Determinants of early chronic kidney disease in patients with recently diagnosed type 2 diabetes mellitus: a retrospective study from the Taiwan Diabetes Registry.

BACKGROUND: We tried to identify the risk factor associate with early chronic kidney disease (CKD) in recently diagnosed type 2 diabetes mellitus patients by utilizing real-world data from Taiwan Diabetes Registry. MATERIALS AND METHODS: Patients with type 2 diabetes mellitus recently diagnosed within 1 year. We divided the study participants into control group and early CKD group. Early CKD was defined as either CKD stage G1 with albuminuria, CKD stage G2 with albuminuria, or CKD stage G3a regardless of albuminuria (Urine-albumin to creatinine ratio (UACR) ≥ 3 mg/mmol). Control group was defined as CKD G1 or CKD G2 without albuminuria. Logistic regression analyses were used to compare differences in clinical characteristics between the subgroups. Linear regression models were employed to examine the factors predicting estimated glomerular filtration rate (eGFR) and UACR. RESULTS: Total 2217 patients with recently diagnosed type 2 diabetes mellitus were included. 1545 patients were assigned to control group and 618 patients were assigned to the early CKD group. Age (odds ratio (OR) 1.215, 95% confidence interval [CI] 1.122-1.316), systolic blood pressure (OR 1.203, 95% CI 1.117-1.296), glycated hemoglobin (OR 1.074, 95% CI 1.023-1.129) and triglyceride (OR 2.18, 95% CI 1.485-3.199) were found to be significant risk factors. Further, presence of bidirectional association between UACR and eGFR was found. CONCLUSIONS: We reported factors associated with early CKD in recently diagnosed type 2 diabetes mellitus patients. Variables that associated with eGFR and UACR were identified respectively, included a mutual influence between UACR and eGFR.

Metformin and the risks of cellulitis, foot infections, and amputation in patients with type 2 diabetes.

BACKGROUND: Patients with diabetes tend to have cellulitis, foot infections, and amputation. We conducted this research to compare the risks of cellulitis, foot infections, and amputation between metformin no-use and use in persons with type 2 diabetes. METHODS: Using propensity score matching, we identified 23 234 pairs of metformin nonusers and users from the National Health Insurance Research Database of Taiwan, since January 1, 2000, to December 31, 2017. Cox proportional hazards models were adopted to examine the risks of incident cellulitis, recurrent cellulitis, foot infections, and amputation between metformin use and no-use. RESULTS: The mean follow-up period of metformin use and no-use was 6.31 (3.93) and 5.54 (3.97) years, respectively. Compared with metformin no-use, the adjusted hazard ratio and 95% confidence interval for metformin use in cellulitis development, recurrent cellulitis, foot infections, and amputation were 1.08 (1.04-1.12), 1.33 (1.14-1.55), 1.91 (1.75-2.09), and 1.88 (1.35-2.62), respectively. The longer cumulative duration of metformin usage had association with higher risks of these outcomes than metformin no-use. CONCLUSION: This population-based cohort study revealed that metformin use had association with significantly higher risks of incident cellulitis, recurrent cellulitis, foot infections, and amputation than metformin no-use in patients with type 2 diabetes.

Residual risk of cardiovascular complications in statin-using patients with type 2 diabetes: the Taiwan Diabetes Registry Study.

BACKGROUND: The residual risks of atherosclerotic cardiovascular disease in statin-treated patients with diabetes remain unclear. This study was conducted to identify factors associated with these residual risks in patients with no prior vascular event. METHODS: Data on 683 statin-using patients with type 2 diabetes mellitus (T2DM) from the Taiwan Diabetes Registry were used in this study. Patients aged < 25 or > 65 years at the time of diabetes diagnosis and those with diabetes durations ≥ 20 years were excluded. The United Kingdom Prospective Diabetes Study risk engine (version 2.01; https://www.dtu.ox.ac.uk/riskengine/ ) was used to calculate 10-year residual nonfatal and fatal coronary heart disease (CHD) and stroke risks. Associations of these risks with physical and biochemical variables, including medication use and comorbidity, were examined. RESULTS: The 10-year risks of nonfatal CHD in oral anti-diabetic drug (OAD), insulin and OAD plus insulin groups were 11.8%, 16.0%, and 16.8%, respectively. The 10-year risks of nonfatal stroke in OAD, insulin and OAD plus insulin groups were 3.0%, 3.4%, and 4.3%, respectively. In the multivariate model, chronic kidney disease (CKD), neuropathy, insulin use, calcium-channel blocker (CCB) use, higher body mass indices (BMI), low-density lipoprotein (LDL), fasting glucose, log-triglyceride (TG), and log-alanine transaminase (ALT) levels were associated with an increased CHD risk. The residual risk of stroke was associated with CKD, neuropathy, CCB use, and lower LDL cholesterol levels, higher BMI and diastolic blood pressure. CONCLUSION: This study indicated that insulin was probably a residual risk factor of CHD but not stroke, and that there was a possible presence of obesity paradox in patients with T2DM on statin therapy. In addition to lowering TG and normalizing fasting glucose levels, lower LDL cholesterol level is better for reduction of risk of CHD on statin therapy. On the other hand, lower LDL cholesterol level could potentially be related to higher risk of stroke among populations receiving statin therapy. These findings suggest potential therapeutic targets for residual cardiovascular risk reduction in patients with T2DM on statin therapy.

Risk, Predictive, and Preventive Factors for Noninfectious Ventriculitis and External Ventricular Drain Infection.

BACKGROUND: External ventricular drain (EVD) is used for monitoring intracranial pressure or diverting cerebrospinal fluid. However, confirmation of an infection is not immediate and requires obtaining culture results, often leading to the excessive use of antibiotics. This study aimed to compare noninfectious ventriculitis and EVD infection in terms of the risk factors, predictors, prognosis, and effectiveness of care bundle interventions. METHODS: This retrospective study was conducted at a medical center with 1,006 beds in northern Taiwan between January 2018 and July 2022. Standard EVD insertion protocols and care bundles have been implemented since 2018, along with the initiation of chlorhexidine. RESULTS: In total, 742 EVD cases were identified. Noninfectious ventriculitis typically presents with fever approximately 8 days following EVD placement, whereas EVD infection typically manifests as fever after 20 days. Aneurysmal subarachnoid hemorrhage was strongly associated with the development of noninfectious ventriculitis (adjusted odds ratio [OR] 2.6, 95% confidence interval [CI] 1.5-4.4). Alcoholism (adjusted OR 3.5, 95% CI 1.1-12.3) and arteriovenous malformation (adjusted OR 13.1, 95% CI 2.9-58.2) significantly increased the risk of EVD infection. The EVD infection rate significantly decreased from 3.6% (14 of 446) to 1.0% (3 of 219) (p = 0.03) after the implementation of chlorhexidine gluconate bathing. CONCLUSIONS: Aneurysmal subarachnoid hemorrhage or fever with neuroinflammation within 2 weeks of EVD placement is indicative of a higher likelihood of noninfectious ventriculitis. Conversely, patients with arteriovenous malformation, alcoholism, or fever with neuroinflammation occurring after more than 3 weeks of EVD placement are more likely to necessitate antibiotic treatment for EVD infection. Chlorhexidine gluconate bathing decreases EVD infection.

Targeting Lung-Gut Axis for Regulating Pollution Particle-Mediated Inflammation and Metabolic Disorders.

Cigarette smoking (CS) or ambient particulate matter (PM) exposure is a risk factor for metabolic disorders, such as insulin resistance (IR), increased plasma triglycerides, hyperglycemia, and diabetes mellitus (DM); it can also cause gut microbiota dysbiosis. In smokers with metabolic disorders, CS cessation decreases the risks of serious pulmonary events, inflammation, and metabolic disorder. This review included recent studies examining the mechanisms underlying the effects of CS and PM on gut microbiota dysbiosis and metabolic disorder development; one of the potential mechanisms is the disruption of the lung-gut axis, leading to gut microbiota dysbiosis, intestinal dysfunction, systemic inflammation, and metabolic disease. Short-chain fatty acids (SCFAs) are the primary metabolites of gut bacteria, which are derived from the fermentation of dietary fibers. They activate G-protein-coupled receptor (GPCR) signaling, suppress histone deacetylase (HDAC) activity, and inhibit inflammation, facilitating the maintenance of gut health and biofunction. The aforementioned gut microbiota dysbiosis reduces SCFA levels. Treatment targeting SCFA/GPCR signaling may alleviate air pollution-associated inflammation and metabolic disorders, which involve lung-gut axis disruption.

Clinical Experience with Ropeginterferon Alfa-2b in the Off-Label Use for the Treatment of COVID-19 Patients in Taiwan.

INTRODUCTION: This study, for the first time to our knowledge, evaluated the efficacy of ropeginterferon alfa-2b, a long-acting pegylated interferon (IFN)-alfa, in the treatment of COVID-19. METHODS: We retrospectively evaluated ropeginterferon alfa-2b administered subcutaneously at a single dose of 250 µg for the treatment of mild and moderate COVID-19. Primary outcome was to compare the overall negative conversion time from the confirmed, last positive SARS-CoV-2 RT-PCR to the first RT-PCR negative conversion between patients receiving ropeginterferon alfa-2b plus standard of care (SOC) and those receiving SOC alone. RESULTS: Thirty-five patients with mild COVID-19 and 37 patients with moderate disease were included. Of them, 19 patients received SOC plus ropeginterferon alfa-2b and 53 patients received SOC alone. All patients with moderate disease in the ropeginterferon alfa-2b group showed RT-PCR negative conversion within 8 days, while a significant portion of patients in the SOC alone group failed to do so. For patients with moderate disease and age ≤ 65 years old, the ropeginterferon alfa-2b group had statistically significant shorter median RT-PCR conversion time than the SOC alone group (7 vs. 11.5 days, p < 0.05). CONCLUSIONS: Ropeginterferon alfa-2b showed the potential for the treatment of moderate COVID-19 patients. A randomized, controlled Phase III study is planned to further assess the effectiveness of ropeginterferon alfa-2b in COVID-19 patients.

Suppressor of variegation 3-9 homologue 1 impairment and neutrophil-skewed systemic inflammation are associated with comorbidities in COPD.

BACKGROUND: Systemic manifestations and comorbidities are characteristics of chronic obstructive pulmonary disease (COPD) and are probably due to systemic inflammation. The histone methyltransferase SUV39H1 controls the Th1/Th2 balance. We previously reported that reduced SUV39H1 expression contributed to abnormal inflammation in COPD. Here, we aimed to determine whether impaired SUV39H1 expression in COPD patients associated with neutrophilic/eosinophilic inflammation responses and comorbidities. METHODS: A total of 213 COPD patients and 13 healthy controls were recruited from the Shuang Ho Hospital, Taipei Medical University. SUV39H1 levels in peripheral blood mononuclear cells (PBMCs) from 13 healthy and 30 COPD participants were measured by immunoblotting. We classified the patients into two groups based on low (fold change, FC < 0.5) and high SUV39H1 expression (FC ≥ 0.5) compared to normal controls. Clinical outcomes including neutrophil or eosinophil counts associated with SUV39H1-related inflammation were evaluated by Chi square analyses or Mann-Whitney U test. The correlations between the percentage of neutrophils and number of COPD comorbidities or Charlson Comorbidity Index (CCI) scores were performed by Spearman's rank analysis. RESULTS: Low SUV39H1 expression group had high neutrophil counts relative to high SUV39H1expression group. In the COPD cohort, the high comorbidity group (≥ 2 comorbidities) had higher counts of whole white blood cell (WBC) and neutrophil, and lower proportion of eosinophil and eosinophil/neutrophil, as compared with low comorbidity group (0 and 1 comorbidities). The quantity of neutrophils was associated with COPD comorbidities (Spearman's r = 0.388, p < 0.001), but not with CCI scores. We also found that the high comorbidity group had more exacerbations per year compared with low comorbidity group (1.5 vs. 0.9 average exacerbations, p = 0.005). However, there were no significant differences between groups with these non-frequent (0-1 exacerbation) and frequent exacerbations per year (> 1 exacerbation) in numbers of WBC and proportion of neutrophils, eosinophils or eosinophil/neutrophil. Finally, patients with high comorbidities had lower SUV39H1 levels in their PBMCs than did those with low comorbidities. CONCLUSION: Blood neutrophil counts are associated with comorbidities in COPD patients. Impaired SUV39H1 expression in PBMCs from COPD patients are correlated with neutrophilic inflammation and comorbidities.

Disseminated Mycobacterium avium complex infection mimicking malignancy in a patient with anti-IFN-γ autoantibodies: a case report.

BACKGROUND: Disseminated nontuberculous mycobacteria (NTM) infections occur mostly in immunocompromised patients. Therefore, it is difficult to diagnose disseminated NTM infections in patients without history of immunocompromised diseases or using immunosuppressant. Patients with anti-interferon-γ (IFN-γ) autoantibodies are vulnerable to intracellular infections, such as disseminated NTM. Currently, there is no widely used and efficient technique for the detection of anti-IFN-γ autoantibodies. Herein, we report a case of an apparently healthy patient with disseminated Mycobacterium avium complex (MAC) infection who tested positive for anti-IFN-γ autoantibodies. CASE PRESENTATION: A 64-year-old non-immunocompromised and apparently healthy Asian male presented to the emergency department with complaints of progressive chest pain for about 6 months and weight loss. A bulging tumour was found in the anterior chest wall. Chest computed tomography showed a lung mass over the right lower lobe and an osteolytic lesion with a soft tissue component at the sternum. Sonography-guided biopsies for the osteolytic lesion and sputum culture confirmed the presence of disseminated MAC infection. In addition, positive test result of anti-IFN-γ autoantibodies was noted. The patient was prescribed antibiotics. The lesions over the right lower lobe and sternum attenuated following the antibiotic treatment. CONCLUSION: Detection of anti-IFN-γ autoantibodies is important among previously healthy people with disseminated NTM infection. Presence of anti-IFN-γ autoantibodies may suggest a high risk of severe intracellular infection, such as disseminated NTM infection.