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BACKGROUND AND STUDY AIMS: Endoscopy Ultra-Sound (EUS)-guided fiducial marker placement in patients with esophageal or rectal cancer who have been referred for radiation therapy lacks data regarding its feasibility and safety. The aim of this study was to assess the success rate of EUS-guided fiducial marker placement in these indications. PATIENTS AND METHODS: This prospective multicenter study enrolled patients with rectal or esophageal tumor, who were treated between March 2017 and June 2021. The primary endpoint was the success of fiducial markers placement under EUS guidance utilizing the preloaded 22-gauge EchoTip Ultra Fiducial needle® (Cook Medical, Limerick, Ireland), defined by the ability to release fiducials at least at proximal and distal ends of the tumor. The secondary endpoints were the adverse events, length of procedure, and remaining fiducial markers throughout radiation therapy. RESULTS: A total of 33 patients were included in this study, with a mean age of 64.2 years ±11.3, and 66.7% of males. Twenty patients had rectal adenocarcinoma, and 13 had esophageal malignancies. The success rate of fiducial markers placement was 93.9%. Markers could only be released at the proximal end of the tumor in two cases. The average procedure time (±SD) was 12.5 min (±4.8). The number of fiducial markers placed for each patient was 3.8 (±0.5). No adverse event was reported. At the end of radiotherapy, markers were still visible on imaging in all patients. CONCLUSION: This prospective multicenter study highlights the safety and high success of the placement of fiducial markers under EUS, for rectal and esophageal tumors, without adverse event, and with a short procedure time. Fiducial markers remain in place over time during radiation therapy. CLINICALTRIALS: gov ID: NCT03057288.
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RATIONALE: Acute hypoxaemic respiratory failure (AHRF) is associated with high mortality in sub-Saharan Africa. This is at least in part due to critical care-related resource constraints including limited access to invasive mechanical ventilation and/or highly skilled acute care workers. Continuous positive airway pressure (CPAP) and high-flow oxygen by nasal cannula (HFNC) may prove useful to reduce intubation, and therefore, improve survival outcomes among critically ill patients, particularly in resource-limited settings, but data in such settings are lacking. The aim of this study is to determine whether CPAP or HFNC as compared with standard oxygen therapy, could reduce mortality among adults presenting with AHRF in a resource-limited setting. METHODS: This is a prospective, multicentre, randomised, controlled, stepped wedge trial, in which patients presenting with AHRF in Uganda will be randomly assigned to standard oxygen therapy delivered through a face mask, HFNC oxygen or CPAP. The primary outcome is all-cause mortality at 28 days. Secondary outcomes include the number of patients with criteria for intubation at day 7, the number of patients intubated at day 28, ventilator-free days at day 28 and tolerance of each respiratory support. ETHICS AND DISSEMINATION: The study has obtained ethical approval from the Research and Ethics Committee, School of Biomedical Sciences, College of Health Sciences, Makerere University as well as the Uganda National Council for Science and Technology. Patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04693403. PROTOCOL VERSION: 8 September 2023; version 5.
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Pressão Positiva Contínua nas Vias Aéreas , Oxigenoterapia , Insuficiência Respiratória , Humanos , Pressão Positiva Contínua nas Vias Aéreas/métodos , Oxigenoterapia/métodos , Insuficiência Respiratória/terapia , Insuficiência Respiratória/mortalidade , Estudos Prospectivos , Uganda , Adulto , Hipóxia/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , Doença Aguda , Região de Recursos LimitadosRESUMO
Although sickle cell disease (SCD) patients carry both significant left atrial (LA) remodeling and increased risk of stroke, the prevalence of atrial arrhythmia (AA) has never been prospectively evaluated. This study aims to investigate the prevalence and predictors of atrial arrhythmia in homozygous SCD (SCA). From 2019 to 2022, 130 patients with SCA were referred to the physiology department to specifically analyze cardiac function and prospectively included in the DREPACOEUR registry. They underwent a 24-hour electrocardiogram monitoring (24h-Holter), transthoracic echocardiography, and laboratory tests on the same day. The primary endpoint was the occurrence of AA, defined by the presence of excessive supraventricular ectopic activity (ESVEA) on ECG-Holter (i.e., >720 premature atrial contractions [PACs] or any run ≥ 20 PACs), recent history of paroxysmal atrial fibrillation (AF), or persistent AF. The mean patient age was 45±12 years and 48% of male. Overall, AA was found in 34 (26%) patients. Age (52±9 vs. 42±12 years, P=0.002), LA dilation (LAVi, 71±24 vs. 52±14 ml/m², P<0.001) and history of stroke without underlying cerebral vasculopathy or other defined cause (26% vs. 5%, P=0.009, OR=6.6 [1.4; 30.3]) were independently associated with AA. Age and LAVi correlated with PAC load per 24 hours on ECG-Holter (R=0.56 and 0.33, P<0.001 respectively) and an age over 47 years or a LAVi >55mL/m² could predict AA with a PPV of 33% and a NPV of 92%. AAs are frequent in SCA patients and increase with age and LA remodeling, leading to a major additional risk factor for ischemic stroke. This study provides arguments and means to early screen for AA potentially preventing cerebral complications.
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BACKGROUND: General practitioners (GPs) were on the front line of the COVID-19 outbreak. Identifying clinical profiles in COVID-19 might improve patient care and enable closer monitoring of at-risk profiles. OBJECTIVES: To identify COVID-19 profiles in a population of adult primary care patients, and to determine whether the profiles were associated with negative outcomes and persistent symptoms. DESIGN, SETTING AND PARTICIPANTS: In a prospective multicentre study, 44 GPs from multiprofessional primary care practices in the Paris area of France recruited 340 consecutive adult patients (median age: 47 years) with a confirmed diagnosis of COVID-19 during the first two waves of the epidemic. METHOD AND OUTCOME: A latent class (LC) analysis with 11 indicators (clinical signs and symptoms) was performed. The resulting profiles were characterised by a 3-month composite outcome (COVID-19-related hospital admission and/or death) and persistent symptoms three and 6 months after inclusion. RESULTS: We identified six profiles: 'paucisymptomatic' (LC1, 9%), 'anosmia and/or ageusia' (LC2, 12.9%), 'influenza-like syndrome with anosmia and ageusia' (LC3, 15.5%), 'influenza-like syndrome without anosmia or ageusia' (LC4, 24.5%), 'influenza-like syndrome with respiratory impairment' (LC5) and a 'complete form' (LC6, 17.7%). At 3 months, 7.4% of the patients were hospitalised (with higher rates in LC5), and 18% had persistent symptoms (with higher rates in LC5 and LC6). At 6 months, 6.4% of the patients had persistent symptoms, with no differences between LCs. CONCLUSION: Our findings might help GPs to identify patients at risk of persistent COVID-19 symptoms and hospital admission and then set up procedures for closer monitoring.
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COVID-19 , Medicina Geral , Análise de Classes Latentes , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/diagnóstico , Pessoa de Meia-Idade , Masculino , Feminino , Estudos Prospectivos , Adulto , Medicina Geral/estatística & dados numéricos , Idoso , França/epidemiologia , Hospitalização/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Paris/epidemiologia , Anosmia/epidemiologia , Ageusia/epidemiologiaRESUMO
BACKGROUND: A notable increase in severe cases of COVID-19, with significant hospitalizations due to the emergence and spread of JN.1 was observed worldwide in late 2023 and early 2024. However, no clinical data are available regarding critically-ill JN.1 COVID-19 infected patients. METHODS: The current study is a substudy of the SEVARVIR prospective multicenter observational cohort study. Patients admitted to any of the 40 participating ICUs between November 17, 2022, and January 22, 2024, were eligible for inclusion in the SEVARVIR cohort study (NCT05162508) if they met the following inclusion criteria: age ≥ 18 years, SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction (RT-PCR) in nasopharyngeal swab samples, ICU admission for acute respiratory failure. The primary clinical endpoint of the study was day-28 mortality. Evaluation of the association between day-28 mortality and sublineage group was conducted by performing an exploratory multivariable logistic regression model, after systematically adjusting for predefined prognostic factors previously shown to be important confounders (i.e. obesity, immunosuppression, age and SOFA score) computing odds ratios (OR) along with their corresponding 95% confidence intervals (95% CI). RESULTS: During the study period (November 2022-January 2024) 56 JN.1- and 126 XBB-infected patients were prospectively enrolled in 40 French intensive care units. JN.1-infected patients were more likely to be obese (35.7% vs 20.8%; p = 0.033) and less frequently immunosuppressed than others (20.4% vs 41.4%; p = 0.010). JN.1-infected patients required invasive mechanical ventilation support in 29.1%, 87.5% of them received dexamethasone, 14.5% tocilizumab and none received monoclonal antibodies. Only one JN-1 infected patient (1.8%) required extracorporeal membrane oxygenation support during ICU stay (vs 0/126 in the XBB group; p = 0.30). Day-28 mortality of JN.1-infected patients was 14.6%, not significantly different from that of XBB-infected patients (22.0%; p = 0.28). In univariable logistic regression analysis and in multivariable analysis adjusting for confounders defined a priori, we found no statistically significant association between JN.1 infection and day-28 mortality (adjusted OR 1.06 95% CI (0.17;1.42); p = 0.19). There was no significant between group difference regarding duration of stay in the ICU (6.0 [3.5;11.0] vs 7.0 [4.0;14.0] days; p = 0.21). CONCLUSIONS: Critically-ill patients with Omicron JN.1 infection showed a different clinical phenotype than patients infected with the earlier XBB sublineage, including more frequent obesity and less immunosuppression. Compared with XBB, JN.1 infection was not associated with higher day-28 mortality.
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This pilot study focusing on Sickle Cell Anemia (SCA) patients offers a comprehensive and integrative evaluation of respiratory, cardiovascular, hemodynamic, and metabolic variables during exercise. Knowing that diastolic dysfunction is frequent in this population, we hypothesize that a lack of cardiac adaptation through exercise might lead to premature increase in blood lactate concentrations in SCA patients, a potential trigger for acute disease complication. SCA patients were prospectively included in PHYSIO-EXDRE study and underwent a comprehensive stress test with a standardized incremental exercise protocol up to 4 mmol L-1 blood lactate concentration (BL4). Gas exchange, capillary lactate concentration and echocardiography were performed at baseline, during stress test (at â¼ 2 mmol L-1) and BL4. The population was divided into two groups and compared according to the median value of percentage of theoretical peak oxygen uptake (% V Ë O 2 p e a k t h ) at BL4. Twenty-nine patients were included (42 ± 12 years old, 48% of women). Most patients reached BL4 at low-intensity exercise [median value of predicted power output (W) was 37%], which corresponds to daily life activities. The median value of % V Ë O 2 p e a k t h at BL4 was 39%. Interestingly, diastolic maladaptation using echocardiography during stress test along with hemoglobin concentration were independently associated to early occurrence of BL4. As BL4 occurs for low-intensity exercises, SCA patients may be subject to acidosis-related complications even during their daily life activities. Beyond assessing physical capacities, our study underlines that diastolic maladaptation during exercise is associated with an early increase in blood lactate concentration.
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Anemia Falciforme , Diástole , Tolerância ao Exercício , Humanos , Anemia Falciforme/fisiopatologia , Anemia Falciforme/complicações , Anemia Falciforme/sangue , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Teste de Esforço , Projetos Piloto , Ecocardiografia , Adaptação Fisiológica , Ácido Láctico/sangue , Estudos Prospectivos , Consumo de Oxigênio , Exercício Físico/fisiologiaRESUMO
OBJECTIVE: To compare reintubation rates after planned extubation and unplanned extubation (UE) in patients in neonatal intensive care units (NICUs), to analyse risk factors for reintubation after UE and to compare outcomes in patients with and without UE. DESIGN: Prospective, observational study nested in a randomised controlled trial (SEPREVEN/Study on Epidemiology and PRevention of adverse EVEnts in Neonates). Outcomes were expected to be independent of the intervention tested. SETTING: 12 NICUs in France with a 20-month follow-up, starting November 2015. PATIENTS: n=2280 patients with a NICU stay >2 days, postmenstrual age ≤42 weeks on admission. INTERVENTIONS/EXPOSURE: Characteristics of UE (context, timing, sedative administration in the preceding 6 hours, weaning from ventilation at time of UE) and patients. MAIN OUTCOME MEASURES: Healthcare professional-reported UE rates, reintubation/timing after extubation, duration of mechanical ventilation, mortality and bronchopulmonary dysplasia (BPD). RESULTS: There were 162 episodes of UE (139 patients, median gestational age (IQR) 27.3 (25.6-31.7) weeks). Cumulative reintubation rates within 24 hours and 7 days of UE were, respectively, 50.0% and 57.5%, compared with 5.5% and 12.3% after a planned extubation. Independent risk factors for reintubation within 7 days included absence of weaning at the time of UE (HR, 95% CI) and sedatives in the preceding 6 hours (HR 1.93, 95% CI 1.04 to 3.60). Mortality at discharge did not differ between patients with planned extubation or UE. UE was associated with a higher risk of BPD. CONCLUSION: In the SEPREVEN trial, reintubation followed UE in 58% of the cases, compared with 12% after planned extubation. TRIAL REGISTRATION NUMBER: NCT02598609.
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BACKGROUND: The systematic use of susceptibility testing and tailored first-line treatment for Helicobacter pylori eradication has yet to be established. AIM: To compare 14-day tailored PCR-guided triple therapy to 14-day non-Bismuth concomitant quadruple therapy for first-line Helicobacter pylori eradication. PATIENTS AND METHODS: We performed a multicenter, parallel-group, randomized noninferiority controlled trial. Naive adult patients with Helicobacter pylori infection were treated with 14-day tailored PCR-guided triple therapy (esomeprazole 40 mg and amoxicillin 1000 mg b.d. plus clarithromycin 500 mg or levofloxacin 500 mg b.d. according to clarithromycin susceptibility) or 14-day non-Bismuth concomitant quadruple therapy (esomeprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and metronidazole 500 mg b.d.). The primary endpoint was H. pylori eradication. RESULTS: We screened 991 patients for eligibility and randomized 241 patients. The first-line eradication rate was 99.2% in the tailored PCR-guided group and 95.9% in the control group (ITT population; absolute difference of +3.30%, with a lower bound of CI at -0.68%). Both first-line therapies were well tolerated, with a formally significant difference in favor of the tailored PCR-guided group (61.4% vs. 41.2%, p = 0.003). Economic analyses revealed a lower cost of the tailored PCR-guided arm, with a 92% chance of being jointly more effective and less expensive than the control arm in the ITT population. CONCLUSION: In a country with a high level of clarithromycin resistance, the results of our study demonstrated the noninferiority of 14-day tailored PCR-guided triple therapy as a first-line H. pylori eradication therapy compared to 14-day non-Bismuth quadruple therapy (ClinicalTrials.gov NCT02576236).
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Antibacterianos , Claritromicina , Quimioterapia Combinada , Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Masculino , Feminino , Pessoa de Meia-Idade , Helicobacter pylori/efeitos dos fármacos , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Adulto , Claritromicina/uso terapêutico , Claritromicina/administração & dosagem , Reação em Cadeia da Polimerase/métodos , Amoxicilina/uso terapêutico , Amoxicilina/administração & dosagem , Idoso , Resultado do Tratamento , Metronidazol/uso terapêutico , Metronidazol/administração & dosagem , Levofloxacino/uso terapêutico , Levofloxacino/administração & dosagem , Adulto JovemRESUMO
BACKGROUND: During the first COVID-19 pandemic wave, COVID-19-associated pulmonary aspergillosis (CAPA) has been reported in up to 11-28% of critically ill COVID-19 patients and associated with increased mortality. As new SARS-CoV-2 variants emerged, the characteristics of critically ill COVID-19 patients have evolved, particularly in the era of Omicron. The purpose of this study is to investigate the characteristics of CAPA in the era of new variants. METHODS: This is a prospective multicenter observational cohort study conducted in France in 36 participating intensive care units (ICU), between December 7th, 2021 and April 26th 2023. Diagnosis criteria of CAPA relied on European Confederation of Medical Mycology (ECMM)/International Society for Human & Animal Mycology (ISHAM) consensus criteria. RESULTS: 566 patients were included over the study period. The prevalence of CAPA was 5.1% [95% CI 3.4-7.3], and rose to 9.1% among patients who required invasive mechanical ventilation (IMV). Univariable analysis showed that CAPA patients were more frequently immunosuppressed and required more frequently IMV support, vasopressors and renal replacement therapy during ICU stay than non-CAPA patients. SAPS II score at ICU admission, immunosuppression, and a SARS-CoV-2 Delta variant were independently associated with CAPA in multivariable logistic regression analysis. Although CAPA was not significantly associated with day-28 mortality, patients with CAPA experienced a longer duration of mechanical ventilation and ICU stay. CONCLUSION: This study contributes valuable insights into the prevalence, characteristics, and outcomes of CAPA in the era of Delta and Omicron variants. We report a lower prevalence of CAPA (5.1%) among critically-ill COVID-19 patients than previously reported, mainly affecting intubated-patients. Duration of mechanical ventilation and ICU stay were significantly longer in CAPA patients.
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INTRODUCTION: The surveillance of hepatocellular carcinoma (HCC) using semi-annual liver ultrasound (US) is justified in patients with cirrhosis. In this context, US has a low sensitivity (<30%) for the detection of HCC at the very early stage (ie, Barcelona clinic liver cancer (BCLC) 0, uninodular tumour <2 cm). The sensitivity of abbreviated liver MRI (AMRI) is reported to exceed 80%, but its use is hampered by costs and availability. Our hypothesis is that AMRI used as a screening examination in patients at high risk of HCC (>3% per year) could increase the rates of patients with a tumour detected at an early stage accessible to curative-intent treatment, and demonstrate its cost-effectiveness in this population. METHODS AND ANALYSIS: The FASTRAK trial is a multicentre, randomised controlled trial with two parallel arms, aiming for superiority and conducted on patients at high risk for HCC (yearly HCC incidence >3%). Randomisation will be conducted on an individual basis with a centralised approach and stratification by centre. After inclusion in the trial, each patient will be randomly assigned to the experimental group (semi-annual US and AMRI) or the control group (semi-annual US alone). The main objective is to assess the cost/quality-adjusted life year and cost/patient detected with a BCLC 0 HCC in both arms. A total of 944 patients will be recruited in 37 tertiary French centres during a 36-month period and will be followed-up during 36 months. ETHICS AND DISSEMINATION: The FASTRAK trial received ethical approval on 4 April 2022. Results will be disseminated via publication in peer-reviewed journals as well as presentation at international conferences. TRIAL REGISTRATION NUMBER: Clinical trial number (ClinicaTrials.gov) NCT05095714.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/etiologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/etiologia , Imageamento por Ressonância Magnética/métodos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico por imagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND AND AIMS: HCC surveillance is challenged by the detection of hepatic focal lesions (HFLs) of other types. This study aimed to describe the incidence, characteristics, outcomes, and costs of non-HCC HFL detected during surveillance. APPROACH AND RESULTS: We retrospectively analyzed nonstandardized workup performed in French patients included in HCC surveillance programs recruited in 57 French tertiary centers (ANRS CirVir and CIRRAL cohorts, HCC 2000 trial). The overall cost of workup was evaluated, with an estimation of an average cost per patient for the entire population and per lesion detected. A total of 3295 patients were followed up for 59.8 months, 391 (11.9%) patients developed HCCs (5-year incidence: 12.1%), and 633 (19.2%) developed non-HCC HFLs (5-year incidence: 21.8%). Characterization of non-HCC HFL required a median additional of 0.7 exams per year. A total of 11.8% of non-HCC HFLs were not confirmed on recall procedures, and 19.6% of non-HCC HFLs remained undetermined. A definite diagnosis of benign liver lesions was made in 65.1%, and malignant tumors were diagnosed in 3.5%. The survival of patients with benign or undetermined non-HCC HFL was similar to that of patients who never developed any HFL (5-year survival 92% vs. 88%, p = 0.07). The average cost of the diagnostic workup was 1087 for non-HCC HFL and 1572 for HCC. CONCLUSIONS: Non-HCC HFLs are frequently detected in patients with cirrhosis, and do not impact prognosis, but trigger substantial costs. This burden must be considered in cost-effectiveness analyses of future personalized surveillance strategies.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/etiologia , Neoplasias Hepáticas/etiologia , Estudos Retrospectivos , Estresse Financeiro , Cirrose Hepática/epidemiologia , Cirrose Hepática/complicaçõesRESUMO
OBJECTIVE: Left atrial appendage closure (LAAC) is recommended to decrease the stroke risk in patients with atrial fibrillation and contraindications to anticoagulation. However, age-stratified data are scarce. The aim of this study was to provide information on the safety and efficacy of LAAC, with emphasis on the oldest patients. METHODS: A nationwide, prospective, multicentre, observational registry was established by 53 French cardiology centres in 2018-2021. The composite primary endpoint included ischaemic stroke, systemic embolism, and unexplained or cardiovascular death. Separate analyses were done in the groups <80 years and ≥80 years. RESULTS: Among the 1053 patients included, median age was 79.7 (73.6-84.3) years; 512 patients (48.6%) were aged ≥80 years. Procedure-related serious adverse events were non-significantly more common in octogenarians (7.0% vs 4.4% in patients aged <80 years, respectively; p=0.07). Despite a higher mean CHA2DS2-VASc score in octogenarians, the rate of thromboembolic events during the study was similar in both groups (3.0 vs 3.1/100 patient-years; p=0.85). By contrast, all-cause mortality was significantly higher in octogenarians (15.3 vs 10.1/100 patient-years, p<0.015), due to a higher rate of non-cardiovascular deaths (8.2 vs 4.9/100 patient-years, p=0.034). The rate of the primary endpoint was 8.1/100 patient-years overall with no statistically significant difference between age groups (9.4 and 7.0/100 patient-years; p=0.19). CONCLUSION: Despite a higher mean CHA2DS2-VASc score in octogenarians, the rate of thromboembolic events after LAAC in this age group was similar to that in patients aged <80 years. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03434015).
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Apêndice Atrial , Fibrilação Atrial , Isquemia Encefálica , Acidente Vascular Cerebral , Tromboembolia , Idoso , Idoso de 80 Anos ou mais , Humanos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Oclusão do Apêndice Atrial Esquerdo , Resultado do Tratamento , Estudos Prospectivos , Isquemia Encefálica/complicações , Fibrilação Atrial/complicações , Fibrilação Atrial/cirurgia , Tromboembolia/epidemiologia , Tromboembolia/etiologia , Tromboembolia/prevenção & controle , Apêndice Atrial/cirurgia , Sistema de Registros , AnticoagulantesRESUMO
Both HIV-1 infection and smoking may contribute to the development of ageing-related manifestations affecting the prognosis of people living with HIV, but it is unclear whether HIV and smoking exert their effects independently or interact by potentiating each other. We conducted a cross-sectional study in 192 people living with HIV aged- and gender-matched with 192 HIV-uninfected controls, assessing the relative effect of HIV-1/smoking status on lung function (FEV1), bone mineral density (BMD), appendicular skeletal muscle mass index (ASMI), aortic pulse-wave velocity (PWV), insulin resistance (HOMA-IR) and renal function. In both unadjusted and adjusted analyses, FEV1, BMD and ASMI significantly differed according to smoking/HIV status, with the worst parameters found in HIV-1 infected patients currently smoking, and BMD and ASMI decreased to a lesser extent in HIV-1 infected patients formerly smoking (> 10 pack-years). Values in people living with HIV with < 10 pack-years exposure were of similar magnitude to those from controls. Regarding PWV, HOMA-R and eGFR, no significant differences were found, with the exception of eGFR values which were globally lower in HIV-1 infected patients. In conclusion HIV infection and smoking acted synergistically and were associated with a wasting phenotype combining muscle mass and bone mineral reduction.Clinical Trial Registration (registrar, website, and registration number), where applicable: CPP 10-023, 09-027, 10-034.
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Infecções por HIV , Soropositividade para HIV , Humanos , Idoso , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Fumar/efeitos adversos , Estudos Transversais , Envelhecimento , Fumar Tabaco , Soropositividade para HIV/complicações , Densidade ÓsseaRESUMO
We previously reported initial clinical results of post-transcriptional gene silencing of BCL11A expression (NCT03282656) reversing the fetal to adult hemoglobin switch. A goal of this approach is to increase fetal hemoglobin (HbF) expression while coordinately reducing sickle hemoglobin (HbS) expression. The resulting combinatorial effect should prove effective in inhibiting HbS polymerization at lower physiologic oxygen values thereby mitigating disease complications. Here we report results of exploratory single-cell analysis of patients in which BCL11A is targeted molecularly and compare results with cells of patients treated with hydroxyurea (HU), the current standard of care. We use single-cell assays to assess HbF, HbS, oxygen saturation, and hemoglobin polymer content in RBCs for nine gene therapy trial subjects (BCLshmiR, median HbF% = 27.9) and compare them to 10 HU-treated subjects demonstrating high and comparable levels of HbF (HU High Responders, median HbF% = 27.0). All BCL11A patients achieved the primary endpoint for NCT03282656, which was defined by an absolute neutrophil count greater than or equal to 0.5 × 109 cells/L for three consecutive days, achieved within 7 weeks following infusion. Flow cytometric assessment of single-RBC HbF and HbS shows fewer RBCs with high HbS% that would be most susceptible to sickling in BCLshmiR vs. HU High Responders: median 42% of RBCs with HbS%>70% in BCLshmiR vs. 61% in HU High Responders (p = 0.004). BCLshmiR subjects also demonstrate more RBCs resistant to HbS polymerization at lower physiologic oxygen tension: median 32% vs. 25% in HU High Responders (p = 0.006). Gene therapy-induced BCL11A down-regulation reverses the fetal-to-adult hemoglobin switch and induces RBCs with higher HbF%, lower HbS%, and greater resistance to deoxygenation-induced polymerization in clinical trial subjects compared with a cohort of highly responsive hydroxyurea-treated subjects.
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Hemoglobina Falciforme , Hidroxiureia , Adulto , Humanos , Hidroxiureia/farmacologia , Hidroxiureia/uso terapêutico , Eritrócitos , Feto , Hemoglobina Fetal/genética , Fatores de TranscriçãoRESUMO
BACKGROUND: Surgical resection (SR) is a potentially curative treatment of hepatocellular carcinoma (HCC) hampered by high rates of recurrence. New drugs are tested in the adjuvant setting, but standardised risk stratification tools of HCC recurrence are lacking. OBJECTIVES: To develop and validate a simple scoring system to predict 2-year recurrence after SR for HCC. METHODS: 2359 treatment-naïve patients who underwent SR for HCC in 17 centres in Europe and Asia between 2004 and 2017 were divided into a development (DS; n = 1558) and validation set (VS; n = 801) by random sampling of participating centres. The Early Recurrence Score (ERS) was generated using variables associated with 2-year recurrence in the DS and validated in the VS. RESULTS: Variables associated with 2-year recurrence in the DS were (with associated points) alpha-fetoprotein (<10 ng/mL:0; 10-100: 2; >100: 3), size of largest nodule (≥40 mm: 1), multifocality (yes: 2), satellite nodules (yes: 2), vascular invasion (yes: 1) and surgical margin (positive R1: 2). The sum of points provided a score ranging from 0 to 11, allowing stratification into four levels of 2-year recurrence risk (Wolbers' C-indices 66.8% DS and 68.4% VS), with excellent calibration according to risk categories. Wolber's and Harrell's C-indices apparent values were systematically higher for ERS when compared to Early Recurrence After Surgery for Liver tumour post-operative model to predict time to early recurrence or recurrence-free survival. CONCLUSIONS: ERS is a user-friendly staging system identifying four levels of early recurrence risk after SR and a robust tool to design personalised surveillance strategies and adjuvant therapy trials.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/patologia , Prognóstico , Estudos Retrospectivos , Período Pós-Operatório , Recidiva Local de Neoplasia/patologia , HepatectomiaRESUMO
BACKGROUND: Despite current broad natural and vaccine-induced protection, a substantial number of patients infected with emerging SARS-CoV-2 variants (e.g., BF.7 and BQ.1.1) still experience severe COVID-19. Real-life studies investigating the impact of these variants on clinical outcomes of severe cases are currently not available. We performed a prospective multicenter observational cohort study. Adult patients with acute respiratory failure admitted between December 7, 2021 and December 15, 2022, in one of the 20 participating intensive care units (17 from the Greater Paris area and 3 from the North of France) were eligible for inclusion if they had SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction (RT-PCR). Full-length SARS-CoV-2 genomes from all included patients were sequenced by means of next-generation sequencing. The primary endpoint of the study was day-28 mortality. RESULTS: The study included 158 patients infected with three groups of Omicron sublineages, including (i) BA.2 variants and their early sublineages referred as "BA.2" (n = 50), (ii) early BA.4 and BA.5 sublineages (including BA.5.1 and BA.5.2, n = 61) referred as "BA.4/BA.5", and (iii) recent emerging BA.5 sublineages (including BQ.1, BQ.1.1, BF.7, BE.1 and CE.1, n = 47) referred as "BQ.1.1". The clinical phenotype of BQ1.1-infected patients compared to earlier BA.2 and BA.4/BA.5 sublineages, showed more frequent obesity and less frequent immunosuppression. There was no significant difference between Omicron sublineage groups regarding the severity of the disease at ICU admission, need for organ failure support during ICU stay, nor day 28 mortality (21.7%, n = 10/47 in BQ.1.1 group vs 26.7%, n = 16/61 in BA.4/BA.5 vs 22.0%, n = 11/50 in BA.2, p = 0.791). No significant relationship was found between any SARS-CoV-2 substitution and/or deletion on the one hand and survival on the other hand over hospital follow-up. CONCLUSIONS: Critically-ill patients with Omicron BQ.1.1 infection showed a different clinical phenotype than other patients infected with earlier Omicron sublineage but no day-28 mortality difference.
RESUMO
BACKGROUND: Early cardiac amyloidosis (CA) diagnosis enables patients to access effective treatments for better long-term outcomes, yet it remains under-recognised, misdiagnosed and inadequately managed. AIM: To reduce diagnostic delays, we aimed to describe the epidemiological and clinical characteristics and changes over an 11-year period. METHODS: This was a retrospective, observational cohort study of all patients referred to the Henri-Mondor Hospital for suspected CA. RESULTS: Overall, 3194 patients were identified and 3022 were included and analysed. Our patients came from varied ethnic backgrounds, and more than half (55.2%) had confirmed CA. Over 11 years, referrals increased 4.4-fold, mostly from cardiologists. Notably, wild-type transthyretin amyloidosis (ATTRwt) became the predominant diagnosis, with referrals increasing 15-fold from 20 in 2010-2012 to 308 in 2019-2020. The number of amyloid light chain (AL) diagnoses increased, whilst variant transthyretin amyloidosis (ATTRv) numbers remained relatively stable. Concerning disease severity, AL patients presented more frequently with severe cardiac involvement whereas an increasing number of ATTRwt patients presented with National Amyloid Centre stage I (22.0% in 2013-2014 to 45.9% in 2019-2020). Lastly, among patients diagnosed with ATTRv in 2019-2020, 83.9% had ATTR Val122Ile cardiac phenotype. CONCLUSIONS: This study shows that increasing cardiologist awareness and referrals have increased CA diagnoses. With improved awareness and non-invasive diagnostic techniques, more patients with ATTRwt with milder disease and more ATTRv Val122Ile mutations are being referred and diagnosed. Although more AL cases are being recognised, patients are diagnosed with severe cardiac involvement.