Multivariate Cox Proportional Hazards Regression Research Articles

Impact of APC mutations on prognosis and tumor microenvironment in colorectal signet ring cell carcinoma.

e15500 Background: Colorectal signet ring cell carcinoma (CRC-SRC) is a malignant tumour characterized by its aggressive nature and unfavourable prognosis. In spite of the fact that numerous studies have examined the molecular profile and therapeutic targets of CRC-SRC, the prognostic biomarkers for this malignancy continue to be unknown. Methods: We conducted a comprehensive analysis of multi-omics in 35 cases of CRC-SRC and 10 cases of colorectal adenocarcinomas (CRC-AC). This analysis involved various techniques, including immunohistochemistry, DNA sequencing, and RNA sequencing. Results: In CRC-SRC, despite a lower frequency of APC mutations at the genomic level (P = 0.01), they rank as the second most prevalent mutations (40%), surpassed only by TP53 mutations (65.71%). The findings revealed that 13 genes associated with immunotherapy response were found to be upregulated in CRC-AC. Additionally, the levels of CD3+, CD8+, and CD3+ & CD8+ T cells were found to be similar in tumor regions in CRC-SRC. These results suggest that CRC-SRC is more likely to have an immunosuppressive tumor immune microenvironment (TiME) compared to CRC-AC. Multivariate Cox proportional hazard regression analysis (hazard ratio: 3.54, 95% confidence interval: 3.93-117.3; p-value = 0.0004), in particular, shows that the presence of APC mutations is associated with a worse prognosis. In contrast, APC-mutant cases of CRC-AC have the same overall survival (OS) rate as APC-wildtype patients in the TCGA cohort. On RNA level, APC-mutant tumors exhibited higher expression levels of VEGFA ( P = 0.028) and Mki67 (P = 0.014), which are implicated in tumour invasion and proliferation. In contrast, APC-mutant CRC-AC did not exhibit differential expression on these genes within the TCGA cohort. GSEA showed that only the E2F hallmark was significantly enriched in APC-mutant CRC-SRC patients ( P = 0.0072). On protein expression level, APC-mutant patients had a significantly lower CD3 or CD68 positive ratio in the tumour region (CD3: P = 0.035; CD68: P = 0.039). This indicated that lymphocyte infiltration is decreased in APC-mutant CRC-SRC. Conclusions: To summarize, APC mutations may have distinct functions in CRC-AC and CRC-SRC. Colorectal cancer (CRC) with APC mutations showed a more unfavourable prognosis and a distinct tumour immune microenvironment compared to CRC with normal APC. Clinical trial information: ChiCTR2300072881.

Association between somatic mutation pathways and treatment response in patients with biliary tract cancers (BTCs).

e16196 Background: Comprehensive somatic genomic profiling has become the standard of care for patients with BTCs, serving to identify targetable mutations and aiding in prognostication. While previous studies have identified individual somatic mutations such as TP53, CDKN1A, and KRAS as negative prognostic markers, little is known about their role as predictive biomarkers. This study aimed to investigate the predictive potential of somatic mutations and pathways using commercially available next-generation sequencing. Methods: We conducted a retrospective cohort study at Beth Israel Deaconess Medical Center (BIDMC) from January 2016 to January 2023, with data censoring in January 2024. Patient characteristics, including age, gender, race, stage, site of metastasis, performance status, and survival status, were collected. Somatic genomic alterations data were extracted from FoundationOneCDx, a commercially available NGS platform designed to capture 324 genetic alterations validated for therapy targets or unambiguous drivers of oncogenesis. Genetic alterations were classified into 14 oncogenic pathways constructed based on the TCGA and Reactome databases. Multivariate Cox proportional hazards regression analysis was performed between pathway alterations, progression-free survival and overall survival, accounting for selected covariates with p < 0.05 or potential known confounders. Results: Among 97 BTCs, 90 were successfully sequenced. Among these, 40 patients received gemcitabine and cisplatin, and 28 received fluorouracil and oxaliplatin (FOLFOX) therapy. Intrahepatic cholangiocarcinoma was present in 70% of cases, perihilar or distal cholangiocarcinoma in 27%, and gallbladder carcinoma in 3%. At presentation, 18% had stage I disease, and 44% had stage IV. The median follow-up time was 15 months. A total of 339 genomic alterations were identified, with 8% of samples harboring FGFR fusion or mutation, 9% IDH1 mutation, 6 % HER2 amplification, 30% KRAS mutation, and 32% with TP53 mutation. The most affected pathways were the cell cycle (66%) and DNA repair (50%). In multivariate regression analysis accounting for age, ECOG, and anatomical location, TP53 mutation was associated with shorter progression-free survival on gemcitabine and cisplatin treatment (n = 11, 2 vs. 6 months, HR 4.19, 95% CI 1.51 – 11.7, p < 0.01), whereas cell cycle pathway mutation was associated with longer progression-free survival (n = 14, 6 vs. 5 months, HR = 0.43, 95% CI 0.19-0.96, p < 0.05). No association was found between oncogenic pathways and treatment response to FOLFOX therapy. Conclusions: TP53 mutation is associated with a worse response, whereas cell cycle pathway mutations are associated with an improved response to gemcitabine and cisplatin therapy in patients with BTCs. Further research is needed to understand the mechanisms contributing to these observed effects.

Racial disparities and survival outcome of patients with locally advanced cervix cancer in the international randomised phase 3 OUTBACK trial (ANZGOG 0902, RTOG 1174, NRG 0274).

1594 Background: OUTBACK was an international multi-center phase 3 trial investigating adjuvant chemotherapy following definitive chemoradiation in locally advanced cervix cancer. We analysed if baseline characteristics were associated with survival outcome. More specifically, we determined whether race held prognostic significance relative to established clinical factors. Methods: We compared baseline characteristics (encompassing demographics, biomarkers and participants’ self-ratings of EORTC QLQ-C30 scores) between racial groups using chi-squared tests. We then explored relationships between baseline characteristics and survival outcomes using univariable and multivariable Cox proportional hazards regression models with stepwise selection. Results: Black or African American participants accounted for 13% (n=121/919) of the OUTBACK study population. There were no evident differences in the proportion of Black or African American participants, as compared to other racial groups, across most baseline characteristics, except for country of residence (USA vs non-USA, p<0.01). When examining the impact of race (Black or African American vs other racial groups) on survival outcomes in locally advanced cervix cancer, we found no evident associations with overall survival (HR 1.2; 95%CI,0.84 – 1.72; p=0.32) or progression free survival (HR 1.29; 95%CI, 0.95 – 1.75; p=0.10). Multivariable analysis identified several independent prognostic factors for overall survival, including performance status (HR 1.43; 95%CI, 1.04-1.95; p=0.03), FIGO stage (HR 2.02; 95%CI, 1.48-2.75; p<0.01), nodal involvement (HR 1.59; 95%CI, 1.18-2.14; p<0.01), and elevated white cell count (HR 1.68; 95%CI, 1.21-2.33; p<0.01). Role function, social function, financial difficulties and eGFR showed significance in univariable analysis for overall survival but did not retain significance in multivariable analysis. These findings were consistent when examining progression-free survival. Conclusions: No discernible disparities in survival outcomes were observed between Black or African American participants and other racial groups undergoing primary treatment for locally advanced cervix cancer. The primary prognostic determinants for this disease continue to be cancer staging and clinical performance status. Enrolment into a clinical trial may have abrogated the historical disparities seen among ethnic and racial groups. Clinical trial information: 12610000732088.

Overall survival with palbociclib (PAL) plus an aromatase inhibitor (AI) versus AI alone in older patients (pts) with de novo, HR+/HER2− metastatic breast cancer: A SEER-Medicare analysis.

1111 Background: Cyclin-dependent kinase 4/6 inhibitor in combination with endocrine therapy (CDK4/6i) is the current standard of care in first line (1L) treatment for hormone receptor–positive and human epidermal growth factor receptor 2-negative (HR+/HER2–) metastatic breast cancer (mBC). Comparative effectiveness evidence assessing overall survival (OS) outcomes are limited, particularly in older pts. Our primary objective was to compare OS in Medicare pts treated with 1L PAL + AI versus AI alone in the current SEER dataset. Methods: We conducted a retrospective analysis of HR+/HER2–mBC pts using the SEER-Medicare database. Medicare-enrolled pts aged ≥65 years diagnosed with de novo HR+/HER2– mBC between February 1, 2015, and December 31, 2019 were included. Pts were followed from the start of 1L therapy line until death, Medicare disenrollment, enrollment in a health maintenance organization plan, or the end of available study follow-up (December 31, 2020), whichever came first. Stabilized inverse probability of treatment weighting (sIPTW) was the primary method used to balance patient characteristics at baseline, with propensity score matching (PSM) and multivariable CPH regression as sensitivity analyses. Median OS and the hazard ratio (HR) were estimated using the weighted Kaplan-Meier (KM) method and the weighted Cox proportional hazard (CPH) regression model, respectively. Results: Of 779 included pts, 296 received PAL+AI and 483 received AI alone. Median follow-up was 23.9 months for the PAL+AI arm and 18.2 months for the AI alone arm. After sIPTW adjustment, median OS was 37.6 months (95% CI=34.8-42.0) for PAL+AI vs 25.5 months (95% CI=22.0-28.9) for AI alone (HR=0.73, 95% CI=0.59-0.91). Results from the PSM and CPH regression analyses were consistent with the primary analysis. Key patient characteristics are presented (Table). Conclusions: This comparative effectiveness study showed that PAL+AI was associated with significantly prolonged OS vs AI alone in the 1L treatment of older pts with de novo HR+/HER2- mBC treated in US clinical practice using the SEER-Medicare database. Our results add to the body of evidence on the survival benefit of PAL+AI in this population. [Table: see text]

Update on the prognostic value of a novel immune-related toxicity grading system (OST score) in patients with advanced solid tumours treated with immune checkpoint inhibitors (ICI).

e14696 Background: Toxicity grading systems have been an asset in managing cancer patients undergoing systemic treatment. In the era of ICI treatment, correlation between toxicity and treatment response is becoming more apparent. A new toxicity score was developed with the aim of better defining the profile of immune-related toxicities (irAEs). Initial analyses also demonstrated its potential in predicting patient outcomes. Here we provide an update on the survival analyses. Methods: Data were collected from the Pathobiology of Adverse Immune Reactions (PAIR) prospective cohort study at Guy’s Hospital from February 2018 until December 2023. Patients with advanced solid tumours naïve to ICI who received at least 1 dose were included. Minimum 6 months of follow-up was required. IrAEs were captured based on the OST score which evaluates the number of affected Organs (O), number of Severe (S) CTCAE (≥G3) toxicities, and Total sum of all grade toxicities (T). OST was calculated as a cumulative score at the end of follow-up or death. Patients were divided in high and low toxicity groups, defined by the median value for each parameter. For the composite OST score analysis, patients were divided in 2 groups based on a point system; 1 point was attributed for each individual OST high parameter; high toxicity OST group included patients with score >1. Descriptive statistics and crude and multivariate survival Cox Proportional Hazards regression analyses were performed accounting for age, tumour type, treatment, and steroid exposure. Results: A total of 148 patients fulfilled the criteria. Median age was 68 years (range 23-87), the majority were white Caucasian (81.8%) and male (56%). Melanoma was the most common tumour type (32.4%) followed by NSCLC (21.6%) and RCC (19.2%). 37.8% of patients received Ipilimumab/Nivolumab, 30.4% Pembrolizumab and 31.8% received other PD(L)-1 monotherapies. Twenty-eight patients (18.9%) had an autoimmune disorder at baseline; hypothyroidism was most common (5.4%). At end of follow-up, 82 deaths (55.4%) had occurred. Across the three OST parameters, Organ (O) was the strongest predictor of survival [HR (95%CI) 0.480 (0.265-0.869)]. After adjustment, multivariate analysis showed that risk of death was significantly lower in the high vs low Organ and Total toxicity groups [HR (95%CI) 0.379 (0.216-0.663) and 0.544 (0.302-0.982) respectively], but not for Severity [0.664 (0.338-1.306)]. In the OST combined score, the high toxicity group had favourable prognosis compared to low groups (mOS 56.6 vs 13 months) [HR (95%CI) 0.439 (0.275-0.702)]. Conclusions: Our new score manages to efficiently capture immune-mediated toxicity profile of patients treated with ICI as well as predict their outcomes. Further prospective evaluation, integration of laboratory markers and external validation is currently ongoing.

Overall survival analysis of first line CDK4/6 inhibitors in a large real-world cohort of patients with hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer.

e13095 Background: Multiple clinical trials have demonstrated the efficacy of the commercially available CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) as upfront therapy in patients (pts) with (HR+)/HER2-negative (HER2-) metastatic breast cancer (MBC). Recently, differences in overall survival (OS) benefit in MBC and invasive disease-free survival benefit in early-stage BC suggest greater potency of abemaciclib and ribociclib compared to palbociclib. Here we report a comprehensive OS analysis of a cohort of pts with HR+/HER2- MBC treated with ribociclib, palbociclib or abemaciclib and ET in 1st line setting. Methods: We retrieved medical records of pts with HR+/HER2- MBC receiving CDK4/6i as 1st line therapy between December 2013 and October 2023 at Memorial Sloan Kettering Cancer Center. We investigated the impact of clinico-pathological characteristics and treatment type as categorical variables on OS using uni- and multivariate Cox (proportional hazard) regression model. Any p-value (p) <0.05 was deemed to be statistically significant. Results: 854 pts were included in the analysis, 838 females (98%) and 16 males at birth. The median age was 56 (IQR: 48-65). Overall, 722 (84%) pts received palbociclib, 88 (11%) abemaciclib, and 44 (5%) ribociclib. Most pts received aromatase inhibitor (AI) as ET backbone (n=634, 74%); 214 received fulvestrant (35%), and 6 received tamoxifen (1%). After a median follow-up of 3.14 years (range: 1.7-4.6), the median OS of the full cohort was 54.7 months (95%CI: 50-63.1). Clinico-pathological characteristics that resulted independently associated with worse OS were: male gender at birth (HR:2, 95%CI:1.4-4), disease-free interval ≤ 2 years (HR:1.64, 95%CI:1.11-2.44), ER-low status (HR: 2.27, 95%CI:1.42-3.63), high grade(HR: 1.28, 95%CI:1.01-1.62), liver involvement (HR: 1.48, 95%CI:1.08-2.03), and number of disease sites >3 (HR:1.35, 95%CI:1.03-1.78). HER2-low status was associated with better OS (HR: 0.75, 95%CI:0.59-0.96). In terms of type of treatment, there was a trend toward improved OS in patients receiving AI rather than fulvestrant or tamoxifen (HR:0.76, 95%: 0.58-1), while the type of CDK4/6i did not affect the outcome. Conclusions: Clinical parameters of early relapse, high disease burden, and intrinsic tumor aggressiveness seem to be the main drivers of poor prognosis in patients with HR+/HER2- MBC in 1st line setting. In this analysis, type of CDK4/6i did not have a significant impact on OS, although pts treated with abemaciclib and ribociclib were underrepresented in the cohort due to the earlier and prevalent use of palbociclib as the first-in-class FDA-approved CDK4/6i. These data are reassuring about the use of palbociclib suggesting that a switch of CKD4/6i is not needed in pts with ongoing treatment and demonstrated benefit.

Right Ventricular Strain Derived from Cardiac MRI Feature Tracking for the Diagnosis and Prognosis of Arrhythmogenic Right Ventricular Cardiomyopathy.

Purpose To demonstrate the myocardial strain characteristics of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), based on revised Task Force Criteria (rTFC), and to explore the prognostic value of strain analysis in ARVC. Materials and Methods This retrospective study included 247 patients (median age, 38 years [IQR, 28-48 years]; 167 male, 80 female) diagnosed with ARVC, based on rTFC, between 2014 and 2018. Patients were divided into "possible" (n =25), "borderline" (n = 40), and "definite" (n = 182) ARVC groups following rTFC. Biventricular global strain parameters were calculated using cardiac MRI feature tracking (FT). The primary outcome was defined as a composite of cardiovascular events, including cardiovascular death, heart transplantation, and appropriate implantable cardioverter defibrillator discharge. Univariable and multivariable cumulative logistic regression and Cox proportional hazards regression analysis were used to evaluate the diagnostic and prognostic value of right ventricle (RV) strain parameters. Results Patients with definite ARVC had significantly reduced RV global strain in all three directions compared with possible or borderline groups (all P < .001). RV global longitudinal strain (GLS) was an independent predictor for disease (odds ratio, 1.09 [95% CI: 1.02, 1.16]; P = .009). During a median follow-up of 3.4 years (IQR, 2.0-4.9 years), 55 patients developed primary end point events. Multivariable analysis showed that RV GLS was independently associated with the occurrence of cardiovascular events (hazard ratio, 1.15 [95% CI: 1.07, 1.24]; P < .001). Kaplan-Meier analysis showed that patients with RV GLS worse than median had a higher risk of combined cardiovascular events (log-rank P < .001). Conclusion RV GLS derived from cardiac MRI FT demonstrated good diagnostic and prognostic value in ARVC. Keywords: MR Imaging, Image Postprocessing, Cardiac, Right Ventricle, Cardiomyopathies, Arrhythmogenic Right Ventricular Cardiomyopathy, Revised Task Force Criteria, Cardiovascular MR, Feature Tracking, Cardiovascular Events Supplemental material is available for this article. © RSNA, 2024.

Oxidative balance score as a useful predictive marker for new-onset type 2 diabetes mellitus in Korean adults aged 60 years or older: The Korean Genome and Epidemiologic Study–Health Examination (KoGES-HEXA) cohort

BackgroundThe oxidative balance score (OBS) is a comprehensive pro- and anti-oxidative marker for assessing the risk of various metabolic diseases and cancers. However, it is not well established whether OBS is related to type 2 diabetes mellitus (T2DM), particularly in elderly populations. Therefore, our objective was to investigate the longitudinal effect of OBS on T2DM in a large cohort of Korean adults aged 60 years and older. MethodsWe assessed the data for 3516 participants aged 60 years and older without diabetes mellitus from the Health Examinees cohort of the Korean Genome and Epidemiology Study. We classified the participants into three groups according to OBS tertiles. We prospectively assessed hazard ratios (HRs) with 95 % confidence intervals (CIs) for new-onset T2DM using multivariable Cox proportional-hazard regression models during the mean 3.5 years following the baseline survey. ResultsA total of 109 participants (3.1 %) developed T2DM during a mean follow-up of 3.5 years. The incidence rates per 1000 person-years were 11.73 for the lowest OBS tertile (T1), 8.19 for the second tertile (T2), and 6.23 for the highest tertile (T3). Adjusting for all confounding factors, compared with the referent T1, the HR (95 % CI) of new-onset T2DM was not significant in T2 (0.71 [0.47–1.07]) but was significant in T3 at (0.47 [0.30–0.75]) (p for trend = 0.002). ConclusionsThe study suggests that a OBS could serve as a valuable predictive marker for new-onset T2DM in older adults. Our study suggests that maintaining an appropriate body weight through healthy lifestyle modification has the potential to lower T2DM incidence in elderly. This implies that the OBS may be a useful tool for assessing the incidence of T2DM even in older individuals.

Association of serum AFP trajectories and hepatocellular carcinoma outcomes after hepatic arterial infusion chemotherapy: A longitudinal, multicenter study.

This study aims to investigate α-fetoprotein (AFP) trajectories for prediction of survival outcomes after hepatic arterial infusion chemotherapy (HAIC) treatment in large hepatocellular carcinoma (HCC). From May 2014 to June 2020, 889 eligible patients with large HCC underwent HAIC were retrospectively enrolled from five hospitals. A latent class growth mixed (LCGM) model was applied to distinguish potential AFP level dynamic changing trajectories. Inverse-probability-of-treatment weighted (IPTW) analyses were performed to eliminate unmeasured confounders through marginal structural models. Multivariate Cox proportional hazard regression analyses were used to determine the overall survival (OS) in patients with large HCC. Performance of these serum markers for survival prediction was compared by areas under receiver operating characteristic analysis with the Delong test. The median follow-up time was 23.7 (interquartile range, 3.8-115.3). A total of 1009 patients with large HCC, who underwent HAIC with AFP repeatedly measured 3-10 times, were enrolled in the study. Three distinct trajectories of these serum AFP were identified using the LCGM model: high stable (37.0%; n = 373), low stable (15.7%; n = 159), and sharp-falling (47.3%; n = 477). Multivariate Cox proportional hazard regression analyses found that ALBI stage 2-3, BCLC-C stage and high-stable AFP trajectories were associated with OS. AFP trajectories yield the optimal predictive performance in all risk factors. The AFP trajectories based on longitudinal AFP change showed outstanding performance for predicting survival outcomes after HAIC treatment in large HCC, which provide a potential monitoring tool for improving clinical decision-making.

Association of CD38+ Immunophenotyping Biomarker With a Better Prognosis in Elderly Acute Myeloid Leukemia Patients.

The relevance of cytogenetic markers as prognostic risk factors has been demonstrated in a vast number of studies, with many prognostication tools utilizing these factors to determine treatment approaches. Patients aged above 60 years represent an important subgroup of acute myeloid leukemia (AML) patients, especially because they usually exhibit a poorer cytogenetic landscape and are less suitable for intensive treatments. The importance of evaluating prognostic parameters in AML, especially in low-income countries, prompted an investigation into CD38 expression and its effects. Medical records of AML patients aged above 60 years from three hospitals in Brazil's northwest region were analyzed. A total of 67 patients were evaluated in terms of overall survival and factors predicting worse outcomes. The risk stratification was performed based on the European LeukemiaNet 2022 guidelines. The analysis of immunophenotyping markers was conducted using multi-parametric flow cytometry. The overall survival of CD38-positive AML patients was higher than that of patients with CD38-negative AML, with survival rates of 15.6 months versus 4 months, respectively (p-value=0.026). The impact of CD38 positivity was relevant also in multivariable Cox proportional hazards regression, demonstrating a positive effect on overall survival, with a hazard ratio of 0.33 (95%CI=0.13-0.79; p-value=0.014). Expression of CD38 in patients with AML was associated with better overall survival and serves as a relevant predictor of improved outcome in patients aged above 60 years.

Time to initiation of antenatal care and its predictors among pregnant women who delivered in Arba Minch town public health facilities, Gamo Zone, southern Ethiopia, 2023: a retrospective follow-up study

BackgroundEarly antenatal care visit is important for optimal care and health outcomes for women and children. In the study area, there is a lack of information about the time to initiation of antenatal care. So, this study aimed to determine the time to initiation of antenatal care visits and its predictors among pregnant women who delivered in Arba Minch town public health facilities.MethodsAn institution-based retrospective follow-up study was performed among 432 women. A systematic random sampling technique was employed to select the study participants. The Kaplan-Meier survival curve was used to estimate the survival time. A Multivariable Cox proportional hazard regression model was fitted to identify predictors of the time to initiation of antenatal care. An adjusted hazard ratio with a 95% confidence interval was used to assess statistical significance.ResultsThe median survival time to antenatal care initiation was 18 weeks (95% CI = (17, 19)). Urban residence (AHR = 2.67; 95% CI = 1.52, 4.71), Tertiary and above level of education of the women (AHR = 1.90; 95% CI = 1.28, 2.81), having pregnancy-related complications in a previous pregnancy (AHR = 1.53; 95% CI = 1.08, 2.16), not having antenatal care for previous pregnancy (AHR = 0.39; 95% CI = 0.21, 0.71) and unplanned pregnancy (AHR = 0.66; 95% CI = 0.48, 0.91) were statistically significant predictors.ConclusionHalf of the women initiate their antenatal care visit after 18 weeks of their pregnancy which is not in line with the recommendation of the World Health Organization. Urban residence, tertiary and above level of education of the women, having pregnancy-related complications in a previous pregnancy, not having previous antenatal care visits and unplanned pregnancy were predictors of the time to initiation of antenatal care. Therefore, targeted community outreach programs including educational campaigns regarding antenatal care for women who live in rural areas, who are less educated, and who have no previous antenatal care experience should be provided, and comprehensive family planning services to prevent unplanned pregnancy are needed.

Twenty-Four-Month Safety and Effectiveness of TCD-17187 Drug-Coated Balloon for Treatment of Atherosclerotic Lesions in Superficial Femoral and Proximal Popliteal Artery

PurposeIn the present trial, the 24-month safety and effectiveness of the TCD-17187 drug-coated balloon (DCB) for the treatment of atherosclerotic lesions in the superficial femoral artery (SFA) and proximal popliteal artery (PA) were evaluated in Japanese patients.MethodsThis was a prospective, multicenter, core laboratory-adjudicated, single-arm trial. From 2019 to 2020, 121 patients with symptomatic peripheral artery disease were enrolled. The primary effectiveness outcome measure was primary patency. The safety outcome measure was the major adverse event (MAE) rate.ResultsAge was 74.5 ± 7.3 years, and diabetes mellitus was present in 67.5%. Lesion length and reference vessel diameter (RVD) were 106.0 ± 52.6 mm and 5.2 ± 0.8 mm, respectively. Chronic total occlusion (CTO) and bilateral calcification rate (Grade 3 and 4 by peripheral arterial calcium scoring system (PACSS)) were 17.5% and 50.8%, respectively. The 24-month primary patency rate by duplex ultrasound was 71.3%, while freedom from clinically driven target lesion revascularization (CD-TLR) was 87.0%. The MAE rate was 13.2% and all events consisted of CD-TLR. There were no instances of device- or procedure-related deaths major amputations throughout the 24 months. Multivariate Cox proportional hazards regression analysis revealed significant differences associated with loss of primary patency in the following characteristics: CTO, restenotic lesion and RVD.ConclusionThis trial confirmed the safety and effectiveness of TCD-17187 DCB for atherosclerotic lesions of the SFA and/or proximal PA for up to 24 months.Level of EvidenceLevel 3, Cohort study.Clinical Trial Registration: URL: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno=R000038612&type=summary&language=J:Registration ID: UMIN000034122. Registration Date: September 13, 2018.

Correlation of hematocrit and cardiovascular events in peritoneal dialysis patients

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

Association Between Changes in Smoking Habits and Incident Fracture After Acute Ischemic Stroke.

Survivors of stroke, particularly the older population, are at an increased risk of falls and incident fractures. Smoking is a widely recognized risk factor for fractures. However, the association between changes in smoking habits before and after an index stroke and increased risk of fracture remains unelucidated. Using the Korean National Health Insurance program, patients with ischemic stroke between 2010 and 2016 were enrolled. Individuals were classified by smoking habits: "never smoker," "former smoker," "smoking quitter," "new smoker," and "sustained smoker." The primary outcome was the composite outcome of the vertebral, hip, and any fractures. Multivariable Cox proportional hazards regression analysis was conducted, using the never-smoker group as the reference. Among 177 787 patients with health screening data within 2 years before and after ischemic stroke, 14 991 (8.43%) patients had any fractures. After multivariable adjustment, the sustained smokers had a significantly increased risk of composite primary outcomes of any, vertebral, and hip fractures (adjusted HR [aHR], 1.222 [95% CI, 1.124-1.329]; aHR, 1.27 [95% CI, 1.13-1.428]; aHR, 1.502 [95% CI, 1.218-1.853], respectively). Additionally, the new smoker group exhibited a similar or higher risk of any fractures and hip fractures (aHR, 1.218 [95% CI, 1.062-1.397]; aHR, 1.772 [95% CI, 1.291-2.431], respectively). Sustained smokers had a significantly increased risk of vertebral and hip fractures after an ischemic stroke. The risk of any hip fractures was higher in new smokers after ischemic stroke. As poststroke fractures are detrimental to the rehabilitation process of patients with stroke, physicians should actively advise patients to stop smoking.

Optimal use of antithrombotic agents in recent small subcortical strokes accompanied by atrial fibrillation.

This study aimed to evaluate the efficacy and safety of anticoagulants (AC) and antiplatelets (APT) in patients with recent small subcortical infarctions (RSSI) and atrial fibrillation (AF). We utilized a prospective multicenter stroke registry database to identify patients with RSSI with a concurrent diagnosis of AF. Propensity score matching analysis was used to balance baseline differences among the AC-only, APT-only, and their combination groups. The main outcomes of interest were time to occurrence of minor and major bleeding, stroke recurrence, and all-cause mortality. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for each outcome were calculated using the multivariable Cox proportional hazard regression analysis. Of the 404 eligible patients, 28.2% received APT only, 53.0% received AC only, and 18.9% received a combination of both. Notable differences were observed between these groups in terms of the 1-year stroke recurrence (APT, 32.5%; AC, 5.6%; APT + AC, 9.2%) and all-cause mortality (APT, 21.9%; AC, 6.1%; APT + AC, 14.5%), whereas the rates of bleeding events were comparable. The multivariable analysis indicated a significant association of AC alone with reduced risks of severe bleeding, stroke recurrence, and all-cause mortality compared with APT alone (aHR 0.64, 95% CI 0.41-0.98; aHR 0.11, 95% CI 0.06-0.22; aHR 0.22, 95% CI 0.11-0.44, respectively). The combination group showed a reduced risk of stroke recurrence compared to APT alone (aHR 0.19, 95% CI 0.08-0.46). These findings remained consistent with the propensity score-matched analysis. AC showed better clinical outcomes than APT in patients with RSSI and AF. Additionally, combination therapy with AC and APT was associated with a lower risk of stroke recurrence than APT alone.

Association between lipid profile and clinical outcomes in COVID-19 patients.

High-density lipoprotein cholesterol (HDL-c) removes cholesterol, an essential component in lipid rafts, and this cholesterol removal can regulate protein attachment to lipid rafts, modulating their functionality in the immune cell response. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can alter the lipid profile, there is little information on the role of HDL-c and other lipids in prognostic of the coronavirus disease 2019 (COVID-19) in Mexican population. This study aims to evaluate the predictive value of HDL-c and lipid profile on severity and survival of 102 patients infected with SARS-CoV-2 during the COVID-19 first wave. Our findings, derived from univariate and multivariate Cox proportional hazards regression models, highlighted age and hypertension as significant predictors of survival (HR = 1.04, p = 0.012; HR = 2.78, p = 0.027), while gender, diabetes, and obesity showed no significant impact. Triglycerides and HDL-c levels notably influenced mortality, with elevated triglycerides and lower HDL-c associated with higher mortality risk (p = 0.032). This study underscores the importance of lipid profiles alongside traditional risk factors in assessing COVID-19 risk and outcomes. It contributes to the understanding of COVID-19 patient management and emphasizes the need for further investigation into the role of dyslipidemia in influencing COVID-19 prognosis, potentially aiding in refined risk stratification and therapeutic strategies.

In-hospital survival of critically ill COVID-19 patients treated with glucocorticoids: a multicenter real-world data study

The COVID-19 pandemic has posed a major challenge to healthcare systems globally. Millions of people have been infected, and millions of deaths have been reported worldwide. Glucocorticoids have attracted worldwide attention for their potential efficacy in the treatment of COVID-19. Various glucocorticoids with different dosages and treatment durations have been studied in patients with different severities, with a suitable dosage and treatment duration not yet defined. This study aimed to investigate whether in-hospital survival differs between critically ill patients treated with low-dose glucocorticoids, high-dose glucocorticoids or no glucocorticoids. All critically ill patients admitted to the intensive care unit of the Charité Hospital—Universitätsmedizin Berlin between February 2020 and December 2021 with COVID-19 pneumonia receiving supplemental oxygen were eligible to participate in this multicenter real-world data study. Patients were retrospectively assigned to one of three groups: the high corticosteroid dose (HighC) group (receiving 6 mg parenteral dexamethasone or an equivalent corticosteroid dosage for ten days), the low corticosteroid dose (LowC) group (receiving less than 6 mg parenteral dexamethasone or an equivalent corticosteroid dosage for ten days), or the no corticosteroid (NoC) group. Overall survival and risk effects were compared among groups within the total observation period, as well as at 35 days after the onset of COVID-19 symptoms. Adjusted multivariable Cox proportional hazard regression analysis was performed to compare the risk of death between the treatment groups. Out of 1561 critically ill COVID-19 patients, 1014 were included in the baseline analysis. In the survival study, 1009 patients were assigned to the NoC (n = 346), HighC (n = 552), or LowC group (n = 111). The baseline characteristics were balanced between groups, except for age, BMI, APACHE II score, SOFA and SAPS II. While the 35-day survival did not show any differences, a landmark analysis of the patients surviving beyond 35 days revealed differences between groups. The restricted mean survival time was 112 days in the LowC group [95% CI: 97 – 128], 133 days in the HighC group [95% CI: 124 – 141] and 144 days in the NoC group [95% CI: 121 – 167]. The multivariable-adjusted Cox proportional hazard analysis indicated that, regardless of age, sex, health status or invasive oxygenation, a low-dose treatment increased the hazard of death of critically ill COVID-19 patients by a factor of 2.09 ([95% CI: 0.99, 4.4], p = 0.05) and a high-dose corticosteroid treatment increased the risk by a factor of 1.07 ([95% CI: 0.53, 2.15], p = 0.85) compared to no treatment with glucocorticoids. The analysis reveals that corticosteroid treatment does not influence the survival of critically ill COVID-19 patients in the intensive care unit within 35 days. Our evaluations further suggest that regardless of ventilation status, the decision-making process for administering corticosteroid therapy should account for the individual severity of the illness.

Long-time exposure to sunlight is associated with the risk of sudden cardiac arrest and coronary heart disease

Abstract Background With ongoing climate change, the duration of sunshine hours will likely increase over the coming decades that escalating air temperature. Little is known about the potential cardiovascular risk from this climate factor. Purpose The aim of this study was to test whether duration of sunlight exposure is associated with incident sudden cardiac arrest (SCA), coronary heart disease (CHD), and hospitalization for heart failure (HF) and whether this association depends on seasonal variation. Methods A total of 308,851 participants from UK Biobank were included and were followed for a median time of 11.8 years. Participants reported how many hours they respectively spent the daylight outdoors on summer and winter typical days. Extreme outliers (&amp;gt;12 hours/day in summer and &amp;gt;8 hours/day in winter) were excluded. Average exposure time was calculated to unify the daylight outdoors time standard. Duration of sunlight exposure (average, summer, and winter) were categorized using quantiles and a restricted cubic spline for outcomes. Multivariate cox proportional hazard regression adjusted by age, sex, demographics, lifestyle, clinical and environmental factors was used for the analysis. Results During a follow-up, 1,572 (0.51%), 11,557 (3.74%) and 2,145 (0.68%) participants were diagnosed with SCA, CHD and hospitalization for HF. Compared with the participants exposed to short-time sunlight (average ≤ 1.5 hours/day), those who exposed to long-term sunlight (average ≥ 3.5 hours/day) had increased risk of SCA (HR 1.22, 95% CI 1.06 to 1.40) and CHD (HR 1.22, 95% CI 1.06 ~1.40). The associations between long-time exposure to sunlight and SCA were largely attributable to summer (HR 1.22, 95% CI 1.06 to 1.39) and not winter (HR 1.02, 95% CI 0.86 to 1.20), respectively. An hour increase of sunlight exposure was associated with increased risk of SCA in summer (HR, 1.03; 95% CI, 1.01 to 1.05), but not in winter (HR, 1.03, 95% CI, 0.99 to 1.06). Subgroup analysis identified that exposure to long-term sunlight was consistently increased risk of SCA, regardless of age, sex, body mass index, previous cardiovascular diseases, total physical activity, types of physical activity in last 4 weeks, use of sun/UV protection, sedentary time, natural environment percentage (buffer 1000m), and PM2.5. Finally, long-time exposure to sunlight was also associated with increased risk of CHD, but not associated with increased risk of HF hospitalization. Conclusions Findings from the present study indicate that daily long-time exposure to sunlight that increase in air temperature is a risk factor for SCA and CHD. These associations revealed graded relationship according to the duration of exposure to sunlight and more pronounced in summer. Our results suggest that public health efforts to reduce cardiovascular risk should take a wide range of exposure time to sunlight into account.

PD-1+ T lymphocyte proportions and hospitalized exacerbation of COPD: a prospective cohort study

ObjectiveTo evaluate the predictive value of PD-1 expression in T lymphocytes for rehospitalization due to acute exacerbations of COPD (AECOPD) in discharged patients.Methods115 participants hospitalized with COPD (average age 71.8 ± 6.0 years) were recruited at Fujian Provincial Hospital. PD1+T lymphocytes proportions (PD1+T%), baseline demographics and clinical data were recorded at hospital discharge. AECOPD re-admission were collected at 1-year follow-up. Kaplan-Meier analysis compared the time to AECOPD readmissions among groups stratified by PD1+T%. Multivariable Cox proportional hazards regression and stratified analysis determined the correlation between PD1+T%, potential confounders, and AECOPD re-admission. ROC and DCA evaluated PD1+T% in enhancing the clinical predictive values of Cox models, BODE and CODEX.Results68 participants (59.1%) were AECOPD readmitted, those with AECOPD readmission exhibited significantly elevated baseline PD-1+CD4+T/CD4+T% and PD-1+CD8 + T/CD8 + T% compared to non-readmitted counterparts. PD1+ T lymphocyte levels statistically correlated with BODE and CODEX indices. Kaplan-Meier analysis demonstrated that those in Higher PD1+ T lymphocyte proportions had reduced time to AECOPD readmission (logRank p < 0.05). Cox analysis identified high PD1+CD4+T and PD1+CD8+T ratios as risk factors of AECOPD readmission, with hazard ratios of 1.384(95%CI [1.043–1.725]) and 1.401(95%CI [1.013–1.789]), respectively. Notably, in patients aged < 70 years and with fewer than twice AECOPD episodes in the previous year, high PD1+T lymphocyte counts significantly increased risk for AECOPD readmission(p < 0.05). The AECOPD readmission predictive model, incorporating PD1+T% exhibited superior discrimination to the Cox model, BODE index and CODEX index, AUC of ROC were 0.763(95%CI [0.633–0.893]) and 0.734(95%CI [0.570–0.899]) (DeLong’s test p < 0.05).The DCA illustrates that integrating PD1+T% into models significantly enhances the utility in aiding clinical decision-making.ConclusionEvaluation of PD1+ lymphocyte proportions offer a novel perspective for identifying high-risk COPD patients, potentially providing insights for COPD management.Trial registrationChinese Clinical Trial Registry (ChiCTR, URL: www.chictr.org.cn/), Registration number: ChiCTR2200055611 Date of Registration: 2022-01-14.

#934 Mortality predictors in advanced chronic kidney disease patients on conservative kidney management: insights from a retrospective multicenter study

Abstract Background and Aims In general, patients with advanced chronic kidney disease (ACKD) on dialysis have a better survival than patients on conservative kidney management (CKM). However, in elderly and frail individuals, with multiple comorbidities, the survival benefits of dialysis seem to be lost. Although the focus of CKM is not quantity but quality of life (QoL), it is important to identify survival modifiers and mortality predictors that may eventually influence QoL and the development of symptoms. Method An observational retrospective and multicenter study of ACKD patients on CKM was conducted from July/2015 to December/2023. Data was retrieved from electronic records, encompassing kidney function, analytical parameters, functional and fragility state, and symptoms evaluation (using Palliative Outcome Scale—Renal). The Kaplan-Meier curves and Cox proportional hazards multivariable regression were used for survival analysis and to evaluate 180-day mortality predictors. Results A total of 212 patients (56.6% females), with a mean age of 83 years old and a mean follow up time of 220 ± 239 days, were included. The follow-up time was determined by the end of the observational period or the patient's death. 56.1% died before a 180-day follow-up period. The main causes for the ACKD were multifactorial (29.7%) and indeterminate (25.9%). The majority (80.7%) had nephrologist oversight before a CKM team initiated its follow-up, and 63.6% opted for CKM as their first treatment choice. Survival at 180 days (Fig. 1) differed significantly depending on sex (51.3 vs 65.6, p = 0.021), age under 80 years-old (51.3 vs 73.9, p = 0.000), provenance (0 vs 39.4 vs 83 vs 93.8, p = 0.000), albumin value (32.7 vs 65.5, p = 0.032), and symptoms such as anorexia and pain (53 vs 95.5, p = 0.000; and 54.5 vs 88.9, p = 0.000). Regarding to mortality predictors (Table 1), albumin under 3g/dL, anorexia and pain were independent predictors of mortality. Conclusion Understanding factors associated with increased mortality and higher rates of survival in CKM patients is crucial to better manage this population. Pain, albumin &amp;lt;3g/dL and anorexia, which may reflect patients with worse nutritional status, were shown to be independent predictors of mortality. Therefore, controlling these symptoms, which often impair QoL, and improving nutritional status appears to have an impact not only on QoL but also on survival of ACKD patients on CKM.