Triglyceride-glucose index and the risk of heart failure: Evidence from two large cohorts and a mendelian randomization analysis.

BACKGROUND: The relationship between triglyceride-glucose (TyG) index, an emerging marker of insulin resistance, and the risk of incident heart failure (HF) was unclear. This study thus aimed to investigate this relationship. METHODS: Subjects without prevalent cardiovascular diseases from the prospective Kailuan cohort (recruited during 2006-2007) and a retrospective cohort of family medicine patients from Hong Kong (recruited during 2000-2003) were followed up until December 31st, 2019 for the outcome of incident HF. Separate adjusted hazard ratios (aHRs) summarizing the relationship between TyG index and HF risk in the two cohorts were combined using a random-effect meta-analysis. Additionally, a two-sample Mendelian randomization (MR) of published genome-wide association study data was performed to assess the causality of observed associations. RESULTS: In total, 95,996 and 19,345 subjects from the Kailuan and Hong Kong cohorts were analyzed, respectively, with 2,726 cases of incident HF in the former and 1,709 in the latter. Subjects in the highest quartile of TyG index had the highest risk of incident HF in both cohorts (Kailuan: aHR 1.23 (95% confidence interval: 1.09-1.39), PTrend <0.001; Hong Kong: aHR 1.21 (1.04-1.40), PTrend =0.007; both compared with the lowest quartile). Meta-analysis showed similar results (highest versus lowest quartile: HR 1.22 (1.11-1.34), P < 0.001). Findings from MR analysis, which included 47,309 cases and 930,014 controls, supported a causal relationship between higher TyG index and increased risk of HF (odds ratio 1.27 (1.15-1.40), P < 0.001). CONCLUSION: A higher TyG index is an independent and causal risk factor for incident HF in the general population. CLINICAL TRIAL REGISTRATION: URL: https://www.chictr.org.cn ; Unique identifier: ChiCTR-TNRC-11,001,489.

Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors vs. Dipeptidyl Peptidase-4 (DPP4) Inhibitors for New-Onset Dementia: A Propensity Score-Matched Population-Based Study With Competing Risk Analysis.

Introduction: The effects of sodium-glucose cotransporter 2 inhibitors (SGLT2I) and dipeptidyl peptidase-4 inhibitors (DPP4I) on new-onset cognitive dysfunction in type 2 diabetes mellitus remain unknown. This study aimed to evaluate the effects of the two novel antidiabetic agents on cognitive dysfunction by comparing the rates of dementia between SGLT2I and DPP4I users. Methods: This was a population-based cohort study of type 2 diabetes mellitus patients treated with SGLT2I and DPP4I between January 1, 2015 and December 31, 2019 in Hong Kong. Exclusion criteria were <1-month exposure or exposure to both medication classes, or prior diagnosis of dementia or major neurological/psychiatric diseases. Primary outcomes were new-onset dementia, Alzheimer's, and Parkinson's. Secondary outcomes were all-cause, cardiovascular, and cerebrovascular mortality. Results: A total of 13,276 SGLT2I and 36,544 DPP4I users (total n = 51,460; median age: 66.3 years old [interquartile range (IQR): 58-76], 55.65% men) were studied (follow-up: 472 [120-792] days). After 1:2 matching (SGLT2I: n = 13,283; DPP4I: n = 26,545), SGLT2I users had lower incidences of dementia (0.19 vs. 0.78%, p < 0.0001), Alzheimer's (0.01 vs. 0.1%, p = 0.0047), Parkinson's disease (0.02 vs. 0.14%, p = 0.0006), all-cause (5.48 vs. 12.69%, p < 0.0001), cerebrovascular (0.88 vs. 3.88%, p < 0.0001), and cardiovascular mortality (0.49 vs. 3.75%, p < 0.0001). Cox regression showed that SGLT2I use was associated with lower risks of dementia (hazard ratio [HR]: 0.41, 95% confidence interval [CI]: [0.27-0.61], P < 0.0001), Parkinson's (HR:0.28, 95% CI: [0.09-0.91], P = 0.0349), all-cause (HR:0.84, 95% CI: [0.77-0.91], P < 0.0001), cardiovascular (HR:0.64, 95% CI: [0.49-0.85], P = 0.0017), and cerebrovascular (HR:0.36, 95% CI: [0.3-0.43], P < 0.0001) mortality. Conclusions: The use of SGLT2I is associated with lower risks of dementia, Parkinson's disease, and cerebrovascular mortality compared with DPP4I use after 1:2 ratio propensity score matching.

Fibrinolytic-Facilitated Chronic Subdural Hematoma Drainage-A Systematic Review.

BACKGROUND: The current treatment options for chronic subdural hematoma (CSDH) include burr hole drainage, twist drill drainage, and craniotomy with or without postoperative catheter drainage. Although generally effective, these treatments have continued to be complicated by recurrence, especially in partially hemolyzed or septated hematomas. Recently, interest in the use of fibrinolytic agents as an adjunct to surgical treatment to address this limitation has been increasing. We conducted a systematic review, focusing on the efficacy and safety profile of fibrinolytic agents and compared the different fibrinolytic agents. METHODS: The PubMed, EMBASE, CINAHL Plus, and Cochrane Library databases were searched for trials relevant to fibrinolytic administration in the treatment of CSDH. The findings are reported in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. The data from 1702 subjects from 6 retrospective observational studies were qualitatively analyzed. In addition, we included 11 case series and reports for discussion. RESULTS: For 1449 patients, the use of urokinase or tissue plasminogen activator improved hematoma drainage and shortened the hospital stay (7.04 days), with an overall hematoma recurrence rate of 1.59%. The incidence of infection, seizure, and intracranial bleeding was 3.18%, 0.80%, and 0.41%, respectively, which compared favorably with previously reported findings for surgical drainage without the use of fibrinolytic agents. CONCLUSIONS: The routine use of intrathecal urokinase and tissue plasminogen activator could be a new direction in the management of CSDH. Conclusive clinical evidence is lacking, however, and further prospective controlled studies are warranted to confirm the benefit and safety of this treatment strategy and to identify the optimal agent and dosing regimen.

Takotsubo cardiomyopathy with low ventricular ejection fraction and apical ballooning predicts mortality: a systematic review and meta-analysis.

Takotsubo cardiomyopathy (TCM) is characterized by temporary wall motion abnormality of the left ventricle. There is much debate upon the prognostic parameters. We conducted a systematic review and meta-analysis to investigate whether LVEF and the presence of apical ballooning predict long-term mortality in TCM. PubMed and Embase were searched through to October 30, 2017 without language restrictions, followed by an additional search through to February 2, 2020. Our search identified 18 studies that met the inclusion criteria, with a total of 5168 patients. Reduced LVEF as a categorical variable was associated with more than threefold increase in mortality risk in TCM patients (HR 3.10; 95% CI 1.78-5.42; P < 0.0001; I2 = 57%). Further subset analyses with the exclusion of studies consisting of patients with coronary artery disease revealed another significant relationship between LVEF and mortality (HR 3.13; 95% CI 1.392-7.031; P < 0.006; I2 = 58%). LVEF as a continuous variable was also found to be associated with increased mortality risk. However, this relationship only retained significance when computing odds ratios instead of hazard ratios (OR 0.95; 95% CI 0.93-0.98; P < 0.001; I2 = 0%). Finally, the existence of apical ballooning failed to demonstrate any link with an increased risk of mortality (HR 1.26; 95% CI 0.97-1.64; P = 0.09; I2 = 34%). LVEF and apical ballooning are both potential prognostic markers for mortality.