Lower Risk Of Death Research Articles

Abstract 4136584: The Association of De Novo Niacin Use with Long-Term Mortality

Introduction: Niacin is a non-statin lipid-lowering therapy that has been shown to lower triglycerides and improve other risk factors for cardiovascular diseases. However, previous studies have reported inconsistent effects of niacin on mortality, and its effect on long-term prognosis has not been well studied. Goals: The aim of this study is to examine the association of niacin therapy with long-term all-cause mortality. Methods: In a nationwide historical cohort of 1,139,630 US Veterans with normal baseline kidney function, we examined the association of de novo niacin prescription from 2004 to 2006 with all-cause mortality during a 14-year follow-up. Associations were examined in Cox proportional hazard models adjusted for demographics, major comorbidities, and laboratory measurements. Prescription time-distribution matching was used to control for survival bias. Results: We identified 133,450 new users of niacin. Overall, patients had a mean (standard deviation) age of 60 (13) years, with 6% female, 78% White, 16% Black, and 6% Hispanic. Niacin users were more likely to be male, White, current, or former smokers and had higher frequencies of comorbidities. Niacin use (vs. non-use) was associated with a lower risk of death (Hazard ratio: 0.89, 95% confidential interval: 0.88-0.90) in the fully adjusted model (Model 4, Figure). Conclusion: In a large national cohort of US Veterans, niacin use was associated with a lower risk of death. Further studies are needed to corroborate the potential benefits of niacin on survival.

Effect of catheter ablation vs medical therapy on cardiovascular outcomes in hypertrophic cardiomyopathy with atrial fibrillation

Abstract Background Atrial fibrillation (AF) increases the risks of stroke and mortality. AF ablation in patients with heart failure (HF) was associated with a lower risk of death and hospitalisation for worsening HF. Whether AF ablation is beneficial to improve cardiovascular outcomes in patients with concomitant hypertrophic cardiomyopathy (HCM) and AF remains unclear. Objective To investigate whether AF ablation is more effective than conventional medical therapy for improving outcomes in HCM. Methods 2,281 patients with HCM and AF undergoing catheter ablation or medical therapy (antiarrhythmic drugs or rate control drugs) in 2005–2015 were identified from the Korean National Health Insurance Service database. The primary composite outcome of death from cardiovascular causes, ischaemic stroke, hospitalization for worsening HF, or acute myocardial infarction was compared between catheter ablation and medical therapy using propensity score overlap weighting. The time-at-risk was counted from the first medical therapy, and catheter ablation was analysed as a time-varying exposure. Results Of the included (41.1% female; median age: 66 years), 145 (6.1%) underwent catheter ablation for AF during the study period. During a mean follow-up of 3.1 (IQR 1.3–5.8) years, a total of 831 composite outcomes occurred including 292 cardiovascular deaths and 401 strokes. Catheter ablation, compared with medical therapy, was associated with lower risks of the primary composite outcome (weighted incidence rate: 3.84 vs. 6.43 per 100 person-years; weighted HR 0.61, 95% CI 0.38–0.96) and ischaemic stroke (weighted HR 0.43, 95% CI 0.19–0.97). The association between ablation and a lower risk of composite outcome was more pronounced in cases of ablation success whereas no significant difference was observed in cases of ablation failure. Conclusions In patients with AF and HCM, catheter ablation was associated with a lower risk of adverse cardiovascular outcomes than medical therapy.

Ezetimibe use and mortality after myocardial infarction: a nationwide cohort study

Abstract Background Inhibition of intestinal cholesterol absorption by ezetimibe improves outcomes after myocardial infarction (MI), yet real-world data on ezetimibe is lacking. Purpose To study usage and outcome impact of ezetimibe after MI. Methods Consecutive MI patients in Finland (2010-2018) were retrospectively studied (N=57,505; 65% men; mean age 69 years). Study data were combined from national registries. The median follow-up was 4.5 (IQR 2.8-7.1) years. Differences between groups were adjusted with multivariable regression. Ezetimibe use was studied with competing risk analyses. Median follow-up was 4.5 (IQR 2.8-7.1) years. Results The cumulative incidence of ezetimibe use was 3.7% at 90-days, 13.4% at 5-years and 19.8% at 10-years. Younger age was the strongest predictor for ezetimibe use (adj. sHR 6.67; CI 5.88-7.69 for patients aged <60 vs. ≥80 years). Women were more likely to use ezetimibe during follow-up than men. The average proportion of patients using ezetimibe during follow-up was 6.8%. (11.7% at 10-years). Ezetimibe was discontinued by 43.6% of patients during the follow-up. Patients with early ezetimibe after MI had lower all-cause mortality during follow-up (33.6% vs. 45.1%; adj. HR 0.77; CI 0.69-0.86; p<0.0001). Early ezetimibe use was associated with lower mortality irrespective of sex, age, atrial fibrillation, diabetes, heart failure, malignancy, revascularization, or statin use. Ongoing ezetimibe therapy during follow-up was associated with lower mortality in time-dependent analysis (adj. HR 0.53; CI 0.48-0.59; p<0.0001). Conclusion Ezetimibe is associated with lower risk of death after MI, but therapy use is limited and discontinuity is frequent.

Adherence to the Atrial Fibrillation Better Care (ABC) pathway and outcomes in patients with chronic kidney disease: A report from the APHRS-AF registry

Abstract Background The Atrial Fibrillation Better Care (ABC) pathway is based on three pillars: "A" avoid stroke with oral anticoagulation, "B" better symptoms control, and "C" optimization of cardiovascular risk factors and lifestyles. This integrated approach has been associated with improved outcomes in atrial fibrillation (AF) patients, but few data are available in patients with chronic kidney disease (CKD). Purpose To investigate the correlation between chronic kidney disease, adherence to the ABC pathway, and the occurrence of adverse events in patients with AF enrolled in the Asian-Pacific Heart Rhythm Society-AF Registry. Methods Logistic regression was used to investigate factors associated with CKD, warfarin use and rhythm control strategies. Cox regression analysis adjusted for age≥75 years, paroxysmal AF, CHA2DS2VASc≥2, chronic obstructive pulmonary disease, cancer, and ABC adherence was used to calculate Hazard Ratios (HRs) and 95% Confidence Interval (CI) for the risk of primary outcomes in patients with CKD (eGFR <60 ml/min/1.73m2). Sensitivity analyses were performed in moderate (eGFR 59-30) and severe CKD (eGFR<30). Interaction analysis investigated the effect of ABC pathway based on presence or absence of CKD. Primary outcomes were the risks of all-cause death, major cardiovascular events (MACE: Cardiovascular death, acute coronary syndromes, thromboembolic events, and acute heart failure) and major bleeding. Results We included 2 578 AF patients without CKD (age 66.5±11.3 years, 32.5% females) and 1 047 AF patients with CKD (75.3±10.3 years, 40.8% females). Lower ABC pathway full adherence was observed in CKD patients (42.1% vs 29.5%, p<0.001), primarily due to low adherence to "A" and "C" criteria. Logistic regressions confirmed the lower likelihood of anticoagulation (Odds Ratio (OR) 0.61, 95%CI 0.44-0.83), a higher use of warfarin (OR 1.50, 95%CI 1.23-1.83) and lower use of rhythm control strategies (OR 0.79, 95%CI 0.66-0.94) in CKD patients. After one-year follow up, patients with CKD had a higher incidence of all-cause death (1.6% vs 7.2%, p<0.001) and MACE (3.4% vs 8.1%, p,0.001) compared to those without CKD. On Cox multivariable analysis (Figure 1, Panel A-D), CKD and ABC adherence were independently associated with the risk of all-cause death (HR 2.54, 95%CI 1.69-3.80 and HR 0.57, 95%CI 0.35-0.93, respectively) and MACE (HR 1.58, 95%CI 1.14-2.20 and HR 0.66, 95%CI 0.46-0.95, respectively). The risk of primary outcomes was the highest in those with severe CKD. No association was found with the risk of major bleeding. The interaction analysis confirmed that the beneficial effect of ABC pathway adherence on death (p int= 658) and MACE (p int= 0.568) was irrespective of CKD. Conclusion AF patients with CKD have low ABC pathway adherence and high risk of all-cause death and MACE. Efforts to improve the ABC pathway adherence in AF patients with CKD are needed to improve their long-term clinical outcomes.Figure 1.Cox regression analyses

Association between reduced risk of gastrointestinal bleeding related to proton pump inhibitor use and subsequent all-cause death in patients with percutaneous coronary intervention

Abstract Background Gastrointestinal bleeding is the leading cause of post-percutaneous coronary intervention (PCI) bleeding complications which are associated with a high risk for subsequent clinical outcomes. The aim of this study was to estimate association between risk of gastrointestinal bleeding events related to proton pump inhibitor (PPI) use and subsequent clinical outcomes in patients with PCI. Methods The Clinical Deep Data Accumulation System (CLIDAS) is a database for inclusive of patient characteristics, medications, laboratory test, physiological test, cardiac catheterization and PCI treatment, all of which were aggregated from electronic medical records in 7 tertiary hospitals in Japan. Data of 6457 patients who underwent PCI between April 2014 and March 2020 and were then followed for 30 days after the index PCI, were analyzed. These patients were divided into two groups based on use of PPI; the PPI group (n=5285; 82%) and the non-PPI group (n=1172; 18%). Clinical outcomes, defined as gastrointestinal bleeding and all-cause death, were assessed using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) models. Results Among the 6457 PCI patients, 90 (1.7%) in the PPI group and 31 (2.6%) in the non-PPI group experienced gastrointestinal bleeding events. Adjusting for baseline demographics, comorbidities, and anti-thrombotic treatments, the multivariable Cox hazard model suggested a trend towards a lower risk of gastrointestinal bleeding with PPI use (HR, 0.70; 95%CI, 0.46-1.05; p=0.087). The PSM analysis confirmed a significant association between PPI use and a lower risk of gastrointestinal bleeding (HR, 0.13; 95%CI, 0.04-0.43; p=0.001), consistent with IPTW model results (HR, 0.60; 95%CI, 0.38-0.95; p=0.031). Subgroup analysis showed that PPI use was associated with a low risk of all-cause death in patients with acute coronary syndrome (ACS) (HR, 0.58; 95%CI, 0.36-0.93; p=0.024). Causal mediation analysis indicated an indirect effect of PPI on reducing all-cause death through the suppression of gastrointestinal bleeding events. Conclusion These findings suggested that use of PPI against gastrointestinal bleeding complications might reduce the risk of subsequent all-cause death in ACS patients undergoing PCI.

Causes and predictors of long-term mortality in patients referred to a cardiac rehabilitation program

Abstract Introduction Cardiac rehabilitation (CR) programs have proven to reduce short-term mortality in patients with ischemic heart disease (IHD) and hospitalization rates in patients with heart failure (HF) (1-3). However, there is insufficient evidence about long-term mortality (>24-36 months) for patients receiving treatments based on recent clinical practice recommendations. Purpose To assess the long-term prognosis and predictors of mortality in a heterogenous group of patients referred to cardiac rehabilitation, and to obtain a detailed overview of death causes. Methods An inferential analysis of consecutive patients referred for exercise-based CR at a single site between January 2016 and January 2021 was performed. Included subjects were classified attending to four indications for referral: IHD, HF, valvular heart disease (VHD) and cancer therapy-related cardiovascular toxicity (CTR-CVT). Patients who did not initiate the CR program or were referred for other indications were excluded. The primary endpoint was all cause death. The secondary endpoint was cardiovascular (CV) death. A survival analysis was performed using Kaplan Meier estimates for each referral indication and a Cox proportional hazards model was fitted to investigate mortality predictors. The initiation of the exercise program was considered the inclusion date, and patients were followed until they met the primary endpoint or censored by January 2024. Results A total of 1180 patients were included in the analysis (81% male, mean age 61 ± 11 years), with a median follow-up of 5.3 years. Most of the patients had been referred due to IHD (87%), while the proportion for HF, VHD, and CTR-CVT was 9.9%, 1.8% and 1.4%, respectively. Seventy-eight patients (6.6%) died during follow-up, with a Kaplan-Meier estimated survival of 94.5% at 5 years (95% CI 93.2%-95.9%). Nineteen patients (24.4%) died due to a cardiovascular event, mostly sudden cardiac death (47%). The predominant non-CV causes of death were infectious disease (36%) and cancer (34%). A multivariate Cox model analysis (Table 1) showed an increased risk of all cause death for patients referred due to HF (HR 2.95, 95% CI 1.33 - 6.55), VHD (HR 5.55, 95% CI 1.19 - 25.9) and CTR-CVT (22.47, 95% IC 7.32 - 68.95) when compared to IHD (Figure 1). Other significant predictors of mortality were LVEF <40%, male sex, age, diabetes, peripheral vascular disease, and multivessel coronary disease. Only LVEF <40%, VHD, CTR-CVT and peripheral vascular disease were independent predictors of CV death. Conclusion Patients who initiated an exercise-based CR program had a low risk of all cause death at 5 years. Indications for CR other than IHD were associated with higher mortality rates after adjusting for confounder variables, likely due to a selection bias of patients in advanced stages of the disease.Table 1.Cox models for all-cause deathFigure 1.KM plot for all-cause death

Comparison of multiple high sensitivity cardiac troponin assays for early low risk rule out of myocardial infarction: SCORECARD

Abstract Background/Introduction The use of a single low high-sensitivity cardiac troponin measurement to rule out myocardial infarction (MI) at presentation is advocated by international guidelines. Studies have not systematically compared high-sensitivity cardiac troponin (hs-cTn) I and T assays to determine which values should be used to rule out MI in patients with suspected acute coronary syndrome. Methods In a pooled analysis from three prospective observational cohort studies the lowest cTn concentration was determined that gave a negative predictive value (NPV) of ≥99.5% for MI or death at 30 days on presentation to the emergency department. EDTA or lithium heparin plasma or serum samples collected at presentation were measured using five hs-cTnI assays (Abbott ARCHITECT i2000, Beckman Coulter Access 2, Siemens Atellica IM, Ortho-Clinical Diagnostics VITROS 5600, LSI Medience PATHFAST) and one hs-cTnT assay (Roche Cobas e411). The diagnostic outcome of MI or death at 30 days was adjudicated according to the Fourth Universal Definition of MI. Optimal thresholds were determined to identify the highest proportion of patients that could be considered for discharge for a NPV of ≥99.5% for each assay. Results Among 941 patients, MI or death at 30 days occurred in 113 (12%). Optimized thresholds varied between assays ranging from <2 to <7 ng/L (Table) that identified between 22% and 60% of patients as low risk (0-1%) for MI or death at 30 days. Conclusions Our data identify differences in the effectiveness of thresholds between hs-cTnI and hs-cTnT assays for the same safety performance to rule out MI on presentation using a single measurement. In some cases, these thresholds differ from those used in clinical practice. Due to lack of assay standardization, optimal decision thresholds should be defined and validated for each high sensitivity cTn assay.

Screening for Atrial Fibrillation (AF) by handheld single-lead ECG and risk of all-cause mortality stratified by non-AF cardiovascular disease

Abstract Purpose Screening for Atrial fibrillation (AF) has been suggested as a strategy to increase early detection of silent AF. We aimed to evaluate all-cause mortality between patients with screen-detected and clinically-diagnosed AF, and the effect of oral anticoagulation therapy (OAC) on mortality. Methods We prospectively enrolled and performed AF screening using handheld single-lead ECG(AliveCor) on consecutive patients who attended medical outpatient clinics during December 2014 and December 2017. Repeat screening was performed among patients who had >1 clinic visits. All participants were divided into 5 cohorts: (i) previously known AF at baseline (kAF); (ii) initial screen-detected AF (S1-AF); (iii) subsequent screen-detected AF (FU-sAF); (iv) clinically-diagnosed AF during follow-up (FU-cAF); and (v) no AF. Risk of all-cause mortality was estimated by adjusted hazard ratio (HR) using COX proportional hazards regression, adjusting for age, gender, co-morbidities, concurrent chronic use of medications including OAC, with AF detection or clinical diagnosis and OAC therapy handled as time-varying variable. Subgroup analysis was conducted to identify heterogeneity of effect across with or without non-AF cardiovascular disease (CVD). Results Of 11,972 subjects (mean age 76.6±7.8, female 49.2%), 18.7% (n=2,236) had previously kAF, 1.9% (n=223) S1-AF, 0.6% (n=71) FU-sAF, 7.3% (n=867) FU-cAF, and 71.6% (n=8,559) no AF. During a median FU duration of 6.8(IQR: 5.2-8.1) years, patients with kAF (HR=1.8(1.6-2.0)), S1-AF (HR=1.6(1.3-1.9)) and FU-cAF (HR=1.6(1.4-1.8)) were at higher risk of all-cause mortality, compared to individuals without AF, whereas FU-sAF (HR=1.0(0.7-1.4)) had similar low risk of death as no AF. Heterogeneity of effect was detected in subgroup analysis. Among patients without non-AF CVD, FU-sAF (HR=6.0(1.8-19.8)) and FU-cAF (HR=4.7(3.3-6.7)) were at markedly higher risk of all-cause mortality. DOAC (HR=0.57(0.38-0.87)) but not VKA (HR=0.72(0.43-1.15) reduced mortality. However, in patients with CVD other than AF, risk of FU-sAF (HR=1.1(0.8-1.6)) decreased to as low as individuals without AF (P for interaction =0.0039).Both DOAC (HR=0.51(0.46-0.58)) and VKA (HR=0.87(0.78-0.98) were beneficial. Conclusion Likely delayed AF detection suggested by groups of FU-cAF and FU-sAF may be associated with significant rise in risk of mortality among patients without non-AF CVD. The effect diminished when non-AF CVD as potential competing risk existed. The role of VKA in reducing all-cause mortality warrants more studies.

Risk of subsequent primary cancers in bladder cancer survivors

We aimed to investigate the risk of bladder cancer (BCa) survivors developing or dying from 15 specific-subsequent primary cancers (SPCs). A total of 229,554 BCa survivors were identified from the Surveillance, Epidemiology, and End Results database. Incidence and mortality per 10,000 person-years, absolute excess risk (AER) per 10,000 person-years, standardized incidence ratios, and standardized mortality ratios were calculated. Among BCa survivors, 38,207 developed SPCs and 17,546 died of SPCs. The risk of developing and dying from SPCs was significantly high for 10 and 6 of the 12 common SPCs in men, respectively, while for 6 and 5 of the 14 common SPCs in women, respectively. The SPCs with high risk of development in men were colorectal, breast, liver, and pancreatic cancer, and the ones with high risk of death were liver and pancreatic cancer. Moreover, SPCs with a high risk of development or death among young BCa survivors include ureter, kidney and renal pelvis, and lung cancer. In addition, BCa survivors within 1 year of diagnosis have a significantly higher risk of development and death from ureter, kidney and renal pelvis, prostate, and cervix cancer, but a lower risk of prostate cancer than the general population after 5 years of diagnosis. Lung cancer had a significantly high risk of development but a low risk of death. Among BCa survivors, the risk of developing or dying from few SPCs is significantly high. These findings may provide an important basis for clinical follow-up of BCa survivors.

Hepatic steatosis estimated by VCTE-derived CAP scores was associated with lower risks of liver-related events and all-cause mortality in patients with chronic liver disease.

The Controlled Attenuated Parameter (CAP) score derived from vibration-controlled transient elastography (VCTE, i.e. Fibroscan®) is a well-validated marker of hepatic steatosis. It is unclear if CAP scores are associated with risks of liver-related outcomes or all-cause mortality. In this retrospective cohort study, we identified 7,587 U.S. Veterans (2,689 with cured hepatitis C [HCV], 1,523 with alcohol-associated liver disease [ALD], 3,375 with metabolic dysfunction-associated steatotic liver disease [MASLD]) who underwent VCTE between 5/2015-12/2021. We followed patients for new hepatic decompensation, hepatocellular carcinoma (HCC), and death from the VCTE date until 1/1/2022. Multivariable Cox-proportional hazards regression was used to assess for the associations between CAP measurements and clinical outcomes, adjusting for age, sex, race/ethnicity, body mass index, Charlson Comorbidity Index, diabetes, liver disease etiology, liver stiffness measurements, and FIB-4, and was reported separately by disease etiology and advanced fibrosis status. Over a median follow-up time of ∼1.9 years, hepatic steatosis (grades 1-3 vs. 0) was associated with a lower risk of death (aHR 0.70, 95% CI: 0.57-0.85). Among patients with MASLD, hepatic steatosis was associated with a lower risk of decompensation (aHR 0.54, 95% CI: 0.32-0.90) and death (aHR 0.52, 95% CI: 0.37-0.73). These associations persisted in subgroup analyses of patients with advanced fibrosis and without cirrhosis. Among patients who underwent VCTE in clinical practice, the presence of substantial hepatic steatosis estimated by the CAP score was associated with lower all-cause mortality among all patients and lower risk of decompensation and death among those with MASLD.

Prognostic impact of switching to the 2021 chronic kidney disease epidemiology collaboration creatinine-based equation in Caucasian patients with type 2 diabetes: the Renal Insufficiency and Cardiovascular events (RIACE) Italian Multicenter Study

BackgroundA Chronic Kidney Disease (CKD) Epidemiology Collaboration (EPI) formula not including a Black race coefficient has been recently developed and is now recommended in the US. The new (2021) equation was shown to yield higher estimated glomerular filtration rate (eGFR) values than the old (2009) one in a non-Black general population sample, thus reclassifying a significant number of individuals to a better eGFR category. However, reclassified individuals were previously shown to have a lower risk of progression to end-stage kidney disease, but higher adjusted risks for all-cause death and morbidity and mortality from cardiovascular disease than those not reclassified. This study evaluated the prognostic impact of switching from the 2009 to the 2021 CKD-EPI equation in non-Black individuals with type 2 diabetes.MethodsThe Renal Insufficiency And Cardiovascular Events (RIACE) was a prospective cohort study enrolling 15,773 Caucasian patients in 19 Italian centers in 2006–2008. Cardiometabolic risk profile, treatments, complications, and comorbidities were assessed at baseline and eGFR was calculated with the two equations. Vital status was retrieved on 31 October 2015 for 15,656 participants (99.3%).ResultsWith the 2021 equation, the eGFR value increased in all patients, except for 293 individuals with a 2009 eGFR ≥ 105 ml·min− 1·1.73 m− 2. The median difference was 4.10 ml·min− 1·1.73 m− 2 and was higher in males, older individuals and those in the G2 category. Reclassification decreased the percentage of patients with reduced eGFR from 17.28 to 13.96% and with any CKD from 36.23 to 34.03%. Reclassified individuals had better cardiometabolic risk profile and lower prevalence of complications and use of medications than non-reclassified individuals. Risk of death versus the 2009 G1 category was lower for reclassified than non-reclassified participants in all eGFR categories and, particularly, in each 2009 eGFR category, though difference was significant only in the G4-G5 category. The Receiver Operator Characteristic curves were statistically, but not clinically different with the two equations.ConclusionChanging from the 2009 to the 2021 CKD-EPI equation results in higher eGFR and lower CKD prevalence, with a lower risk of death in reclassified patients with an eGFR < 30 ml·min− 1·1.73 m− 2, but virtually no impact on mortality prediction.Trial registration: ClinicalTrials.gov, NCT00715481, retrospectively registered 15 July, 2008.

Temporal Trends and Mortality Patterns in Peripheral Arterial Disease: A Comprehensive Analysis of Hospitalized Patients in Kazakhstan between 2014 and 2021.

Peripheral artery disease (PAD) is a global health concern associated with arterial narrowing or blockage, leading to significant morbidity and mortality. The aim of this study is to assess the disease burden and trends in mortality utilizing nationwide administrative health data. This retrospective study utilized data from the Unified National Electronic Healthcare System (UNEHS) from 2014 to 2021. Patients meeting PAD criteria were included, with demographic and clinical data analyzed. Cox regression and Competing Risk Analysis assessed mortality risks. Between 2014 and 2021, 19,507 individuals were hospitalized due to PAD, with 8,332 (43%) being women and 11,175 (57%) men. The incidence of PAD increased markedly over the observation period, rising from 79 individuals per million population (PMP) in 2014 to 309 PMP in 2021. Concurrent heart failure (HF), acute myocardial infarction (AMI), diabetes, and essential hypertension were prevalent in 50%, 27%, 27%, and 26% of the PAD patients, respectively. Competing Risk Analysis showed a subdistribution hazard ratio (SHR) of 6.53 [95% CI: 4.65-9.19] for individuals over 80 years. Heart failure was associated with lower all-cause HR [0.80, 95% CI: 0.76-0.86, p < 0.001] but higher SHR [1.30, 95% CI: 1.18-1.44, p < 0.001]. Comorbidities such as heart failure, stroke, and acute myocardial infarction significantly increased mortality risks, while essential hypertension was associated with lower risk of death. The significant rise in the incidence rate of PAD underscores the growing burden of the disease, highlighting the urgent need for targeted preventive and management strategies in Kazakhstan.

Pesticide exposure and oxidative stress generation are linked to poor prognosis outcomes in breast cancer women carrying the allelic variant rs7438135 in the UGT2B7 gene.

Pesticide exposure is a risk factor for the development of several diseases, including breast cancer (BC). The enzyme UGT2B7 participate in detoxification of pesticides and the presence rs7438135 (G > A) variant in your gene increases its glucuronidation potential, contributing to oxidative stress metabolites neutralization. Here we investigated the impact of occupational pesticide exposure on the systemic oxidative stress generation from 228 women with BC depending on their UGT2B7 rs7438135 (G > A) status. q-PCR investigated the presence of the rs7438135 variant, and oxidative stress markers (lipid peroxidation levels, total antioxidant capacity-TRAP, and nitric oxide metabolites-NOx) were measured in plasma. Pesticide exposure induced significant augment in the systemic lipid peroxidation in the presence of the variant for several clinicopathological conditions, including tumors with high proliferation index (ki67) and with high aggressiveness. NOx was augmented in high ki67, positive progesterone receptors, high-grade and triple-negative/Luminal B tumors, and low-risk stratified patients. TRAP was depleted in young patients at menopause and those with triple-negative/Luminal B tumors, as well as those stratified as at low risk for death and recurrence. These findings showed that the presence of the variant was not able to protect from pesticide-induced oxidative stress generation in BC patients.

COMPARATIVE EFFICACY OF METHYLPREDNISOLONE AND TOCILIZUMAB IN PATIENTS WITH A SEVERE FORM OF COVID-19

Background. Recently, we have again noted an increase in the incidence of COVID-19. The treatment of patients with severe coronavirus infection poses a significant medical challenge. Objectives. The purpose of this research was to compare the efficacy of standard therapy and pulses of methylprednisolone in combination with or without tocilizumab in patients with a severe form of COVID-19. Patients and methods. In a retrospective study, the medical charts of 220 patients with a severe course of COVID-19 were reviewed. Patients were divided into four groups: those on daily methylprednisolone at a dose of 32 mg enterally; patients who received methylprednisolone pulses (500 mg daily intravenously for three consecutive days, with a subsequent change to the 32 mg of methylprednisolone daily); patients who received a single dose of 400 mg tocilizumab in combination with a 32 mg of methylprednisolone daily; patients who received a single dose of 400 mg tocilizumab in combination with methyl­prednisolone pulse therapy. At the end of therapy, 28-day mortality and the number of intubations in each group one week after the end of therapy were analyzed. Results. Patients treated with a combination of tocilizumab and pulse methylprednisolone therapy had the lowest risk of death (p&lt;0.001), OR=0.03 (95 % CI 0.01-0.16), compared to patients treated only with 32 mg of methylprednisolone. Conclusions. Methylprednisolone pulses therapy is more effective than therapy with methylprednisolone at a daily dose of 32 mg. The combination of methylprednisolone and tocilizumab is more effective than the isolated administration of methylprednisolone. The combination of tocilizumab with methylprednisolone pulse therapy had the highest therapeutic effect.

Glucagon-like peptide-1 receptor agonists improve outcomes in individuals with type 2 diabetes with and without heart failure

BackgroundThe effectiveness of glucagon-like peptide-1 receptor agonists (GLP1Ras) for prevention of heart failure (HF) in patients with type 2 diabetes (T2DM) without HF and for risk of death in patients with T2DM with HF has not been fully elucidated in routine clinical practice. MethodsUsing the real-world global electronic medical record TriNetX database, individuals with T2DM and with or without HF who initiated either GLP1Ras or sitagliptin from 2017 to 2020 were retrospectively analyzed. In individuals with T2DM without HF, the primary outcome was a composite of all-cause mortality and a new diagnosis of HF within three years. In individuals with T2DM with HF, the primary outcome was all-cause mortality within three years. Propensity-score (PS) matching was used to adjust for over 100 baseline characteristics. ResultsA total of 65,598 individuals with T2DM without HF starting a GLP1Ras were PS matched with 65,598 starting sitagliptin. GLP1Ras were associated with a lower incidence of the composite endpoint (10.5 % versus 11.8 %, hazard ratio [HR] 0.82, [0.80–0.85], p < 0.001), mortality (HR 0.66 [0.63–0.69]) and new diagnosis of HF (HR 0.92 [0.88–0.96]). There were 6002 individuals in each group matched for T2DM and HF. Mortality was lower in the GLP1Ras group (17.6 % versus 22.8 %, HR 0.70 [0.65–0.76], p < 0.001). Results were consistent across subgroups. ConclusionsIn this global real-world data analysis, GLP1Ra use was associated with a lower risk of death and HF in individuals with T2DM without HF, and lower risk of death in those with HF.

Survival status and influencing factors of death risk of HIV-infected patients in Hangzhou, 2004-2023

Objective: To analyze the survival status and death factors of confirmed HIV-infected patients in Hangzhou to provide a basis for the formulation of AIDS prevention and treatment strategies. Methods: A retrospective cohort study was conducted. The data were from the HIV/AIDS Comprehensive Response Information Management System of the Chinese Disease Control and Prevention Information System.Epidemiological characteristics of HIV-infected patients were comparied in Hangzhou City from 2004 to 2023 by using chi-square Test. The survival rate of HIV-infected patients in Hangzhou was calculated by the life table method, the survival curves of different subgroups were described by the Kaplan-Meier method, and the Cox proportional hazard regression model was used to analyze the influencing factors of death risk. The SPSS 26.0 software was used for statistical analysis. Results: Among the 9 457 subjects, the total follow-up time was 58 004.18 person-years, 494 patients died, fatality rate of all-cause cases was 0.85 per 100 person-years.The average survival time was 18.59 (95%CI:18.40-18.78) years. Malignant neoplasms and pneumocystis pneumonia were the first (14.37%,71/494) and second (10.73%, 53/494) causes of death, respectively. Death within 6 months after diagnosis accounted for 42.51% (210/494), and suicide accounted for 4.25% (21/494). Multivariate Cox regression analysis showed that compared with those who received antiviral treatment (ART) within 3 months of diagnosis, those who received ART outside 3 months and those who did not receive ART had a 1.65 (95%CI:1.25-2.19) and 20.68 (95%CI:15.80-27.06) times risk of death, respectively. The HIV-infected patients with high CD4+T lymphocytes (CD4) counts for the first time had a lower risk of death. The risk of death of patients with baseline CD4 counts of 200-349 cells/µl, 350-499 cells/µl, and ≥500 cells/µl was 0.38 (95%CI:0.29-0.49), 0.26 (95%CI:0.19-0.36), 0.21 (95%CI:0.14-0.31) times higher than that of baseline CD4 counts <200 cells/µl, respectively. Conclusions: The overall survival of the HIV-infected patients was good in Hangzhou from 2004 to 2023. Early detection of HIV infection and timely mobilization to participate in ART was the key to improving the survival rate of patients. At the same time, given the suicide problem of HIV-infected patients, suicide surveillance and depression and anxiety screening of HIV-infected patients should be further strengthened, and targeted psychological intervention policies should be implemented.

Textbook oncologic outcome is an easy-to-use composite quality measure that is strongly associated with survival in advanced-stage ovarian cancer

ObjectiveTextbook oncologic outcome (TOO) has been validated in surgical oncology as a composite quality measure correlated with oncologic outcomes. We aimed to assess the association between TOO and overall survival (OS) in patients undergoing primary treatment for advanced epithelial tubo-ovarian cancer (AEOC). MethodsPatients undergoing surgery for AEOC between 2008 and 2019 were identified in the National Cancer Database (NCDB). Primary debulking surgery (PDS) and interval debulking surgery (IDS) cohorts were analyzed separately. TOO was defined as achieving complete debulking, length of hospital stay <10 days, no 30-day readmission, no death within 90 days, and initiation of adjuvant chemotherapy within 42 days. The Kaplan-Meier method was used to estimate 5-year OS by TOO status and Cox regression to evaluate the relationship between TOO and death within 5 years. ResultsA total of 21,657 patients were included: 51.4% in the PDS cohort and 48.6% in the IDS cohort. TOO was achieved (TOO+) in 20.5% of the PDS cohort and 39.2% of the IDS cohort. For the PDS cohort, achieving TOO was associated with improved 5-year OS: 59.0% TOO+ vs. 39.5% TOO- (HR 0.53, 95% CI 0.49–0.57). For the IDS cohort, a similar benefit was seen for 5-year OS: 43.9% TOO+ vs. 31.2% TOO- (HR 0.67, 95% CI 0.63–0.70). Multivariable analysis demonstrated that patients achieving TOO were at lower risk of death within 5 years in both the PDS cohort (HR 0.58, 95% CI 0.54–0.62) and the IDS cohort (HR 0.69, 95% CI 0.65–0.73). ConclusionsThe TOO composite measure is associated with improved long-term survival and could be a useful quality assessment tool for patients undergoing primary treatment for AEOC, irrespective of surgical timing. This tool reflects the ability to deliver risk-based individualized decision-making using a multidisciplinary approach.

Disorder of Glucose Metabolism and Therapy: Implications on the Natural History of Advanced Chronic Liver Disease

Introduction: Hepatogenous diabetes (HD) is a disorder of glucose metabolism (DGM) that develops as a complication of advanced chronic liver disease (ACLD) with an estimated prevalence of 20–70%. It appears to be associated with a larger number of decompensations, but its impact on the natural history of the disease is unclear. The treatment of DGM is hampered by the fact that some therapeutic agents are associated with a risk of complications in ACLD. The aim of this work was to study DGM in a population of patients with ACLD: prevalence, liver disease decompensation episodes, mortality analysis and study of the impact of antidiabetic therapies in patients with ACLD who developed DGM. Materials and Methods: A cohort of consecutive patients with ACLD without previous DGM, who attended a Hepatology clinic in the period of January to June 2015 was selected. Follow-up was carried out for 5 years. Data on age, gender, date of diagnosis and etiology of ACLD, Child-Pugh and MELD-Na classifications at enrollment, development of DGM, and antidiabetic therapy were collected. Logistic regression models for hospitalizations due to decompensated ACLD, ascites, hepatic encephalopathy (HE), upper gastrointestinal bleeding (UGB), hepatocellular carcinoma (HCC), portal vein thrombosis (PVT), infectious complications, acute-on-chronic liver failure (ACLF), and death were built. A survival analysis for patients with and without DGM was also performed. Treatment effectiveness for patients with DGM was assessed. Results: Initially, 221 patients were included, 154 (69.7%) of whom developed DGM after the diagnosis of ACLD. DGM patients presented a significantly higher number of hospitalizations. Odds ratio (OR) for death was not significantly related with DGM. At 5 years of follow-up, 68.9% of patients with DGM were alive, against 81.8% without DGM (p = 0.087). From the 154 patients who were diagnosed with DGM, 42.9% were not receiving pharmacological treatment for DGM. Treated patients were prescribed with either biguanides (34.8%), a SGLT2 inhibitor (8.6%), or insulin (7.7%). Only 1 patient was treated with a GLP-1 analogue. A tendency of OR favoring treatment was observed for biguanides and SGLT2 inhibitors in all outcomes except ascites. In the univariable analysis, the use of biguanides was associated with lower risk of death (OR: 0.84 [95% CI: 0.73–0.96]) and HE (OR: 0.85 [95% CI: 0.73–0.98]). Conclusion: DGM occurs with high prevalence in patients with ACLD and it seems to be related to more hospitalizations, which highlights the importance of its early identification and appropriate therapeutic approach. In the absence of contraindications, biguanides should be considered for treatment of patients with ACLD and DGM as they appear to be associated with a tendency to better outcomes and may present some advantage in terms of survival.

Comparing percutaneous coronary intervention and coronary artery bypass grafting for left main stenosis on the basis of current regional registry evidence

ObjectivesThere is an ongoing debate whether percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) is the better choice for treatment of left main (LM) stenosis. We aimed to provide external validation for the recently reviewed guideline recommendations for invasive LM therapy by evaluating the impact of CABG or PCI on long-term survival from local reports of different regions in the world. We performed a systematic review and meta-analysis to address contemporary registry studies comparing PCI and CABG for patients with LM stenosis. MethodsThree databases were assessed. Our primary end point was long-term all-cause mortality. Secondary end points were major adverse cardiovascular events (MACE), myocardial infarction, repeat revascularization, stroke, and periprocedural mortality. Reconstruction of time-to-event data was performed. ResultsA total of 2477 studies were retrieved. Seven studies with risk-adjusted populations were selected for the analysis. Four studies favored CABG and 3 studies showed no difference for the primary end point. Compared with PCI, patients who underwent CABG had lower risk of death (hazard ratio, 1.15; 95% confidence interval, 1.05-1.26, P < .01) and MACE (hazard ratio, 1.54; 95% confidence interval, 1.40-1.69, P < .01) during follow-up. Moreover, PCI was associated with more myocardial infarction, repeat revascularization, but less strokes when compared with CABG. There was no significant difference regarding periprocedural mortality. The MACE rate was lower after CABG in both early and late phase, which outweighs the higher rate of periprocedural stroke after CABG. ConclusionsRegional registry evidence supports the current notion of superior long-term endpoints with CABG compared with PCI for the treatment of LM stenosis over time.

A cross-sectional study of the association between blood cadmium and mortality among adults with myocardial infarction.

Cadmium (Cd) plays a key role in the occurrence of myocardial infarction (MI). We aimed to explore the association between blood Cd levels and all-cause mortality of MI on the basis of the National Health and Nutrition Examination Survey databases. This study included 800 adults with MI to obtain blood Cd concentrations and their follow-up information. The association between Cd concentrations and mortality was analyzed using Cox regression, restricted cubic spline (RCS) models, mediation analysis, receiver operating characteristic curve, and Kaplan-Meier curves. All the patients were divided into 4 groups according to the quartiles of blood Cd levels (Q1, Q2, Q3, and Q4). Cox regression analysis with adjustment for covariates indicated that Cd was the promoting factor of mortality, and patients with higher Cd had a higher death risk. The RCS model indicated an "inverted checkmark" shaped correlation between Cd levels and mortality, and a turning point of 1.06 μg/L was found. A significant positive correlation was observed on the left of the turning point. Grouped patients by turning point into 2 groups, Kaplan-Meier analysis showed that the low-concentration group had a lower death risk than the high-concentration group. Subgroup analysis revealed that the prognostic effect of Cd was more pronounced in patients with former smoking history, and receiver operating characteristic curve showed that blood Cd had a better-predicting function in patients with MI. Blood Cd levels were significantly related to all-cause mortality in patients with MI, especially in patients with Cd < 1.06 μg/L.