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IntroductionPatients with idiopathic inflammatory myopathies (IIMs) are sometimes complicated with life-threatening conditions requiring intensive care unit (ICU) admission. In the past, owing to the low incidence of IIM, little was known about such patients. Our aim was to investigate the clinical features and outcomes of these patients and identify their risk factors for mortality.MethodsA retrospective study was performed of IIM patients admitted over an 8-year period to the medical ICU of a tertiary referral center in China. We collected data regarding demographic features, IIM-related clinical characteristics, reasons for admission, organ dysfunction, and outcomes. Independent predictors of ICU mortality were identified through multivariate logistic regression analysis.ResultsOf the 102 patients in our cohort, polymyositis (PM), dermatomyositis (DM), and clinically amyopathic dermatomyositis (CADM) accounted for 23.5%, 64.7%, and 11.7% respectively. The median duration from the onset of IIM to ICU admission was 4.3 months (interquartile range [IQR], 2.6–9.4 months). Reasons for ICU admission were infection alone (39.2%), acute exacerbation of IIM alone (27.5%), the coexistence of both (27.5%), or other reasons (5.8%). Pneumonia accounted for 97% of the infections; 63.2% of infections with documented pathogens were caused by opportunistic agents. Rapid progressive interstitial lung disease (RP-ILD) was responsible for 87.5% of acute exacerbation of IIM. The median Acute Physiology and Chronic Health Evaluation II (APACHE II) score on ICU day 1 was 17 (IQR 14–20). On ICU admission, acute respiratory failure (ARF) was the most common type (80.4%) of organ failure. The mortality rate in the ICU was 79.4%. Factors associated with increased ICU mortality included a diagnosis of DM (including CADM), a high APACHE II score, the presence of ARF, a decreased PaO2/FiO2 ratio, and a low lymphocyte count at the time of ICU admission.ConclusionsThe outcome of IIM patients admitted to the ICU was extremely poor. A diagnosis of DM/CADM, the presence and severity of ARF, and the lymphocyte counts at ICU admission were shown to be valuable for predicting outcome. Opportunistic infections and rapidly progressive interstitial lung disease warrant concern in treating these patients.

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Rationale: β-Adrenoceptor activation contributes to sudden death risk in heart failure. Chronic β-adrenergic stimulation, as occurs in patients with heart failure, causes potentially arrhythmogenic reductions in slow delayed-rectifier K + current (I Ks ). Objective: To assess the molecular mechanisms of I Ks downregulation caused by chronic β-adrenergic activation, particularly the role of exchange protein directly activated by cAMP (Epac). Methods and Results: Isolated guinea pig left ventricular cardiomyocytes were incubated in primary culture and exposed to isoproterenol (1 μmol/L) or vehicle for 30 hours. Sustained isoproterenol exposure decreased I Ks density (whole cell patch clamp) by 58% ( P <0.0001), with corresponding decreases in potassium voltage-gated channel subfamily E member 1 (KCNE1) mRNA and membrane protein expression (by 45% and 51%, respectively). Potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) mRNA expression was unchanged. The β1-adrenoceptor antagonist 1-[2-((3-Carbamoyl-4-hydroxy)phenoxy)ethylamino]-3-[4-(1-methyl-4-trifluoromethyl-2-imidazolyl)phenoxy]-2-propanol dihydrochloride (CGP-20712A) prevented isoproterenol-induced I Ks downregulation, whereas the β 2 -antagonist ICI-118551 had no effect. The selective Epac activator 8-pCPT-2′-O-Me-cAMP decreased I Ks density to an extent similar to isoproterenol exposure, and adenoviral-mediated knockdown of Epac1 prevented isoproterenol-induced I Ks /KCNE1 downregulation. In contrast, protein kinase A inhibition with a cell-permeable highly selective peptide blocker did not affect I Ks downregulation. 1,2-Bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetate-AM acetoxymethyl ester (BAPTA-AM), cyclosporine, and inhibitor of nuclear factor of activated T cell (NFAT)-calcineurin association-6 (INCA6) prevented I Ks reduction by isoproterenol and INCA6 suppressed isoproterenol-induced KCNE1 downregulation, consistent with signal-transduction via the Ca 2+ /calcineurin/NFAT pathway. Isoproterenol induced nuclear NFATc3/c4 translocation (immunofluorescence), which was suppressed by Epac1 knockdown. Chronic in vivo administration of isoproterenol to guinea pigs reduced I Ks density and KCNE1 mRNA and protein expression while inducing cardiac dysfunction and action potential prolongation. Selective in vivo activation of Epac via sp-8-pCPT-2′-O-Me-cAMP infusion decreased I Ks density and KCNE1 mRNA/protein expression. Conclusions: Prolonged β 1 -adrenoceptor stimulation suppresses I Ks by downregulating KCNE1 mRNA and protein via Epac-mediated Ca 2+ /calcineurin/NFAT signaling. These results provide new insights into the molecular basis of K + channel remodeling under sustained adrenergic stimulation.

Restriction of third-generation cephalosporin use may improve the antibiotic susceptibility and reduce infection-related hospital mortality in critically ill patients.

In combination with a mildly reduced-calorie diet, orlistat significantly reduces body weight, and improves glycaemic control and several cardiovascular risk factors in overweight and obese Chinese patients with newly diagnosed Type 2 diabetes.

A multicenter study was performed to evaluate the value of testing gastric aspirate (GA) with Xpert MTB/RIF Ultra assay (Ultra) for childhood TB detection in China. Totally, 129 children with active tuberculosis (TB) and 173 children without TB were enrolled. The sensitivity of Ultra in bacteriologically confirmed TB and probable TB cases was 87.5% (42/48) and 44.4% (36/81), respectively. The specificity of Ultra was high (99.4%, 172/173). When Ultra, culture, and acid-fast bacilli outcomes were integrated as a composite reference standard, the percentage of children with definite TB increased from 37.2% (48/129) to 67.4% (87/129). The sensitivity of Ultra is 80.0% (40/50) in children aged <4 years, which is significantly higher than that in older children (48.1%, 38/79) (p < 0.001). The Ultra assay conducted using GA samples can provide faster results, allowing an early and accurate TB diagnosis, especially in younger children with difficulty producing sputum.

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