To demonstrate the safety of transendocardial stem cell injection (TESI) with autologous MSCs and BMCs in patients with ICM.• To assess prespecified outcomes of efficacy.
Oxypurinol did not produce clinical improvements in unselected patients with moderate-to-severe heart failure. However, post-hoc analysis suggests that benefits occur in patients with elevated SUA in a manner correlating with the degree of SUA reduction. Serum uric acid may serve as a valuable biomarker to target XO inhibition in heart failure. (Oxypurinol Compared With Placebo for Class III-IV NYHA Congestive Heart Failure; NCT00063687).
Given the high risk of infection-related mortality, patients with end-stage kidney disease (ESKD) may be at increased risk with COVID-19. To assess this, we compared outcomes of patients with and without ESKD, hospitalized with COVID-19. This was a retrospective study of patients admitted with COVID-19 from 13 New York. hospitals from March 1, 2020, to April 27, 2020, and followed through May 27, 2020. We measured primary outcome (in-hospital death), and secondary outcomes (mechanical ventilation and length of stay), Of 10,482 patients with COVID-19, 419 had ESKD. Patients with ESKD were older, had a greater percentage self-identified as Black, and more comorbid conditions. Patients with ESKD had a higher rate of inhospital death than those without (31.7% vs 25.4%, odds ratio 1.38, 95% confidence interval 1.12-1.70). This increase rate remained after adjusting for demographic and comorbid conditions (adjusted odds ratio 1.37, 1.09-1.73). The odds of length of stay of seven or more days was higher in the group with compared to the group without ESKD in both the crude and adjusted analysis (1.62, 1.27-2.06; vs 1.57, 1.22-2.02, respectively). There was no difference in the odds of mechanical ventilation between the groups. Independent risk factors for in-hospital death for patients with ESKD were increased age, being on a ventilator, lymphopenia, blood urea nitrogen and serum ferritin. Black race was associated with a lower risk of death. Thus, among patients hospitalized with COVID-19, those with ESKD had a higher rate of in-hospital death compared to those without ESKD.
Rationale
While accumulating data support the efficacy of intramyocardial cell-based therapy to improve LV function in patients with chronic ischemic cardiomyopathy undergoing CABG, the underlying mechanism and impact of cell injection site remain controversial.Mesenchymal stem cells (MSCs) improve LV structure and function through several effects including: reducing fibrosis, neoangiogenesis and neomyogenesis.
Objective
To test the hypothesis that the impact on cardiac structure and function following intramyocardial injections of autologous MSCs results from a concordance of pro-recovery phenotypic effects.
Methods and Results
Six patients were injected with autologous MSCs into akinetic/hypokinetic myocardial territories not receiving bypass graft for clinical reasons. MRI was used to measure scar, perfusion, wall thickness and contractility at baseline, 3, 6 and 18 months and to compare structural and functional recovery in regions that received MSC injections alone, revascularization alone, or neither. A composite score of MRI variables was used to assess concordance of antifibrotic effects, perfusion, and contraction at different regions. After 18 months, subjects receiving MSCs exhibited increased LVEF (+9.4±1.7%, p=0.0002) and decreased scar mass (-47.5±8.1%; p<0.0001) compared to baseline. MSC-injected segments had concordant reduction in scar size, perfusion and contractile improvement (concordant score: 2.93±0.07), whereas revascularized (0.5±0.21) and non-treated segments (-0.07±0.34) demonstrated non-concordant changes (p<0.0001 vs. injected segments).
Conclusions
Intramyocardial injection of autologous MSCs into akinetic yet non-revascularized segments produces comprehensive regional functional restitution, which in turn drives improvement in global LV function. These findings, although inconclusive due to lack of placebo group, have important therapeutic and mechanistic hypothesis-generating implications.
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