Treatment of COVID-19-associated ARDS with umbilical cord-derived mesenchymal stromal cells in the STROMA-CoV-2 multicenter randomized double-blind trial: long-term safety, respiratory function, and quality of life.

BACKGROUND: The STROMA-CoV-2 study was a French phase 2b, multicenter, double-blind, randomized, placebo-controlled clinical trial that did not identify a significant efficacy of umbilical cord-derived mesenchymal stromal cells in patients with SARS-CoV-2-induced acute respiratory distress syndrome. Safety on day 28 was found to be good. The aim of our extended study was to assess the 6- and 12-month safety of UC-MSCs administration in the STROMA-CoV-2 cohort. METHODS: A detailed multi-domain assessment was conducted at 6 and 12 months following hospital discharge focusing on adverse events, lung computed tomography-scan, pulmonary and muscular functional status, and quality of life in the STROMA-CoV-2 cohort including SARS-CoV-2-related early (< 96 h) mild-to-severe acute respiratory distress syndrome. RESULTS: Between April 2020 and October 2020, 47 patients were enrolled, of whom 19 completed a 1-year follow-up. There were no significant differences in any endpoints or adverse effects between the UC-MSCs and placebo groups at the 6- and 12-month assessments. Ground-glass opacities persisted at 1 year in 5 patients (26.3%). Furthermore, diffusing capacity for carbon monoxide remained altered over 1 year, although no patient required oxygen or non-invasive ventilatory support. Quality of life revealed declines in mental, emotional and physical health throughout the follow-up period, and the six-minute walking distance remained slightly impaired at the 1-year patient assessment. CONCLUSIONS: This study suggests a favorable safety profile for the use of intravenous UC-MSCs in the context of the first French wave of SARS-CoV-2-related moderate-to-severe acute respiratory distress syndrome, with no adverse effects observed at 1 year.

Lung Ultrasound Score on Postoperative Day 1 Is Predictive of the Occurrence of Pulmonary Complications after Major Abdominal Surgery: A Multicenter Prospective Observational Study.

BACKGROUND: Postoperative pulmonary complications after major abdominal surgery are frequent and carry high morbidity and mortality. Early identification of patients at risk of pulmonary complications by lung ultrasound may allow the implementation of preemptive strategies. The authors hypothesized that lung ultrasound score would be associated with pulmonary postoperative complications. The main objective of the study was to evaluate the performance of lung ultrasound score on postoperative day 1 in predicting pulmonary complications after major abdominal surgery. Secondary objectives included the evaluation of other related measures for their potential prediction accuracy. METHODS: A total of 149 patients scheduled for major abdominal surgery were enrolled in a bicenter observational study. Lung ultrasound score was performed before the surgery and on days 1, 4, and 7 after surgery. Pulmonary complications occurring before postoperative day 10 were recorded. RESULTS: Lung ultrasound score on postoperative day 1 was higher in patients developing pulmonary complications before day 10 (median, 13; interquartile range, 8.25 to 18; vs. median, 10; interquartile range, 6.5 to 12; Mann-Whitney P = 0.002). The area under the curve for predicting postoperative pulmonary complications before day 10 was 0.65 (95% CI, 0.55 to 0.75; P = 0.003). Lung ultrasound score greater than 12 had a sensitivity of 0.54 (95% CI, 0.40 to 0.67), specificity of 0.77 (95% CI, 0.67 to 0.85), and negative predictive value of 0.74 (95% CI, 0.65 to 0.83). Lung ultrasound score greater than 17 had sensitivity of 0.33 (95% CI, 0.21 to 0.47), specificity of 0.95 (95% CI, 0.88 to 0.98), and positive predictive value of 0.78 (95% CI, 0.56 to 0.93). Anterolateral lung ultrasound score and composite scores using lung ultrasound score and other patient characteristics showed similar predictive accuracies. CONCLUSIONS: An elevated lung ultrasound score on postoperative day 1 is associated with the occurrence of pulmonary complications within the first 10 days after major abdominal surgery.

Herpes Simplex Virus Hepatitis in Patients Requiring Intensive Care Unit Admission: A Retrospective, Multicenter, Observational Study.

The clinical features and short-term prognosis of patients admitted to the intensive care unit for herpes hepatitis are lacking. Of 33 patients admitted between 2006 and 2022, 22 were immunocompromised, 4 were pregnant women, and 23 died. Sixteen patients developed a hemophagocytic syndrome. Acyclovir was initiated a median (interquartile range) of 1 (0-3) day after admission.

Early renal recovery after acute kidney injury in patients on venoarterial extracorporeal membrane oxygenation: A retrospective study.

PURPOSE: The impact of VA-ECMO on early renal recovery (within 7 days after ECMO onset) in patients with pre-ECMO acute kidney injury and cardiogenic shock is unknown. MATERIAL AND METHODS: This retrospective single-center study included adult patients with cardiogenic shock rescued by VA-ECMO and severe AKI occurring before ECMO implantation (pre-ECMO AKI). Patients with early renal recovery (defined as at least a 50% decrease in peak serum creatinine or weaning from renal replacement therapy) were compared to patients without early renal recovery. RESULTS: During 7 years, 145 patients with severe pre-ECMO AKI were included. Eighty-two patients had no early renal recovery whereas 63 had early renal recovery within 7 days after VA-ECMO onset. The median time to early renal recovery was 4 (3,6) days. Nephrotoxic antibiotics (HR = 0.35 [95% CI, 0.21-0.59], p < 0.001), median fluid balance during the first 7 days of VA-ECMO (HR = 0.77 [95% CI, 0.64-0.93], p = 0.008), pre-ECMO AKI stage 3 (HR = 0.36 [95% CI, 0.20-0.64], p < 0.001) and median vasoactive-inotropic score (HR = 0.99 [95% CI, 0.98,1.00], p = 0.035) were independently associated with no early renal recovery. CONCLUSIONS: Only 43% of patients with severe pre-ECMO AKI had early renal recovery after VA-ECMO initiation.

Therapeutic potentials of mesenchymal stromal cells-derived extracellular vesicles in liver failure and marginal liver graft rehabilitation: a scoping review.

Liver failure includes distinct subgroups of diseases: Acute liver failure (ALF) without preexisting cirrhosis, acute-on-chronic liver failure (ACLF) (severe form of cirrhosis associated with organ failures and excess mortality), and liver fibrosis (LF). Inflammation plays a key role in ALF, LF, and more specifically in ACLF for which we have currently no treatment other than liver transplantation (LT). The increasing incidence of marginal liver grafts and the shortage of liver grafts require us to consider strategies to increase the quantity and quality of available liver grafts. Mesenchymal stromal cells (MSCs) have shown beneficial pleiotropic properties with limited translational potential due to the pitfalls associated with their cellular nature. MSC-derived extracellular vesicles (MSC-EVs) are innovative cell-free therapeutics for immunomodulation and regenerative purposes. MSC-EVs encompass further advantages: pleiotropic effects, low immunogenicity, storage stability, good safety profile, and possibility of bioengineering. Currently, no human studies explored the impact of MSC-EVs on liver disease, but several preclinical studies highlighted their beneficial effects. In ALF and ACLF, data showed that MSC-EVs attenuate hepatic stellate cells activation, exert antioxidant, anti-inflammatory, anti-apoptosis, anti-ferroptosis properties, and promote regeneration of the liver, autophagy, and improve metabolism through mitochondrial function recovery. In LF, MSC-EVs demonstrated anti-fibrotic properties associated with liver tissue regeneration. Normothermic-machine perfusion (NMP) combined with MSC-EVs represents an attractive therapy to improve liver regeneration before LT. Our review suggests a growing interest in MSC-EVs in liver failure and gives an appealing insight into their development to rehabilitate marginal liver grafts through NMP.

Accuracy of clinicians' ability to predict the need for renal replacement therapy: a prospective multicenter study.

PURPOSE: Identifying patients who will receive renal replacement therapy (RRT) during intensive care unit (ICU) stay is a major challenge for intensivists. The objective of this study was to evaluate the performance of physicians in predicting the need for RRT at ICU admission and at acute kidney injury (AKI) diagnosis. METHODS: Prospective, multicenter study including all adult patients hospitalized in 16 ICUs in October 2020. Physician prediction was estimated at ICU admission and at AKI diagnosis, according to a visual Likert scale. Discrimination, risk stratification and benefit of physician estimation were assessed. Mixed logistic regression models of variables associated with risk of receiving RRT, with and without physician estimation, were compared. RESULTS: Six hundred and forty-nine patients were included, 270 (41.6%) developed AKI and 77 (11.8%) received RRT. At ICU admission and at AKI diagnosis, a model including physician prediction, the experience of the physician, SOFA score, serum creatinine and diuresis to determine need for RRT performed better than a model without physician estimation with an area under the ROC curve of 0.90 [95% CI 0.86-0.94, p < 0.008 (at ICU admission)] and 0.89 [95% CI 0.83-0.93, p = 0.0014 (at AKI diagnosis)]. In multivariate analysis, physician prediction was strongly associated with the need for RRT, independently of creatinine levels, diuresis, SOFA score and the experience of the doctor who made the prediction. CONCLUSION: As physicians are able to stratify patients at high risk of RRT, physician judgement should be taken into account when designing new randomized studies focusing on RRT initiation during AKI.