: Base Sequence, 01 natural sciences, Gene flow, MESH: Variation (Genetics), Clade, MESH: Phylogeny, Phylogeny, 2. Zero hunger, 0303 health sciences, education.field_of_study, Multidisciplinary, Phylogenetic tree, MESH: Haploidy, Biological Sciences, Genes, Mitochondrial, Human evolution, Female, Gene pool, Gene Flow, Molecular Sequence Data, Population, Black People, Biology, MESH: Genes, Mitochondrial, DNA, Mitochondrial, 010603 evolutionary biology, 03 medical and health sciences, Phylogenetics, Humans, Africa, Central, education, MESH: Gene Flow, 030304 developmental biology, MESH: Molecular Sequence Data, MESH: Humans, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Base Sequence, MESH: DNA, Mitochondrial, Genetic Variation, Sequence Analysis, DNA, MESH: Male, MESH: Population, MESH: Africa, Central, Evolutionary biology, MESH: African Continental Ancestry Group, MESH: Female
Abstract

Two groups of populations with completely different lifestyles—the Pygmy hunter–gatherers and the Bantu-speaking farmers—coexist in Central Africa. We investigated the origins of these two groups and the interactions between them, by analyzing mtDNA variation in 1,404 individuals from 20 farming populations and 9 Pygmy populations from Central Africa, with the aim of shedding light on one of the most fascinating cultural transitions in human evolution (the transition from hunting and gathering to agriculture). Our data indicate that this region was colonized gradually, with an initial L1c-rich ancestral population ultimately giving rise to current-day farmers, who display various L1c clades, and to Pygmies, in whom L1c1a is the only surviving clade. Detailed phylogenetic analysis of complete mtDNA sequences for L1c1a showed this clade to be autochthonous to Central Africa, with its most recent branches shared between farmers and Pygmies. Coalescence analyses revealed that these two groups arose through a complex evolutionary process characterized by ( i ) initial divergence of the ancestors of contemporary Pygmies from an ancestral Central African population no more than ≈70,000 years ago, ( ii ) a period of isolation between the two groups, accounting for their phenotypic differences, ( iii ) long-standing asymmetric maternal gene flow from Pygmies to the ancestors of the farming populations, beginning no more than ≈40,000 years ago and persisting until a few thousand years ago, and ( iv ) enrichment of the maternal gene pool of the ancestors of the farming populations by the arrival and/or subsequent demographic expansion of L0a, L2, and L3 carriers.

Published
2008

90. Eight previously unidentified mutations found in the OA1 ocular albinism gene

Author

Josseline Kaplan, Elise Heon, Daniel F. Schorderet, Helene Mayeur, Alex V. Levin, Dominique Bonneau, Maurice Menasche, Marc Abitbol, Hélène Dollfus, Joanne Sutherland, Eedy Mezer, Dominique Marchant, Cécile Marsac, Didier Lacombe, Olivier Roche, Jean-Louis Dufier, Carolina Jaliffa, Francis L. Munier, Edith Said, Christelle Vêtu, EA no 2502 du ministère de la Recherche, de l'Enseignement Supérieur et la Technologie, Université Paris Descartes - Paris 5 (UPD5)-CERTO, Service d'ophtalmologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de génétique médicale, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service de génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Jules Gonin Eye Hospital, Institut de Recherche en Ophtalmologie (IRO), Institut de Recherche en Ophtalmologie, Department of Ophthalmology and Vision Sciences, The Hospital for sick children [Toronto] (SickKids), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Department of Pediatrics and Medical Genetics, St. Luke's Hospital, Alberto Moscona Department of Ophthalmology, Rambam Health Care Campus, Handicaps génétiques de l'enfant (Inserm U393), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), We would like to thank Rétina France, Président Claude Foucher, Pr Jean- Louis Dufier, Dean Patrick Berche, Genespoir, Fondation pour la Recherche Médicale, Fondation de France, Lions Club de France, Fondation de L'Avenir, Association Française contre les Myopathies, ORPHANET, INSERM, CNRS, Ministère de la Recherche, de l'Enseignement Supérieur et de la Technologie, Faculté de Médecine René Descartes, Brandan's Eye Research Fund (AL) and Essilor for their support., Autard, Delphine, Université Paris Descartes - Paris 5 ( UPD5 ) -CERTO, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université d'Angers ( UA ) -CHU Angers, Institut de Recherche en Ophtalmologie ( IRO ), The Hospital for Sick Children, Université de Bordeaux ( UB ) -CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Handicaps génétiques de l'enfant ( Inserm U393 ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
MESH : Point Mutation, Male, MESH : Molecular Sequence Data, genetic structures, MESH: Membrane Glycoproteins, DNA Mutational Analysis, MESH : Membrane Glycoproteins, MESH: RNA Splice Sites, MESH: Amino Acid Sequence, [SDV.GEN] Life Sciences [q-bio]/Genetics, medicine.disease_cause, MESH: Research Support, Non-U.S. Gov't, Exon, 0302 clinical medicine, MESH : Research Support, Non-U.S. Gov't, MESH: Eye Proteins, Gene duplication, MESH : Female, Genetics(clinical), MESH: DNA Mutational Analysis, Genetics (clinical), Sequence Deletion, Genetics, 0303 health sciences, Mutation, Membrane Glycoproteins, MESH : Amino Acid Sequence, Albinism, Ocular, Amino Acid Sequence, Eye Proteins, Female, Humans, Molecular Sequence Data, Pedigree, Point Mutation, RNA Splice Sites, MESH: Sequence Deletion, 3. Good health, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, [ SDV.MHEP.OS ] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Ocular albinism type 1, MESH : Mutation, MESH : RNA Splice Sites, Research Article, Ocular albinism, lcsh:Internal medicine, MESH: Mutation, lcsh:QH426-470, MESH: Pedigree, MESH : Male, MESH : DNA Mutational Analysis, Biology, 03 medical and health sciences, MESH : Eye Proteins, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, lcsh:RC31-1245, Gene, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, MESH: Albinism, Ocular, MESH: Point Mutation, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, MESH: Molecular Sequence Data, MESH : Albinism, Ocular, Point mutation, MESH : Sequence Deletion, Alternative splicing, MESH : Humans, medicine.disease, Molecular biology, MESH: Male, eye diseases, lcsh:Genetics, MESH : Pedigree, 030221 ophthalmology & optometry, sense organs, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, MESH: Female
Abstract

Background Ocular albinism type 1 (OA1) is an X-linked ocular disorder characterized by a severe reduction in visual acuity, nystagmus, hypopigmentation of the retinal pigmented epithelium, foveal hypoplasia, macromelanosomes in pigmented skin and eye cells, and misrouting of the optical tracts. This disease is primarily caused by mutations in the OA1 gene. Methods The ophthalmologic phenotype of the patients and their family members was characterized. We screened for mutations in the OA1 gene by direct sequencing of the nine PCR-amplified exons, and for genomic deletions by PCR-amplification of large DNA fragments. Results We sequenced the nine exons of the OA1 gene in 72 individuals and found ten different mutations in seven unrelated families and three sporadic cases. The ten mutations include an amino acid substitution and a premature stop codon previously reported by our team, and eight previously unidentified mutations: three amino acid substitutions, a duplication, a deletion, an insertion and two splice-site mutations. The use of a novel Taq polymerase enabled us to amplify large genomic fragments covering the OA1 gene. and to detect very likely six distinct large deletions. Furthermore, we were able to confirm that there was no deletion in twenty one patients where no mutation had been found. Conclusion The identified mutations affect highly conserved amino acids, cause frameshifts or alternative splicing, thus affecting folding of the OA1 G protein coupled receptor, interactions of OA1 with its G protein and/or binding with its ligand.

Published
2006

91. Coagulation and Placenta-Mediated Complications

Author

Jean-Christophe Gris, Anat Aharon, Benjamin Brenner, Ian A. Greer, University of Liverpool, Rambam Health Care Campus, Technion - Israel Institute of Technology [Haifa], Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1)-Université de Montpellier (UM), and Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)

Subjects
Pediatrics, medicine.medical_specialty, lcsh:Medicine, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Thrombophilia, Placenta-mediated complications, Placenta, Medicine, thrombophilia, lcsh:R5-920, Pregnancy, Fetus, recurrent pregnancy loss, Placental abruption, business.industry, Obstetrics, lcsh:R, General Medicine, medicine.disease, Pathophysiology, New Insights in Clinical Medicine, 3. Good health, Venous thrombosis, medicine.anatomical_structure, Gestation, lcsh:Medicine (General), business
Abstract

International audience; Pregnancy is a physiological hypercoagulable state, preparing the mother for the hemostatic challenge of delivery. However, this is associated with an increased risk of venous thrombosis and placenta-mediated complications, which present major challenges for mother and fetus. Although these conditions are heterogeneous in their pathophysiology, hereditary and acquired thrombophilia has been associated with recurrent pregnancy loss and gestational vascular complications, such as early-onset pre-eclampsia and placental abruption. Prevention of such placenta-mediated complications, which collectively complicate up to 15% of pregnancies, is a major issue for women's health. Prospective interventional studies stratified by current knowledge of pathophysiological mechanisms related to placental and systemic hemostatic alterations will impact on the management of pregnancies at risk of these complications.

Published
2014

92. A Nonsense Mutation in the Human Homolog of Drosophila rogdi Causes Kohlschutter–Tonz Syndrome

Author

Efrat Dagan, Serge Amselem, Adi Mory, Philippe Duquesnoy, Sveva Romani, Hanna Mandel, Barbara Illi, Shikma Mordechai, Ruth Gershoni-Baruch, Enza Maria Valente, Ishai Shahor, Nivin Hawash-Moustafa, Technion - Israel Institute of Technology [Haifa], Rambam Health Care Campus [Haifa, Israel], University of Haifa [Haifa], Istituto CSS Mendel [Rome, Italy], Physiopathologie des maladies génétiques d'expression pédiatrique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Couvet, Sandrine

Subjects
Male, Amelogenesis Imperfecta, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SDV]Life Sciences [q-bio], [SDV.GEN] Life Sciences [q-bio]/Genetics, Severity of Illness Index, 0302 clinical medicine, Amelogenesis imperfecta, Genetics(clinical), Global developmental delay, Age of Onset, Israel, Child, Genetics (clinical), media_common, Genetics, 0303 health sciences, Homozygote, Chromosome Mapping, Nuclear Proteins, Disease gene identification, Arabs, 3. Good health, [SDV] Life Sciences [q-bio], Codon, Nonsense, Child, Preschool, Chromosomal region, Drosophila, Female, Adolescent, media_common.quotation_subject, Molecular Sequence Data, Nonsense, Nonsense mutation, Genes, Recessive, Biology, Kohlschütter-Tönz syndrome, Young Adult, 03 medical and health sciences, Report, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Humans, Allele, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, Epilepsy, Base Sequence, Membrane Proteins, medicine.disease, [SDV.BA.ZI]Life Sciences [q-bio]/Animal biology/Invertebrate Zoology, [SDV.BA.ZI] Life Sciences [q-bio]/Animal biology/Invertebrate Zoology, Dementia, Lod Score, Chromosomes, Human, Pair 16, 030217 neurology & neurosurgery
Abstract

International audience; Kohlschutter-Tonz syndrome (KTS) is a rare autosomal-recessive disorder of childhood onset, and it is characterized by global developmental delay, spasticity, epilepsy, and amelogenesis imperfecta. In 12 KTS-affected individuals from a Druze village in northern Israel, homozygosity mapping localized the gene linked to the disease to a 586,513 bp region (with a LOD score of 6.4) in chromosomal region 16p13.3. Sequencing of genes (from genomic DNA of an affected individual) in the linked region revealed chr16: 4,848,632 G>A, which corresponds to ROGDI c.469C>T (p.Arg157(∗)). The nonsense mutation was homozygous in all affected individuals, heterozygous in 10 of 100 unaffected individuals from the same Druze community, and absent from Druze controls from elsewhere. Wild-type ROGDI localizes to the nuclear envelope; ROGDI was not detectable in cells of affected individuals. All affected individuals suffered seizures, were unable to speak, and had amelogenesis imperfecta. However, age of onset and the severity of mental and motor handicaps and that of convulsions varied among affected individuals homozygous for the same nonsense allele.

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93. Serotype 15C Streptococcus pneumoniae resistant to classical complement deposition and agglutination by polyclonal rabbit anti-capsular 15B sera.

Author

Kochis EJ, Shaik-Dasthagirisaheb YB, Munarriz N, Kretzmann I, Nahm M, Pelton SI, and Lapidot R

Abstract

Background: S. pneumoniae (SP) serotypes 15B and 15C are frequent causative agents of invasive pneumococcal disease (IPD), otitis media, and nasopharyngeal colonization in the post PCV13 era. The principal difference between serotypes 15B and 15C is the presence of an O-acetyl group on the pentasaccharide repeating unit of 15B polysaccharide. It remains unclear if antibodies against SP15B polysaccharide demonstrate functional cross reaction with SP15C strains. We compared functional activity of polyclonal rabbit anti-capsular 15B sera against SP15B and SP15C isolates., Methods: Using flow cytometry we measured complement factors C3c and C4d deposition on SP15B and 15C in the presence of polyclonal rabbit anti capsular 15B sera. We measured the binding of C3c, common to all complement pathways, and C4d, specific to classical pathway, on SP serotypes 15B and 15C when co-incubated with polyclonal rabbit anti capsular 15B sera and antibody depleted complement. Both the proportion of bacteria with complement deposition and the fluorescence intensity were measured. We also measured agglutination as the increase in forward and side scatter., Results: Polyclonal rabbit anti-capsular 15B sera activated classical pathway resulting in deposition of C4d and C3c at high intensity on all SP15B cells but only achieved limited deposition and intensity of C4 with SP15C. Similarly, polyclonal rabbit anti-capsular 15B sera induced agglutination of SP15B strains in a dose dependent manner and limited agglutination of SP15C., Conclusions: Anti-capsular 15B sera induce limited C4d and C3c deposition, and minimal agglutination with SP15C strains, reflecting lower classical pathway activation in contrast to high C4d and C3c deposition and agglutination of SP15B. These observations support limited functional cross reactivity of anti-15B to SP15C strains and are consistent with the reduction in opsonophagocytic killing of SP15C reported following immunization with vaccines containing 15B polysaccharide., Competing Interests: Declaration of competing interest Dr. Pelton has research support to Boston Medical Center from Pfizer, Inc. and Merck Vaccines related to pneumococcal vaccine. He received honorarium and consulting fees from Pfizer, Inc., Merck Vaccines, GSK, and Sanofi for participation in advisory boards related to Pneumococcal vaccine, Participation in DSMB, and consulting on research design in collaboration with Aval ere Health. Dr. Lapidot has research support to Boston Medical Center and Rambam Healthcare Campus from Pfizer, Inc. and Merck Vaccines. She received honorarium from Pfizer, Inc. and Merck Vaccines for Participation in advisory boards and symposium related to Pneumococcal disease/vaccines. Dr. Moon Nahm received honorarium and consulting fees from MSD., (Copyright © 2024. Published by Elsevier Ltd.)

Published
2024
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94. Cytomegalovirus (CMV) Prophylaxis in Pediatric Liver Transplantation (PLT): A Comparison of Strategies Across the SPLIT Consortium.

Author

Knackstedt ED, Anderson SG, Anand R, Mitchell J, Arnon R, Book L, Ekong U, Elisofon SA, Furuya K, Himes R, Jain AK, Ovchinsky N, Sundaram SS, Bucuvalas J, and Danziger-Isakov L

Abstract

Although cytomegalovirus (CMV) is a common complication after pediatric liver transplantation (PLT), the optimal method for CMV prevention is uncertain and lacks multi-centered investigation. We compared the effectiveness of short (<120d) versus long (>180d) CMV primary antiviral prophylaxis to prevent CMV disease in PLT, through a prospective cohort study of primary PLT (<18 yrs of age) recipients enrolled in the Society of Pediatric Liver Transplantation (SPLIT) registry from 2015 to 2019 with either donor or recipient CMV seropositivity. Participants were grouped into short or long prophylaxis based on their center's practice and intended duration. 199 PLT recipients were enrolled including 112 (56.3%) short and 87 (43.7%) long prophylaxis. End-organ disease was rare and similar between groups (2.7% and 1.1%; p=0.45). CMV DNAemia and syndrome were more common in the short compared to long (26.8% v. 13.8%; p=0.03 and 18.8% v. 6.9%; p=0.02). Neutropenia occurred more commonly with long prophylaxis (55.2% vs. 16.1%; p<0.001). Graft and patient survival were similar. Consideration of a short prophylaxis must weigh increased risk of CMV syndrome/DNAemia against medication burden and neutropenia of longer prophylaxis., Competing Interests: Declaration of Competing Interest Dr. Lara Danziger-Isakov serves as a consultant for Takeda and participates in contracted clinical research paid to her institution from Takeda and Merck. The remaining authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024. Published by Elsevier Inc.)

Published
2024
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96. Attenuation of Colitis-Induced Visceral Hypersensitivity and Pain by Selective Silencing of TRPV1-Expressing Fibers in Rat Colon.

Author

Mazor Y, Engelmayer N, Nashashibi H, Rottenfußer L, Lev S, and Binshtok AM

Subjects
Animals, Male, Rats, Disease Models, Animal, Nociceptors metabolism, Rats, Sprague-Dawley, Visceral Pain etiology, Visceral Pain drug therapy, Visceral Pain metabolism, Capsaicin pharmacology, Capsaicin analogs & derivatives, Colitis chemically induced, Colitis metabolism, Colitis complications, Colon metabolism, Colon pathology, Lidocaine pharmacology, Lidocaine analogs & derivatives, TRPV Cation Channels metabolism, TRPV Cation Channels genetics, TRPV Cation Channels antagonists & inhibitors
Abstract

Background: Transient receptor potential vanilloid 1 (TRPV1) cation channels, expressed on nociceptors, are well established as key contributors to abdominal pain in inflammatory bowel disease (IBD). Previous attempts at blocking these channels have been riddled with side effects. Here, we propose a novel treatment strategy, utilizing the large pore of TRPV1 channels as a drug delivery system to selectively inhibit visceral nociceptors., Methods: We induced colitis in rats using intrarectal dinitrobenzene sulfonic acid. Visceral hypersensitivity, spontaneous pain, and responsiveness of the hind paws to noxious heat stimuli were examined before and after the intrarectal application of membrane-impermeable sodium channel blocker (QX-314) alone or together with TRPV1 channel activators or blockers., Results: Intrarectal co-application of QX-314 with TRPV1 channel activator capsaicin significantly inhibited colitis-induced gut hypersensitivity. Furthermore, in the model of colitis, but not in naïve rats, QX-314 alone was sufficient to reverse gut hypersensitivity. The blockade of TRPV1 channels prevented this effect of QX-314. Finally, applying QX-314 alone to the inflamed gut inhibited colitis-induced ongoing pain., Conclusions: Selective silencing of gut nociceptors by a membrane-impermeable sodium channel blocker entering via exogenously or endogenously activated TRPV1 channels diminishes IBD-induced gut hypersensitivity. The lack of effect on naïve rats suggests a selective analgesic effect in the inflamed gut. Our results suggest that in the colitis model, TRPV1 channels are tonically active. Furthermore, our results emphasize the role of TRPV1-expressing nociceptive fibers in colitis-induced pain. These findings provide proof of concept for using charged activity blockers for the blockade of IBD-associated abdominal pain., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Published
2024
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97. Inhibition of nucleo-cytoplasmic proteasome translocation by the aromatic amino acids or silencing Sestrin3-their sensing mediator-is tumor suppressive.

Author

Livneh I, Fabre B, Goldhirsh G, Lulu C, Zinger A, Shammai Vainer Y, Kaduri M, Dahan A, Ziv T, Schroeder A, Ben-Neriah Y, Zohar Y, Cohen-Kaplan V, and Ciechanover A

Subjects
Animals, Humans, Mice, Amino Acids, Aromatic metabolism, Cell Nucleus metabolism, Cell Line, Tumor, Cytoplasm metabolism, TOR Serine-Threonine Kinases metabolism, Signal Transduction, Protein Transport, Nuclear Proteins metabolism, Nuclear Proteins genetics, Proteasome Endopeptidase Complex metabolism
Abstract

The proteasome, the catalytic arm of the ubiquitin system, is regulated via its dynamic compartmentation between the nucleus and the cytoplasm, among other mechanisms. Under amino acid shortage, the proteolytic complex is translocated to the cytoplasm, where it stimulates proteolysis to supplement recycled amino acids for essential protein synthesis. This response is mediated via the mTOR pathway and the lack of the three aromatic amino acids Tyr, Trp, and Phe (YWF). mTOR activation by supplementation of the triad inhibits proteasome translocation, leading to cell death. We now show that tumoral inherent stress conditions result in translocation of the proteasome from the nucleus to the cytosol. We further show that the modulation of the signaling cascade governed by YWF is applicable also to non-starved cells by using higher concentration of the triad to achieve a surplus relative to all other amino acids. Based on these two phenomena, we found that the modulation of stress signals via the administration of YWF leads to nuclear proteasome sequestration and inhibition of growth of xenograft, spontaneous, and metastatic mouse tumor models. In correlation with the observed effect of YWF on tumors, we found - using transcriptomic and proteomic analyses - that the triad affects various cellular processes related to cell proliferation, migration, and death. In addition, Sestrin3-a mediator of YWF sensing upstream of mTOR-is essential for proteasome translocation, and therefore plays a pro-tumorigenic role, positioning it as a potential oncogene. This newly identified approach for hijacking the cellular "satiety center" carries therefore potential therapeutic implications for cancer., (© 2024. The Author(s).)

Published
2024
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98. Topical nonsteroidal anti-inflammatory drugs for management of pain after PRK: systematic review and network meta-analysis.

Author

Ben Ephraim Noyman D, Sommer AC, Naaman E, Gonzalez-Lugo JH, and Mimouni M

Subjects
Humans, Eye Pain drug therapy, Network Meta-Analysis, Administration, Topical, Ophthalmic Solutions, Pain Management methods, Anti-Inflammatory Agents, Non-Steroidal administration & dosage, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Pain, Postoperative drug therapy, Photorefractive Keratectomy
Abstract

Topic: Topical nonsteroidal anti-inflammatory drugs (NSAIDs) for management of pain in patients after photorefractive keratectomy (PRK)., Clinical Relevance: Pain after PRK is a major concern for both patients and surgeons. Although evidence supports the use of NSAIDs postoperatively, no consensus exists regarding the preferred regimen. The study aimed to compare the efficacy and safety of different topical NSAIDs., Methods: This study was prospectively registered with PROSPERO (ID: CRD42023417651). A systematic search of electronic databases was performed, for randomized controlled trials reporting topical NSAIDs' outcomes of corneal re-epithelization, rescue analgesics intake, and pain in days 0 to 3 after PRK (postoperative days [PODs] 0 to 3). Studies were graded for risk of bias. Data were extracted, and standardized mean differences (SMDs) were evaluated in a network meta-analysis in accordance with the Cochrane's guidelines, to which a frequentist approach model was fitted. Transitivity was assessed using the net split method. Treatment effectiveness was ranked using forest plots based on comparison with placebo. P-scores (P) and league tables were used to examine combined direct and indirect comparisons., Results: Of 1540 studies identified, 27 were included. These encompassed 2286 patients across 11 countries, evaluating 7 distinct topical NSAIDs. At POD0, ketorolac (P 0.764), flurbiprofen (P 0.763), and bromfenac (P 0.717) were the most efficient drugs overall and displayed significantly lower pain scores than placebo. Other than that, flurbiprofen held the highest rank for reported pain throughout, significantly outperforming placebo on POD1 (P 0.874, SMD -1.19, 95% CI -1.86 to -0.52), POD2 (P 0.882, SMD -1.05, 95% CI -1.82 to -0.27), and POD3 (P 0.939, SMD -1.14, 95% CI -2.1 to -0.18). Other NSAIDs were significantly better than placebo only on POD1 and POD0. Rescue analgesic intake analysis favored indomethacin (P 0.834, SMD -0.8, 95% CI -1.33 to -0.27), ketorolac, and diclofenac. Compared with placebo, re-epithelization was slowed to different significances with all NSAIDs but flurbiprofen (P 0.991, SMD -0.7, 95% CI -1.38 to -0.03)., Conclusions: Flurbiprofen was favorable in pain scores on typically painful postoperative days and re-epithelization times. However, analgesics intake, a more objective outcome, suggested superiority of other NSAIDs. Inconsistencies may be explained by the small sample size. For clinical interpretation, NSAID effect sizes should be taken into consideration., (Copyright © 2024 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Published
2024
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99. Clinical Significance of Mucor in Airway Culture of Immunocompetent Patients With Chronic Lung Disease.

Author

Rizik S, Bentur L, Bar-Yoseph R, Szwarcwort M, Pollak D, Gur M, and Meir M

Subjects
Humans, Retrospective Studies, Male, Female, Adolescent, Adult, Young Adult, Chronic Disease, Bronchiectasis microbiology, Bronchiectasis physiopathology, Mucormycosis microbiology, Sputum microbiology, Bronchoalveolar Lavage Fluid microbiology, Mucorales isolation & purification, Lung Diseases microbiology, Immunocompetence, Clinical Relevance, Mucor isolation & purification, Cystic Fibrosis microbiology, Cystic Fibrosis complications
Abstract

Objectives: Mucor within the airways of immunocompromised patients often signifies an invasive life-threatening infection. However, its significance in immunocompetent patients with chronic lung diseases is less clear. We aimed to assess the clinical implication of mucor in airway-secretion cultures of these patients., Methods: A single-center retrospective cohort study was performed. Patients with cystic fibrosis (CF), primary ciliary dyskinesia (PCD) or non-CF/non-PCD bronchiectasis followed in our Pediatric Pulmonary Institute, with sputum or bronchoalveolar lavage cultures growing Mucorales molds in the years 2010-2022, were included. Demographic and clinical parameters such as body mass index and spirometry values (forced expiratory volume at 1 second) were collected and compared with values up to 12 months prior to and following the index (positive culture) visit., Results: A total of 27 patients of whom 22 (82%) patients were with CF, 3 with PCD (11%) and 2 (7%) with non-CF/non-PCD bronchiectasis were included. Median age was 21.8 (14.9-32.1) years, with forced expiratory volume at 1 second of 62.8% ± 21.9% at the index visit. None of the patients developed disseminated disease, none had clinical or radiological evidence of fungal disease and none required antifungal therapy. Throughout the 12 months prior to and following the positive cultures, no significant changes were noted in body mass index, forced expiratory volume at 1 second, frequency of pulmonary exacerbations, days of hospitalization or days of antibiotic treatment., Conclusions: Evidence of mucor in airway cultures of immunocompetent patients with chronic lung disease does not necessarily signify clinical deterioration nor suggests invasive fungal disease. Larger, long-term prospective studies are required to obviate the need for a thorough evaluation in these patients., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Published
2024
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100. Intraoperative diagnosis of breast cancer metastasis in axillary lymph nodes: Cytological Smear vs. Frozen Section.

Author

Malkiely G, Ashkenazi I, Malkin L, Zohar Y, and Hoffman A

Subjects
Humans, Female, Retrospective Studies, Middle Aged, Adult, Aged, Intraoperative Period, Sensitivity and Specificity, Sentinel Lymph Node Biopsy methods, Breast Neoplasms pathology, Breast Neoplasms surgery, Frozen Sections, Lymphatic Metastasis pathology, Lymphatic Metastasis diagnosis, Axilla, Lymph Nodes pathology
Abstract

Background: Intraoperative evaluation of axillary lymph nodes is sometimes required to determine the extent of surgery. In this study, we wished to assess the reliability of cytologic smear (CS) in determining lymph node involvement with tumor. Theoretically, CS provides more substance for examination than touch-imprint cytology and is faster to perform than frozen section (FS). We hypothesized that CS sensitivity for tumor cell detection in the lymph nodes would be similar to FS, at least 0.90., Methods: This was a retrospective observational study at the Rambam Health Care Campus (January, 2013-June, 2020). Lymph nodes underwent intraoperative evaluation using either CS or FS, based on the availability of a cytologist at the time of the examination. Both intraoperative evaluations were compared to the final pathology following fixation with formalin., Results: Eighty-eight patients undergoing intraoperative analysis were analyzed (51 CS, 37 FS). False-negative tests were recorded in only 1 patient evaluated by each of the 2 methods. This resulted in sensitivity 0.91 (95%CI 0.59, 1.00) for CS and 0.88 (95%CI 0.47, 1.00) for FS, specificity 1.00 (95%CI 0.91, 1.00) for CS and 1.00 (95%CI 0.88, 1.00) for FS, positive predictive value 1.00 (95%CI 0.69, 1.00) for CS and 1.00 (95%CI 0.59, 1.00) for FS, and negative predictive value 0.98 (95%CI 0.87, 1.00) for CS and 0.97 (95%CI 0.83, 1.00) for FS., Conclusions: The sensitivity of the CS in this study is comparable to that of FS and due to shorter analysis time required is the preferred method at our institution., Competing Interests: Disclosure None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Published
2024
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