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Background: While the survival benefits of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are firmly established in the general population, their efficacy within patient undergoing dialysis with coronary artery disease (CAD) remains controversial. Methods: Between January 2015 and June 2021, 1168 patients undergoing dialysis with CAD were assessed from 30 tertiary medical centers. The primary outcome was all-cause death, and the secondary outcome was cardiovascular death. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for between-group differences. Results: Overall, ACEI or ARB were prescribed to 518 patients (44.3%) upon discharge. After a median follow-up of 22.2 months, 361 (30.9%) patients died, including 243 cardiovascular deaths. The use of ACEI or ARB was associated with a significantly lower risk of all-cause (25.3% vs 35.4%, hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.52–0.82, p < 0.001) and cardiovascular death (17.0% vs 23.8%; HR 0.64, 95% CI 0.48–0.83, p = 0.001). These findings remained consistent across IPTW and PSM analyses. Sensitivity analyses for ACEI and ARB use separately yielded similar results. Conclusions: Our findings suggested that among patients undergoing dialysis with CAD, ACEI or ARB use was associated with a lower risk of all-cause and cardiovascular death. [ABSTRACT FROM AUTHOR]

As a biomarker of inflammation and a core component in the coagulation pathway, fibrinogen contributes to atherosclerosis and subsequent adverse cardiovascular events and is modified by the occurrence of diabetes mellitus. However, the association between fibrinogen, diabetes status, and mortality in patients with end-stage renal disease (ESRD) and acute coronary syndrome (ACS) remains scarce. Methods: A multi-center cohort study enrolled 1079 patients with ESRD and ACS between January 2015 and June 2021. Patients were classified into three groups based on fibrinogen tertiles and were further categorized by diabetes status. The primary outcome was all-cause mortality, while the secondary outcome was cardiovascular mortality. Results: During a median 21.5 months of follow-up, 386 cases of all-cause mortality were recorded, including 262 cases of cardiovascular mortality. Multivariable Cox regression model revealed that patients with the third tertile of fibrinogen and those with diabetes experienced a significantly increased risk of all-cause mortality (fibrinogen: hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.32– 2.19; diabetes: HR, 1.36; 95% CI, 1.10– 1.68). When patients were stratified by both fibrinogen levels and diabetes status, patients in the third fibrinogen tertile with diabetes had the highest risk of all-cause mortality (HR 2.43, 95% CI 1.69– 3.48) compared to those in the first fibrinogen tertile without diabetes. Similar associations were observed for cardiovascular mortality. Notably, incorporating the combined fibrinogen and diabetes status into the Global Registry of Acute Coronary Events (GRACE) score or baseline risk model led to significant improvements in the C-statistics for predicting mortality, surpassing the advancements achieved with any single biomarker. Conclusion: In patients with ESRD and ACS, elevated fibrinogen and diabetes were associated with an increased risk of all-cause and cardiovascular mortality. Categorizing patients based on fibrinogen levels and diabetes status could provide valuable information for risk stratification of these patients. [ABSTRACT FROM AUTHOR]

Background Targeted cancer drugs (TCDs) have revolutionized oncology but vary in clinical benefit and patient out-of-pocket (OOP) costs. The American Society of Clinical Oncology (ASCO) Value Framework uses survival, toxicity, and symptom palliation data to quantify the net health benefit (NHB) of cancer drugs. We evaluated associations between NHB, uptake, and spending on oral TCDs. Methods We conducted a retrospective cohort study of patients aged 18-64 years with an incident oral TCD pharmacy claim in 2012-2020 in a nationwide deidentified commercial claims dataset. TCDs were categorized as having high (>60), medium (40-60), and low (<40) NHB scores. We plotted the uptake of TCDs by NHB category and used standard descriptive statistics to evaluate patient OOP and total spending. Generalized linear models evaluated the relationship between spending and TCD NHB, adjusted for cancer indication. Results We included 8524 patients with incident claims for 8 oral TCDs with 9 first-line indications in advanced melanoma, breast, lung, and pancreatic cancer. Medium- and high-NHB TCDs accounted for most TCD prescriptions. Median OOP spending was $18.78 for the first 28-day TCD supply (interquartile range [IQR] = $0.00-$87.57); 45% of patients paid $0 OOP. Median total spending was $10 118.79 (IQR = $6365.95-$10 600.37) for an incident 28-day TCD supply. Total spending increased $1083.56 for each 10-point increase in NHB score (95% confidence interval = $1050.27 to $1116.84, P  <  .01 for null hypothesis H0 = $0). Conclusion Low-NHB TCDs were prescribed less frequently than medium- and high-NHB TCDs. Total spending on oral TCDs was high and positively associated with NHB. Commercially insured patients were largely shielded from high OOP spending on oral TCDs. [ABSTRACT FROM AUTHOR]

Functionalization of Si‐bound methyl group provides an efficient access to diverse organosilanes. However, the asymmetric construction of silicon‐stereogenic architectures by functionalization of Si‐bound methyl group has not yet been described despite recent significant progress in producing chiral silicon. Herein, we disclosed the enantioselective silylmethyl functionalization involving the aryl to alkyl 1,5‐palladium migration to access diverse naphthalenes possessing an enantioenriched stereogenic silicon center, which are inaccessible before. It is worthy to note that the realization of asymmetric induction at the step of metal migration itself remains challenging. Our study constitutes the first enantioselective aryl to alkyl 1,5‐palladium migration reaction. The key to the success is the discovery and fine‐tuning of the different substituents of α,α,α,α‐tetraaryl‐1,3‐dioxolane‐4,5‐dimethanol (TADDOL)‐based phosphoramidites, which ensure the enantioselectivity and desired reactivity. [ABSTRACT FROM AUTHOR]