Atrial fibrillation after cardiac surgery: Prevention and management: The Australasian experience

Background

Atrial fibrillation (AF) after cardiac surgery is a major health problem that is associated with a significant financial burden. This paper aims to highlight this problem and review the current guidelines in the prevention and management of AF after cardiac surgery, providing our experience in the Australasian centers.

Young children with perforated appendicitis benefit from prompt appendectomy

Background/PurposeTo identify factors associated with nonoperative treatment failure in pediatric perforated appendicitis compared to immediate appendectomy.MethodsAfter IRB approval, between September 2016 and August 2017, prospective data were recorded for children (age: 1–18 years) with completed appendectomies and pathologist-confirmed perforations. Children were treated according to clinician-designated preference. Nonoperative treatment was considered failed if a nonresolving obstruction developed or any return of symptoms before the planned interval. The median time from pain onset to treatment initiation was 3 days (range: 1–14). Presentation on days 1 or 2 (early) was compared to day 3 or after(late). The nonoperatives were compared to appendectomies stratified by presentation time. Variables were compared by chi-square, Fisher exact or t-tests. Logistic regression evaluated for independence.ResultsOf 201 suspected perforations, 176 were included, 101 (57%) immediate appendectomies and 75 (43%) nonoperatives. Of 75, 24 (32%) failed; 6 (25%) in hospital, 18 (75%) after discharge. In 51 (68%), nonoperative treatment succeeded. Significantly younger children failed nonoperative treatment (p = 0.03). Failure was independently associated with treatment initiation within 2.75 days from pain onset (OR: 0.07, 95% CI: 0.57–0.98) (p = 0.010) and lower WBC at presentation (OR: 0.03, 95% CI: 0.81–0.98) (p = 0.014). When compared to immediate appendectomy, nonoperatives had more morbidity.ConclusionYounger children fail nonoperative treatment, perforate rapidly and have a significantly lower WBC, but benefit from immediate appendectomy.Level of evidenceTreatment Study Level II.     

Misfinancing global health: a case for transparency in disbursements and decision making

To address the gap between health investments and financial flows worldwide, we identified the patterns in allocation of funds by the four largest donors--ie, the World Bank, Bill & Melinda Gates Foundation (BMGF), the US Government, and the Global Fund to Fight HIV/AIDS, Tuberculosis and Malaria--in 2005. We created a disbursement database with information gathered from the annual reports and budgets. Funding per death varied widely according to type of disease--eg, US$1029.10 for HIV/AIDS to $3.21 for non-communicable diseases. The World Bank, US Government, and Global Fund provided more than 98% of their funds to service delivery, whereas BMGF gave most of its funds to research. BMGF grants in 2005 were given largely to private research organisations, universities, and civil societies in rich countries, whereas the US Government and Global Fund primarily disbursed grants to sub-Saharan Africa. Publicly available data for global health disbursements is incomplete and not standardised. Continued attention is needed to develop country ownership, particularly in planning and priority setting.     

A simple, rapid, and convenient Luminex-compatible method of tissue isolation

Various pathological conditions are associated with changes in multiple protein biomarkers, and these changes can be assessed using xMAP beads and the Luminex platform. Although this platform is most commonly utilized in the analysis of biomarkers in serum, plasma, or urine, it is often desirable to measure these analytes in tissues (e.g., biopsy specimens). We have developed a simple, rapid method of tissue isolation in which excised tissues are permeabilized in RNAlater at 4 degrees C overnight, followed by Luminex analysis for inflammatory biomarkers (cytokines). This method was compared with flash-freezing in both mouse liver and human debrided wound specimens, and may be of utility in other clinical settings.     

Activation of latent transforming growth factor-β1 by nitric oxide in macrophages: Role of soluble guanylate cyclase and MAP kinases

The inducible nitric oxide (NO) synthase and the cytokine transforming growth factor-β1 (TGF-β1), both central modulators of wound healing, interact reciprocally: TGF-β1 generally suppresses iNOS expression, while NO can induce and activate latent TGF-β1. We have shown that chemical NO activates recombinant human latent TGF-β1 by S-nitrosation of the latency-associated peptide (LAP), a cleaved portion of pro-TGF-β1 that maintains TGF-β1 in a biologically-inactive state. We hypothesized that cell-associated TGF-β1 could be activated by NO via known NO-inducible signaling pathways (soluble guanylate cyclase [sGC] and mitogen-activated protein [MAP] kinases). Treatment of mouse RAW 264.7 macrophage-like cells with the NO donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP) led to a dose- and time-dependent increase in cell-associated active and latent TGF-β1, as assessed by quantitative immunocytochemistry for active TGF-β1 vs. LAP and partially validated by western blot analysis. Treatment with the sGC inhibitor 1,H-[1,2,4]oxadiazole[4,3-a]quinoxalon-1-one (ODQ) reduced both active and latent TGF-β1 dose-dependently. SNAP, in the presence or absence of ODQ or the MAP kinase inhibitors, did not affect steady-state TGF-β1 mRNA levels. Treatment with inhibitors specific for JNK1/2, ERK1/2, and p38 MAP kinases suppressed SNAP-induced active and latent TGF-β1. Treatment with the cell-permeable cGMP analog 8-Br-cGMP increased both active and latent TGF-β1. However, TGF-β1 activation induced by 8-Br-cGMP was not blocked by MAP kinase inhibitors. Our findings suggest that NO activates latent TGF-β1 via activation of sGC and generation of cGMP and separately via MAP kinase activation, and may shed insight into the mechanisms by which both cGMP production and MAP kinase activation enhance wound healing.