Cumulative Hazard Research Articles

Identification of Neighborhood Hotspots via the Cumulative Hazard Index: Results From a Community-Partnered Low-Cost Sensor Deployment.

The Strathcona neighborhood in Vancouver is particularly vulnerable to environmental injustice due to its close proximity to the Port of Vancouver, and a high proportion of Indigenous and low-income households. Furthermore, local sources of air pollutants (e.g., roadways) can contribute to small-scale variations within communities. The aim of this study was to assess hyperlocal air quality patterns (intra-neighborhood variability) and compare them to average Vancouver concentrations (inter-neighborhood variability) to identify possible disparities in air pollution exposure for the Strathcona community. Between April and August 2022, 11 low-cost sensors (LCS) were deployed within the neighborhood to measure PM2.5, NO2, and O3 concentrations. The collected 15-min concentrations were down-averaged to daily concentrations and compared to greater Vancouver region concentrations to quantify the exposures faced by the community relative to the rest of the region. Concentrations were also estimated at every 25m grid within the neighborhood to quantify the distribution of air pollution within the community. Using population information from census data, cumulative hazard indices (CHIs) were computed for every dissemination block. We found that although PM2.5 concentrations in the neighborhood were lower than regional Vancouver averages, daily NO2 concentrations and summer O3 concentrations were consistently higher. Additionally, although CHIs varied daily, we found that CHIs were consistently higher in areas with high commercial activity. As such, estimating CHI for dissemination blocks was useful in identifying hotspots and potential areas of concern within the neighborhood. This information can collectively assist the community in their advocacy efforts.

The fatty acid-related gene signature stratifies poor prognosis patients and characterizes TIME in cutaneous melanoma

BackgroundThe aim of this study is to build a prognostic model for cutaneous melanoma (CM) using fatty acid-related genes and evaluate its capacity for predicting prognosis, identifying the tumor immune microenvironment (TIME) composition, and assessing drug sensitivity.MethodsThrough the analysis of transcriptional data from TCGA-SKCM and GTEx datasets, we screened for differentially expressed fatty acids-related genes (DEFAGs). Additionally, we employed clinical data from TCGA-SKCM and GSE65904 to identify genes associated with prognosis. Subsequently, utilizing all the identified prognosis-related fatty acid genes, we performed unsupervised clustering analysis using the ConsensusClusterPlus R package. We further validated the significant differences between subtypes through survival analysis and pathway analysis. To predict prognosis, we developed a LASSO-Cox prognostic signature. This signature's predictive ability was rigorously examined through multivariant Cox regression, survival analysis, and ROC curve analysis. Following this, we constructed a nomogram based on the aforementioned signature and evaluated its accuracy and clinical utility using calibration curves, cumulative hazard rates, and decision curve analysis. Using this signature, we stratified all cases into high- and low-risk groups and compared the differences in immune characteristics and drug treatment responsiveness between these two subgroups. Additionally, in this study, we provided preliminary confirmation of the pivotal role of CD1D in the TIME of CM. We analyzed its expression across various immune cell types and its correlation with intercellular communication using single-cell data from the GSE139249 dataset.ResultsIn this study, a total of 84 DEFAGs were identified, among which 18 were associated with prognosis. Utilizing these 18 prognosis-related genes, all cases were categorized into three subtypes. Significant differences were observed between subtypes in terms of survival outcomes, the expression of the 18 DEFAGs, immune cell proportions, and enriched pathways. A LASSO-Cox regression analysis was performed on these 18 genes, leading to the development of a signature comprising 6 DEFAGs. Risk scores were calculated for all cases, dividing them into high-risk and low-risk groups. High-risk patients exhibited significantly poorer prognosis than low-risk patients, both in the training group (p < 0.001) and the test group (p = 0.002). Multivariate Cox regression analysis indicated that this signature could independently predict outcomes [HR = 2.03 (1.69–2.45), p < 0.001]. The area under the ROC curve for the training and test groups was 0.715 and 0.661, respectively. Combining risk scores with clinical factors including metastatic status and patient age, a nomogram was constructed, which demonstrated significant predictive power for 3 and 5 years patient outcomes. Furthermore, the high and low-risk subgroups displayed differences in the composition of various immune cells, including M1 macrophages, M0 macrophages, and CD8+ T cells. The low-risk subgroup exhibited higher StromalScore, ImmuneScore, and ESTIMATEScore (p < 0.001) and demonstrated better responsiveness to immune therapy for patients with PD1-positive and CTLA4-negative or positive expressions (p < 0.001). The signature gene CD1D was found to be mainly expressed in monocytes/macrophages and dendritic cells within the TIME. Through intercellular communication analysis, it was observed that cases with high CD1D expression exhibited significantly enhanced signal transductions from other immune cells to monocytes/macrophages, particularly the (HLA-A/B/C/E/F)-CD8A signaling from natural killer (NK) cells to monocytes/macrophages (p < 0.01).ConclusionsThe prognostic signature constructed in this study, based on six fatty acid-related genes, exhibits strong capabilities in predicting patient outcomes, identifying the TIME, and assessing drug sensitivity. This signature can aid in patient risk stratification and provide guidance for clinical treatment strategies. Additionally, our research highlights the crucial role of CD1D in the CM's TIME, laying a theoretical foundation for future related studies.

Effects of simplified group housing on behavior, welfare, growth performance, and health of preweaned dairy calves on a California dairy

Most US dairy calves are raised in individual hutches (IH) for biocontainment purposes and to facilitate monitoring and handling of calves. However, individual hutches typically restrict calves' activity and social interactions. Previous studies showed that group housing (GH) is beneficial to calf welfare and is associated with social benefits. The adoption of group housing (GH) on dairies is hindered by several concerns, with the primary concern being the potential for increased transmission of diseases due to heightened calf-to-calf contact. In light of this, our study aimed to compare the behavior, health, and growth outcomes of calves housed in groups of 3 to individually housed (IH) calves during the preweaning period. A total of 42 Holstein heifer calves on a commercial dairy in Northern California were enrolled in groups of 3 to different housing treatments; IH (n = 21) or GH (n = 21) between July and October 2020. Each treatment was composed of 7 groups of 3 calves each. Calves in the GH treatment were housed in groups of 3 from 6 to 10 d until 70 d of age. Individual pens consisted of one polyethylene hutch with a 1.5 m x 1.2 m outside exercise area. Group pens were constructed by assembling 3 polyethylene hutches with a 1.5 m x 3.6 m outside exercise area of wire panel fencing. Calves were weighed and measured for height at birth and weaning. Diarrhea and bovine respiratory disease (BRD) scores were recorded daily throughout the preweaning period. Cumulative incidence and hazard ratios were estimated for BRD and diarrhea for GH and IH. A Mixed model with pen as a random effect was specified to evaluate the effect of treatment. Group-housed calves gained 0.64 ± 0.02 kg/d while IH calves gained 0.65 ± 0.02 kg/d (P = 0.40). Similarly, there was no evidence for treatment differences in withers height gain in GH calves (0.22 ± 0.01cm/d) compared with IH calves (0.21 ± 0.01 cm/d) (P = 0.14). The cumulative incidence of BRD based on California scoring system in GH calves was 75 ± 9.68 compared with 66.66 ± 10.28% in IH calves (P = 0.73). Group-housed calves had a BRD hazard of 1.14 times that of IH calves (95% CI: 1.21-2.40; P = 0.74). The cumulative incidence of diarrhea (fecal score 3) in GH calves was 100% in comparison to 95.20 ± 4.66% in IH calves (P = 0.99). The mean proportion of scan observations of calves feeding on concentrates was significantly higher in GH (0.145 ± 0.004 per h) compared with IH calves (0.076 ± 0.003 per h) during the preweaning period (P < 0.001). The study results provide evidence that this simplified group housing system provides benefits of GH without detrimental short-term impacts during the preweaning period on calf growth and health.

Epidemiology of spinal cord injury and spinal cord injury–induced urinary tract stones in Taiwan: A 2005–2015 population-based cohort study

Context Patients with spinal cord injury (SCI) can develop urinary tract stones (UTSs) up to years after the injury, which is especially common in the first few months. However, relevant epidemiological studies and up-to-date epidemiological data for SCI in Taiwan are lacking. Purpose To estimate SCI and SCI-induced UTS incidence and trauma severity, neurological deficits, and injury site in patients with SCI-induced UTSs in Taiwan. Design Retrospective cohort study. Patient sample: Taiwan National Health Insurance Research Database (NHIRD) data and death data from the Department of Health and Welfare Data Science Center (HWDC) collected over 2005–2015 from 13,977 patients with SCI aged >18 years. Outcome measures Cumulative incidence (CI), incidence density (ID), relative ratios (RRs), odds ratios (ORs), and hazard ratios (HRs) were measured. Methods By using Cox regression, we assessed UTS risk in patients with SCI. Results Although standardized SCI incidence demonstrated a decreasing trend annually, the average annual incidence remained at 60.4 per million. Most (65.7%) of the included patients were men. SCI incidence was 1.98 times higher in men than in women. The most common injury site was the cervical spine (63.8%); the incidence at this site was 2.83 times higher in men than in women. Most (76.1%) of the patients had traumatic SCI (TSCI), and the standardized incidence of TSCI and non-TSCI was 45.9 and 14.4 per million, respectively. 46.1% of the patients had severe SCI (RISS ≥ 16). Over the 11-year follow-up period, UTSs occurred in 10.4% of the patients, with a standardized incidence of 2.39 per 100 person-years, and UTS risk was 1.56 times higher in men than in women. Age of 45–65 years, SCIs at multiple sites, and neurological deficits (e.g. paraplegia) were noted to be UTS risk factors. Finally, UTS onset mainly occurred in the first year after SCI. Conclusion The risk of UTS among patients with SCI is influenced by age, sex, injury site, and paraplegia but not by paralysis resulting from other neurological deficits. Even though SCI incidence is declining annually, severe SCI remains a significant issue. Therefore, continuing to reduce SCI incidence and strengthening urinary tract management in patients with SCI are essential for reducing UTS occurrence and their impact on health.

Risk Factors for Hospital Readmission in Patients With Interstitial Lung Disease.

Little is known about the rates, causes, or risk factors for hospital readmission among patients with interstitial lung disease (ILD). We investigated the prevalence, features, and comorbidities of subjects hospitalized with ILD and their subsequent re-hospitalizations in this retrospective study. A retrospective analysis of subjects enrolled in the University of Chicago ILD Natural History registry was conducted. Demographic data, comorbidities, and timing and cause of subsequent hospitalizations were collected from the medical record. The primary outcome was time to first readmission via a cause-specific Cox hazards model with a sensitivity analysis with the Fine-Gray cumulative hazard model; the secondary outcome was the number of hospitalizations per subject via a Poisson multivariable model. Among 1,796 patients with ILD, 443 subjects were hospitalized, with 978 total hospitalizations; 535 readmissions were studied, 282 (53%) for a respiratory indication. For the outcome of time to readmission, Black race was the only subject characteristic associated with an increased hazard of readmission in the Cox model (hazard ratio 1.50, P = .03) while Black race, hypersensitivity pneumonitis, and sarcoidosis were associated with increased hazard of readmission in the Fine-Gray model. Black race, female sex, atrial fibrillation, obstructive lung disease, and pulmonary hypertension were associated with an increased number of hospitalizations in the Poisson model. We demonstrated that hospital readmission from any cause was a common occurrence in subjects with ILD. Further efforts to improve quality of life among these subjects could focus on risk scores for readmission, mitigating racial health disparities, and treatment of comorbidities.

Comparison of mortality rates in patients with carbapenem-resistant Enterobacterales bacteremia according to carbapenemase production: a multicenter propensity-score matched study

The spread of carbapenem-resistant Enterobacterales (CRE) poses a public health threat worldwide. We aimed to compare the mortality rates between the carbapenemase-producing (CP) and non-CP CRE bacteremia. We conducted a retrospective cohort study in patients with CRE bacteremia after propensity score (PS) matching. We performed a Kaplan–Meier curve analysis to identify the cumulative hazard for 30-day mortality. There were 318 patients with CRE between January 1, 2018, and December 31, 2022. There were 252 patients with CP-CRE and 66 with non-CP-RE, respectively. Before PS matching, the 30-day mortality rates were 40.9% in the non-CP-CRE group and 53.2% in the CP-CRE group (p = 0.097). In patients in the intensive care unit (ICU), the mortality rates were 49.0% in the non-CP-CRE group and 57.1% in the CP-CRE group (p = 0.340). After PS matching, the hazard ratio (HR) for mortality in the CP-CRE group was 1.49 (95% confidence interval [CI] 0.74–3.03), p = 0.266). In ICU patients, the HR of CP-CRE was 1.11 (95% CI 0.36–3.39, p = 0.860). The Kaplan–Meier curve for 30-day mortality showed no difference in cumulative hazard. After PS matching, there was no difference in 30-day mortality between patients with CP-CRE and non-CP-CRE bacteremia.

Infection risk in patients with autoimmune cytopenias and immune dysregulation treated with mycophenolate mofetil and sirolimus.

Autoimmune cytopenias (AICs) are a group of disorders characterized by immune-mediated destruction of blood cells. In children, they are often secondary to immune dysregulation that may require long-lasting immunosuppression. Mycophenolate mofetil and sirolimus represent two well-tolerated options to treat these disorders, often as a steroid-sparing option. However, no data are available on the infection risk for patients undergoing long-lasting treatments. The rate of severe infective events was calculated in episodes per 100 persons/months at risk (p/m/r) documented by the analysis of hospitalization charts between January 2015 and July 2023 of patients treated with mycophenolate mofetil or sirolimus given for isolated AIC or AICs associated with autoimmune lymphoproliferative syndrome (ALPS)/ALPS-like syndromes in two large Italian pediatric hematology units. From January 2015 to July 2023, 13 out of 96 patients treated with mycophenolate mofetil or sirolimus developed 16 severe infectious events requiring hospitalization. No patients died. Overall infection rate was 0.24 person/*100 months/risk (95% CI 0.09-0.3). Serious infectious events incidence was higher in patients with ALPS-like compared to others (0.42 versus 0.09; p = 0.006) and lower in patients who underwent mycophenolate treatment alone compared to those who started sirolimus after mycophenolate failure (0.04 versus 0.29, p = 0.03). Considering only patients who started treatment at the beginning of study period, overall cumulative hazard was 18.6% at 60 months (95% CI 3.4-31.4) with higher risk of infectious events after 5 years in ALPS-like patients (26.1%; 95% CI 3.2-43.5) compared to other AICs (4%; 95% CI 0-11.4; p = 0.041). To the best of our knowledge, this is the first study to describe the infectious risk related to mycophenolate and sirolimus chronic treatment in patients with AICs and immune dysregulation. Our data highlight that infection rate is very low and mainly related to the underlying hematological condition. Mycophenolate and sirolimus represent a safe immunosuppressive therapy in AICs and immune dysregulation syndromes.

A New Version of Gumbel Distribution Using Sine Technique Family: Properties, Parameter Estimation, and Data Analysis and Comparison with Fuzzy Data

In this paper, we propose a new version of the Gumbel Distribution using a sine technique family. We discuss the key properties of this distribution, such as the probability density function, the cumulative distribution function, the survival function, the hazard function, the cumulative hazard, and the moments. Additionally, we present a method for estimating the distribution's parameters. We then analyze a dataset using the original and generalized distributions, comparing the results and using goodness-of-fit measures to determine which distribution best fits the data. Finally, we provide conclusions based on our findings, with many examples and valid comparisons applied on fuzzy data.

Association of D-dimer to albumin ratio with adverse cardiovascular outcomes in ischaemic heart failure patients with diabetes mellitus: a retrospective cohort study

ObjectiveTo determine the association of D-dimer to albumin ratio (DAR) with major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) in ischaemic heart failure patients with diabetes mellitus.DesignA retrospective...

Model Regresi Cox Untuk Data Masa Studi (Studi Kasus: Data Masa Studi Mahasiswa Fakultas Teknik Universitas Bangka Belitung)

Student study time is the time needed by students to complete their education, which starts from the time they enter college until they are declared graduated or have completed their study period. In the study period data, survival time observations were only carried out partially or not until the failure event. In other words, termination occurs until the observation deadline. This termination occurred due to several factors that allegedly influenced the student's study period. Using study period data for students of the Faculty of Engineering, University of Bangka Belitung, class of 2015/2016, this study used the Kaplan Meier Estimation to see the survival function of each factor causing the length of study period graphically and the Log Rank Test statistically. Meanwhile, to look at the factors that determine the length of a student's study period, researchers used the Cox Regression and Maximum Likelihood Estimation (MLE) models to find the best model. The results of the data analysis show that there are differences in the survival function in each category for all variables graphically, while the statistical comparison of the results of the estimation of the survival function curve based on gender and organizational status is not significantly different. The results of the analysis also show that the proportional hazard assumption is fulfilled through the cumulative hazard log so that categorical variables can be used in the Cox Regression model. Based on the results of the likelihood estimation, the variables that have a significant effect on the study period of Engineering Faculty students are majors and GPA variables. Furthermore, from the interpretation of the model parameters, it is obtained that the Hazard Ratio (HR) value for the study period of Mechanical, Mining and Electrical Engineering students is faster than that of Civil Engineering students, while students with GPA ≥ 3.00 have a shorter study period than students with GPA &lt; 3.00.

A New Life-Time Model with Bathtub and Inverted Bathtub Failure Rate Function

In this paper, a three parameter model called Zubair- Kumaraswamy (Z-Kum) distribution is proposed. The extension was done using Zubair G-Family [1] of continuous probability distribution to extend the well knownKumaraswamy distribution to make it more flexible in modeling and predicting real world phenomenon. Some basic structural properties of the new distributions like cdf, pdf, quantile functions, moments, moment generating functions, characteristics functions and order statistics was obtained. Survival function, hazard function, reversed hazard rate function and a cumulative hazard rate function was also obtained. Behavior of the hazard rate plot exhibit increase, decrease, Bathtub and inverted Bathtub shape. Maximum likelihood estimate was used to estimate the Z-Kum distribution parameters. Monte Carlo simulation was carried out to evaluate the performance of MLE method adopted. Result of the simulation studies indicates that MLE is good for the estimation of our distribution parameters. To compare the proposed model with the other fitted existing models, analytical measure of goodness of fit of some information criterion was considered using three real life data sets. From the results obtained, it is evident that our proposed model gives better fit than the other competing models and therefore, our proposed model provide greater flexibility in modeling real world phenomenon.

A dynamic time-to-event model for prediction of acute graft-versus-host disease in patients after allogeneic hematopoietic stem cell transplantation.

Acute graft-versus-host disease (aGvHD) is a major cause of death for patients following allogeneic hematopoietic stem cell transplantation (HSCT). Effective management of moderate to severe aGvHD remains challenging despite recent advances in HSCT, emphasizing the importance of prophylaxis and risk factor identification. In this study, we analyzed data from 1479 adults who underwent HSCT between 2005 and 2017 to investigate the effects of aGvHD prophylaxis and time-dependent risk factors on the development of grades II-IV aGvHD within 100 days post-HSCT. Using a dynamic longitudinal time-to-event model, we observed a non-monotonic baseline hazard overtime with a low hazard during the first few days and a maximum hazard at day 17, described by Bateman function with a mean transit time of approximately 11 days. Multivariable analysis revealed significant time-dependent effects of white blood cell counts and cyclosporine A exposure as well as static effects of female donors for male recipients, patients with matched related donors, conditioning regimen consisting of fludarabine plus total body irradiation, and patient age in recipients of grafts from related donors on the risk to develop grades II-IV aGvHD. Additionally, we found that higher cumulative hazard on day 7 after allo-HSCT are associated with an increased incidence of grades II-IV aGvHD within 100 days indicating that an individual assessment of the cumulative hazard on day 7 could potentially serve as valuable predictor for later grades II-IV aGvHD development. Using the final model, stochastic simulations were performed to explore covariate effects on the cumulative incidence over time and to estimate risk ratios. Overall, the presented model showed good descriptive and predictive performance and provides valuable insights into the interplay of multiple static and time-dependent risk factors for the prediction of aGvHD.

Adherence to an integrated care pathway for stroke is associated with lower risk of major cardiovascular events: A report from the Athens Stroke Registry

BackgroundA recent European Society of Cardiology (ESC) Council on Stroke position paper proposed a holistic integrated care management approach for stroke patients, to improve cardiovascular outcomes. The impact of implementing the ABCstroke pathway ‘concept’ on clinical outcomes has never been estimated before. In order to investigate the potential effect of ABCstroke pathway adherence to cardiovascular outcomes post stroke, we performed a post-hoc analysis from the Athens Stroke Registry. Methods and resultsThis analysis was performed in the Athens Stroke Registry, which includes all consecutive patients with acute first-ever ischemic stroke. The Kaplan–Meier product limit was used to estimate the cumulative hazard of each outcome according to adherence with the ABCstroke pathway.We studied 2513 patients [median (IQR) age 71 (62–78) years; 37.7 % female] with ischemic stroke with median follow-up period of 30 (6–75) months. Full adherence to the ABC pathway was identified in 156 (6.2 %) of the patients, while 192 (7.6 %) did not adhere to any of the therapeutic pillars of ABCstroke. Full adherence to ABC treatment pathway was associated with significant reduction of stroke recurrence, compared to patients with no or partial adherence (aHR: 0.61; 95 %CI: 0.37–0.99), as well as a lower risk of MACE (HR: 0.59; 0.39–0.88) and death (aHR: 0.22; 95 %CI: 0.12–0.41). ConclusionFull adherence to the ABCstroke pathway based on the current guidelines was evident in only 6.2 % of our ischaemic stroke cohort but was independently associated with lower risks of stroke recurrence, major cardiovascular events and mortality. This highlights a potential opportunity to improve clinical outcomes post-stroke with a holistic or integrated care management approach.

Age-Related Incidence and Peak Occurrence of Contralateral Breast Cancer

Young patients with breast cancer have higher risk for developing contralateral breast cancer (CBC) and have epidemiologic characteristics different from those of older patients. To examine the incidence and peak occurrence of CBC according to age at primary breast cancer (PBC) surgery. This cohort study included patients who were diagnosed with and underwent surgery for unilateral nonmetastatic breast cancer at Asan Medical Center, Korea, between January 1, 1999, and December 31, 2013, with follow-up through December 31, 2018. Data were analyzed from December 1, 2021, through April 30, 2023. Patients were divided into 2 groups according to their age at surgery for PBC: younger (≤35 years) vs older (>35 years). The main outcomes were cumulative incidence and hazard rate of CBC in the entire study population and in subgroups divided by cancer subtype, categorized according to hormone receptor (HR) and ERBB2 status. A total of 16 251 female patients with stage 0 to III breast cancer were analyzed; all patients were Korean. The mean (SD) age was 48.61 (10.06) years; 1318 patients (8.11%) were in the younger group, and 14 933 (91.89%) were in the older group. Median follow-up was 107 months (IQR, 79-145 months). Compared with the older group, the younger group had significantly higher incidence of CBC (10-year cumulative incidence, 7.1% vs 2.9%; P < .001) and higher risk (hazard ratio, 2.10; 95% CI, 1.62-2.74) of developing CBC. The hazard rate, which indicates risk for developing CBC at a certain time frame, differed according to the subtype of primary cancer. In patients with the HR+/ERBB2- subtype, the risk increased continuously in both age groups. In patients with the triple negative subtype, the risk increased until approximately 10 years and then decreased in both age groups. Meanwhile, in the HR-/ERBB2+ subtype, risk peaked earlier, especially in the younger group (1.7 years since first surgery in the younger group and 4.8 years in the older group). In this cohort study, patients aged 35 years or younger with breast cancer had a higher risk of developing CBC than older patients. Moreover, young patients with the HR-/ERBB2+ subtype tended to have a shorter interval for developing CBC. These findings might be useful in guiding treatment decisions, such as contralateral prophylactic mastectomy.

Long-term late effects in older gastric cancer survivors: Survival analysis using Cox hazard regression model by retrospective electronic health records

PurposeBecause the population of older gastric cancer survivors (GCSs) is growing, understanding the long-term late effects experienced by these GCSs and their impact on survival outcomes is crucial for optimizing survivorship care. This study aims to identify and characterize these effects and investigate their association with survival outcomes.MethodsA retrospective analysis of electronic health records was conducted on 9,539 GCSs diagnosed between 2011 and 2017. The GCSs were divided into two age groups (< 65 and ≥ 65 years) and the long-term late effects were categorized by age using Cox proportional hazard models. The impact of clinical factors and age-specific late effects on survival was evaluated in the older GCSs.ResultsAmong the total GCSs, 37.6% were over and 62.4% were under 65 years of age. Significant differences between the age groups were observed in the cumulative hazard ratios (HRs) for iron and vitamin B12 levels and prognostic nutritional index (PNI) scores. In older GCSs, abnormal iron levels (HR 1.98, 95% CI 1.16–3.41, p = .013) and poor PNI scores (HR 1.59, 95% CI 1.03–2.47, p = .038) were associated with poorer survival outcomes. Additionally, being female was identified as a risk factor for lower survival rates (if male, HR 0.42, 95% CI 0.18–0.98, p = .045).ConclusionThis study highlights the typical long-term late effects experienced by older GCSs. By tailoring survivorship care to address nutritional-, age-, and gender-related factors, the overall survival and quality of life of older GCSs can be improved.

Does sex influence the prognosis of laryngeal cancer? A systematic review and a meta-analysis

PurposeLaryngeal cancer (LC) represents the tumor with the highest male-to-female sex ratio, yet the prognostic significance of sex remains uncertain. This study aimed to assess whether sex serves as an independent predictor of tumor control and survival in patients with laryngeal cancer. MethodsA systematic review and a meta-analysis of the literature was performed by querying the PubMed, Scopus, and Google Scholar databases. Outcome measures were overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). Cumulative hazard ratios (HRs) with 95 % CI are presented for the reported outcomes. QUIPS tool was used for evaluating biases. ResultsOut of a total of 16,592 retrieved articles, a total of 19 articles were included for quantitative analyses. A total of 1195 women affected by LC were analyzed, and compared to 7966 male patients: pooled analysis for survival revealed no significant sex-based differences (OS: HR = 0.786, 95 % CI: 0.590–1.047; DFS: HR = 0.465, 95 % CI 0.150–1.437; DSS: HR = 0.152, 95 % CI 0.01–12.82). All the included studies showed a low to moderate overall risk of bias. ConclusionsThis meta-analysis suggests that sex does not represent a significant independent prognostic factor for patients affected by laryngeal cancer.

Recurrent Event Analysis in the Presence of Real-Time High Frequency Data via Random Subsampling

Digital monitoring studies collect real-time high frequency data via mobile sensors in the subjects’ natural environment. This data can be used to model the impact of changes in physiology on recurrent event outcomes such as smoking, drug use, alcohol use, or self-identified moments of suicide ideation. Likelihood calculations for the recurrent event analysis, however, become computationally prohibitive in this setting. Motivated by this, a random subsampling framework is proposed for computationally efficient, approximate likelihood-based estimation. A subsampling-unbiased estimator for the derivative of the cumulative hazard enters into an approximation of log-likelihood. The estimator has two sources of variation: the first due to the recurrent event model and the second due to subsampling. The latter can be reduced by increasing the sampling rate; however, this leads to increased computational costs. The approximate score equations are equivalent to logistic regression score equations, allowing for standard, “off-the-shelf” software to be used in fitting these models. Simulations demonstrate the method and efficiency-computation tradeoff. We end by illustrating our approach using data from a digital monitoring study of suicidal ideation. Supplementary materials for this article are available online.

P85: Risks of suicide among family members of suicide victims: A nationwide sample of South Korea

Objective:Identifying the risks of completed suicide in suicide survivors is essential for policies supporting family members of suicide victims. We aimed to determine the suicide risk of suicide survivors and identify the number of suicides per 100,000 population of suicide survivors, bereaved families of traffic accident victims, and bereaved families with non-suicide deaths.Methods:This was a nationwide population-based cohort study in South Korea. The data were taken from the Korean National Health Insurance and Korea National Statistical Office between January 2008 and December 2017. The relationship between the decedent and the bereaved family was identified using the family database of the National Health Insurance Data. Age and gender were randomly matched 1:1 among 133,386 suicide deaths and non-suicide deaths. A proportional hazard model regression analysis was conducted after confirming the cumulative hazard using Kaplan-Meier curves to obtain the hazard ratio (HR) of completed suicide in suicide survivors.Results:Using 423,331 bereaved families of suicide victims and 420,978 bereaved families of non-suicide deaths as the control group, HR of completed suicide in suicidal survivors was found to be 2.755 [95% confidence limit (CL): 2.550-2.977]. HR for wives committing suicide after husbands' suicide was 5.096 (95% CL: 3.982-6.522), which was the highest HR among all relationships with suicide decedents. The average duration from suicide death to suicide of family members was 25.4 months. Among suicide survivors, the number of suicides per 100,000 people was 586, thrice that of people in bereaved families of traffic accident victims and in bereaved families of non-suicide deaths.Conclusion:The risk of completed suicide was three times higher in suicide survivors than in bereaved families with non-suicide deaths, and it was highest in wives of suicide decedents. Thus, socio-environmental interventions for suicidal survivors must be expanded.

Validation and Retraining of the Stellae-123 Gene Expression Signature Improved Risk Stratification in Taiwanese Acute Myeloid Leukemia Patients

The European Leukemia Net (ELN) recommendations provide valuable guidance in treatment decisions of patients with acute myeloid leukemia (AML). However, the genetic complexity and heterogeneity of AML are not fully covered, despite the critical role of gene expression analysis in risk stratification. Addressing this gap, the Stellae-123 score, an AI-based model that captures gene expression patterns, has demonstrated promising results in predicting survival of AML patients in four western cohorts. This study aims to assess the applicability of Stellae-123 in a Taiwanese cohort. Our cohort included 233 de novo AML patients, who were diagnosed and treated at the National Taiwan University Hospital and received standard induction therapy with 7+3 chemotherapy (or 5+2 in elder fit patients). All patients had sufficient bone marrow samples for DNA and RNA sequencing at diagnosis. The median age of the cohort was 41 years. Among the patients, ELN-2022 risk groups were distributed as follows: favorable (53.4%), intermediate (27.6%), and adverse (19%). Appling the original Stellae-123 model, which derived gene expression signatures from the BeatAML cohort RNA-seq data, our patients were categorized into low-, intermediate-, and high-risk groups, each representing 33% of the cohort. Overall, there were no differences in clinical features among these risk groups. The Stellae-123 risk groups partially aligned with the ELN risk groups, with more ELN low-risk patients in the Stellae-123 low-risk group and a higher proportion of ELN-high risk patients in the Stellae-123 high-risk group. Intriguingly, aside from mutations listed in ELN-2022, the Stellae-123 high-risk group had significantly less NRAS mutations than others. Cumulative hazards predicted by Stellae-123 model yielded a c-index of 0.612 for overall survival (OS), and the three risk groups had significantly different OS (p&amp;lt;0.001). We next postulated that since Stellae-123 relies on molecular features derived from the leukemic cells, it might serve as a biomarker of biological risk to predict relapse-free survival (RFS). The c-index calculated by Stellae-123 to predict RFS was 0.607, suggesting a reasonable ability to discriminate between different risk levels for RFS. Recognizing the potential variation between the original training cohort and the Taiwanese population, we addressed this concern by retraining the Stellae-123 model using Taiwanese RNAseq data. As a result, the model retraining led to significant improvements in the cross-validated c-indexes, with values of 0.656 (OS) and 0.636 (RFS), leading to an even more robust risk stratification (p&amp;lt;0.001, Figure 1A). As we noticed overlapping grouping between Stellae-123 and ELN-2022 in both pretrained and retrained models, we explored if Stellae-123's prognostic power was independent of ELN risk status by conducting a multivariable analysis. Remarkably, in both the pretrained and retrained Stellae-123 models, whether calculated as continuous values or categorized into three groups, they consistently demonstrated discriminative power in predicting OS and RFS, irrespective of age and ELN-2022 risk, suggesting that Stellae-123 could offer additional valuable information in predicting patient outcomes. Considering recent data showing that incorporating age helped improve the prognostication performance of ELN-2022 and that age was an independent risk factor for inferior outcome in our cohort, we examined how age could complement current risk stratification. Serial model testing revealed significant improvement of the prognostic models when age and transcriptomic data, especially the locally retrained Stellae-123 model, were combined with ELN-2022, evident by drastically declined Akaike Information Criterion (AIC) values. Time-dependent ROC curve analysis confirmed the potential of incorporating Stellae-123 and age to complement current risk stratification system (Figure 1B). In summary, we showed that the Stellae-123 predicted both OS and relapse risk in AML patients from Taiwan. Furthermore, we demonstrated that model retraining could improve prognostication by adapting the Stellae-123 to the particularities of Taiwanese patients. Given the remarkable extrapolation of the signature, it's suggested gene expression profile be incorporated in the risk stratification of AML patients who are candidates to intensive therapy.

Patients with High-Risk Myelodysplastic Neoplasms Do Not Benefit from Remission Induction with Azacitidine Prior to Hematopoietic Cell Transplantation: A Retrospective, Single-Center Analysis with Extended Follow-up

Background: The value of remission induction in high-risk myelodysplastic neoplasms (MDS) with increased blasts prior to allogeneic hematopoietic cell transplantation (HCT) remains controversial. The new ELN recommendations include the re-designation of patients with 10-20% blasts as AML/MDS, raising the question of whether these patients should receive induction chemotherapy before HCT. An alternative is treatment with hypomethylating agents (HMA) such as azacitidine, for which allo-sensitizing effects have been proposed. In contrast, bridging to HCT with HMA may increase drop-out rate for allogeneic HCT, while at the same time not further benefiting patients who subsequently receive HCT. Methods: We report on 135 patients diagnosed with MDS, chronic myelomonocytic leukemia or myelodysplastic/myeloproliferative neoplasm who received HCT at our center between 2010 and 2022. Median age was 60 years (range 26 to 77 years) and 44.4% of patients were female. IPSS-R score was high in 25.8% of patients and very high in 44.8% of patients. 33.3% of patients received remission induction prior to HCT, 28.8% of all patients with HMA. Conditioning regimens were myeloablative in 8.1%, FLAMSA-based reduced intensity conditioning (RIC) in 26.7%, and RIC in 60.7% of cases. Donors were matched (8/8) related in 23.7%, matched (8/8) unrelated in 53.3%, and mismatched (7/8 or haploidentical) in 23%. Relationships between outcomes and patient, treatment and disease parameters were analyzed using multivariate Cox proportional hazards regression and, in the case of relapse, non-relapse mortality (NRM) and graft-versus-host disease (GVHD), competing risk analysis. P-values were adjusted for multiple comparisons using false discovery rate adjustment. Results: Median follow-up after HCT was 46 months. Kaplan-Meier estimates for OS and RFS at 5 years were 56.6% and 43%, respectively. The cumulative incidences of relapse, NRM, acute GVHD grade II to IV, and chronic GVHD at 5 years were 39%, 17.8%, 36.4%, and 40%, respectively. OS was significantly correlated with the IPSS-R cytogenetic risk category but not with the percentage of blasts in bone marrow before treatment initiation. In multivariate regression analysis, OS was significantly worse in patients with poor or very poor IPSS-R cytogenetic category (HR 1.56; p&amp;lt;0.001) but not in patients with a pre-treatment bone marrow blast count exceeding 10% (HR 1.25; p=0.19). Similarly, cytogenetic risk, but not bone marrow blast count, was significantly associated with worse RFS (HR 1.5 vs. 1.2; p&amp;lt;0.001 vs. 0.199) and higher cumulative hazard of relapse (HR 1.74 vs. 1.36; &amp;lt;0.0001 vs. p=0.31). Bridging or induction treatment with azacitidine before HCT by trend showed a higher cumulative hazard of relapse (HR 2.3; p=0.057) and worse RFS (HR 1.7; p=0.088). In exploratory subgroup analyses of patients with a bone marrow blast count above 10% (n=69), OS was not significantly different between patients who received remission induction prior to HCT and those who did not (HR 1.3; p=0.5), while the cumulative hazard of relapse by trend even increased in the first group (HR 1.85; p=0.13). Furthermore, there was no significant difference in OS between patients with a bone marrow blast count above 10% who received intensified sequential conditioning with FLAMSA-RIC versus fludarabine/treosulfan (n=44; HR 1.45; p=0.52). Donor mismatch was the only parameter significantly associated with higher NRM (HR 2.4 and p=0.044), and GVHD prophylaxis with anti-thymocyte globulin and/or tacrolimus the only parameters associated with a significant reduction of chronic GVHD severity (f²=0.05 and 0.06; p=0.03 and 0.02), while no single parameter was associated with a significant difference in acute GVHD severity. Conclusions: This study reports promising long-term outcomes for MDS patients undergoing HCT in the real-world setting. In our analysis, cytogenetic risk, but not bone marrow blast count, was the main determinant of transplantation outcomes. Furthermore, remission induction prior to HCT with azacitidine, which is commonly used in patients with increased bone marrow blasts, was not associated with a survival benefit but by trend even with higher relapse risk and worse RFS in multivariate analysis. This suggests that the perceived role of azacitidine as a bridge-to-transplant should be questioned. Rather, eligible patients should receive HCT as soon as possible.