Implications of Obesity on Endoscopic Sinus Surgery Postoperative Complications: An Analysis of the NSQIP Database.

OBJECTIVE: To evaluate the influence of body mass index on postoperative adverse events in adult patients undergoing endoscopic sinus surgery. STUDY DESIGN: Retrospective cohort study. SETTING: Database of the American College of Surgeons NSQIP (National Surgical Quality Improvement Program) from 2006 to 2018. METHODS: The NSQIP database was queried for adult patients undergoing endoscopic sinus surgery. The total sample (N = 1546) was stratified by nonobese (18.5 kg/m2≤ body mass index <30 kg/m2) and obese (≥30 kg/m2). Demographics, comorbidities, intraoperative variables, and postoperative adverse events were compared via chi-square analysis and multivariable logistic regression. RESULTS: Obese patients accounted for 49.7% (n = 768) of the cohort. Obese patients had a higher American Society of Anesthesiologists classification (class III, 45.1% vs 29.5%; P < .001), rate of diabetes (18.2% vs 7.2%, P < .001), and rate of hypertension requiring medication (43.1% vs 23.0%, P < .001). Nonobese patients were more likely to be >58 years of age (23.4% vs 29.0%, P = .02) and have disseminated cancer (<1% vs 3.2%, P < .001). The obese cohort had a lower frequency of surgical complications (3.0% vs 5.4%, P = .027), driven by frequency of perioperative bleeding (1.8% vs 3.7%, P = .022). There was no statistical difference in medical complications (P = .775), unplanned readmissions (P = .286), unplanned reoperations (P = .053), or 30-day mortality (P > .999). After multivariable adjustment, obese subjects had decreased odds of any surgical complication (adjusted odds ratio [aOR], 0.567; 95% CI, 0.329-0.979), perioperative bleeding (aOR, 0.474; 95% CI, 0.239-0.942), and any adverse postoperative event (aOR, 0.740; 95% CI, 0.566-0.968). CONCLUSION: Obesity does not increase the risk of 30-day adverse outcomes following endoscopic sinus surgery and may even be protective against perioperative bleeding.

Burden of cardiovascular morbidity and mortality following humanitarian emergencies: a systematic literature review.

BACKGROUND: The global burden of cardiovascular mortality is increasing, as is the number of large-scale humanitarian emergencies. The interaction between these phenomena is not well understood. This review aims to clarify the relationship between humanitarian emergencies and cardiovascular morbidity and mortality. METHODS: With assistance from a research librarian, electronic databases (PubMed, Scopus, CINAHL, and Global Health) were searched in January 2014. Findings were supplemented by reviewing citations of included trials. Observational studies reporting the effect of natural disasters and conflict events on cardiovascular morbidity and mortality in adults since 1997 were included. Studies without a comparison group were not included. Double-data extraction was utilized to abstract information on acute coronary syndrome (ACS), acute decompensated heart failure (ADHF), and sudden cardiac death (SCD). Review Manager 5.0 (Version 5.2, The Nordic Cochrane Centre; Copenhagen Denmark,) was used to create figures for qualitative synthesis. RESULTS: The search retrieved 1,697 unique records; 24 studies were included (17 studies of natural disasters and seven studies of conflict). These studies involved 14,583 cardiac events. All studies utilized retrospective designs: four were population-based, 15 were single-center, and five were multicenter studies. Twenty-three studies utilized historical controls in the primary analysis, and one utilized primarily geographical controls. DISCUSSION: Conflicts are associated with an increase in long-term morbidity from ACS; the short-term effects of conflict vary by study. Natural disasters exhibit heterogeneous effects, including increased occurrence of ACS, ADHF, and SCD. CONCLUSIONS: In certain settings, humanitarian emergencies are associated with increased cardiac morbidity and mortality that may persist for years following the event. Humanitarian aid organizations should consider morbidity from noncommunicable disease when planning relief and recuperation projects.

Mesenchymal stem cells stimulate protective genetic reprogramming of injured cardiac ventricular myocytes.

Since massive irreversible loss of cardiac myocytes occurs following myocardial injury, injection of human mesenchymal stem cells (hMSCs) has emerged as a promising therapeutic intervention. Despite the growing enthusiasm for this approach, the understanding of how hMSCs evoke cardiac improvement is ever more controversial. The present study critically tests hypothesis that hMSCs provide specific benefit directly to damaged ventricular myocytes. Cultures of neonatal mouse ventricular cardiac myocytes (nMCM) were subjected to two distinct acute stress protocols; incubations with either endotoxin, lipopolysaccharide (LPS) or toxic cytokine, IL-1ß. Myocyte injury was assessed in intracellular Ca(2+) signaling assays in fluo-3-loaded nMCMs that were imaged with high temporal resolution by fluorescent microscopy. Following LPS or IL-1ß treatment there was profound myocyte injury, manifest by chaotic [Ca(2+)](i) handling, quantified as a 3- to 5-fold increase in spontaneous [Ca(2+)](i) transients. Antibody neutralization experiments reveal such damage is mediated in part by interleukin-18 and not by tumor necrosis factor-α (TNF-α). Importantly, normal [Ca(2+)](i) signaling was preserved when cardiomyocytes were co-cultured with hMSCs. Since normal [Ca(2+)](i) handling was maintained in transwell cultures, where nMCMs and hMSCs were separated by a permeable membrane, a protective paracrine signaling cascade is operable. hMSCs provoke a genetic reprogramming of cardiomyocytes. LPS provokes release of TNFα from nMCMs which is blocked by hMSCs grown in co- or transwell cultures. Consistent with cytokine release, flow cytometry analyses reveal that hMSCs also block the LPS- and IL-1ß-dependent activation of cardiac transcription factor, NF-κB. Importantly, hMSC-conditioned medium restores normal Ca(2+) signaling in LPS- and IL-1ß-damaged nMCMs. These results reveal new evidence that hMSCs elicit protective and reparative effects on cardiac tissue through molecular reprogramming of the cardiac myocytes themselves. Thus these studies provide novel new insight into the cellular and molecular mechanisms that underlie the therapeutic benefit of hMSCs in the setting of heart failure. This article is part of a special issue entitled, "Cardiovascular Stem Cells Revisited".

Novel function of cardiac protein kinase D1 as a dynamic regulator of Ca2+ sensitivity of contraction.

Although the function of protein kinase D1 (PKD) in cardiac cells has remained enigmatic, recent work has shown that PKD phosphorylates the nuclear regulators HDAC5/7 (histone deacetylase 5/7) and CREB, implicating this kinase in the development of dysfunction seen in heart failure. Additional studies have shown that PKD also phosphorylates multiple sarcomeric substrates to regulate myofilament function. Initial studies examined PKD through adenoviral vector expression of wild type PKD, constitutively active PKD (caPKD), or dominant negative PKD in cultured adult rat ventricular myocytes. Confocal immunofluorescent images of these cells reveal a predominant distribution of all PKD forms in a non-nuclear, Z-line localized, striated reticular pattern, suggesting the importance of PKD in Ca(2+) signaling in heart. Consistent with an established role of PKD in targeting cardiac troponin I (cTnI), caPKD expression led to a marked decrease in contractile myofilament Ca(2+) sensitivity with an unexpected electrical stimulus dependence to this response. This desensitization was accompanied by stimulus-dependent increases in cTnI phosphorylation in control and caPKD cells with a more pronounced effect in the latter. Electrical stimulation also provoked phosphorylation of regulatory site Ser(916) on PKD. The functional importance of this phospho-Ser(916) event is demonstrated in experiments with a phosphorylation-defective mutant, caPKD-S916A, which is functionally inactive and blocks stimulus-dependent increases in cTnI phosphorylation. Dominant negative PKD expression resulted in sensitization of the myofilaments to Ca(2+) and blocked stimulus-dependent increases in cTnI phosphorylation. Taken together, these data reveal that localized PKD may play a role as a dynamic regulator of Ca(2+) sensitivity of contraction in cardiac myocytes.