Association between sex and survival after non-traumatic out of hospital cardiac arrest: A systematic review and meta-analysis.

BACKGROUND: Existing studies have shown conflicting results regarding the relationship of sex with survival after out of hospital cardiac arrest (OHCA). This systematic review evaluates the association of female sex with survival to discharge and survival to 30 days after non-traumatic OHCA. METHODS: We searched Medline, Embase, CINAHL, Web of Science, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews from inception through June 2021 for studies evaluating female sex as a predictor of survival in adult patients with non-traumatic cardiac arrest. Random-effects inverse variance meta-analyses were performed to calculate pooled odds ratios (ORs) with 95% confidence intervals (CI). The GRADE approach was used to assess evidence quality. RESULTS: Thirty studies including 1,068,788 patients had female proportion of 41%. There was no association for female sex with survival to discharge (OR 1.03, 95% CI 0.95-1.12; I2 = 89%). Subgroup analysis of low risk of bias studies demonstrated increased survival to discharge for female sex (OR 1.20, 95% CI 1.18-1.23; I2 = 0%) and with high certainty, the absolute increase in survival was 2.2% (95% CI 0.1-3.6%). Female sex was not associated with survival to 30 days post-OHCA (OR 1.02, 95% CI 0.92-1.14; I2 = 79%). CONCLUSIONS: In adult patients experiencing OHCA, with high certainty in the evidence from studies with low risk of bias, female sex had a small absolute difference for the outcome survival to discharge and no difference in survival at 30 days. Future models that aim to stratify risk of survival post-OHCA should focus on sex-specific factors as opposed to sex as an isolated prognostic factor.

Supporting the Ross procedure: preserving root physiology while mitigating autograft dilatation.

PURPOSE OF REVIEW: The purpose of this article is to describe the optimized approach to nonrepairable aortic valve disease in young adults with a Ross procedure, while preserving the dynamic physiology of the aortic root. RECENT FINDINGS: As the techniques for supporting pulmonary autografts continue to be refined, and the applicability of the Ross procedure continues to expand, an assessment of the various techniques based on aortic root physiology is warranted. Semi-resorbable scaffolds show promise in ovine models for improving the Ross procedure. Recent long-term outcomes for the Dacron inclusion technique in comparison to more physiologic methods of support emphasize the importance of balancing the prevention of early dilatation with the preservation of root haemodynamics. As this review will synthesize, the dynamic physiology of the root may be preserved even in patients at a higher risk of autograft dilatation. SUMMARY: The favourable long-term outcomes of the Ross procedure can be partly attributed to the ability of the autograft to restore dynamism to the neoaortic root. Patient-specific modifications that respect root physiology can tailor the Ross procedure to address each patient's risk factors for early dilatation and late failure. As such, the Ross procedure should be recognized as an increasingly favourable solution for a wide spectrum of nonpreservable aortic valve disease in young adults.

Cyclic lactam hybrid α-MSH/Agouti-related protein (AGRP) analogues with nanomolar range binding affinities at the human melanocortin receptors.

A novel hybrid melanocortin pharmacophore was designed based on the topographical similarities between the pharmacophores of Agouti related protein (AGRP) an endogenous melanocortin antagonist, and α-melanocyte-stimulating hormone (α-MSH), an endogenous melanocortin agonist. When employed in two different 23-membered macrocyclic lactam peptide templates, the designed hybrid AGRP/MSH pharmacophore yielded non-competitive ligands with nanomolar range binding affinities. The topography-based pharmacophore hybridization strategy will prove useful in development of unique non-competitive melanocortin receptor modulators.

Development of cyclic gamma-MSH analogues with selective hMC3R agonist and hMC3R/hMC5R antagonist activities.

A series of cyclic lactam analogues of gamma-MSH (H-Tyr1-Val2-Met3-Gly4-His5-Phe6-Arg7-Trp8-Asp9-Arg10-Phe11-Gly12-OH) with a bulky hydrophobic residue in the direct proximity to the pharmacophore (Xaa-D-Phe/D-Nal(2')-Arg-Trp) were designed and synthesized by solid-phase methods. A variety of amino acids with a broad range of hydrophobic/hydrophilic properties was introduced in position 5 to further explore their complementary role in receptor selectivity. Biological evaluation of these peptides revealed several analogues with potent hMC3R agonist and hMC3R/hMC5R antagonist activities, and good receptor selectivity. Analogue 4, c[Nle-Arg-D-Phe-Arg-Trp-Glu]-NH2, was found to be a very potent and selective hMC3R agonist (EC50=1.2 nM, 112% act). In addition, analogue 13, c[Nle-Val-D-Nal(2')-Arg-Trp-Glu]-NH2, was identified as an hMC3R/hMC5R antagonist with the best selectivity against the hMC4R in this series (pA2(hMC3R)=8.4; pA2(hMC5R)=8.7). These results indicate the significance of steric factors in melanocortin receptor selectivity and suggest that introduction of bulky residues in the direct proximity to the melanocortin pharmacophore is an effective approach to design of novel hMC3R and hMC5R selective ligands.