Systemic lupus erythematosus-related acute lung disease.

INTRODUCTION: Systemic lupus erythematosus (SLE) is non-organ specific autoimmune disease with mainly skin, joint, and kidney involvement. SLE-related acute lung disease (ALD) is rare, poorly investigated and can lead to acute respiratory failure. We conducted a retrospective study aiming to describe clinical features, treatments and outcome of SLE-related APD. METHODS: We retrospectively included all patients with SLE and ALD admitted from November 1996 and September 2018 to La Pitié-Salpêtrière Hospital, after exclusion of viral or bacterial lung infection, cardiac failure or any other alternate diagnosis. RESULTS: During the time of the study, 14 patients with 16 episodes were admitted to our center: female 79%, mean age ± SD at admission 24 ± 11 years. ALD was inaugural of the SLE in 70% cases. SLE main organ involvement were: arthritis 93%, skin 79%, serositis 79%, hematological 79%, kidney 64%, neuropsychiatric 36% and cardiac 21%. 11 episodes required ICU admission for a median time of 8 days. Chest CT-scan revealed mostly basal consolidation and ground-glass opacities. When available, bronchoalveolar lavage mostly revealed a neutrophilic alveolitis with alveolar hemorrhage in 67% cases. Symptomatic respiratory treatments were: oxygen 81%, high-flow nasal canula oxygen 27%, non-invasive ventilation 36%, mechanical ventilation 64% and venovenous extracorporeal membrane oxygenation 18%. SLE-specific treatments were: corticosteroids 100%, cyclophosphamide 56% and plasma exchange 25%. All patients but one survived to ICU and hospital discharge. Two patients had a relapse of SLE-related ALD but none had interstitial lung disease during follow-up. CONCLUSION: Systemic lupus erythematosus-related acute respiratory failure is a severe event, mostly occurring at SLE onset, typical harboring a basal consolidation pattern on chest CT-scan and alveolar hemorrhage on BAL pathological examination. Mortality in our cohort is lower than previously reported but these results needs to be confirmed in further larger studies.

FX06 to rescue SARS-CoV-2-induced acute respiratory distress syndrome: a randomized clinical trial.

BACKGROUND: Vascular leakage is a major feature of acute respiratory distress syndrome (ARDS). We aimed to evaluate the efficacy of FX06, a drug under development that stabilizes interendothelial cell junctions, at reducing vascular leakage during SARS-CoV-2-induced ARDS. METHODS: This multicenter, double-blinded, randomized trial included adults with COVID-19-associated ARDS who had received invasive mechanical ventilation for < 5 days and were randomized to receive either intravenous FX06 (400 mg/d, for 5 days) or its vehicle as placebo. The primary endpoint was the lowering-from day 1 to day 7-of the transpulmonary thermodilution-derived extravascular lung-water index (EVLWi). RESULTS: Twenty-five patients were randomized to receive FX06 and 24 the placebo. Although EVLWi was elevated at baseline (median [IQR] 15.6 mL/kg [13.5; 18.5]), its declines from day 1 to day 7 were comparable for FX06 recipients and controls (respectively, - 1.9 [- 3.3; - 0.5] vs. - 0.8 [- 5.5; - 1.1] mL/kg; estimated effect - 0.8 [- 3.1; + 2.4], p = 0.51). Cardiac indexes, pulmonary vascular permeability indexes, and fluid balances were also comparable, as were PaO2/FiO2 ratios and durations of mechanical ventilation. Adverse event rates were similar for the 2 groups, although more FX06 recipients developed ventilator-associated pneumonia (16/25 (64%) vs. 6/24 (24%), p = 0.009). CONCLUSIONS: In this unique-dosing-regimen study, FX06 did not lower SARS-CoV-2-induced pulmonary vascular leakage. Future investigations will need to evaluate its efficacy at earlier times during the disease or using other regimens. Trial registration NCT04618042. Registered 5 November 2020.

Cytological patterns of bronchoalveolar lavage fluid in mechanically ventilated COVID-19 patients on extracorporeal membrane oxygenation.

INTRODUCTION: Coronavirus disease-2019 (COVID-19) may lead to acute respiratory distress syndrome requiring extracorporeal membrane oxygenation (ECMO). Patterns of inflammatory bronchoalveolar cells in COVID-19 patients treated with ECMO are not well described. OBJECTIVE: We aimed to describe inflammatory cell subpopulations in blood and bronchoalveolar lavages (BALs) obtained in critically ill COVID-19 patients shortly after ECMO implementation. METHODS: BAL was performed in the middle lobe in 12 consecutive ECMO-treated COVID-19 patients. Trained cytologists analyzed peripheral blood and BAL cells using flow cytometry and routine staining, respectively. Data were interpreted in relation to dexamethasone administration and weaning from ECMO and ventilator. RESULTS: High neutrophil proportions (66% to 88% of total cells) were observed in the absence of bacterial superinfection and more frequently in dexamethasone-free patients (83% [82-85] vs. 29% [8-68], P = 0.006), suggesting that viral infection could be responsible of predominantly neutrophilic lung inflammation. Successful weaning from ECMO/ventilator could not be predicted by the peripheral white blood and BAL cell pattern. CONCLUSION: High neutrophil proportions can be observed in critically ill COVID-19 patients despite the lack of microbiological evidence on BAL of bacterial superinfection. Dexamethasone was associated with lower neutrophil proportions in BAL. Our study was probably underpowered to provide BAL cell pattern helpful to predict weaning from ECMO/ventilator.

Impact of Early Limitation of Therapeutic Effort in Elderly COVID-19 Patients Admitted to the Intensive Care Unit-A Cohort Study.

(1) Background: Admission to the ICU and intensity of care provided to elderly COVID-19 patients are difficult choices guided by the expected patient-centered benefits. However, the impact of an early discussion of limitation of therapeutic effort (LTE) has been poorly investigated. (2) Methods: We performed a single-center retrospective cohort study including all ≥70-year-old COVID-19 patients admitted to the ICU. Factors associated with early LTE discussion (defined as before or up to 2 days post-ICU admission) and in-hospital mortality were evaluated. (3) Results: Eighty-two patients (59 M/23 F; 78 years (74−82) [median (interquartile range)]; 43/82 with LTE) were included. The in-hospital mortality rate was 55%. Early LTE was decided upon for 22/82 patients (27%), more frequently in older (p < 0.001) and frailer patients (p = 0.004). Using a multivariable logistic regression model including clinical frailty scale grade ≥4, hospital acquisition of COVID-19, ventilation support modality and SOFA score on admission, early LTE was not associated with mortality (adjusted odds ratio = 0.57 (0.15−2.00), p = 0.39). LTE resulted in less frequent invasive mechanical ventilation (23% versus 65%, p = 0.001), renal replacement therapy (5% versus 27%, p = 0.03) and norepinephrine infusion (23% versus 60%, p = 0.005), and shorter ICU stay (6 days (2−12) versus 14 days (7−24), p = 0.001). (4) Conclusions: In this small sample exploratory study, we were unable to demonstrate any increase in in-hospital mortality associated with early LTE discussion in elderly COVID-19 patients while reducing the use of organ support techniques. These findings require confirmation in larger studies.

Fatal Multiorgan Failure Syndrome in a Strongyloides-HTLV-1 Coinfected Patient, after Treatment with Ivermectin.

Because of its characteristic features of autoinfection, the parasitic nematode Strongyloides stercoralis can infect patients for years. An acceleration of its autoinfective cycle can be triggered by human T-lymphotropic virus-1 (HTLV-1) infection, mainly by the deviation of the protective Th2- to Th1-type immune response and can lead to severe disease by dissemination of Strongyloides stercoralis larvae carrying intestinal bacteria to multiple organs. Meningitis caused by enteric Gram-negative bacteria is a potentially fatal complication of disseminated strongyloidiasis. Herein, we present the case of a Strongyloides-HTLV-1 coinfected patient, admitted for E. coli meningitis. One day after initiation of ivermectin, the patient developed significant S. stercoralis dissemination, complicated by multiorgan failure syndrome, and died from neurological failure. While the initial clinical scenario of our case has already been well described in the literature, its course after antihelminthic treatment initiation remains unclear and needs to be discussed.