In COVID-19 Patients Who Suffer In-Hospital Cardiac Arrest, Cardiopulmonary Resuscitation Outcomes May Be Impacted by Arrest Etiology and Local Pandemic Conditions

OBJECTIVES: The utility and risks to providers of performing cardiopulmonary resuscitation after in-hospital cardiac arrest in COVID-19 patients have been questioned. Additionally, there are discrepancies in reported COVID-19 in-hospital cardiac arrest survival rates. We describe outcomes after cardiopulmonary resuscitation for in-hospital cardiac arrest in two COVID-19 patient cohorts. DESIGN: Retrospective cohort study. SETTING: New York-Presbyterian Hospital/Columbia University Irving Medical Center in New York, NY. PATIENTS: Those admitted with COVID-19 between March 1, 2020, and May 31, 2020, as well as between March 1, 2021, and May 31, 2021, who received resuscitation after in-hospital cardiac arrest. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Among 103 patients with coronavirus disease 2019 who were resuscitated after in-hospital cardiac arrest in spring 2020, most self-identified as Hispanic/Latino or African American, 35 (34.0%) had return of spontaneous circulation for at least 20 minutes, and 15 (14.6%) survived to 30 days post-arrest. Compared with nonsurvivors, 30-day survivors experienced in-hospital cardiac arrest later (day 22 vs day 7; = 0.008) and were more likely to have had an acute respiratory event preceding in-hospital cardiac arrest (93.3% vs 27.3%; \u3c 0.001). Among 30-day survivors, 11 (73.3%) survived to hospital discharge, at which point 8 (72.7%) had Cerebral Performance Category scores of 1 or 2. Among 26 COVID-19 patients resuscitated after in-hospital cardiac arrest in spring 2021, 15 (57.7%) had return of spontaneous circulation for at least 20 minutes, 3 (11.5%) survived to 30 days post in-hospital cardiac arrest, and 2 (7.7%) survived to hospital discharge, both with Cerebral Performance Category scores of 2 or less. Those who survived to 30 days post in-hospital cardiac arrest were younger (46.3 vs 67.8; = 0.03), but otherwise there were no significant differences between groups. CONCLUSIONS: Patients with COVID-19 who received cardiopulmonary resuscitation after in-hospital cardiac arrest had low survival rates. Our findings additionally show return of spontaneous circulation rates in these patients may be impacted by hospital strain and that patients with in-hospital cardiac arrest preceded by acute respiratory events might be more likely to survive to 30 days, suggesting Advanced Cardiac Life Support efforts may be more successful in this subpopulation

Human placenta-derived cells (PDA-001) for the treatment of moderate-to-severe Crohn\u27s disease: A phase 1b/2a study

Background: PDA-001 (cenplacel-L), a preparation of placenta-derived mesenchymal-like adherent cells with immunomodulatory effects, previously demonstrated safety and tolerability in an open-label Crohn\u27s disease (CD) study. The current phase 1b/2a study evaluated the safety and efficacy of PDA-001 in subjects with moderate-to-severe CD. Methods: Subjects had active inflammation on colonoscopy or elevated fecal calprotectin and inadequate response to conventional therapy. Concomitant therapy with stable doses of immunomodulators and/or biologics was permitted. Subjects received 8 units of PDA-001 (1.5 × 10 cells per unit) in the phase 1b open-label study. In the phase 2a double-blind study, subjects were randomly assigned placebo, 1 unit, or 4 units of PDA-001 (2 infusions 1 wk apart). The primary endpoint was induction of clinical response (≥100 points and/or 25% decrease in Crohn\u27s Disease Activity Index) at 4 and 6 weeks. Results: Fifty subjects were enrolled (safety analysis, 50 subjects; efficacy analysis, 48 subjects). Four subjects received 8 units of PDA-001 (phase 1b study); 46 subjects were subsequently randomized to 1 or 4 units of PDA-001 or placebo (phase 2a study). The primary endpoint was achieved in 10/28 (36%) of PDA-001 subjects compared with placebo (0%, P = 0.026). Clinical remission was achieved in 4/28 (14%) of PDA-001 subjects compared with placebo (0%, P = 0.3). One treatment-related serious adverse event occurred (systemic hypersensitivity reaction at 8 units). In the phase 2a study, serious adverse events occurred in 9/28 (32%) of PDA-001 subjects and 1/16 (7%) of placebo subjects. Conclusions: A 2-infusion regimen of PDA-001 induced clinical response in subjects with moderate-to-severe CD. Additional studies are warranted

Stem cells as an emerging paradigm in Stroke 3: enhancing the development of clinical trials

No abstract available

Stem Cell Therapy as an Emerging Paradigm for Stroke (STEPS) II

Cell-based therapies represent a new therapeutic approach for stroke. In 2007, investigators from academia, industry leaders, and members of the National Institutes of Health crafted recommendations to facilitate the translational development of cellular therapies as a novel, emerging modality for stroke from animal studies to clinical trials. This meeting was called Stem Cell Therapies as an Emerging Paradigm in Stroke (STEPS) and was modeled on the format of the Stroke Therapy Academic Industry Roundtable (STAIR) meetings. Since publication of the original STEPS guidelines, there has been an explosive growth in the number of cellular products and in the number of new laboratory discoveries that impact the safety and potential efficacy of cell therapies for stroke. Any successful development of a cell product will need to take into consideration several factors, including the preclinical safety and efficacy profile, cell characterization, delivery route, in vivo biodistribution, and mechanism of action. In 2010, a second meeting called STEPS 2 was held to bring together clinical and basic science researchers with industry, regulatory, and National Institutes of Health representatives. At this meeting, participants identified critical gaps in knowledge and research areas that require further studies, updated prior guidelines, and drafted new recommendations to create a framework to guide future investigations in cell-based therapies for stroke

A Randomized Trial Comparing Antibiotics with Appendectomy for Appendicitis.

BACKGROUND: Antibiotic therapy has been proposed as an alternative to surgery for the treatment of appendicitis. METHODS: We conducted a pragmatic, nonblinded, noninferiority, randomized trial comparing antibiotic therapy (10-day course) with appendectomy in patients with appendicitis at 25 U.S. centers. The primary outcome was 30-day health status, as assessed with the European Quality of Life-5 Dimensions (EQ-5D) questionnaire (scores range from 0 to 1, with higher scores indicating better health status; noninferiority margin, 0.05 points). Secondary outcomes included appendectomy in the antibiotics group and complications through 90 days; analyses were prespecified in subgroups defined according to the presence or absence of an appendicolith. RESULTS: In total, 1552 adults (414 with an appendicolith) underwent randomization; 776 were assigned to receive antibiotics (47% of whom were not hospitalized for the index treatment) and 776 to undergo appendectomy (96% of whom underwent a laparoscopic procedure). Antibiotics were noninferior to appendectomy on the basis of 30-day EQ-5D scores (mean difference, 0.01 points; 95% confidence interval [CI], -0.001 to 0.03). In the antibiotics group, 29% had undergone appendectomy by 90 days, including 41% of those with an appendicolith and 25% of those without an appendicolith. Complications were more common in the antibiotics group than in the appendectomy group (8.1 vs. 3.5 per 100 participants; rate ratio, 2.28; 95% CI, 1.30 to 3.98); the higher rate in the antibiotics group could be attributed to those with an appendicolith (20.2 vs. 3.6 per 100 participants; rate ratio, 5.69; 95% CI, 2.11 to 15.38) and not to those without an appendicolith (3.7 vs. 3.5 per 100 participants; rate ratio, 1.05; 95% CI, 0.45 to 2.43). The rate of serious adverse events was 4.0 per 100 participants in the antibiotics group and 3.0 per 100 participants in the appendectomy group (rate ratio, 1.29; 95% CI, 0.67 to 2.50). CONCLUSIONS: For the treatment of appendicitis, antibiotics were noninferior to appendectomy on the basis of results of a standard health-status measure. In the antibiotics group, nearly 3 in 10 participants had undergone appendectomy by 90 days. Participants with an appendicolith were at a higher risk for appendectomy and for complications than those without an appendicolith. (Funded by the Patient-Centered Outcomes Research Institute; CODA ClinicalTrials.gov number, NCT02800785.)