IMPORTANCEOveractivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.ObjectiveTo determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.DESIGN, SETTING, AND PARTICIPANTSIn an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).INTERVENTIONSPatients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days.MAIN OUTCOMES AND MEASURESThe primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.RESULTSOn February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).CONCLUSIONS AND RELEVANCEIn this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT02735707

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Background: Yellow fever vaccine exists for over 80 years and is considered to be relatively safe. However, in rare cases it can produce serious neurotropic and viscerotropic complications. We report a case of a patient who presented both viscerotropic and neurological manifestations after yellow fever vaccination. Case presentation: We describe the case of a 37 years old man who developed after the yellow fever vaccination a yellow fever vaccine-associated viscerotropic disease followed by acute uveitis. Prolonged detection of yellow fever RNA in blood and urine was consistent with yellow fever vaccine-associated adverse event. The final outcome was good, although with persistent fatigue over a few months. Conclusions: Even if the yellow fever vaccine is relatively safe, physicians should be aware of its possible serious adverse effects.

IntroductionSeasonal epidemic influenza and SARS-CoV-2 are the most frequent viruses causing acute respiratory distress syndrome (ARDS). To what extent these two etiologies differ in ICU patients remains uncertain. We, therefore, aimed at comparing the severity and outcomes of influenza and SARS-CoV-2-induced ARDS in mechanically ventilated patients.MethodsThis retrospective, analytic, single-center study was conducted in the medical ICU of Nancy University Hospital in France. Adult patients hospitalized with confirmed influenza (from 2009 to 2019) or SARS-CoV-2-induced ARDS (between March 2020 and May 2021) and those under mechanical ventilation were included. Each patient with influenza was matched with two patients with COVID-19, with the same severity of ARDS. The primary endpoint was death in ICU on day 28. The secondary endpoints were the duration of vasopressors, the use of renal replacement therapy, the duration of mechanical ventilation, and the ICU length of stay.ResultsA total of 42 patients with influenza were matched with 84 patients with COVID-19. They had similar sex distribution, age, Charlson comorbidity index, and ARDS severity. On day 28, 11 (26.2%) patients in the influenza group and nine (10.7%) patients in the COVID-19 group had died (p = 0.0084, HR = 3.31, CI 95% [1.36–8.06]). In the univariate Cox model, being infected with SARS-CoV-2, SOFA and SAPS II scores, initial arterial pH, PaCO2, PaO2/FiO2, serum lactate level, platelet count, and use of renal replacement therapy were significantly associated with mortality. In the multivariate Cox model, the SOFA score at admission (p < 0.01, HR = 1.284, CI 95% [1.081; 1.525]) and the initial pH (p < 0.01, HR = 0.618, CI 95% [0.461; 0.828]) were the only predictors of mortality. The type of virus had no influence on mortality, though patients with COVID-19 underwent longer mechanical ventilation and received more neuromuscular blockers and prone positioning.ConclusionIn mechanically ventilated patients with ARDS, 28-day mortality was higher among patients with influenza as compared to patients with COVID-19 because of a higher initial extra-pulmonary severity. However, the type of virus was not, by itself, correlated with mortality.

Case report: A 64‐year‐old man was hospitalized in the intensive care unit with pneumonia, lactic acidosis, and hypoglycemia. Investigations revealed a kappa light chain multiple myeloma. The patient underwent chemotherapy by bortezomib, lenalidomide, and dexamethasone. Serum lactate level and glycemia normalized. Evaluation at day 28 showed a disease progression. Lenalidomide was switched for daratumumab, bortezomib, and dexamethasone. In front of the inefficiency of the chemotherapy, the patient underwent third‐line chemotherapy by melphalan. There was a correlation between the evolution of the myeloma, serum lactate level, and hypoglycemia, with a normalization after chemotherapy, and a rise at myeloma's relapse. Daratumumab was continued as a maintenance treatment. The patient died 4 months and 10 days after his first hospital admission. Discussion: Our case is consistent with a type B tumor‐associated aerobic glycolytic lactic acidosis, called the Warburg effect. It is well described in association with other hematologic malignancies, but rarely in association with myeloma. All reported cases of myeloma with type B lactic acidosis died within 1 year. Conclusion: When associated with multiple myeloma, tumor‐associated aerobic glycolytic lactic acidosis is correlated with the disease progression and has a very high mortality rate. Significance Statement : Aerobic glycolytic lactic acidosis also known as the Warburg effect can be encountered in multiple myeloma, resulting of a metabolic shift to increased glycolysis operating in malignant cells. Together with hypoglycemia, it is well correlated with the disease progression and has a very poor outcome.