Survival Analysis Research Articles

Nivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: Results of Polish multicenter observational study.

Patients with head and neck squamous cell carcinoma (HNSCC) who have progressed following primary treatment (PT) have a poor prognosis. In this group, nivolumab has been demonstrated to significantly improve outcomes. This study presents the efficacy of nivolumab in Polish patients with recurrent and/or metastatic (R/M) HNSCC using real-world data. The analyzed group consisted of 324 adult patients with R/M HNSCC following platinum-based therapy. Patients were divided into 3 groups based on the time from completion of PT to nivolumab initiation (tPT-N): within 6 months (refractory), between 6 and 24 months (sensitive, tPT-N ≤24), and beyond 24 months (sensitive, tPT-N >24). Survival analysis and the Cox proportional hazards model were performed to evaluate how various risk factors affect patient outcomes. The 1-year and 2-year overall survival (OS) was 19.1%, 6.1%, 30.7%, 9.4%, and 45.7%, 29.1% in refractory, sensitive tPT-N ≤24, sensitive tPT-N >24 patients, respectively and was higher for both sensitivity groups vs. refractory (p = .004) and for sensitive tPT-N >24 versus refractory and sensitive tPT-N ≤24 (p <.001). Patients with nasopharyngeal cancer had OS significantly higher than patients with other primary tumor localization. The multivariate Cox analysis showed a significant favorable effect of tPT-N >24 (HR = 0.53, p = .001) and nasopharyngeal cancer on OS (HR = 0.20, p = .008). Conversely, female sex was identified as an unfavorable factor for OS (HR = 1.48, p = .020). In our study, we established that the benefit of nivolumab increases with the increasing tPT-N. The probability of death is significantly lower in male patients and patients with nasopharyngeal cancer regardless of tPT-N.

Different approach to M descriptor for future staging of oligometastatic disease in SCLC: A cross-sectional survival analysis.

This study aimed to investigate the impact of oligometastasis and the M descriptor on survival insmall cell lung cancer (SCLC). This multicenter, retrospectivestudy included patients with newly diagnosed extensive-stage SCLC(ES-SCLC) from 2010 to 2020. Subgroups: Group 1: single metastasis in a single organ, Group 2: 2-5 metastases in a single organ, Group 3: 6 or more metastases in a single organ, and Group 4: metastases in two or more organs. This classification was based on the 9th Staging-M descriptor. Three-year progression-free survival (PFS) and overall survival (OS) analyses were conducted. The mean age of the 439 patients was 62 ± 10years, and 89.5% of them were male. The mean PFS for Groups 1, 2, 3,4 was 10.7months (95% CI 8.9-12.5), 7.5months (95% CI 5.6-9.4), 4.3months (95% CI 2.9-5.7), and 5.4months (95% CI 4.7-6.1), respectively. PFS in Group 2 was significantly higher. The mean OS for Groups 1, 2, 3,4 was 13.3months (95% CI 11.2-15.3), 9.5months (95% CI 7.1-11.9), 7.1months (95% CI 4.5-9.7), and 6.9months (95% CI 6.0-7.9), respectively.OS in Group 1 was significantly higher. OS and PFS in the M1b group were significantly higher than in the M1c1 and M1c2 groups (p < 0.05) with no statistical difference between the M1c1 and M1c2 groups. There is no significant difference in survival between the M1c1 and M1c2 groups.In ES-SCLC, the number of metastases may be a more predictive factor for prognosis than the number of metastatic organs.

Resilience and spiritual well-being as resources for coping with radiotherapy and surviving in patients with glioblastoma.

The primary aims of this multicenter, prospective observational study were to investigate spiritual well-being, resilience, and psychosocial distress in an Italian sample of glioblastoma patients undergoing radiochemotherapy. The secondary aim was to explore the influence of demographic, clinical, and psychological characteristics on survival. The assessment was conducted only once, within the first week of radiochemotherapy treatment. Spiritual well-being was evaluated by the Functional Assessment of Chronic Illness Therapy-Spiritual Well-being (FACIT-Sp-12), and religious/spiritual beliefs and practices were evaluated by the System of Belief Inventory. Resilience was evaluated by the Connor-Davidson Resilience Scale (CD-RISC). Psychosocial distress was evaluated the by Distress Thermometer and Hospital Anxiety Depression Scale. We conducted an univariable analysis of overall survival (OS) using data from the most recent follow-up available, considering demographic and clinical variables that could influence survival. Follow-up was defined as either the time of death or the latest follow-up visit recorded. We recruited 104 patients, and the median follow-up time was 18.3 months. "Distressed" patients had lower scores than "not distressed" patients on the FACIT-Sp-12 and CD-RISC. While OS was not significant according to the FACIT-Sp-12 threshold, the Kaplan-Meier log-rank test was 0.05 according to the CD-RISC threshold. Among demographic variables, age showed significant associations with OS (p = 0.011). Resilience showed significant associations with OS (p = 0.025). Data showed that high spiritual well-being was associated with high resilience and an absence of psychosocial distress in our sample of glioblastoma patients undergoing radiochemotherapy. Patients with greater resilience survived longer than those with lesser resilience. Profiling spiritual well-being and resilience in glioblastoma patients undergoing radiochemotherapy can be seen as a resource to identify novel characteristics to improve clinical take-in-charge of glioblastoma patients.

Scalable log-ratio lasso regression for enhanced microbial feature selection with FLORAL.

Identifying predictive biomarkers of patient outcomes from high-throughput microbiome data is of high interest, while existing computational methods do not satisfactorily account for complex survival endpoints, longitudinal samples, and taxa-specific sequencing biases. We present FLORAL, an open-source tool to perform scalable log-ratio lasso regression and microbial feature selection for continuous, binary, time-to-event, and competing risk outcomes, with compatibility for longitudinal microbiome data as time-dependent covariates. The proposed method adapts the augmented Lagrangian algorithm for a zero-sum constraint optimization problem while enabling a two-stage screening process for enhanced false-positive control. In extensive simulation and real-data analyses, FLORAL achieved consistently better false-positive control compared to other lasso-based approaches and better sensitivity over popular differential abundance testing methods for datasets with smaller sample sizes. In a survival analysis of allogeneic hematopoietic cell transplant recipients, FLORAL demonstrated considerable improvement in microbial feature selection by utilizing longitudinal microbiome data over solely using baseline microbiome data.

Association between prognostic nutritional index and mortality risk in patients with community-acquired pneumonia: a retrospective study

BackgroundThe prognostic nutritional index (PNI), reflecting the body’s immune-nutritional status, has been established as a correlate of prognosis across various diseases. However, its significance in community-acquired pneumonia (CAP) remains unclear. This study investigated the relationship between PNI and clinical outcomes in CAP patients.MethodsIn this retrospective cohort study, we aimed to evaluate the prognostic value of the PNI in adults with CAP admitted to the ICU. Participants were selected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and categorized into quartiles (Q1–Q4) according to their PNI values. We employed Kaplan-Meier survival analysis, multivariate Cox regression, and restricted cubic spline (RCS) models to explore the association between PNI and the clinical outcomes of these CAP patients.ResultsIn this study, we included 1,608 patients with CAP. The observed 30-day and 90-day mortality rates stood at 30.85% and 39.99%, respectively. Patients with higher PNI levels exhibited a reduced risk of both 30-day and 90-day mortality. Following adjustment for confounders, PNI showed a significant negative association with 30-day mortality [HR, 0.93 (0.91–0.94), P < 0.001] and 90-day mortality [HR, 0.94 (0.92–0.95), P < 0.001]. RCS analysis revealed a consistent trend of declining all-cause mortality risk corresponding to increasing PNI values. PNI demonstrated predictive value for 30-day and 90-day mortality in CAP patients, with AUCs of 0.71 and 0.68, respectively. Combining PNI with CURB-65 enhanced the predictive value of CURB-65.ConclusionOur investigation identified a significant negative association between the PNI and the risk of mortality in patients with CAP. Additionally, the PNI demonstrated superior predictive value for mortality risk in CAP patients when compared to the CURB-65 scoring system.

Profiling Plasma Extracellular Vesicle Metabotypes and miRNAs: An Unobserved Clue for Predicting Relapse in Patients with Early-Stage NSCLC

Background and Objective: Lung cancer, the second most prevalent cancer globally, poses significant challenges in early detection and prognostic assessment. Despite advancements in targeted therapies and immunotherapy, the timely identification of relapse remains elusive. Blood-based liquid biopsy biomarkers, including circulating tumor cells (CTCs), cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), circulating-free RNAs (cfRNAs), and extracellular vesicles (EVs)/exosomes, offer promise for non-invasive monitoring. Methods: We employ a comprehensive approach integrating miRNA/lncRNA/metabolomic datasets, following a mixed-methods content analysis, to identify candidate biomarkers in NSCLC. NSCLC-associated miRNA/gene/lncRNA associations were linked to in silico-derived molecular pathways. Results: For data validation, mass spectrometry-based untargeted metabolomics of plasma EVs highlighted miRNA/lncRNA/metabotypes, linking “glycerophospholipid metabolism” to lncRNA H19 and “alanine, aspartate and glutamate metabolism” to miR-29a-3p. Prognostic significance was established for miR-29a-3p, showing lower expression in NSCLC patients with disease progression compared to stable disease (p = 0.004). Kaplan–Meier survival analysis indicated that patients with miR-29a-3p under-expression had significantly shorter overall survival (OS) (p = 0.038). Despite the expression of lncRNA H19 in plasma EVs being undetected, its expression in plasma cfRNAs correlated significantly with disease progression (p = 0.035). Conclusions: Herein, we showcase the potential of plasma EV-derived miR-29a-3p as a prognostic biomarker and underscore the intricate interplay of miRNAs, lncRNAs, and metabolites in NSCLC biology. Our findings offer new insights and avenues for further exploration, contributing to the ongoing quest for effective biomarkers in early-stage NSCLC.

Exploring the Dynamic Interplay of Deleterious Variants on the RAF1-RAP1A Binding in Cancer: Conformational Analysis, Binding Free Energy, and Essential Dynamics.

The RAF1-RAP1A interaction activates the MAPK/ERK pathway which is very crucial in the carcinogenesis process. This protein complex influences tumor formation, proliferation, and metastasis. Understanding aberrant interactions driven by clinical mutations is vital for targeted therapies. Hence, the current study focuses on the screening of clinically reported substitutions in the RAF1 and RAP1A genes using predictive algorithms integrated with all-atoms simulation, essential dynamics, and binding free energy methods. Survival analysis results revealed a strong association between RAF1 and RAP1A expression levels and diminished survival rates in cancer patients across different cancer types. Integrated machine learning algorithms showed that among the 134 mutations reported for these 2 proteins, only 13 and 35 were classified as deleterious mutations in RAF1 and RAP1P, respectively. Moreover, one mutation in RAF1 reported elevated levels of binding between RAF1 and RAP1P while in RAP1A, 7 mutations were reported to increase the binding affinity. The high-binding mutations, P34Q and V60F, were subjected to protein-protein coupling which confirmed the increase in the binding affinity. Wild-type and mutant RAF1-RAP1P bound complexes were subjected to molecular simulation investigation, revealing enhanced structural stability, increased compactness, and stabilized residue fluctuations of the mutant systems in contrast to the wild-type. In addition, hydrogen bonding analysis revealed a variation in the binding paradigm which further underscores the impact of these substitutions on the coupling of RAF1 and RAP1A. Principal component analysis (PCA) and free energy landscape (FEL) evaluation further determined dynamical variations in the wild-type and mutant complexes. Finally, the Gibbs free energy for each complex was estimated and found to be -71.94 ± 0.38 kcal/mol for the wild-type, -95.57 ± 0.37 kcal/mol for the V60F, and -85.76 ± 0.72 kcal/mol for P34Q complex. These findings confirm the effect of these variants on increasing the binding affinity of RAF1 to RAP1P. These mutations can therefore be targeted for cancer therapy to modulate the activity of the MAPK/ERK signaling pathway.

TBL2 Promotes Tumorigenesis via PRMT5/WDR77-Mediated AKT Activation in Breast Cancer.

Breast cancer (BC) is a common malignancy that affects women worldwide. Although transducing beta-like 2 (TBL2), a member of the WD40 repeat protein family, has been implicated in various intracellular signaling pathways, its precise function in BC remains unclear. The expression of TBL2 is analyzed using real-time PCR, western blotting, and immunohistochemistry in BC patient specimens. Kaplan-Meier survival analysis is employed to assess its prognostic significance. Proteomic analysis, immunoprecipitation tests, and protein immunoblotting are employed to examine the impact of TBL2 on AKT phosphorylation activation. The findings reveal selective overexpression of TBL2 in BC, correlating significantly with various clinicopathological characteristics and poor survival outcomes in patients with BC. Through in vivo and in vitro experiments, it is observed that TBL2 suppression inhibits BC cell proliferation, while TBL2 overexpression has the opposite effect. Mechanistically, TBL2 is identified as a scaffolding protein that promotes PRMT5 and WDR77 interaction. This interaction enhances the methyltransferase activity of PRMT5, leading to increased AKT phosphorylation activation and promotion of breast cancer cell proliferation. In conclusion, this study uncovers a novel function of TBL2 in the activation of AKT by PRMT5 and suggests TBL2 as a potential therapeutic target for BC treatment.

Negative Impact of Systemic Therapy on Survival in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Low-Grade Metastatic Appendiceal Adenocarcinoma.

Despite studies demonstrating that patients with peritoneal metastases from low-grade appendiceal adenocarcinoma (AA) do not respond well to systemic chemotherapy (SC), patients frequently undergo combination of SC with cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) regardless of grade. A nationwide retrospective analysis using the National Cancer Database evaluated patients with AA with peritoneal metastasis from 2016 to 2021. Cox proportional hazards model was used to evaluate the impact of SC in addition to CRS/HIPEC on overall survival (OS) stratified by tumor grade. A total of 1,449 patients were included: 481 low-grade, 428 intermediate-grade, and 540 high-grade tumors. Clinical variables, such as age, sex, and comorbidity index, were similar across tumor grades. Cytoreductive surgery/hyperthermic intraperitoneal chemotherapy without SC was utilized in 65.73% of low-grade cases compared with 41.01% in intermediate-grade and 11.11% in high-grade cases. Systemic chemotherapy was utilized alone in 17.74% and with CRS/HIPEC in 16.53% of low-grade cases. In adjusted survival analysis, addition of SC to CRS/HIPEC was associated with worse OS for patients with low-grade AA (hazard ratio [HR] 2.77, 95% confidence interval [CI] 1.18-6.50) but not for intermediate (HR 1.65, 95% CI 0.82-3.35) and high-grade tumors (HR 1.18, 95% CI 0.67-2.45). The addition of time to definitive surgery variable nullified the negative impact of adding SC to CRS/HIPEC in low-grade AA (HR 1.76, 95% CI 0.68-4.53). Negative OS impact of SC may be mediated by delays in effective surgical/intraoperative therapy. If CRS/HIPEC is planned for patients with metastatic low-grade AA, avoiding SC may facilitate earlier surgical intervention and improve survival.

How long does purchase intention exist? “Buying intention survival”: a new insight into forecasting purchase intention abandonment

PurposeThe purpose of this study is to predict the probability and duration of “Buying Intention Survival” (BIS) and to propose a conceptual framework illustrating its determinants. More specifically, it aims to determine the likelihood of buying intention abandonment (BIA) and the time frame in which the intention abandonment might occur.Design/methodology/approachThe data for this study were collected using an online survey of a sample of 573 Tunisian consumers. The data were then subjected to a survival analysis. This method is used for the first time in this context.FindingsResults show that the average duration of the BIS could extend over 162 months. Findings also suggest that involvement, anticipated regret linked to a no-purchase decision and social influence have a positive effect on BIS, whereas anticipated regret linked to purchase influences BIS negatively.Practical implicationsAccurately anticipating the date of BIA is of paramount importance for marketers as it allows them to implement strategies that reduce the risk of abandonment and encourage customers to promptly fulfill their purchasing intentions.Originality/valueThis paper introduces a new concept, namely, BIS, and applies a survival analysis method to determine whether purchase intention disappears over time, how soon it may disappear, and possible reasons this may occur.

Association Between Atrial Fibrillation and Long-term Mortality in Acute MI Patients

Background: AF is a common complication of an acute MI (AMI) and goes along with adverse events. Nevertheless, the therapeutical guidelines and pharmacological possibilities have improved over the past years. Therefore, this contemporary study aimed to clarify the effect of AF on long-term mortality in patients with incident AMI. Methods: This study included 2,313 patients aged 25–84 years with initial AMI that occurred from 2009 until 2017, documented within the population-based Augsburg Myocardial Infarction Registry. Patients were monitored from hospital admission, with a median follow-up duration of 4.5 years (interquartile range 4.4 years). Survival analysis and multivariable Cox regression analysis were conducted to explore the relationship between AF and long-term all-cause and cardiovascular disease mortality. Results: Altogether, 156 individuals had AF on their admission ECG, while the remaining 2,157 presented with sinus rhythm (SR). Patients with AF were significantly older, more frequently had arterial hypertension, non-ST-segment elevation MI, worse kidney function, smaller AMIs, and were more often former and non-smokers. An increased long-term all-cause mortality was observed among the AF group. (AF patients 39.1%, SR group 16.7%), Upon multivariable adjustment, a HR of 1.40 (95% CI [1.05–1.87]; p=0.023) was calculated when comparing the AF with SR patients. Conclusion: An independently increased risk of long-term mortality for patients with AF compared with patients with SR in case of incident AMI was identified. Therefore, AF should be considered as a serious risk factor in AMI patients, and must be treated aggressively to reduce mortality risk.

Assessing variable importance in survival analysis using machine learning

SUMMARY Given a collection of features available for inclusion in a predictive model, it may be of interest to quantify the relative importance of a subset of features for the prediction task at hand. For example, in HIV vaccine trials, participant baseline characteristics are used to predict the probability of HIV acquisition over the intended follow-up period, and investigators may wish to understand how much certain types of predictors, such as behavioral factors, contribute toward overall predictiveness. Time-to-event outcomes such as time to HIV acquisition are often subject to right censoring, and existing methods for assessing variable importance are typically not intended to be used in this setting. We describe a broad class of algorithm-agnostic variable importance measures for prediction in the context of survival data. We propose a nonparametric efficient estimation procedure that incorporates flexible learning of nuisance parameters, yields asymptotically valid inference, and enjoys double-robustness. We assess the performance of our proposed procedure via numerical simulations and analyze data from the HVTN 702 vaccine trial to inform enrollment strategies for future HIV vaccine trials.

Single-cell RNA sequencing analysis identifies acute changes in the tumor microenvironment induced by interferon α gene therapy in a murine bladder cancer model

IntroductionNadofaragene firadenovec (Ad-IFNα/Syn3) is now approved for BCG-unresponsive bladder cancer (BLCA). IFNα is a pleiotropic cytokine that causes direct tumor cell killing via TRAIL-mediated apoptosis, angiogenesis inhibition, and activation of the innate and adaptive immune system. We established an immunocompetent murine BLCA model to study the effects of murine adenoviral IFNα (muAd-Ifnα) gene therapy on cancer cells and the tumor microenvironment using a novel murine equivalent of Nadofaragene firadenovec (muAd-Ifnα).MethodsTumors were induced by instilling MB49 cells into the bladders of mice; luciferase imaging confirmed tumor development. Mice were treated with adenovirus control (Ad-Ctrl; empty vector), or muAd-Ifnα (3x1011 VP/mL), and survival analysis was performed. For single-cell sequencing (scRNAseq) analysis (72h), bladders were harvested and treated with collagenase/hyaluronidase and TrypLE for cell dissociation. Single cells were suspended in PBS/1% FBS buffer; viability was assessed with Vicell cell counter. scRNAseq analysis was performed using 10X genomics 3’ sequencing. Raw RNAseq data were pre-processed using Cell Ranger single-cell software. Seurat (R package) was used to normalize and cluster the scRNA data. Pooled differential gene expression analysis in specific cell clusters was performed with DESeq2.ResultsWe identified 16 cell clusters based on marker expression which were grouped into epithelial (tumor), uroplakin-enriched, endothelial, T-cells, neutrophils, and macrophage clusters. Top differentially expressed genes between muAd-Ifnα and Ad-Ctrl were identified. Within the specific cell clusters, IPA analysis revealed significant differences between muAd-Ifnα and control. IFNα signaling and hypercytokinemia/chemokinemia were upregulated in all clusters. Cell death pathways were upregulated in tumor and endothelial clusters. T-cells demonstrated upregulation of the immunogenic cell death signaling pathway and a decrease in the Th2 pathway genes. Macrophages showed upregulation of PD1/PD-L1 pathways along with downregulation of macrophage activation pathways (alternate and classical). Multiplex immunofluorescence confirmed increased infiltration with macrophages in muAd-Ifnα treated tumors compared to controls. PD1/PD-L1 expression was reduced at 72h.DiscussionThis single-cell analysis builds upon our understanding of the impact of Ad-IFNα on tumor cells and other compartments of the microenvironment. These data will help identify mechanisms to improve patient selection and therapeutic efficacy of Nadofaragene firadenovec.

Prognostic Impact of a Histologic Grading Scheme in Dogs Diagnosed With Rib Chondrosarcoma.

Data regarding the outcome of canine rib chondrosarcoma is sparse and varied. While grade of tumour is associated with outcome for canine appendicular chondrosarcoma, the association of grade with outcome for canine rib chondrosarcoma is unclear. This study aimed to correlate the grade of canine rib chondrosarcoma with median survival time. Retrospectively, cases of primary rib chondrosarcoma were identified, and tumours were graded based on a 3-tier adapted human grading scheme. Twenty-two patients were included in the survival analysis. The median survival time was 1427 days (range: 27-3354 days). This was not significantly different for patients with grade I versus II versus III (p = 0.82), grade I-II versus III (p = 0.34), or grade I versus II-III (p = 0.49). No variables assessed including age, weight, tumour location (cranial vs. caudal thorax; left vs. right hemithorax), tumour location on rib (proximal, middle, and distal), radiographic appearance (lytic, proliferative, or mixed), elevated serum alkaline phosphatase activity, grade, grade specific histologic features (matrix production, architecture, pleomorphism, cellularity, necrosis, and total score), adjunct therapy post-surgical excision, development of metastatic disease post-surgery, or local recurrence post-surgery were found to impact the risk of death due to chondrosarcoma. In this limited group of patients, the grading scheme reported here, and the other variables assessed did not appear to offer additional prognostic information. However, this data must be interpreted considering the small sample size and thus low statistical power. Additional studies are needed to determine the true impact of grade on outcome for canine rib chondrosarcomas.

Transcriptomic Analysis of Cell Stress Response in Wickerhamomyces anomalus H4 Under Octanoic Acid Stress

The purified yeast strain H4, identified as W. anomalus through morphological, genetic, and phylogenetic analyses, was characterized and compared to a commercial Saccharomyces cerevisiae strain X16. W. anomalus H4 exhibited distinct morphological features. It demonstrated notable tolerance to 11% ethanol, 220 g/L glucose, and 200 mg/L octanoic acid, similar to X16, except for having a lower tolerance to SO2. Survival analysis under various stress conditions revealed that ethanol and octanoic acid had the most detrimental effects, with 56% cell mortality at 13% ethanol and 400 mg/L octanoic acid. Transcriptomic analysis under octanoic acid stress showed that at 200 mg/L, 3369 differentially expressed genes (DEGs) were induced, with 1609 being upregulated and 1760 downregulated, indicating broad transcriptional reprogramming. At 400 mg/L, only 130 DEGs were detected, suggesting a more limited response. KEGG pathway analysis indicated that most DEGs at 200 mg/L were associated with the “ribosome” and “proteasome” pathways, reflecting disruptions in protein synthesis and turnover. At 400 mg/L, the DEGs were primarily related to “DNA replication” and “pyruvate metabolism”. These findings highlight the adaptive mechanisms of W. anomalus H4 to environmental stresses, particularly octanoic acid, and its potential for use in brewing and fermentation processes.

Novel family of probability generating distributions: Properties and data analysis

Abstract Current probability distributions often fall short when modeling lifespan data with non-monotonic hazard rate shapes, highlighting a gap in probability theory. To address this issue, this study introduces the novel family of probability-generating distributions (NP-G) as a solution to capture complex data patterns better. This research aims to develop and validate the NP-G distributions, which include a two-parameter continuous model based on the Weibull distribution. The study extensively explores the mathematical properties of the NP-G distributions, including series expansions of probability density functions, and evaluates various probabilistic measures such as moments, stress strength, mean deviations, entropy measures, and order statistics. Using the maximum likelihood method for parameter estimation and conducting a numerical simulation analysis, the study assesses the performance of the proposed extended exponentiated Weibull model. The findings demonstrate that this new model offers superior fit and accuracy compared to existing distributions when applied to two referenced datasets. This advancement is significant as it provides a more effective tool for analyzing lifespan data with non-monotonic hazard rates, enhancing both theoretical understanding and practical applications in fields such as reliability engineering and survival analysis.

Efficacy of rechallenge after first-line immunotherapy for advanced gastric cancer: A retrospective real-world study

ABSTRACT We aimed to explore the efficacy of rechallenge after first-line immunotherapy in advanced gastric cancer (AGC) and to analyze the factors affecting prognosis based on clinical characteristics. Eighty-five AGC patients who underwent rechallenged after the failure of first-line treatment with immune checkpoint inhibitors (ICIs) were retrospectively collected from July 2019 to December 2022 in Jiangsu Cancer Hospital. Potential factors affecting prognosis were analyzed by univariate and multivariate Cox analysis. Survival analysis was performed by Kaplan–Meier method and Log rank test. Stratified factors included human epidermal growth factor receptor 2 (HER-2) and programmed cell death-ligand 1 combined positive score (PD-L1 CPS). The objective response rate (ORR) was 15.3%, and the disease control rate (DCR) was 74.1%. The median progression-free survival (PFS) was 4.8 months. Results showed that patients in the I + C group had the best response. The ORR was 20.0% VS 8.7% in the I + C group and I + C + AAD group. The DCR was 78.0% VS 65.2%, and the median PFS was 6.7 VS 4.7 months [hazard ratio (HR): 0.55, 95% confidence interval (CI): 0.30–1.00, p = .022]. The ORR was 20.0% VS 8.3% in the I + C group and I + C + ADC group. The DCR was 78.0% VS 75.0%, and the median PFS was 6.7 VS 4.4 months (HR: 0.59, 95%CI: 0.26–1.30, p = .112). The median PFS was 4.7 VS 4.4 months in the I + C + AAD group and I + C + ADC group (HR: 1.21, 95%CI: 0.60–2.47, p = .580). Adverse events (AEs) were found in 34 patients, mainly including leukopenia 9 (10.6%), and neutropenia 8 (9.4%). The incidence of grade 3–4 AEs was 8.2%. There were no drug-related deaths and all AEs were manageable. Rechallenge after first-line immunotherapy showed good survival benefit and acceptable safety in the therapy of AGC. Especially for patients with HER-2-positive and PD-L1 CPS ≥ 1%, rechallenge may be an effective treatment modality.

The neutrophil–lymphocyte ratio is associated with all-cause and cardiovascular mortality in cardiovascular patients

This study investigates the relationship of neutrophil–lymphocyte ratio (NLR) with the risk of all-cause and cardiovascular mortality in patients with cardiovascular disease. The data for this analysis came from 2239 participants with cardiovascular disease of the National Health and Nutrition Examination Survey conducted between 1999–2018. The optimal cutoff point for NLR was determined using maximally selected rank statistics. Survival analysis was performed using Cox regression models to assess the impact of NLR on the risk of all-cause mortality and cardiovascular mortality. Restricted cubic spline was used to visualize the association of NLR with mortality risk. Subgroup analysis was performed to examine the relationship between NLR and mortality within subgroups based on age, sex, diabetes and hypertension. During a median follow-up period of 6.7 (IQR, 3.3–10.9) years, 992 all-cause deaths occurred, including 381 cardiovascular deaths. Our study revealed that NLR is a risk factor for all-cause mortality (HR: 1.15 95%Cl: 1.11 ~ 1.19) and cardiovascular mortality (HR: 1.14 95%Cl: 1.08 ~ 1.2) among patients with cardiovascular disease. The restricted cubic spline regression analysis showed a non-linear association between NLR and all-cause mortality (p < 0.05 for nonlinearity) in cardiovascular patients. This association remained robust in subgroup analyses stratified by age, sex, diabetes, and hypertension. Conclusion NLR stands as a significant risk factor for both all-cause and cardiovascular mortality among patients with cardiovascular disease.

On the Estimation of Survival Rate Using Ranked Set Sampling Design

The Nigerian pensioners have high expectations from the government to ensure an effective implementation of pension regulations existing in the country. These expectations arise from the need to have sustainable standard of living in retirement and their benefits paid as at when due. However, the government does not know how many retirees will be alive at a particular period of time to draw fund from the pension account. This calls for regular verification of pensioners by Pension Transitional Arrangements Directorate (PTAD) at national level, office of the accountant general for State level and Local Government Pensions Board for Unified Local Government Council. This process exposed pensioners to stress related problems and some pensioners even die during such verification exercise. Again, it gives rise to varying set of problems that limit the capacity of the stakeholders within Nigeria pension industry to meet pensioner’s expectations. Survival rate of these retirees is key important statistic to the government for adequate preparation for their terminal benefits and to provide other social packages for this vulnerable group of people. However, this statistic is lacking in the State. Consequently, this work intends to address this problem by using the theory of Ranked Set Sampling (RSS) for Survival analysis to estimate the Survival rate of the retirees which will help the government in making adequate budgetary provisions to the Nigeria Pension Industry. Analysis and evaluation are presented.

A structural description of biases that generate immortal time.

Immortal time arises when individuals in the analysis are either selected based on post-assignment eligibility criteria or assigned to treatment strategies based on post-eligibility information. Explicit target trial emulation prevents the introduction of immortal time in survival analyses of observational data because it synchronizes eligibility and treatment assignment at the start of follow-up. Describing the structure of the biases that generate immortal time is facilitated by specifying the target trial so that the procedures to determine eligibility and assignment can be appropriately evaluated. Selection based on eligibility criteria applied after treatment assignment at the start of follow-up results in immortal time when the analysis starts the follow-up at assignment. Misclassification of assignment to treatment strategies based on treatment received after the start of follow-up results in immortal time when the treatment strategies are not distinguishable at the start of follow-up. The above selection and misclassification can be represented using causal diagrams. We summarize analytic approaches that prevent immortal time when longitudinal data are available from the time of treatment assignment. The term "immortal time bias" suggests that the source of the bias is the immortal time, but it is selection or misclassification that generates the immortal time, leading to bias.