Cox Proportional Hazards Regression Research Articles

Reassessing the Role of Low PSA in Prognosis Across Grades of Prostate Cancer: A Cohort Study.

Prior studies have concentrated exclusively on how different prostate-specific antigen (PSA) levels affect the prognosis of high-grade prostate cancer (PCa), often overlooking the prognosis of low-grade PCa. The present cohort study included individuals diagnosed with PCa from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2021. The all-cause mortality (ACM) and prostate cancer-specific mortality (PCSM) for each treatment group was calculated stratified by the four PSA levels (≤ 4.0, 4.1-10.0, 10.1-20.0, and > 20.0 ng/mL). Fine and Gray competing-risks analyses were conducted to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Cox proportional hazards regression analyses using PSA as a continuous variable with restricted cubic splines (RCS) were conducted to allow for potential nonlinear relationships. This study encompassed 416,825 male patients diagnosed with PCa. Compared to individuals with PSA value between 4.1 and 10.0 ng/mL, a significant association between low levels of PSA (≤ 4.0 ng/mL) and an increased risk of ACM (AHR = 1.15, 95% CI: 1.12-1.19; p < 0.001) and PCSM (AHR = 1.49, 95% CI: 1.38-1.61; p < 0.001) was observed. Additionally, the increased risk of ACM (AHR = 1.35, 95% CI: 1.29-1.40; p < 0.001) and PCSM (AHR = 1.84, 95% CI: 1.67-2.02; p < 0.001) are more pronounced within the first 5 years post-diagnosis. In most subgroups, similar results were observed. The RCS curves further corroborated the correlation between PSA value and the risk of mortality. Low PSA levels are notably linked to a heightened risk for both ACM and PCSM, irrespective of the grade of PCa being high or low. There is a need to initiate new studies that tackle novel diagnostics and therapeutics.

Association of oxidative balance score with the risk of all-cause and CVD mortality in younger US adults with diabetes

Oxidative balance score (OBS) is a composite measures that assess the balance between pro-oxidant and antioxidant factors in an individual’s diet and lifestyle, with higher scores indicating greater antioxidant exposure. Despite its potential significance, there is a limited body of research exploring the relationship between OBS and all-cause and cardiovascular disease (CVD) mortality specifically in younger patients with diabetes. We aimed to investigate the possible relationship between OBS and all-cause and CVD mortality in younger patients with diabetes. Data for this study were obtained from the 2003–2018 NHANES. This study enrolled 3501 participants. The endpoints were all-cause and CVD mortality, determined by the National Death Index (NDI). OBS, which consists of 16 dietary factors and 4 lifestyle factors, is categorized into pro-oxidants and antioxidants. The OBS was categorized into four quartiles (Q1-Q4). We used multivariable Cox proportional hazards regression models to examine the association between continuous and quartile measures of OBS, lifestyle OBS (lifestyle antioxidants such as physical activity, etc., and lifestyle pro-oxidants such as alcohol, smoking, etc.), and dietary OBS (dietary antioxidants such as fiber, β-carotene, riboflavin, etc., and dietary pro-oxidants, such as total fat, etc.) with all-cause and CVD mortality. Additionally, we explored restricted cubic spline (RCS) analysis and also performed subgroup analyses and interaction tests. The occurrence of 409 all-cause deaths (11.7%) and 108 CVD-related deaths (3.1%) was recorded during the follow-up period. Our results found that OBS, lifestyle OBS, and dietary OBS were negatively associated with patients’ all-cause and CVD mortality. The RCS analysis further validated the association of a linear negative correlation between OBS and all-cause and CVD mortality. The results of our subgroup analyses revealed that the negative association between OBS and CVD mortality may be influenced by alcohol use. In conclusion, results from a nationally representative study of younger American patients with diabetes suggest a negative association between OBS, lifestyle OBS, and dietary OBS and all-cause and CVD mortality. Antioxidant-rich diets and lifestyle improvements are essential for reducing all-cause and CVD mortality in patients.

Prognostic impact of one-year permanent pacemaker implantation after mitral valve surgery with the Cox-maze procedure.

This study aimed to evaluate the prognostic impact of permanent pacemaker (PPM) implantation within the first year after mitral valve (MV) surgery combined with the Cox-maze procedure, focusing on long-term outcomes, including overall mortality, infective endocarditis (IE), and ischaemic stroke. We conducted a retrospective cohort study using data from the National Health Insurance Service (NHIS) in South Korea, identifying 10,127 patients who underwent MV surgery with the Cox-maze procedure between 2005 and 2020. Patients were classified into the PPM and non-PPM groups based on PPM implantation within one year postoperatively. The primary outcome was overall mortality, and secondary outcomes included risk factors for overall mortality, IE and ischaemic stroke. Multivariable Cox proportional hazards regression and Fine-Gray competing risk models were utilized for statistical analysis. Of the total cohort, 178 patients (1.76%) underwent PPM implantation. The overall mortality during the follow-up period was 20.5%, with no significant difference between the PPM and non-PPM groups. PPM implantation was not a significant risk factor for overall mortality (Hazard ratio [HR], 0.825; 95% confidence interval [CI], 0.598-1.140; p = 0.244) or ischaemic stroke. However, PPM implantation was associated with a significantly increased risk of IE (HR, 2.015; 95% CI, 1.179-3.442; p = 0.010). PPM implantation within the first year after MV surgery with the Cox-maze procedure does not significantly impact long-term mortality or ischaemic stroke risk but is associated with an increased risk of IE. The Cox-maze procedure remains advisable for patients with atrial fibrillation undergoing MV surgery.

Stratified Impact of Therapies on Anaplastic Thyroid Cancer Outcomes in the Pre-Gene-Targeted Therapy Era.

Anaplastic thyroid cancer (ATC) is a highly lethal disease, often diagnosed with advanced locoregional and distant metastases, resulting in a median survival of just 3-5 months. This study determines the stratified effectiveness of baseline treatments in all combinations, enabling precise prognoses prediction and establishing benchmarks for advanced therapeutic options. The study extracted a cohort of pathologically confirmed ATC patients from the Surveillance, Epidemiology, and End Results program. Overall, 1879 patients from 2000 to 2018 were identified from the database. Kaplan-Meier survival curve estimation and Cox proportional hazard regression were applied. Overall, compared with no treatment, surgery raised 1-year overall survival (OS) from 0.6% to 30% and median survival from <1 month to 3 months in ATC patients. For stage IVa, surgery increased 1-year OS from 21.5% to 71.8% and median survival from 2 to 23.5 months, and in stage IVb, surgery increased 1-year OS from 9.4% to 41.3% and median survival from 2 to 7 months; however, in stage IVc, the benefits of surgery were not markedly different from non-surgical approaches. When combined with surgery, other effective non-surgical ATC treatments demonstrated a surgery-dominant synergistic effect, particularly for stages IVa and IVb ATC, but not for stage IVc ATC. Our study provides insights into stratified baseline treatments for patients with ATC in all stages, emphasizing surgery's vital role in a multimodal approach.

Prediction of hip fracture by high-resolution peripheral quantitative computed tomography in older Swedish women.

The socioeconomic burden of hip fractures, the most severe osteoporotic fracture outcome, is increasing and the current clinical risk assessment lacks sensitivity. This study aimed to develop a method for improved prediction of hip fracture by incorporating measurements of bone microstructure and composition derived from high-resolution peripheral quantitative computed tomography (HR-pQCT). In a prospective cohort study of 3028 community-dwelling women aged 75 to 80, all participants answered questionnaires and underwent baseline examinations of anthropometrics and bone by dual x-ray absorptiometry (DXA) and HR-pQCT. Medical records, a regional x-ray archive, and registers were used to identify incident fractures and death. Prediction models for hip, major osteoporotic fracture (MOF), and any fracture were developed using Cox proportional hazards regression and machine learning algorithms (neural network, random forest, ensemble, and XGBoost). In the 2856 (94.3%) women with complete HR-pQCT data at 2 tibia sites (distal and ultra-distal), the median follow-up period was 8.0years, and 217 hip, 746 MOF, and 1008 any type of incident fracture occurred. In Cox regression models adjusted for age, BMI, clinical risk factors (CRF), and femoral neck bone mineral density (FN BMD) the strongest predictors of hip fracture were tibia total volumetric BMD and cortical thickness. The performance of the Cox regression-based prediction models for hip fracture was significantly improved by HR-pQCT (time-dependent AUC; area under receiver operating characteristic curve at 5years of follow-up 0.75 [0.64-0.85]), compared to a reference model including CRFs and FN BMD (AUC = 0.71 [0.58-0.81], p<.001) and a FRAX risk score model (AUC = 0.70 [0.60-0.80], p<.001). The Cox regression model for hip fracture had a significantly higher accuracy than the neural network-based model, the best-performing machine learning algorithm, at clinically relevant sensitivity levels. We conclude that the addition of HR-pQCT parameters improves the prediction of hip fractures in a cohort of older Swedish women.

Opportunistic assessment of steatotic liver disease in lung cancer screening eligible individuals.

Steatotic liver disease (SLD) is a potentially reversible condition but often goes unnoticed with the risk for end-stage liver disease. To opportunistically estimate SLD on lung screening chest computed tomography (CT) and investigate its prognostic value in heavy smokers participating in the National Lung Screening Trial (NLST). We used a deep learning model to segment the liver on non-contrast-enhanced chest CT scans of 19,774 NLST participants (age 61.4±5.0 years; 41.2% female) at baseline and on the 1-year follow-up scan if no cancer was detected. SLD was defined as hepatic fat fraction (HFF) ≥5% derived from Hounsfield unit measures of the segmented liver. Participants with SLD were categorized as lean (body mass index [BMI]<25kg/m2) and overweight (BMI≥25kg/m2). The primary outcome was all-cause mortality. Cox proportional hazard regression assessed the association between (1) SLD and mortality at baseline and (2) the association between a change in HFF and mortality within 1 year. There were 5.1% (1000/19,760) all-cause deaths over a median follow-up of 6 (range, 0.8-6) years. At baseline, SLD was associated with increased mortality in lean but not in overweight/obese participants as compared to participants without SLD (hazard ratio [HR] adjusted for risk factors: 1.93 [95% confidence interval 1.52-2.45]; p=0.001). Individuals with an increase in HFF within 1 year had a significantly worse outcome than participants with stable HFF (HR adjusted for risk factors: 1.29 [1.01-1.65]; p=0.04). SLD is an independent predictor for long-term mortality in heavy smokers beyond known clinical risk factors.

Cumulative Burden of Lifestyle Risk Factors on Cancer in Older Korean Men: A Nationwide Retrospective Cohort Study

Background/Objectives: Cancer prevalence is increasing globally due to aging populations. Certain lifestyles are associated with cancer; however, the long-term combined effects of lifestyle factors on cancer has not been investigated. This study aimed to investigate the cumulative effect of lifestyle risk factors over 8 years on cancer in older Korean men. Methods: We assessed 64,756 men aged ≥65 years at the baseline year (2008–2009) using data from the National Health Insurance Service-Senior Cohort. Lifestyle factors, including smoking status, alcohol consumption, and physical activity, were evaluated over four consecutive phases (2002–2003, 2004–2005, 2006–2007, and 2008–2009) of health check-ups, and each participant’s overall lifestyle risk score was calculated after considering the value of a single poor lifestyle factor in each phase as 1, with a cumulative score ranging between 0 and 12. According to the lifestyle risk scores, the hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard regression analysis. Results: Of the 64,756 men, 13,130 cases of cancer developed. The risk of cancer increased as the number of poor lifestyle factors and lifestyle risk score increased from the baseline year during the four phases. Compared to a score of 0–2, the HRs for cancer were 1.10 (0.98–1.23), 1.54 (1.37–1.73), and 1.72 (1.48–1.99) for scores of 3–5, 6–8, and 9–12, respectively. Conclusions: The risk of cancer increased as the cumulative burden of poor lifestyle habits over 8 years increased. Therefore, practicing and maintaining healthy lifestyles is crucial to preventing cancer in older Korean men.

Impact of time in tight range on all-cause and cardiovascular mortality in type 2 diabetes: A prospective cohort study.

Currently, there is a lack of evidence regarding time in tight range (TITR) and long-term adverse outcomes. We aimed to investigate the association between TITR and the risk of all-cause and cardiovascular mortality among patients with type 2 diabetes. A total of 6061 patients with type 2 diabetes were prospectively recruited in a single centre. TITR was measured with continuous glucose monitoring (CGM) at baseline and was defined as the percentage of time in the target glucose range of 3.9-7.8 mmol/L (70-140 mg/dL) during a 24-h period. Cox proportion hazard regression models were used to examine the association between TITR and the risk of all-cause and cardiovascular mortality. During a median follow-up period of 10.9 years, 1898 (31.3%) death events were confirmed, with 689 (11.4%) due to cardiovascular mortality. The restricted cubic spline revealed significant linear relationships between lower TITR and higher risks of all-cause and cardiovascular mortality (p for linearity <0.01). In the fully adjusted model including glycated haemoglobin A1c, each 10% decrease in TITR was associated with 4% (95% confidence interval, 1.01-1.06) increased risk of all-cause mortality and 4% (95% confidence interval, 1.00-1.08) increased risk of cardiovascular mortality. Subgroup analyses showed that the linear relationship between TITR and all-cause mortality risk was sustained in patients with haemoglobin A1c <7.0% and patients with fasting plasma glucose <7.0 mmol/L. Lower TITR is associated with an increased risk of all-cause and cardiovascular mortality in patients with type 2 diabetes, indicating that tight glycaemic control within the physiological range may be crucial for reducing long-term mortality risk, especially in those with seemingly well-controlled diabetes.

Association Between Liver Fibrosis and Risk of Incident Stroke and Mortality: ALarge Prospective Cohort Study.

There is a well-established relationship between liver conditions and cardiovascular diseases. However, uncertainty persists regarding the contribution of liver fibrosis to major stroke types including ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage at the population level. In this large prospective cohort study, participants without previous stroke or coronary heart disease at baseline from the UK Biobank were included. We identified participants at high probability of advanced liver fibrosis using the Fibrosis-4 index >2.67 or aspartate aminotransferase to platelet ratio index ≥1.0. Multivariable Cox proportional hazard regression analyses were conducted to estimate hazard ratios (HRs) for liver fibrosis with the incidence of major stroke types, stroke-related death, and all-cause death. Among 379 953 participants (mean age, 56.2 [SD, 8.1] years; 44.6% men), 7396 (1.9%) had a Fibrosis-4 index >2.67 at baseline. During a median follow-up of 12.75 (interquartile range, 12.03-13.48) years, 7143 (1.9%) incident stroke cases were documented. Advanced liver fibrosis assessed by the Fibrosis-4 index was associated with an increased risk of ischemic stroke (HR, 1.94 [95% CI, 1.70-2.22]), intracerebral hemorrhage (HR, 2.14 [95% CI, 1.63-2.81]), subarachnoid hemorrhage (HR, 1.90 [95% CI, 1.27-2.84), stroke-related death (HR, 2.20 [95% CI, 1.73-2.80]), and all-cause death (HR, 2.59 [95% CI, 2.46-2.73]). Using the aspartate aminotransferase to platelet ratio index as an alternative score, liver fibrosis was correlated with magnified risk of intracerebral hemorrhage (HR, 3.76 [95% CI, 2.38-5.93]) and subarachnoid hemorrhage (HR, 3.05 [95% CI, 1.51-6.13]) compared with ischemic stroke (HR, 1.58 [95% CI, 1.17-2.14]). Restricted cubic spline analysis showed nonlinear associations of the Fibrosis-4 index and aspartate aminotransferase to platelet ratio index with stroke incidence and all-cause death. Liver fibrosis is associated with increased risk of incident stroke and death among people without previous stroke or cardiovascular events, with particularly greater risk of intracerebral hemorrhage and subarachnoid hemorrhage. Noninvasive indices of liver fibrosis may serve as an easily accessible marker to detect individuals facing elevated risk of stroke and death in the primary prevention settings.

Risk factors for pancreatic cancer in individuals with intraductal papillary mucinous neoplasms and no high-risk stigmata during up to 5 years of surveillance: a prospective longitudinal cohort study

BackgroundCyst size, its growth rate, and diameter of the main pancreatic duct (MPD) are all associated with pancreatic carcinoma prevalence in intraductal papillary mucinous neoplasms (IPMNs).ObjectiveTo examine the above factors...

The obesity paradox in osteoporosis risk among older adults is mostly driven by women: a population-based prospective study

ObjectivesThe obesity paradox is common among older adults at risk for various diseases. Although this paradox has also been observed in the association between obesity and osteoporosis, the available evidence remains controversial. This study aimed to investigate the association between obesity and OP risk in an older population.MethodsA cross-sectional and prospective study was conducted using data from 177,734 participants in the UK Biobank. The association of body mass index (BMI), waist circumference (WC), and fat percentage with BMD was examined using Spearman correlation analysis with baseline BMD data. Cox proportional hazards regression analysis was used to investigate the association between obesity and OP risk. Restricted cubic spline (RCS) were used to assess the nonlinear associations of BMI, WC, and fat percentage with OP.ResultsBaseline cross-sectional analyses revealed a significant positive association between BMI, WC, and fat percentage with BMD in women, whereas this association was very weak in men. A total of 8,998 OP patients were identified during a median follow-up period of 13.7 years. Cox analyses showed that obesity as defined by BMI, WC, and fat percentage was associated with a 33%, 23%, and 31% reduction in the risk of OP in older women but not in men, respectively. Conjoint analysis showed that lower BMI was associated with increased risk of OP in older adults, whereas the lowest risk was observed in women with higher BMI and higher body fat. RCS revealed an inverse J-shaped nonlinear association between obesity metrics and OP risk in women.ConclusionLower BMI is an independent risk factor for OP in older adults, and the obesity paradox for OP risk exists only in women.

Can HIV Post-Exposure Prophylaxis Services Change the Sexual Behavior Characteristics of Men Who Have Sex with Men? A Cohort Study in Guangzhou, China.

This study examines the impact of HIV post-exposure prophylaxis (PEP) on sexual behavior changes in men who have sex with men (MSM), aiming to assess a comprehensive HIV prevention strategy integrating biomedical and behavioral interventions to maximize PEP service effectiveness. From a Guangzhou MSM cohort, participants without prior PEP experience were included. The exposed group received PEP services during follow-up (June 2019-April 2022), while controls did not. Cox proportional hazard regression models assessed PEP's effects on sexual behavior changes. Of 411 participants (mean age: 30.72), 14.1% received PEP during follow-up. The exposed group showed a higher likelihood of reducing Internet partner-seeking (aHR: 3.58, 95%CI: 1.80-7.10, P < 0.001), decreasing anal intercourse partners (aHR: 3.81, 95%CI: 2.14-6.82, P < 0.001) in the past 6months, lowering last week's anal intercourse occurrences (aHR: 3.95, 95%CI: 2.33-6.68, P < 0.001), and improving condom use during past 6months' anal intercourse (aHR: 3.94, 95%CI: 1.75-8.90, P = 0.001) and the most recent anal intercourse (aHR: 4.96, 95%CI: 1.77-13.88, P = 0.002) compared to controls. To sum up, PEP services contribute significantly to positive sexual behavior changes in MSM. Strengthening behavioral interventions at PEP's baseline and follow-up stages is crucial for maximizing comprehensive preventive impact on both biomedical and behavioral aspects in MSM.

Habitual sleep duration, healthy eating, and digestive system cancer mortality

BackgroundLifestyle choices, such as dietary patterns and sleep duration, significantly impact the health of the digestive system and may influence the risk of mortality from digestive system cancer.MethodsThis study aimed to examine the associations between sleep duration, dietary habits, and mortality from digestive system cancers. The analysis included 406,584 participants from the UK Biobank cohort (54.1% women; age range: 38–73 years), with sleep duration classified as short (≤ 6 h, 24.2%), normal (7–8 h, 68.4%), and long (≥ 9 h, 7.4%). Healthy eating habits were defined as a daily intake of at least 25 g of fibre, seven portions of fruits and vegetables, and fewer than four servings of meat per week. These dietary factors were combined into a score ranging from 0 (least healthy) to 3 (healthiest). Cox proportional hazards regression analyses were conducted, with a median follow-up period of 12.6 years, ending on September 30, 2021.Results3949 participants died from cancer of the digestive system. Both short and long sleep duration were associated with an increased risk of mortality from cancer of the digestive system (1.09 (1.01–1.18) and 1.14 (1.03–1.27), respectively). Additionally, a diet score ≥ 1 was linked to a lower cancer risk (0.72–0.91 (0.59–0.96)). Adjusting for smoking, type 2 diabetes, and body mass index (BMI) status eliminated the association between sleep duration and digestive cancer mortality. The association between healthy dietary patterns and the risk of digestive system cancer mortality did not vary by sleep duration.ConclusionsAberrant sleep durations may increase the risk of mortality from digestive system cancer, potentially through smoking, higher BMI, and type 2 diabetes. However, aberrant sleep durations do not seem to reduce the protective effects of a healthy dietary pattern.

Preoperative Anemia as a Prognostic Risk Factor for Inferior Oncological Survival Following Resection for Pancreatic Ductal Adenocarcinoma.

A significant proportion of patients undergoing surgery for pancreatic ductal adenocarcinoma (PDAC) are anemic at the time of resection. In these patients, blood transfusions are omitted due to their potential negative impact on oncological outcomes. The aim of the present study was to determine the prognostic value of preoperative anemia in resected PDAC patients, irrespective of blood transfusion status. In this retrospective two-center cohort study patients who underwent resection for histologically confirmed PDAC between 2013 and 2022 were included. The prognostic role of preoperative anemia was investigated using Cox proportional-hazard regression analysis. A subgroup analysis was performed in which PDAC patients who received a perioperative blood transfusion were excluded. Among the 280 PDAC patients who were included, 110 (39%) were found to have anemia prior to surgery. Preoperative anemia was associated with increased use of blood transfusions, with a total of 44 patients (16%) requiring transfusion perioperatively. In the whole cohort, preoperative anemia was found to be an independent predictor of lower disease-free survival (DFS) (HR=1.518; 95% CI 1.103-2.090; P=0.011), but not overall survival (OS). However, when patients who received a perioperative blood transfusion were excluded from the analysis, preoperative anemia was independently associated with both lower DFS (HR=1.636; 95% CI 1.113-2.404; P=0.012) and OS (HR=1.484; 95% CI 1.036-2.127; P=0.031). Preoperative anemia was shown to be an independent risk factor for inferior oncological survival after resection for PDAC. These results support the need for increased awareness regarding the potential adverse effects of preoperative anemia on oncological outcomes in PDAC.

Abstract B002: Pre-vaccine radiation and CTLA-4 blockade increase adjuvant effects of SARS-COV-2 mRNA vaccines

Abstract Background: We recently reported that SARS-CoV-2 mRNA vaccines stimulate massive production of interferon-⍺ (IFN-⍺) (Grippin, et al., SITC, 2024) that drives a near-doubling of median OS and three-year overall survival (OS) in patients with non-small cell lung cancer (NSCLC) and metastatic melanoma (p&amp;lt;0.003) (Grippin, et al., ESMO, 2024). However, design of prospective clinical trials to validate this effect is limited by insufficient understanding of the interaction of mRNA vaccines, ICIs, and local therapies. We therefore analyzed our clinical dataset to understand whether radiation and specific ICIs augment the adjuvant effects of mRNA vaccines. Methods: We utilized institutional databases to identify and extract clinical data for patients with Stage III and Stage IV non-small cell lung cancer (NSCLC) (n=2406) and metastatic melanoma (n=756) with biopsy specimens between August 2019 and August 2023. Differences in survival between groups were assessed with Gehan-Breslow-Wilcoxon tests. Results: After controlling for 34 covariates including performance status, clinical stage, steroid use, tumor proportion score (TPS) of PDL1, disease burden at presentation, cycle of therapy, mutation status, concurrent therapies, and comorbidities with multivariate Cox-proportional hazards regression, we found that receipt of a COVID mRNA vaccine within 100 days of initiation of treatment with ICI was associated with substantial survival advantage in patients with Stage III (HR 0.46, 05% CI 0.31-0.70) and Stage IV NSCLC (HR 0.46, 95% CI 0.36-0.59). Moreover, patients with Stage III disease treated with chemoradiation followed by durvalumab experienced the greatest benefits of vaccination (HR 0.17, 95% CI 0.06-0.49). Since dual agent immunotherapy was uncommon in patients with NSCLC, we then reviewed data from patients with Stage IV melanoma treated with different ICI regimens. We found that adjuvant effects of mRNA vaccines were magnified in patients who received combination therapy with dual inhibition of CTLA-4 and PD-1 (HR 0.32, 95% CI 0.17-0.60) compared to single-agent PD-1 blockade (HR 0.63, 95% CI 0.33-1.3). Conclusions: Together, this data suggests that pre-vaccine radiation therapy and combination therapy with CTLA-4 blockade enhance the adjuvant effects of mRNA vaccines. Future work will include validation of these findings in preclinical models and prospective clinical trials. Citation Format: Adam Grippin, Sage Copling, Andrew Kim, Elliana Young, Betty Kim, John Heymach, Wen Jiang, Steven H Lin. Pre-vaccine radiation and CTLA-4 blockade increase adjuvant effects of SARS-COV-2 mRNA vaccines. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr B002.

The association between Chlamydia pneumoniae infection and prognosis in lung cancer patients: a prospective study

BackgroundThe prognostic value of Chlamydia pneumoniae (Cpn) infection in postoperative lung cancer patients remains unclear. This study aimed to evaluate the association between Cpn infection and survival in lung cancer patients.MethodsThis study included 309 newly diagnosed primary lung cancer patients from three hospitals in Fuzhou, China. Chlamydia pneumoniae IgG and IgA antibodies were detected using a micro-immunofluorescence kit and a unified questionnaire was used to collect demographic and clinical information. Follow-up was conducted every six months until August 25, 2022, or death. Patients were followed up for a median duration of 74 months. Overall survival was compared between Cpn IgA and IgG positive/negative patients. Statistical analysis included the χ2 test, Kaplan-Meier method, Log-rank test, and Cox proportional hazards regression model.ResultsCpn IgA infection status was found to be associated with lymph node metastasis in lung cancer patients. The overall survival of patients with Cpn IgA(++) was shorter compared to negative and positive patients(with IgA(-) group as the control group, P < 0.001, HR = 5.441, 95%CI: 2.341–12.645). Serum IgA positivity indicated chronic infection and was associated with poor prognosis. Multivariate analysis confirmed that Cpn IgA(++) infection was an independent risk prognostic factor for operable lung cancer patients (with IgA(-) group as the control group, HR = 3.39, 95%CI: 1.41–8.17).ConclusionThis study suggests that Cpn infection is an independent prognostic factor in lung cancer patients. Further research is needed to understand the underlying mechanisms and explore the potential of Cpn as a biomarker or therapeutic target for lung cancer.

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) and mortality among survivors of liver cirrhosis: a prospective cohort study

BackgroundCirrhosis is a medical condition marked by persistent liver damage, which leads to the development of fibrous tissue and compromised liver function. In the present study, we decided to investigate the possibility of a connection between the consumption of fermentable olig-, di-, monosaccharides, and polyols (FODMAPs) and mortality rates in cirrhotic patients by utilizing data obtained from a prospective cohort study.MethodsThis cohort study enrolled 166 ambulatory patients from two hospitals in Tehran, Iran, between 2016 and 2018, and followed them up for 5 48 months until April 30, 2022. During the 3,955 person-months of follow-up, 43 fatalities were recorded (36 men and 7 women). The study classified participants into three groups based on their FODMAPs consumption and assessed the risk of mortality using Cox proportional hazards regression models.ResultsTotal FODMAPs intake was associated with increased overall mortality risk (T3 vs. T1, HR = 3.5; 95%CI: 1.05, 11.7; P-trend = 0.036). This significant trend was also observed for total fructans (T3 vs. T1, HR = 5.15; 95% CI: 1.15, 23.2; P-trend = 0.006) and fructose (T3 vs. T1, HR = 5.55; 95% CI: 0.54, 57.14; P-trend = 0.018). Mortality risk was U-shaped with galactooligosaccharide intake, a lower mortality risk was observed with lactose intake and a higher mortality risk with polyols intake, although these associations did not reach statistical significance.ConclusionIn conclusion, this study highlights a higher risk of mortality with higher intake of fructans, excess fructose and total FODMAPs.

Association between triglyceride glucose index and adverse cardiovascular prognosis in patients with atrial fibrillation without diabetes: a retrospective cohort study

BackgroundAtrial fibrillation (AF) is the most prevalent arrhythmia encountered in clinical practice. Triglyceride glucose index (Tyg), a convenient evaluation variable for insulin resistance, has shown associations with adverse cardiovascular outcomes. However, studies on the Tyg index’s predictive value for adverse prognosis in patients with AF without diabetes are lacking.MethodsThis retrospective study utilized electronic medical records to collect data on patients with AF hospitalized at West China Hospital from January to June 2020. Participants were categorized into three groups based on their Tyg index levels. The primary outcome, major adverse cardiovascular events, included cardiac death, stroke, and myocardial infarction. Kaplan–Meier curve, Cox proportional hazards regression model, and restricted cubic spline were employed to explore the relationship between the Tyg index and outcomes. The predictive performance of the CHA2DS2-VASc model was evaluated after incorporating the Tyg index.ResultsThe study comprised 864 participants (mean age 67.69 years, 55.32% male, 57.52% paroxysmal AF). Patients with high Tyg index had a significantly higher risk of developing major adverse cardiovascular events (MACE) (P < 0.001, hazard ratio: 2.05, 95% confidence interval:1.65–2.56). The MACE risk in the middle Tyg group was similar to that in the low Tyg group (P = 0.1) during the 48-month follow-up period. However, focusing on the last 24 months revealed a higher MACE risk (P = 0.015) in the middle Tyg group. The restricted cubic spline analysis revealed an S-shaped correlation between Tyg and MACE. The CHA2DS2-VASc model combined with the Tyg index showed improved predictive performance and net benefit.ConclusionsA high Tyg index is associated with poorer prognosis in patients with AF without diabetes. Integrating the Tyg index into the CHA2DS2-VASc model may enhance its predictive performance, offering clinical utility.

Development and validation of a risk stratification model for stroke recurrence after acute ischemic stroke in young adults: A nomogram-based, multicenter retrospective study.

The prevalence of ischemic stroke in young adults has increased dramatically. However, factors associated with prognosis in this cohort have not been well studied. This study primary aimed to construct and validate a nomogram for predicting stroke recurrence and to achieve risk stratification of young adults after acute ischemic stroke (AIS). In this retrospective, multicenter study, we identified AIS patients aged 18-50 years in Tianjin Huanhu Hospital (training cohort) and The Affiliated Hospital of Chengde Medical College (validation cohort) from September 2019 to September 2021, respectively. Demographics and clinical characteristics data were systematically collected. A stepwise Cox proportional hazards regression analysis was used to identify the independent predictors of stroke recurrence in the training cohort and employed to construct the best-fit nomogram. Patients were stratified into low-, medium-, and high-risk groups based on the total points. Receiver operating characteristic (ROC) analysis and calibration curves were used to assess the discrimination and calibration of the nomogram. The discriminate value of risk stratification was verified using Kaplan-Meier curves, and external validation was performed with the validation cohort. A total of 467 young adult AIS patients were enrolled in this study. The overall prevalence of young adults in AIS patients was 13.3 % (95 % confidence interval, 12.2 %-14.5 %). Hyperlipidemia (Hazard ratio, 2.4 [1.2-4.9]), current smoking (5.9 [2.7-12.8]), stroke subtype (small-vessel occlusion, 3.7 [1.8-7.6]; stroke of undetermined cause/ others, 14.5 [3.0-70.2]), and stenosis (11.4 [4.5-28.9]) were significant independent predictors of stroke recurrence. A nomogram was constructed with the above predictors and achieved a satisfactory prediction in the validation cohort. Patients were classified into low-, medium-, and high-risk groups based on the total points with the cutoff value of 110.8 and 185.2. The log-rank test showed significant discrimination among the Kaplan-Meier curves of different risk groups (P < 0.001). The nomogram can satisfactory prediction of stroke recurrence-free rate in young adult patients and achieved risk stratification, may help to personalize management of patients.

Characterization of tumor prognosis and sensitive chemotherapy drugs based on cuproptosis-related gene signature in ovarian cancer

BackgroundCuproptosis is a novel form of cell death, acting on the tricarboxylic acid cycle in mitochondrial respiration and mediated by protein lipoylation. Other cancer cell death processes, such as necroptosis, pyroptosis, and ferroptosis, have been shown to play crucial roles in the therapy and prognosis of ovarian cancer. However, the role of cuproptosis in ovarian cancer remains unclear.MethodsThe expression profiles of 10 cuproptosis-related genes were extracted from GSE140082. Kaplan-Meier survival and Cox proportional hazards regression were used to identify prognostic genes for constructing risk models. Following this, Least Absolute Shrinkage and Selection Operator regression was employed to construct a risk score model. Next, a nomogram was constructed to predict overall survival in ovarian cancer. Ultimately, our analysis compared the two groups across various dimensions, including clinical characteristics, tumor progression, metabolism-related pathways, immune landscape, and drug sensitivity.ResultsMTF1 and LIAS were identified as protective factors in ovarian cancer, with patients in the higher risk group being significantly associated with poorer survival. Furthermore, integrating the risk score with clinical characteristics in the nomogram demonstrated high specificity and sensitivity in predicting survival. A higher propotion of M2 macrophages, follicular helper T cells, and resting mast cells was observed in the high-risk group. Additionally, the IC50 values of Dasatinib, Bortezomib, Parthenolide, and Imatinib were significantly lower in the high-risk group.ConclusionsThe study highlights the prognostic significance of cuproptosis-related genes and provides new insights into developing pharmacological therapeutic strategies targeting cuproptosis for the prevention and treatment of ovarian cancer.