IsaB Inhibits Autophagic Flux to Promote Host Transmission of Methicillin-Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a major nosocomial pathogen that is widespread in both health-care facilities and in the community at large, as a result of direct host-to-host transmission. Several virulence factors are associated with pathogen transmission to naive hosts. Immunodominant surface antigen B (IsaB) is a virulence factor that helps Staphylococcus aureus to evade the host defense system. However, the mechanism of IsaB on host transmissibility remains unclear. We found that IsaB expression was elevated in transmissible MRSA. Wild-type isaB strains inhibited autophagic flux to promote bacterial survival and elicit inflammation in THP-1 cells and mouse skin. MRSA isolates with increased IsaB expression showed decreased autophagic flux, and the MRSA isolate with the lowest IsaB expression showed increased autophagic flux. In addition, recombinant IsaB rescued the virulence of the isaB deletion strain and increased the group A streptococcus (GAS) virulence in vivo. Together, these results reveal that IsaB diminishes autophagic flux, thereby allowing MRSA to evade host degradation. These findings suggest that IsaB is a suitable target for preventing or treating MRSA infection

The relationship between gallbladder status and recurrent biliary complications in patients with choledocholithiasis following endoscopic treatment

AbstractBackgroundEndoscopic methods are currently the treatment of choice for patients with common bile duct (CBD) stones, but subsequent management of the intact gallbladder for patients following endoscopic treatment is still controversial. The primary aim of this study was to discover the association between gallbladder status and recurrent biliary complications for patients with CBD stones after endoscopic treatment. Additionally, we also sought to determine risk factors for recurrent biliary complications in these patients.MethodsThe records of 1625 patients with CBD stones following endoscopic treatment were reviewed. A total of 681 patients were enrolled and subsequently categorized into four groups: Group 1 (n = 201), calculous gallbladder; Group 2 (n = 140), acalculous gallbladder; Group 3 (n = 175), elective cholecystectomy after endoscopic treatment; and Group 4 (n = 165), prior cholecystectomy. The basic demographics and recurrent biliary complications during follow-up among these four groups were analyzed by Chi-square test, ANOVA, Kaplan-Meier analysis, and log-rank test.ResultsDuring the median follow-up period of 34 months, 133 patients (20%) with recurrent biliary complications were identified. The recurrence rates of Groups 1, 2, 3, and 4 were 29%, 11%, 15%, and 19%, respectively. Kaplan-Meier analysis showed that patients with calculous gallbladder had a significantly higher rate of recurrent biliary complication. In multivariate analysis, patients with a history of cirrhosis, juxta-papillary diverticulum, calculous gallbladder, CBD size ≥1.5 cm, and endoscopic management with endoscopic sphincterotomy were at a higher risk for developing biliary complications (p = 0.029, p = 0.039, p < 0.001, p = 0.002, p = 0.021, respectively.)ConclusionPatients with cholecystolithiasis and CBD stones had a higher incidence of recurrent biliary complications. For some of these patients, elective cholecystectomy following endoscopic treatment may be considered. However, routine elective cholecystectomy in patients with normal gallbladder is not appropriate because of the low recurrence of biliary complications. Whether gallbladder function affects the biliary clearance and biliary complications requires further research

The Efficacy of Endoscopic Papillary Balloon Dilation for Patients with Acute Biliary Pancreatitis

Background. No study investigated the efficacy and safety of endoscopic papillary balloon dilation (EPBD) for the treatment of acute biliary pancreatitis (ABP). Method. We retrospectively reviewed the effects of EPBD on patients with ABP from February 2003 to December 2012. The general data, findings of image studies, details of the procedure, and outcomes after EPBD were analyzed. Result. Total 183 patients (male/female: 110/73) were enrolled. The mean age was 65.9 years. Among them, 155 patients had mild pancreatitis. The meantime from admission to EPBD was 3.3 days. Cholangiogram revealed filling defects inside the common bile duct (CBD) in 149 patients. The mean dilating balloon size was 10.5 mm and mean duration of the dilating procedure was 4.3 minutes. Overall, 124 patients had gross stones retrieved from CBD. Four (2.2%) adverse events and 2 (1.1%) intraprocedure bleeding incidents but no procedure-related mortality were noted. Bilirubin and amylase levels significantly decreased after EPBD. On average, patients resumed oral intake within 1.4 days. The clinical parameters and outcomes were similar in patients with different severity of pancreatitis. Conclusion. EPBD can be effective and safe for the treatment of ABP, even in patients presenting with severe disease

Chronic Hepatitis B with Spontaneous Severe Acute Exacerbation

Chronic hepatitis B virus (HBV) infection is a major global health problem with an estimated 400 million HBV carriers worldwide. In the natural history of chronic hepatitis B (CHB), spontaneous acute exacerbation (AE) is not uncommon, with a cumulative incidence of 10%–30% every year. While exacerbations can be mild, some patients may develop hepatic decompensation and even die. The underlying pathogenesis is possibly related to the activation of cytotoxic T lymphocyte-mediated immune response against HBV. An upsurge of serum HBV DNA usually precedes the rise of alanine aminotransferase (ALT) and bilirubin. Whether antiviral treatment can benefit CHB with severe AE remains controversial, but early nucleos(t)ide analogues treatment seemed to be associated with an improved outcome. There has been no randomized study that compared the effects of different nucleos(t)ide analogues (NA) in the setting of CHB with severe AE. However, potent NAs with good resistance profiles are recommended. In this review, we summarized current knowledge regarding the natural history, pathogenetic mechanisms, and therapeutic options of CHB with severe AE

Comparison of urodynamic bladder dysfunction in male patients with pelvic organ malignancies

Objective: Bladder dysfunction is a common complication after pelvic cancer treatments (radical pelvic surgery or chemoradiotherapy) that may affect patient satisfaction and quality of life. The aim of this study is to compare urodynamic bladder dysfunction among male patients with different pelvic organ malignancies (POMs). Materials and Methods: Data were collected from male patients with POM undergoing urodynamic studies (UDSs). Patients were stratified into three groups based on the origin of cancer (prostate, bladder, and colorectum). Selected data, including age, clinical tumor staging, lower urinary tract symptoms or acute urinary retention, and the parametric values of UDSs, were compared among the groups. SPSS 17.0.1 for Windows and Microsoft Office Excel 2007 were used for all statistical analysis. Results: A total of 640 patients with POM from the prostate (40.9%), bladder (33.5%), and colorectum (25.6%) were investigated. Patient age ranged from 39 to 89 years (mean 72.93 ± 9.08 years). In uroflowmetry (525 patients), the maximal urine flow rate was significantly lower in the prostate group (11.49 ± 5.53 ml/s). Cystometrograms (115 patients) showed that the first desire was more sensitive in the bladder group (85.52 ± 49.78 ml). Cystometric capacity was decreased in the prostate group (161.50 ± 94.29 ml); the maximum voiding pressure and compliance were significantly lower in the colorectum group (64.58 ± 50.09 cmH2O). Conclusion: Patients with POM may suffer from urination dysfunction. Impaired bladder function is more predominant in the colorectum oncology compared with urological pelvic organ (prostate or bladder) malignancies. Physicians are encouraged to be aware of these urinary complications after POM treatment

Sofosbuvir-based regimen for genotype 2 HCV infected patients in Taiwan: A real world experience.

BACKGROUND:Sofosbuvir (SOF)-based regimens achieve excellent efficacy and safety in the treatment of chronic hepatitis C (CHC) with various genotypes. There are few real-world instances of the use of SOF-based regimens to treat genotype 2 CHC. This study determines the effectiveness and safety of SOF/Ribavirn (RBV), SOF/Daclatasvir (DCV) and SOF/DCV/RBV in the treatment of genotype 2 CHC patients in Taiwan. MATERIAL AND METHODS:Patients with genotype 2 CHC were treated for 12 weeks with SOF/RBV, SOF/DCV or SOF/DCV/RBV under the National Health Insurance reimbursement program in three hospitals in Taiwan. The sustained virological response at 12 weeks (SVR12) was determined. Adverse events were recorded for a safety analysis. RESULTS:A total of 467 genotype 2 CHC patients were enrolled from January to October 2018. One hundred and eleven patients (24%) had cirrhosis, including 10 patients (2.1%) with hepatic decompensation. Fifty-five patients (12%) had already experienced interferon-alpha/RBV treatment. Forty-two patients (9%) had a history of hepatocellular carcinoma (HCC) in the baseline. Three hundred and fifty-five patients received SOF/RBV, forty-seven patients received SOF/DCV and sixty-two patients received SOF/DCV/RBV. The SOF/DCV group featured a greater HCV viral load than the SOF/RBV or SOF/DCV/RBV groups. SVR12 was achieved in 94.6% of the SOF/RBV group, 95.7% of the SOF/DCV group and 96.8% of then SOF/DCV/RBV group (P = NS). Thirteen out of 352 patients (3.7%) in the SOF/RBV group, 1 out of 62 patients (1.6%) in the SOF/DCV/RBV group and 1 out of 47 patients (2.1%) in the SOF/DCV group developed virological failure. There are no differences in virological failure between the three groups (P = NS). Multi-variate analysis shows that history of HCC is an independent factor that is associated with the failure of treatment in the SOF/RBV group (odds ratio:4.905, 95% confidence interval (CI): 1.321-18.205, P = 0.017). Hemoglobin levels at 12 weeks are significantly lower in the SOF/RBV and the SOF/RBV/DCV group than in the SOF/DCV group (P<0.05). Serious adverse events (SAE) occurred in six patients (1.6%) in the SOF/RBV group and in one patient (1.6%) in the SOF/RBV/DCV group. No patients in the SOF/DCV group experienced SAE. CONCLUSIONS:SOF/RBV, SOF/DCV or SOF/DCV/RBV for 12 weeks all achieve very high SVR rates and are equally effective in the treatment of genotype 2 CHC patients in the real world in Taiwan. Patients in the SOF/RBV group who have a history of HCC exhibit a lower SVR rate

The Risk of Gastrointestinal Bleeding between Non-Vitamin K Antagonist Oral Anticoagulants and Vitamin K Antagonists in the Asian Atrial Fibrillation Patients: A Meta-Analysis

Background: Non-vitamin K antagonist oral anticoagulants (NOACs) are more commonly used to prevent atrial fibrillation (AF) patients from thromboembolic events than vitamin K antagonists (VKAs). However, the gastrointestinal bleeding (GIB) risk in the Asian AF patients associated with NOACs in comparison with VKAs remained unaddressed. Materials and Methods: A systematic search of studies on NOACs and VKAs in the Asian AF patients was conducted in PubMed, Cochrane Library, and ClinicalTrials.gov. The primary outcome was the hazard ratio (HR) of any GIB associated with NOACs versus VKAs. The secondary outcome was the GIB risks in different kinds of NOACs compared with VKAs. Results: This meta-analysis included two randomized controlled trials (RCTs) and four retrospective studies, comprising at least 200,000 patients in total. A significantly lower HR of GIB risks was found in all kinds of NOACs than VKAs in the Asian AF patients (HR: 0.633; 95% confidence interval: 0.535&ndash;0.748; p &lt; 0.001). Additionally, the GIB risks of different NOACs were apixaban (HR: 0.392), edoxaban (HR: 0.603), dabigatran (HR: 0.685), and rivaroxaban (HR: 0.794), respectively. Conclusions: NOACs significantly reduced the risk of GIB in the Asian AF patients compared with VKAs. In the four NOACs compared with VKAs, apixaban probably had a trend of the least GIB risk. We need further head-to-head studies of different NOACs to confirm which NOAC is the most suitable for Asian AF patients and to know the optimal dosage regimen of different NOACs

IsaB Inhibits Autophagic Flux to Promote Host Transmission of Methicillin-Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a major nosocomial pathogen that is widespread in both health-care facilities and in the community at large, as a result of direct host-to-host transmission. Several virulence factors are associated with pathogen transmission to naive hosts. Immunodominant surface antigen B (IsaB) is a virulence factor that helps Staphylococcus aureus to evade the host defense system. However, the mechanism of IsaB on host transmissibility remains unclear. We found that IsaB expression was elevated in transmissible MRSA. Wild-type isaB strains inhibited autophagic flux to promote bacterial survival and elicit inflammation in THP-1 cells and mouse skin. MRSA isolates with increased IsaB expression showed decreased autophagic flux, and the MRSA isolate with the lowest IsaB expression showed increased autophagic flux. In addition, recombinant IsaB rescued the virulence of the isaB deletion strain and increased the group A streptococcus (GAS) virulence in vivo. Together, these results reveal that IsaB diminishes autophagic flux, thereby allowing MRSA to evade host degradation. These findings suggest that IsaB is a suitable target for preventing or treating MRSA infection