Cox Proportional Hazards Regression Models Research Articles

Sleep Pattern, Genetic Susceptibility, and Abdominal Aortic Aneurysm in UK Biobank Participants: Large-Scale Cohort Study

BackgroundAbdominal aortic aneurysm (AAA) is an important cause of cardiovascular mortality. ObjectivesThe authors aimed to explore the associations between sleep patterns and genetic susceptibility to AAA. MethodsWe included 344,855 UK Biobank study participants free of AAA at baseline. A sleep pattern was defined by chronotype, sleep duration, insomnia, snoring, and daytime sleepiness, and an overall sleep score was constructed with a range from 0 to 5, where a high score denotes a healthy sleep pattern. Polygenic risk score based on 22 single nucleotide polymorphisms was categorized into tertiles and used to evaluate the genetic risk for AAA. Cox proportional hazards regression models were used to assess the association between sleep, genetic factors, and the incidence of AAA. ResultsDuring a median of 12.59 years of follow-up, 1,622 incident AAA cases were identified. The HR per 1-point increase in the sleep score was 0.91 (95% CI: 0.86-0.96) for AAA. Unhealthy sleep patterns, defined as a sleep score ranging from 0 to 3, were found to be associated with a higher risk of AAA for the intermediate (HR: 1.18, 95% CI: 1.06-1.31) and poor sleep patterns (HR: 1.40, 95% CI: 1.13-1.73), respectively, compared to the healthy pattern. Participants with poor sleep patterns and high genetic risks had a 2.5-fold higher risk of AAA than those with healthy sleep patterns and low genetic risk. ConclusionsIn this large prospective study, healthy sleep patterns were associated with a lower risk of AAA among participants with low, intermediate, or high genetic risk.

Focal high-intensity focused ultrasound therapy for localized prostate cancer: An interim analysis of the multinational FASST study.

High-intensity focused ultrasound (HIFU) emerged as a novel approach for the treatment of localized prostate cancer (PCa). However, prospective studies on HIFU-related outcomes and predictors of treatment failure (TF) remain scarce. We conducted a multinational prospective cohort study among patients undergoing HIFU therapy for localized, low- to intermediate-risk PCa. Follow-up data on serial prostate specific antigen (PSA), multi-parametric magnetic resonance imaging (mpMRI), targeted/systematic biopsies, adverse events and functional outcomes were collected. The primary endpoint was TF, defined as histologically confirmed PCa requiring whole-gland salvage treatment. Uni- and multi-variable adjusted hazard ratios (HRs) were calculated using Cox proportional hazard regression models. At baseline, mean (standard deviation) age was 64.14 (7.19) years, with the majority of patients showing T-stage 1 (73.9%) and International Society of Urological Pathology grading system Grade 2 (58.8%). PSA nadir (median, 1.70 ng/mL) was reached after 6 months. Of all patients recruited, 16% had clinically significant PCa, as confirmed by biopsy, of which 13.4% had TF. Notably, T-stage and number of positive cores at initial biopsy were independent predictors of TF during follow-up (HR [95% CI] 1.27 [1.02-1.59] and 5.02 [1.80-14.03], respectively). Adverse events were minimal (17% and 8% early and late adverse events, respectively), with stable or improved functional outcomes in the majority of patients. This interim analysis of a multinational study on HIFU therapy for the management of low-to-intermediate-risk PCa reveals good functional outcomes, minimal adverse events and low incidence of TF over the short-term. Data on long-term outcomes, specifically as it relates to oncological outcomes, are awaited eagerly.

Enterotoxin-related genes PPFIA4 and SCN3B promote colorectal cancer development and progression.

To identify the role of enterotoxin-related genes in colorectal cancer (CRC) development and progression. Upregulated differentially expressed genes shared by three out of five Gene Expression Omnibus (GEO) data sets were included to screen the key enterotoxin-induced oncogenes (EIOGs) according to criteria oncogene definition, enrichment, and protein-protein interaction (PPI) network analysis, followed by prognosis survival, immune infiltration, and protential drugs analyses was performed via integration of RNA-sequencing data and The Cancer Genome Atlas-derived clinical profiles. We screened nine common key EIOGs from at least three GEO data sets. A Cox proportional hazards regression models verified that more alive cases, decreased overall survival, and highest 4-year survival prediction in CRC patients with high-risk score. Protein tyrosine phosphatase receptor type F polypeptide-interacting protein alpha-4 (PPFIA4), STY11, SCN3B, and SPTBN5 were shared in the same PPI network. Immune infiltration results showed that SCN3B and synaptotagmin 11 expression were obviously associated with B cell, macrophage, myeloid dendritic cell, neutrophils, and T cell CD4+ and CD8+ in both colon adenocarcinoma and rectal adenocarcinoma. CHIR-99021, MLN4924, and YK4-279 were identified as the potential drugs for treatment. Finally, upregulated EIOGs genes PPFIA4 and SCN3B were found in colon adenocarcinoma and PPFIA4 and SCN3B were proved to promote cell proliferation and migration in vitro. We demonstrated here that EIOGs promoting a malignancy phenotype was related with poor survival and prognosis in CRC, which might be served as novel therapeutic targets in CRC management.

Autism Spectrum Disorder Diagnoses and Congenital Cytomegalovirus.

To examine the association between congenital cytomegalovirus (cCMV) and autism spectrum disorder (ASD) administrative diagnoses in US children. Cohort study using 2014 to 2020 Medicaid claims data. We used diagnosis codes to identify cCMV (exposure), ASD (outcome), and covariates among children enrolled from birth through ≥4 to <7 years. Covariates include central nervous system (CNS) anomaly or injury diagnosis codes, including brain anomaly, microcephaly within 45 days of birth, cerebral palsy, epilepsy, or chorioretinitis. We used Cox proportional hazards regression models to estimate hazard ratios and 95% confidence intervals, overall and stratified by sex, birth weight and gestational age outcome (low birth weight or preterm birth), and presence of CNS anomaly or injury. Among 2 989 659 children, we identified 1044 (3.5 per 10 000) children with cCMV and 74 872 (25.0 per 1000) children with ASD. Of those with cCMV, 49% also had CNS anomaly or injury diagnosis codes. Children with cCMV were more likely to have ASD diagnoses (hazard ratio: 2.5; 95% confidence interval: 2.0-3.2, adjusting for birth year, sex, and region). This association differed by sex and absence of CNS anomaly or injury but not birth outcome. Children with (versus without) cCMV diagnoses in Medicaid claims data, most of whom likely had symptomatic cCMV, were more likely to have ASD diagnoses. Future research investigating ASD risk among cohorts identified through universal cCMV screening may help elucidate these observed associations.

Correlation of hematocrit and cardiovascular events in peritoneal dialysis patients

Objective: To investigate the correlation between hematocrit (HCT) and cardiovascular events in peritoneal dialysis (PD) patients. Methods: Patients undergoing maintenance PD in the PD center of Guizhou Provincial People's Hospital from March 19, 2012 to July 9, 2020 were included. Demographic, baseline clinical and laboratory data of the patients were collected and patients were followed up until April 8, 2022. The primary endpoint was the first occurrence of a cardiovascular event. According to the tertiles of baseline HCT, the patients were divided into group Q1 (HCT≤26.6%), group Q2 (HCT>26.6%-32.4%), and group Q3 (HCT>32.4%). Laboratory indexes and cardiovascular events were compared among the three groups. Kaplan-Meier survival curve, Cox regression analysis and sensitivity analysis were used to analyze the effect of HCT on cardiovascular outcomes. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of HCT for cardiovascular events in PD patients. Results: A total of 860 PD patients were included, including 494 males (57.4%) and 366 females (42.6%), with a mean age of (41.5±15.0) years. There were 287 cases in group Q1, 289 cases in group Q2, and 284 cases in group Q3, respectively. A total of 265 (30.8%) patients experienced first cardiovascular events during the follow-up period. The incidence of cardiovascular events in groups Q1, Q2 and Q3 was 36.2% (104/287), 34.3% (99/289), and 21.8% (62/284), respectively, with a statistically significant difference (P<0.001). The incidence of cardiovascular events decreased with the increase of HCT. Multivariate Cox proportional hazards regression model analysis showed that decreased HCT was a risk factor for cardiovascular events. Compared with group Q3, the risk of cardiovascular events in group Q1 increased by 50.7% (group Q2: HR=1.444, 95%CI: 1.029-2.028, P=0.034; group Q1: HR=1.570, 95%CI: 1.096-2.250, P=0.014). In the sensitivity analysis, using kidney transplantation as the competition event, the risk of cardiovascular events was lower in group Q3 than that in group Q1 (subdistributional HR=1.413, 95%CI: 1.006-1.990, P=0.046). Kaplan-Meier survival curve showed that compared with the other two groups, the cardiovascular events-free survival rate of patients in group Q1 was significantly lower (log-rank χ2=9.722, P=0.008). ROC analysis showed that the area under the curve (AUC) of HCT for predicting cardiovascular events in PD patients was 0.583 (95%CI: 0.542-0.623, P<0.001), with the sensitivity of 40.6% and the specificity of 75.1%. Conclusion: Low-level HCT is associated with an increased risk of the first cardiovascular event in PD patients.

Patent Foramen Ovale Closure in Older Patients With Stroke: Patient Selection for Trial Feasibility.

Whether patent foramen ovale (PFO) closure benefits older patients with PFO and cryptogenic stroke is unknown because randomized controlled trials (RCTs) have predominantly enrolled patients younger than 60 years of age. Our objective was to estimate anticipated effects of PFO closure in older patients to predict the numbers needed to plan an RCT. Effectiveness estimates are derived from major observational studies (Risk of Paradoxical Embolism [RoPE] Study and Oxford Vascular Study, together referred to as the "RoPE-Ox" database) and all 6 major RCTs (Systematic, Collaborative, PFO Closure Evaluation [SCOPE] Consortium). To estimate stroke recurrence risk, observed outcomes were calculated for patients older than 60 years in the age-inclusive observational databases (n = 549). To estimate the reduction in the rate of recurrent stroke associated with PFO closure vs medical therapy based on the RoPE score and the presence of high-risk PFO features, a Cox proportional hazards regression model was developed on the RCT data in the SCOPE database (n = 3,740). These estimates were used to calculate sample sizes required for a future RCT. Five-year risk of stroke recurrence using Kaplan-Meier estimates was 13.7 (95% CI 10.5-17.9) overall, 14.9% (95% CI 10.2-21.6) in those with high-risk PFO features. Predicted relative reduction in the event rate with PFO closure was 12.9% overall, 48.8% in those with a high-risk PFO feature. Using these estimates, enrolling all older patients with cryptogenic stroke and PFO would require much larger samples than those used for prior PFO closure trials, but selectively enrolling patients with high-risk PFO features would require totals of 630 patients for 90% power and 471 patients for 80% power, with an average of 5 years of follow-up. Based on our projections, anticipated effect sizes in older patients with high-risk features make a trial in these subjects feasible. With lengthening life expectancy in almost all regions of the world, the utility of PFO closure in older adults is increasingly important to explore.

Physical frailty, genetic predisposition, and incident dementia: a large prospective cohort study.

Physical frailty and genetic factors are both risk factors for increased dementia; nevertheless, the joint effect remains unclear. This study aimed to investigated the long-term relationship between physical frailty, genetic risk, and dementia incidence. A total of 274,194 participants from the UK Biobank were included. We applied Cox proportional hazards regression models to estimate the association between physical frailty and genetic and dementia risks. Among the participants (146,574 females [53.45%]; mean age, 57.24 years), 3,353 (1.22%) new-onset dementia events were recorded. Compared to non-frailty, the hazard ratio (HR) for dementia incidence in prefrailty and frailty was 1.396 (95% confidence interval [CI], 1.294-1.506, P < 0.001) and 2.304 (95% CI, 2.030-2.616, P < 0.001), respectively. Compared to non-frailty and low polygenic risk score (PRS), the HR for dementia risk was 3.908 (95% CI, 3.051-5.006, P < 0.001) for frailty and high PRS. Furthermore, among the participants, slow walking speed (HR, 1.817; 95% CI, 1.640-2.014, P < 0.001), low physical activity (HR, 1.719; 95% CI, 1.545-1.912, P < 0.001), exhaustion (HR, 1.670; 95% CI, 1.502-1.856, P < 0.001), low grip strength (HR, 1.606; 95% CI, 1.479-1.744, P < 0.001), and weight loss (HR, 1.464; 95% CI, 1.328-1.615, P < 0.001) were independently associated with dementia risk compared to non-frailty. Particularly, precise modulation for different dementia genetic risk populations can also be identified due to differences in dementia risk resulting from the constitutive pattern of frailty in different genetic risk populations. In conclusion, both physical frailty and high genetic risk are significantly associated with higher dementia risk. Early intervention to modify frailty is beneficial for achieving primary and precise prevention of dementia, especially in those at high genetic risk.

Should major trauma fractures be part of a fracture liaison service's remit: a cost-benefit estimate.

To compare the 3-year refracture rate following minimal trauma (MT) and non-minimal trauma (non-MT) injuries and evaluate the cost of extending fracture liaison service (FLS) operations to non-MT presentations. Patients aged 50, or above presenting to the John Hunter Hospital with a fracture in calendar year 2018 were identified through the Integrated Patient Management System (IPMS) of the Hunter New England Health Service's (HNEHS), and re-presentation to any HNEHS facility over the following 3years monitored. The refracture rate of MT and non-MT presentations was compared and analysed using Cox proportional hazards regression models. The cost of including non-MT patients was estimated through the use of a previously conducted micro-costing analysis. The operational fidelity of the FLS to the previous estimate was confirmed by comparing the 3-year refracture rate of MT presentations in the two studies. The 3-year refracture rate following a MT injury was 8% and after non-MT injury 4.5%. Extension of FLS activities to include non-MT patients in 2022 would have cost an additional $198,326 AUD with a notional loss/saving of $ - 26,625/ + 26,913 AUD through refracture risk reduction. No clinically available characteristic at presentation predictive of increased refracture risk was identified. The 3-year refracture after a non-MT injury is about half (57%) that of the refracture rate after a MT injury. Extending FLS activity to non-MT patients incurs a significant additional direct cost but remains cost neutral if notional savings gained through reduction in refracture risk are taken into account.

Influence of radiotherapy interruption on esophageal cancer with intensity-modulated radiotherapy: a retrospective study

BackgroundRadiotherapy interruption (RTI) prolongs the overall total treatment time and leads to local control loss in many cancers, but it is unclear in esophageal cancer. We aimed to evaluate the influence of RTI on the overall survival (OS), progression-free survival (PFS), and local-regional recurrence-free survival (LRFS) of patients with esophageal cancer undergoing chemoradiotherapy.MethodsA total of 299 patients with esophageal squamous cell carcinoma from 2017 to 2019 were retrospectively analyzed to investigate the effect of RTI on OS, PFS, and LRFS. The delayed time of radiotherapy interruption was calculated as the actual radiation treatment time minus the scheduled time. The univariate and multivariate analyses were performed by the COX proportional hazards regression models, and the survival analysis was performed through the Kaplan‒Meier method, and compared with the log-rank test.ResultsThe 3-year OS, PFS, and LRFS rates were 53.0%, 42.0%, and 48.0%, respectively. The univariate and multivariate analyses showed that the delayed time > 3 days was an independent adverse prognostic factor for OS (HR = 1.68, 95% CI 1.10–2.55, p = 0.016), and LRFS (HR = 1.74, 95% CI 1.18–2.57, p = 0.006). The patient with a delayed time of > 3 days had poorer survival rates of OS, and LRFS than patients with a delayed time of ≤ 3 days (OS, p = 0.047; LRFS, p = 0.013), and the survival outcomes of patients with shorter delayed time (1–3 days) were slightly different from the patients without interruptions. The impact of delay time on PFS is not statistically significant, but the survival outcomes of the two groups were slightly different.ConclusionThere was a significant correlation between delayed time and local control of esophageal cancer. The delayed time for more than 3 days might decrease the survival outcome, and increase the local recurrence risk.

Nonlinear associations between the ratio of family income to poverty and all-cause mortality among adults in NHANES study

Socioeconomic status (SES) has been linked to mortality rates, with family income being a quantifiable marker of SES. However, the precise association between the family income-to-poverty ratio (PIR) and all-cause mortality in adults aged 40 and older remains unclear. A cross-sectional study was conducted using data from NHANES III, including 20,497 individuals. The PIR was used to assess financial status, and various demographic, lifestyle, and clinical factors were considered. Mortality data were collected from the NHANES III linked mortality file. The study revealed a non-linear association between PIR and all-cause mortality. The piecewise Cox proportional hazards regression model showed an inflection point at PIR 3.5. Below this threshold, the hazard ratio (HR) for all-cause mortality was 0.85 (95% CI 0.79–0.91), while above 3.5, the HR decreased to 0.66 (95% CI 0.57–0.76). Participants with lower income had a higher probability of all-cause mortality, with middle-income and high-income groups showing lower multivariate-adjusted HRs compared to the low-income group. This study provides evidence of a non-linear association between PIR and all-cause mortality in adults aged 40 and older, with an inflection point at PIR 3.5. These findings emphasize the importance of considering the non-linear relationship between family income and mortality when addressing socioeconomic health disparities.

Effects of diagnosis-to-ablation time and antiarrhythmic drug responsiveness on the rhythm outcomes of atrial fibrillation catheter ablation

Abstract Background Atrial fibrillation (AF) is a progressive disease. Additionally, delaying AF catheter ablation (AFCA) for a year, during antiarrhythmic drug (AAD) therapy does not reduce the efficacy of this ablation. This study explored AFCA rhythm outcomes based on the diagnosis-to-ablation time (DAT) and AAD responsiveness in participants with either paroxysmal AF (PAF) or persistent AF (PeAF). Methods We included the data of 1,038 participants with AAD-resistant PeAF, all of whom had a clear time point for the diagnosis of PeAF and had undergone an AFCA for the first time. Participants who experienced recurrences of the paroxysmal type, while on AAD therapy, were analyzed as a cohort of AAD-partial-responders; whereas those who consistently maintained a PeAF, while on AAD therapy were analyzed as a cohort of AAD-non-responders. We calculated the DAT cutoff to determine long-term rhythm outcomes, using a maximum log-likelihood approach, based on the Cox proportional hazards regression model. Results Of the participants, 79.8% were male, and the median age was 61 years. The cohort of AAD-non-responders had a higher body mass index and larger left atrial diameter than that of the cohort of AAD-partial-responders. Furthermore, the cohort of AAD-non-responders showed a significantly higher incidence of AF recurrence subsequent to AFCA (adjusted hazard ratio= 1.75, 95% confidence interval: 1.33–2.30; log-rank test: p&amp;lt; 0.001) than that of the cohort of AAD-partial-responders. The log-likelihood graphs of the Cox proportional hazards regression models showed bimodal morphology for the cutoff values of 22 and 40 months. The cutoff value of DAT that most optimally discriminated between rhythm outcomes was 22 months. Conclusions Thus, both the DAT and AAD responsiveness affected the rhythm outcomes of AFCA. Delaying AFCA to a DAT of longer than 22 months was inadvisable, particularly in the participants in whom PeAF progressed to PAF during AAD therapy.

Associations of cognitive impairment and functional limitation with all-cause mortality risk in older adults: A population-based study from the National Health and Nutrition Examination Survey

Cognitive impairment and functional limitation are commonly observed in older adults. They have a complex correlation, and both are risk factors for mortality. This prospective cohort study aimed to explore the independent and joint impact of cognitive impairment and functional limitations on all-cause mortality in older adults. A total of 3,759 participants aged ≥ 60 years who had available information on mortality data, cognitive function, physical function, and covariates were enrolled. Cox proportional hazards regression models were employed to assess the independent and joint impacts of cognitive impairment and functional limitation on all-cause mortality. Smoothing curve fitting was used to show the nonlinear relationship between the Digit Symbol Coding (DSC) score and all-cause mortality. An interaction between cognitive impairment and functional limitation was identified when examining their associations with all-cause mortality. Cognitive impairment and functional limitation independently correlated with all-cause mortality risk even after adjusting for covariates and performing mutual adjustments (HR for cognitive impairment: 1.34, 95% CI 1.15–1.56; HR for functional limitation: 1.50, 95% CI 1.32–1.70). When the DSC score was > 18, as the score increased, the risk of death significantly decreased (HR 0.99, 95% CI 0.98–0.99). Participants with both cognitive impairment and functional limitation had the highest hazard ratio for all-cause mortality (HR 1.98, 95%CI 1.63–2.40). In summary, cognitive impairment and functional limitation independently correlated with increased all-cause mortality risk. A higher DSC score was a protective factor reducing the premature mortality risk. Older adults with cognitive impairment and functional limitation demonstrated the highest all-cause mortality risk.

Red cell distribution width to total serum calcium ratio and in-hospital mortality risk in patients with acute ischemic stroke: A MIMIC-IV retrospective analysis.

We investigated the relationship among red cell distribution width (RDW), to total serum calcium (TSC) ratio (RCR), and in-hospital mortality in patients with acute ischemic stroke (AIS). This study was a retrospective analysis. The data of 2700 AIS patients was retrospectively analyzed from the Medical Information Mart for Intensive Care database (version IV). The main outcome of interest was in-hospital mortality. A Cox proportional hazards regression model was used to determine whether RCR was independently associated with in-hospital mortality. The Kaplan-Meier method was used to plot the survival curves for RCR. Subgroup analyses were performed to measure the mortality across various subgroups. The area under curve (AUC) of receiver operating characteristic curve (ROC) was calculated to ascertain the quality of RCR as a predictor of in-hospital mortality in patients with AIS. In the multivariate analysis, statistically significant differences were identified in age, ethnicity, length of ICU stay, mechanical ventilation, sequential organ failure assessment (SOFA) score, RDW, hemoglobin, RCR, whether taking anticoagulants, hyperlipidemia, and atrial fibrillation (P < .05). A threshold inflection point value of 1.83 was obtained through a two-piecewise regression model. There was a non-linear relationship between RCR and hospital mortality in patients with AIS. The hazard ratio (HR) and the 95% confidence intervals (CI) on the right and left of the inflection point were 0.93 (0.57-1.51; P = .7660) and 2.96 (1.37-6.42; P = .0060), respectively. The Kaplan-Meier curve indicated that survival rates were higher when RCR was ≤ 1.83 and lower when RDW was > 1.83 after adjustment for age, gender, BMI, ethnicity. The area under curve (AUC) of RCR was 0.715. A higher RCR was associated with an increased risk of in-hospital mortality in patients with AIS.

Genetic and clinical risk factors for stroke recurrence with different impact by assessment age: data from the UK Biobank

Abstract Background The predictive utility of genetic risk factors added to clinical risk factors for stroke recurrence is unclear. Furthermore, whether those predictive utility change in different age groups is uncertain. This study aimed to compare the association of genetic and clinical risk factors with recurrent stroke. Methods Data were collected from 5,378 patients with a history of stroke from the UK Biobank. Cox proportional hazards regression models were used to assess the associations of genetic, demographic, lifestyle, and comorbidity risk factors with stroke recurrence, both in overall and three age-based groups. Results Over a median follow-up of 11.5 (interquartile range [IQR] 10.6–12.3) years, 417 patients had recurrent stroke. The hazard ratio (HR) for recurrent stroke was most pronounced for diabetes mellitus (HR 2.28, 95% confidence interval [CI] 1.83-2.86). Additionally, current smoking, hypertension, age, and polygenic risk score for ischemic stroke (stroke PRS) were also significantly associated with recurrent stroke. Based on concordance index (C-index, 95% CI), the strongest predictors were diabetes mellitus (0.578, 0.556-0.599) followed by age, hypertension and stroke PRS. However, the stroke PRS (0.577, 0.527-0.627) was the strongest predictor in the younger 1/3 patient group (median age 54, IQR 50-57). In addition to demographic, lifestyle, and comorbidity risk factors, genetic risk factor improved C-index of the prediction model from 0.640 (0.592-0.688) to 0.652 (0.602-0.703) in the younger group. Conclusions Recurrent stroke is significantly associated with genetic and clinical risk factors. Genetic risk factor enhances the predictive model`s accuracy, particularly in younger patients.Prediction of stroke recurrence

#210 Effects of serum magnesium level on kidney disease progression and major cardiovascular outcome in patients with chronic kidney disease

Abstract Background and Aims Magnesium is known for its anti-inflammatory, anti-apoptotic, and anti-oxidative effects, potentially inhibiting renal fibrosis. Additionally, it is believed that magnesium can inhibit vascular calcification, potentially improving cardiovascular outcomes. However, this remains a topic of controversy. This study aims to investigate the association between serum magnesium levels and CKD progression as well as cardiovascular outcomes. Method We analyzed 1,893 patients from The KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD), which is a prospective cohort study. These patients were categorized into three groups based on their baseline magnesium levels: Mg1 (hypomagnesemia, &amp;lt;1.8 mg/dL), Mg2 (normomagnesemia, 1.8-2.4 mg/dL), and Mg3 (hypermagnesemia, &amp;gt;2.4 mg/dL). The primary outcome was defined as meeting one or more of the following criteria during the follow-up period: initiation of dialysis or transplantation, a two-fold increase in baseline serum creatinine levels, or a 50% decline in the estimated glomerular filtration rate. The secondary outcome was a composite of major adverse cardiovascular events (MACEs). We used Cox proportional hazard regression model. Results A total of 673 patients (35.6%) experienced the composite renal outcome. The Mg1 group showed significantly increased adverse renal outcomes compared to the Mg2 group (HR, 1.885; 95% CI, 1.137-3.124; p = 0.013), however, Mg3 group did not show a significant difference (HR, 0.927; 95% CI, 0.783-1.097; p = 0.379). The composite cardiovascular outcome occurred in 138 patients (7.3%). The risk of composite cardiovascular outcomes significantly increased in the Mg1 group compared to the Mg2 group (HR 3.472; 95% CI, 1.492-8.076; p = 0.003). However, we observed no statistically significant differences in the Mg3 group (HR 1.021; 95% CI, 0.689; p = 0.913). The cubic spline curves demonstrated a U-shaped association between serum magnesium levels and both renal and cardiovascular outcomes. Conclusion Hypomagnesemia is associated with the progression of renal disease and a significant increase in MACEs. Beyond a certain level, hypermagnesemia may also be associated with worsening renal and cardiovascular outcomes.

Fertility-Sparing Surgery for Stage I Epithelial Ovarian Cancer.

To describe population-level utilization of fertility-sparing surgery and outcome of reproductive-aged patients with early epithelial ovarian cancer who underwent fertility-sparing surgery in the United States. This retrospective study queried the National Cancer Institute's Surveillance, Epidemiology, and End Result Program. The study included 3,027 patients younger than age 50 years with stage I epithelial ovarian cancer receiving primary surgical therapy from 2007 to 2020. Fertility-sparing surgery was defined as preservation of one ovary and the uterus for unilateral lesion and preservation of the uterus for bilateral lesions. Temporal trend of fertility-sparing surgery was assessed with linear segmented regression with log-transformation. Overall survival associated with fertility-sparing surgery was assessed with Cox proportional hazard regression model. A total of 534 patients (17.6%) underwent fertility-sparing surgery. At the cohort level, the utilization of fertility-sparing surgery was 13.4% in 2007 and 21.8% in 2020 (P for trend=.009). Non-Hispanic White individuals (2.8-fold), those with high-grade serous histology (2.2-fold), and individuals with stage IC disease (2.3-fold) had a more than twofold increase in fertility-sparing surgery utilization during the study period (all P for trend<.05). After controlling for the measured clinicopathologic characteristics, patients who received fertility-sparing surgery had overall survival comparable with that of patients who had nonsparing surgery (5-year rates 93.6% vs 92.1%, adjusted hazard ratio 0.87, 95% CI, 0.57-1.35). This survival association was consistent in high-grade serous (5-year rates 92.9% vs 92.4%), low-grade serous (100% vs 92.2%), clear cell (97.5% vs 86.1%), mucinous (92.1% vs 86.6%), low-grade endometrioid (95.7% vs 97.7%), and mixed (93.3% vs 83.7%) histology (all P>.05). In high-grade endometrioid tumor, fertility-sparing surgery was associated with decreased overall survival (5-year rates 71.9% vs 93.8%, adjusted hazard ratio 2.90, 95% CI, 1.09-7.67). Among bilateral ovarian lesions, fertility-sparing surgery was not associated with overall survival (5-year rates 95.8% vs 92.5%, P=.364). Among 41,914 patients who had epithelial ovarian cancer with any age and stage, those younger than age 50 years with stage I disease increased from 8.6% to 10.9% during the study period (P for trend=.002). Nearly one in five reproductive-aged patients with stage I epithelial ovarian cancer underwent fertility-sparing surgery in recent years in the United States. More than 90% of reproductive-aged patients with stage I epithelial ovarian cancer who underwent fertility-sparing surgery were alive at the 5-year timepoint, except for those with high-grade endometrioid tumors.

#673 Predictive value of insulin resistance and GFR-adjusted uricemia on all-cause mortality: the URRAH study

Abstract Background and Aims Uric acid (UA) and insulin resistance (IR) are interlinked: UA contributes to adversely affects the insulin signaling pathway, while IR predicts the development of hyperuricemia. Both UA and IR are related to metabolic syndrome, which is nowadays one of the most prevalent risk factors for mortality. In the clinical scenario, the triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio has been proved to have a high correlation with IR. Lipoprotein-based markers of IR are at least as strongly associated with subclinical atherosclerosis and with newly developing atherosclerotic manifestations than Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). The aim of the research was to explore the extent of interaction between IR and GFR-adjusted uricemia in determining mortality risk in a large population cohort study. Method data from 18,694 subjects were included from Uric acid Right foR heArt Healt (URRAH) database. Differences between TG/HDL-C ratio quintiles were evaluated by t-test or chi-square test. We evaluated the association between TG/HDL-C ratio and GFR-adjusted uricemia, and the development of outcomes during the follow-up study period. The primary endpoint was all-cause mortality. The Kaplan-Meier method was used to calculate the cumulative survival rate. Cox proportional hazard regression models were used to analyze the prognosis associated with IR. Results after a mean follow-up of 124 ± 64 months, there were 2,665 (14.2%) deaths for all causes. The incidence of fatal, non-fatal cardiovascular events, and all-cause mortality increased in parallel with the increase of TG/HDL-C quintiles. In both diabetic and non-diabetic patients, TG/HDL-C ratio showed a positive association with increasing of GFR-adjusted uricemia (UA/GFR ratio). TG/HDL-C ratio and GFR-adjusted uricemia significantly interact in determining all-cause mortality, even in non-diabetic patients (P &amp;lt; 0.0001). Subjects with higher TG/HDL-C ratio quintile had a statistically significantly higher rate of mortality than patients with lower quintiles (Fig. 1, log rank test P &amp;lt; 0.0001), independently by uricemia, GFR, the presence of diabetes and body mass index (BMI). Multivariate analysis showed that the TG/HDL-C ratio increase the mortality risk even after adjustment for potential confounding factors included age, diabetes, UA/GFR, BMI and statins treatment (Table 1). Conclusion For practical purposes, the easily obtainable TG/HDL-C ratio may suffice to determine the impact of insulin resistance as a risk factor. TG/HDL-C ratio interacts with GFR-adjusted uricemia in predicting mortality, even in non-diabetic patients. In conclusion, Both IR and GFR-adjusted UA levels seems to have an important predictive role on all-cause mortality, independently of age, gender, diabetes, hypertension and statins.

Cancer Incidence After Diagnosis of Abdominal Aortic Aneurysm.

Epidemiological and mechanistic data support a potential causal link between cardiovascular disease (CVD) and cancer. Abdominal aortic aneurysms (AAAs) represent a common form of CVD with at least partially distinct genetic and biologic etiology from other forms of CVD. The risk of cancer and how this risk differs compared with other forms of CVD, is unknown among AAA patients. We conducted a retrospective cohort study using the IBM MarketScan Research Database to test whether individuals with AAA have a higher cancer risk independent of traditional shared risk factors. All individuals ≥18 years of age with ≥36 months of continuous coverage between 2008 and 2020 were enrolled. Those with potential Mendelian etiologies of AAA, aortic aneurysm with nonspecific anatomic location, or a cancer diagnosis before the start of follow-up were excluded. A subgroup analysis was performed of individuals having the Health Risk Assessment records including tobacco use and body mass index. The following groups of individuals were compared: (1) with AAA, (2) with non-AAA CVD, and (3) without any CVD. The propensity score-matched cohort included 58 993 individuals with AAA, 117 986 with non-AAA CVD, and 58 993 without CVD. The 5-year cumulative incidence of cancer was 13.1% (12.8%-13.5%) in participants with AAA, 10.1% (9.9%-10.3%) in participants with non-AAA CVD, and 9.6% (9.3%-9.9%) in participants without CVD. Multivariable-adjusted Cox proportional hazards regression models found that patients with AAA exhibited a higher cancer risk than either those with non-AAA CVD (hazard ratio, 1.28 [95% CI, 1.23-1.32]; P<0.001) or those without CVD (hazard ratio, 1.32 [95% CI, 1.26-1.38]; P<0.001). Results remained consistent after excluding common smoking-related cancers and when adjusting for tobacco use and body mass index. Patients with AAA may have a unique risk of cancer requiring further mechanistic study and investigation of the role of enhanced cancer screening.

Greenness, air pollution, and mortality risk: a retrospective cohort study of patients with lung cancer in China

ABSTRACT The association between long-term exposure to air pollution and mortality from lung cancer has been established, yet evaluations of the potential mitigating effects of greenness on this impact are scarce. We conducted a cohort study in Pingyi County. A two-level Cox proportional hazards regression model was used to examine the associations among long-term exposure to air pollution, residential greenness, and lung cancer mortality. Among the examined pollutants, nitrogen dioxide exhibited the most significant adverse effects and highest risk of lung cancer mortality, with hazard ratio (HR) = 2.783 (95% confidence interval [CI]: 1.885–4.107) for all-cause mortality, HR = 2.492 (95%CI: 1.659–3.741) for tumour-related mortality, and HR = 2.431 (95%CI: 1.606–3.678) for lung cancer mortality. Higher greenness values were associated with a reduced risk of lung cancer mortality. These findings suggest the importance of implementing strategies for increasing greenness to reduce the health impacts of air pollution.

#986 Sarcopenia and chronic kidney disease among adults over 45 years old: findings from CHARLS

Abstract Background and Aims Little is known about the association between sarcopenia and chronic kidney disease (CKD) among Chinese adults older than 45. The present study sought to investigate the relationship between sarcopenia and CKD based on a large, nationally representative survey. Method The China Health and Retirement Longitudinal Study (CHARLS) provided data for the study in four waves in 2011, 2013, 2015, and 2018. Based on the Asia Working Group for Sarcopenia 2019 (AWGS 2019) criteria, sarcopenia and possible sarcopenia were defined. CKD was defined as eGFR less than 60 mL/min/1.73 m2, calculated according to the CKD Epidemiology Collaboration (CKD-EPI) equation, or self-reported CKD. Logistic regression models were conducted to analyze the cross-sectional relationship between sarcopenia and CKD. Cox proportional hazards regression models were used to examine the effect of sarcopenia on CKD. Stratified analyses were used to assess the association between sarcopenia status and CKD in various subgroups. Results Totally, 12323 participants over 45 years old (48.2% males; mean age 59.3 ± 9.5 years) were enrolled in a cross-sectional study in 2011, and further 10445 individuals were followed up in 2013, 2015 and 2018. The prevalence of CKD was 8.4% (1040/12323) in general populations, 7.2% (556/7703) in individuals without sarcopenia, 10.1% (380/3760) in adults with possible sarcopenia, and 12.1% (104/860) in individuals with sarcopenia, respectively. In cross-sectional study, possible sarcopenia [OR (95% CI): 1.236 (1.069-1.430)] was significantly associated with CKD (P &amp;lt; 0.01). While sarcopenia was not significantly associated with CKD. 783 cases (7.5%) with incident CKD events were identified during the 7 years of follow-up. In subgroup analyses, the incidence of CKD was 1.855 (95% CI 1.176-2.928) in the sarcopenia group compared with non-sarcopenia group among the female participants. The sarcopenia group (HR: 1.639, 95% CI 1.099-2.443) was independently associated with a higher incidence of CKD among non-smokers. Low muscle mass alone was not significantly associated with an increased risk of incident CKD (P &amp;gt; 0.05). Conclusion In our cross-sectional analysis, possible sarcopenia determined by AWGS2019 criteria was associated with a higher prevalence of CKD. In our longitudinal study, sarcopenia assessed using AWGS2019 criteria was associated with a higher risk of CKD in Chinese women over 45 years old or non-smokers.