Metformin use and hospital attendance-related resources utilization among diabetic patients with prostate cancer on androgen deprivation therapy: A population-based cohort study

Background Androgen deprivation therapy (ADT), used increasingly in the treatment of prostate cancer (PCa), negatively influences glycemic control in diabetes and is associated with an increased risk of diabetes complications where hospitalization commonly ensues. Metformin could decrease the metabolic consequences of ADT and enhance its effect. This study examined the association of metformin use with healthcare resources utilization among diabetic, PCa patients receiving ADT. Methods Diabetic adults with PCa on ADT in Hong Kong between December 1999 and March 2021 were identified. Patients with <6 months of concurrent metformin and ADT use were excluded. All included patients were followed up until September 2021. The outcomes were hospital attendances and related costs. Results In total, 1,284 metformin users and 687 non-users were studied. Over 8,045 person-years, 9,049 accident and emergency (A&E), and 21,262 inpatient attendances, with 11,2781 days of hospitalization were observed. Metformin users had significantly fewer A&E attendances (incidence rate ratio (IRR): 0.61 [95% confidence interval 0.54–0.69], p < 0.001), inpatient attendances (IRR: 0.57 [0.48–0.67], p < 0.001), and days of hospitalization (IRR: 0.55 [0.42–0.72], p < 0.001). Annual attendance costs were lower for metformin users than non-users (cost ratio: 0.28 [0.10–0.80], p = 0.017). Conclusions Metformin use was associated with decreased hospital attendances, days of hospitalization, and associated costs, which could help reduce healthcare resource utilization following ADT in the treatment of PCa

Bacterial Microbiota Profiling in Gastritis without Helicobacter pylori Infection or Non-Steroidal Anti-Inflammatory Drug Use

Recent 16S ribosomal RNA gene (rRNA) molecular profiling of the stomach mucosa revealed a surprising complexity of microbiota. Helicobacter pylori infection and non-steroidal anti-inflammatory drug (NSAID) use are two main contributors to gastritis and peptic ulcer. However, little is known about the association between other members of the stomach microbiota and gastric diseases. In this study, cloning and sequencing of the 16S rRNA was used to profile the stomach microbiota from normal and gastritis patients. One hundred and thirty three phylotypes from eight bacterial phyla were identified. The stomach microbiota was found to be closely adhered to the mucosa. Eleven Streptococcus phylotypes were successfully cultivated from the biopsies. One to two genera represented a majority of clones within any of the identified phyla. We further developed two real-time quantitative PCR assays to quantify the relative abundance of the Firmicutes phylum and the Streptococcus genus. Significantly higher abundance of the Firmicutes phylum and the Streptococcus genus within the Firmicutes phylum was observed in patients with antral gastritis, compared with normal controls. This study suggests that the genus taxon level can largely represent much higher taxa such as the phylum. The clinical relevance and the mechanism underlying the altered microbiota composition in gastritis require further functional studies

Temporal trends and patterns of infective endocarditis in a Chinese population:A territory-wide study in Hong Kong (2002-2019)

BACKGROUND: The characteristics of infective endocarditis (IE) in Asians are poorly understood. Therefore, we aim to describe the epidemiological trends and clinical features of IE in Hong Kong. METHODS: All patients with incident IE from 2002–2019 in a territory-wide clinical database in Hong Kong were identified. We studied the age- and sex-adjusted and one-year mortality of IE between 2002 and 2019 and identified significant contributors to 1-year all-cause death using the attributable fraction. We used propensity score and inverse propensity of treatment weighting to study the association of surgery with mortality. FINDINGS: A total of 5139 patients (60.4 ± 18.2years, 37% women) were included. The overall incidence of IE was 4.9 per 100,000 person-year, which did not change over time (P = 0.17). Patients in 2019 were older and more comorbid than those in 2002. The one-year crude mortality rate was 30% in 2002, which did not change significantly over time (P = 0.10). Between 2002 and 2019, the rate of surgery increased and was associated with a 51% risk reduction in 1-year all-cause mortality (Hazard Ratio 0.49 [0.28–0.87], P = 0.015). Advanced age (attributable fraction 19%) and comorbidities (attributable fraction 15%) were significant contributors to death. INTERPRETATION: The incidence of IE in Hong Kong did not change between 2002 and 2019. Patients with IE in 2019 were older and had more comorbidities than those in 2002. Mortality of IE remains persistently high in Hong Kong. Together, these data can guide public health strategies to improve the outcomes of patients with IE. FUNDING: This work was supported by Sanming Project of Medicine in Shenzhen, China [No. SZSM201911020] and HKU-SZH Fund for Shenzhen Key Medical Discipline [No. SZXK2020081]

Carboxyl-terminal truncated HBx regulates a distinct microRNA transcription program in Hepatocellular carcinoma development

Background: The biological pathways and functional properties by which misexpressed microRNAs (miRNAs) contribute to liver carcinogenesis have been intensively investigated. However, little is known about the upstream mechanisms that deregulate miRNA expressions in this process. In hepatocellular carcinoma (HCC), hepatitis B virus (HBV) X protein (HBx), a transcriptional trans-activator, is frequently expressed in truncated form without carboxyl-terminus but its role in miRNA expression and HCC development is unclear. Methods: Human non-tumorigenic hepatocytes were infected with lentivirus-expressing full-length and carboxyl-terminal truncated HBx (Ct-HBx) for cell growth assay and miRNA profiling. Chromatin immunoprecipitation microarray was performed to identify the miRNA promoters directly associated with HBx. Direct transcriptional control was verified by luciferase reporter assay. The differential miRNA expressions were further validated in a cohort of HBV-associated HCC tissues using real-time PCR. Results: Hepatocytes expressing Ct-HBx grew significantly faster than the full-length HBx counterparts. Ct-HBx decreased while full-length HBx increased the expression of a set of miRNAs with growth-suppressive functions. Interestingly, Ct-HBx bound to and inhibited the transcriptional activity of some of these miRNA promoters. Notably, some of the examined repressed-miRNAs (miR-26a, -29c, -146a and -190) were also significantly down-regulated in a subset of HCC tissues with carboxyl-terminal HBx truncation compared to their matching non-tumor tissues, highlighting the clinical relevance of our data. Conclusion: Our results suggest that Ct-HBx directly regulates miRNA transcription and in turn promotes hepatocellular proliferation, thus revealing a viral contribution of miRNA deregulation during hepatocarcinogenesis. © 2011 Yip et al.published_or_final_versio

Early IgA nephropathy: paradigm evolving from a clinical concept into a histological measure

AbstractThe designation of “early” IgA nephropathy is often used in patients with normal renal function, no or mild proteinuria, and absence of other features, but the term is in fact poorly defined judging from the varying norms adopted. Even with stringent clinical criteria used to characterize clinical early IgA nephropathy, these may not be correlated with the prediction of disease outcome, nor with the severity of renal lesions. Due to such limitations, the clinical reference to early IgA nephropathy represents more a concept than an accurate measure. The histological definition of “early” IgA nephropathy appears to be different as the grading of biopsy permits one to segregate by semiquantitation patients with early renal lesion and very low risk of progression. This review puts the emphasis on the morphologic definition of early IgA nephropathy based on objective criteria, and on its practical consequences. The clinical implications include a better patient selection in therapy, and the potential to enhance results of treatment as well as for the appraisal of clinical trials. We also suggest that all patients suspected for IgA nephropathy, including those in early clinical stage should undergo renal biopsy because the information yielded are critical to the management and therapy

Peritoneal dialysis-related peritonitis caused by Pseudomonas species: Insight from a post-millennial case series.

Pseudomonas peritonitis is a serious complication of peritoneal dialysis (PD). However, the clinical course of Pseudomonas peritonitis following the adoption of international guidelines remains unclear.We reviewed the clinical course and treatment response of 153 consecutive episodes of PD peritonitis caused by Pseudomonas species from 2001 to 2015.Pseudomonas peritonitis accounted for 8.3% of all peritonitis episodes. The bacteria isolated were resistant to ceftazidime in 32 cases (20.9%), and to gentamycin in 18 cases (11.8%). In 20 episodes (13.1%), there was a concomitant exit site infection (ESI); in another 24 episodes (15.7%), there was a history of Pseudomonas ESI in the past. The overall primary response rate was 53.6%, and complete cure rate 42.4%. There was no significant difference in the complete cure rate between patients who treated with regimens of 3 and 2 antibiotics. Amongst 76 episodes (46.4%) that failed to respond to antibiotics by day 4, 37 had immediate catheter removal; the other 24 received salvage antibiotics, but only 6 achieved complete cure.Antibiotic resistance is common amongst Pseudomonas species causing peritonitis. Adoption of the treatment guideline leads to a reasonable complete cure rate of Pseudomonas peritonitis. Treatment with three antibiotics is not superior than the conventional two antibiotics regimen. When there is no clinical response after 4 days of antibiotic treatment, early catheter removal should be preferred over an attempt of salvage antibiotic therapy

Metformin use and hospital attendance‐related resources utilization among diabetic patients with prostate cancer on androgen deprivation therapy: A population‐based cohort study

Background: Androgen deprivation therapy (ADT), used increasingly in the treatment of prostate cancer (PCa), negatively influences glycemic control in diabetes and is associated with an increased risk of diabetes complications where hospitalization commonly ensues. Metformin could decrease the metabolic consequences of ADT and enhance its effect. This study examined the association of metformin use with healthcare resources utilization among diabetic, PCa patients receiving ADT. Methods: Diabetic adults with PCa on ADT in Hong Kong between December 1999 and March 2021 were identified. Patients with <6 months of concurrent metformin and ADT use were excluded. All included patients were followed up until September 2021. The outcomes were hospital attendances and related costs. Results: In total, 1,284 metformin users and 687 non-users were studied. Over 8,045 person-years, 9,049 accident and emergency (A&E), and 21,262 inpatient attendances, with 11,2781 days of hospitalization were observed. Metformin users had significantly fewer A&E attendances (incidence rate ratio (IRR): 0.61 [95% confidence interval 0.54–0.69], p < 0.001), inpatient attendances (IRR: 0.57 [0.48–0.67], p < 0.001), and days of hospitalization (IRR: 0.55 [0.42–0.72], p < 0.001). Annual attendance costs were lower for metformin users than non-users (cost ratio: 0.28 [0.10–0.80], p = 0.017). Conclusions: Metformin use was associated with decreased hospital attendances, days of hospitalization, and associated costs, which could help reduce healthcare resource utilization following ADT in the treatment of PCa

Asymptomatic fluid overload predicts survival and cardiovascular event in incident Chinese peritoneal dialysis patients.

BACKGROUND:Fluid overload is common among asymptomatic peritoneal dialysis (PD) patients. We aim to determine the prevalence and prognostic significance of fluid overload, as measured by bioimpedance spectroscopy, in asymptomatic incident PD patients. METHODS:We performed a single-center study on 311 incident PD patients. Volume status was represented by the volume of overhydration (OH), OH/extracellular water (ECW) ratio, ECW/total body water (TBW) ratio, and ECW to intracellular water (ICW) ratio (E:I ratio). Patient survival, technique survival and cardiovascular event-free survival were determined. RESULTS:The median period of follow up was 27.3 months. Fluid overload was present in 272 patients (87.5%) when defined as OH volume over 1.1L. All hydration parameters significantly correlated with Charlson Comorbidity Index, and inversely with total Kt/V, and serum albumin. Multivariate cause-specific Cox analysis showed that volume status independently predicted patient survival; every 0.1 unit increase in E:I ratio was associated with 24.5% increase in all-cause mortality (adjusted cause-specific hazard ratio [ACSHR] 1.245, p = 0.002). Hydration status was also an independent predictor of cardiovascular event-free survival after excluding hospital admission for congestive heart failure; each 0.1 unit increase in E:I ratio was associated with 18.7% decrease in cardiovascular event-free survival (ACSHR 1.187, p = 0.011). In contrast, hydration parameters were not associated with technique survival. CONCLUSIONS:Fluid overload is common in asymptomatic incident PD patients and is a strong predictor of patient survival and cardiovascular event. The impact of bioimpedance spectroscopy-guided fluid management on the outcome of PD patients deserves further study