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Targeted therapy for capillary-venous malformations

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3024-3039页

作者： Lola Zerbib Sophia Ladraa Antoine Fraissenon Charles Bayard Marina Firpion Quitterie Venot Sanela Protic Clément hoguin Amandine Thomas Sylvie Fraitag Jean-Paul Duong Sophie Kaltenbach Estelle Balducci Coline Lefevre Patrick Villarese Vahid Asnafi Christine Broissand nicolas Goudin Ivan nemazanyy Gwennhael Autret Bertrand Tavitian Christophe Legendre nadia Arzouk Veronique Minard-Colin Caroline Chopinet Michael Dussiot denise MAdams Tristan Mirault Laurent Guibaud Paul Isenring Guillaume Canaud UniversitéParis Cité ParisFrance InSERM U1151 Institut Necker-Enfants MaladesParisFrance service d’Imagerie Pédiatrique Hôpital Femme-Mère-EnfantHCLBronFrance CREATIS UMR 5220 Villeurbanne 69100France service de Radiologie Mère-Enfant Hôpital NordSaint EtienneFrance service d’Anatomie pathologique Hôpital Necker-Enfants MaladesAP-HPParisFrance Laboratoire d’Oncohématologie Hôpital Necker-Enfants MaladesAP-HPParisFrance Pharmacie Hôpital Necker-Enfants MaladesAP-HPParisFrance necker Bio-Image Analysis INSERM US24/CNRS UMS 3633ParisFrance Platform for Metabolic Analyses Structure Fédérative de Recherche NeckerINSERM US24/CNRS UMS 3633ParisFrance Plateforme Imageries du Vivant Universitéde ParisPARCCINSERMParisFrance service de néphrologie Transplantation AdultesHôpital Necker-Enfants MaladesAP-HPParisFrance service de Transplantation Hôpital La PitiéSalpétrièreAP-HPParisFrance department of Pediatric and Adolescent Oncology INSERM 1015Gustave RoussyUniversitéParis-SaclayVillejuifFrance service de Physiologie&Explorations Fonctionnelles Cardiovasculaires CHU de LilleLille 59000France InSERM U1163 Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic ImplicationsLaboratoire d’Excellence GR-ExParisFrance Division of Oncology Comprehensive Vascular Anomalies ProgramChildren’s Hospital of PhiladelphiaPhiladelphiaPAUSA service de Médecine Vasculaire hôpital Européen Georges-PompidouParisFrance nephrology Research Group L’Hôtel-Dieu de Québec Research CenterDepartment of MedicineFaculty of MedicineLaval UniversityQuebecQC G1R2J6Canada Unitéde médecine translationnelle et thérapies ciblées Hôpital Necker-Enfants MaladesAP-HPParisFrance CnRS UMR8253 Institut Necker-Enfants MaladesParisFrance

Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of PIK3CA or TEK,an endothelial transmembrane receptor signaling through *** malformations are associated with pain,bleedings,thrombosis,pulmonary embolism,esthetic deformities and,in severe cases,life-threatening *** authorized medical treatment exists for patients with venous ***,we created a genetic mouse model of PIK3CA-related capillary venous malformations that replicates patient *** showed that these malformations only partially signal through AKT *** compared the efficacy of different drugs,including rapamycin,a mTORC1 inhibitor,miransertib,an AKT inhibitor and alpelisib,a PI3Kαinhibitor at improving the lesions seen in the mouse *** demonstrated the effectiveness of alpelisib in preventing vascular malformations’occurrence,improving the already established ones,and prolonging *** these findings,we were authorized to treat 25 patients with alpelisib,including 7 children displaying PIK3CA(n=16)or TEK(n=9)-related capillary venous malformations resistant to usual therapies including sirolimus,debulking surgical procedures or percutaneous *** assessed the volume of vascular malformations using magnetic resonance imaging(MRI)for each *** demonstrated improvement in all 25 *** malformations previously considered intractable were reduced and clinical symptoms were *** showed a decrease of 33.4%and 27.8%in the median volume of PIK3CA and TEK malformations respectively,over 6 months on *** conclusion,this study supports PI3Kαinhibition as a promising therapeutic strategy in patients with PIK3CA or TEK-related capillary venous malformations.

关键词： PIK3CA malformations venous

Visceral Leishmaniasis at the national Reference University hospital Center of n’Djamena (Chad): Epidemiological, Clinical, Diagnostic, Therapeutic and Prognostic Aspects

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Advances in Infectious Diseases 2024年第2期14卷 478-486页

作者： Joseph Mad-Toïngué Mahamat Ali Ahmat Oumaïma Mahamat Djarma Alifa Adjibera Philippe Ali Mahamat Moussa ngakoutou Rangar Choua Ouchemi Mahamat Ali Bolti Djiddi Ali Sougoudi Mamissou Didi Mahamat Doungous Atim service des Maladies Infectieuses CHU de Référence Nationale N’Djamena Chad service de Gastroentérologie et Médecine Interne CHU de Référence Nationale N’Djamena Chad service de Pneumologie et Phtisiologie CHU de Référence Nationale N’Djamena Chad service de Chirurgie viscérale CHU de Référence Nationale N’Djamena Chad service de Médecine CHU de la Renaissance N’Djamena Chad

Introduction: leishmaniasis is a group of parasitic diseases caused by a parasite of the genus Leishmania transmitted by the bite of an infected vector called a sandfly. There are four forms. Visceral leishmaniasis is the most severe form. The aim of our work is to study the epidemiological, clinical, diagnostic, therapeutic and prognostic aspects of the disease in the Infectious Diseases department of the Centre hospitalier Universitaire de Référence nationale in n'Djaména. Methodology: Patients were recruited on the basis of clinical signs suggestive of visceral leishmaniasis, i.e. prolonged fever, splenomegaly and altered general condition. Biological confirmation was performed with a rapid diagnostic test using recombinant K39 parasite antigen, which is known to have good specificity and sensitivity. Epidata version 3.1 software was used to process patient data. Results: From 05/04/21 to 15/12/23, 153 positive cases were managed. The mean age of patients was 18 years, with a sex ratio of 9.2. Of these patients, 103 (67.3%) had recently stayed at gold mining sites. Patients testing positive were treated with sodium stibogluconate combined with paromomycin for 17 days. The mortality rate was 13.2%. Conclusion: Leishmaniasis is a serious and little-known disease in Chad. In order to respond to the disease, it is necessary to reinforce the capacities of health structures and to carry out appropriate actions in the outbreaks.

关键词： Visceral Leishmaniasis Gold Mining Sites Chad

Associations between physical activity levels and ATPase inhibitory factor 1 concentrations in older adults

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Journal of Sport and health Science 2024年第3期13卷 409-418页

作者： Jérémy Raffin Yves Rolland Annelise Genoux Guillaume Combes Mikael Croyal Bertrand Perret Sophie Guyonnet Bruno Vellas Laurent O.Martinez Philipe de Souto Barreto For the MAPT/DSA Group Institut du Vieillissement Gérontopôle de ToulouseCentre Hospitalo-Universitaire de ToulouseToulouse 31000France Centre d'Epidémiologie et de Recherche en Santédes Populations UnitéMixte de Recherche 1295Institut National de la Santéet de la Recherche MédicaleUniversitéToulouse-III-Paul-SabatierToulouse 31000France LimitAging Team Institut des Maladies Métaboliques et CardiovasculairesUnitéMixte de Recherche 1297Institut National de la Santéet de la Recherche MédicaleUniversitéToulouse III-Paul SabatierToulouse 31432France service de Biochimie Pôle de biologieHôpital de PurpanCentre Hospitalo-Universitaire de ToulouseToulouse 31300France L'Institut du Thorax Institut National de la Santéet de la Recherche MédicaleCentre National de la Recherche ScientifiqueCentre Hospitalo-Universitaire de NantesNantes UniversitéNantes 44000France BioCore US16Structure Fédérative de Recherche BonamyInstitut National de la Santéet de la Recherche MédicaleCentre National de la Recherche ScientifiqueCentre Hospitalo-Universitaire de NantesNantes UniversitéNantes 44000France Plate-forme de spectrométrie de masse Centre de Recherche en Nutrition HumaineOuestNantes 44000France 不详

Background:Adenosine triphosphatase inhibitory factor 1(IF1)is a key protein involved in energy ***1 has been linked to various agerelated diseases,although its relationship with physical activity(PA)remains ***,the apolipoprotein A-I(apoA-I),a PA-modulated lipoprotein,could play a role in this relationship because it shares a binding site with IF1 on the cell-surface ATP *** examined here the associations between chronic PA and plasma IF1 concentrations among older adults,and we investigated whether apoA-I mediated these ***:In the present work,1096 healthy adults(63.8%females)aged 70 years and over who were involved in the Multidomain Alzheimer Prevention Trial study were ***1 plasma concentrations(square root of ng/mL)were measured at the 1-year visit of the Multidomain Alzheimer Prevention Trial,while PA levels(square root of metabolic equivalent task min/week)were assessed using questionnaires administered each year from baseline to the 3-year *** linear regressions were performed to investigate the associations between the first-year mean PA levels and IF1 *** analyses were conducted to examine whether apoA-I mediated these *** linear regressions were carried out to investigate whether the 1-year visit IF1 concentrations predicted subsequent changes in ***:Multiple linear regressions indicated that first-year mean PA levels were positively associated with IF1 concentrations(B=0.021;SE=0.010;p=0.043).Mediation analyses revealed that about 37.7%of this relationship was mediated by apoA-I(B_(ab)=0.008;SE=0.004;p=0.023).Longitudinal investigations demonstrated that higher concentrations of IF1 at the 1-year visit predicted a faster decline in PA levels over the subsequent 2 years(time×IF1:B=0.148;SE=0.066;p=0.025).Conclusion:This study demonstrates that regular PA is associated with plasma IF1 concentrations,and it suggests that apoA-I partly med

关键词： Aging Apolipoprotein Bioenergetics Exerkine Mitochondria

COVID-19 Vaccination Status and Severe Outcomes among Patients hospitalized for COVID-19 in West Africa, Togo, 2021

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Advances in Infectious Diseases 2024年第1期14卷 87-104页

作者： Awèréou Kotosso Yao Rodion Konu Lidaw Déassoua Bawe Sarakawabalo Assenouwe Yawovi Mawufemo Tsevi Koffi Atsu Aziagbe Akouda Akessiwe Patassi Bawoubadi Abaltou Gnimdou Tchamdja Lampouguini nebona Komi Séraphin Adjoh Didier Ekouevi Majesté Ihou Wateba Faculté des Sciences de la Santé Université de Lomé Lomé Togo Centre hospitalier Régional Lomé Commune Lomé Togo service des Maladies Infectieuses Centre Hospitalier Universitaire Sylvanus-Olympio Lomé Togo Unité de Recherche Mixte 1219 Bordeaux Population Health Centre University of Bordeaux National Institute for Health and Medical Research (INSERM) Research Institute for Sustainable Development (IRD) Bordeaux France Département de Santé Publique Université de Lomé Lomé Togo Faculté des Sciences de la Santé Université de Kara Kara Togo service d’Anesthésie et Réanimation Centre Hospitalier Universitaire Kara Kara Togo service de néphrologie et d’hémodialyse Centre Hospitalier Universitaire Sylvanus-Olympio Lomé Togo service de Pneumo-Phtisiologie Centre Hospitalier Universitaire Sylvanus-Olympio Lomé Togo

Objectives: More than a year after its introduction, COVID-19 vaccination coverage was low in the Togolese population and little data were available on its benefits for hospitalized patients. This study aimed to describe the impact of COVID-19 vaccination on the prognosis of hospitalized patients. Methods: This was a retrospective cohort study of patients admitted to the Centre hospitalier Régional Lomé Commune (Togo) between June 1, 2021 and May 31, 2022. Primary outcomes (admission to the intensive care unit and death) were presented with frequency and proportion. Mortality rates were presented by sociodemographic and clinical characteristics and compared by appropriate statistical tests. Factors associated with inpatient death were described by performing a Cox proportional hazard regression. Results: A total of 604 patients were hospitalized (50.0% women). The mean age was 54.03 ±17.1 years. Only 55 patients were fully vaccinated (9.1%). ICU admission was significantly more frequent in unvaccinated patients than in vaccinated ones (63.0% vs. 38.2%;p Conclusion: COVID-19 vaccination had a significant benefit for patients with COVID-19 infection in terms of reducing the risk of death. Based on real-world data from sub-Saharan Africa, this information can help optimize the benefit of COVID-19 vaccination by raising community awareness and increasing vaccine coverage while reducing hesitancy.

关键词： COVID-19 Vaccination Prognosis Mortality Sub-Saharan Africa

Eradication Treatment of helicobacter pylori Infection: Evaluation of Therapeutic Strategies in n’Djamena

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Open Journal of Gastroenterology 2024年第2期14卷 59-67页

作者： Mayanna habkréo Ali Mahamat Moussa Tahir Mahamat Saleh Djerabet Franckly Fany haby Mairé dehainssala Adama ngaré Mahamat Ali hachim service de Medecine Interne et Gastroenterologie Centre Hospitalier Universitaire La Reference Nationale N’Djamena Tchad service de Medecine Interne Centre Hospitalier Universitaire La Renaissance N’Djamena Tchad service de Médecine Hopital de l’Amitié Tchad-Chine N’Djamena Tchad

Background: helicobacter pylori (hp) infection is the most widespread bacterial infection in the world. The infection is generally acquired in childhood, but can persist into adulthood. Eradication therapy has undergone several modifications. The aim of this study was to evaluate the different therapeutic strategies used in the eradication of helicobacter pylori infection in the Centre hospitalier Universitaire La Reference nationale of n’Djaména. Patients and Methods: This was a prospective, descriptive analytical study spread over one year, from September 2021 to September 2022. Patients at least 15 years of age presenting with dyspeptic symptoms, seen consecutively in a hepato-gastroenterology consultation and with a positive stool test for h. pylori infection, were included in the study. Equally, 1/3 of patients were treated with dual or triple therapy. The remaining third received quadritherapy. Results: A total of 268 patients were included in the study (mean age 38.40 ± 14.66 with extremes of 16 and 80 years). Males predominated in 58% of cases. Overall therapeutic efficacy was 88.9%. According to different therapeutic strategies, efficacy was 90.75% for dual therapy with PPI (Rabeprazole) and Amoxicillin. On the other hand, efficacy was 87% and 88.88% for PPI-based triple therapy and dual antibiotic therapy, and for PPI-based quadruple therapy and triple antibiotic therapy. Conclusion: h. pylori infection is a common disease in Chad. Dual therapy with rabeprazole combined with a high dose of amoxicillin over a period of at least two weeks showed similar if not better efficacy than triple or quadruple therapy.

关键词： helicobacter pylori Therapeutic Strategies Eradication Dyspepsia Chad

Risk Factors for neonatal Mortality at the Institute of nutrition and Child health of the Donka/Guinea-Conakry national hospital

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Open Journal of Pediatrics 2024年第2期14卷 327-337页

作者： Bangoura Mmah Aminata Kolié Ouo Ouo Camara Salématou hassimiou Baldé Mariama Bangoura Kaba Diop Mamadou Moustapha Camara Emmanuel Diallo Fatoumata Binta Doukouré Mamadou Aliou Mamadou Mouctar Sow Bémy Pé néabey Institut de nutrition et de Santé de l’Enfant Conakry Guinea service de Pédiatrie hô pital National Donka Conakry Guinea service de Pédiatrie hô pital National d’Ignace Deen Conakry Guinea

Introduction: The birth of a baby is a moment of joy and celebration. however, the neonatal period is a very delicate phase of life. neonatal mortality rates remain high in low-income countries. In Guinea, after 20 years, this rate has fallen from 34.2% in 1998 to 32% in 2018. Objective: To identify the main risk factors for neonatal mortality. Methods: This was an observational, analytical case-control study, lasting 6 months from January 1 to June 30, 2019, conducted at the Institut de nutrition et de la Santé de l’Enfant (InSE) at Donka national hospital. Results: We collected 242 cases and 242 controls, i.e. a total of 484 records. 748 patients were registered, with 32.35% deaths. 82.86% of deaths occurred in the early neonatal period. Statistical analysis revealed the main risk factors: prematurity (RQ 7.39 95% CI 3.27 - 16.61 p = 0.0000003), hypothermia (RQ 2.29 95% CI 1.51 - 3.46 p = 0.0001), acute fetal distress (RQ 2.13 95% CI 1.33 - 3.43 p = 0.0016), low birth weight (QR 1.91 95% CI 1.12 - 3.24 p = 0.016), home birth (QR 3.26 95% CI 1.25 - 8.46 p = 0.015). Conclusion: neonatal mortality is a health problem in the InSE neonatology department. To reduce the mortality rate in this referral facility, it is essential to equip it and provide ongoing training for staff.

关键词： neonatal Mortality InSE Guinea-Conakry

Massive abdominal muscle atrophy during prolonged mechanical ventilation: Implications for tracheostomy removal

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Journal of Intensive Medicine 2024年第1期4卷 133-135页

作者： Pascal Beuret Florian Michelin Audrey Tientcheu Laurane Chalvet Benedicte Philippon-Jouve Jean-Charles Chakarian Xavier Fabre service de Réanimation et Soins continus Centre Hospitalier de RoanneRoanneFrance

Introduction Maintaining the functional integrity of respiratory muscles is crucial for critically ill patients to be weaned from mechanical ventilation and decannulated if *** of the diaphragm is frequent in patients under mechanical ventilation and has been associated with a longer duration of weaning.[1,2]Studies on expiratory muscles are *** recent studies demonstrated the feasibility and reproducibility of ultrasound in measuring the thickness of abdominal muscles,[3,4]with one study showing abdominal muscle atrophy in 22%of mechanically ventilated critically ill patients during the first week of mechanical ventilation.[4]

关键词： critically mechanical abdominal

Advancing immunosuppression in liver transplantation: A narrative review

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hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 441-448页

作者： Samuele Iesari Francesca Laura nava Ilaria Elena Zais Laurent Coubeau Mariano Ferraresso Evaldo Favi Jan Lerut General Surgery and Kidney Transplantation Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico15 Via della Commenda20122 MilanItaly Institut de Recherche Expérimentale et Clinique Universitécatholique de Louvain10 Avenue Hippocrate1200 BrusselsBelgium service de Chirurgie et Transplantation Abdominale Cliniques Universitaires Saint-Luc55 Avenue Hippocrate1200 BrusselsBelgium department of Clinical Sciences and Community health Universitàdegli Studi di Milano19 Via della Commenda20122 MilanItaly

Immunosuppression is essential to ensure recipient and graft survivals after liver transplantation(LT). however, our understanding and management of the immune system remain suboptimal. Current immunosuppressive therapy cannot selectively inhibit the graft-specific immune response and entails a significant risk of serious side effects, i.e., among others, de novo cancers, infections, cardiovascular events, renal failure, metabolic syndrome, and late graft fibrosis, with progressive loss of graft function. Pharmacological research, aimed to develop alternative immunosuppressive agents in LT, is behind other solidorgan transplantation subspecialties, and, therefore, the development of new compounds and strategies should get priority in LT. The research trajectories cover mechanisms to induce T-cell exhaustion, to inhibit co-stimulation, to mitigate non-antigen-specific inflammatory response, and, lastly, to minimize the development and action of donor-specific antibodies. Moreover, while cellular modulation techniques are complex, active research is underway to foster the action of T-regulatory cells, to induce tolerogenic dendritic cells, and to promote the function of B-regulatory cells. We herein discuss current lines of research in clinical immunosuppression, particularly focusing on possible applications in the LT setting.

关键词： Liver transplantation Immunosuppression Drug development Long-term results Clinical operational tolerance

Profile of Autoantibodies and Clinical Symptoms in Guinean Patients with Connective Tissue Diseases

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Open Journal of Immunology 2024年第1期14卷 1-10页

作者： Mariama Sadjo Diallo Doufin Traore Adame Diouf Djiba Kaba Issiaga Diallo Doudou Georges Massar niang Alimou Camara Oumar Mouctar Diallo Boh Fanta Diane Abdoulaye Barry Ouo-Ouo Yaramon Kolie Moustapha Mbow Aly Badra Kamissoko Djibril Sylla Babacar Mbengue Mohamed Cisse Faculté des Sciences et Techniques de la Santé Université Gamal Abdel Nasser de Conakry Conakry Guinée Laboratoire de Biologie Moléculaire nestor BAnGOURA/helene LABROUSSE H&#244pital de jour Donka CHU Donka Conakry Guinée Centre d’Excellence Africain Pour la Prévention et le Contrô le des Maladies Transmissibles Conakry Guinée Laboratoire d’Immunologie Université Cheikh Anta Diop Dakar Sénégal service de dermatologie-Vénérologie CHU Donka Conakry Guinée service de Rhumatologie H&#244pital National Ignace Deen Conakry Guinée service de Médecine Interne CHU Donka Conakry Guinée

Connective tissue diseases (CTDs) are Autoimmune diseases (AIDs) characterized by the appearance of autoantibodies, which are diagnostic markers. Investigations of these autoantibodies play a major role in the management of several autoimmune diseases. The objective of this study was to describe the profile of anti-EnA antibodies according to the clinical symptoms of mixed CTDs in Conakry teaching hospital. We performed a cross-sectional study during six months. A total of 20 patients was recruited and we measured antibodies using the ELISA technique. The mean age of our patients was 36.5 years, with a predominance of females. Cutaneous and rheumatological signs were the main clinical manifestations. SLP was the most frequent CTDs;the threshold of EnA antibodies positivity was higher in scleroderma with and SLP. Anti-EnA identification reveals the frequency of anti-SSA (83.33%), anti-U1RnP (66.66%) and anti-histone (50%) antibodies. Antinuclear antibodies (AnA) react with various components of the cell nucleus. Their detection is of major interest in the diagnosis of CTDs. Our results highlight the importance of determining the specificity of these antibodies to guide differential diagnosis.

关键词： Autoantibodies Extractible nuclear Antigen (EnA) Connective Tissue Diseases ELISA