The clinical impacts of lung microbiome in bronchiectasis with fixed airflow obstruction: a prospective cohort study.

BACKGROUND: Airflow obstruction is a hallmark of disease severity and prognosis in bronchiectasis. The relationship between lung microbiota, airway inflammation, and outcomes in bronchiectasis with fixed airflow obstruction (FAO) remains unclear. This study explores these interactions in bronchiectasis patients, with and without FAO, and compares them to those diagnosed with chronic obstructive pulmonary disease (COPD). METHODS: This prospective observational study in Taiwan enrolled patients with either bronchiectasis or COPD. To analyze the lung microbiome and assess inflammatory markers, bronchoalveolar lavage (BAL) samples were collected for 16S rRNA gene sequencing. The study cohort comprised 181 patients: 86 with COPD, 46 with bronchiectasis, and 49 with bronchiectasis and FAO, as confirmed by spirometry. RESULTS: Patients with bronchiectasis, with or without FAO, had similar microbiome profiles characterized by reduced alpha diversity and a predominance of Proteobacteria, distinctly different from COPD patients who exhibited more Firmicutes, greater diversity, and more commensal taxa. Furthermore, compared to COPD and bronchiectasis without FAO, bronchiectasis with FAO showed more severe disease and a higher risk of exacerbations. A significant correlation was found between the presence of Pseudomonas aeruginosa and increased airway neutrophilic inflammation such as Interleukin [IL]-1ß, IL-8, and tumor necrosis factor-alpha [TNF]-α, as well as with higher bronchiectasis severity, which might contribute to an increased risk of exacerbations. Moreover, in bronchiectasis patients with FAO, the ROSE (Radiology, Obstruction, Symptoms, and Exposure) criteria were employed to classify individuals as either ROSE (+) or ROSE (-), based on smoking history. This classification highlighted differences in clinical features, inflammatory profiles, and slight microbiome variations between ROSE (-) and ROSE (+) patients, suggesting diverse endotypes within the bronchiectasis with FAO group. CONCLUSION: Bronchiectasis patients with FAO may exhibit two distinct endotypes, as defined by ROSE criteria, characterized by greater disease severity and a lung microbiome more similar to bronchiectasis without FAO than to COPD. The significant correlation between Pseudomonas aeruginosa colonization and increased airway neutrophilic inflammation, as well as disease severity, underscores the clinical relevance of microbial patterns. This finding reinforces the potential role of these patterns in the progression and exacerbations of bronchiectasis with FAO.

Association of dipeptidyl peptidase-4 inhibitor and recurrent pancreatitis risk among patients with type 2 diabetes: A retrospective cohort study.

Introduction: Following the introduction of incretin-based drugs to the market, instances of acute pancreatitis have been reported, leading the FDA to mandate a warning label. Incretin-based therapy has been linked to a rare yet significant adverse event known as acute pancreatitis. However, these concerns of use of incretin therapy remained an ongoing debate. Methods: This retrospective cohort study was extracted data from the National Health Insurance (NHI) program in Taiwan focused on those having prior hospitalization history of acute pancreatitis. We identified adult patients with type 2 diabetes, all patients who received new prescriptions one year after the diagnosis of hospitalization for acute pancreatitis for DPP-4 inhibitors (index date). Study participants were divided into two groups: those taking DPP-4 inhibitors (the DPP-4 inhibitors group, n = 331) and those not taking DPP-4 inhibitors (the non- DPP-4 inhibitors group, n = 918). The outcome of interest is the recurrence of hospitalization of acute pancreatitis. Results: The incidence density (per 1000 person-years) of acute pancreatitis was 23.16 for DPP-4 inhibitors group and 19.88 for non-DPP-4 inhibitor group. The relative risk is 0.86 (95% confidence interval (CI) 0.53-1.38). Results from the Cox proportional hazard model (HR) analysis, the DPP-4 inhibitor was associated with a neutral risk of acute pancreatitis HR 0.68; 95% CI: 0.42-1.09. Conclusions: In this extensive nationwide cohort study conducted in Taiwan, involving a substantial number of newly diagnosed cases, the utilization of DPP-4 inhibitors appears to show no significant correlation with an elevated risk of acute pancreatitis, even among diabetic patients deemed to be at a high risk. These results extend the safety reassurance of incretin-based therapy to individuals considered high-risk for such complications.

Kidney outcomes with SGLT2is for type 2 diabetes patients: does background treatment with metformin or RASis matter?

Introduction: There is a lack of real-world evidence regarding the impact of concomitant metformin and renin-angiotensin system inhibitors (RASis) on sodium-glucose cotransporter-2 inhibitor (SGLT2i)-associated kidney outcomes. This study was aimed to investigate whether SGLT2i-associated kidney outcomes were modified by the concomitant use of metformin or RASis in patients with type 2 diabetes. Methods: SGLT2i users were identified from three electronic health record databases during May 2016 and December 2017 and categorized into those with and without concomitant use of metformin or RASis. Propensity score matching was performed to minimize baseline differences between groups. Study outcomes were mean estimated glomerular filtration rate (eGFR) change and time to 30%, 40%, and 50% eGFR reductions. A meta-analysis was performed to combine the estimates across databases. Results: After matching, there were 6,625 and 3,260 SGLT2i users with and without metformin, and 6,654 and 2,746 SGLT2i users with and without RASis, respectively. The eGFR dip was similar in SGLT2i users with and without metformin therapy, but was greater in SGLT2i users with RASis compared to those without RASis. Neither metformin nor RASi use had a significant effect on SGLT2i-associated eGFR reductions, as evidenced by the hazard ratios (95% CIs) of 30% eGFR reductions for SGLT2is with versus without metformin/RASis, namely 1.02 (0.87-1.20)/1.09 (0.92-1.31). Such findings were also observed in the outcomes of 40% and 50% eGFR reductions. Conclusion: Using metformin or RASis did not modify SGLT2i-associated kidney outcomes in type 2 diabetes.

Antibiotic use and risk of autism spectrum disorder and attention-deficit/hyperactivity disorder: a population-based cohort study.

BACKGROUND: The gut microbiota is believed to influence neurodevelopment through the gut-brain axis, but prior studies have shown inconsistent results regarding early childhood antibiotic exposure and subsequent risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). The purpose of this study was to evaluate the hypothesis that exposure to antibacterial agents in the first 2 years of life increases the risk of ASD and/or ADHD. METHODS: This was a retrospective cohort study using 2003-2019 data from the National Health Insurance Research Database in Taiwan. Livebirths born between 2004 and 2016 were identified and separated into singleton, full sibling, and exposure-discordant sibling pair cohorts. The exposure group included children who filled at least one prescription for antibacterial agents between 0 and 2 years old in outpatient settings. The outcome, ASD and/or ADHD, was defined by at least one inpatient or outpatient diagnosis. The maximum follow-up age was 15 years in this study. Potential neonatal, maternal and paternal confounders were adjusted for. Cox proportional hazards models were used to estimate the relative event risk. RESULTS: The final sample contained 946,581 children in the singleton cohort, 1,142,693 children in the full sibling cohort, and 352,612 children in the exposure-discordant sibling pair cohort. Antibiotic exposure marginally increased the risk of ASD and/or ADHD in the singleton cohort (adjusted hazard ratio [aHR]: 1.06, 95% confidence interval [CI]: 1.04-1.07) and in the full sibling cohort (aHR: 1.03, 95% CI: 1.01-1.04). A slight decrease in the risk of ASD and/or ADHD was observed in the exposure-discordant sibling pair cohort (aHR: 0.92, 95% CI: 0.90-0.94). CONCLUSIONS: The results suggest that early life antibiotic exposure has minimal impact on the risk of ASD and/or ADHD. Given that the estimated effects are marginal and close to null, concerns about ASD and/or ADHD risk increase should not postpone or deter timely and reasonable antibiotic use.

Resveratrol Propionate Ester Supplement Exerts Antihypertensive Effect in Juvenile Rats Exposed to an Adenine Diet via Gut Microbiota Modulation.

Resveratrol, acting as a prebiotic, and propionate, functioning as a postbiotic, hold promise for preventing hypertension in chronic kidney disease (CKD). Previously, we employed propionate to enhance the bioavailability of resveratrol through esterification, resulting in the production of a resveratrol propionate ester (RPE) mixture. In this study, we purified 3-O-propanoylresveratrol (RPE2) and 3,4'-di-O-propanoylresveratrol (RPE4) and investigated their protective effects in a juvenile rat adenine-induced CKD model. To this end, male Sprague Dawley rats aged three weeks (n = 40) were divided into five groups: control; CKD (rats fed adenine); CKRSV (CKD rats treated with 50 mg/L resveratrol); CDRPE2 (CKD rats treated with 25 mg/L RPE2); and CKRPE4 (CKD rats treated with 25 mg/L RPE 4). RPE2 and PRE4 similarly exhibited blood pressure-lowering effects comparable to those of resveratrol, along with increased nitric oxide (NO) availability. Furthermore, RPE2 and RPE4 positively influenced plasma short-chain fatty acid (SCFA) levels and induced distinct alterations in the gut microbial composition of adenine-fed juvenile rats. The supplementation of RPE2 and RPE4, by restoring NO, elevating SCFAs, and modulating the gut microbiota, holds potential for ameliorating CKD-induced hypertension.

The association of depression and sleep disorders in patients with type 1 diabetes in Taiwan.

The association between depression and sleep disorders in patients with type 1 diabetes mellitus (T1DM) in Taiwan is underexplored. We used a nationwide population-based dataset to evaluate the association of T1DM with these conditions in Taiwan from 2001 to 2019. Patients with T1DM were identified as cases, and 2 control groups were used for comparison: patients with type 2 diabetes mellitus (T2DM) and nondiabetic patients. Age, sex, date of diagnosis, and multiple comorbidities were included and matched using propensity score matching between cases and controls. The primary outcome of this study was to identify new occurrences of the first diagnosis of depression or sleep disorders. After matching, this study included 27,029 T1DM cases, 54,058 T2DM controls, and 108,116 nondiabetic controls. Patients with T1DM exhibited a 1.55-fold higher risk of developing depression (hazard ratio [HR] 1.55, 95% confidence intervals [CI] 1.48-1.61) and a 1.41-fold higher risk of experiencing sleep disorders (HR 1.41, 95% CI 1.37-1.46) compared to nondiabetic controls. Similarly, patients with T2DM displayed elevated risks of both depression (HR 1.39, 95% CI 1.34-1.43) and sleep disorders (HR 1.40, 95% CI 1.37-1.44) relative to non-diabetic controls. When comparing the T1DM and T2DM groups, T1DM patients demonstrated a slightly higher risk of depression (HR 1.11, 95% CI 1.07-1.16) but no significant difference in the risk of sleep disorders compared to T2DM patients. These results were consistent regardless of different ages or sexes. This study demonstrates a significant association between diabetes mellitus and the risk of depression and sleep disorders in a large cohort of Taiwanese patients.

Hydrogen-Rich Water (HRW) Reduces Fatty Acid-Induced Lipid Accumulation and Oxidative Stress Damage through Activating AMP-Activated Protein Kinase in HepG2 Cells.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by excessive fat accumulation in the liver. Intracellular oxidative stress induced by lipid accumulation leads to various hepatocellular injuries including fibrosis. However, no effective method for mitigating MASLD without substantial side effects currently exists. Molecular hydrogen (H2) has garnered attention due to its efficiency in neutralizing harmful reactive oxygen species (ROS) and its ability to penetrate cell membranes. Some clinical evidence suggests that H2 may alleviate fatty liver disease, but the precise molecular mechanisms, particularly the regulation of lipid droplet (LD) metabolism, remain unclear. This study utilized an in vitro model of hepatocyte lipid accumulation induced by free fatty acids (FFAs) to replicate MASLD in HepG2 cells. The results demonstrated a significant increase in LD accumulation due to elevated FFA levels. However, the addition of hydrogen-rich water (HRW) effectively reduced LD accumulation. HRW decreased the diameter of LDs and reduced lipid peroxidation and FFA-induced oxidative stress by activating the AMPK/Nrf2/HO-1 pathway. Overall, our findings suggest that HRW has potential as an adjunctive supplement in managing fatty liver disease by reducing LD accumulation and enhancing antioxidant pathways, presenting a novel strategy for impeding MASLD progression.

2024 multidisciplinary consensus on image-guided lung tumor ablation from the Taiwan Academy of Tumor Ablation.

In this article, the multidisciplinary team of the Taiwan Academy of Tumor Ablation, who have expertise in treating lung cancer, present their perspectives on percutaneous image-guided thermal ablation (IGTA) of lung tumors. The modified Delphi technique was applied to reach a consensus on clinical practice guidelines concerning ablation procedures, including a comprehensive literature review, selection of panelists, creation of a rating form and survey, and arrangement of an in-person meeting where panelists agreed or disagreed on various points. The conclusion was a final rating and written summary of the agreement. The multidisciplinary expert team agreed on 10 recommendations for the use of IGTA in the lungs. These recommendations include terms and definitions, line of treatment planning, modality, facility rooms, patient anesthesia settings, indications, margin determination, post-ablation image surveillance, qualified centers, and complication ranges. In summary, IGTA is a safe and feasible approach for treating primary and metastatic lung tumors, with a relatively low complication rate. However, decisions regarding the ablation technique should consider each patient's specific tumor characteristics.

Correction: Valuation of the EQ-5D-5L in Taiwan.

[This corrects the article DOI: 10.1371/journal.pone.0209344.].

Type 2 Biomarkers and Their Clinical Implications in Bronchiectasis: A Prospective Cohort Study.

PURPOSE: Bronchiectasis is predominantly marked by neutrophilic inflammation. The relevance of type 2 biomarkers in disease severity and exacerbation risk is poorly understood. This study explores the clinical significance of these biomarkers in bronchiectasis patients. METHODS: In a cross-sectional cohort study, bronchiectasis patients, excluding those with asthma or allergic bronchopulmonary aspergillosis, underwent clinical and radiological evaluations. Bronchoalveolar lavage samples were analyzed for cytokines and microbiology. Blood eosinophil count (BEC), serum total immunoglobulin E (IgE), and fractional exhaled nitric oxide (FeNO) were measured during stable disease states. Positive type 2 biomarkers were defined by established thresholds for BEC, total IgE, and FeNO. RESULTS: Among 130 patients, 15.3% demonstrated BEC ≥ 300 cells/µL, 26.1% showed elevated FeNO ≥ 25 ppb, and 36.9% had high serum total IgE ≥ 75 kU/L. Approximately 60% had at least one positive type 2 biomarker. The impact on clinical characteristics and disease severity was variable, highlighting BEC and FeNO as reflective of different facets of disease severity and exacerbation risk. The combination of low BEC with high FeNO appeared to indicate a lower risk of exacerbation. However, Pseudomonas aeruginosa colonization and a high neutrophil-to-lymphocyte ratio (NLR ≥ 3.0) were identified as more significant predictors of exacerbation frequency, independent of type 2 biomarker presence. CONCLUSIONS: Our study underscores the distinct roles of type 2 biomarkers, highlighting BEC and FeNO, in bronchiectasis for assessing disease severity and predicting exacerbation risk. It advocates for a multi-biomarker strategy, incorporating these with microbiological and clinical assessments, for comprehensive patient management.

Risk of diabetes mellitus based on the interactive association between G6PD rs72554664 polymorphism and sex in Taiwan Biobank individuals.

The presence of glucose-6-phosphate dehydrogenase (G6PD) deficiency may increase the risk of type 2 diabetes mellitus (T2DM), with differing prevalence between males and females. Although G6PD deficiency is an X-linked genetic condition, its interaction with sex regarding T2DM risk among the Taiwanese population has not been fully explored. This study aimed to investigate the association between G6PD deficiency and T2DM risk in the Taiwanese population, focusing on the potential influence of sex. Data were obtained from the Taiwan Biobank (TWB) database, involving 85,334 participants aged 30 to 70 years. We used multiple logistic regression analysis to assess the interaction between G6PD rs72554664 and sex in relation to T2DM risk. The T2DM cohort comprised 55.35% females and 44.65% males (p < 0.001). The TC + TT genotype of rs72554664 was associated with an increased risk of T2DM, with an odds ratio (OR) of 1.95 (95% CI: 1.39-2.75), and males showed an OR of 1.31 (95% CI: 1.19-1.44). Notably, the G6PD rs72554664-T allelic variant in hemizygous males significantly elevated the T2DM risk (OR), 4.57; p < 0.001) compared to females with the CC genotype. Our findings suggest that the G6PD rs72554664 variant, in conjunction with sex, significantly affects T2DM risk, particularly increasing susceptibility in males. The association of the G6PD rs72554664-T allelic variant with a higher risk of T2DM highlights the importance of sex-specific mechanisms in the interplay between G6PD deficiency and T2DM.

Assessing herpes zoster vaccine efficacy in patients with diabetes: A community-based cohort study.

The effectiveness of herpes zoster (HZ) vaccines in patients with diabetes over the age of 50 remains an active area of research. Utilizing a real-world database from the US community, this study spanning from 2006 to 2023, aimed to evaluate the impact of HZ vaccination on newly diagnosed diabetes patients who received an HZ vaccination within 1 year of diagnosis. Exclusion criteria were established to omit patients with immune deficiencies. The cohort consisted of 53 885 patients, with an average age of 63.5 years, including 43% females and 58% whites. After implementing 1:1 propensity score matching for age, sex, race, comorbidities, diabetes medication, and hemoglobin A1c to ensure comparability, the study population was further stratified into four groups: N1 comparing any HZ vaccination to non-HZ vaccination (53 882 matched pairs), N2 for Shingrix versus non-HZ vaccination (16 665 matched pairs), N3 for Zostavax versus non-HZ vaccination (12 058 matched pairs), and N4 for Shingrix versus Zostavax (11 721 matched pairs). Cox proportional hazards regression analysis revealed a hazard ratio (HR) for HZ incidence post any HZ vaccination of 0.92 (95% confidence interval [CI]: 0.83-1.01). Additional analyses yielded HRs of 1.12 (95% CI: 0.93-1.34) for Shingrix versus non-HZ vaccine, 1.02 (95% CI: 0.86-1.20) for Zostavax versus non-HZ vaccine, and 1.06 (95% CI: 0.87-1.29) for Shingrix versus Zostavax. Subgroup analyses across age, sex, and follow-up duration also showed no significant differences. These findings underscore the lack of a significant benefit from HZ vaccination in newly diagnosed diabetes patients aged over 50, highlighting the necessity for further prospective research.

Amino Acids during Pregnancy and Offspring Cardiovascular-Kidney-Metabolic Health.

Amino acids are essential for normal pregnancy and fetal development. Disruptions in maternal amino acid metabolism have been associated with various adult diseases later in life, a phenomenon referred to as the developmental origins of health and disease (DOHaD). In this review, we examine the recent evidence highlighting the significant impact of amino acids on fetal programming, their influence on the modulation of gut microbiota, and their repercussions on offspring outcomes, particularly in the context of cardiovascular-kidney-metabolic (CKM) syndrome. Furthermore, we delve into experimental studies that have unveiled the protective effects of therapies targeting amino acids. These interventions have demonstrated the potential to reprogram traits associated with CKM in offspring. The discussion encompasses the challenges of translating the findings from animal studies to clinical applications, emphasizing the complexity of this process. Additionally, we propose potential solutions to overcome these challenges. Ultimately, as we move forward, future research endeavors should aim to pinpoint the most effective amino-acid-targeted therapies, determining the optimal dosage and mode of administration. This exploration is essential for maximizing the reprogramming effects, ultimately contributing to the enhancement of cardiovascular-kidney-metabolic health in offspring.

The Impact of the Aryl Hydrocarbon Receptor on Antenatal Chemical Exposure-Induced Cardiovascular-Kidney-Metabolic Programming.

Early life exposure lays the groundwork for the risk of developing cardiovascular-kidney-metabolic (CKM) syndrome in adulthood. Various environmental chemicals to which pregnant mothers are commonly exposed can disrupt fetal programming, leading to a wide range of CKM phenotypes. The aryl hydrocarbon receptor (AHR) has a key role as a ligand-activated transcription factor in sensing these environmental chemicals. Activating AHR through exposure to environmental chemicals has been documented for its adverse impacts on cardiovascular diseases, hypertension, diabetes, obesity, kidney disease, and non-alcoholic fatty liver disease, as evidenced by both epidemiological and animal studies. In this review, we compile current human evidence and findings from animal models that support the connection between antenatal chemical exposures and CKM programming, focusing particularly on AHR signaling. Additionally, we explore potential AHR modulators aimed at preventing CKM syndrome. As the pioneering review to present evidence advocating for the avoidance of toxic chemical exposure during pregnancy and deepening our understanding of AHR signaling, this has the potential to mitigate the global burden of CKM syndrome in the future.

Carbohydrate-Mediated Pregnancy Gut Microbiota and Neonatal Low Birth Weight.

The effects of gut microbiota on the association between carbohydrate intake during pregnancy and neonatal low birth weight (LBW) were investigated. A prospective cohort study was conducted with 257 singleton-born mother-child pairs in Taiwan, and maternal dietary intake was estimated using a questionnaire, with each macronutrient being classified as low, medium, or high. Maternal fecal samples were collected between 24 and 28 weeks of gestation, and gut microbiota composition and diversity were profiled using 16S rRNA amplicon gene sequencing. Carbohydrates were the major source of total energy (56.61%), followed by fat (27.92%) and protein (15.46%). The rate of infant LBW was 7.8%, which was positively correlated with maternal carbohydrate intake. In the pregnancy gut microbiota, Bacteroides ovatus and Dorea spp. were indirectly and directly negatively associated with fetal growth, respectively; Rosenburia faecis was directly positively associated with neonatal birth weight. Maternal hypertension during pregnancy altered the microbiota features and was associated with poor fetal growth. Microbiota-accessible carbohydrates can modify the composition and function of the pregnancy gut microbiota, thus providing a potential marker to modulate deviations from dietary patterns, particularly in women at risk of hypertension during pregnancy, to prevent neonatal LBW.

Optimizing lipid control in Taiwanese diabetic patients: A collaborative consensus by the Diabetes Association of the Republic of China (Taiwan) and the Taiwanese Association of Diabetes Educators.

We present an in-depth analysis of dyslipidemia management strategies for patients with diabetes mellitus in Taiwan. It critically examines the disparity between established guideline recommendations and actual clinical practices, particularly in the context of evolving policies affecting statin prescriptions. The focus is on synthesizing the most recent findings concerning lipid management in patients with diabetes mellitus, with a special emphasis on establishing consensus regarding low-density lipoprotein cholesterol treatment targets. The article culminates in providing comprehensive, evidence-based recommendations tailored to the unique needs of those living with diabetes mellitus in Taiwan. It underscores the criticality of personalized care approaches, which incorporate multifaceted factors, and the integration of novel therapeutic options to enhance cardiovascular health outcomes.

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.

The association between trajectory of serum cholesterol, statin dosage, and the risk of recurrent biliary stone diseases.

BACKGROUND: Statins may reduce the risk of recurrent gallstone disease by decreasing bile cholesterol saturation and pathogenicity. However, limited studies have investigated this issue. This study aimed to assess whether statin doses and serum cholesterol levels were associated with a decreased risk of recurrent biliary stone diseases after the first event index, with a follow-up time of 15 years. METHODS: Based on the Chang Gung Research Database (CGRD) between January 1, 2001, and December 31, 2020, we enrolled 68,384 patients with the International Classification of Diseases, Ninth and Tenth Revision codes of choledocholithiasis. After exclusions, 32,696 patients were divided into non-statin (<28 cDDD, cumulative defined daily doses) (n = 27,929) and statin (≥28 cDDD) (n = 4767) user groups for analysis. Serum cholesterol trajectories were estimated using group-based trajectory modeling (n = 8410). RESULTS: The statin users had higher Charlson Comorbidity Index (CCI) scores than the non-statin users. Time-dependent Cox regression analysis showed that statin use >365 cDDD was associated with a significantly lower risk of recurrent biliary stones (adjusted hazard ratio [aHR] = 0.28, 95% CI, 0.24-0.34; p < 00.0001), acute pancreatitis (aHR = 0.24, 95% CI, 0.17-0.32, p < 00.0001), and cholangitis (aHR = 0.28, 95% CI, 0.25-0.32, p < 00.0001). Cholecystectomy was also a protective factor for recurrent biliary stones (aHR = 0.41, 95% CI, 0.37-0.46; p < 00.0001). The higher trajectory serum cholesterol group (Group 3) had a lower risk trend for recurrent biliary stones (aHR = 0.79, p = 0.0700) and a lower risk of cholangitis (aHR = 0.79, p = 0.0071). CONCLUSION: This study supports the potential benefits of statin use and the role of cholecystectomy in reducing the risk of recurrent biliary stone diseases.

Gestational Exposure to Maternal Systemic Glucocorticoids and Childhood Risk of CKD.

RATIONALE & OBJECTIVE: The potential effects of antenatal glucocorticoid exposure on the health of children are unclear. We examined the association of gestational exposure to maternal systemic glucocorticoids and the risk of developing chronic kidney disease (CKD) in childhood. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Newborns cared for at the largest health care delivery system in Taiwan between 2004 and 2018. EXPOSURE: Maternal prescriptions for systemic glucocorticoids between the last menstrual period and birth as a proxy for gestational exposure. OUTCOME: Incidence of childhood CKD, including congenital anomalies of the kidney and urinary tract (CAKUT) and other kidney diseases (non-CAKUT), over 10 years. ANALYTICAL APPROACH: Cox proportional hazards models with stabilized inverse probability of treatment weighting and robust sandwich estimator were used to estimate the average association between systemic glucocorticoids and incident CKD after adjustment for offspring characteristics (adjusted HR: AHR). RESULTS: Among 23,363 singleton-born children, gestational systemic glucocorticoid exposure was significantly associated with a higher risk of childhood CKD (AHR, 1.69 [95% CI, 1.01-2.84]). Stratified analyses showed stronger associations between systemic glucocorticoids and childhood CKD within the strata of birth<37 weeks' gestational age (AHR, 2.38 [95% CI, 1.19-4.78]), male sex (AHR, 1.89 [95% CI, 1.00-3.55]), gestational exposure in the second trimester (AHR, 6.70 [95% CI, 2.17-20.64]), and total dose of>24mg hydrocortisone equivalent (AHR, 1.91 [95% CI, 1.05-3.47]). LIMITATIONS: Study was limited to the Taiwan health care delivery system and childhood CKD events through the age of 10 years. CONCLUSIONS: The findings of this study suggest that gestational exposure to systemic glucocorticoids is associated with the occurrence of kidney disease in childhood. If these findings are confirmed, they may inform clinicians who are considering prescribing systemic glucocorticoids during pregnancy. PLAIN-LANGUAGE SUMMARY: In a singleton-born cohort of neonates, maternal exposure to antenatal systemic glucocorticoids was significantly associated with a 1.7-fold increased risk of the children developing chronic kidney disease over the first 10 years of life. Children of mothers who received>24mg of hydrocortisone equivalent, systemic glucocorticoid treatment in second trimester of gestation, and children born at<37 weeks of gestational age had a higher risk of childhood kidney disease after gestational systemic glucocorticoid exposure. If these findings are confirmed, they may inform clinicians who are considering prescribing systemic glucocorticoids during pregnancy.

The Renin-Angiotensin System and Cardiovascular-Kidney-Metabolic Syndrome: Focus on Early-Life Programming.

The identification of pathological links among metabolic disorders, kidney ailments, and cardiovascular conditions has given rise to the concept of cardiovascular-kidney-metabolic (CKM) syndrome. Emerging prenatal risk factors seem to increase the likelihood of CKM syndrome across an individual's lifespan. The renin-angiotensin system (RAS) plays a crucial role in maternal-fetal health and maintaining homeostasis in cardiovascular, metabolic, and kidney functions. This review consolidates current preclinical evidence detailing how dysregulation of the RAS during pregnancy and lactation leads to CKM characteristics in offspring, elucidating the underlying mechanisms. The multi-organ effects of RAS, influencing fetal programming and triggering CKM traits in offspring, suggest it as a promising reprogramming strategy. Additionally, we present an overview of interventions targeting the RAS to prevent CKM traits. This comprehensive review of the potential role of the RAS in the early-life programming of CKM syndrome aims to expedite the clinical translation process, ultimately enhancing outcomes in cardiovascular-kidney-metabolic health.