Introduction Acute respiratory distress syndrome (ARDS) is a major public health problem, accounting for 23% of intubated patients and associated with high mortality rates. Although lifesaving, invasive mechanical ventilation can worsen lung injury when ventilator settings are poorly adjusted to lung physiology. We hypothesise that individualising ventilator settings via (1) the bedside assessment of lung recruitability using a one-breath derecruitment manoeuvre and measurement of airway opening pressure to set positive end-expiratory pressure (PEEP), (2) controlling the distending pressure and (3) controlling respiratory drive improves ARDS outcomes.Methods and analysis The CAreful Ventilation In ARDS trial is an investigator-led multicentre (33 centres in eight countries), open-label, randomised controlled basket trial comparing two ventilation strategies in two subpopulations of moderate-to-severe ARDS: induced or not by COVID-19. A total of 740 patients will be randomised (370 in each substudy) in a 1:1 ratio to individualised ventilator settings or to using traditional PEEP to inspired fraction of oxygen tables for PEEP setting. Indications for proning and weaning strategies are similar in both arms. The primary outcome is all-cause mortality at day 60. Secondary outcomes include duration of mechanical ventilation, duration of intensive care unit (ICU) and hospital stay, organ dysfunction, barotrauma and mortality in ICU, at day 28 and in hospital.Ethics and dissemination Ethics approval has been obtained for all participating centres: Unity Health Toronto Research Ethics Board (for three centres: St Michael’s Hospital, Toronto General Hospital and Toronto Western Hospital); Comité de Ética de Investigación con Medicamentos del Hospital Universitari Vall d’Hebron; Comité de protection des personnes Ile de France III; Comité d'Ética de la Investigatción con Medicamentos de la Fundació de Gestió Sanitària del Hospital de la Santa Creu i Sant Pau; Comitato Etico—Fondazione Policlinico Gemelli; Comitato Etico di Area Vasta Emilia Centro; NYU Langone Health Institutional Review Board; Comité Ético Científico de Ciencias de la Salud; Il Comitato Etico Area 1 dell’Azienda Ospedaliero-Universitaria ‘Ospedali Riuniti’ di Foggia; HIGA ‘Eva Perón’ Comité de Bioética; Comité de Revisión Institucional del Hospital Británico Comité de Ética en Investigación; Complejo Médico Churruca-Visca Comité de Ética Biomédica; Comité de Ética SATI Comité de Ética en Investigación; Comité de Ética en Investigación del CEMIC; Comité de Ética SATI Comité de Ética en Investigación; Medical Research Ethics Committees United. Findings will be disseminated in peer review journals and conference presentations.Trial registration number NCT03963622.

IntroductionCOVID-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.MethodsHere, 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.ResultsIn 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.DiscussionKnowing 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 numbershttps://clinicaltrials.gov, identifier NCT04355351; https://clinicaltrials.gov, identifier NCT04429594.

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.

Abstract Background: Acute myeloid leukemia (AML) is associated with a high rate of life-threatening early complications. Patients presenting with hyperleukocytosis >50x10⁹/L and/or promyelocytic leukemia at the time of AML diagnosis can be considered at high risk of early complications (HReC) and thus at high risk of mortality. At our institution, we propose preemptive ICU admission to HReC patients. In so doing, our goal is to prevent complication occurrence, or, failing that, to provide rapid life-sustaining treatment (LST). In the present retrospective study, we sought to determine whether preemptive ICU admission improves survival for patients newly diagnosed with AML. Results: We analyzed a total study population of 634 patients within a ten-year period. Of that population, 24.7% (n=157) was admitted to the ICU, 20.5% (n=130) due to complications and 4.2% (n=27) preemptively. Delays to ICU admission were 12.9 hours, 7 days and 181 days for respectively the preemptive, early complications and late complications groups, p<0.001. The preemptive group showed significantly better survival at one month post ICU admission (66.7%) compared to the early (37.7%) and late (46.4%) complications groups, p=0.039. Furthermore, LST recourse in the ICU was significantly lower in the preemptive group (41% (n=11)) compared to the early (73% (n=56)) and late (73% (n=41)) complications groups, p<0.001. However, when considering survival at one-month post AML diagnosis, no significant differences were observed between patients admitted preemptively and those admitted following complications. Additionally, Cox regression identified preemptive ICU admission as a predictive factor for mortality at one month post AML diagnosis (hazard ratio 2.72, p<0.013). These contradictory data may be explained by selection and chronological biases when the analysis is limited to only ICU patients. Conclusion: Preemptive ICU admission does not improve survival for patients with AML. Suggested benefits for preemptive ICU admission may reflect analysis biases.

Introduction The use of two quality-of-life questionnaires in a single clinical trial with an economic component can be challenging due to the associated workload in terms of data collection and an increased risk of missing data. The aim of our study was to determine whether the questionnaire chosen to measure health status, the St. George’s Respiratory Questionnaire (SGRQ), could be administered on its own without adding the EuroQol five dimensions questionnaire (EQ-5D) for economic evaluation in emphysema studies. Materials and Methods Data were prospectively collected during the REVOLENS trial assessing endobronchial coil treatment in severe emphysema. To quantify the association between the two questionnaires, correlations between the EQ-5D and the SGRQ were first tested and the concordance was then studied in order to know whether the two questionnaires were interchangeable. Finally, the Starkie et al algorithm predicting EQ-5D utility values from the SGRQ was used on REVOLENS’s individual patient data. The Student’s t-test, correlation and concordance between EQ-5D individual value (from the REVOLENS study) and predicted value (from the Starkie et al algorithm) were studied to test this algorithm. Results Results showed a strong correlation but no concordance between the EQ-5D and the SGRQ, demonstrating that the two questionnaires are not interchangeable. Moreover, the algorithm predicting EQ-5D utilities from the SGRQ did not provide utility values comparable to those observed in the REVOLENS study. Indeed, our study demonstrated a strong correlation between predicted and individual EQ-5D values but no concordance. Conclusion The use of both the EQ-5D and the SGRQ in a clinical study with an economic component is justified. Based on our results, the SGRQ should not be used to obtain a utility score to calculate the incremental cost-effectiveness ratio and conclude on the efficiency of an intervention in emphysema patients.

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.

Clinical practice guidelines that recommend women avoid pregnancy immediately after bariatric surgery, highlighting the need for effective contraception. However, women with a history of malabsorptive bariatric procedures should generally not use oral contraceptives, as these procedures may decrease oral contraceptive effectiveness.To identify provider characteristics associated with knowledge of combined oral contraceptive (COC) effectiveness.United States.We analyzed weighted survey data collected from national samples of public-sector health centers and office-based physicians who regularly provide family planning services (N = 2060). We asked providers about the effectiveness of COCs for women with a history of malabsorptive procedures compared with healthy women, giving them the response options of more/equally effective, less effective, and do not know. We used multinomial logistic regression to calculate adjusted odds ratios and 95% confidence intervals to identify characteristics associated with knowledge of COC effectiveness.Approximately 55% of providers correctly answered that COCs are less effective for women with malabsorptive procedures; 25% considered COCs more/equally effective, and 20% were uncertain. Among public-sector providers, the adjusted odds of uncertainty were significantly higher for those whose clinical focus was not reproductive health, for nurses versus advanced practice clinicians, and for providers working in clinics without Title X funding. For office-based physicians, adolescent medicine providers had higher odds of uncertainty versus obstetrician-gynecologists. Physicians practicing in settings classified as “other” (such as community health centers) had higher odds of considering COCs effective compared with those practicing in hospital or university clinics.Substantial proportions of surveyed providers had inadequate knowledge of COC effectiveness for women with a history of malabsorptive procedures.

Non-coding RNAs have recently gained widespread attention given their broad implication in the initiation and progression of various complex diseases. Whereas previous studies on fibrotic lung disorders, especially the idiopathic form (IPF), have mainly focused on miRNAs, the precise contribution of other class of non-coding RNAs in lung fibrogenesis is unclear. Given the paucity of effective treatment in 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 for this devastating disease. Here we identify a long non-coding RNA, termed DNM3OS, which tightly controls the various cellular and molecular phenotypic changes occurring during lung fibroblast activation in response to TGF-β. Notably, DNM3OS regulates these processes in trans by giving rise to 3 distinct profibrotic miRNAs (i.e. miR-199a-5p/3p and miR-214-3p), which repress distinct but functionally related targets within TGF-β signaling cascade. Finally, we provide in vivo evidence that interfering with DNM3OS function may be a promising strategy for the treatment of lethal fibrotic diseases such as IPF.

Key PointsQuestionAmong mechanically ventilated patients at high risk of extubation failure, does the use of high-flow nasal oxygen with noninvasive ventilation after extubation reduce the risk of reintubation compared with high-flow nasal oxygen alone? FindingsIn this randomized clinical trial that included 641 patients, high-flow nasal oxygen with noninvasive ventilation, compared with high-flow nasal oxygen alone, significantly decreased the rate of reintubation within the first 7 days after extubation (11.8% vs 18.2%). MeaningIn patients at high risk of extubation failure, the use of high-flow nasal oxygen with noninvasive ventilation after extubation significantly decreased the risk of reintubation compared with high-flow nasal oxygen alone. ImportanceHigh-flow nasal oxygen may prevent postextubation respiratory failure in the intensive care unit (ICU). The combination of high-flow nasal oxygen with noninvasive ventilation (NIV) may be an optimal strategy of ventilation to avoid reintubation. ObjectiveTo determine whether high-flow nasal oxygen with prophylactic NIV applied immediately after extubation could reduce the rate of reintubation, compared with high-flow nasal oxygen alone, in patients at high risk of extubation failure in the ICU. Design, Setting, and ParticipantsMulticenter randomized clinical trial conducted from April 2017 to January 2018 among 641 patients at high risk of extubation failure (ie, older than 65 years or with an underlying cardiac or respiratory disease) at 30 ICUs in France; follow-up was until April 2018. InterventionsPatients were randomly assigned to high-flow nasal oxygen alone (n=306) or high-flow nasal oxygen with NIV (n=342) immediately after extubation. Main Outcomes and MeasuresThe primary outcome was the proportion of patients reintubated at day 7; secondary outcomes included postextubation respiratory failure at day 7, reintubation rates up until ICU discharge, and ICU mortality. ResultsAmong 648 patients who were randomized (mean [SD] age, 70 [10] years; 219 women [34%]), 641 patients completed the trial. The reintubation rate at day 7 was 11.8% (95% CI, 8.4%-15.2%) (40/339) with high-flow nasal oxygen and NIV and 18.2% (95% CI, 13.9%-22.6%) (55/302) with high-flow nasal oxygen alone (difference, -6.4% [95% CI, -12.0% to -0.9%]; P=.02). Among the 11 prespecified secondary outcomes, 6 showed no significant difference. The proportion of patients with postextubation respiratory failure at day 7 (21% vs 29%; difference, -8.7% [95% CI, -15.2% to -1.8%]; P=.01) and reintubation rates up until ICU discharge (12% vs 20%, difference -7.4% [95% CI, -13.2% to -1.8%]; P=.009) were significantly lower with high-flow nasal oxygen and NIV than with high-flow nasal oxygen alone. ICU mortality rates were not significantly different: 6% with high-flow nasal oxygen and NIV and 9% with high-flow nasal oxygen alone (difference, -2.4% [95% CI, -6.7% to 1.7%]; P=.25). Conclusions and RelevanceIn mechanically ventilated patients at high risk of extubation failure, the use of high-flow nasal oxygen with NIV immediately after extubation significantly decreased the risk of reintubation compared with high-flow nasal oxygen alone. Trial RegistrationClinicalTrials.gov Identifier: NCT03121482 This randomized clinical trial compares the effect of high-flow nasal oxygen with prophylactic noninvasive ventilation applied immediately after extubation vs high-flow nasal oxygen alone on the rate of reintubation in patients at high risk of extubation failure in the intensive care unit (ICU).

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.

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.

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.

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.

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.