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Abstract Given the limited head-to-head comparison of cardiovascular and renal outcomes between liraglutide and dulaglutide, our study aimed to investigate the clinical outcomes between dulaglutide and liraglutide in a real-world setting. In this new-user design, comparative and retrospective cohort study, patients with type 2 diabetes mellitus with prescription for GLP-1RAs from January 1, 2016 to December 31, 2022 (n = 8,278) were included. Primary outcome was composite cardiovascular outcomes which was composed of cardiovascular death, non-fatal myocardial infarction, and non-fatal ischemic stroke. The composite renal outcome was also interested, including new macroalbuminuria, doubling of serum creatinine, worsening of estimated glomerular filtration rate (eGFR), and progression to dialysis. A total of 3,210 subjects receiving liraglutide and 5,068 subjects receiving dulaglutide were identified. In the adjusted cohort by applying inverse probability of treatment weighting, the incidence of composite cardiovascular outcomes was 18.4 and 18.7 events per 1000 person-years in the liraglutide and dulaglutide groups, respectively. The risk of cardiovascular outcomes did not significantly differ between groups (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.85–1.15). Moreover, the risk of composite renal outcomes was also comparable between groups (subdistribution HR 1.07, 95% CI 0.995–1.16). Liraglutide and dulaglutide demonstrated comparable cardiovascular and renal outcomes in a real-world setting.

Abstract Controversies regarding the benefits of statin treatment on clinical outcomes in coronary artery spasm (CAS) without obstructive coronary artery disease (CAD) persist due to limited data. In this retrospective nationwide population‐based cohort study from the Taiwan National Health Insurance Research Database during the period 2000–2012, the matched cohorts consisted of 12,000 patients with CAS. After propensity score matching with 1:1 ratio, 2216 patients were eligible for outcome analysis in either statin or nonstatin group, with the mean follow‐up duration of 4.8 and 4.6 years, respectively. Statin users versus nonusers had a significantly reduced risk of major adverse cardiovascular events (MACEs) (6.7% vs. 9.5%, hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.55–0.84) and all‐cause mortality (6.0% vs. 7.6%; HR 0.77; 95% CI 0.61–0.96). While the results of MACEs were mainly contributed by cardiovascular death (1.9% vs. 3.2%; HR 0.56; 95% CI 0.38–0.83) and ischemic stroke (3.8% vs. 5.4%; subdistribution HR 0.69; 95% CI 0.52–0.91), they were primarily driven by reductions in ischemic but not hemorrhagic stroke. The benefit of statins was significantly pronounced in patients with hypertension and diabetes. Nevertheless, the effect on MACEs was consistent irrespective of age, sex, dyslipidemia, and mental disorder. Statins significantly reduced the risk of MACEs and all‐cause mortality in CAS patients. The benefit of statin therapy in reducing MACEs appeared to be linear, with greater risk reduction with higher doses and longer duration without upper threshold, reflecting the dose‐dependent relationship of statins with MACEs in CAS patients.

Abstract Background and aims Clinical comparisons of angiotensin receptor–neprilysin inhibitors (ARNI) and sodium–glucose cotransporter 2 inhibitors (SGLT2i) treatment in patients with HFrEF and T2DM are limited. This study evaluated the clinical outcomes and treatment benefits of SGLT2i versus ARNI treatment in patients with HFrEF and T2DM in a large real-world data set. Methods We identified 1487 patients with HFrEF and T2DM who were undergoing ARNI or SGLT2i treatment for the first time (n = 647 and 840, respectively) between January 1, 2016, and December 31, 2021, and with clinical outcomes of CV death, hospitalization for heart failure (HHF), composite CV outcomes, or renal outcomes. Results The HHF risk reduction conferred by SGLT2i treatment was more significant than that conferred by ARNI treatment (37.7% vs. 30.4%; 95% confidence interval [CI] 1.06–1.41). SGLT2i use conferred significantly greater renal protection against the doubling of serum creatinine (13.1% vs. 9.3%; 95% CI 1.05–1.75), an estimated glomerular filtration rate decline of > 50% (24.9% vs. 20.0%; 95% CI 1.02–1.45), and progression to end-stage renal disease (3.1% vs. 1.5%; 95% CI 1.62–5.23). The improvements in echocardiographic parameters were comparable between the groups. Conclusions Compared with ARNI treatment, SGLT2i treatment was associated with a more significant HHF risk reduction and greater preservation of renal function in patients with HFrEF and T2DM. This study also supports the prioritization of SGLT2i use in these patients when patients' conditions or economic resources need to be considered.

Abstract Background To determine whether glucagon-like peptide 1 receptor agonists (GLP-1RAs) have cardiovascular and renal protective effects in patients with advanced diabetic kidney disease (DKD) with an estimated glomerular filtration rate (eGFR)

Cardiovascular disease (CVD) is a serious issue demanding world attention, not only because of its role in increased mortality, but also in conjunction with the aging population and growing prevalence of other co-morbidities, such as hypertension, diabetes, etc [...]

Abstract Background Previous findings on the associations of thiazide use with skin cancers were conflicting. This study aimed to examine the associations of individual thiazide use with skin cancer risk, differentiated by subtypes of skin cancers, geographic regions, and cumulative doses of individual thiazides. Methods We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for relevant studies on January 5, 2022, scanned the references of included studies, and consulted experts. We included case-control and cohort studies or randomized trials reporting the associations of individual thiazide or thiazide-like diuretics use with skin cancers. Non-melanoma skin cancer (NMSC) and melanoma were analysed separately. A random-effects model meta-analysis was conducted for pooled odds ratio (OR) and hazard ratio (HR) for skin cancers related to individual thiazide use. Results We included 15, 5, and 5 case-control or cohort studies reporting the risk for skin cancers associated with hydrochlorothiazide, bendroflumethiazide, and indapamide use, respectively, with 17,848,313 participants. The meta-analysis showed associations of hydrochlorothiazide use with increased risk of NMSC (OR 1.16, 95% CI 1.08–1.24; HR 1.26, 95% CI 1.04–1.54), squamous cell carcinoma (SCC) (OR 1.32, 95% CI 1.06–1.65; HR 1.61, 95% CI 0.97–2.67), and melanoma (OR 1.11, 95% CI 1.02–1.20; HR 1.03, 95% CI 0.93–1.14). The increased risks for SCC were associated with high cumulative doses of hydrochlorothiazide (OR 2.56, 95% CI 1.43–4.57; HR 1.20, 95% CI 1.00–1.45). Hydrochlorothiazide use was associated with different subtypes of melanoma including superficial spreading (OR 1.18, 95% CI 1.05–1.33), nodular (OR 1.23, 95% CI 1.08–1.39), and lentigo maligna melanoma (OR 1.33, 95% CI 1.08–1.65). Various cumulative doses of hydrochlorothiazide were associated with increased odds for melanoma. However, the associations of hydrochlorothiazide use with increased risk of NMSC and melanoma only appeared in non-Asian countries. No meaningful increase in the risk for skin cancers was associated with bendroflumethiazide and indapamide. Conclusions Hydrochlorothiazide is associated with an increased risk for NMSC (especially SCC) and melanoma in non-Asian countries, whereas bendroflumethiazide and indapamide are not associated with a meaningful risk for skin cancers. Healthcare professionals and patients should be informed of the different risk profiles of skin cancers associated with different thiazides, cumulative doses, and regions. Trial registration PROSPERO CRD42021234317 .

We conducted a multi-institutional study in Taiwan and a systematic review of the literature for reports of Guillain-​Barré syndrome after coronavirus disease vaccination. This condition, mostly the classic form and the acute inflammatory demyelinating polyneuropathy subtype, has been reported in 39 cases and has occurred within 2 weeks of vaccine administration.

Abstract Background The treatment effects on hospitalization for heart failure (hHF) from sodium-glucose cotransporter 2 (SGLT2) inhibitors may vary among type 2 diabetes (T2D) patients depending on whether or not they have established atherosclerotic cardiovascular diseases (ASCVD). We aimed to examine differences in hHF outcomes after dapagliflozin or empagliflozin use between T2D patients with and without a history of established ASCVD. Methods We conducted a retrospective multi-institutional cohort study in Taiwan. We included T2D patients newly receiving dapagliflozin or empagliflozin during 2016–2019, and followed them up until December 31, 2020. We implemented 1:1 propensity score matching to create homogenous groups for comparisons. We generated Cox proportional hazard models to compare the risk of hHF between dapagliflozin and empagliflozin (reference group). We included interaction terms of SGLT2 inhibitor and ASCVD history in the regression models to examine effect modification by ASCVD. Results We included a total cohort of 9,586 dapagliflozin new users and 9,586 matched empagliflozin new users. The overall hHF risks were similar for dapagliflozin and empagliflozin (HR: 0.90, 95% CI 0.74–1.09). However, differential hHF risks between dapagliflozin and empagliflozin were observed only in the subgroup without ASCVD (HR: 0.67, 95% CI 0.49–0.90), while not in the subgroup with ASCVD (HR: 1.12, 95% 0.87–1.45), and the p-value for examining interaction was 0.0097. Conclusion In this study, history of established ASCVD was associated with different hHF risks among SGLT2 inhibitors. For T2D patients without ASCVD, dapagliflozin may offer a more favorable hHF reduction effect, compared to empagliflozin, in clinical practice. Future prospective studies should be conducted to validate our findings.

Background: Flipped classroom (FC) style Australian faculty development program Teaching on the Run (TOTR) was introduced into Chang Gung Memorial Hospital since 2014. However, its effectiveness in Taiwan has not been formally assessed. This work intended to examine the learning gain of TOTR and identify the moderators of FC outcome by using TOTR as a representative model of FC. Methods: A non-controlled before-after study was undertaken by retrospective analysis of learning data collected during TOTR workshop. Multiple choice questions were tested at baseline (pre-test), after pre-class learning (mid-test) and after classroom activity (post-test) to assess the learning gain. All available demographic and learning variables were included in the moderator analysis. Results: Stepwise and significant improvement in exam scores was noted from pre-test to mid-test and post-test (p

Background and Objectives: The demand for permanent pacemaker (PPM) implantation for extremely old patients is increasing. Prior to implanting PPMs, life expectancy evaluation is essential but difficult. We aimed to develop and validate a scoring system for all-cause mortality risk stratification prior to PPM implantation in patients aged ≥80. Materials and Methods: A total of 210 patients aged ≥80 who received PPM implantation were included. Multivariable analysis was performed to assess the effects of different variables on all-cause mortality in a derivation cohort (n = 100). We developed the MELODY score for stratifying all-cause mortality prior to PPM implantation and tested the scoring system in a validation cohort (n = 102). Results: After 4.0 ± 2.7 years of follow-up, 54 patients (54%) had died. The 0.5-, 1- and 2-year all-cause mortality rates were 7%, 10% and 24%, respectively. The MELODY score based on body mass index 2 (HR: 2.21, 95% CI: 1.06–4.61), estimated glomerular filtration rate 2 (3.35, 1.77–6.35), length of hospitalization before PPM implantation >7 days (1.87, 1.02–3.43) and dyspnea as the major presenting symptom (1.90, 1.03–3.50) successfully distinguished patients at high risk of mortality. Patients with MELODY scores ≥3 had a higher risk of mortality compared to those with MELODY scores Conclusions: The novel scoring system is a simple and effective tool for all-cause mortality risk stratification prior to PPM implantation in patients aged ≥80.

Abstract Atorvastatin 40 mg (ATOR 40) and ezetimibe 10 mg/simvastatin 20 mg (EZ-SIM 20) have similar reductions of low-density lipoprotein cholesterol (LDL-C) but cardiovascular (CV) outcomes between these two therapies are unclear. Our real-world cohort study is to test the hypothesis of pleiotropic effects of purely higher dose statin on CV outcomes beyond similar reductions of LDL-C, especially for extremely CV risk patients. Between January 1, 2007 and December 31, 2013, a total of 3,372 patients with type 2 diabetes mellitus (T2DM) admitted due to acute coronary syndrome (ACS) or acute ischemic stroke (AIS) were selected as the study cohort from the Taiwan National Health Insurance Research Database. Clinical outcomes were evaluated by ATOR 40 group (n = 1686) matched with EZ-SIM 20 group (n = 1686). Primary composite outcome includes CV death, non-fatal myocardial infarction, and non-fatal stroke. Secondary composite outcome includes hospitalization for unstable angina (HUA), percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). With a mean follow-up of 2.4 years, no significant difference of primary composite outcome was observed between ATOR 40 and EZ-SIM 20 groups (subdistribution hazard ratio [SHR], 1.09; 95% confidence interval [CI], 0.95–1.25). Nevertheless, ATOR 40 group had lower risks of HUA (SHR, 0.50; 95% CI, 0.35–0.72), PCI (SHR, 0.82; 95% CI, 0.69–0.97) and CABG (SHR, 0.62; 95% CI, 0.40–0.97) than EZ-SIM 20 group. For T2DM patients after ACS or AIS, ATOR 40 and EZ-SIM 20 had similar major CV outcomes, which still supported the main driver for CV risk reductions is LDL-C lowering.

Abstract Background Sodium glucose cotransporter 2 (SGLT2) inhibitors have shown greater reductions of cardiovascular event risks than dipeptidyl peptidase-4 (DPP4) inhibitors, whereby possible mechanisms may involve the better pleiotropic effects of SGLT2 inhibitors. However, no published data are currently available to directly compare glycemic and pleiotropic effects in real-world type 2 diabetes patients initiating SGLT2 inhibitors or DPP4 inhibitors. Method We conducted a retrospective cohort study by analyzing the Chang Gung Research Database, the largest multi-institutional electronic medical records database in Taiwan. We included patients newly receiving SGLT2 inhibitor or DPP4 inhibitor intensification therapy for type 2 diabetes from 2016 to 2017. We matched SGLT2 inhibitor users to DPP4 inhibitor users (1:4) by propensity scores to ensure comparable characteristics between the groups. We primarily evaluated 1-year post-treatment changes of hemoglobin A1c (HbA1c) after SGLT2 inhibitor or DPP4 inhibitor initiation, using two-tailed independent t-test. We also evaluated post-treatment changes in body weight, systolic blood pressure (SBP), alanine aminotransferase (ALT) and estimated glomerular filtration rate (eGFR) values, associated with SGLT2 inhibitors and DPP4 inhibitors. Results We identified a cohort of 2028 SGLT2 inhibitors and 8112 matched DPP4 inhibitors new users. SGLT2 inhibitors and DPP4 inhibitors showed similar HbA1c reductions (− 1.0 vs. − 1.1%; P = 0.076), but patients receiving SGLT2 inhibitors had greater improvements in body weight (− 1.5 vs. − 1.0 kg; P = 0.008), SBP (− 2.5 vs. − 0.7 mmHg; P

Background Cardiac troponins are important markers for diagnosis of acute myocardial infarction (AMI) in general population; however, chronically-elevated troponins levels are often seen in patients with renal insufficiency, which reduce their diagnostic accuracy. The aim of our study was to access the diagnostic values of initial high-sensitive cardiac troponin T (hs-cTnT) and relative change of hs-cTnT for AMI in patients with and without renal insufficiency. Methods Cardiac care unit patients with elevated hs-cTnT levels in 2017–2018 were enrolled. Receiver operating characteristic (ROC) curves were used to evaluate initial hs-cTnT levels and relative changes after 3 h of enrollment for diagnosis of AMI in patients with estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 (low), and eGFR ≥ 60 mL/min/1.73 m2 (normal). Results Of 359 patients, 240 patients had low eGFR, and 119 patients had normal eGFR. The area under the ROC curve (AUC) for the initial hs-cTnT levels was 0.58 (95% CI, 0.5–0.65, p = 0.053) among patients with low eGFR and 0.54 (95% CI, 0.4–0.67, p = 0.612) among patients with normal eGFR. AUCs for relative changes of hs-cTnT were 0.82 (95% CI, 0.76–0.88, p

Abstract Aims/Introduction The cardiovascular (CV) outcomes of vildagliptin – a dipeptidyl peptidase‐4 inhibitor – in patients with type 2 diabetes mellitus after acute coronary syndrome or acute ischemic stroke are unclear. Materials and Methods We analyzed data from the Taiwan National Health Insurance Research Database on 3,750 type 2 diabetes mellitus patients with acute coronary syndrome or acute ischemic stroke within 3 months between 1 August 2011 and 31 December 2013. Clinical outcomes were evaluated by comparing 1,250 participants receiving vildagliptin with 2,500 propensity score‐matched participants. The primary composite outcome included CV death, non‐fatal myocardial infarction and non‐fatal stroke. Results The primary composite outcome occurred in 122 patients (9.8%) in the vildagliptin group and 263 patients (10.5%) in the control group (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.72–1.11) with a mean follow‐up period of 9.9 months. No significant between‐group differences were observed for CV death (HR 0.93, 95% CI 0.56–1.52), non‐fatal myocardial infarction (HR 0.79, 95% CI 0.46–1.36) and non‐fatal stroke (HR 0.96, 95% CI 0.74–1.24). The vildagliptin group was at similar risks of hospitalization for heart failure (HF) or coronary intervention to the control group (P = 0.312 and 0.430, respectively). For patients with HF at baseline, the risk of hospitalization for HF was similar between the vildagliptin and control groups (HR 1.04, 95% CI 0.57–1.88). Conclusions Among patients with type 2 diabetes mellitus after a recent acute coronary syndrome or acute ischemic stroke, treatment with vildagliptin was not associated with increased risks of CV death, non‐fatal myocardial infarction, non‐fatal stroke and hospitalization for HF.

Coronary artery spasm (CAS) is a dynamic coronary stenosis causing vasospastic angina (VSA). However, VSA is a potentially lethal medical condition with multiple presentations, including sudden cardiac death. Despite investigations to explore its pathogenesis, no single mechanism has been found to explain the entire process of VSA occurrence. The roles of elevated local and systemic inflammation have been increasingly recognized in VSA. Treatment strategies to decrease local and systemic inflammation deserve further investigation.

Background and Objectives: An elevated heart rate is an independent risk factor for cardiovascular disease; however, the relationship between heart rate control and the long-term outcomes of patients with heart failure with reduced ejection fraction (HFrEF) remains unclear. This study explored the long-term prognostic importance of heart rate control in patients hospitalized with HFrEF. Materials and Methods: We retrieved the records of patients admitted for decompensated heart failure with a left ventricular ejection fraction (LVEF) of ≤40%, from 1 January 2005 to 31 December 2019. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure (HHF) during follow-up. We analyzed the outcomes using Cox proportional hazard ratios calculated using the patients’ heart rates, as measured at baseline and approximately 3 months later. The mean follow-up duration was 49.0 ± 38.1 months. Results: We identified 5236 eligible patients, and divided them into five groups on the basis of changes in their heart rates. The mean LVEFs of the groups ranged from 29.1% to 30.6%. After adjustment for all covariates, the results demonstrated that lesser heart rate reductions at the 3-month screening period were associated with long-term cardiovascular death, HHF, and all-cause mortality (p for linear trend = 0.033, 0.042, and 0.003, respectively). The restricted cubic spline model revealed a linear relationship between reduction in heart rate and risk of outcomes (p for nonlinearity > 0.2). Conclusions: Greater reductions in heart rate were associated with a lower risk of long-term cardiovascular death, HHF, and all-cause mortality among patients discharged after hospitalization for decompensated HFrEF.

Diabetic kidney disease is the most common primary disease of end-stage kidney disease globally; however, a sensitive and accurate biomarker to predict this disease remains awaited. microRNAs are endogenous single-stranded noncoding RNAs that have intervened in different post-transcriptional regulations of various cellular biological functions. Previous literatures have reported its potential role in the pathophysiology of diabetic kidney disease, including regulation of Transforming Growth Factor-β1-mediated fibrosis, extracellular matrix and cell adhesion proteins, cellular hypertrophy, growth factor, cytokine production, and redox system activation. Urinary microRNAs have emerged as a novel, non-invasive liquid biopsy for disease diagnosis. In this review, we describe the available experimental and clinical evidence of urinary microRNA in the context of diabetic kidney disease and discuss the future application of microRNA in routine practice.

Background: Carbon monoxide (CO) poisoning is the leading cause of poisoning death worldwide, but associations between CO poisoning and weather remain unclear.Objective: To quantify the influence of climate parameters (e.g., temperature, relative humidity, and wind speed) on the incidence risk of acute CO poisoning in Taiwan.Methods: We used negative binomial mixed models (NBMMs) to evaluate the influence of weather parameters on the incidence risk of acute CO poisoning. Subgroup analyses were conducted, based on the seasonality and the intentionality of acute CO poisoning cases.Results: We identified a total of 622 patients (mean age: 32.9 years old; female: 51%) with acute CO poisoning in the study hospital. Carbon monoxide poisoning was associated with temperature (beta: −0.0973, rate ratio (RR): 0.9073, p < 0.0001) but not with relative humidity (beta: 0.1290, RR: 1.1377, p = 0.0513) or wind speed (beta: −0.4195, RR: 0.6574, p = 0.0806). In the subgroup analyses, temperature was associated with the incidence of intentional CO poisoning (beta: 0.1076, RR: 1.1136, p = 0.0333) in spring and unintentional CO poisoning (beta: −0.1865, RR: 0.8299, p = 0.0184) in winter.Conclusion: Changes in temperature affect the incidence risk for acute CO poisoning, but the impact varies with different seasons and intentionality in Taiwan. Our findings quantify the effects of climate factors and provide fundamental evidence for healthcare providers to develop preventative strategies to reduce acute CO poisoning events.

Abstract Background To compare the cardiovascular event risk in type 2 diabetes patients newly receiving dapagliflozin vs. empagliflozin. Methods We conducted a retrospective cohort study by analyzing a multi-institutional electronic medical records database (Chang Gung Research Database) in Taiwan and included adult type 2 diabetes patients who were newly receiving sodium–glucose co-transporter 2 (SGLT2) inhibitors from 2016 to 2017. The primary outcome was a composite of cardiovascular death, myocardial infarction, ischemic stroke and heart failure. We followed up patients from initiation of SGLT2 inhibitors until the occurrence of cardiovascular events before December 31, 2018. We performed multivariable Cox proportional hazard modeling, adjusting for patients’ age, sex, laboratory data, co-morbidities, and concomitant medications. Results We identified 12,681 new SGLT2 inhibitor users with a mean age of 58.9 (SD 11.8) years, of whom 43.9% were female and 45.8% were new dapagliflozin users. A total of 10,442 person-years of dapagliflozin use and 12,096 person-years of empagliflozin use were included. Compared to empagliflozin users, new users of dapagliflozin were found to have similar risks for primary composite outcome (adjusted HR: 0.91; 95% CI 0.73–1.14), cardiovascular death (adjusted HR: 0.54; 95% CI 0.14–2.12), myocardial infarction (adjusted HR: 0.77, 95% CI 0.49–1.19) and ischemic stroke (adjusted HR: 1.15; 95% CI 0.80–1.65), but a lower risk of heart failure (adjusted HR: 0.68; 95% CI 0.49–0.95). Conclusion The risk of cardiovascular events was similar between dapagliflozin and empagliflozin new users, but dapagliflozin may have a better outcome in the reduction of heart failure in type 2 diabetes patients. Future prospective studies are required to confirm the findings.

Background and objectives: Chronic musculoskeletal (MS) pain is common in chronic kidney disease (CKD) patients. The association of chronic MS pain and CKD progression has not yet been established. Method: We conducted a prospective cohort study to evaluate the association of chronic MS pain and CKD progression of pre-dialysis CKD patients. Result: A total of 53.2% of pre-dialysis CKD patients had chronic MS pain. Patients classified as progression and non-progression had a similar prevalence of chronic MS pain at baseline, and similar baseline use of NSAIDs and Chinese herbal medicines. Univariate Cox analysis indicated that chronic MS pain and baseline NSAID or Chinese herbal medicine use were not significantly associated with progression of CKD. But multivariate Cox regression found chronic MS pain was independently significantly associated with all-cause mortality (HR, 2.912, 95% CI, 1.004–8.444; p = .049). However, serum levels of hs-CRP were similar between those chronic MS pain patients and without chronic MS pain patients (4.96 ± 9.4 vs. 4.25 ± 13.3 mg/L, p = .535). Conclusion: The CKD patients with chronic MS pain was independently and significantly associated with all-cause mortality, but not independently and significantly associated with CKD progression and composite endpoints. The inflammatory marker-hs-CRP was similar between CKD patients with and without chronic MS pain.

Introduction Sodium glucose co-transporter 2 (SGLT2) inhibitors have been reported to benefit liver functions in patients with type 2 diabetes (T2D) with non-alcoholic fatty liver disease (NAFLD). The aim of this study is to critically appraise existing systematic reviews in order to consolidate evidence associating the use of SGLT2 inhibitors with beneficial hepatic results for patients with T2D with NAFLD.Methods This umbrella review searched relevant published systematic reviews of clinical trials from PubMed and Embase between inception and September 16, 2020. Two independent investigators appraised study quality using AMSTAR2 (Assessment of Multiple Systematic Reviews 2). The hepatic effects from SGLT2 inhibitors were summarized based on liver enzymes, liver fat, liver histology, liver cirrhosis and liver cancer.Results Of 25 screened potential systematic reviews, we ultimately included 7 in this study. However, none of them could be rated as being of high methodological quality. Five systematic reviews indicated that SGLT2 inhibitors could effectively decrease liver fat and liver parameters of alanine aminotransferase and gamma-glutamyl transferase in patients with NAFLD. Two systematic reviews indicated that SGLT2 inhibitors could reduce hepatosteatosis, as supported by biopsy-proven evidence of improvement from a small clinical trial, but no evidence of liver fibrosis improvement was found.Conclusions There is some association between SGLT2 inhibitor use and observed benefits to liver functions in patients with T2D with NAFLD, although the quality of current systematic reviews remains relatively low. Further evaluation of long-term liver outcomes with SGLT2 inhibitors in cases of liver cirrhosis and liver cancer is warranted.

BACKGROUND:Acute myocardial infarction (AMI) complicates the clinical management of atrial fibrillation (AF) because coronary stenting may influence subsequent antithrombotic therapy. We investigated the use of a bare-metal stent (BMS) or a drug-eluting stent (DES) and associated outcomes in patients with pre-existing AF and first AMI undergoing percutaneous coronary intervention. METHODS AND RESULTS:Patient records in this population-based study were retrospectively collected from the Taiwan National Health Insurance Research Database. Using propensity score matching (PSM), we used 1:2 ratio stratification into a DES group of 436 and a BMS group of 785 patients from 2007 to 2011. The mean follow-up of matched cohorts was 1.7 years. After PSM, DESs were associated with lower rates of cardiovascular death (7.8%, hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.39-0.86 and 10.1%, HR 0.64, 95% CI 0.45-0.90) and primary composite outcome (35.1%, HR 0.76, 95% CI 0.63-0.92 and 48.2%, HR 0.81, 95% CI 0.69-0.96) than BMSs within the first year and at the end of follow-up. Although the greatest benefit from DESs, irrespective of the first- and second- generation DESs, implantation was observed within the first year only, this benefit was not observed in patients with diabetes, chronic kidney disease, or dialysis. CONCLUSIONS:Use of DESs in AMI patients with pre-existing AF is associated with significantly lower rates of cardiovascular death and primary composite outcome within the first year follow-up. However, the effect is not apparent in patients with diabetes, chronic kidney disease or dialysis.

Background: Intradialytic hypotension (IDH) is a frequent and grave complication of hemodialysis (HD). However, the dynamic hemodynamic changes and cardiac performances during each dialytic session have been rarely explored in patients having IDH. Methods: Seventy-six HD patients (IDH = 40, controls = 36) were enrolled. Echocardiography examinations were performed in all patients at the pre-HD, during-HD and post-HD phases of a single HD session. A two-way analysis of variance was applied to compare differences of echocardiographic parameters between IDH and controls over time. The risk association was estimated by using a logistic regression analysis. Results: The IDH patients had a higher ejection fraction during HD followed by a greater reduction at the post-HD phase than the controls. Significant decreases in septal ratios of transmitral flow velocity to annular velocity (E/e’) over times were detected between IDH patients and controls after adjusting for gender, age and ultrafiltration (p = 0.016). A lower septal E/e’ ratio was independently associated with IDH (OR = 0.040; 95% CI = 0.003–0.606; p = 0.02). In contrast, significant systolic and diastolic dysfunctions over time were found in diabetic IDH compared to non-diabetic counterparts. Conclusion: The septal E/e’ ratio was a significant predictor for IDH.

Heart failure (HF) is a global pandemic public health burden affecting one in five of the general population in their lifetime. For high-risk individuals, early detection and prediction of HF progression reduces hospitalizations, reduces mortality, improves the individual’s quality of life, and reduces associated medical costs. In using an artificial intelligence (AI)-assisted genome-wide association study of a single nucleotide polymorphism (SNP) database from 117 asymptomatic high-risk individuals, we identified a SNP signature composed of 13 SNPs. These were annotated and mapped into six protein-coding genes (GAD2, APP, RASGEF1C, MACROD2, DMD, and DOCK1), a pseudogene (PGAM1P5), and various non-coding RNA genes (LINC01968, LINC00687, LOC105372209, LOC101928047, LOC105372208, and LOC105371356). The SNP signature was found to have a good performance when predicting HF progression, namely with an accuracy rate of 0.857 and an area under the curve of 0.912. Intriguingly, analysis of the protein connectivity map revealed that DMD, RASGEF1C, MACROD2, DOCK1, and PGAM1P5 appear to form a protein interaction network in the heart. This suggests that, together, they may contribute to the pathogenesis of HF. Our findings demonstrate that a combination of AI-assisted identifications of SNP signatures and clinical parameters are able to effectively identify asymptomatic high-risk subjects that are predisposed to HF.

This study investigated the feasibility of using waste limestone sludge, waste stone sludge, iron oxide sludge, and spent catalyst as raw materials in the production of eco-cement. The compressive strength development of the Eco Cement-A (ECO-A) paste was similar to that of ordinary Portland cement (OPC) pastes. The compressive strength development of the ECO-B paste was higher than that of OPC pastes. In addition, the C2S (Ca2SiO4, C2S) and C3S (Ca3SiO5) minerals in the eco-cement paste were continuously utilized to hydrate the Ca(OH)2 and calcium silicate hydrates gel (Ca6Si3O12·H2O, C–S–H) throughout the curing time. When ECO-C clinker contained 8% spent catalyst, the C3S mineral content decreased and C3A (3 CaO·Al2O3) content increased, thereby causing the structure to weaken and compressive strength to decrease. The results showed that the developed eco-cement with 4% spent catalyst possessed compressive strength properties similar to those of OPC pastes.

ObjectiveWhether the cardiovascular (CV) outcomes of second-generation limus-eluting stents (LESs) differ from those of paclitaxel-eluting stents (PESs) in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) is still unclear.MethodsWe used the Taiwan National Health Insurance Research Database to analyse data of 516 patients with AMI and CS diagnosed from January 2007 to December 2011. We used propensity score matching to adjust for the imbalance in covariate baseline values between these two groups. We evaluated clinical outcomes by comparing 197 subjects who used second-generation LESs to 319 matched subjects who used PESs.ResultsThe risk of the primary composite outcomes (i.e., myocardial infarction, coronary revascularisation or CV death) was significantly lower in the second-generation LES group than in the PES group [37.3% vs. 51.8%; hazard ratio (HR), 0.73; 95% CI: 0.56-0.95] at the 12-month follow-up. The patients who received second-generation LESs had a lower risk of coronary revascularisation (HR 0.62; 95% CI: 0.41-0.93) than those who used PESs. However, the risks of myocardial infarction (HR 0.56; 95% CI: 0.26-1.24), ischemic stroke (HR 0.73; 95% CI: 0.23-2.35), or CV death (HR 0.90; 95% CI: 0.63-1.28) were not significantly different between the two groups.ConclusionsAmong patients with CS-complicating AMI, second-generation LES implantation significantly reduced the risk of coronary revascularisation and composite CV events compared to PES implantation at the 12-month follow-up.

Prior studies have suggested intraaortic balloon pump (IABP) have a neutral effect on acute myocardial infarction (AMI) patients with cardiogenic shock (CS). However, the effects of IABP on patients with severe CS remain unclear. We therefore investigated the benefits of IABP in AMI patients with severe CS undergoing coronary revascularization.This study identified 14,088 adult patients with AMI and severe CS undergoing coronary revascularization from Taiwan's National Health Insurance Research Database between January 1, 1997 and December 31, 2011, dividing them into the IABP group (n = 7044) and the Nonusers group (n = 7044) after propensity score matching to equalize confounding variables. The primary outcomes included myocardial infarction(MI), cerebrovascular accidents or cardiovascular death. In-hospital events including dialysis, stroke, pneumonia and sepsis were secondary outcomes. Primary outcomes were worse in the IABP group than in the Nonusers group in 1 month (Hazard ratio (HR) = 1.97, 95% confidence interval (CI) = 1.84-2.12). The MI rate was higher in the IABP group (HR = 1.44, 95% CI = 1.16-1.79), and the cardiovascular death was much higher in the IABP group (HR = 2.07, 95% CI = 1.92-2.23). The IABP users had lower incidence of dialysis (8.5% and 9.5%, P = 0.04), stroke (2.6% and 3.8%, P

OBJECTIVE: Little is known about long-term outcomes among patients who receive percutaneous angioplasty (PTA) for peripheral artery disease (PAD) then undergo below-knee or above-knee amputations. We sought to determine clinical outcomes associated with below-knee or above-knee amputation, along with possible explanatory factors and treatment strategies. METHODS: Using data from Taiwan's National Health Insurance Research Database from 1997 to 2010, 7,568 adult patients were divided into three groups: lower extremity preserved (LE), below-knee amputation (BK) and above-knee amputation (AK). We assessed outcomes including major adverse cardiovascular events (MACE) and associated risk factors. RESULTS: Overall MACE was significantly higher in the AK group compared to the LE and BK groups, over a mean follow-up of 2.45 years (hazard ratio [HR]: 1.81; 95% confidence interval [CI]: 1.50-2.18 for AK vs. LE; HR: 1.67; 95% CI: 1.36-2.06 for AK vs. BK). However MACE were similar for the BK and LE groups (HR: 1.08; 95% CI: 0.98-1.20). Overall mortality was highest in the AK group (HR: 1.65, 95% CI: 1.34-2.04 for AK vs. BK). As for patient characteristics, atrial fibrillation was more prevalent in the AK group than in the BK group (17% vs. 7%). Independent risk factors associated with death after above- or below-knee amputation included advanced age, heart failure, dialysis, male gender and high patient volume. CONCLUSION: The MACE rate was highest in the AK group, whereas the LE and BK groups were similar in this regard. Furthermore, overall mortality increased with larger area of amputation.

The prevalence of coronary vasospasm and also the factors associated with coronary vasospasm in CKD is still unclear. In this cross-sectional study of 859 consecutive CKD patients with angina pectoris received coronary catheterization, we evaluated the factors associated with coronary vasospasm. Patients with vasospasm were older and had higher peripheral blood white cell counts, higher peripheral blood monocyte cell counts, higher haemoglobin levels, higher hs-CRP levels, and lower levels of serum creatinine than patients without vasospasm. The results of multivariate logistic regression analysis revealed that peripheral blood monocyte count and hs-CRP level were independently associated with coronary vasospasm in patients with stage 1 CKD. Only peripheral blood monocyte count but not hs-CRP was independently associated with coronary vasospasm in patients with stages 2 and 3 of CKD. In conclusion, peripheral blood monocyte count is independently associated with coronary vasospasm in patients with stage 1–3 CKD, whereas hs-CRP is only independently associated with coronary vasospasm in patients with stage 1 CKD.

BACKGROUND: While hypertension is negatively associated with coronary artery spasm (CAS), scarce data are available on diabetes mellitus in relation to CAS. In addition, outcome prediction in patients with CAS is challenging due to the lack of appropriate biomarkers. Therefore, we sought to identify the roles that gender, high-sensitivity C-reactive protein (hs-CRP), diabetes mellitus and hypertension play in CAS development and prognosis. METHODOLOGY/PRINCIPAL FINDINGS: Patients (350 women and 547 men) undergoing diagnostic coronary angiography with or without proven CAS but without obstructive stenosis were evaluated at long-term follow-up (median 102 months). Diabetic women and diabetic men with low hs-CRP levels had a low and high risk of CAS (odds ratio [OR]: 0.16, 95% confidence interval [CI]: 0.01-1.88 and OR: 5.02, 95% CI: 1.03-24.54, respectively). The ORs of CAS in both women and men with the highest hs-CRP tertile (>3 mg/L) reduced from 4.41 to 1.45 and 2.98 to 1.52, respectively, if they had diabetes mellitus, and from 9.68 to 2.43 and 2.60 to 1.75, respectively, if they had hypertension. Hypertension had a more negative effect on CAS development in diabetic than non-diabetic women, which was not observed in men. The highest hs-CRP tertile was an independent predictor of adverse outcomes. Patients with the highest hs-CRP tertile had more coronary events than patients with the lowest hs-CRP tertitle (p = 0.021, log-rank test). CONCLUSIONS: Diabetes mellitus contributes to CAS development in men with low hs-CRP levels, but not in women. There are negative effects of diabetes mellitus and hypertension on CAS development in patients with high hs-CRP levels and especially in women. Elevated hs-CRP level independently predicts adverse outcomes.

Objective To understand the efficacy of aspirin use for preventing ischaemic stroke after central retinal artery occlusion (CRAO). Design The retrospective cohort study was conducted using the National Health Insurance Research Database from 1998 to 2013. Setting A population-based study. Participants A total of 9437 participants with newly diagnosed CRAO were identified. Participants who had a previous stroke and/or retinal vascular occlusion, were aged <20 years and used aspirin 3 months before the event were excluded. There were 3778 eligible participants matched by propensity score, and they were divided into aspirin (n=434) and aspirin-naive (n=1736) groups after the matching. Methods Cox proportional hazard models and cumulative survival curves were used to assess ischaemic stroke in the study groups, along with log-rank tests to compare group differences. Main outcome measures Incidence of ischaemic stroke in the aspirin and aspirin-naive groups 1 year after CRAO. Results Of the 3778 patients with newly diagnosed CRAO, 151 (4%) had a subsequent ischaemic stroke within 1 year. The risk was especially high during the first week of the CRAO. No difference between the aspirin and aspirin-naive groups was found in risk of ischaemic stroke, haemorrhagic stroke, gastrointestinal bleeding, major bleeding, acute coronary syndrome, retinal vein occlusion, new-onset glaucoma, undergoing panretinal photocoagulation or all-cause mortality. Risk factors for ischaemic stroke within 1 year of CRAO included male gender (p=0.031; HR=1.46) and age (p=0.032; HR=1.14). Conclusions Aspirin use after a CRAO showed no benefit on attenuating the risk of ischaemic stroke. The risk of ischaemic stroke was increased after CRAO especially during the first week. Male gender and age were risk factors for ischaemic stroke after CRAO. [ABSTRACT FROM AUTHOR]