A Randomized Trial of Mesenchymal Stromal Cells for Moderate to Severe Acute Respiratory Distress Syndrome from COVID-19.

Rationale: There are limited therapeutic options for patients with coronavirus disease (COVID-19)-related acute respiratory distress syndrome with inflammation-mediated lung injury. Mesenchymal stromal cells offer promise as immunomodulatory agents. Objectives: Evaluation of efficacy and safety of allogeneic mesenchymal cells in mechanically-ventilated patients with moderate or severe COVID-19-induced respiratory failure. Methods: Patients were randomized to two infusions of 2 million cells/kg or sham infusions, in addition to the standard of care. We hypothesized that cell therapy would be superior to sham control for the primary endpoint of 30-day mortality. The key secondary endpoint was ventilator-free survival within 60 days, accounting for deaths and withdrawals in a ranked analysis. Measurements and Main Results: At the third interim analysis, the data and safety monitoring board recommended that the trial halt enrollment as the prespecified mortality reduction from 40% to 23% was unlikely to be achieved (n = 222 out of planned 300). Thirty-day mortality was 37.5% (42/112) in cell recipients versus 42.7% (47/110) in control patients (relative risk [RR], 0.88; 95% confidence interval, 0.64-1.21; P = 0.43). There were no significant differences in days alive off ventilation within 60 days (median rank, 117.3 [interquartile range, 60.0-169.5] in cell patients and 102.0 [interquartile range, 54.0-162.5] in control subjects; higher is better). Resolution or improvement of acute respiratory distress syndrome at 30 days was observed in 51/104 (49.0%) cell recipients and 46/106 (43.4%) control patients (odds ratio, 1.36; 95% confidence interval, 0.57-3.21). There were no infusion-related toxicities and overall serious adverse events over 30 days were similar. Conclusions: Mesenchymal cells, while safe, did not improve 30-day survival or 60-day ventilator-free days in patients with moderate and/or severe COVID-19-related acute respiratory distress syndrome.

Veno-venous ECLS rescue for a heart transplant recipient with COVID-19, a case report.

The potential for increased rates of morbidity of SARS-CoV-2 within immunocompromised populations has been of concern since the pandemic's onset. Transplant providers and patients can face particularly challenging situations, in the current settings as data continues to emerge for the prevention and treatment of the immunocompromised subpopulation. This case report details a patient 9-months post orthotopic heart transplant that developed SARS-CoV-2 infection despite two prior doses of the Pfizer-BioNtech COVID-19 vaccine, and had successful rescue from refractory hypoxemia with veno-venous extracorporeal membrane oxygenation (VV ECLS).

Did Jesus Die by Suffocation?: An Appraisal of the Evidence.

A majority of medical and lay articles regarding crucifixion, and specifically the crucifixion of Jesus Christ, now state that suffocation was the primary cause of death from crucifixion. An in-depth analysis reveals that this theory is based on a form of torture unrelated to crucifixion and that no evidence directly linking suffocation to crucifixion has been published. Indeed, a thorough review of available ancient evidence from literature, artwork, graffiti, and modern archeology and re-enactment studies reveals no evidence in favor of suffocation and much evidence against suffocation as the cause of death in typically-portrayed crucifixions, and particularly for the crucifixion of Jesus Christ. Researchers are encouraged to look elsewhere for the most likely cause or causes of death from crucifixion. It may be time to abandon the idea that suffocation was the primary cause of death in crucifixion.

Pneumocystis colonization, airway inflammation, and pulmonary function decline in acquired immunodeficiency syndrome.

As a result of improved diagnosis, treatment, and supportive care for HIV-infected patients, AIDS in developed countries has now become a chronic infection with prolonged survival time, but longterm complications are increasing contributors to morbidity and mortality. HIV-infected patients are at increased risk for the development of pulmonary complications, including chronic obstructive pulmonary disease (COPD); however, the mechanisms associated with this increased susceptibility have not been defined. Infectious agents may contribute to the development of COPD by upregulating inflammatory mediators in the lung that act in concert with cigarette smoke to promote lung pathology. Studies in human subjects and non-human primate models of AIDS suggest that the inflammatory response to asymptomatic carriage or colonization by the opportunistic pathogen, Pneumocystis sp. (Pc), is similar to that of COPD, which is characterized by influx of CD8+ T cells, neutrophils, and macrophages into the lungs. We have shown a high frequency of Pc colonization among asymptomatic HIV-infected subjects and in non-HIV infected subjects with COPD. To investigate the role of Pc in the progression of obstructive lung disease in HIV infections, we developed a non-human primate model of Pc colonizatoin and infection in simian immunodeficiency virus (SIV)-infected macaques. These animals develop a prolonged colonization state characterized by a persistent influx of CD8+ T cells and neutrophils, and local increases in IL-8, IFN-gamma, and TNF-alpha. SIV-infected Pc-colonized monkeys show progressive decline in pulmonary function compared to SIV-infected monkeys. We hypothesize that in the context of AIDS-immune dysfunction, Pc colonization induces inflammatory responses leading to changes in pulmonary function and architecture similar to that seen in emphysema. Information gained from these studies will lead to the development of interventions to prevent lung injury associated with Pc colonization and the development of HIV-associated COPD.