Objective The significance of the liver-microbiome axis has been increasingly recognised as a major modulator of autoimmunity. The aim of this study was to take advantage of a large well-defined corticosteroids treatment-naïve group of patients with autoimmune hepatitis (AIH) to rigorously characterise gut dysbiosis compared with healthy controls. Design We performed a cross-sectional study of individuals with AIH (n=91) and matched healthy controls (n=98) by 16S rRNA gene sequencing. An independent cohort of 28 patients and 34 controls was analysed to validate the results. All the patients were collected before corticosteroids therapy. Results The gut microbiome of steroid treatment-naïve AIH was characterised with lower alpha-diversity (Shannon and observed operational taxonomic units, both p<0.01) and distinct overall microbial composition compared with healthy controls (p=0.002). Depletion of obligate anaerobes and expansion of potential pathobionts including Veillonella were associated with disease status. Of note, Veillonella dispar , the most strongly disease-associated taxa (p=8.85E–8), positively correlated with serum level of aspartate aminotransferase and liver inflammation. Furthermore, the combination of four patients with AIH-associated genera distinguished AIH from controls with an area under curves of approximately 0.8 in both exploration and validation cohorts. In addition, multiple predicted functional modules were altered in the AIH gut microbiome, including lipopolysaccharide biosynthesis as well as metabolism of amino acids that can be processed by bacteria to produce immunomodulatory metabolites. Conclusion Our study establishes compositional and functional alterations of gut microbiome in AIH and suggests the potential for using gut microbiota as non-invasive biomarkers to assess disease activity.
Despite rapid advances in the treatment of prostate cancer (PCa), the optimal treatment for elderly patients with PCa remains unclear due to a lack of high-quality evidence. This study aimed to evaluate whether surgical procedures are beneficial for PCa patients aged 75 years and older and compare the effects of focal ablation and prostatectomy. Male patients aged 75 years and older who were diagnosed with Tis-T2/N0/M0 PCa between 2000 and 2017 were retrospectively identified from the Surveillance, Epidemiology, and End Results program database. Cox regression models were used to test for statistical differences between the overall survival (OS) and disease-specific survival (DSS). A total of 114,506 patients aged 75 years and older with PCa were included in this study, among which 60,131 died during the study period. The most prevalent surgical procedure for these patients was focal ablation. The local excision rate increased with advancing age, while the prostatectomy rate decreased sharply with age. The proportion of the elderly patients who underwent a focal ablation also increased with the age at diagnosis. The survival rate of patients aged 75 years and older who underwent a focal ablation was significantly worse than that for those who did not undergo any surgical procedures (OS: HR, 1.32, P<0.001; DSS: HR, 1.58, P<0.001). Although only a few of the patients underwent prostatectomy, the procedure was still related to improved OS and DSS (OS: HR, 0.60, P< 0.001; DSS: HR, 0.37, P<0.001) rates. Focal ablation has gradually replaced prostatectomy as the most common surgical procedure for elderly patients with PCa in the United States. However, our results revealed that the procedure might not provide benefits for elderly patients with PCa; instead, we found that focal ablation resulted in increased negative effects on patient prognoses. Elderly patients should have the same opportunity to be treated with standard surgical interventions as younger patients.
To analyze the clinical characteristics of infective endocarditis in patients with hypertrophic obstructive cardiomyopathy.Clinical characteristics from 5 patients with infective endocarditis and hypertrophic obstructive cardiomyopathy hospitalized from January 2000 to December 2010 in our hospital were analyzed.Four patients were diagnosed with left ventricular outflow tract obstructive cardiomyopathy with outflow pressure gradient from 36 to 140 mm Hg (1 mm Hg = 0.133 kPa) and left atrial size 44 - 68 mm. Another patient was diagnosed as ventricular hypertrophic cardiomyopathy with significant right-ventricular outflow tract hypertrophy (30 mm), high pressure gradient (164 mm Hg) and enlarged right atrial (56 mm × 53 mm), there was a 17 mm × 8 mm vegetation on right-ventricular outflow tract in this patient. Blood cultures were positive for streptococcus viridans in all five patients, and enterococcus faecium was revealed in one aortic valve vegetation culture. Transthoracic echocardiogram was performed 2 - 4 times for each patient, the vegetations of two patients was detected only by transesophageal echocardiography. The mitral valve vegetation was detected in two patients, the aortic and mitral valve vegetations were detected in one patients, mitral and tricuspid vegetations in one patient and right ventricular outflow tract vegetation in one patient. The four hemodynamically stable patients were successfully treated with antibiotic therapy, one patient received urgent surgery (replacement of the aortic and mitral valve as well as septal myectomy). All patients recovered and follow-up (1 - 6 years) was available in 4 patients and no complication was observed.The risk of infective endocarditis complicating hypertrophic obstructive cardiomyopathy is the highest in patients with both outflow obstruction and marked valve insufficiency, these patients should receive prophylactic antibiotic therapy during procedures that predispose to infective endocarditis.
Patients with connective tissue disease have a poor prognosis after receiving cardiac surgery. This study described the clinical scenarios and investigated factors correlated with acute kidney injury (AKI) after on-pump cardiac surgery in patients with systemic lupus erythematosus (SLE) or vasculitis.Patients with SLE or vasculitis who underwent on-pump cardiac surgery from March 2002 to March 2022 were enrolled, while patients with preoperative renal dysfunction were excluded. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Uni- and multivariable analyses were performed to identify potential factors associated with postoperative AKI.Among 123 patients enrolled, 39 (31.7%) developed AKI within seven days after receiving on-pump cardiac surgery. Four patients died in the hospital, resulting in an overall in-hospital mortality of 3.3%, and all deaths occurred in the AKI group. Patients in the AKI group also had longer ICU stays (median difference 3.0 day, 95% CI: 1.0-4.0, P < 0.001) and extubation time (median difference 1.0 days, 95% CI: 0-2.0, P < 0.001) than those in the non-AKI group. Multivariable logistic regression revealed that BMI over 24 kg/m2 (OR: 3.00, 95% CI: 1.24-7.28) and comorbid SLE (OR: 4.73, 95% CI: 1.73-12.93) were independently correlated with postoperative AKI.Factors potentially correlated with AKI following on-pump cardiac surgery in patients with connective tissue disease were explored. Clinicians should pay more attention to preoperative evaluation and intraoperative management in patients with risk factors.
Abstract Background and Aim Persistent hepatocellular secretory failure (PHSF) is a rare condition of severe cholestasis caused by drugs, toxins, infection, or temporary biliary obstruction. Real‐world data on rifampicin in cholestasis, particularly among patients with deep jaundice, are scarce. We aimed to expand the knowledge on the efficacy and safety of rifampicin treatment in PHSF patients. Methods Sixteen patients with PHSF who had received rifampicin treatment (150–300 mg/d) at our institution from September 2016 to July 2020 were included. Treatment efficacy was assessed by 20% improvement in serum total bilirubin (TBIL) concentration at 4 weeks. Follow‐up was continued until the concentration of TBIL returned to normal. Results Among the 16 enrolled patients, 12 had predisposing factors (drugs, infection, or transient biliary obstruction). ATP8B1 or ABCB11 mutations were detected in the other four patients without trigger events. UGT1A1 mutations were found in 7/10 patients. Before rifampicin treatment, the median TBIL level was 352 μmol/L (range 171–591 μmol/L). TBIL > 20% improvement was observed in 14 patients at 4 weeks. TBIL levels of 14 patients eventually returned to normal after 6–12 weeks of rifampicin treatment. The remaining two patients who did not respond to rifampicin finally recovered after nasobiliary drainage. Except for one patient with transient drug‐induced hepatitis, no other serious adverse events were observed. Conclusions Rifampicin could be a promising option for most PHSF patients. Most PHSF patients have UGT1A1 deficiency, which may be the target of rifampicin.
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