Association of postoperative atrial fibrillation with higher dosing ratios of protamine-to-heparin.

Background: Postoperative atrial fibrillation (POAF) is defined as new-onset AF in the immediate postoperative period. The relatively high incidence of POAF after cardiac surgery is well described, but pathophysiological mechanisms underlying the initiation, maintenance, and progression of POAF may be multifactorial and have not yet been comprehensively characterized. One of the mechanisms includes altered Ca2+ kinetics. Accumulating evidence has suggested that altered atrial cytosolic calcium handling contributes to the development of POAF, protamine reversibly modulates the calcium release channel/ryanodine receptor 2 (RyR2) and voltage-dependent cardiac RyR2. However, it is currently unknown whether such abnormalities contribute to the arrhythmogenic substrate predisposing patients to the development of POAF. Methods: We have retrospectively analyzed 147 patients who underwent cardiac surgery with cardiopulmonary bypass support. Of these, 40 patients were excluded from the analysis because of pre-existing AF. All patients received heparin followed by protamine at different dosing ratios of protamine-to-heparin, depending on the periods studied. Results: The dosing ratio of protamine-to-heparin = 1.0 was compared with higher dosing ratios of protamine-to-heparin >1.0 up to 1.7. POAF developed in 15 patients (15/107 = 14%), of these, 5 out of 57 patients (33.3%) in the dosing ratio of protamine-to-heparin = 1.0 and 10 out of 35 patients (66.7%) in the higher dosing ratios of protamine-to-heparin. Statistical significance was observed in patients with higher dosing ratios of protamine-to-heparin, compared with the dosing ratio of protamine-to-heparin = 1.0 (odds ratio = 3.890, 95% CI = 1.130-13.300, p-value = 0.031). When types of diseases were analyzed in terms of higher dosing ratios of protamine-to-heparin, only valvular disorders were significantly associated with POAF (p = 0.04). Conclusions: Protamine is clinically utilized to reverse heparin overdose and has been shown to display immunological and inflammatory alterations. However, its association with POAF has not been reported. Our results provide evidence that higher dosing ratios of protamine-to-heparin may increase the incidence of POAF.

Specificity of tuberculin skin test improved by BCG immunization schedule change in Japan.

INTRODUCTION: Tuberculin skin test (TST) has been used to diagnose tuberculosis (TB) and latent tuberculosis infection (LTBI). However, in Bacillus Calmette-Guérin (BCG) vaccinated patients, TST tends to produce false-positive results. According to the previous vaccination schedule, Japanese people were mandated to receive up to three doses of BCG-vaccine. The vaccination schedule was changed in 2003 and as per the new schedule, only infants are administered a dose of BCG vaccine. Our hypothesis is that this change can lead to a reduction in the cross-reaction to TST. METHODS: We evaluated the TST results obtained from 1097 recruits from six defense camps and 667 recruits from an air base. These TST data were divided into two groups according to the date of birth: a new group and an old group according to the BCG immunization schedule. We then analyzed positive and negative reaction of TST and erythema sizes. RESULTS: We confirmed that the change in BCG-vaccination schedule significantly decreased TST false-positive reaction (Pmeta = 1.4 × 10-18; risk ratio = 0.83; 95% confidence interval: 0.80-0.87) and erythema size (Pmeta = 1.1 × 10-4; mean difference = 6.6 mm; 95% confidence interval: 3.2 mm-9.9 mm). CONCLUSIONS: We showed the reduction in BCG cross-reaction to TST, in the new BCG vaccination schedule group, compared to the old group, we also have extracted information on the improvement in the specificity of TST for LTBI and TB diagnosis, which resulted from BCG schedule change.

Activating prostaglandin E2 receptor subtype EP4 increases secreted mucin from airway goblet cells.

Prostaglandin E2 (PGE2) is a ligand of the E-type prostanoid receptors, EP1-4. PGE2 secretion is increased in the airways of patients with asthma by secretory phospholipases A2, which also increases MUC5AC mucin in goblet cells. We hypothesized that PGE2 would also increase MUC5AC mRNA and secreted protein through specific EP receptor activation. We sought to assess the effect of specific EP receptor activation on MUC5AC secretion from ciliated-enriched cells or goblet-enriched cells induced by IL-13. We develop an enriched goblet cell epithelium by growing normal human bronchial epithelial cells at air liquid interface for 14 days in the presence of IL-13. We examined exposure to 4 specific EP receptor agonists at 24 h and 14 days in cells grown with or without IL-13 exposure, and measured MUC5AC mRNA and secreted protein, as well as airway culture morphology, and EP receptor expression. In ciliated-enriched cells grown in the absence of IL-13, the EP4 receptor agonist modestly increased both MUC5AC mRNA and secretion (p < 0.001, 241% increase of transcripts and p < 0.01, 86% increase of secreted protein) but did not visibly change cell morphology. In goblet-enriched cells grown in the presence of IL-13, the EP4 receptor agonist greatly increased both MUC5AC mRNA and protein (p < 0.001, 315% increase of transcripts and 92% increase of secreted protein). Specific activation of the other EP receptor had no effect on secreted mucin. EP4 receptor mRNA and protein were significantly increased in goblet-enriched cells, while the other receptor mRNA were decreased. We conclude that PGE2 stimulates airway mucin production predominantly by EP4 receptor activation in association with increased EP4 receptor expression. This may contribute to mucus hypersecretion as seen in severe asthma.

A systematic review of diagnostic methods to differentiate acute lung injury/acute respiratory distress syndrome from cardiogenic pulmonary edema.

BACKGROUND: Discriminating acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) from cardiogenic pulmonary edema (CPE) is often challenging. This systematic review examines studies using biomarkers or images to distinguish ALI/ARDS from CPE. METHODS: Three investigators independently identified studies designed to distinguish ALI/ARDS from CPE in adults. Studies were identified from PubMed, and the Cochrane Central Register of Controlled Trials database until July 3, 2017. RESULTS: Of 475 titles and abstracts screened, 38 full texts were selected for review, and we finally included 24 studies in this systematic review: 21 prospective observational studies, two retrospective observational studies, and one retrospective combined with prospective study. These studies compared various biomarkers to differentiate subjects with ALI/ARDS and in those with CPE, and 13 calculated the area under the receiver operator characteristic curve (AUC). The most commonly studied biomarker (four studies) was brain natriuretic peptide (BNP) and the discriminatory ability ranged from AUC 0.67-0.87 but the timing of measurement varied. Other potential biomarkers or tools have been reported, but only as single studies. CONCLUSIONS: There were no identified biomarkers or tools with high-quality evidence for differentiating ALI/ARDS from CPE. Combining clinical criteria with validated biomarkers may improve the predictive accuracy.