Multivariate Cox Proportional Hazards Model Research Articles

Postoperative Radiotherapy in Advanced Stage Squamous Cell Carcinoma Requiring Maxillectomy.

To evaluate whether postoperative radiotherapy (PORT) improves survival among patients who received maxillectomy for pT4aN0 maxillary gingival or hard palate squamous cell carcinoma (SCC) with respect to tumor size. Retrospective analysis. National Cancer Database from 2004 to 2019. Included adult patients who received maxillectomy (partial, subtotal, or total) and neck dissection for treatment-naive margin negative pT4aN0 SCC of the maxillary gingiva or hard palate. Adjusted for age, gender, race, insurance status, income, education, urban/rural, facility type, region, comorbidity index, tumor grade, and tumor extension. Inverse probability weights were incorporated into a multivariable Cox proportional hazards model. A priori post hoc subgroup analysis was performed according to tumor size. We included 416 patients who underwent maxillectomy for pT4aN0 SCC of the maxillary gingiva or hard palate (mean [standard deviation] age, 71.5 [11.3] years; male, 190 [45.7%]; tumor size 2 cm, 362 [87%]). Overall, 49.3% of patients received PORT (205 patients). PORT was associated with a 50% improvement in survival compared to surgery alone (adjusted hazard ratio [aHR], 0.50; 95% confidence interval [95% CI], 0.32-0.81). On subgroup analysis, PORT was associated with improved survival for tumors 2 cm (aHR, 0.47; 95% CI, 0.29-0.77), but not for tumors < 2 cm (aHR, 1.15; 95% CI, 0.33-4.08). The vast majority of patients with pT4aN0 bone-invading SCC of the maxillary gingiva and hard palate benefit from PORT. Patients with tumors < 2 cm did not demonstrate a survival benefit from adjuvant treatment, suggesting that bony invasion alone may not be sufficient criteria for treatment escalation.

Associations of biological age accelerations and genetic risk with incident endometrial cancer: a prospective analysis in UK Biobank.

Endometrial cancer (EC) is one of the gynecologic malignancy cancer with increasing incidence and mortality rates, partly due to aging populations and genetic risks. This study explores the associations between biological age accelerations (BAA) and risk of incident EC and assesses the joint effect of genetic factor and BAA. Based on the UK Biobank cohort, 132,315 women participants were included for primary analysis and 124,119 white participants for genetic risk analysis. Biological age(BA) was calculated using the Klemera-Doubal (KDM) and PhenoAge method based on clinical biomarkers. We calculated two metrics for BAA (including KDM residual and PhenoAge residual) using residual analysis, comparing them against chronological age. The risk of incident EC was evaluated using multivariable Cox proportional-hazards models, adjusting for relevant covariates. Polygenic risk scores (PRS) were computed from known EC-associated SNPs. Both KDM and PhenoAge residual, were significantly associated with increased EC risk. In fully adjusted models, the highest tertile of KDM and PhenoAge residual was significantly associated with incident EC compared with the lowest group, with HRs of 1.278 (P=0.0044) and 1.424 (P<0.0001), repectively. The population-attributable fractions were 7.84% for KDM residual (P=0.0044), 9.78% for PhenoAge residual (P=0.0005), and 8.47% for genetic risk (P=0.0005). Additionally, joint associations of BAA and genetic risk with incident EC was evaluated. Compared with low genetic risk and low BAA, high genetic risk and high BAA was significantly associated with the incidence of EC with HRs of up to 2.172 (95% CI 1.592-2.963) for KDM and 2.226 (95% CI 1.640-3.022) for PhenoAge. Overall, higher levels of PhenoAge residual were consistently associated with an increased risk of incident EC, regardless of genetic risk. BAA and genetics both enhance the risk of incident EC. The effect of the PhenoAge residual is greater than that of the investigated genes, which in turn is greater than that of the KDM residual. These findings highlight the importance of considering both BAA and genetic factors in EC prevention.

Asymptomatic Intracranial Artery Stenosis/Occlusion in Heterozygous Familial Hypercholesterolemia: Its Frequency and Implications for Cerebrovascular and Cardiovascular Events.

The atherogenic characteristics of heterozygous familial hypercholesterolemia (HeFH) increase the risk of premature atherosclerotic cardiovascular disease including not only coronary artery disease but ischemic stroke. Asymptomatic intracranial artery stenosis/occlusion (IASO) is a major cause of ischemic stroke, but it has not yet been fully characterized in patients with HeFH. This study analyzed 147 clinically diagnosed subjects with HeFH who underwent magnetic resonance imaging/magnetic resonance angiography imaging for evaluation of IASO (≥50% diameter stenosis). Major adverse cerebrovascular and cardiovascular events (cardiac death, ischemic stroke, and acute coronary syndrome) were compared in patients with HeFH with and without asymptomatic IASO. Asymptomatic IASO was observed in 13.6% of patients with HeFH. The untreated low-density lipoprotein cholesterol level (240±95 versus 244±75 mg/dL; P=0.67) did not differ between the 2 groups. Despite the use of lipid-lowering therapies (statin, P=0.71; high-intensity statin, P=0.81; ezetimibe, P=0.33; proprotein convertase subxilisin/kexin type 9 inhibitor, P=0.39; low-density lipoprotein apheresis, P=0.14), on-treatment low-density lipoprotein cholesterol level in patients with both HeFH and IASO was still suboptimally controlled (97±62 versus 105±50 mg/dL; P=0.17), accompanied by a higher triglyceride level (median, 109 versus 79 mg/dL; P=0.001). During the 12.4-year observational period (interquartile range, 6.2-24.6 years), asymptomatic IASO exhibited a 4.04-fold greater likelihood of experiencing a major adverse cardiovascular event (95% CI, 1.71-9.55; P=0.001) in patients with HeFH. This increased risk of a major adverse cardiovascular event was consistently observed in a multivariate Cox proportional hazards model adjusting clinical characteristics (hazard ratio, 4.32 [95% CI, 1.71-10.9]; P=0.002). A total of 13.6% of Japanese subjects with HeFH presented with asymptomatic IASO. Despite lipid-lowering therapies, patients with both HeFH and IASO more likely had elevated risk of cerebrovascular and cardiovascular events. Our findings highlight asymptomatic IASO as a phenotypic feature of HeFH-related atherosclerosis, which ultimately affects future outcomes.

Association of atherogenic index of plasma with cardiovascular disease mortality and all-cause mortality in the general US adult population: results from NHANES 2005–2018

BackgroundThe atherogenic index of plasma (AIP) is a critical metric for predicting cardiovascular outcomes. However, its associations with cardiovascular disease mortality (CVM) and all-cause mortality (ACM) remain unclear. This study aims to elucidate the relationship between baseline AIP levels and CVM and ACM among a broad cohort of US adults.MethodsUtilizing data from the National Health and Nutrition Examination Survey (2005–2018), we analyzed 18,133 adults aged ≥ 18. Baseline triglycerides and high-density lipoprotein cholesterol levels were measured to calculate the AIP. Mortality outcomes were determined through linkage with the National Death Index database, with follow-up through December 31, 2019. Multivariable Cox proportional hazard models examined the associations between baseline AIP and mortality risks. Additionally, restricted cubic splines were utilized to investigate potential non-linear relationships, with subgroup analyses conducted across strata defined by age, gender, body mass index, diabetes, hypertension, and metabolic syndrome to assess variability in these associations.ResultsOver a median 95.0-month follow-up, there were 1870 all-cause deaths and 579 cardiovascular disease-related deaths. Our findings indicate a J-shaped association between the AIP and ACM (threshold = 0.0905); specifically, when baseline AIP exceeded 0.0905, a significant positive association with ACM emerged (hazard ratio, HR (95% confidence interval, CI): 1.61(1.08–2.37)). However, after adjusting for confounders, the relationship between AIP and CVM was not statistically significant (HR 1.31, 95% CI 0.93–1.86). Notably, in the 40–60-year age group, AIP was significantly positively associated with ACM and CVM, with HRs and 95% CIs of 1.51 (1.08v2.10) and 2.63 (1.39–4.98), respectively.ConclusionsA J-shaped relationship was observed between baseline AIP levels and ACM within the general US population, with a threshold of 0.0905. Moreover, AIP could potentially be an effective predictor for future ACM or CVM, particularly among individuals aged 40–60. Further investigation is warranted to corroborate these findings.

Clinical characteristics and prognosis of childhood acute lymphoblastic leukemia with CD123 expression

To investigate the expression of CD123 in children with acute lymphoblastic leukemia (ALL) and its effect on the clinical characteristics and prognosis of children with B-lineage acute lymphoblastic leukemia (B-ALL). A retrospective analysis was conducted on the clinical data of 251 children with ALL who were admitted to the Department of Hematology and Oncology, Children's Hospital of Kunming Medical University, from December 2019 to June 2022. According to the expression of CD123 at initial diagnosis, the children were divided into CD123+ group and CD123- group, and the two groups were compared in terms of clinical characteristics and treatment outcome. The factors influencing the prognosis were analyzed. Among the 251 children with ALL, there were 146 children (58.2%) in the CD123+ group. The B-ALL group had a significantly higher positive expression rate of CD123 than the acute T lymphocyte leukemia group (P<0.05). Compared with the CD123- group, the CD123+ group had significantly lower peripheral blood leukocyte count and percentage of juvenile cells and a significantly higher proportion of children with high hyperdiploid karyotype or an age of 1-10 years, with a relatively low proportion of children with E2A-PBX1 fusion gene (P<0.05). The multivariate Cox proportional-hazards regression model analysis showed that compared with the >10 years group, the 1-10 years group had a significantly higher overall survival rate (P<0.05), and compared with the high risk group, the moderate risk group had a significantly higher event-free survival rate in children with B-ALL (P<0.05). CD123 is widely expressed in children with B-ALL, and positive expression of CD123 might be an indicator for good prognosis in children with B-ALL, which is of great significance for evaluating the efficacy of remission induction therapy and survival prognosis of children with B-ALL.

The impact of discharge letter content on unplanned hospital readmissions within 30 and 90 days in older adults with chronic illness – a mixed methods study

BackgroundCare transitions are high-risk processes, especially for people with complex or chronic illness. Discharge letters are an opportunity to provide written information to improve patients’ self-management after discharge. The aim of this study is to determine the impact of discharge letter content on unplanned hospital readmissions and self-rated quality of care transitions among patients 60 years of age or older with chronic illness.MethodsThe study had a convergent mixed methods design. Patients with chronic obstructive pulmonary disease or congestive heart failure were recruited from two hospitals in Region Stockholm if they were living at home and Swedish-speaking. Patients with dementia or cognitive impairment, or a “do not resuscitate” statement in their medical record were excluded. Discharge letters from 136 patients recruited to a randomised controlled trial were coded using an assessment matrix and deductive content analysis. The assessment matrix was based on a literature review performed to identify key elements in discharge letters that facilitate a safe care transition to home. The coded key elements were transformed into a quantitative variable of “SAFE-D score”. Bivariate correlations between SAFE-D score and quality of care transition as well as unplanned readmissions within 30 and 90 days were calculated. Lastly, a multivariable Cox proportional hazards model was used to investigate associations between SAFE-D score and time to readmission.ResultsAll discharge letters contained at least five of eleven key elements. In less than two per cent of the discharge letters, all eleven key elements were present. Neither SAFE-D score, nor single key elements correlated with 30-day or 90-day readmission rate. SAFE-D score was not associated with time to readmission when adjusted for a range of patient characteristics and self-rated quality of care transitions.ConclusionsWhile written summaries play a role, they may not be sufficient on their own to ensure safe care transitions and effective self-care management post-discharge.Trial registrationClinical Trials. giv, NCT02823795, 01/09/2016.

Endoscopic ultrasound-guided hepaticogastrostomy vs. antegrade metal stent placement keeping an access route in patients with malignant biliary obstruction.

Few studies have compared endoscopic ultrasound (EUS)-guided hepaticogastrostomy (HGS) with EUS-guided antegrade metal stent placement (AGMS). The purpose of this study was to compare times to recurrent biliary obstruction (TRBO) in patients who underwent HGS using metal stents (MS) and those who underwent AGMS keeping access routes with plastic stents (AGMS-AR). This study retrospectively evaluated consecutive patients who underwent HGS or AGMS between September 2016 and December 2022. TRBO, overall survival (OS), and adverse event (AE) rates were compared in the two groups. The risk factors for RBO were determined using a multivariable Cox proportional hazards model. This study included 32 patients in the HGS group and 30 in the AGMS-AR group. Technical success rate was significantly higher in the HGS than in the AGMS-AR group (100 vs. 80%; P = 0.009). The technical success rate without tract dilation was significantly higher in the AGMS-AR than in the HGS group (83 vs. 38%; P < 0.001). RBO rates were significantly higher in the HGS than in the AGMS-AR group (53 vs. 17%; P = 0.024), whereas AE rates did not differ significantly. TRBO differed significantly in the HGS and AGMS-AR groups (159days vs. not reached, P = 0.011), whereas OS did not differ significantly. Multivariable analysis revealed that HGS was an independent risk factor for RBO (hazard ratio, 6.48, P = 0.014). TRBO was significantly longer in patients who underwent AGMS with PS than HGS. AGMS with PS may be effective after the failure of ERCP in patients with malignant biliary obstruction.

Associations of different combinations of moderate-vigorous physical activity and muscle-strengthening activity with mortality among US lung cancer survivors

BackgroundTo investigate the associations of different combinations of moderate to vigorous physical activity (MVPA) and muscle strengthening activity (MSA) with all-cause and cancer mortality among lung cancer survivors.MethodsThis nationwide prospective cohort study used data from the US National Health Interview Survey 2009–2018. A total of 785 lung cancer survivors were included in the study. Participants were linked to the National Death Index through December 31, 2019. Self-reported MVPA and MSA frequency data were used to obtain 4 mutually exclusive exposure categories. Multivariate Cox proportional hazard models were applied to explore the association between exposure categories and outcomes.ResultsThe mean (standard deviation [SD]) age of the study population was 69.1 (11.3) years and 429 (54.6%) were female. Among them, 641 (81.7%) were White and 102 (13.0%) were Black. The median follow-up time was 3 years (2526 person-years), and 349 (44.5%) all-cause deaths and 232 (29.6%) cancer deaths occurred. Compared to the MVPA < 60 min/week and MSA < 2 sessions/week group, individuals in the MVPA ≥ 60 min/week and MSA < 2 sessions/week group showed hazard ratios (HRs) of 0.50 (95% CI, 0.36–0.69) for all-cause mortality and 0.37 (95% CI, 0.20–0.67) for cancer mortality after the adjustment of covariates. Those in the MVPA ≥ 60 min/week and MSA ≥ 2 sessions/week group exhibited HRs of 0.52 (95% CI, 0.35–0.77) for all-cause mortality and 0.27 (95% CI, 0.12–0.62) for cancer mortality when compared to the MVPA < 60 min/week and MSA < 2 sessions/week group. We also identified distinct non-linear relationships between MVPA and outcomes risk among two MSA frequency subgroups.ConclusionThis cohort study demonstrated that higher levels of MVPA and MSA combined might be associated with optimal reductions of mortality risk in lung cancer survivors.

A comparison of natalizumab and ocrelizumab on disease progression in multiple sclerosis.

No direct comparisons of the effect of natalizumab and ocrelizumab on progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) events are currently available. We aimed to compare the risk of achieving first 6 months confirmed PIRA and RAW events and irreversible Expanded Disability Status Scale (EDSS) 4.0 and 6.0 in a cohort of naïve patients treated with natalizumab or ocrelizumab from the Italian Multiple Sclerosis Register. Patients with a first visit within 1 year from onset, treated with natalizumab or ocrelizumab, and ≥3 visits were extracted. Pairwise propensity score-matched analyses were performed. Risk of reaching the first PIRA, RAW, and EDSS 4.0 and 6.0 events were estimated using multivariable Cox proportional hazards models. Kaplan-Meier curves were used to show cumulative probabilities of reaching outcomes. In total, 770 subjects were included (natalizumab = 568; ocrelizumab = 212) and the propensity score-matching retrieved 195 pairs. No RAW events were found in natalizumab group and only 1 was reported in ocrelizumab group. A first PIRA event was reached by 23 natalizumab and 25 ocrelizumab exposed patients; 7 natalizumab- and 10 ocrelizumab-treated patients obtained an irreversible EDSS 4.0, while 13 natalizumab- and 15 ocrelizumab-treated patients reached an irreversible EDSS 6.0. No differences between the two groups were found in the risk (HR, 95%CI) of reaching a first PIRA (1.04, 0.59-1.84; p = 0.88) event, an irreversible EDSS 4.0 (1.23, 0.57-2.66; p = 0.60) and 6.0 (0.93, 0.32-2.68; p = 0.89). Both medications strongly suppress RAW events and, in the short term, the risk of achieving PIRA events, EDSS 4.0 and 6.0 milestones is not significantly different.

Endothelial biomarkers (Von willebrand factor, BDCA3, urokinase) as predictors of mortality in COVID-19 patients: cohort study

BackgroundSARS-CoV-2 is a systemic disease that affects endothelial function and leads to coagulation disorders, increasing the risk of mortality. Blood levels of endothelial biomarkers such as Von Willebrand Factor (VWF), Thrombomodulin or Blood Dendritic Cell Antigen-3 (BDCA3), and uUokinase (uPA) increase in patients with severe disease and can be prognostic indicators for mortality. Therefore, the aim of this study was to determine the effect of VWF, BDCA3, and uPA levels on mortality.MethodsFrom May 2020 to January 2021, we studied a prospective cohort of hospitalized adult patients with polymerase chain reaction (PCR)-confirmed COVID-19 with a SaO2 ≤ 93% and a PaO2/FiO2 ratio < 300. In-hospital survival was evaluated from admission to death or to a maximum of 60 days of follow-up with Kaplan-Meier survival curves and Cox proportional hazard models as independent predictor measures of endothelial dysfunction.ResultsWe recruited a total of 165 subjects (73% men) with a median age of 57.3 ± 12.9 years. The most common comorbidities were obesity (39.7%), hypertension (35.4%) and diabetes (30.3%). Endothelial biomarkers were increased in non-survivors compared to survivors. According to the multivariate Cox proportional hazard model, those with an elevated VWF concentration ≥ 4870 pg/ml had a hazard ratio (HR) of 4.06 (95% CI: 1.32–12.5) compared to those with a lower VWF concentration adjusted for age, cerebrovascular events, enoxaparin dose, lactate dehydrogenase (LDH) level, and bilirubin level. uPA and BDCA3 also increased mortality in patients with levels ≥ 460 pg/ml and ≥ 3600 pg/ml, respectively.ConclusionThe risk of mortality in those with elevated levels of endothelial biomarkers was observable in this study.

Longitudinal Analysis of Diabetes Mellitus Risk: Smoking Status and Smoking Cessation.

Background/Objectives: Smoking cessation is acknowledged for its health benefits. However, it paradoxically increases diabetes mellitus (DM) risk shortly after quitting due to weight gain. This research aimed to investigate how smoking status could affect the development of DM, focusing on how the risk of acquiring diabetes changed over time after quitting smoking, independent of variables such as weight gain. Methods: The data of 386,558 participants of the Kangbuk Samsung Health Study, excluding those with pre-existing DM, were examined. Smoking status and its long-term effects on DM risk were assessed using multivariate Cox proportional hazards models. Lifestyle factors, including weight change, physical activity levels, and alcohol intake, were adjusted as time-varying covariates throughout the follow-up period. Results: Modified hazard ratios (HRs) indicated no notable disparity in DM risk between individuals who previously smoked and those who had never smoked (HR: 1.04, 95% CI: 0.999-1.08, p-value < 0.001). In contrast, current smokers exhibited a significantly increased DM risk (HR: 1.29, 95% CI: 1.24-1.35, p-value < 0.001). Within the first six years post-cessation, former smokers initially faced a higher DM risk than never smokers (0-2 years, HR: 1.22, 95% CI: 1.15-1.31, p-value < 0.001; 3-5 years, HR: 1.11, 95% CI: 1.04-1.20, p-value < 0.001). After 12 years, they realigned with never smokers (12-46 years, HR: 0.92, 95% CI: 0.86-0.98, p-value = 0.002). Current smokers consistently showed a higher DM risk (0-9 years, HR: 1.29, 95% CI: 1.14-1.46, p-value < 0.001). Adjusting for covariates such as weight change and physical activity did not alter these findings. Conclusions: Our results indicated that former smokers initially experienced an elevated risk of DM relative to never smokers. This increased risk aligned with the risk of never smokers after six years, and the risk continued to improve after 12 years compared to never smokers. This contrasted with current smokers, who maintained a heightened risk of DM, even when adjustments were made for weight change, physical activity, and alcohol intake as time-varying covariates.

Nonlinear association between PD-L1 expression levels and the risk of postoperative recurrence in non-small cell lung cancer

Accurate prediction of postoperative recurrence is important for optimizing the treatment strategies for non-small cell lung cancer (NSCLC). Previous studies identified the PD-L1 expression in NSCLC as a risk factor for postoperative recurrence. This study aimed to examine the contribution of PD-L1 expression to predicting postoperative recurrence using machine learning. The clinical data of 647 patients with NSCLC who underwent surgical resection were collected and stratified into training (80%), validation (10%), and testing (10%) datasets. Machine learning models were trained on the training data using clinical parameters including PD-L1 expression. The top-performing model was assessed on the test data using the SHAP analysis and partial dependence plots to quantify the contribution of the PD-L1 expression. Multivariate Cox proportional hazards model was used to validate the association between PD-L1 expression and postoperative recurrence. The random forest model demonstrated the highest predictive performance with the SHAP analysis, highlighting PD-L1 expression as an important feature, and the multivariate Cox analysis indicated a significant increase in the risk of postoperative recurrence with each increment in PD-L1 expression. These findings suggest that variations in PD-L1 expression may provide valuable information for clinical decision-making regarding lung cancer treatment strategies.

A case-cohort study of per- and polyfluoroalkyl substance concentrations and incident prostate cancer in the cancer prevention Study-II LifeLink cohort study

IntroductionPer- and polyfluoroalkyl substances (PFAS) are environmentally persistent, potentially carcinogenic chemicals. Previous studies investigating PFAS exposure and prostate cancer yielded mixed findings. We aimed to investigate associations between PFAS exposure and incident prostate cancer in a large cohort of U.S. men, overall and by selected demographic, lifestyle, and medical-related characteristics. MethodsWe conducted a case-cohort study among Cancer Prevention Study-II LifeLink Cohort participants who, at baseline (1998–2001), had serum specimens collected and no prior cancer diagnosis. The study included all men diagnosed with prostate cancer (n = 1610) during follow-up (baseline–June 30, 2015) and a random sub-cohort of 500 men. PFAS concentrations [perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorooctanoic acid (PFOA)] were measured in stored serum specimens. We used multivariable Cox proportional hazards models to estimate associations between PFAS concentrations and prostate cancer, overall and by selected characteristics (grade, stage, family history, age, education, smoking status, and alcohol consumption). ResultsProstate cancer hazards were slightly higher among men with concentrations in the highest (Q4) vs lowest quartile (Q1) for PFHxS [hazard ratio (HR) (95% CI): 1.18 (0.88–1.59)] and PFOS [HR (95% CI): 1.18 (0.89–1.58)], but not for PFNA or PFOA. However, we observed heterogeneous associations by age, family history of prostate cancer (PFHxS), alcohol consumption (PFHxS), and education (PFNA). For example, no meaningful associations were observed among men aged <70 years at serum collection, but among men aged ≥70 years, HRs (95% CIs) comparing Q4 to Q1 were PFHxS 1.54 (1.02–2.31) and PFOS 1.62 (1.08–2.44). No meaningful heterogeneity in associations were observed by tumor grade or stage. ConclusionsOur findings do not clearly support an association between the PFAS considered and prostate cancer. However, positive associations observed in some subgroups, and consistently positive associations observed for PFHxS warrant further investigation.

Impact of frozen section on long-term outcomes in robot-assisted laparoscopic prostatectomy.

To compare 1-year functional and 5-year oncological outcomes of men undergoing robot-assisted laparoscopic prostatectomy (RALP) with neurovascular structure-adjacent frozen-section examination (NeuroSAFE) with those in men undergoing RALP without NeuroSAFE (standard of care [SOC]). Men undergoing RALP in our centre between 1 January 2009 and 30 June 2018 were enrolled from a prospectively maintained database. Patients were excluded if they had undergone preoperative therapy or postoperative adjuvant therapy or were enrolled in clinical trials. Patients were grouped based on use of NeuroSAFE. Follow-up was censored at 5 years. The primary outcome was difference in time to biochemical recurrence (BCR) on multivariable analysis, defined as prostate-specific antigen (PSA) >0.2 ng/L on two consecutive measurements. Secondary outcomes were difference in 1-year erectile dysfunction and incontinence. In the enrolment period, 1199 consecutive men underwent RALP, of whom 1140 were eligible, including 317 with NeuroSAFE and 823 with SOC. The median PSA follow-up was 60 months in both groups. Rates of 5-year BCR were similar on Kaplan-Meier survival curve analysis (11% vs 11%; P = 0.9), as was time to BCR on multivariable Cox proportional hazards modelling (hazard ratio 1.2; P = 0.6). Compared with the SOC group at 1 year, the NeuroSAFE group had similar unadjusted rates of incontinence (5.1% vs 7.7%) and lower unadjusted impotence (57% vs 80%). On multivariable analysis, NeuroSAFE patients had equivalent risk of incontinence (odds ratio [OR] 0.59, 95% CI 0.17-1.6; P = 0.4) but significantly reduced risk of erectile dysfunction (OR 0.37, 95% CI 0.22-0.60; P < 0.001). For men undergoing RALP, compared with SOC, NeuroSAFE patients had equivalent time to BCR and risk of 1-year incontinence, and significantly lower risk of 1-year erectile dysfunction.

Association of the systemic immune-inflammation index with all-cause and cardiovascular mortality in individuals with rheumatoid arthritis

The systemic immune-inflammation index (SII), a metric reflecting systemic inflammatory response and immune activation, remains underexplored concerning its correlation with mortality among rheumatoid arthritis (RA) patients. This study aimed to delineate the association between SII and both all-cause and cardiovascular mortality within the cohort of American adults diagnosed with RA, utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018. The investigation extracted data from NHANES cycles between 1999 and 2018, identifying RA patients through questionnaire responses. The SII was computed based on complete blood counts, employing the formula: (platelets × neutrophils) / lymphocytes. The optimal SII cutoff value for significant survival outcomes was determined using maximally selected rank statistics. Multivariable Cox proportional hazards models assessed the relationship between SII levels and mortality (all-cause and cardiovascular) among RA patients, with subgroup analyses examining potential modifications by clinical confounders. Additionally, restricted cubic spline (RCS) analyses were conducted to explore the linearity of the SII-mortality association. The study encompassed 2070 American adults with RA, among whom 287 exhibited a higher SII (≥ 919.75) and 1783 a lower SII (< 919.75). Over a median follow-up duration of 108 months, 602 participants died. After adjustments for demographic, socioeconomic, and lifestyle variables, a higher SII was associated with a 1.48-fold increased risk of all-cause mortality (hazard ratio [HR] = 1.48, 95% confidence interval [CI] 1.21–1.81, P < 0.001) and a 1.51-fold increased risk of cardiovascular mortality (HR = 1.51, 95% CI 1.04–2.18, P = 0.030) compared to a lower SII. Kaplan–Meier analyses corroborated significantly reduced survival rates within the higher SII cohort for both all-cause and cardiovascular mortality (Pall-cause mortality < 0.0001 and Pcardiovascular mortality = 0.0004). RCS analyses confirmed a positive nonlinear relationship between SII and mortality rates. In conclusion, the SII offers a straightforward indicator of the equilibrium between detrimental innate inflammation and beneficial adaptive immunity. Our investigation, utilizing a comprehensive and nationally representative sample, reveals that elevated SII levels independently forecast a greater risk of mortality from all causes, as well as cardiovascular-specific mortality, in individuals suffering from RA. These insights underscore the clinical relevance of the SII as an affordable and readily accessible biomarker. Its incorporation into regular clinical practice could significantly enhance the precision of risk assessment and forecasting for patients with RA, facilitating more tailored and effective management strategies. Specifically, patients with high SII levels could be identified for more stringent cardiovascular risk management, including closer monitoring, lifestyle interventions, and aggressive pharmacological treatments to mitigate their increased risk of mortality.

The role of sarcopenic obesity for the prediction of prognosis of patients with gastrointestinal cancer.

Sarcopenic obesity (SO) in patients with gastrointestinal cancer is associated with a poor prognosis. We aimed to investigate the prognostic impact of SO in patients with gastrointestinal cancer, as well as the diagnostic cut-off value of SO in patients with gastrointestinal cancer among Chinese population. We conducted a consecutive cohort study. Between January 2017 and January 2019, 289 patients diagnosed with gastrointestinal cancer were included in our study. Skeletal muscle area, total fat area, and subcutaneous fat area were measured by CT scan. All patients were followed up for 5 years. Receiver operating characteristic curves (ROC) were adopted to determine the cut-off values of visceral fat obesity for the prediction of sarcopenia. Based on the cut-off values, patients with sarcopenia combined with visceral fat obesity were divided into the SO group, and the others were divided into the non-sarcopenic obesity (NSO) group. Kaplan-Meier curves and univariate and multivariate Cox proportional hazard models were employed to explore the associations of body composition profiles with 5-year overall survival and disease-specific survival. Obtained from Youden's Index for ROC for the prediction of 5-year survival, skeletal muscle mass index (SMI) ≤40.02 cm2/m2 with VFA ≥ 126.30 cm2 in men and SMI ≤32.05 cm2/m2 with VFA ≥72.42 cm2 in women indicate a risk of poor prognosis in patients diagnosed with gastrointestinal cancer. Patients with SO had poorer 5-year overall survival (OS) than patients with NSO (6.74% vs. 82.84%, p < 0.001), and poorer 5-year DFS (6.74% vs. 81.82%, p < 0.001). In multivariate analysis, we found that the long-term mortality risk was approximately 13-fold higher among patients in the SO group compared to those with no conditions. Preoperative assessment of SO is useful not only for monitoring nutritional status but also for predicting 5-year OS in gastrointestinal cancer patients.

Epicardial Pacing Outcomes in Infants with Heart Block: Lead and Device Complications from a Multicenter Experience

Infants with complete heart block (CHB) require epicardial pacemaker (PM) insertion. Prior studies described epicardial pacing outcomes in infants and children though were limited by small and/or heterogeneous populations. To explore patient and procedural-level associations with device complications in infants with CHB who received a permanent PM. Multicenter, retrospective cohort study including infants receiving an epicardial PM between 2000-2021 for CHB. The primary outcome was time to device-related adverse event (DRAE): (1) lead failure requiring revision; (2) pocket infection; (3) exit block requiring increased pacing output; or (4) lead-related coronary artery compression. Time to event analysis was performed using the Kaplan-Meier method with a multivariable Cox proportional hazards model. 174 infants received an epicardial PM (282 bipolar, 39 unipolar leads) for CHB. Median age and weight at PM were 93.5 days and 4.5 kg, respectively. Pacing indication was postoperative CHB in 63% and congenital CHB in 37%. The median follow-up was 2.1 years. The primary outcome occurred in 26 infants at a median time to event of 0.6 years. Age ≤90 days at PM was the most significant risk factor for DRAE (HR 7.02, p<0.001), primarily driven by pocket infections. Lead failure occurred in 3% of leads with a 5- and 10-year freedom from failure of 93% and 83%, respectively. Device complications affect 15% of infants receiving a permanent PM for heart block. Age ≤90 days at PM implant is especially associated with infectious complications. Epicardial lead durability appears similar to previously reported pediatric experiences.

Social factors associated with the risk of glaucoma suspect conversion to glaucoma: analysis of the nationwide All of Us Program

To examine social factors associated with the 5-year risk of glaucoma suspects (GS) converting to open-angle glaucoma (OAG). Retrospective cohort analysis. We screened for participants diagnosed with GS in the All of Us database. Cases that converted to OAG within 5 years of GS diagnosis (the "conversion group") were compared with control cases that did not convert. Demographic, socioeconomic and healthcare utilization data of the cases were extracted and compared between the conversion group and the control group. Multivariable Cox proportional hazards modeling was used to identify potential factors associated with the risk of conversion. Hazard ratios (HRs) of significant factors associated with the risk of conversion. A total of 5274 GS participants were identified, and 786 (15%) cases converted to OAG within 5-year follow-up. The two groups showed significant differences in age, race, gender, employment status, income/education level, history of intra-ocular surgery, and healthcare utilization patterns. In the multivariable model, African American/Black race (HR [95% confidence interval] =1.70 [1.44-2.00]), older age at GS diagnosis (1.17 [1.09-1.25]), male gender (1.30 [1.13-1.50], no history of recreational drug use (1.23 [1.07-1.42]), history of intra-ocular surgery (1.60 [1.02-1.53]) and having more reasons for delayed healthcare access (2.27 [1.23-4.18]) were associated with a greater hazard of conversion, while being employed (0.71 [0.60-0.86]) was associated with a smaller hazard of conversion (P<0.05 for all). Several social factors were associated with the conversion from GS to OAG, which may help to identify patients at higher risk of disease progression. Future studies are needed to examine the basis for these findings and the potential interventions that could address them.

Serum S-adenosylhomocysteine, rather than homocysteine, is associated with hepatocellular carcinoma survival: a prospective cohort study

BackgroundEmerging evidence suggested that S-adenosylhomocysteine (SAH) may be a better serum biomarker for cardiovascular disease than homocysteine (Hcy). However, the role of SAH in hepatocellular carcinoma (HCC) prognosis remains unclear. ObjectivesWe aimed to prospectively explore the relationships between serum SAH and related metabolites (Hcy, S-adenosylmethionine [SAM]) with HCC survival, and to evaluate the effect modifications by gene polymorphisms in one-carbon metabolism key enzymes. MethodsWe included 1,080 newly diagnosed HCC patients from the Guangdong Liver Cancer Cohort. Serum SAH, Hcy, and SAM were measured utilizing HPLC-MS/MS. Gene polymorphisms in one-carbon metabolism key enzymes were identified using competitive allele-specific PCR (KASP). Primary outcomes were liver cancer-specific survival (LCSS) and overall survival (OS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using multivariate Cox proportional hazards models. ResultsAfter a median follow-up of 3.6 years, 601 deaths occurred, with 552 (92%) attributed to HCC. Multivariable analysis revealed that patients in the highest quartile of serum SAH concentrations were significantly associated with worse survival compared to those in the lowest quartile, with HRs of 1.58 (95% CI: 1.19, 2.10; P-trend = 0.002) for LCSS and 1.54 (95% CI: 1.18, 2.02; P-trend = 0.001) for OS. There were no significant interactions between serum SAH concentrations and genetic variants of one-carbon metabolism key enzymes. No significant associations were found between serum Hcy, SAM concentrations and SAM/SAH ratio with LCSS or OS. ConclusionsHigher serum SAH concentrations, rather than homocysteine, were independently associated with worse survival in HCC patients, regardless of the genetic variants of one-carbon metabolism key enzymes. These findings suggesting that SAH may serve as a novel metabolism-related prognostic biomarker for HCC.

Discrepancy between estimated glomerular filtration rate by creatinine versus cystatin C in different patient care settings

ObjectiveEstimated glomerular filtration rate (eGFR) calculated by cystatin C (cysC) has been recommended for broader adoption. This study assessed the discrepancy between eGFR calculated by cysC (eGFRcys) and creatinine (eGFRcr) in different patient care settings and explored potential contributing factors to such discrepancies. MethodsThis retrospective study included 2072 patients with paired cystatin C and creatinine results in different patient care settings. Delta eGFRcr-cys (eGFRcr − eGFRcys) was analyzed in relationship to patient care settings and the Elixhauser Comorbidity index. The 90-day survival in patients with different delta eGFR was assessed by Kaplan-Meier analysis, univariate and multivariate Cox proportional hazard models. In addition, discrepancy between eGFRcys and eGFRcr was analyzed in 50 ambulatory patients with systemic inflammation but normal kidney function. ResultsInpatients had higher cysC (median 1.91 mg/L), lower eGFRcys (median 31 mL/min/1.73 m2), and larger delta eGFRcr-cys (median 18 mL/min/1.73 m2) than outpatients (cysC median 1.53 mg/L, p < 0.0001, eGFRcys median 41 mL/min/1.73 m2, p < 0.0001, delta eGFRcr-cys median 4 mL/min/1.73 m2, p < 0.0001). Higher Elixhauser Comorbidity index correlated with lower eGFRcys and larger delta eGFRcr-cys, with median delta eGFRcr-cys 11 and 6 mL/min/1.73 m2 in patients with a Comorbidity index > 15 and ≤ 15, respectively (p < 0.0001). Increased delta eGFRcr-cys was associated with worse 90-day survival. Patients with systemic inflammation but normal kidney function had lower eGFRcys (median 77.5 mL/min/1.73 m2) than eGFRcr (median 97 mL/min/1.73 m2, p < 0.001), with red blood cell abnormalities as associated factors. ConclusionInflammation and comorbidities are associated with decreased eGFRcys and large discrepancies between eGFRcr and eGFRcys independent of kidney function and are most apparent in inpatients. Creatinine-cysC combined eGFR reduces this discrepancy and should be broadly adopted.