Clinical outcomes in myocardial infarction and multivessel disease after a cardiac rehabilitation programme: Partial versus complete revascularization

Background Current guideline recommendations encourage culprit vessel only percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease. However, recent studies have shown a better clinical outcome in patients who receive multivessel PCI. Aim To measure and compare clinical outcomes between partial revascularization (PR) versus complete revascularization (CR) in patients with STEMI and multivessel disease who underwent a cardiac rehabilitation programme. Methods We retrospectively reviewed the medical records of 282 patients with STEMI and multivessel disease who received PR or CR and were subsequently enrolled in a cardiac rehabilitation programme between July 2006 and November 2013 at La Paz University Hospital. The incidences of cardiovascular events, new PCI, hospital admissions for cardiovascular reasons and mortality were compared between the PR and CR groups. Results Overall, 143 patients received PR and 139 received CR. Baseline characteristics were similar in both groups, except for mean age (59.3 vs. 56.7 years; P = 0.02), diabetes mellitus prevalence (34.3% vs. 20.1%; P = 0.01) and number of arteries with stenosis (2.6 vs. 2.3; P = 0.001). During the mean follow-up of 48.0 ± 25.9 months, a cardiovascular event occurred in 23 (16.1%) PR patients and 20 (14.4%) CR patients, with no statistically significant differences in the early (hazard ratio: 0.61, 95% confidence interval: 0.19–1.89) or late (hazard ratio: 1.40, 95% confidence interval: 0.62–3.14) follow-up periods. Cox regression, adjusted for age, sex, presence of diabetes mellitus and number of affected coronary vessels, showed no difference in new cardiovascular event risk. Conclusions There were no statistical differences in clinical outcomes between PR and CR among patients who received cardiac rehabilitationLuis Furuya-Kanamori is funded by an Endeavour Postgraduate Scholarship (#3781 2014), an Australian National University Higher Degree Scholarship and a Fondo para la Innovación, Ciencia y Tecnologia Scholarship (#095-FINCyTBDE-2014)

Selective inhibition of inhibitory kappa B kinase-β abrogates induction of nitric oxide synthase in lipopolysaccharide-stimulated rat aortic smooth muscle cells

1. In this study, we utilised a number of adenoviral constructs in order to examine the role of intermediates of the NF-κB pathway in the regulation of inducible nitric oxide synthase (iNOS) induction in rat aortic smooth muscle cells (RASMCs). 2. Lipopolysaccharide (LPS) stimulated a significant increase in iNOS induction and NF-κB DNA binding. These parameters were substantially reduced by overexpression of a wild-type Iκ-Bα adenoviral construct (Ad.Iκ-Bα), confirming a role for NF-κB in iNOS induction. 3. Infection with a dominant-negative IKKα adenoviral construct (Ad.IKKα(+/−)) did not significantly affect iNOS induction, NF-κB DNA binding or Iκ-Bα loss. Infection of RASMCs with adenovirus encoding a dominant-negative IKKβ (Ad.IKKβ(+/−)) essentially abolished iNOS induction and activation of the NF-κB pathway. 4. Pretreatment of RASMCs with a novel specific inhibitor of IKKβ, SC-514, significantly reduced iNOS induction, NF-κB DNA binding and I-κBα loss in a concentration-dependent manner. 5. In both RASMCs and human umbilical vein endothelial cells (HUVECs), infection with Ad.IKKβ(+/−) also inhibited COX-2 expression in response to LPS. However, Ad.IKKα(+/−) was again without effect. 6. These data suggest that IKKβ plays a predominant, selective role in the regulation of NF-κB-dependent induction of iNOS in RASMCs

Subcutaneous anti-COVID-19 hyperimmune immunoglobulin for prevention of disease in asymptomatic individuals with SARS-CoV-2 infection: a double-blind, placebo-controlled, randomised clinical trialResearch in context

Summary: Background: Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. Methods: We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141. Findings: 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, −3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; −9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. Interpretation: Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19. Funding: Grifols