Estimate Survival Probabilities Research Articles

Clinical features and prognostic factors of patients with inoperable hepatocellular carcinoma treated with chemotherapy: a population-based study.

In inoperable hepatocellular carcinoma (HCC), chemotherapy is a common treatment strategy. However, there is a lack of reliable methods to predict the prognosis of patients with inoperable HCC after chemotherapy. Therefore, the aim of this study was to identify the clinical characteristics of patients with inoperable HCC and to establish and validate nomogram models for predicting the survival outcomes in this patient group following chemotherapy. The data of patients diagnosed with HCC from the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively collected. Logistic regression analyses were used to identify potential factors for inoperability in patients with HCC. Kaplan-Meier analyses were applied to evaluate the impact of chemotherapy on prognosis. Additionally, Cox regression analyses were performed to identify the potential risk factors associated with overall survival (OS) and cancer-specific survival (CSS) in patients with inoperable HCC treated with chemotherapy. Finally, we constructed prognostic nomograms for predicting the 1- and 3-year survival probabilities. A total of 3,519 operable patients with HCC and 4,656 patients with inoperable HCC were ultimately included in this study. Logistic regression analyses revealed a significant association between patient age, gender, race, tumor, node, metastasis (TNM) stage, tumor size, pretreatment alpha fetoprotein (AFP) levels, and marital status with inoperability. Moreover, Kaplan-Meier analyses revealed a significant improvement in both OS and CSS with the administration of chemotherapy. Moreover, 1,456 patients with inoperable HCC were enrolled in the training group and 631 patients with inoperable HCC were enrolled in the validation group to develop and validate the prognostic models. Cox regression models indicated that TNM stage, tumor size, and pretreatment AFP were independent risk factors for predicting OS and CSS in patients with inoperable HCC receiving chemotherapy. These factors were subsequently integrated into the predictive nomograms. We preliminarily developed survival models with strong predictive capabilities for estimating survival probabilities in patients with HCC following chemotherapy. These models hold potential for clinical application and warrant further exploration through additional studies.

Real Clinical Practice of Combined Atezolizumab Plus Chemotherapy in Patients With Small Cell Lung Cancer.

Atezolizumab, an anti-PD-L1 antibody, has been increasingly administered in combination with chemotherapy to patients with small cell lung cancer (SCLC). This study aimed to determine how patients with extensive disease (ED) -SCLC responded to atezolizumab with chemotherapy and found factors affecting long-term response and survival. This study focused on patients with SCLC who were treated with a combination of atezolizumab and chemotherapy in Japan between 2019 and 2023. Patient information and tumor response were analyzed, along with adverse events. We compared data and estimated survival probabilities. In our clinical trial, 95 patients with SCLC who received this treatment had a median progression-free survival of 6.0 months and a median overall survival of 15.0 months. Immune-related adverse events were observed in 13.7% of the patients, with grade 3 or higher in 5.3%. The efficacy and immune-related adverse events associated with this treatment regimen were comparable to those reported in previous clinical trials. Progression-free survival >2 years was observed in a small number of patients (5.3%). Our research will offer important insights for the future care of patients with extensive-stage SCLC by utilizing atezolizumab in combination with chemotherapy. Accumulation and confirmation of clinical practice results will have important implications for the future implementation of this therapy.

Overall survival in patients with acute lymphoblastic leukemia treated with protocol CALGB 9511 at a tertiary hospital in the state of Ceará.

Introduction: Acute lymphoblastic leukemia (ALL) is the most common neoplasm in childhood and has high survival rates. In adults, due to the biological characteristics of the disease and chemotherapy-related toxicity, survival is lower. CALGB 9511 is a chemotherapy protocol based on pediatric regimens with high remission rates after induction. Objectives: To evaluate the survival of patients with ALL undergoing the CALGB 9511 protocol at Walter Cantídio University Hospital (HUWC); to describe the impact of risk factors: presence of measurable residual disease, BCR-ABL fusion gene status, and allogeneic bone marrow transplant (BMT) on the survival of this group. Methodology: Retrospective evaluation of medical records of patients with ALL treated with this protocol between 2011 and 2022. Statistical analysis was performed using the Kaplan-Meier method to estimate survival probability. Results: 79 patients were eligible; 19% were BCR-ABL positive; the mean 2-year overall survival was 44%; The 2-year survival rate for patients undergoing HSCT was approximately 78%.. Conclusion: The survival curves of the study conducted at HUWC are similar to those described in the literature and corroborate the severity of the disease. Accessibility to new therapeutic modalities is a strategy that can improve the survival of these patients.

FLT3-MUTATED ACUTE MYELOID LEUKEMIA OUTCOMES IN A NORTHEAST BRAZILIAN UNIVERSITY HOSPITAL

Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene occur in approximately 25-45% of new diagnoses of Acute myeloid leukemia. The addition of FLT3 inhibitors to conventional protocols improves overall survival in this condition. Objectives: To assess the incidence of FLT3 gene mutation among patients diagnosed with AML at Walter Cantídio University Hospital; Describe access to FLT3 inhibitors and bone marrow transplantation (BMT), and the overall survival of this group. Methodology: Retrospective evaluation of medical records of patients treated for AML between 2020 and 2022. Statistical analysis was performed using the Kaplan-Meier method to estimate survival probability. Results: 47 patients were diagnosed with AML during this period, of whom 17% had FLT3+ mutation. 3/8 patients accessed FLT3 inhibitors. The median survival with FLT3+ mutation was 9.1 months vs. 12.9 months in FLT3- (p = 0.196). The overall survival of AML patients was 30.9% at 2 years. 11/47 patients underwent allogeneic BMT. Conclusion: The addition of targeted therapies and BMT may contribute to reduce mortality in AML. Elderly patients and those not undergoing HSCT have worse outcomes.

RRP8, associated with immune infiltration, is a prospective therapeutic target in hepatocellular carcinoma

BackgroundRibosomal RNA Processing 8 (RRP8) is a nucleolar Rossman fold-like methyltransferase that exhibits increased expression in many malignant tumours. However, the role of RRP8 in hepatocellular carcinoma (HCC) is still uncertain. We explored the relationships between RRP8 and prognosis and immune infiltration, as well as the putative pathological function and mechanism of RRP8 in HCC.MethodsAnalysis of RRP8 expression across cancers was performed by using multiple databases. Associations between RRP8 expression and clinicopathological factors were further examined. Gene enrichment analysis was used to identify various putative biological activities and regulatory networks of RRP8 in HCC. The relationship between RRP8 expression and immune infiltration was confirmed by single-sample gene set enrichment analysis (ssGSEA). Univariate and multivariate Cox regression analyses were conducted to assess the impact of clinical variables on patient outcomes. Furthermore, a nomogram was constructed to estimate survival probability based on multivariate Cox regression analysis. Functional validation of RRP8 in HCC was performed with two different systems: doxycycline-inducible shRNA knockdown and CRISPR-Cas9 knockout.ResultsRRP8 was markedly overexpressed in HCC clinical specimens compared to adjacent normal tissues. Further analysis demonstrated that RRP8 was directly connected to multiple clinical characteristics and strongly associated with various immune markers in HCC. Moreover, elevated RRP8 expression indicated an unfavourable prognosis. Our functional studies revealed that both knockdown and knockout of RRP8 dramatically attenuated liver cancer cells to proliferate and migrate. Knockout of RRP8 decreased the phosphorylation of MEK1/2 and β-catenin-(Y654) signalling pathway components; downregulated downstream signalling effectors, including Cyclin D1 and N-cadherin; and upregulated E-cadherin.ConclusionsRRP8 is strongly implicated in immune infiltration and could be a potential therapeutic target in HCC.

Juvenile survival of little owls decreases with snow cover.

Global environmental changes are associated with warmer average temperatures and more extreme weather events, potentially affecting wildlife population dynamics by altering demographic processes. Extreme weather events can reduce food resources and survival in all seasons of the year. Estimates of season-specific survival probabilities are therefore crucial to understand the moderating effect of extreme events on annual mortality. Here, we analysed survival probabilities of 307 radio-tracked juvenile little owls (Athene noctua) over two-week periods from fledging to their first breeding attempt in the following spring to assess the contribution of extreme weather events. Survival probabilities were typically lowest during the first weeks after fledging in summer but were moderated by seasonal extremes in winter. The duration of snow cover in winter had a strong negative effect on survival probability, while being food supplemented during the nestling stage increased survival during the first weeks after fledging in summer and ultimately led to a larger proportion of birds surviving the first year. Overall annual survival probability over the first year varied by 34.3% between 0.117 (95% credible interval 0.052-0.223) and 0.178 (0.097-0.293) depending on the severity of the winter, and was as high as 0.233 (0.127-0.373) for food-supplemented fledglings. In years with mild winters, the season with the lowest survival was the summer post-fledging period (0.508; 0.428-0.594), but in years with extensive snow cover the winter was the season with the lowest survival (0.481; 0.337-0.626). We therefore show that extreme weather events occurring in a particular season reduced the proportion of first-year survivors. Increasing extreme weather events can moderate seasonal survival probability through altering food supply of juvenile little owls either during the nestling period or in winter, with similarly large effects on annual survival and the viability of populations.

A survey of the high-cycle fatigue performance of additively manufactured alloy 718

This paper presents a survey of the published high-cycle fatigue (hcf) data for the nickel–iron superalloy alloy 718 fabricated by additive manufacture. Approximately 680 fatigue data points were collected from the published literature and the reported data are presented in the form of stress versus cycles to failure curves for load ratios of R = −1, 0 and 0.1. Following this, curves showing estimated survival probabilities of 0.5, 0.95 and 0.99 are constructed using a statistical analysis based on the Weibull probability density function. Finally, a comparison between the fatigue performance of additively manufactured and wrought alloy 718 under fully reversed loading conditions ( R = −1) is provided.

Factors Associated With Mortality During the First Year Post Infarction: Survival Analysis of Patients With Acute Myocardial Infarction in Colombia.

Cardiovascular diseases account for over 80% of global deaths. Risk factors and social determinants influence mortality in patients post acute myocardial infarction (AMI). To evaluate factors associated with post-AMI mortality during the one-year follow-up. The study is a prospective cohort study of adults aged 18 years and older with type 1 AMI conducted between October 2021 and January 2024. Intrahospital and outpatient information was collected. Statistical analyses included the Kaplan-Meier survival curve and Cox regression analysis. Proportional hazards and model predictive capacity were evaluated. A total of 1873 patients were included, with a 9.4% mortality rate in the first year. At one year, the estimated survival probability was 88.61% (95% CI: 86.82-90.18). Cox analysis identified several factors associated with mortality, highlighting age (HR = 1.04, 95% CI: 1.02-1.06, p = 0.001), diabetes (HR = 1.77, 95% CI: 1.09-2.87, p = 0.020), renal insufficiency (HR = 2.25, 95% CI: 1.32-3.84, p = 0.003), and type of intervention. The model evaluation showed strong predictive capacity. It is essential to emphasize the importance of comprehensive management in AMI patients with risk factors such as diabetes and chronic kidney disease, as they are significant predictors of mortality during the first year post infarction.

A bivariate survival model for events with dependent failure times based on Archimedean copula functions. Application case: A sample of HIV patients

This paper proposes a bivariate survival model for dependent failure times based on copula functions of the Archimedean family and the mean cumulative function for non-recurrent events of different types (MCFR ̅E) and uses it to estimate the probability of survival from the occurrence of events of different types on the same HIV/AIDS patient. The copula functions evaluate the dependence structure between the failure times of the events experienced by the same patient throughout their follow-up period, and the MCFR ̅E generates the marginal survival function for each event. The marginal function is a nonparametric estimator that gives the same estimated survival probability as the Kaplan-Meier estimator if the failure times of the different types of events are independent. If each patient experiences at least one event, a subset of them generates a compound event that affects the estimated probability of survival. The results show that the traditionally estimated survival probabilities are biased if dependent failure times are treated as independent.

Systematic analysis of PANoptosis-related genes identifies XIAP as a functional oncogene in breast cancer

BackgroundBreast cancer (BC) is the most prevalent malignant disease affecting women globally. PANoptosis, a novel form of cell death combining features of pyroptosis, apoptosis, and necroptosis, has recently gained attention. However, its precise function in BC and the predictive values of PANoptosis-related genes remain unclear. MethodsWe used the expression data and clinical information of BC tissues or normal breast tissues from public databases, and then successfully developed and verified a BC PANoptosis-related risk model through a combination of univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and Kaplan-Meier (KM) analysis. A nomogram was constructed to estimate survival probability, and its accuracy was assessed using calibration curves. ResultsAmong 37 PANoptosis-related genes, we identified 4 differentially expressed genes related to overall survival (OS). Next, a risk model incorporating these four PANoptosis-related genes was established. Patients were stratified into low/high-risk groups based on the median risk score, with the low-risk group showing better prognoses and higher levels of immune infiltration. Utilizing the risk score and clinical features, we developed a nomogram to predict 1-, 3- and 5-year survival probability. X-linked inhibitor of apoptosis protein (XIAP) emerged as a potentially risky factor with the highest hazard ratio. In vitro experiments demonstrated that XIAP inhibition enhances the antitumor effect of doxorubicin through the PANoptosis pathway. ConclusionPANoptosis holds an important role in BC prognosis and treatment.

Small intestinal submucosa graft bulbar urethroplasty is a viable technique: results compared to buccal mucosa graft urethroplasty after propensity score matching.

Small intestinal submucosa (SIS) graft urethroplasty has been employed to decrease buccal mucosa morbidity and facilitate the procedure. The first published series had a short follow-up, inhomogeneous patient selection, and a lack of a control group. Our purpose is to report treatment outcomes at 13years in a propensity score-matched cohort comparing bulbar urethroplasty with SIS (SISU) or buccal mucosa (BMU). From our institutional database of 1132 bulbar urethroplasties, we used propensity score matching with the nearest-neighbor method without replacement to generate a study sample of 25 BMU and 25 SISU. Failure was defined as any treatment after urethroplasty. Survival analyses were used to analyze treatment failure occurrence with data censored at 156mo. Matching resulted in a complete correction of bias between the two samples except for the follow-up duration, which was slightly longer in the SIS group. The cumulative treatment success probability of BMU and SISU at 156mo was 83.4% and 68%, respectively. At multivariable Cox regression, SIS graft, previous urethrotomy, stricture length, and lower postoperative Qmax (within 2mo after catheter removal) were predictors of failure. Stricture length had a more remarkable effect in SISU, with estimated survival probabilities from the Cox model lower than 80% in strictures > = 3cm. SIS has poorer outcomes compared to BM but may still be useful when BM grafting is not possible. The best candidates for SISU, with similar success to BMU, are patients with strictures shorter than 3cm, preferably without a history of DVIU.

Survival implications of diversion entrainment for out‐migrating juvenile Chinook Salmon and steelhead

AbstractObjectiveEfforts to ameliorate the negative effects of diversion dams on aquatic species of concern are important in rivers where water withdrawal supports agricultural economies, and they are likely to become increasingly important with impending climate change. A multi‐year study was conducted to evaluate the survival consequences of diversion dam passage for juvenile Chinook Salmon Oncorhynchus tshawytscha and steelhead O. mykiss in the highly managed Yakima River, Washington. Canal entrainment and passage were evaluated at four diversion dams in the lower Yakima River where seaward‐migrating juvenile salmon and steelhead either pass dams via spill bays or enter canals with downstream fish‐screening facilities designed to collect entrained fish and return them to the main‐stem river.MethodsWe used acoustic telemetry to monitor the downstream migration behavior of 4403 juvenile Chinook Salmon and steelhead during 2018–2021.ResultPercent entrainment into canals was substantial (6–59%) at three of the four diversion dams studied, and entrainment probability was positively associated with the proportion of streamflow diverted into canals. Survival probability estimates for groups of tagged fish that were entrained into canals were lower than survival probability estimates for tagged fish that passed through spill bays on the dams. Absolute differences in survival probabilities between routes ranged from 0.099 to 0.369, demonstrating that canal entrainment reduced the survival of outmigrating juvenile Chinook Salmon and steelhead. We also found that entrainment resulted in migration delays, which could further affect survival because fish are increasingly exposed to predation and decreased water quality as water temperature increases throughout the migration season.ConclusionCanal entrainment resulted in increased mortality and travel time through the study area, highlighting the need to limit the entrainment of juvenile salmon and steelhead at diversion dams in rivers where salmon recovery is important.

Continuous sound from a marine vibrator causes behavioural responses of free-ranging, spawning Atlantic cod (Gadus morhua)

Marine vibrators are a new technology being developed for seismic surveys. These devices can transmit continuous instead of impulsive sound and operate over a narrower frequency band and at lower peak pressure than airguns, which is assumed to reduce their environmental impacts. We exposed spawning Atlantic cod (Gadus morhua) to sound produced by a prototype, but full-scale, marine vibrator, and monitored behavioural responses of tagged cod using acoustic telemetry. Fish were exposed to 10 × 3 h continuous sound treatments over a 4-day period using a randomised-block design. Sound exposure levels were comparable to airgun exposure experiments conducted previously with the same set-up ranging from ∼115 to 145 dB re 1 μPa2s during exposure. Telemetry data were used to assess 1) whether marine vibrator exposure displaced cod from the spawning ground, through estimation of residence and survival probabilities, and 2) fine-scale behavioural responses within the test site, namely swimming depth, activity levels, displacement, and home ranges. Forty-two spawning cod were tagged prior to the exposure, with 22 present during the exposure. All 22 tags were equipped with pressure sensors and ten of these additionally with accelerometers. While no premature departure from the spawning site was observed, cod reacted to the exposure by decreasing their activity levels (by up to 50%, SE = 7%) and increasing their swimming depth (by up to 2.5 m, SE = 1.0 m) within the test site during the exposure period. These behavioural responses varied by sex and time of day. Cod reactions to a marine vibrator may be more pronounced than reactions to airguns, possibly because continuous sound is more disturbing to fish than intermittent sound at the same exposure levels. However, given sample size limitations of the present study, further studies with continuous sound are necessary to fully understand its impact and biological significance.

Delay of Surgery for Spinal Metastasis due to the COVID-19 Outbreak Affected Patient Outcomes.

The present study is to analyze the effects of the coronavirus disease 2019 (COVID 2019) outbreak and the subsequent lockdown on the outcomes of spinal metastasis patients. The study was a retrospective analysis of data from a prospective cohort study. All patients underwent surgical intervention for spinal metastases between January 2019 and December 2021 and had at least 3 months of postoperative follow-up. The primary outcome was overall mortality during the 4 different stages (pre-COVID-19 era, COVID-19 pandemic except in Taiwan, national lockdown, lifting of the lockdown). The secondary outcomes were the oncological severity scores, medical/surgical accessibility, and patient functional outcome during the 4 periods as well as survival/mortality. A total of 233 patients were included. The overall mortality rate was 41.20%. During the Taiwan lockdown, more patients received palliative surgery than other surgical methods, and no total en bloc spondylectomy was performed. The time from surgeon visit to operation was approximately doubled after the COVID-19 outbreak in Taiwan (75.97, 86.63, 168.79, and 166.91 hours in the 4 periods, respectively). The estimated survival probability was highest after the national lockdown was lifted and lowest during the lockdown. In the multivariate analysis, increased risk of mortality was observed with delay of surgery, with emergency surgery having a higher risk with delays above 33 hours, urgent surgery (below 59 and above 111 hours), and elective surgery (above 332 hours). The COVID-19 pandemic and related policies have altered daily clinical practice and negatively impacted the survival of patients with spinal metastases.

Determinants of survival of adolescents receiving antiretroviral therapy in the Centre Region of Cameroon: a multi-centered cohort-analysis

BackgroundIn spite of the global decreasing mortality associated with HIV, adolescents living with HIV (ADLHIV) in sub-Saharan Africa still experience about 50% mortality rate. We sought to evaluate survival rates and determinants of mortality amongst ADLHIV receiving antiretroviral therapy (ART) in urban and rural settings.MethodsA multi-centered, 10-year retrospective, cohort-study including ADLHIV on ART ≥ 6 months in the urban and rural settings of the Centre Region of Cameroon. Socio-demographic, clinical, biological, and therapeutic data were collected from files of ADLHIV. The Kaplan–Meier method was used to estimate survival probability after ART initiation; the log rank test used to compare survival curves between groups of variables; and the Cox proportional hazard model was used to identify the determinants of mortality.ResultsA total of 403 adolescents’ records were retained; 340 (84%) were from the urban and 63 (16%) from the rural settings. The female to male ratio was 7:5; mean age (Standard deviation) was 14.1 (2.6) years; at baseline, 64.4% were at WHO clinical stages I/II, 34.9% had ≥ 500 CD4 cells/mm3, 91.1% were anemic, and the median [Inter Quartile Range] duration on ART was5.3 [0.5–16] years. The survival rate at 1, 5 and 10 years on ART was respectively 97.0%, 55.9% and 8.7%; with mean survival time of 5.8 years (95% CI 5.5–6.1). In bivariate analysis, living in the rural setting, non-disclosed HIV status, baseline CD4 count < 500 cells/mm3, not being exposed to nevirapine prophylaxis at birth and being horizontally infected were found to be the determinants of higher mortality with poor retention in care slightly associated with mortality. In multivariate analysis, living in rural settings, poor retention in care and anemia were independent predictors of mortality (p < 0.05).ConclusionAlthough ADLHIV have good survival rate on ART after 1 year, we observe poor survival rates after 5 years and especially 10 years of treatment experience. Mitigating measures against poor survival should target those living in rural settings, anemic at baseline, or experiencing poor retention in care.

Multimodal deep learning for personalized renal cell carcinoma prognosis: Integrating CT imaging and clinical data

Background and Objective: Renal cell carcinoma represents a significant global health challenge with a low survival rate. The aim of this research was to devise a comprehensive deep-learning model capable of predicting survival probabilities in patients with renal cell carcinoma by integrating CT imaging and clinical data and addressing the limitations observed in prior studies. The aim is to facilitate the identification of patients requiring urgent treatment.Methods: The proposed framework comprises three modules: a 3D image feature extractor, clinical variable selection, and survival prediction. Based on the 3D CNN architecture, the feature extractor module predicts the ISUP grade of renal cell carcinoma tumors linked to mortality rates from CT images. Clinical variables are systematically selected using the Spearman score and random forest importance score as criteria. A deep learning-based network, trained with discrete LogisticHazard-based loss, performs the survival prediction. Nine distinct experiments are performed, with varying numbers of clinical variables determined by different thresholds of the Spearman and importance scores.Results: Our findings demonstrate that the proposed strategy surpasses the current literature on renal cancer prognosis based on CT scans and clinical factors. The best-performing experiment yielded a concordance index of 0.84 and an area under the curve value of 0.8 on the test cohort, which suggests strong predictive power.Conclusions: The multimodal deep-learning approach developed in this study shows promising results in estimating survival probabilities for renal cell carcinoma patients using CT imaging and clinical data. This may have potential implications in identifying patients who require urgent treatment, potentially improving patient outcomes. The code created for this project is available for the public on: GitHub

A Unified Nonparametric Fiducial Approach to Interval-Censored Data

Censored data, where the event time is partially observed, are challenging for survival probability estimation. In this article, we introduce a novel nonparametric fiducial approach to interval-censored data, including right-censored, current status, case II censored, and mixed case censored data. The proposed approach leveraging a simple Gibbs sampler has a useful property of being “one size fits all,” that is, the proposed approach automatically adapts to all types of noninformative censoring mechanisms. As shown in the extensive simulations, the proposed fiducial confidence intervals significantly outperform existing methods in terms of both coverage and length. In addition, the proposed fiducial point estimator has much smaller estimation errors than the nonparametric maximum likelihood estimator. Furthermore, we apply the proposed method to Austrian rubella data and a study of hemophiliacs infected with the human immunodeficiency virus. The strength of the proposed fiducial approach is not only estimation and uncertainty quantification but also its automatic adaptation to a variety of censoring mechanisms. Supplementary materials for this article are available online.

PP47 Experience And Its Implication For Reassessment Of The Transcatheter Aortic Valve Implantation Using Real World Data

IntroductionSouth Korea has introduced conditionality to coverage decisions for certain difficult or high-risk procedures. The transcatheter aortic valve implantation (TAVI) was included in the coverage with evidence development (CED) in 2014. This study reviewed the results of reassessment for the TAVI using real world data (RWD) and suggested its implications.MethodsHealthcare providers authorized to use the promising technologies are required to collect the RWD for suitability evaluation, safety monitoring, and cost-effectiveness, differing from the general reassessment process. In 2021, 45 healthcare providers collected clinical information for TAVI patients. Their registries were linked with the national health insurance claims, which provided data on 19 items to assess safety and effectiveness such as overall mortality, reoperation rates, hospital readmission rates, and degree of functional improvement.ResultsAccording to the Society of Thoracic Surgeons’ predicted risk of mortality (STS), 988 TAVI patients were classified into three groups; high (STS &gt;8 percent, n=347), intermediate (STS 4-8 percent, n=272), and low (STS &lt;4 percent, n=369); We compared main outcomes and estimated survival probabilities between subgroups. Within 30 days, the overall mortality rates were 4.9 percent (high), 2.6 percent (intermediate), and 1.4 percent (low); major bleeding rates were 7.6 percent (high), 6.2 percent (intermediate),and 1.4 percent (low); incidence of new atrial fibrillation were 6.8 percent (high), 4.2 percent (intermediate), and 3.2 percent (low). Based on the quantitative results using RWD and systematic review for the safety and effectiveness, TAVI is reported to have essential benefits for high-risk group and elderly patients (&gt;80 years). Whereas, intermediate and low-risk groups have out-of-pocket payment rates of 50 percent and 80 percent, respectively.ConclusionsThe reassessment system through RWD accumulation enabled the evidence-based evaluation for the TAVI. Based on the transition to CED for essential benefits, a systematic framework such as RWD collection from treatment commencement should be introduced to broaden RWD use for benefit management of medical technologies with uncertain levels of evidence. Therefore, this ensures overall quality of care and effective coverage in health.

Comparative Analysis of Methods for Analyzing Clinical Results of Immuno-Oncology Therapy with Delayed Treatment Effects

Introduction: CAR-T therapy is a groundbreaking therapy that involves modifying patient's T cells to recognize and combat cancer cells. This therapy requires a period of CAR-T manufacture following apheresis, delaying the actual receipt of the CAR-T. During this period the patient may receive bridging therapy. CAR-T therapies are increasingly being studied in randomized controlled clinical trials and delays potentially affect the proportional hazards assumption, reduce log-rank test statistical power, and complicate reporting and interpretation. To address this, we assessed available statistical methods for analyzing immune-oncology outcomes, specifically CAR-T therapy's delayed treatment effects, with a focus on current and emerging tools to improve analysis and reporting. Methods: We systematically reviewed and compared existing and emerging tools to evaluate survival analysis methods suitable for assessing outcomes in CAR-T studies. These methods included standard, stratified, and weighted log-rank tests, cox proportional hazards (time dependent), parametric survival (weibull, etc.), time-dependent covariates, landmark analysis, joint modeling and restricted mean survival time (RMST). We simulated trial results, highlighted features, underlying assumptions, and interpretability. Results: Results were based on a simulated dataset (N=240) and revealed distinct characteristics and implications of each method used to analyze data (Table). Standard log-rank tests, which give equal weight to all time points and assumes proportional hazards, resulted in less discerning outcome measurements compared to weighted techniques such as censored weighted estimation/constant piecewise weighted (CWE/CPW) and Fleming-Harrington which do not assume proportional hazards and can be weighted towards early or late events. RMST summarized average time until progression, which may be a more intuitive measure for clinicians and patients and was presented along with other analytical techniques. Cox proportional hazards modeling provided ratios to quantify and compare efficacy across different time points. Parametric survival models captured survival dynamics and offered precise estimation of survival probabilities at specific intervals. Time-dependent covariates accounted for time-varying factors influencing treatment response, while landmark analysis evaluated treatment efficacy beyond a specific duration and was used in combination with other analytical techniques. Joint modeling simultaneously assessed treatment effects on both longitudinal and survival outcomes, accounting for their interdependencies. Stratification identified patient subgroups with differential treatment responses and outcomes, enabling precise reporting of categorical CAR-T treatment approaches. Conclusions: Our comparative analysis of analytical techniques underscores the critical role of selecting an appropriate approach in the context of CAR-T therapies. Conventional methods such cox regression and the standard log-rank test, while useful in most contexts, may underestimate key outcomes associated with CAR-T therapy due to violations of proportional hazard assumption. Weighted techniques, which can be weighted towards early or late events, may provide a more nuanced picture, and better accommodate CAR-T therapies. Similarly, the RMST offers an intuitive average time to progression, offering complementary insights to other methods. These findings highlight the importance of careful method selection in survival analysis for CAR-T therapy studies. Rigorous, tailored analytical approaches will be crucial in accurately determining the efficacy of these promising therapies and informing future clinical study designs. By considering these methods, researchers can gain deeper insights regarding CAR-T therapy and improve the design and analysis of clinical trials, ultimately advancing the understanding and application of this transformative therapy.

Allogeneic Hematopoietic Cell Transplantation for Acute Megakaryocytic Leukemia: A Single Center Study

Introduction Acute megakaryocytic leukemia (AMKL) comprises 4-15% of all acute myeloid leukemia (AML) diagnoses in pediatric patients. Unlike patients with Down syndrome who have a &amp;gt;80% expected survival with dose-reduced chemotherapy, the 5-year overall survival (OS) in patients with de novo AMKL is dismal and ranges between 14-49%. While treatment intensification has marginally improved the outcome of these patients over the last few decades, the role of hematopoietic cell transplantation (HCT) in these patients in first complete remission (CR) is often debated. To better define the role of HCT, we evaluated the outcomes of pediatric patients who underwent their first HCT for AMKL at our institution from October 1990 to January 2021. Methods We conducted a retrospective analysis using patient, disease, and transplant-related data collected during routine clinical care and evaluated these variables for their prognostic value. Kaplan-Meier curves were generated to estimate survival probabilities in pre-specified groups and compared using the log-rank test. Multivariable analysis was performed using Cox proportional hazards models to assess the role of various patient and transplant-related factors on survival. The cumulative incidence of relapse (with death as competing risk) was estimated by the Fine-Gray multivariable models and compared using Gray's test. Results Our study included 53 patients. The median age at HCT was 2.3 (range 0.9-19.7) years. The median time of follow-up was 10.3 (range 0.9-346.6) months. At the time of HCT, 56.6% of patients were in CR1, 5.7% were in CR2 and 37.7% had active/refractory disease. Nine (17%) patients received an HCT from a matched sibling donor, 25 (47.2%) from a matched unrelated donor, and 19 (35.8%) from a haploidentical donor. Twenty-two (41.5%) patients relapsed after HCT at a median duration of 2.8 (range 0.6-10.5) months, and 31 (58.5%) patients died at a median duration of 4.3 (range 0.9-15.9) months. The one-year OS estimates trended higher in patients undergoing transplant in more recent decades (1990-2000: 32%, 2000-2010: 46%, 2010-2020: 67%; P = 0.2). Patients who underwent HCT in CR had a significantly higher 1-year OS (57% versus 30%; P &amp;lt; 0.001) and decreased rate of relapse (24% versus 70%; P &amp;lt; 0.001) compared to those who underwent HCT with active/refractory disease. Similarly, in multivariable analysis, being in CR during HCT was associated with improved OS (Hazard Ratio [HR] 0.17, 95% Confidence Interval [CI] 0.07-0.41) and decreased risk of relapse (HR 0.18, 95% CI 0.07-0.46) after adjusting for other pre-specified variables. Conclusion While the overall outcome of patients who undergo HCT for AMKL has improved in the last few decades, it remains suboptimal. Patients who underwent HCT in CR had superior outcomes. Our data supports the notion that patients with de novo AMKL would benefit from HCT when they first achieve CR while we await novel strategies in treating relapsed or refractory AMKL.