Umbilical cord mesenchymal stem cells for COVID-19 acute respiratory distress syndrome: A double-blind, phase 1/2a, randomized controlled trial.

Acute respiratory distress syndrome (ARDS) in COVID-19 is associated with high mortality. Mesenchymal stem cells are known to exert immunomodulatory and anti-inflammatory effects and could yield beneficial effects in COVID-19 ARDS. The objective of this study was to determine safety and explore efficacy of umbilical cord mesenchymal stem cell (UC-MSC) infusions in subjects with COVID-19 ARDS. A double-blind, phase 1/2a, randomized, controlled trial was performed. Randomization and stratification by ARDS severity was used to foster balance among groups. All subjects were analyzed under intention to treat design. Twenty-four subjects were randomized 1:1 to either UC-MSC treatment (n = 12) or the control group (n = 12). Subjects in the UC-MSC treatment group received two intravenous infusions (at day 0 and 3) of 100 ± 20 × 106 UC-MSCs; controls received two infusions of vehicle solution. Both groups received best standard of care. Primary endpoint was safety (adverse events [AEs]) within 6 hours; cardiac arrest or death within 24 hours postinfusion). Secondary endpoints included patient survival at 31 days after the first infusion and time to recovery. No difference was observed between groups in infusion-associated AEs. No serious adverse events (SAEs) were observed related to UC-MSC infusions. UC-MSC infusions in COVID-19 ARDS were found to be safe. Inflammatory cytokines were significantly decreased in UC-MSC-treated subjects at day 6. Treatment was associated with significantly improved patient survival (91% vs 42%, P = .015), SAE-free survival (P = .008), and time to recovery (P = .03). UC-MSC infusions are safe and could be beneficial in treating subjects with COVID-19 ARDS.

Spinal epidural abscess in hemodialysis patients: a case series and review.

Spinal epidural abscess (SEA) is a rare but potentially devastating condition. We noticed an increase in the number of cases of SEA, with the majority in hemodialysis (HD) patients. This prompted a retrospective chart review of all cases of SEA admitted from 2000 to 2005 and a literature search of similar cases. We identified 19 SEA cases treated at Long Island College Hospital during this 6-year period, of which six were on HD: four were dialyzed via catheter, one via arteriovenous fistula, and in one the method of dialysis was not documented. Four patients had bacteremia with Staphylococcus aureus. Four patients presented with paresis or paralysis; only one improved. The mortality rate was 33% (2/6). We found 30 other cases of SEA in patients on HD from the literature. These 36 HD cases were compared with 85 SEA cases that were not on HD (13 from our study and 72 described in two large case series). The mortality rate was noted to be much higher in HD patients (23% [6/26] versus 7% [6/85]). Neurologic deficit at presentation was noted in 47% (17/36) of HD patients versus 69% (59/85) of non-HD patients, but neurologic improvement was higher in non-HD patients (71% [42/59] versus 29% [5/17]). This is the largest literature review of SEA in patients on HD. When compared with non-HD patients, HD patients had a higher mortality rate and were less likely to improve neurologically.

Parenteral polymyxin B use in patients with multidrug-resistant gram-negative bacteremia and urinary tract infections: a retrospective case series.

BACKGROUND: Parenteral polymyxin use declined after the 1960s, due to safety concerns. An increase in multidrug-resistant (MDR) gram-negative infections and a shortage of new agents have prompted increased use of parenteral polymyxin. OBJECTIVE: To describe our clinical experience with parenteral polymyxin B for MDR gram-negative bacteremia and urinary tract infection (UTI). METHODS: Paper pharmacy records were used to identify patients aged 18 years or older, presence of MDR gram-negative bacteremia or UTI, and use of parenteral polymyxin B for at least 48 hours. Electronic and paper patient records were then retrospectively reviewed. Polymyxin B susceptibility was evaluated using the Kirby-Bauer method. MDR isolates were defined as resistant to at least 3 antimicrobial classes, excluding polymyxin B. Microbiologic clearance was defined by 1 repeat urine or 2 repeat blood cultures that were sterile or growing different organisms. Secondary outcomes included hospital mortality and nephrotoxicity, defined as an increase in serum creatinine of 0.5 mg/dL or more, or a 50% reduction in creatinine clearance. RESULTS: Seventeen infections in 16 patients were treated with polymyxin B (1 pt. had 2 infections that were analyzed separately). Microbiologic clearance occurred in 14 of 16 (88%) cases of MDR gram-negative bacteremia or UTI in which repeat cultures were done. Ten of 16 patients died (all-cause mortality 63%). Five patients required hemodialysis prior to polymyxin B use. Six (55%) of the remaining 11 patients with baseline renal insufficiency developed nephrotoxicity, and none of them required hemodialysis. The mean +/- SD number of days from the initiation of therapy to the onset of nephrotoxicity was 7.5 +/- 2.3 (range 4-10) days. Three (50%) of 6 patients with nephrotoxicity died. CONCLUSIONS: Our data suggest that polymyxin B may be effective for MDR gram-negative infections in patients with limited therapeutic options, but precautions should be taken to avoid toxicity.