Safety of DW-MSC infusion in patients with low clinical risk COVID-19 infection: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Due to their immunomodulatory properties, mesenchymal stem cells (MSCs) have been proposed to have therapeutic potential to improve clinical outcomes in COVID-19. However, the safety and efficacy profile of MSC infusion therapy in patients with non-severe COVID-19 infection has not been completely established; there is, in particular, a substantial void in the literature on dose-dependent studies of MSC infusion in patients with low clinical risk COVID-19 infection. METHODS: This phase 1 double-blind, placebo-controlled, randomized clinical trial examines the safety, feasibility, and tolerability of 2 doses (high and low) of DW-MSC in patients with low clinical risk COVID-19. A total of 9 patients were enrolled in this study and randomized into low-dose (TL), high-dose (TH), and placebo (C) groups. Subjects in the TL and TH groups received single intravenous infusions of 5.0 × 107 cells and 1.0 × 108 cells, respectively. The main outcome was the occurrence of treatment-emergent adverse events (TEAE) during the 28-day study period. Vital signs and various inflammatory markers were also monitored weekly during the observation period. RESULTS: There were no apparent differences in clinical characteristics between study groups (TL, TH, and C) at baseline. All patients did not show the progression of severity during the study period. During the course of the study, 6 episodes of TEAE were observed in 5 subjects; however, none of the TEAEs were severe. During the follow-up period, 8 subjects recovered and were discharged from the hospital without complications. A subject exhibited abnormal liver function biomarkers at the end of the study period. Changes in inflammatory markers throughout the clinical course were not vastly different across study groups. CONCLUSIONS: Our clinical trial has provided reliable results regarding the safety of MSCs in low clinical risk COVID-19 subjects treated with MSCs. However, further confirmation of the therapeutic efficacy aspects of MSC will require large-scale randomized controlled trials in subjects with varying severity profiles for COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04535856. Registered 2 September 2020, https://clinicaltrials.gov/ct2/show/NCT04535856.

Excess mortality attributable to antimicrobial-resistant bacterial bloodstream infection at a tertiary-care hospital in Indonesia.

The burden of antimicrobial-resistant (AMR) infections in low and middle-income countries (LMICs) is largely unknown. Here, we evaluate attributable mortality of AMR infections in Indonesia. We used routine databases of the microbiology laboratory and hospital admission at Dr. Wahidin Sudirohusodo Hospital, a tertiary-care hospital in South Sulawesi from 2015 to 2018. Of 77,752 hospitalized patients, 8,341 (10.7%) had at least one blood culture taken. Among patients with bacteriologically confirmed bloodstream infections (BSI), the proportions of patients with AMR BSI were 78% (81/104) for third-generation cephalosporin-resistant (3GCR) Escherichia coli, 4% (4/104) for 3GCR plus carbapenem-resistant E. coli, 56% (96/171) for 3GCR Klebsiella pneumoniae, 25% (43/171) for 3GCR plus carbapenem-resistant K. pneumoniae, 51% (124/245) for methicillin-resistant Staphylococcus aureus, 48% (82/171) for carbapenem-resistant Acinetobacter spp., and 19% (13/68) for carbapenem-resistant Pseudomonas aeruginosa. Observed in-hospital mortality of patients with AMR BSI was 49.7% (220/443). Compared with patients with antimicrobial-susceptible BSI and adjusted for potential confounders, the excess mortality attributable to AMR BSI was -0.01 (95% CI: -15.4, 15.4) percentage points. Compared with patients without a BSI with a target pathogen and adjusted for potential confounders, the excess mortality attributable to AMR BSI was 29.7 (95%CI: 26.1, 33.2) percentage points. This suggests that if all the AMR BSI were replaced by no infection, 130 (95%CI: 114, 145) deaths among 443 patients with AMR BSI might have been prevented. In conclusion, the burden of AMR infections in Indonesian hospitals is likely high. Similar large-scale evaluations should be performed across LMICs to inform interventions to mitigate AMR-associated mortality.

Comparison of Different Early Enteral Feeding Formulas on Critically Ill Patients.

Critically ill patients are physiologically unstable, often have complex hypermetabolic responses to trauma. These patients are facing a high risk of death, multi-organ failure, and prolonged ventilator use. Nutrition is one of therapy for critical illness, however, patients often experience malnutrition caused by disease severity, delays in feeding, and miscalculation of calorie needs. The study aims to evaluate clinical improvement in critically ill participants that were given 3 kinds of early enteral feeding formulas, which were control (5% Dextrose), high-protein polymeric, or oligomeric formulas. A total of 55 critically ill participants admitted to the intensive care unit (ICU) between October 2017-March 2018 and assigned in this controlled trial. Early enteral feeding was initiated within 24-48 h after ICU admission. Each enteral feeding group were categorized to traumatic brain injury (TBI) or non-TBI. The primary endpoints were changes in white blood cell count, Acute Physiologic and Chronic Health Evaluation (APACHE) II score, and Nutrition Risk in the Critically Ill (NUTRIC) score from baseline to day 3. Baseline characteristics were similar between control (n=22), high-protein polymeric (n=19) and oligomeric (n=14) groups. There were significant decreases for white blood cell count (13,262.5±6,963.51 to 11,687.5±7,420.92; p=0.041), APACHE II score (17.33±3.31 to 13.83±1.95; p=0.007), and NUTRIC scores changes (3.08±1.44 to 1.92±1.00; p=0.022) in non-TBI participants receiving highprotein polymeric compared those in control or oligomeric participants. But there is no significant clinical improvement in TBI patients. In conclusion, non-TBI patients benefit from early enteral feeding with high-protein polymeric formula.