RESUMO
We describe a rare case of severe disseminated monkeypox (MPox) virus infection complicated by peritonitis in a 44-year-old man living with well-controlled HIV. The patient was successfully treated with tecovirimat without requiring surgery. MPox should be considered in the differential diagnosis of non-bacterial peritonitis in patients at risk of infection.
Assuntos
Mpox , Peritonite , Masculino , Humanos , Adulto , Monkeypox virus , Peritonite/diagnóstico , Peritonite/tratamento farmacológico , Peritonite/etiologia , Benzamidas , Diagnóstico DiferencialRESUMO
Rationale: Given the paucity of effective treatments for idiopathic pulmonary fibrosis (IPF), new insights into the deleterious mechanisms controlling lung fibroblast activation, the key cell type driving the fibrogenic process, are essential to develop new therapeutic strategies. TGF-ß (transforming growth factor-ß) is the main profibrotic factor, but its inhibition is associated with severe side effects because of its pleiotropic role. Objectives: To determine if downstream noncoding effectors of TGF-ß in fibroblasts may represent new effective therapeutic targets whose modulation may be well tolerated. Methods: We investigated the whole noncoding fraction of TGF-ß-stimulated lung fibroblast transcriptome to identify new genomic determinants of lung fibroblast differentiation into myofibroblasts. Differential expression of the long noncoding RNA (lncRNA) DNM3OS (dynamin 3 opposite strand) and its associated microRNAs (miRNAs) was validated in a murine model of pulmonary fibrosis and in IPF tissue samples. Distinct and complementary antisense oligonucleotide-based strategies aiming at interfering with DNM3OS were used to elucidate the role of DNM3OS and its associated miRNAs in IPF pathogenesis. Measurements and Main Results: We identified DNM3OS as a fibroblast-specific critical downstream effector of TGF-ß-induced lung myofibroblast activation. Mechanistically, DNM3OS regulates this process in trans by giving rise to three distinct profibrotic mature miRNAs (i.e., miR-199a-5p/3p and miR-214-3p), which influence SMAD and non-SMAD components of TGF-ß signaling in a multifaceted way. In vivo, we showed that interfering with DNM3OS function not only prevents lung fibrosis but also improves established pulmonary fibrosis. Conclusions: Pharmacological approaches aiming at interfering with the lncRNA DNM3OS may represent new effective therapeutic strategies in IPF.
Assuntos
Fibroblastos/metabolismo , Fibrose Pulmonar Idiopática/genética , RNA Longo não Codificante/genética , Fator de Crescimento Transformador beta/metabolismo , Animais , Caveolina 1/metabolismo , Fibrose Pulmonar Idiopática/metabolismo , Camundongos , MicroRNAs/metabolismo , Miofibroblastos/metabolismo , Transdução de Sinais , Proteínas Smad/metabolismo , Via de Sinalização WntRESUMO
Capsule endoscope aspiration is an increasingly reported complication, potentially responsible for respiratory distress and asphyxia. This adverse event is primarily managed by rigid bronchoscopy when spontaneous expulsion does not occur. This complication is all the more detrimental to patients as it can delay or jeopardize further digestive exploration. We report direct repositioning of the capsule in the stomach at the same time as bronchoscopy, thus making second-line gastrointestinal endoscopy needless.
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Asfixia/cirurgia , Brônquios/cirurgia , Broncoscopia/métodos , Cápsulas Endoscópicas , Corpos Estranhos/cirurgia , Aspiração Respiratória/cirurgia , Idoso , Asfixia/diagnóstico , Asfixia/etiologia , Humanos , Masculino , Radiografia Torácica , Aspiração Respiratória/complicações , Aspiração Respiratória/diagnósticoRESUMO
BACKGROUND: Data concerning phenotypes in bronchiectasis are scarce. OBJECTIVE: The aim of this study was to describe the clinical, functional and microbiological phenotypes of patients with bronchiectasis. METHODS: A monocentric retrospective study in a university hospital in France was conducted over 10 years (2002-2012). Non-cystic fibrosis patients with tomographic confirmation of bronchiectasis were included. The clinical, functional and microbiological data of patients were analyzed relying on the underlying etiology. RESULTS: Of the 311 included patients, an etiology was found for 245 of them. At the time of diagnosis, the median age was 61 years and the mean FEV1 was 63% of predicted. The main causes of bronchiectasis were post-infectious (50%, mostly related to tuberculosis), chronic obstructive pulmonary disease (COPD; 13%) and idiopathic (11%). Other causes were immune deficiency (6%), asthma (4%), autoimmunity (3%), tumor (2%) and other causes (4%). The comparison of phenotypic traits shows significant differences between COPD, congenital and idiopathic groups in term of sex (p = 0.0175), tobacco status (p < 0.0001), FEV1 (p = 0.0412) and age at diagnosis (p < 0.001), Pseudomonas aeruginosa (PA) colonization (p = 0.0276) and lobectomy (0.0093). Functional follow-up was available in 30% of patients with a median duration of 2.7 years. Presence of PA was associated with a lower median FEV1 at diagnosis (43% p < 0.003) but not with a faster rate of decline in FEV1. CONCLUSION: Distinctive clinical, functional and microbiological features were found for idiopathic, congenital and COPD-related bronchiectasis. A prospective follow-up of these subgroups is necessary to validate their relevance in the management of bacterial colonization and specific complications of these bronchiectases.
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Bronquiectasia/microbiologia , Adolescente , Adulto , Idoso , Bronquiectasia/epidemiologia , Criança , Pré-Escolar , Feminino , França/epidemiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fenótipo , Pseudomonas aeruginosa/isolamento & purificação , Estudos Retrospectivos , Adulto JovemRESUMO
Introduction: COVID-19 vaccines are expected to provide effective protection. However, emerging strains can cause breakthrough infection in vaccinated individuals. The immune response of vaccinated individuals who have experienced breakthrough infection is still poorly understood. Methods: Here, we studied the humoral and cellular immune responses of fully vaccinated individuals who subsequently experienced breakthrough infection due to the Delta variant of SARS-CoV-2 and correlated them with the severity of the disease. Results: In this study, an effective humoral response alone was not sufficient to induce effective immune protection against severe breakthrough infection, which also required effective cell-mediated immunity to SARS-CoV-2. Patients who did not require oxygen had significantly higher specific (p=0.021) and nonspecific (p=0.004) cellular responses to SARS-CoV-2 at the onset of infection than those who progressed to a severe form. Discussion: Knowing both humoral and cellular immune response could allow to adapt preventive strategy, by better selecting patients who would benefit from additional vaccine boosters. Trial registration numbers: https://clinicaltrials.gov, identifier NCT04355351; https://clinicaltrials.gov, identifier NCT04429594.
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COVID-19 , Vacinas , Humanos , SARS-CoV-2 , Vacinas contra COVID-19 , Infecções Irruptivas , COVID-19/prevenção & controleAssuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Sarcoidose Pulmonar/induzido quimicamente , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Dispneia/etiologia , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pessoa de Meia-Idade , Sarcoidose/induzido quimicamente , Sarcoidose Pulmonar/complicações , Sarcoidose Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Cardiac injury has been reported in up to 30% of coronavirus disease 2019 (COVID-19) patients. However, cardiac injury is defined mainly by troponin elevation without description of associated structural abnormalities and its time course has not been studied. RESEARCH QUESTION: What are the ECG and echocardiographic abnormalities as well as their time course in critically ill COVID-19 patients? STUDY DESIGN AND METHODS: The cardiac function of 43 consecutive COVID-19 patients admitted to two ICUs was assessed prospectively and repeatedly, combining ECG, cardiac biomarker, and transthoracic echocardiographic analyses from ICU admission to ICU discharge or death or to a maximum follow-up of 14 days. Cardiac injury was defined by troponin elevation and newly diagnosed ECG or echocardiographic abnormalities, or both. RESULTS: At baseline, 49% of patients demonstrated a cardiac injury, and 70% of patients experienced cardiac injury within the first 14 days of ICU stay, with a median time of occurrence of 3 days (range, 0-7 days). The most frequent abnormalities were ECG or echocardiographic signs, or both, of left ventricular (LV) abnormalities (87% of patients with cardiac injury), right ventricular (RV) systolic dysfunction (47%), pericardial effusion (43%), new-onset atrial arrhythmias (33%), LV relaxation impairment (33%), and LV systolic dysfunction (13%). Between baseline and day 14, the incidence of pericardial effusion and of new-onset atrial arrhythmias increased and the incidence of ECG or echocardiographic signs, or both, of LV abnormalities as well as the incidence of LV relaxation impairment remained stable, whereas the incidence of RV and LV systolic dysfunction decreased. INTERPRETATION: Cardiac injury is common and early in critically ill COVID-19 patients. ECG or echocardiographic signs, or both, of LV abnormalities were the most frequent abnormalities, and patients with cardiac injury experienced more RV than LV systolic dysfunction.
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COVID-19 , Ecocardiografia/métodos , Eletrocardiografia/métodos , Cardiopatias , Troponina/sangue , Disfunção Ventricular Esquerda , Biomarcadores/sangue , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/fisiopatologia , COVID-19/terapia , Estado Terminal/epidemiologia , Estado Terminal/terapia , Feminino , França/epidemiologia , Cardiopatias/sangue , Cardiopatias/diagnóstico , Cardiopatias/epidemiologia , Cardiopatias/etiologia , Humanos , Incidência , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
INTRODUCTION: Recent practice guidelines suggest applying non-invasive ventilation (NIV) to prevent postextubation respiratory failure in patients at high risk of extubation failure in intensive care unit (ICU). However, such prophylactic NIV has been only a conditional recommendation given the low certainty of evidence. Likewise, high-flow nasal cannula (HFNC) oxygen therapy has been shown to reduce reintubation rates as compared with standard oxygen and to be as efficient as NIV in patients at high risk. Whereas HFNC may be considered as an optimal therapy during the postextubation period, HFNC associated with NIV could be an additional means of preventing postextubation respiratory failure. We are hypothesising that treatment associating NIV with HFNC between NIV sessions may be more effective than HFNC alone and may reduce the reintubation rate in patients at high risk. METHODS AND ANALYSIS: This study is an investigator-initiated, multicentre randomised controlled trial comparing HFNC alone or with NIV sessions during the postextubation period in patients at high risk of extubation failure in the ICU. Six hundred patients will be randomised with a 1:1 ratio in two groups according to the strategy of oxygenation after extubation. The primary outcome is the reintubation rate within the 7 days following planned extubation. Secondary outcomes include the number of patients who meet the criteria for moderate/severe respiratory failure, ICU length of stay and mortality up to day 90. ETHICS AND DISSEMINATION: The study has been approved by the ethics committee and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03121482.
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Unidades de Terapia Intensiva , Ventilação não Invasiva , Oxigenoterapia/métodos , Desmame do Respirador , Extubação , Mortalidade Hospitalar , Humanos , Tempo de Internação , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Respiratória/prevenção & controle , RetratamentoRESUMO
M. pneumoniae respiratory infection is usually mild and self-limiting. We report a case of acute respiratory distress syndrome (ARDS) due to M. pneumoniae infection in a 60 years old woman. Quick diagnosis was established by multiplex PCR assay for detection of pneumonia-causing bacteria. Outcome was favorable. The factors accounting for the severity of pneumonia caused by M. pneumoniae are discussed.