Cox Proportional Hazards Regression Models Research Articles

Simultaneous Measurement of Calciprotein Particles with Different Assays and Clinical Outcomes in CKD

Background: Mineral metabolism abnormalities are an almost universal feature of chronic kidney disease (CKD) and are thought to contribute to the development of many adverse events. Calciprotein particles (CPP) form spontaneously in biological fluids from calcium and phosphate together with the glycoprotein fetuin-A. While CPP formation is a part of normal mineral homeostasis, levels are chronically elevated in CKD. Several assays have been developed to measure serum CPP, each linking high CPP levels to adverse clinical outcomes in CKD. However, direct comparisons among these assays are lacking. This exploratory study aims to compare these assays to assess their association with CKD progression and mortality. Methods: We measured baseline CPP levels using various methods on stored serum samples from 189 participants in a prospective observational cohort study of CKD stage 3/4 patients. Three assays were used to measure CPP: (1) ELISA (Fetuin-A CPP), (2) low-density (L-CPP) and high-density CPP (H-CPP) via gel filtration, and (3) primary (CPP-I) and secondary CPP (CPP-II) via flow cytometry. We examined the association of each CPP measure with all-cause mortality and CKD progression using unadjusted and covariate-adjusted Cox proportional hazard regression models. Results: In fully adjusted models, H-CPP (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.05 – 2.23, p=0.028) and CPP-II (HR 3.11, 95% CI 1.97 – 4.98, p<0.001) were significantly associated with an increased risk of all-cause mortality. Additionally, L-CPP (HR 1.91, 95% CI 1.43 – 2.62, p<0.001), CPP-I (HR 1.31, 95% CI 1.04 – 1.65, p=0.023), and CPP-II (HR 1.66, 95% CI 1.20 – 2.29, p=0.002) were significantly associated with CKD progression. Conclusions: In a cohort of individuals with CKD stages 3 and 4, serum CPP-II levels demonstrated the strongest association with all-cause mortality, while L-CPP levels showed the strongest association with CKD progression.

Associations between the Global Diet Quality Score and risk of type 2 diabetes: Tehran lipid and glucose study

Background Previous studies reported that focusing on healthy lifestyle, especially high diet quality is necessary for preventing type 2 diabetes (T2D). This study investigated the association between the innovative index, the Global Diet Quality Score (GDQS), and the risk of Type 2 Diabetes incidence. Methods In this secondary analysis, we included elective adult participants (n = 5948) from the third and fourth survey of the Tehran Lipid and Glucose Study. Participants checked out until the sixth phase with an average follow-up of 6.65 years. Expert nutritionists collected dietary data using a valid and reliable semi-quantitative food frequency questionnaire. The GDQS were calculated, including healthy and unhealthy food group scores. Biochemical and anthropometric characteristics were assessed during the first and follow-up surveys. Multivariable Cox proportional hazards regression models were used to estimate the progression of T2D in association with the GDQS. Results This study was implemented on 2,688 men and 3,260 women, respectively with the mean (SD) age of 41.5(14.1) and 39.3(13.02) years. A total of 524 subjects were found to have had T2D incidence. The healthy component of GDQS was conversely associated with T2D incidence [HR: 1, 0.91 (0.84–0.98), 0.91 (0.84–0.98), 0.84 (0.77–0.92) P trend = <0.001] in an adjusted model. The unhealthy component of GDQS was conversely associated with T2D incidence in an adjusted model [HR: 1, 0.86 (0.80–0.92), 0.93 (0.86–1.01), 0.89 (0.81–0.98) P trend = 0.009]. Conclusion The results of this study suggested that higher adherence to the healthy component of GDQS and lower intake of the unhealthy component decreased the risk of T2D incidence.

The Association between Serum Polychlorinated Biphenyls and Incident Cardiovascular Disease among Type 2 Diabetes

Abstract Background Polychlorinated biphenyls (PCBs) were associated with cardiovascular disease (CVD) in the general population. However, it is unclear whether PCBs exposure increases the additional risk of CVD among type 2 diabetes (T2D) cases. This study aims to investigate the associations between serum concentrations of PCBs and incident CVD among T2D cases. Methods The study population was derived from Dongfeng-Tongji cohort in 2008 and followed up until December 31, 2018, with a total of 2,806 participants with type 2 diabetes included and 1180 of them developed CVD during the follow-up. Cox proportional hazard regression models and quantile g-computation method were conducted for the associations of serum PCB levels with incident CVD risk. Results Compared with the first quartile, the risk of incident CVD was increased by 25%, 30%, and 28% in the fourth quartile of serum concentrations of PCB28, PCB52, and PCB101, respectively. Similar results were obtained for lower-chlorinated PCBs (PCB28 + PCB52 + PCB101) with HR (95% CI) of 1.257 (1.063, 1.486), and 1.346 (1.139, 1.589) in the third and fourth quartiles, respectively (P trend = 0.001). Quantile g-computation indicated that mixed exposure to PCBs increased the risk of CVD and the top three weights of PCB congeners were PCB101, PCB52, and PCB28. Conclusions Serum PCB independently increased the risk of incident CVD among T2D cases, in which lower-chlorinated PCBs played a dominant role.

Genetic Predisposition to Low-Density Lipoprotein Cholesterol and Incident Type 2 Diabetes.

Treatment to lower high levels of low-density lipoprotein cholesterol (LDL-C) reduces incident coronary artery disease (CAD) risk but modestly increases the risk for incident type 2 diabetes (T2D). The extent to which genetic factors across the cholesterol spectrum are associated with incident T2D is not well understood. To investigate the association of genetic predisposition to increased LDL-C levels with incident T2D risk. In this large prospective, population-based cohort study, UK Biobank participants who underwent whole-exome sequencing and genome-wide genotyping were included. Participants were separated into 7 groups with familial hypercholesterolemia (FH), predicted loss of function (pLOF) in APOB or PCSK9 variants, and LDL-C polygenic risk score (PRS) quintiles. Data were collected between 2006 and 2010, with a median follow-up of 13.7 (IQR, 12.9-14.5) years. Data were analyzed from March 1 to November 1, 2024. LDL-C level, LDL-C PRS, FH, or pLOF variant status. Cox proportional hazards regression models adjusted for age, sex, genotyping array, lipid-lowering medication use, and the first 10 genetic principal components were fitted to assess the association between LDL-C genetic factors and incident T2D and CAD risks. Among the 361 082 participants, mean (SD) age was 56.8 (8.0) years, 194 751 (53.9%) were female, and mean (SD) baseline LDL-C level was 138.0 (33.6) mg/dL. During the follow-up period, 22 619 (6.3%) participants developed incident T2D and 17 966 (5.0%) developed incident CAD. The hazard ratio for incident T2D was lowest in the FH group (0.65; 95% CI, 0.54-0.77), while the highest risk was in the pLOF group (1.48; 95% CI, 1.18-1.86). The association between LDL-C PRS and incident T2D was 0.72 (95% CI, 0.66-0.79) for very high LDL-C PRS, 0.87 (95% CI, 0.84-0.90) for high LDL-C PRS, 1.13 (95% CI, 1.09-1.17) for low LDL-C PRS, and 1.26 (95% CI, 1.15-1.38) for very low LDL-C PRS. CAD risk increased directly with the LDL-C PRS. In this cohort study, LDL-C and T2D risks were inversely associated across genetic mechanisms for LDL-C variation. Further elucidation of the mechanisms associating low LDL-C risk with increased risk of T2D is warranted.

Longitudinal increase in physical activity and adverse cardiovascular outcomes following the diagnosis of acute coronary syndrome

ObjectivesPhysical activity (PA) provides protective effects against cardiovascular diseases, including ischaemic heart disease. However, recommending moderate to vigorous PA (MVPA) to patients with recent acute coronary syndrome (ACS) raises concerns...

Suppression of MCP-1, IFN-γ and IL-6 production of HNSCC ex vivo by pembrolizumab added to docetaxel and cisplatin (TP) exceeding those of TP alone is linked to improved survival

BackgroundAdding pembrolizumab, an anti-PD-1 antibody approved for treatment of head and neck squamous cell carcinoma (HNSCC) to neoadjuvant (induction-) chemotherapy utilizing docetaxel and cisplatin (TP) followed by radiotherapy may improve outcome in larynx organ-preservation (LOP) that is investigated in the European Larynx-Organ preservation Study (ELOS). As biomarkers for response to TP and pembrolizumab +TP are missing but may include cytokines, this work aims on determining cytokines potentially linked to outcome as prognostic markers sufficient to predict and/or monitor response to successful LOP.MethodsCollagenase IV digests were generated from 47 histopathological confirmed HNSCC tumor samples and seeded in 96-well plates containing pembrolizumab, docetaxel, cisplatin either solely or in binary or ternary combination. According to the FLAVINO protocol, supernatants were collected after 3 days, adherent cells fixed using ethanol, air-dried and pan-cytokeratin positive epithelial cells counted using fluorescence microscopy. The cytokines IL-6, IL-8, IFN-γ, IP-10, MCP-1, TNF-α, and VEGF in the supernatant were quantified by sandwich ELISA.ResultsThe mode of interaction between pembrolizumab and TP was assessed and correlated to outcome (overall, disease-specific and progression-free survival of patients). Suppression of MCP-1, IFN-γ and IL-6 production by pembrolizumab + TP exceeding the suppressive effect of TP was detected in the majority of samples and linked to improved survival. Multivariate Cox proportional hazard regression modeling revealed MCP-1, IFN-γ and IL-6 as independent outcome predictors.ConclusionsComparing response to TP vs. pembrolizumab vs. TP + pembrolizumab may allow for identification of patients with superior outcome independent from treatment applied.

Baseline and cumulative Chinese visceral adiposity index and diabetic kidney disease: A prospective cohort study.

Diabetic kidney disease (DKD) makes up nearly half of all chronic kidney disease cases and is a major cause of mortality for people with diabetes. However, the study of the association of longitudinal Chinese visceral adiposity index (CVAI) with DKD is still missing. This prospective cohort study included 7874 diabetes patients from the Kailuan study. These participants had complete repeated waist circumference, body mass index, triglycerides and high-density lipoprotein cholesterol measurements that formed the continuous CVAI records. DKD was defined by increased proteinuria or decreased estimated glomerular filtration rate (eGFR), preceded by diabetes. Cox proportional hazard regression models were used to examine the associations between baseline and cumulative CVAI and the risk of DKD. There is a positive association between the CVAI level, whether baseline or cumulative, and the incidence of DKD among diabetic patients (p for log-rank tests <0.001). Compared to low CVAI level, the high baseline CVAI level was positively associated with the risk of DKD (HR: 1.24, 95% CI: 1.09-1.42), as well as the high cumulative CVAI level (HR: 1.62, 95% CI: 1.29-2.04). In addition, the assumption of linearity for the positive associations between both baseline (P-nonlinear = 0.264, p for overall <0.001) and cumulative (P-nonlinear = 0.765, p for overall <0.001) CVAI with incident DKD was satisfied. Higher baseline and cumulative CVAI are associated with a higher risk of DKD. This finding suggests the health benefits of low levels of CVAI and the importance of its regular surveillance among individuals with diabetes.

Incidence and risk of infections in patients with ankylosing spondylitis receiving biologic therapies: A prospective observational study using the KOBIO registry

ObjectiveThis study aimed to assess infection occurrence of infection and risk factors among ankylosing spondylitis (AS) patients treated with biologics in a real-world setting.MethodsThis prospective observational cohort study included AS patients from the Korean College of Rheumatology BIOlogics (KOBIO) registry who initiated or switched to biologic agent between December 2012 and July 2023. The primary outcome was the first occurrence of any infection, ranging from mild to severe, classified by organ system. The infection rate per 1,000 person-years (PY), with a 95% confidence interval were calculated using the Poisson distribution method. Cox proportional hazard regression models, adjusted for confounders, estimated hazard ratios for infection risk, considering only the first infection event.ResultsThis analysis included 2,129 patients with a total of 7,107.67 PY of follow-up. The predominant infections observed were of the upper and lower respiratory tract (25.89/1000 PY), followed by herpes zoster (HZ) (6.13/1000 PY). Multivariate Cox regression analysis revealed significant risk factors for infection, including age, ischemic heart disease, complicated diabetes, chronic kidney disease (CKD), and peripheral arthritis. In contrast, male sex was identified as a protective factor against the development of infections.ConclusionThe infection rate was 39 events/1,000 PY with respiratory tract infections being most common, followed by HZ. Significant risk factors included age, female sex, ischemic heart disease, complicated diabetes, CKD and peripheral arthritis for the occurrence of infection in patients with AS treated with biologics.

Impact of Frailty on Antihypertensive Treatment in Older Adults.

The association between systolic blood pressure and all-cause mortality differs between frail and nonfrail individuals, highlighting uncertainties about the effectiveness of antihypertensive treatments in frail populations. Using data from the SHEP trial (Systolic Hypertension in the Elderly Program), a baseline frailty index (FI), including 55 variables, was constructed. Fine-Gray subdistribution hazard models and Cox proportional hazards regression models were used to explore the association between baseline FI and the risks of stroke, cardiovascular disease, and all-cause death, as well as to examine whether the impact of antihypertensive treatment on these outcomes was modified by baseline FI. A total of 4692 participants (mean age, 72.1 years; 56.7% women) were included, with a mean (SD) FI of 0.134 (0.061). During a median follow-up period of 4.4 years, FI was associated with a higher risk of stroke (subdistribution hazard ratio, 1.24 [95% CI, 1.10-1.39]; per SD higher FI), cardiovascular disease (subdistribution hazard ratio, 1.18 [95% CI, 1.09-1.26]), and all-cause death (hazard ratio, 1.37 [95% CI, 1.26-1.50]), after adjustment for age, sex, race, and treatment group. Although those with higher levels of frailty were at higher risk for all outcomes, there was no evidence of an interaction between baseline FI and antihypertensive treatment (P for interaction >0.05 for all outcomes). In individuals with isolated systolic hypertension, antihypertensive treatment improved associated outcomes even among those with a higher degree of frailty. These findings from the SHEP trial reinforce evidence from other seminal antihypertensive trials, which collectively inform the appropriate treatment of frail individuals with hypertension. URL: https://www.clinicaltrials.gov; Unique identifier: NCT00000514.

Nomogram-derived immune-inflammation-nutrition score could act as a novel prognostic indicator for patients with head and neck squamous cell carcinoma

AimThis study aims to create and validate a novel systematic immune-inflammation-nutrition (SIIN) score to provide a non-invasive and accurate prognostic tool for head and neck squamous cell carcinoma (HNSCC) patients.Methods259 participants diagnosed with HNSCC from the First Affiliated Hospital of Xi’an Jiaotong University between 2008 and 2017 was included in this retrospective study. Patients were assigned to training (n=181) and validation (n=78) sets. A LASSO Cox regression model was employed to identify significant biomarkers for constructing a SIIN nomogram and to create SIIN score from this nomogram. The prognostic accuracy of the SIIN score was assessed by exploiting receiver operating characteristic (ROC) analysis, Kaplan-Meier survival analysis, Cox proportional hazard regression models, calibration and DCA curves.ResultsThe SIIN score was formulated based on six biomarkers-platelet-lymphocyte ratio (PLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), albumin-bilirubin index (ALBI), fibrinogen (FIB) and monocyte count-identified by LASSO regression analysis. (1)The SIIN score demonstrated superior predictive value, achieving area under the ROC curve (AUC) values of 0.736 and 0.700 for 3- and 5-year OS. For recurrence-free survival (RFS), the AUC values were 0.752 for 3-year and 0.701 5-year RFS, as assessed in the training set. Validated as an independent prognostic factor in both cohorts, the SIIN score showed strong correlation with adverse clinicopathological outcomes.ConclusionThe SIIN score is a promising prognostic tool that integrates immune, inflammatory, and nutritional factors for predicting clinical outcomes in HNSCC patients. It offers enhanced predictive accuracy compared to existing markers and has the potential to guide personalized treatment strategies and clinical decision-making.

Esophageal Candida Infection and Esophageal Cancer Risk in Patients With Achalasia.

Patients with achalasia face a higher risk of developing esophageal cancer (EC), but the surveillance strategies for these patients remain controversial due to the long disease duration and the lack of identified risk factors. To investigate the prevalence of esophageal Candida infection among patients with achalasia and to assess the association of Candida infection with EC risk within this population. This retrospective cohort study included patients with achalasia diagnosed at or referred for treatment and monitoring to the Erasmus University Medical Center in Rotterdam, the Netherlands, between January 1, 1980, and May 31, 2024. Data analysis was conducted from August 1 to October 31, 2024. Esophageal Candida infection. The primary outcomes were the prevalence of esophageal Candida infection and its association with EC development among patients with achalasia. Associations were estimated using time-dependent Cox proportional hazards regression models with esophageal Candida infection as a time-varying covariate, adjusting for age at diagnosis and sex. This study included 234 patients with achalasia (median [IQR] age at diagnosis, 45 [32-63] years; 117 [50%] male), with a median follow-up time of 13 (4-22) years. Esophageal Candida infection was identified in 29 patients (12%), while EC was observed in 24 patients (10%). Esophageal cancer risk analysis was performed for 207 patients with 2 or more consecutive endoscopy follow-up visits (median [IQR] age at diagnosis, 43 [32-60] years; 104 [50%] male). The median (IQR) follow-up time for this subgroup was 16 (9-26) years. Among these patients, esophageal Candida infection was independently associated with an increased risk of EC (adjusted hazard ratio [AHR], 8.24 [95% CI, 2.97-22.89]). Additionally, age at diagnosis (AHR, 1.06 [95% CI, 1.03-1.10]) and male sex (AHR, 3.34 [95% CI, 1.08-10.36]) were independently associated with EC risk. This retrospective cohort study found that prior esophageal Candida infection, older age at diagnosis, and male sex were associated with increased risk of EC among patients with achalasia. These findings provide an important rationale for optimizing the monitoring of patients with achalasia.

The association of biological sex and long-term outcomes in older patients with physical restraint at the emergency department

BackgroundThe worldwide population is ageing and self-arm can be prevented with many techniques. Among them coercive measure consisting of physical restraint (PR) is one of the techniques. This study aims to assess the effects of the biological sex on the long-term survival after PR in geriatric patients during the initial emergency department (ED) visit.MethodsThis retrospective study included patients between November 2019 to March 2021. All consecutive hospitalized patients after emergency department visit older than 75 years with PR were included. The population was compared according to the biological sex. One-year all-cause mortality was plotted with the Kaplan-Meier curve. Hazard ratios (HRs) for 1-year mortality were calculated using a Cox proportional hazards regression model. Mortality was monitored over a 3-year period.ResultsPR was used in 149 patients representing 4.6% of 3210 hospitalized patients older than 75 years after ED visit. Women represented 52% of the study population. Compared to men, women were older [median (IQR) age 89 (85–93) vs. 85 (81–90) years, P = 0.002]. Women more often presented dementia (93 vs. 80%, P = 0.031). Both sexes presented the same limited independence. All-cause mortality was significantly lower for women than men after one year (25 vs. 51%, respectively, P = < 0.001). Likewise, adjusted HR of 1-year all-cause mortality was higher in men [a HR 3.4 (95% confidence interval 1.7–7.1), P < 0.001].ConclusionThis study suggested that the use of physical restraint in older adults was a more related factor of mortality in men than women. Women were older with lower expectancy life but PR use seemed to be a sign of global health decline in men. Further prospective studies are needed to assess if mortality after PR use is a cause or a consequence of a global health decline.

Determining timeframes to death for imminently dying patients: a retrospective cohort study

BackgroundClinicians are frequently asked ‘how long’ questions at end-of-life by patients and those important to them, yet predicting timeframes to death remains uncertain, even in the last weeks and days of life. Patients and families wish to know so they can ask questions, plan, make decisions, have time to visit and say their goodbyes, and have holistic care needs met. Consequently, this necessitates a more accurate assessment of empirical data to better inform prognostication and reduce uncertainty around time until death. The aims of this study were to determine the timeframes for palliative care patients (a) between becoming comatose and death, and (b) between being totally dependent and bedfast, and then comatose, or death, using Australia-modified Karnofsky Performance Status (AKPS) scores. The secondary aim was to determine if covariates predicted timeframes.MethodThis is a large retrospective cohort study of 2,438 patients, 18 years and over, cared for as hospice inpatients or by community palliative care services, died between January 2017 and December 2021, and who collectively had 49,842 AKPS data points. An Interval-Censored Cox Proportional Hazards regression model was used.ResultsOver 53% (n = 1,306) were comatose (AKPS 10) for longer than one day before death (mean = 2 days, median = 1, SD = 2.0). On average, patients were found to be totally dependent and bedfast (AKPS 20) for 24 days, before progressing to being comatose. A difference in life expectancy was observed at AKPS 20 among people with cancer (mean = 14.4, median = 2, SD = 38.8) and those who did not have cancer (mean = 53.3, median = 5, SD = 157.1).ConclusionResults provide clinicians with validated data to guide communication when answering ‘how long’ questions at end-of-life. Knowledge of projected time to death can prompt timely conversations while the patient can understand and engage in meaningful conversations. The importance of considering covariates such as location and diagnosis in determining timeframes has been highlighted. Shared decision-making and essential person-centered end-of-life care can be planned.

Breast Cancer MRI Screening of Patients After Multiplex Gene Panel Testing.

Enhanced breast cancer screening with magnetic resonance imaging (MRI) is recommended to women with elevated risk of breast cancer, yet uptake of screening remains unclear after genetic testing. To evaluate uptake of MRI after genetic results disclosure and counseling. This multicenter cohort study was conducted at the University of Southern California Norris Cancer Hospital, the Los Angeles General Medical Center, and the Stanford University Cancer Institute. Patients were recruited from July 1, 2014, through November 30, 2016. Following multiplex gene panel testing and genetic counseling, patients responded to surveys about breast MRI screening at 3, 6, 12, and 24 months and to a final survey between 3 and 4 years after counseling. Participants met standard clinical criteria for genetic testing or had a 2.5% or greater probability of inherited cancer susceptibility. Patients were categorized based on breast cancer risk from genetic testing results and Tyrer-Cuzick model-calculated risk as having (1) a BRCA or other high-risk pathogenic variant (PV), (2) a moderate-risk PV, (3) a higher lifetime breast cancer risk (≥20%), or (4) a lower lifetime breast cancer risk (<20%). Analysis was conducted from September 28 to November 9, 2023. Genetic testing with a 25- or 28-gene panel, and pretest and posttest genetic counseling by a genetic counselor or an advanced practice genetics nurse practitioner, which included cancer-specific screening recommendations. MRI screening adherence over time across risk groups was estimated using Cox proportional hazards regression modeling. Likelihood of screening adherence (odds ratios [ORs] with 95% CIs), controlling for potential confounders, was estimated using logistic regression. This study included 638 patients, with a mean (SD) age of 50.7 (13.3) years at testing. There were 43 patients (6.7%) with a BRCA or other high-risk PV, 16 (2.5%) with a moderate-risk PV, 146 (22.9%) with higher lifetime breast cancer risk, and 433 (67.9%) with lower lifetime breast cancer risk. A total of 52 patients (8.2%) identified as Asian, 21 (3.3%) as Black, 271 (42.5%) as Hispanic, and 255 (40.0) as White. Compared with patients with lower lifetime breast cancer risk, patients with a BRCA or other high-risk PV and those with a moderate-risk PV were approximately 10 times (OR, 9.81 [95% CI, 4.05-23.86]; P < .001) and 4 times (OR, 4.12 [95% CI, 1.10-14.35]; P = .03) as likely to undergo MRI, respectively. Patients with a BRCA or other high-risk PV were nearly 16 times (OR, 15.81 [95% CI, 5.17-48.31]) as likely to report consistent yearly MRI screening compared with patients with lower lifetime risk. In this study, women with inherited PVs conferring increased breast cancer risk had higher and more consistent MRI uptake than women with lower estimated risk. These findings emphasize the importance of genetic cancer risk assessment for effective enhanced breast cancer screening.

Association Between Chewing Capacity and Mortality Risk: The Role of Diet and Ageing.

Masticatory dysfunction due to tooth loss is a potentially modifiable risk for mortality, but the pathway behind that remains to be investigated. This prospective study aimed to examine the role of diet and ageing in the associations between chewing capacity and long-term mortality. Data were obtained from participants (aged ≥ 20) in the National Health Nutritional and Health Survey (NHANES 1999-2010, n = 22,900). The mortality follow-up ended on 31 December 2019. Chewing capacity was determined by the number of functional tooth units (FTUs). Diet information in NHANES was collected using a 24-h-recall questionnaire, and diet quality was measured by three index-based dietary patterns, namely the nutrition index (NI), energy-adjusted dietary inflammatory index (E-DII) and healthy eating index-2015 (HEI-2015). The biological ageing process was reflected using phenotypic age acceleration (PhenoAgeAccel) and frailty index. Mediation analyses were conducted to assess the role of diet quality in the association between FTUs and ageing, as well as the role of ageing in the association between impaired chewing capacity (ICC) and mortality. Participants with more FTUs were found to have a slower biological ageing process. Diet quality scores were estimated to mediate 9.0%-23.0% of the association between chewing capacity and biological ageing. Multivariable Cox proportional hazards regression models found a positive association between ICC and all-cause mortality (hazard ratio = 1.282 [95% confidence interval: 1.189-1.382]). Also, ICC was significantly associated with a 28.9% higher risk of mortality due to cardiovascular disease (CVD) and a 32.7% higher risk of mortality due to cancer. Mediation analyses indicated that PhenoAgeAccel mediated the effect of ICC on all-cause, CVD and cancer mortality with proportions of 18.1%, 17.3% and 12.5%, respectively. Similar mediating proportions were observed in the frailty index (range: 11.6%-23.5%). ICC was associated with poorer diet quality and accelerated ageing, resulting in higher mortality risk. Therefore, it is plausible that dietary interventions and oral rehabilitation would promote healthy longevity, although further investigations are needed.

Analysis of the efficacy and influencing factors of immunotherapy in gastric cancer liver metastasic patients

Objective: To explore the efficacy and factors affecting the treatment of gastric cancer liver metastasis (GCLM) with immune checkpoint inhibitors (ICI). Methods: This is a retrospective cohort study. Clinical and pathological data of 588 patients with GCLM treated at the Department of General Surgery, First Medical Center, People's Liberation Army General Hospital, from January 2018 to December 2022 were retrospectively collected. There were 491 males and 97 females, aged (M(IQR)) 60(14) years (range: 18 to 86 years). Patients were divided into an ICI treatment group (n=142) and a non-ICI treatment group (n=446) based on whether they received ICI therapy. Clinical and pathological data between the two groups were compared using the χ2 test or Mann-Whitney U test. Propensity score matching (PSM) was performed with cT stage, cN stage, surgical treatment, targeted therapy, and biomarkers as covariates, using a 1∶1 nearest neighbor matching method with a caliper value of 0.2. Univariate and multivariate analyses were conducted using Cox proportional hazards regression models, with relevant variables selected through forward stepwise regression. Survival curves were plotted using the Kaplan-Meier method, and group differences were compared using the Log-rank test. Subgroup analysis was conducted to identify potential beneficiary populations for ICI through forest plots. Results: After PSM, 114 patients were included in each group, and there were no statistically significant differences in the baseline data between the two groups (all P>0.05). The results of Cox multivariate analysis after PSM showed that cN2-3 stage (HR=1.348, 95%CI: 1.091 to 1.665, P=0.006) and peritoneal metastasis (HR=1.877, 95%CI:1.360 to 2.590, P<0.01) were independent risk factors for survival in GCLM patients; radical surgery (HR=0.391, 95%CI: 0.305 to 0.501, P<0.01), immunotherapy (HR=0.630, 95%CI: 0.503 to 0.788, P<0.01), and deficient DNA mismatch repair (dMMR) or combined positive score (CPS)≥5 (HR=0.454, 95%CI: 0.320 to 0.644, P<0.01) were independent protective factors for survival in GCLM patients. After PSM, the overall survival was 12.4 (13.0) months in the non-immunotherapy group and 17.6 (17.8) months in the immunotherapy group (Log-rank test:P=0.029). Subgroup analysis showed that female patients, those with primary tumors located in the upper stomach, cN2-3 stage, one liver metastasis, synchronous liver metastasis, receiving targeted therapy, and those with dMMR or CPS≥5 were more likely to benefit from ICI therapy (all P<0.05). Conclusions: ICI prolongs overall survival in GCLM patients. Female patients, those with primary tumors located in the upper stomach, cN2-3 stage, one liver metastasis, synchronous liver metastasis, receiving targeted therapy, and those with dMMR or CPS≥5 are more likely to benefit from ICI therapy.

Cervical stromal invasion and molecular characterization in stage II-IV endometrial cancers.

The optimal treatment for patients with cervical stromal invasion (CSI) in endometrial cancer (EC) remains unclear. We aimed to test the prognostic role of molecular classification in EC patients with CSI. A retrospective, multicenter review of EC patients with CSI was performed. EC cases were assigned to one of the molecular classes: POLE mutated (POLEmut), MMR deficient (MMRd), p53 abnormal (p53abn), or no specific molecular profile (NSMP). Three-year recurrence-free survival (RFS) from surgery was estimated using the Kaplan-Meier method. Cox proportional hazards regression models were fit to adjust for confounders. Overall, 162 EC patients with CSI were identified: 70 (43.2%) NSMP, 49 (30.2%) p53abn, 40 (24.7%) MMRd, 3 (1.9%) POLEmut. POLEmut cases were excluded from further analysis, because of the small number of patients identified. At univariate analysis, molecular class was significantly associated with recurrence within 3years after surgery (p=0.04). Three-year RFS was 59.9% (95% confidence interval [CI], 46.1-77.8%) for NSMP, 50.6% (95% CI, 34.9-73.2%) for MMRd, and 33.1% (95% CI, 19.7-55.3%) for p53abn. After adjusting for stage and grade, molecular class was no longer significantly associated with recurrence within three years (p=0.28). Traditional risk factors such as grade and stage remain critical in determining the prognosis of endometrial cancer with cervical stromal invasion. This study highlights the importance of integrating both molecular and morphological features in determining the prognosis of endometrial cancer, with particular emphasis on endometrioid histotypes.

Sugar-sweetened or artificially sweetened beverage consumption, physical activity and risk of type 2 diabetes in US adults.

A positive association between sugar-sweetened beverages (SSBs) and diabetes risk has been shown, with inconsistent evidence between artificially sweetened beverages (ASBs) and diabetes. Moreover, it is uncertain if physical activity can mitigate the negative effects of these beverages on diabetes development. Therefore, we aimed to evaluate the independent and joint associations between SSB or ASB consumption and physical activity on the risk of type 2 diabetes. We followed 64,029 women in the Nurses' Health Study (1980-2016), 88,340 women in the Nurses' Health Study II (1991-2017) and 39,436 men in the Health Professionals Follow-up Study (1986-2016). SSB and ASB consumption was calculated from food-frequency questionnaires administered every 4 years, while physical activity data were collected biennially. A validated supplementary questionnaire on diabetes symptoms, diagnostic tests and treatment confirmed type 2 diabetes cases. Multivariable Cox proportional hazards regression models were used to calculate HRs and 95% CIs for developing type 2 diabetes. During 5,105,351 person-years of follow-up, we recorded 19,940 new cases of type 2 diabetes. Compared with those who never or rarely consumed SSBs or ASBs, those who consumed ≥2 servings/day had a 41% (HR 1.41 [95% CI 1.33, 1.50]) and 11% (HR 1.11 [95% CI 1.07, 1.16]) higher risk of type 2 diabetes, respectively. For participants meeting physical activity guidelines (≥7.5 metabolic equivalent of task [MET] h/week) and consuming ≥2 servings/week of SSBs or ASBs, the risk was 22% (HR 1.22 [95% CI 1.15, 1.29]) and 7% (HR 1.07 [95% CI 1.02, 1.12]) higher, respectively, compared with those who met physical activity guidelines and never or rarely (<1 serving/month) consumed these beverages. For participants meeting the physical activity guidelines and consuming 1-4 servings/month of SSBs, there was a 9% (HR 1.09 [95% CI 1.02, 1.15]) higher risk of type 2 diabetes. Compared with the reference group (those who met physical activity guidelines and consumed <1 SSB serving/month), adults who did not meet physical activity guidelines (<7.5 MET h/week) and who never or rarely (<1 serving/month) consumed SSBs, had 1-4 SSB servings/month, or had ≥2 SSB servings/week, the HRs (95% CIs) were 1.22 (1.13, 1.31), 1.28 (1.20, 1.37), and 1.51 (1.43, 1.61), respectively. Similarly, for ASB consumption, adults who did not meet physical activity guidelines and who never or rarely (<1 serving/month) consumed ASBs, had 1-4 servings/month, or had ≥2 servings/week, the HRs (95% CIs) were 1.21 (1.14, 1.28), 1.21 (1.13, 1.30), and 1.30 (1.23, 1.37) compared with the reference group (who met physical activity guidelines and consumed <1 ASB serving/month). Even when individuals were physically active, a higher consumption of SSBs or ASBs was associated with a higher risk of type 2 diabetes. Meeting physical activity guidelines reduced the impact of SSB and ASB consumption on diabetes risk, underscoring the need to promote physical activity as part of lifestyle modifications to lower diabetes incidence.

Morbidity in males with 45,X/46,XY resembles the morbidity pattern in Turner syndrome: a national population-based study.

Few studies have reported on males with 45,X/46,XY mosaicism. Most studies stem from pediatric settings and knowledge of natural history and long-term health outcomes are therefore lacking. To describe long-term health outcomes in males with 45,X/46,XY in comparison to the general population. A national population-based registry study. A public uniform health care system. All males in Denmark diagnosed with 45,X/46,XY mosaicism from 1967-2016 (n=135) and 1:100 age-matched males from the background population. Hospital diagnoses, prescribed medication and surgery codes were analyzed using a Cox proportional hazards regression model yielding hazard ratios (HR). 45,X/46,XY was associated with an increased risk of being admitted to hospital (HR=1.6, CI:1.3-1.9), undergoing surgery (HR=1.8, CI:1.4-2.2), and being prescribed medication (HR=1.2, CI:1.03-1.5). This risk applied to 15/18 diagnostic groups, 6/14 medication groups, and 10/16 surgery groups. Diagnoses with increased HRs included diabetes, thyroid disorders, obesity, hypertension, ischemic heart disease, osteoporosis, and inflammatory bowel disease. Half of all 45,X/46,XY males (69/135) had ≥1 diagnosis related to the genitourinary system and nearly one-third (39/135) underwent urogenital surgery. 45,X/46,XY mosaicism in males impacts long-term health significantly. The morbidity pattern includes a wide range of diseases, most known to occur at increased frequencies in Turner syndrome. The study underscores the importance of identifying these males and follow them with systematic screening as in Turner syndrome.

Association between urate-lowering therapy and kidney failure in patients with chronic kidney disease.

Hyperuricemia is a hallmark of gout and a suspected risk factor for the progression of chronic kidney disease (CKD). However, the impact of urate-lowering therapy on CKD progression is subject to debate. The objective of the present study was to describe the prevalence of inappropriate urate-lowering therapy prescriptions and evaluate the association between urate-lowering therapy prescription and the progression of kidney disease in patients with CKD. CKD-REIN is a French, nationwide, prospective cohort of 3,033 nephrology outpatients with CKD (eGFR < 60mL/min/1.73 m2). Prescriptions of urate-lowering therapy drugs (allopurinol or febuxostat) were recorded prospectively. The appropriateness of each prescription was evaluated according to the patient's kidney function at baseline and during follow-up. Propensity score-matched, cause-specific Cox proportional hazards regression models were used to assess the association between incident urate-lowering therapy use and CKD progression (defined as the initiation of kidney replacement therapy (KRT) but also in other ways). At baseline, 987 of the 3009 patients included in this study (median age: 69; men: 66%) were receiving urate-lowering therapy; 396 of these 987 patients were receiving an inappropriate prescription with regard to their kidney function. During a 5-year follow-up period, 70% of the 396 urate-lowering therapy prescriptions remained inappropriate. In the propensity score-matched cohort (n = 674), 136 patients started KRT. Compared with non- urate-lowering therapy use, urate-lowering therapy use was not significantly associated with a slowing in CKD progression, regardless of the definition used (HRKRT 0.89, 95% CI 0.67-1.20). Our real-world data emphasized the lack of reassessment of urate-lowering therapy prescriptions in patients with CKD. Urate-lowering therapy was not associated with a slowing of CKD progression.