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Bullous pemphigoid (BP) is a chronic debilitating autoimmune blistering disease that frequently occurs in the elderly population. Previous studies have suggested a high morbidity and mortality associated with BP. However, relatively few studies have investigated prognostic factors of BP mortality, and they showed considerably various results. This meta-analysis aimed to quantitatively assess the association between several potential prognostic factors and risk of mortality in bullous pemphigoid. A comprehensive search was performed using Pubmed, Embase, and Cochrane Library. Cohort studies that assessed prognostic factors of BP mortality were included. Random-effects model was utilized to calculate the pooled hazard ratio (HR). Publication bias was evaluated qualitatively by constructing a funnel plot and quantitatively by conducting Egger’s test. 14 studies were included comprising 2499 patients. Combined HRs suggested that advanced age (HR 1.63, 95% CI 1.34–1.97), presence of circulating antibodies (HR 1.77, 95% CI 1.20–2.62), concomitant dementia (HR 2.01, 95% CI 1.22–3.33), and concomitant stroke (HR 1.86, 95% CI 1.29–2.67) have an unfavorable impact on patient survival. Gender, disease extent, mucosal involvement, and indirect immunofluorescence result were not shown to be linked to mortality by our analysis. This study indicated that BP patients with older age, circulating antibodies, dementia, and stroke are at greater risk of mortality. Clinicians should be aware of this association and utilize this information in patient education and treatment process.Electronic supplementary materialThe online version of this article (doi:10.1007/s00403-017-1736-1) contains supplementary material, which is available to authorized users.

Tolvaptan is a promising aquaretic for the treatment of refractory ascites in patients with decompensated liver cirrhosis.

Covalent organic frameworks (COFs) are an emerging type of porous crystalline material for efficient catalysis of the oxygen evolution reaction (OER). However, it remains a grand challenge to address the best candidates from thousands of possible COFs. Here, we report a methodology for the design of the best candidate screened from 100 virtual M–N x O y (M = 3d transition metal)-based model catalysts via density functional theory (DFT) and machine learning (ML). The intrinsic descriptors of OER activity of M–N x O y were addressed by the machine learning and used for predicting the best structure with OER performances. One of the predicted structures with a Ni–N 2 O 2 unit is subsequently employed to synthesize the corresponding Ni–COF. X-ray absorption spectra characterizations, including XANES and EXAFS, validate the successful synthesis of the Ni–N 2 O 2 coordination environment. The studies of electrocatalytic activities confirm that Ni–COF is comparable with the best reported COF-based OER catalysts. The current density reaches 10 mA cm –2 at a low overpotential of 335 mV. Furthermore, Ni–COF is stable for over 65 h during electrochemical testing. This work provides an accelerating strategy for the design of new porous crystalline-material-based electrocatalysts.

BackgroundDexamethasone is a common adjuvant for local anesthetics in regional anesthesia, but the optimal route of administration is controversial. Therefore, we did a systematic review and meta-analysis of randomized controlled trials to assess the effect of perineural versus intravenous dexamethasone on local anesthetic regional nerve-blockade outcomes.Materials and methodsMedline (through PubMed), Embase, Cochrane, Web of Science, and Biosis Previews databases were systematically searched (published from inception of each database to January 1, 2017) to identify randomized controlled trials. The data of the selected trials were statistically analyzed to find any significant differences between the two modalities. The primary outcome was the duration of analgesia. Secondary outcomes included duration of motor block, postoperative nausea and vomiting, and postoperative analgesic dose at 24 hours. We conducted a planned subgroup analysis to compare the effects between adding epinephrine or not.ResultsTen randomized controlled trials met the inclusion criteria of our analysis, with a total of 749 patients. Without the addition of epinephrine, the effects of perineural and intravenous dexamethasone were equivalent concerning the duration of analgesia (mean difference 0.03 hours, 95% CI –0.17 to 0.24). However, with the addition of epinephrine, the analgesic duration of perineural dexamethasone versus intravenous dexamethasone was prolonged (mean difference 3.96 hours, 95% CI 2.66–5.27). Likewise, the impact of epinephrine was the same on the duration of motor block. The two routes of administration did not show any significant differences in the incidence of postoperative nausea and vomiting, nor on postoperative analgesic consumption at 24 hours.ConclusionOur results show that perineural dexamethasone can prolong the effects of analgesic duration when compared to the intravenous route, only when epinephrine is coadministered. Without epinephrine, the two modalities show equivalent effect as adjuvants on regional anesthesia.

Volatile anesthetics induce hyperactivity during induction while producing anesthesia at higher concentrations. They also bidirectionally modulate many neuronal functions. However, the neuronal mechanism is unclear. The effects of isoflurane on sodium channel currents were analyzed in acute mouse brain slices, including sodium leak (NALCN) currents and voltage-gated sodium channels (Na v) currents. Isoflurane at sub-anesthetic concentrations increased the spontaneous firing rate of CA3 pyramidal neurons, whereas anesthetic concentrations of isoflurane decreased the firing rate. Isoflurane at sub-anesthetic concentrations enhanced NALCN conductance but minimally inhibited Na v currents. Isoflurane at anesthetic concentrations depressed Na v currents and action potential amplitudes. Isoflurane at sub-anesthetic concentrations depolarized resting membrane potential (RMP) of neurons, whereas hyperpolarized the RMP at anesthetic concentrations. Isoflurane at low concentrations induced hyperactivity in vivo, which was diminished in NALCN knockdown mice. In conclusion, enhancement of NALCN by isoflurane contributes to its bidirectional modulation of neuronal excitability and the hyperactivity during induction.

BackgroundIt is difficult to diagnose spontaneous bacterial peritonitis (SBP) early in decompensated liver cirrhotic ascites patients (DCPs). The aim of the study was to measure serum procalcitonin (PCT) levels and peripheral blood leukocyte/platelet (WBC/PLT) ratios to obtain an early diagnostic indication of SBP in DCPs.MethodsOur cohort of 129 patients included 112 DCPs (94 of whom had infections) and 17 cases with compensated cirrhosis as controls. Bacterial cultures, ascitic fluid (AF) leukocyte and peripheral WBC/PLT counts, and serum PCT measurements at admission were carried out prior to the use of antibiotics. Receiver operating characteristic (ROC) curves were generated to test the accuracies and cut-off values for different inflammatory markers.ResultsAmong the 94 infected patients, 66 tested positive by bacterial culture, for which the positivity of blood, ascites and other secretions were 25.8%, 30.3% and 43.9%, respectively. Lung infection, SBP and unknown sites of infection accounted for 8.5%, 64.9% and 26.6% of the cases, respectively. Serum PCT levels (3.02 ± 3.30 ng/mL) in DCPs with infections were significantly higher than those in control patients (0.15 ± 0.08 ng/mL); p < 0.05. We used PCT ≥0.5 ng/mL as a cut-off value to diagnose infections, for which the sensitivity and specificity was 92.5% and 77.1%. The area under the curve (AUC) was 0.89 (95% confidence interval: 0.84–0.91). The sensitivity and specificity were 62.8% and 94.2% for the diagnosis of infections, and were 68.8% and 94.2% for the diagnosis of SBP in DCPs when PCT ≥2 ng/mL was used as a cut-off value. For the combined PCT and WBC/PLT measurements, the sensitivity was 76.8% and 83.6% for the diagnosis of infections or SBP in DCPs, respectively.ConclusionSerum PCT levels alone or in combination with WBC/PLT measurements seem to provide a satisfactory early diagnostic biomarker in DCPs with infections, especially for patients with SBP.

Background: Circulating cell-free DNA (cfDNA) methylation has been demonstrated to be a promising approach for non-invasive cancer diagnosis. However, the high cost of whole genome bisulfite sequencing (WGBS) hinders the clinical implementation of a methylation-based cfDNA early detection biomarker. We proposed a novel strategy in low-pass WGBS (~5 million reads) to detect methylation changes in circulating cell-free DNA (cfDNA) from patients with liver diseases and hepatocellular carcinoma (HCC). Methods: The effective small sequencing depth were determined by 5 pilot cfDNA samples with relative highdepth WGBS. CfDNA of 51 patients with hepatitis, cirrhosis, and HCC were conducted using low-pass WGBS. The strategy was validated in an independent WGBS cohort of 32 healthy individuals and 26 early-stage HCC patients. Fifteen paired tumor tissue and buffy coat samples were used to characterize the methylation of hepatitis B virus (HBV) integration regions and genome distribution of cfDNA.