Cox Proportional Hazards Regression Models Research Articles

Dietary amino acids intake and all-cause and cause-specific mortality: results from the Golestan Cohort Study

BackgroundLess is known whether the amino acid composition of dietary protein sources effects on long-term health outcomes. We aimed to evaluate the association between dietary amino acid composition and all-cause and cause-specific mortality.MethodsThis study used data from the Golestan Cohort Study, which was performed in the Golestan Province of Iran from January 2004 to June 2008. Mortality, which was the primary outcome, was ascertained through September 2022. The Cox proportional hazards regression models were used to determine the adjusted hazard ratios (HR) and 95% confidence intervals (CI) for mortality according to the quintiles of amino acid consumption, taking the third quintile as the reference.ResultsA total of 47,337 participants (27,293 [57.7%] women) with a mean (standard deviation) age of 51.9 (8.9) years were included. During a median follow-up of 15 years, 9,231 deaths were documented. Regarding essential amino acid intakes, the HRs of all-cause mortality were 1.16 (95% CI, 1.07–1.26) in the first quintile, compared with the reference group (P for non-linear trend < 0.001). Similarly, non-linear associations were observed between risk of all-cause mortality and intake of branched-chain, aromatic, sulfur-containing, or non-essential amino acids (P for non-linear trend < 0.001 for all comparisons), with higher HRs for participants in the first quintiles. There was an age interaction for the associations between dietary amino acids and mortality (P for interaction ˂0.05). While high amino acid diets were detrimental in middle-aged adults (< 65 years), increased hazards of mortality were observed among older adults (≥ 65 years) with low amino acid intake.ConclusionsThis study showed the non-linear trend between amino acids intake and risk of mortality in the middle-aged and older Iranian population. Overall, our findings suggest that diets lower in amino acids were associated with increased hazards of mortality, particularly among older adults.

Association of commission on cancer accreditation with receipt of guideline‐concordant care and survival among patients with colon cancer

AbstractBackgroundGuideline‐concordant care (GCC) is associated with improved survival for patients with cancer; however, variations in receipt of GCC remain a concern. The objective of this study was to evaluate the association of Commission on Cancer (CoC) hospital accreditation status with receipt of GCC and survival among patients with colon cancer.MethodsThis retrospective observational study identified patients diagnosed with stage I–IV colon cancer from 2018 to 2020 from the National Program of Cancer Registries and Surveillance, Epidemiology, and End Results Program Database. Guideline concordance was defined as receipt of stage‐appropriate lymphadenectomy or chemotherapy. Multivariable logistic regression models investigated associations with receipt of GCC. Cox proportional hazards regression models assessed 3‐year cancer‐specific mortality risk.ResultsOf 222,583 patients with colon cancer, 146,629 (91.2%) of eligible patients received guideline‐concordant lymphadenectomy and 70,586 (81.9%) of the eligible patients received guideline‐concordant chemotherapy. Treatment at CoC‐accredited hospitals was the strongest modifiable predictor for receipt of guideline‐concordant lymphadenectomy (odds ratio [OR] 1.82; 95% confidence interval [CI] 1.75–1.88) and chemotherapy (OR 2.14; 95% CI 2.06–2.23). Among patients treated at CoC‐accredited hospitals, risk adjusted mortality was decreased for patients with stage I–II disease (hazard ratio [HR] 0.94; 95% CI 0.80–0.99), stage III disease (HR 0.93; 95% CI 0.88–0.98), and stage IV disease (HR 0.88; 95% CI 0.84–0.92).ConclusionsFor patients with colon cancer, treatment at CoC‐accredited hospitals was associated with increased receipt of GCC and decreased mortality risk. Benchmarking data may serve as a valuable accountability tool for quality assessment to improve cancer treatment and outcomes.

Non-linear relationship between lipid accumulation products and risk of diabetes in Japanese adults

The lipid accumulation product (LAP) is a novel, sex-specific indicator of lipid accumulation. While previous studies have investigated the relationship between LAP and diabetes, they have not specifically addressed potential sex differences in this association. The present study explores the potential sex-specific differences in the relationship between LAP and diabetes mellitus (DM) risk in the Japanese population. From 2004 to 2015, a total of 15,263 Japanese individuals without DM underwent physical assessments at Murakami Memorial Hospital. The association between LAP and incident diabetes was analyzed using Cox proportional hazards regression models, incorporating cubic spline functions and smooth curve fitting to identify potential non-linear relationships. Subgroup and sensitivity analysis assessments were conducted to validate the robustness of our findings. After adjusting for covariates, a positive association between LAP and DM risk was observed in both females (HR: 1.02, 95% CI: 1.00-1.03, P = 0.0138) and males (HR: 1.01, 95% CI: 1.00-1.01, P = 0.0314). A non-linear association between LAP and incident DM was identified for both sexes. The inflection points for LAP were 16.58 for females and 11.11 for males. In females, the HR to the left and right of the inflection point were 1.09 (95% CI: 1.02–1.17) and 1.01 (95% CI: 1.00-1.03), respectively. In males, the HR to the left and right of the inflection point were 0.92 (95% CI: 0.86–0.98) and 1.01 (95% CI: 1.00-1.01), respectively. Sensitivity analysis indicated a stronger association between LAP and DM risk. Elevated baseline LAP levels were associated with an increased risk of incident DM, with the relationship exhibiting non-linear characteristics. These findings suggest that maintaining lower LAP levels may help mitigate the risk of developing diabetes.

Risk Score for Hepatocellular Cancer in Adults Without Viral Hepatitis or Cirrhosis

Hepatocellular carcinoma (HCC) is typically detected only at advanced stages when treatment options are limited. Most of the current HCC risk models focus on patients with viral hepatitis or diagnosed cirrhosis or require variables not routinely available in clinical care. To identify modifiable HCC risk factors in the general population and to develop a risk score to inform HCC screening and risk-factor modification interventions for high-risk individuals without viral hepatitis or decompensated cirrhosis. This cohort study analyzed demographic, clinical, laboratory, and diagnostic data from the US Department of Veterans Affairs (VA) electronic health records. Data were divided into development and validation samples. Veterans aged 30 to 95 years were included, and those with hepatitis B or C virus infection, hepatic decompensation, or prevalent HCC were excluded. Patients were followed up until the occurrence of HCC diagnosis, death, or December 31, 2021. A Cox proportional hazards regression model for 10-year risk of HCC was developed and used to create an HCC risk score, and performance in development and validation samples and in patient subgroups was evaluated. One outpatient visit date per person at least 18 months after VA entry, between October 1, 2007, and March 31, 2020, was randomly selected and used as the index date for the start of follow-up. Analyses were performed from March 2023 to May 2024. Age, sex, race and ethnicity, body mass index, liver fibrosis (detected with Fibrosis-4 Index [FIB-4]), diabetes status, smoking status, and alcohol use. First HCC diagnosis during follow-up. This information was ascertained from VA national cancer registry topography and histology codes and from International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes for the inpatient or outpatient visits. This study of 6 509 288 veterans included 6 048 917 males (92.9%), with a median (IQR) age of 65 (54-74) years, who identified as being of Hispanic (5.3%), non-Hispanic Black (15.0%), non-Hispanic White (68.9%), or other (4.6%) race and ethnicity. Overall, 15 142 patients (0.2%) developed HCC, 69.5% of whom had FIB-4 of 3.25 or lower at baseline. While FIB-4 was the most important variable, age, sex, race and ethnicity, body mass index, diabetes, smoking, and alcohol use were also informative. Discrimination in the development sample was better than FIB-4 alone (C statistic, 0.83 [95% CI, 0.82-0.85] vs 0.79 [95% CI, 0.77-0.80]). The HCC risk score performed consistently well in the validation sample and in all subgroups. A FIB-4 threshold of 3.25 would screen 5.0% of the cohort at a cost of 28 false-positives for every true-positive; a model risk score of 58 would screen 4.7% of the cohort at a cost of 23 false-positives for every true-positive. Results of this study suggest that a multivariable risk score that uses routinely available clinical data outperforms FIB-4 alone in identifying patients at risk of HCC who do not have viral hepatitis or hepatic decompensation at baseline.

Hemagglutination-Inhibition Antibodies and Protection against Influenza Elicited by Inactivated and Live Attenuated Vaccines in Children.

Hemagglutinin (HA)-inhibiting antibodies contribute to the immune defense against influenza infection. However, there are insufficient data on the extent of correlation between vaccine-elicited HA antibodies and protection in children against different influenza strains, particularly when comparing live attenuated influenza vaccines (LAIV) versus inactivated influenza vaccines (IIV). We measured postvaccination hemagglutination-inhibition (HAI) titers in 3-15-year-old participants of a cluster-randomized controlled trial of trivalent LAIV(3) versus IIV(3) in Canadian Hutterite colonies. We assessed HAI titers as predictors of symptomatic, reverse transcription polymerase chain reaction (RT-PCR)-confirmed influenza over 3 influenza seasons using Cox proportional hazards regression models with vaccine type as a covariate. For each log2 unit increase in postvaccination HAI against A/H1N1 in 2013-2014, A/H3N2 2014-2015, and B/Yamagata in 2013-2014 (each the predominant circulating strain for the respective influenza season), the reduction in the risk of confirmed influenza was equal to 29.6% (95% confidence interval [CI], 17.1%-39.5%), 34.8% (95% CI, 17.2%-47.9%), and 31.8% (95% CI, 23.8%-38.5%), respectively. No reduction in the risk of influenza was observed with B/Yamagata-specific HAI titers in 2012-2013, which was dominated by a mixture of Yamagata and Victoria strains. Despite the overall lower HAI titers in the LAIV3 group, both H1N1 and H3N2 HAI titers were associated with protection against subtype matched influenza. Both LAIV3- and IIV3-elicited HA antibodies are associated with protection against influenza infection in seasons when the vaccine strains match the circulating influenza strain subtypes, supporting the use of HAI as a correlate of protection for both vaccine types in children.

Impact of Precision in Staging Acute Kidney Injury and Chronic Kidney Disease on Treatment Outcomes: An Observational Study

(1) Background: “Kidney Disease: Improving Global Outcomes” (KDIGO) provides guidelines for identifying the stages of acute kidney injury (AKI) and chronic kidney disease (CKD). A data-driven rule-based engine was developed to determine KDIGO staging compared to KD-related keywords in discharge letters. (2) Methods: To assess potential differences in outcomes, we compare the patient subgroups with exact KDIGO staging to imprecise or missing staging for all-cause mortality, in-hospital mortality, selection bias and costs by applying Kaplan–Meier analysis and the Cox proportional hazards regression model. We analysed 63,105 in-patient cases from 2016 to 2023 at a tertiary hospital with AKI, CKD and acute-on-chronic KD. (3) Results: Imprecise and missing CKD staging were associated with an 85% higher risk of all-cause and in-hospital mortality (CI: 1.7 to 2.0 and 1.66 to 2.03, respectively) compared to exact staging for any given disease status; imprecise or missing AKI staging increased in-hospital mortality risk by 56% and 57% (CI: 1.43 to 1.70 and 1.37 to 1.81, respectively) in patients with AKI. (4) Conclusions: Exact staging is associated with better outcomes in KD management. Our study provides valuable insight into potential quality and outcome improvements and lower costs, considering elderly patients, women and patients with acute-on-chronic KD as the most vulnerable.

Recovery time and its predictors of severe acute malnutrition among under five children admitted at the therapeutic feeding center of Hiwot Fana comprehensive specialized hospital, eastern Ethiopia, 2024: a semi-parametric model

BackgroundEarly recovery is a performance indicator of quality care for children under five admitted due to severe acute malnutrition (SAM) at therapeutic feeding centers. Despite the available interventions to tackle such nutritional problems, there is limited information on the time to recovery and its predictors among children with severe acute malnutrition in Ethiopia, more particularly in the study setting.ObjectiveThe study aimed to assess the time to recovery from severe acute malnutrition and its predictors among children aged 6–59 months admitted to the therapeutic feeding center (TFC) of Hiwot Fana Comprehensive Specialized Hospital (HFCSH), eastern Ethiopia, from 1st September 2019 to 1st March 012024.MethodsA retrospective cohort study was conducted at the therapeutic feeding center of HFCSH among a randomly selected sample of 349 patients with severe acute malnutrition who were undergoing therapeutic feeding. Data were collected using a data abstraction tool and then stored in Epi-data version 4.6 and STATA version 17.0 statistical software. Descriptive statistics, Kaplan–Meier (KM) plots, median survival times, the log-rank test, and the Cox proportional hazards regression model were used to report the findings of this study. After performing the Cox proportional hazards regression, the model goodness of fit and assumptions were checked. Finally, the association between independent variables and the time to recovery in days was assessed using the multivariable Cox proportional hazards model, and the variables with a p-value &amp;lt;0.05 were considered statistically significant.ResultsThe median survival time to recovery among the patients with severe acute malnutrition was 17 days [95% confidence interval (CI): 16–18]. The incidence density recovery rate was 5.7 (95%CI, 4.9–6.6) per 100 person-days of observation. Factors that affected the time to recovery included residing in rural areas [adjusted hazard ratio (AHR) = 2.072; 95%CI = 1.336–3.215], being vaccinated according to age (AHR = 1.848; 95%CI = 1.162–2.939), and lack of analgesic administration (AHR = 0.685; 95%CI = 0.472–0.995).ConclusionThe median survival time to recovery in this study was found to be optimal. Residency, vaccination status of the child, and analgesic administration were the determinant factors. Paying attention to vaccination coverage, fever management, and pain management as part of the protocol helps reduce the length of hospital stay by facilitating recovery rates among severely malnourished children under five in Ethiopia.

Incidence, risk factors for metabolic syndrome and health systems capacity for its management amongst people living with HIV, Accra-Ghana: A study protocol.

Metabolic syndrome (MetS) refers to the clustering of three or more metabolic disorders including high blood pressure, glucose impairment, abdominal obesity, high triglycerides, and low high-density lipoproteins. MetS is increasingly being considered an epidemic among People Living With HIV (PLWH) with reports of association between HIV infection and/or antiretroviral therapy (ART) usage and development of MetS. MetS predisposes PLWH to the development of cardiovascular, kidney diseases and diabetes, decreases the quality of life, and burdens the health system. This study aims to establish the incidence, time to development and risk factors for development of MetS and it's components, and to assess the capacity of the health system to manage MetS and it's components among ART naive PLWH in Accra, Ghana. We will conduct a mixed methods study with quantitative and qualitative data collection. Our prospective cohort study would enroll adults of 18 years and above with none or less than three MetS components at baseline and follow them up at six months and one year. Demographic, lifestyle data, anthropometric, and laboratory data will be collected using an adapted WHO Steps Survey questionnaire. The WHO Service Availability and Readiness Questionnaire (SARA) will be adapted to collect information on capacity across the six WHO building blocks. Key informant interviews will be conducted with HIV coordinators at the national, regional, and facility levels. In-depth interviews will be conducted with PLWH from the cohort who develop MetS or MetS components during their follow-up. Data will be analysed using proportions, Kaplan Mier time to event analysis, fitting of Cox proportional hazard regression models for risk factors, and generation of themes from qualitative data. This study will generate data on the incidence, time to development, risk factors for MetS and MetS components development, and health systems capacity for MetS management among PLWH. Findings would inform revisions to the guidelines and policies for HIV care in Ghana, Africa, and beyond, ultimately improving MetS prevention and management among the vulnerable population of PLWH.

Racial disparities in presenting stage and surgical management among octogenarians with breast cancer: a national cancer database analysis.

As the US faces a diverse aging population, racial disparities in breast cancer outcomes among elderly patients remain poorly understood. We evaluate the association of race with presenting stage, treatment, and survival of invasive breast cancer among octogenarians. Women (≥ 80years) with invasive breast cancer were identified in 2004-2020 NCDB. To facilitate comparison, only non-Hispanic Black and non-Hispanic White patients were included; patients of Hispanic ethnicity were excluded. Demographics, tumor characteristics, and treatments were assessed by race. Overall survival was compared using the logrank test. Multivariable logistic and Cox proportional hazard regression models were developed to evaluate the independent association of race with outcomes of interest. Of 222,897 patients, 19,059 (8.6%) were Black. Most patients had stage I ER + HER2- invasive ductal carcinoma. Black patients more frequently had greater comorbidities, low income and education, and advanced stage (p < 0.001 each; ref: White). Following adjustment, Black women had increased likelihood of Stage III/IV over time, as well as increased odds of chemotherapy (AOR 1.22, 95% CI 1.15 - 1.29) and non-operative management (AOR 1.82, 95% CI 1.72 - 1.92; ref: White). Although Black patients had lower survival rates compared to White, race was not associated with 5-year mortality following adjustment for stage, receipt of surgery, and adjuvant treatments (p = 0.34). Inferior survival among elderly Black patients appears be driven by advanced stage at presentation. While such disparities are narrowing in the present era, future work must consider upstream interventions to ensure equitable outcomes for all races.

Association of serum uric acid with all-cause and cardiovascular mortality in cardiovascular disease patients

The relationship between serum uric acid (SUA) and mortality in patients with cardiovascular disease (CVD) remains controversial. We aimed to explore the relationship between SUA and all-cause mortality (ACM) and cardiovascular mortality (CVM) in adult patients with CVD. This cohort study included 3977 patients with CVD from the National Health and Nutrition Examination Survey (2005–2018). Death outcomes were determined by linking National Death Index (NDI) records through December 31, 2019. We explored the association of SUA with mortality using weighted Cox proportional hazards regression models, subgroup analysis, Kaplan-Meier survival curves, weighted restricted cubic spline (RCS) models, and weighted threshold effect analysis among patients with CVD. During a median follow-up of 68 months (interquartile range, 34–110 months), 1,360 (34.2%) of the 3,977 patients with cardiovascular disease died, of which 536 (13.5%) died of cardiovascular deaths and 824 (20.7%) died of non-cardiovascular deaths. In a multivariable-adjusted model (Model 3), the risk of ACM (HR 1.38, 95% CI 1.16–1.64) and the risk of CVM (HR 1.39, 95% CI 1.04–1.86) for participants in the SUA Q4 group were significantly higher. In patients with CVD, RCS regression analysis revealed a nonlinear association (p < 0.001 for all nonlinearities) between SUA, ACM, and CVM in the overall population and in men. Subgroup analysis showed a nonlinear association between ACM and CVM with SUA in patients with CVD combined with chronic kidney disease (CKD), with thresholds of 5.49 and 5.64, respectively. Time-dependent ROC curves indicated areas under the curve of 0.61, 0.60, 0.58, and 0.55 for 1-, 3-, 5-, and 10-year survival for ACM and 0.69, 0.61, 0.59, and 0.56 for CVM, respectively. We demonstrate that SUA is an independent prognostic factor for the risk of ACM and CVM in patients with CVD, supporting a U-shaped association between SUA and mortality, with thresholds of 5.49 and 5.64, respectively. In patients with CVD combined with CKD, the association of the ACM and the CVM with SUA remains nonlinear.

Durvalumab Following Chemoradiotherapy for Stage III Non-small Cell Lung Cancer: Differences in Survival Based on Age and Post-Progression Systemic Therapy.

Concurrent chemoradiotherapy (cCRT) followed by 1 year of the immune checkpoint inhibitor (ICI) durvalumab is standard of care for patients with unresectable stage III nonsmall cell lung cancer (NSCLC). The purpose of this study was to evaluate survival outcomes of (1) cCRT followed by durvalumab in patients older versus younger than 75 years of age and (2) post-progression treatment with ICI alone versus chemotherapy alone versus combined ICI and chemotherapy. Patients with unresectable stage III NSCLC treated between January 2018 and July 2023 with cCRT followed by durvalumab were identified retrospectively. Progression-free survival (PFS) and overall survival (OS) from ICI start were analyzed in three cohorts aged < 65, 65-74, and ≥ 75 years. Multivariable Cox proportional hazard regression modelling of factors associated with OS was undertaken. Logistic regression analysis identified risk factors of early durvalumab discontinuation for toxicity. Time from first salvage drug treatment to death (OS-2) was described. A total of 472 patients were analyzed: the proportions aged < 65, 65-74, and ≥ 75 years were 34.3%, 42.8%, and 22.9%, respectively. Odds of early durvalumab discontinuation was 2.2-fold greater in the oldest (versus youngest) cohort. Age associated differences in median PFS (26.7months, 20.3months, and 14.2months; p< 0.001) and OS (60.8months, 44.4 months, and 27.6 months; p< 0.001) were observed. On multivariable analysis, factors associated with shorter OS were age ≥ 75years (versus < 65), performance status 2/3 (versus 0/1), stage IIIC (versus IIIA), neutrophil to lymphocyte ratio (per 7.43 unit increase), Charlson comorbidity index (per 1 unit increase), tumoral PD-L1 expression < 1% (versus ≥ 50%, 1-49%, or unknown), and squamous histology (versus non-squamous). Of 264 patients with disease progression, 48.5% received subsequent drug therapy. Median OS-2 was longer with ICI alone (9.9 months) or ICI-chemotherapy (11.8 months) than platinum doublet chemotherapy (6.7 months.) For recurrences < 6 months from the last durvalumab infusion, OS-2 were similar across treatment groups. In the studied cohort, OS was significantly shorter for patients ≥ 75 years of age treated with cCRT followed by durvalumab compared to those < 65 years. Post-progression systemic therapy was associated with modest efficacy, underscoring the need for new therapies.

Patterns of protein intake and mortality in patients with type 2 diabetes: results from NHANES

We aimed to look at the potential relationship between patterns of protein intake and risk of death in adults with type 2 diabetes. We included 4646 adults with type 2 diabetes participating in NHANES (1999–2018). We estimated intake of proteins from 11 animal- and plant-based food groups and then, used principal component analysis to explore data-driven patterns of protein intake. All-cause mortality was ascertained through linkage to National Death Index until December 31, 2019 (n = 969 deaths). Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Four dietary protein patterns were identified: “healthy” (high in proteins from legumes, fruits, nuts, seeds, and fish and low in red meat protein), “red meat and egg” (high in red meat and egg proteins and low in fish and poultry proteins), “vegetables/fish” and “dairy/nuts” patterns. The HRs of all-cause mortality for the highest compared to the lowest quartile of “healthy” and “red meat and egg” protein patterns were, respectively, 0.77 (95%CI: 0.62, 0.97; Ptrend = 0.014) and 1.28 (95%CI: 1.06, 1.54; Ptrend = 0.033). Greater adherence to a healthy protein pattern may be associated with a reduced risk of death in patients with type 2 diabetes, while greater adherence to a dietary pattern rich in red meat and egg proteins and low in fish and poultry proteins may be associated with a higher risk.

Association between dietary omega-3 fatty acid intake and all-cause mortality in patients with osteoarthritis: a population-based prospective cohort study

A correlation between omega-3 polyunsaturated fatty acids (omega-3 PUFAs) and osteoarthritis (OA) incidence has been established, but research on the long-term outlook of OA patients remains limited. This study investigates the association between omega-3 PUFA intake and the risk of all-cause and cardiovascular (CV) mortality in the U.S. OA population. A cohort of 3,467 OA patients from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018 was studied. Cox proportional hazards regression models, Kaplan-Meier curves, and subgroup analyses were used to evaluate the relationship between omega-3 PUFA intake and mortality. The dose-response relationship was examined using a restricted cubic spline (RCS) model. Among the 3,467 OA patients, there were 459 all-cause deaths and 175 CV deaths. Omega-3 PUFAs were significantly negatively correlated with all-cause mortality (95% CI: 0.59–0.93, p = 0.011) but not with CV mortality (95% CI: 0.29–1.04, p = 0.056). Higher omega-3 PUFA intake was associated with a 49% decrease in all-cause mortality. Kaplan-Meier curves showed lower all-cause mortality rates in those with higher omega-3 PUFA intake. The inverse correlation was more pronounced among individuals living with a partner. The dose-response analysis indicated a linear negative relationship between omega-3 PUFA intake and all-cause mortality. Increased intake of omega-3 PUFAs is associated with a decreased risk of all-cause mortality in OA patients.

The Prognostic Significance of Plasma Beta2-Glycoprotein I Levels in Hepatocellular Carcinoma Patients.

Beta2-glycoprotein I (β2-GPI) is a plasma glycoprotein with multiple physiological functions, but its relationship with hepatocellular carcinoma (HCC) is still poorly understood. HCC is one of the most common forms of liver cancer and is a leading cause of cancer-related death worldwide. This study aimed to investigate the association between β2-GPI and liver cancer and further validate its potential as a biomarker for HCC. Thirty-six patients diagnosed with HCC at the Division of Gastroenterology and Hepatology, E-Da Hospital, Taiwan, were included in the study. The expression levels of β2-GPI in plasma specimens from patients with HCC were determined by enzyme immunoassay and analyzed in relation to clinicopathological variables using the Chi-square test or Fisher's exact test. The predictive significance of β2-GPI for both overall survival (OS) and disease-free survival (DFS) was assessed using Kaplan-Meier estimates, and the statistical significance of differences was evaluated through the log-rank test. Cox proportional hazards regression models were used to evaluate the association between OS/DFS time and clinicopathological characteristics. Results: Plasma β2-GPI levels were significantly lower in patients with HCC compared to non-cancer controls and significantly correlated with aspartate aminotransferase (AST) levels of HCC. High plasma β2-GPI levels were significantly associated with better OS and DFS in HCC patients. Furthermore, in multiple variates analyses, OS was found to be significantly better in HCC patients with higher plasma β2-GPI expression. Elevated levels of β2-GPI protein in the plasma of HCC patients were identified as an independent factor predictive of improved OS and DFS. Activating β2-GPI in individuals at high risk could serve as a promising way for mitigating the progression of HCC.

The Frequency of Meal-Replacement Products Drinking and All-Cause, CVD, and Cancer Mortality

Objectives: Our study aimed to assess the associations between meal-replacement (MR) drinking and risks of all-cause, cardiovascular and cerebrovascular disease (CVD), and cancer mortality. Methods: The study was based on 6770 adults aged 20 years or older from the National Health and Nutrition Examination (NHANES) 2003–2006 with linked mortality data from the National Death Index for linked mortality records (until 31 December 2019). Respondents were categorized into four groups according to the frequency of MR drinking: ≤1 time per month (seldom), 2–3 times per month (monthly), 1–6 times per week (weekly), and ≥1 time per day (daily). The adjusted hazard ratios (aHRs) of MR drinking with all-cause, CVD, and cancer mortality were estimated by Cox proportional hazards regression models. Likelihood ratio tests were used to find potential interactions of MR drinking with age, sex, and BMI. Results: During a median follow-up of 14.4 years, a total of 1668 death events were recorded among the study population. Compared to respondents who seldom drank MR, daily and weekly drinkers had greater risks of all-cause mortality (aHRs and 95% confidence intervals [CI]: 1.52 [1.17–1.97] for daily; 1.54 [1.24–1.91] for weekly). Stratified analyses indicated that the effects of MR on all-cause mortality were different between females and males and were more substantial among females (P for interaction: 0.003; daily female drinkers vs. daily male drinkers: 2.01 [1.40–2.90] vs. 1.24 [0.85–1.81]; weekly female drinkers vs. weekly male drinkers: 1.68 [1.26–2.24] vs. 1.36 [0.97–1.91]). Conclusions: Daily and weekly MR drinking might increase the risk of all-cause mortality.

Taxane/anthracycline combinations reduced incidence of breast cancer recurrence in young women across molecular subtypes: a real-world evidence of Taiwan from 2011 to 2019.

Adolescent and young adult (AYA) patients with breast cancer generally have poor prognoses and a higher risk of secondary cancers compared to those at the same cancer stage. Notably, AYA patients in Asia exhibit a higher incidence rate of breast cancer, with Luminal A as the predominant molecular subtype, which contrasts with the trends observed in Western countries. This study aims to compare the efficacy of Taxane/Anthracycline combination-based regimens (TACB) versus Anthracycline-based regimens (AB) in AYA patients with stage I-II breast cancer, focusing on different molecular subtypes. This study utilized data from the Taiwan National Health Insurance Research Database (NHIRD) and the Taiwan Cancer Registry (TCR) from 2011 to 2019. The study cohort included patients aged 15 to 39years who were diagnosed with stage I-II breast cancer and received either TACB or AB regimens. Propensity score matching and Cox proportional hazards regression models were used to calculate the hazard ratios (HR) for recurrence. The results showed that TACB regimens significantly reduced the risk of recurrence compared to AB regimens across all patients (aHR 0.73, 95% CI 0.55-0.97). Specifically, for low/middle-recurrence risk groups, the aHR was 0.68 (95% CI 0.49-0.96), and for high-recurrence risk groups, it was 0.43 (95% CI 0.21-0.87). The analysis further indicated no significant differences in recurrence risk between AYA and non-AYA patients using TACB regimens. The TACB regimens showed a more favorable prognosis than AB regimens across all molecular subtypes. Furthermore, TACB regimens not only outperformed AB treatments but also closed the gap in prognostic outcomes between AYA and non-AYA patients. We believe the findings of this study are highly reliable and can provide valuable guidance for physicians in choosing the most appropriate treatment strategies for AYA patients with stage I-II breast cancer.

Erectile Dysfunction Risk Among Patients With Diabetes Mellitus Using Sodium-Glucose Cotransporter 2 Inhibitors.

The aim of this study was to explore the incidence of new-onset erectile dysfunction (ED) in diabetes mellitus (DM) patients with sodium-glucose cotransporter 2 inhibitors (SGLT2I) use compared with a control group of non-SGLT2I use by propensity score matching approach. Cox proportional hazards regression models were used to examine the effect of SGLT2I and risk factors on the risk of developing ED, presented as a hazard ratio with a 95% confidence interval. One lakhs fifty nine thousand seven hundred seventy three patients with DM using SGLT2I and 159,773 propensity score matching patients with DM who had never used SGLT2I were included. SGLT2I users had a higher risk of ED than the non-SGLT2I users (adjusted hazard ratio = 1.55, 95% confidence interval = 1.40-1.72). The likelihood of developing ED was higher in patients with SGLT2I use was found.

Associations of polycyclic aromatic hydrocarbons exposure with mortality and effect modification by folate biomarkers in a prospective population

The associations of folate biomarkers and polycyclic aromatic hydrocarbons (PAHs) in the general population remain unclear. Therefore, this study aimed to examine whether folate biomarkers are associated with PAHs, and whether folate biomarkers can mitigate adverse health outcome caused by PAHs. This prospective cohort study included 11,246 participants from the National Health and Nutrition Examination Survey (NHANES), which documented 1303 deaths over a mean follow-up of 9.1 years. Multivariable linear regression models were used to examine the relationship between urinary individual PAHs and folate biomarkers. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios and 95 % CIs for the associations of PAHs and folate biomarkers with CVDs mortality and all-cause mortality. We found negative associations between folate in red blood cells (RBC) and urinary 1-Hydroxyphenanthrene (percentage change for a 2·7 fold-increase in folate −4.19 %, 95 % CI -5.80 % to −2.56 %CI), 2-Hydroxyfluorene (−6.66 %, −7.84 % to −5.49 %), 3-Hydroxyfluorene (−5.78 %, −6.77 % to −4.78 %)) and 1-Hydroxynapthalene (−2.75 %, −3.48 % to −2.01 %). The associations between serum folate and PAHs were consistent with those observed for RBC folate, and negative associations were also found between serum folate and 2-Hydroxynapthalene (−4.10 %, −5.26 % to −2.94 %). Within the lowest quartile of folate levels in RBC, there are strong associations of 2-Hydroxyfluorene, 3-Hydroxyfluorene, 1-Hydroxynapthalene, and 2-Hydroxynapthalene with elevated risk of CVDs mortality [HRs (95 % CI) >1]. As folate levels in RBC increase to the third and fourth quartiles, these associations no longer exist [HRs (95 % CI) <1, P-interaction<0.05]. The positive associations between urinary PAHs and CVDs mortality are also eliminated as serum folate levels rise (HRs (95 % CI) <1, P-interaction<0.05). Furthermore, we also found higher levels of folate in both RBC and serum can greatly reduce the adverse impact of 1-Hydroxynapthalene on all-cause mortality. Consistent results were also validated in daily dietary folate and the folic acid supplement intake. Our study highlighted a robust negative relationship between urinary PAHs and folate. Additionally, folate was found to effectively mitigate mortality caused by PAHs, although we did not observe a direct reduction in mortality attributable to folate.

PD-L1 (22C3) expression and prognostic implications in esophageal squamous cell carcinoma

Programmed cell death-ligand 1 (PD-L1) clone 22C3 is the only Food and Drug Administration-approved companion diagnostic test for pembrolizumab for the treatment of esophageal squamous cell carcinoma (ESCC). However, prior studies conducted in Asia and Europe have used various PD-L1 antibody clones other than 22C3. We aimed to study the expression profile of PD-L1, specifically of clone 22C3, in ESCC and its significance with regards to histological features, clinical parameters, and overall survival in a case series from two large US hospital systems. PD-L1 (22C3) immunohistochemistry was performed on 82 specimens obtained from 75 patients. Electronic medical records were reviewed to obtain the clinical and follow-up data. Of these specimens, 39 % (32/82) were negative for PD-L1 (22C3) expression (combined positive score (CPS) of 0). The remaining 50 specimens were positive, with CPSs ranging from 1 to 100. Treated specimens showed decreased PD-L1 (22C3) expression compared to untreated specimens. In the multivariate Cox proportional hazards regression model, PD-L1 (22C3) expression was shown to be a favorable prognostic factor for overall survival (p = 0.03, hazard ratio 0.16) only when the CPSs were ≥ 25, independent of surgery, definitive chemotherapy and/or radiotherapy, immunotherapy, and initial clinical stages. We performed a comprehensive study to investigate the expression profile of PD-L1 clone 22C3 in the US patients with ESCC. Our analysis showed that PD-L1 (22C3) expression decreased in treated specimens, and a CPS of ≥25 was associated with a favorable prognosis.

Association between the triglyceride to high density lipoprotein cholesterol ratio and the incidence of metabolic dysfunction-associated fatty liver disease: a retrospective cohort study

BackgroundThe triglyceride to high density lipoprotein cholesterol ratio (TG/HDL-C) is a confirmed predictive factor for insulin resistance and is suggested to be closely related to metabolic dysfunction-associated fatty liver disease (MAFLD), but previous research is inconclusive. The association between TG/HDL-C and MAFLD incidence was further explored in this large-sample, long-term retrospective cohort study.MethodsIndividuals who participated in the Kailuan Group health examination from July 2006 to December 2007 (n = 49,518) were included. Data from anthropometric and biochemical indices, epidemiological surveys, and liver ultrasound examinations were collected and analysed statistically, focusing on the association between TG/HDL-C and the incidence of MAFLD.ResultsDuring a mean follow-up period of 7.62 ± 3.99 years, 24,838 participants developed MAFLD. The cumulative MAFLD incidence rates associated with the first to fourth quartiles of TG/HDL-C were 59.16%, 65.04%, 71.27%, and 79.28%, respectively. The multivariate Cox proportional hazards regression model revealed that the hazard ratios (HRs) (95% CIs) for MAFLD in the second, third, and fourth quartiles were 1.20 (1.16–1.25), 1.50 (1.45–1.56), and 2.02 (1.95–2.10) (P for trend < 0.05), respectively, and the HR (95% CI) corresponding to an increase of one standard deviation in TG/HDL-C was 1.10 (1.09–1.11) (P < 0.05). Subsequent subgroup and sensitivity analyses yielded results similar to those of the main analyses.ConclusionsTG/HDL-C is independently associated with MAFLD risk, with higher TG/HDL-C indicating greater MAFLD risk.