Survival Time Research Articles

Simulating Data From Marginal Structural Models for a Survival Time Outcome.

Marginal structural models (MSMs) are often used to estimate causal effects of treatments on survival time outcomes from observational data when time-dependent confounding may be present. They can be fitted using, for example, inverse probability of treatment weighting (IPTW). It is important to evaluate the performance of statistical methods in different scenarios, and simulation studies are a key tool for such evaluations. In such simulation studies, it is common to generate data in such a way that the model of interest is correctly specified, but this is not always straightforward when the model of interest is for potential outcomes, as is an MSM. Methods have been proposed for simulating from MSMs for a survival outcome, but these methods impose restrictions on the data-generating mechanism. Here, we propose a method that overcomes these restrictions. The MSM can be, for example, a marginal structural logistic model for a discrete survival time or a Cox or additive hazards MSM for a continuous survival time. The hazard of the potential survival time can be conditional on baseline covariates, and the treatment variable can be discrete or continuous. We illustrate the use of the proposed simulation algorithm by carrying out a brief simulation study. This study compares the coverage of confidence intervals calculated in two different ways for causal effect estimates obtained by fitting an MSM viaIPTW.

Mixture Cure Semiparametric Accelerated Failure Time Models With Partly Interval-Censored Data.

In practical survival analysis, the situation of no event for a patient can arise even after a long period of waiting time, which means a portion of the population may never experience the event of interest. Under this circumstance, one remedy is to adopt a mixture cure Cox model to analyze the survival data. However, if there clearly exhibits an acceleration (or deceleration) factor among their survival times, then an accelerated failure time (AFT) model will be preferred, leading to a mixture cure AFT model. In this paper, we consider a penalized likelihood method to estimate the mixture cure semiparametric AFT models, where the unknown baseline hazard is approximated using Gaussian basis functions. We allow partly interval-censored survival data which can include event times and left-, right-, and interval-censoring times. The penalty function helps to achieve a smooth estimate of the baseline hazard function. We will also provide asymptotic properties to the estimates so that inferences can be made on regression parameters and hazard-related quantities. Simulation studies are conducted to evaluate the model performance, which includes a comparative study with an existing method from the smcure R package. The results show that our proposed penalized likelihood method has acceptable performance in general and produces less bias when faced with the identifiability issue compared to smcure. To illustrate the application of our method, a real case study involving melanoma recurrence is conducted and reported. Our model is implemented in our R package aftQnp which is available from https://github.com/Isabellee4555/aftQnP.

Surgically managed incarcerated umbilical hernias in calves hold favorable prognosis: a retrospective analysis of 19 cases (2004-2021).

To describe the clinical signs, surgical management, postoperative complications, and outcomes following herniorrhaphy in calves with incarcerated umbilical hernias. This was a retrospective case series. The electronic medical record databases of 2 veterinary teaching hospitals were searched to identify the records of calves that underwent herniorrhaphy for correction of irreducible umbilical hernias between January 1, 2004, and December 31, 2021. Data collected included signalment, medical history, results of clinical examination and laboratory testing, ultrasonographic and surgical findings (incarceration vs strangulation), postoperative complications, and outcome. 19 calves with incarcerated umbilical hernias underwent surgical correction. The incarcerated gastrointestinal tract was identified as the abomasum in 11 calves and jejunum in 8 calves. In 9 calves, the intraoperative identification of strangulation led to 4 intestinal resections and 4 partial abomasectomies, with 1 calf being euthanized intraoperatively. Postoperative complications were reported in 3 calves that underwent intestinal resection. Sixteen calves (84%) survived to discharge and had a median survival time of 1,995 days after surgery. No statistically significant differences were observed between calves with or without gastrointestinal tract strangulation in the short-term survival rate, survival time, or number of lactations after surgery. This study demonstrated that herniorrhaphy for incarcerated umbilical hernias in calves is associated with a favorable prognosis. Postoperative complications are, however, more frequent in calves with strangulated gastrointestinal tract. Surgical intervention for incarcerated umbilical hernias in calves generally yields a positive prognosis, particularly in the absence of gastrointestinal tract strangulation, highlighting the importance of timely diagnosis and treatment.

Innovative Nanomaterials for Targeting Hypoxia to Improve Treatment for Triple-negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer with a high rate of metastases, a short overall survival time, and a poor response to targeted therapy. Improving tumor hypoxia by lowering the oxygen consumption rate of breast tumor cells is a powerful strategy. A viable way to address this issue is to improve therapeutic efficacy by improving the effectiveness of radiation and overcoming drug resistance in TNBC treatment by controlling hypoxia in the tumor microenvironment. The failure of radiation and chemotherapy in TNBC is frequently caused by hypoxia. In TNBC therapy, novel nanomaterials are used for oxygen delivery or generation to affect the tumor microenvironment to improve the effects of ionizing radiation using nanoplatforms. One of the growing fields is novel nano-based drug delivery devices for hypoxic regions and hypoxia- inducible factor-1 (HIF1) targeted therapeutics. Biocompatible nanoparticles may be used in the treatment of TNBC patients in the clinic. Because of the rising market and competition, intellectual property rights (IPR), patents, and tactics may be critically considered. To better comprehend the current state of IPR and patents in cancer nanotechnology, this overview examines recent advances and sophisticated protection measures in this area.

Liang-Ge-San protects against viral infection-induced acute lung injury through inhibiting α7nAChR-mediated mitophagy.

Acute lung injury (ALI) is the main cause of death in clinical respiratory virus infection. Liang-Ge-San (LGS), a famous traditional Chinese formula, has been proved to be effective in treating ALI caused by lipopolysaccharide. However, the effects of LGS on ALI induced by viral infections remain uncertain. To investigate the effect and mechanism of action of LGS on viral infection-induced ALI. The inhibitory effects of LGS on virus-induced inflammation in vitro were evaluated by qRT-PCR and ELISA. The protein expression of α7nAChR was examined by Western blotting. α7nAChR was inhibited by the transfection of siRNA or methyllycaconitine citrate (MLA, an α7nAChR inhibitor) to investigate the role of α7nAChR in the anti-inflammatory effect of LGS. Adoptive culture and co-culture systems of macrophages RAW264.7 and alveolar epithelial cells MLE-12 were established to mimic their interaction. Western blotting, immunofluorescence, flow cytometry and transmission electron microscopy were used to examine the effects of LGS on mitophagy inhibition. In vivo, ALI mouse models induced by SARS-CoV-2, H1N1 or Poly(I:C) infection were established to explore the therapeutic effect and mechanism of LGS. LGS reduced the release of IL-6, TNF-α and IL-1β and increased the expression of α7nAChR in virus-infected RAW264.7 cells. The blockage of α7nAChR counteracted the anti-inflammatory effect of LGS. Moreover, LGS significantly inhibited autophagy in MLE-12 cells induced by Poly(I:C) in adoptive culture and co-culture systems of RAW264.7 and MLE-12 cells, which could be attenuated after the inhibition of α7nAChR in RAW264.7 cells by decreasing the secretion of IL-6, TNF-α and IL-1β. Further study showed that LGS suppressed TNF-α-induced mitochondrial damage and mitophagy by inhibiting the generation of ROS in MLE-12 cells. In vivo, LGS significantly prolonged the survival time, alleviated pathological injury and acute inflammation of ALI mice induced by SARS-CoV-2, H1N1 or Poly(I:C) infection which were associated with the inhibition of α7nAChR-mediated mitophagy. This study first demonstrates that LGS inhibits virus infection-induced inflammation in RAW246.7 cells by increasing the expression of α7nAChR, thereby inhibiting mitophagy induction in MLE-12 cells to alleviate ALI. This work indicates that LGS may serve as a candidate drug for treating ALI/ARDS caused by viral infection.

Naringenin Nanoformulations for Neurodegenerative Diseases.

Glioblastoma (GBM) is a grade-IV astrocytoma, which is the most common and aggressive type of brain tumor, spreads rapidly and has a life-threatening catastrophic effect. GBM mostly occurs in adults with an average survival time of 15 to 18 months, and the overall mortality rate is 5%. Significant invasion and drug resistance activity cause the poor diagnosis of GBM. Naringenin (NRG) is a plant secondary metabolite byproduct of the flavanone subgroup. NRG can cross the blood-brain barrier and deliver drugs into the central nervous system when conjugated with appropriate nanocarriers to overcome the challenges associated with gliomas through naringenin-loaded nanoformulations. Here, we discuss several nanocarriers employed that are as delivery systems, such as polymeric nanoparticles, micelles, liposomes, solid lipid nanoparticles (SLNs), nanosuspensions, and nanoemulsions. These naringenin-loaded nanoformulations have been tested in various in vitro and in vivo models as a potential treatment for brain disorders. This review nanoformulations of NRG can a possible therapeutic alternative for the treatment of neurological diseases are discussed.

Bayesian Analysis of the Generalized Additive Proportional Hazards Model: Asymptotic Studies

In this paper, we study Bayesian asymptotic properties of the proportional hazards model where the link function is modeled by the generalized additive model. As the standard generalized additive model is, the generalized additive proportional hazards model is a useful tool in finding the nonlinearity of covariate effects to survival times. We develop a data-dependent sieve prior for the generalized additive link function and use the Bayesian bootstrap prior for the baseline hazard function. We prove that the posterior contraction rate of the generalized additive link function is minimax optimal up to a logn term when the prior is carefully selected. By analyzing simulated as well as real data, we verify our theoretical results and compare with exisiting algorithms for the generalized additive proportional hazards model to illustrate that the proposed Bayesian model is a useful inference tool.

The Relationship between Framingham Stroke Risk Profile on Incident Dementia and Alzheimer's Disease: A 40-Year Follow-Up Study Highlighting Female Vulnerability.

Sex differences in the association between cardiovascular risk factors and the incident all-cause dementia and the subtype Alzheimer's disease (AD) risk are unclear. Framingham Heart Study (FHS) participants (n = 4,171, 54% women, aged 55 to 69 years) were included at baseline and followed up to 40 years. The Framingham Stroke Risk Profile (FSRP) was dichotomized into 2 levels (cutoff: 75th percentile of the FSRP z-scores). Cause-specific hazard models, with death as a competing event, and restricted mean survival time (RMST) model were used to analyze the association between FSRP levels and incident all-cause dementia and AD. Interactions between FSRP and sex were estimated, followed by a sex-stratified analysis to examine the sex modification effect. High FSRP was significantly associated with all-cause dementia (hazard ratio [HR] = 1.25, robust 95% confidence interval [CI] = 1.21 to 1.29, p < 0.001) and AD (HR = 1.58, robust 95% CI = 1.57 to 1.59, p < 0.001) in cause-specific hazard models. High FSRP was significantly associated with incident dementia (HR = 2.81, robust 95% CI = 2.75 to 2.87, p < 0.001) and AD (HR = 2.96, robust 95% CI = 2.36 to 3.71, p < 0.001) in women, but not in men. Results were consistent in the RMST models. Current diabetes and high systolic blood pressure as FSRP components were significantly associated with dementia and AD in women but not in men. High FSRP in mid- to early late life is a critical risk factor for all-cause dementia and AD, particularly in women. Sex-specific interventions and further research to elucidate underlying mechanisms are warranted. ANN NEUROL 2024;96:1124-1134.

Antipsychotic discontinuation in nonaffective first-episode psychosis after clinical remission: Insights from the PEPsNa naturalistic study

The predictors of clinical evolution after nonaffective first-episode psychosis (NAFEP) have yet to be fully elucidated. It is important to weigh the long-term benefits of maintained antipsychotic (AP) treatment against the risks of relapse upon discontinuation. Between January 2017 and December 2022, we recruited 211 NAFEP patients from the Programa de Primeros Episodios Psicóticos de Navarra (PEPsNa) who achieved clinical remission within two years and continued follow-up. Clinicians recommended discontinuation of antipsychotics for 47 participants, resulting in significantly fewer relapses (10.6%, p≤ 0.05) and a longer relapse-free survival time (95% confidence interval= 16.9 to 18.2 months). For every four individuals out of 72 who voluntarily discontinued APs (in contrast to those who were advised to discontinue APs), there was one more relapse (number needed to harm= 4; p≤ 0.01). Moreover, one additional relapse was prevented for every seven individuals who continued APs instead of voluntarily discontinuing APs (number needed to treat= 7; p≤ 0.05). Lower premorbid risk factors and better clinical profiles, such as shorter DUP, shorter time to remission, good real-world performance, better neurocognitive functioning, lack of a schizophrenia spectrum diagnosis, and a lower average dose of APs led clinicians to recommend AP discontinuation after achieving remission from NAFEP. This guided discontinuation of APs did not lead to a higher risk of relapse, but participants who voluntarily withdrew from treatment had a higher risk of relapse.

Understanding the impact of non-linearity in the SIS model

The SIS model is a classic model from epidemiology that formalizes a variety of diffusion processes on networks, such as biological infections and information dissemination. In this model, vertices are either infected or susceptible to an infection. Infected vertices infect their neighbors independently at a rate λ>0, and each infected vertex becomes susceptible at a rate of 1. Overall, these dynamics imply that each susceptible vertex with exactly m infected neighbors becomes infected at rate λm, that is, linear in m. However, it has been observed that various processes exhibit a non-linear scaling of the infection rate with respect to m. For these kinds of processes, no fully rigorous guarantees exist so far.We address this shortcoming by considering a variant of the SIS model in which vertices get infected at a rate that scales polynomially in the number of their infected neighbors, weighted by the infection coefficient λ. We give the first fully rigorous results for thresholds of λ at which the expected survival time becomes super-polynomial. For cliques we show that when the infection rate scales sub-linearly, the threshold only shifts by a poly-logarithmic factor, compared to the standard SIS model. In contrast, super-linear scaling changes the process considerably and shifts the threshold by a polynomial term. For stars, sub-linear and super-linear scaling behave similar and both shift the threshold by a polynomial factor. Our bounds are almost tight, as they are only apart by at most a poly-logarithmic factor from the lower thresholds, at which the expected survival time is logarithmic.

The prophylactic application of low-dose rabbit antithymocyte globulin in matched siblings HSCT with high-risk factors for graft-versus-host disease

Relapse and graft-versus-host disease (GVHD) are currently the predominant causes of mortality post allogeneic hematopoietic stem cell transplantation (allo-HSCT). The contentious use of antithymocyte globulin (ATG) for preventing GVHD in matched sibling HSCT scenarios has been a topic of significant debate. A retrospective analysis was conducted on matched sibling HSCT cases with high-risk factors for GVHD in our center from January 2018 to June 2023. Our assessment revealed that the group administered with ATG exhibited a 30 % incidence of acute GVHD (aGVHD), in contrast to 81.8 % in the non-ATG cohort (P = 0.037) among matched sibling HSCT cases with high GVHD risk factors. Furthermore, chronic GVHD (cGVHD) occurred in 20 % of the ATG group and 72.7 % of the non-ATG group (P = 0.03). Notably, the administration of ATG did not significantly impact disease relapse (p = 0.149), infection rates (p = 0.64), granulocyte recovery time (p = 0.15), platelet recovery time (p = 0.12), overall survival (p = 0.889), or disease-free survival time (p = 0.787). The use of rabbit antithymocyte globulin (r-ATG) at a 5 mg/kg dosage demonstrated a notable reduction in aGVHD and cGVHD incidences within sibling matched HSCT cases with high-risk factors for GVHD, without increasing rates of disease recurrence or infections. These findings highlight the potential benefit of using low-dose r-ATG in high-risk of GVHD sibling matched allogeneic HSCTs, although further validation with a larger cohort is necessary.

The clinical features and prognostic implications of the co-mutated TP53 gene in advanced non-small cell lung cancer.

TP53 is a frequently mutated oncogene within non-small cell lung cancer (NSCLC). However, the clinical and prognostic significance of co-mutations in TP53 in patients with advanced NSCLC has not been fully elucidated. A total of 174 patients with advanced NSCLC were enrolled in this study. All patients were subjected to sequencing analysis of tumor-related genes and information such as PD-L1 expression, TMB, and co-mutation changes were collected. Patients were categorized into TP53 mutant and TP53 wild-type groups according to their TP53 mutation status and then statistically analyzed. TP53 mutations were the most common among all patients, accounting for 56.32%, followed by epidermal growth factor receptor mutations at 48.27%. The most common mutation sites in the TP53 mutation group were exons 5-8.TP53 mutations were significantly associated with PD-L1 and TMB levels. Univariate Cox analysis showed that gender and EGFR mutation affected the prognosis of TP53-mutated NSCLC patients, and multivariate Cox regression analysis identified EGFR mutation as an independent risk factor. The OS of NSCLC patients in the TP53 mutation group was significantly shorter than that of the TP53wt group. Survival curves in the TP53/EGFR combined mutation group showed that patients with combined EGFR mutation had a lower survival rate. TP53 mutations are associated with different clinical indicators and have important implications in clinical treatment. TP53 is a poor prognostic factor for NSCLC patients, and TP53/EGFR co-mutation will affect the survival time of patients. TP53/EGFR co-mutation may be a new prognostic marker for NSCLC.

Correlation between Immune Microenvironment and Clinicopathological Characteristics and Prognosis of Primary Large B-cell Lymphoma of Immune-Privileged Sites

ObjectivesTo explore the correlation between tumor-associated macrophages (TAMs), tumor-infiltrating lymphocytes (TILs), and tumor-associated angiogenesis (TAA) in the tumor microenvironment with the clinicopathological characteristics and prognosis of primary large B-cell lymphoma of immune-privileged sites (LBCL-IP).MethodsA total of 46 cases of LBCL-IP from the Department of Pathology, the Third Affiliated Hospital of Xinjiang Medical University, from January 2010 to February 2024, were collected, along with clinical and follow-up data of LBCL-IP patients. Immunohistochemistry and triple immunofluorescence were used to detect related proteins of TAMs, TILs, and TAA, and to analyze the correlation between TAMs, TILs, TAA, and the polarization of TAMs with the clinical and prognostic factors of LBCL-IP patients.ResultsThere are 30 cases (65.2%) showed high expression of CD68 proteins, 32 cases (69.6%) showed high expression of CD163 proteins, 19 cases (41.3%) showed high expression of CD4 proteins, 34 cases (73.9%) showed high expression of CD8 proteins, and 25 cases (54.3%) showed high expression of CD34 proteins. A total of 27 cases (58.7%) showed CD68+CD163+/CD68+CD86+≥1. The chi-square tests showed that high expression of CD163 proteins was positively correlated with elevated LDH and BMG values, and the count of CD68+CD163+/CD68+CD86+≥1 was positively correlated with ECOG scores ≥2, Ann Arbor staging III-IV, and increased BMG value. High expression of CD8 proteins was positively correlated with a Ki-67 proliferation index ≥70%, and high MVD values were positively correlated with Ann Arbor staging III-IV. The Kaplan-Meier estimator analysis showed that LBCL-IP patients with low expression of CD68 proteins, high expression of CD163 proteins, CD68+CD163+/CD68+CD86+≥1, low expression of CD8 proteins, high MVD values, ECOG scores ≥2, Ann Arbor staging III-IV, LDH ≥250U/L, BMG ≥2.2mg/L, and IPI scores ≥2 had shorter survival times. Multivariate Cox regression analysis showed that low expression of CD8 proteins, CD68+CD163+/CD68+CD86+≥1, LDH ≥250U/L, and ECOG scores ≥2 are independent risk factors affecting the survival of LBCL-IP patients.ConclusionM2-polarized TAMs and low infiltration of CD8+ TILs were more strongly correlated with poor clinical pathological indicators and worse prognosis, and MVD values may serve as an aiding means for the diagnosis and prognostic prediction of LBCL-IP disease.

Nivolumab plus Ipilimumab in Microsatellite-Instability–High Metastatic Colorectal Cancer

BackgroundPatients with microsatellite-instability–high (MSI-H) or mismatch-repair–deficient (dMMR) metastatic colorectal cancer have poor outcomes with standard chemotherapy with or without targeted therapies. Nivolumab plus ipilimumab has shown clinical benefit in nonrandomized studies of MSI-H or dMMR metastatic colorectal cancer.MethodsIn this phase 3 open-label trial, we randomly assigned patients with unresectable or metastatic colorectal cancer and MSI-H or dMMR status according to local testing to receive, in a 2:2:1 ratio, nivolumab plus ipilimumab, nivolumab alone, or chemotherapy with or without targeted therapies. The dual primary end points, assessed in patients with centrally confirmed MSI-H or dMMR status, were progression-free survival with nivolumab plus ipilimumab as compared with chemotherapy as first-line therapy and progression-free survival with nivolumab plus ipilimumab as compared with nivolumab alone in patients regardless of previous systemic treatment for metastatic disease. At this prespecified interim analysis, the first primary end point (involving nivolumab plus ipilimumab vs. chemotherapy) was assessed.ResultsA total of 303 patients who had not previously received systemic treatment for metastatic disease were randomly assigned to receive nivolumab plus ipilimumab or chemotherapy; 255 patients had centrally confirmed MSI-H or dMMR tumors. At a median follow-up of 31.5 months (range, 6.1 to 48.4), progression-free survival outcomes (the primary analysis) were significantly better with nivolumab plus ipilimumab than with chemotherapy (P<0.001 for the between-group difference in progression-free survival, calculated with the use of a two-sided stratified log-rank test); 24-month progression-free survival was 72% (95% confidence interval [CI], 64 to 79) with nivolumab plus ipilimumab as compared with 14% (95% CI, 6 to 25) with chemotherapy. At 24 months, the restricted mean survival time was 10.6 months (95% CI, 8.4 to 12.9) longer with nivolumab plus ipilimumab than with chemotherapy, a finding consistent with the primary analysis of progression-free survival. Grade 3 or 4 treatment-related adverse events occurred in 23% of the patients in the nivolumab-plus-ipilimumab group and in 48% of the patients in the chemotherapy group.ConclusionsProgression-free survival was longer with nivolumab plus ipilimumab than with chemotherapy among patients who had not previously received systemic treatment for MSI-H or dMMR metastatic colorectal cancer. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 8HW ClinicalTrials.gov number, NCT04008030.)

Analysis of therapeutic effect of cell reduction combined with intraperitoneal thermoperfusion chemotherapy in treatment of peritoneal pseudomyxoma

BACKGROUND Pseudomyxoma peritonei is a rare tumor that can produce a biological behavior similar to that of a malignant tumor. Surgical resection combined with chemotherapy is the traditional treatment method, but the effect is not good. Cell reduction (CRS) combined with intraperitoneal thermoperfusion chemotherapy (HIPEC) has become a new method for the treatment of peritoneal pseudomyxoma (PMP). AIM To find out if CRS and HIPEC can be used safely and effectively to treat PMP. METHODS This is an observational study. Clinical data of PMP patients treated with CRS + HIPEC at our hospital from January 2013 to June 2023 was collated and analyzed. The main outcome measures were overall survival (OS), and the secondary outcome measures were the incidence of surgical complications and serious adverse events. Complications were graded according to common adverse event evaluation criteria. Peritoneal tumor staging was performed using the peritoneal tumor index (PCI) scoring system, and a cell reduction degree (CCR) score was performed after CRS. CCR-0 and CCR-1 were considered satisfactory CRS. RESULTS A total of 186 patients with PMP were included, with a median age of 56 (48-64) years, 65 (34.9%) years in males, and 121 (65.1%) years in females. The median PCI score was 28 (20-34) points. The median operative time was 300 (211-430) minutes, and no significant complications occurred. 91.4% (170/186) were from the appendix, 53.2% (99/186) were from the low grade, and 30.6% (57/186) were from the high grade. CCR scores showed that 55 patients (29.6%) achieved satisfactory CRS, and 113 patients (60.8%) did not achieve satisfactory CRS. The fatality rate at 30 days after surgery was 2.7% (5/186), 1.6% (3/186) needed a second operation, and the fatality rate at 90 days was 4.3% (8/186). The total incidence of III-IV complications was 43.0% (80/186), among which the higher incidence was mainly anemia (27.4%, 51/186), electrolyte disturbance (11.6%, 21/181), and albumin decrease (7.5%, 14/186). The main complications associated with abdominal surgery were gastrointestinal anastomotic leakage (2.2%, 4/186), abdominal hemorrhage (2.2%, 4/186), and abdominal infection (4.3%, 8/186). The median follow-up was 38.1 (95%CI: 31.2-45.1) months. The 5-year OS of PMP patients treated with CRS + HIPEC was 50.3% (95%CI: 40.7%-59.9%), and the median survival time was 66.1 (95%CI: 43.1-89.1) months. The results of the survival analysis showed that patients with a low pathological grade, a low PCI, and a satisfactory CCR score had a higher survival rate (all P &lt; 0.05). 5-year OS was 88.9% (95%CI: 68.3%-100.0%) in CCR-0 patients, 77.6% (95%CI: 62.7%-92.5%) in CCR-1 patients, and 42.0% (95%CI: 29.5%-54.5%) in CCR-2/3 patients. CONCLUSION The application of CRS + HIPEC in PMP is safe and feasible, and the survival benefit is high, especially in those who achieve satisfactory CRS, which can significantly extend the OS.

Developing a utility value set for the Gambling Quality of Life Scale-Brief (GQoLS-Brief) using a discrete choice experiment.

The Gambling Quality of Life Scale -brief (GQoLS-Brief) assesses the impact of gambling disorder (GD) on quality of life (QoL). Preference-based measures are essential for obtaining the quality adjustment weight (i.e. utility score) needed to calculate quality-adjusted life years (QALYs) in economic evaluations. We aimed to derive a value set for the GQoLS-Brief. We employed a discrete choice experiment for preference elicitation. An online survey was administered (n = 928). Respondents completed 10 choice tasks, each presenting two GQoLS-Brief health states alongside life expectancy. Conditional logit regression, parameterized to fit the QALY framework, was used for data analysis. QALY weights for each health state defined by the GQoLS-Brief were calculated. The estimated coefficients from the conditional logit models aligned with expectations: utility increased with survival time and decreased with QoL impairment. Utility values for health states ranged from -1.48 (worse than death) to 1.0. "Financial difficulties" exhibited the highest utility decrement, followed by "Sleep disturbance related to financial difficulties." This reference set facilitates the calculation of QALYs for economic evaluations of GD interventions. The weight of subjective financial difficulties underscores the need for therapeutic interventions to target this aspect.

The impact of positive resection margin in perihilar cholangiocarcinoma, ductal margin vs radial margin.

Resection margin status is the important prognostic factor in resected perihilar cholangiocarcinoma (pCCA). Although the impact of ductal margin (DM) was reported in many studies, the influence of radial margin (RM) is unclear. This study aims to investigate the effect of positive RM on survival. Patients with pCCA underwent curative resection between 2013 and 2018 were retrospectively reviewed. Resection margin status was divided into negative resection margin (R0) and positive resection margin (R1); positive RM alone (RM+) and positive DM with or without positive RM (DM+). Of the 167 pCCA patients, 62 (37.1%) had R1 margin. Among 62 R1 patients; 17 (27.4%) had positive DM alone, 20 (32.3%) had positive RM alone and 25 (40.3%) had both positive DM and RM. The R1 patients had a significantly greater number of lymph node metastasis (LNM) and advanced tumor staging than R0 patients, however there was no difference between the RM + and DM + patients. The median survival time of patients with RM + was significantly poorer than R0 patients (13.8 vs. 24.5 months; p < 0.001, respectively) and similar to the DM + patients (9.1 months, p = 0.556). However, in patients with LNM, those who underwent R0 resection had no statistically significant difference in survival outcomes compared to those with R1 resection. Positive resection margin remains the important prognostic factor, and positive RM is common in these patients. Positive RM also had a comparable effect on survival as positive DM. As a result, in pCCA, surgical resection should target both RM and DM.

Duration Diabetes Survival Times Modelling Using Some Extended Lomax Distribution

The precise modeling of survival time in diabetes is essential for accurately estimating the potential lifespan of individuals diagnosed with diabetes. One of the key factors in assessing the potential survival times of diabetes patients in a specific region is the probability distribution of diabetes survival times. Therefore, data on diabetes survival times are necessary to conduct statistical modeling, particularly in determining the most suitable probability distribution. Statistical models are developed to draw conclusions about the probability distribution of diabetic patients at the Mandau Regional General Hospital (RSUD) in Bengkalis Regency, Riau Province. To achieve this, six distributions will be utilized and evaluated to identify the best model for describing diabetes survival times. The primary objective of this research is to identify the most appropriate distribution to represent the survival times of diabetes patients from 50 individuals in the Bengkalis region, using the Lomax (LM) distribution, three parameters modified Lomax distributions (Rayleigh Lomax (RL), Logistics Lomax (LL), New Rayleigh Lomax (NRL)) and four parameters modified Lomax Distribution (Odd Lomax Log Logistics (OL), Novel Extended Power Lomax (PL)). The maximum likelihood method will be employed to estimate the parameter values of the distributions used in this study. Additionally, graphical assessments (density-density plot) and numerical criteria (Akaike’s Information Criterion (AIC), -log likelihood (-l)) will be utilized to determine the best-fitting model. In most instances, the results obtained from graphical assessments were consistent but differed from the numerical criteria. The model with the lowest values of AIC and -l was selected as the best fit. Overall, the RL and OL distributions was identified as the most suitable model.

Multiple Instance Bagging and Risk Histogram for Survival Time Analysis Based on Whole Slide Images of Brain Cancer Patients

This study tackles the challenges in computer-aided prognosis for glioblastoma multiforme, a highly aggressive brain cancer, using only whole slide images (WSIs) as input. Unlike traditional methods that rely on random selection or region-of-interest (ROI) extraction to choose meaningful subsets of patches representing the whole slide, we propose a multiple instance bagging approach. This method utilizes all patches extracted from the whole slide, employing different subsets in each training epoch, thereby leveraging information from the entire slide while keeping the training computationally feasible. Additionally, we developed a two-stage framework based on the ResNet-CBAM model which estimates not just the usual survival risk, but also predicts the actual survival time. Using risk scores of patches estimated from the risk estimation stage, a risk histogram can be constructed and used as input to train a survival time prediction model. A censor hinge loss based on root mean square error was also developed to handle censored data when training the regression model. Tests using the Cancer Genome Atlas Program’s glioblastoma public database yielded a concordance index of 73.16±2.15%, surpassing existing models. Log-rank testing on predicted high- and low-risk groups using the Kaplan–Meier method revealed a p-value of 3.88×10−9, well below the usual threshold of 0.005, indicating the model’s ability to significantly differentiate between the two groups. We also implemented a heatmap visualization method that provides interpretable risk assessments at the patch level, potentially aiding clinicians in identifying high-risk regions within WSIs. Notably, these results were achieved using 98% fewer parameters compared to state-of-the-art models.

Efficacy of neoadjuvant therapy and lymph node dissection in advanced gallbladder cancer without distant metastases: a SEER database analysis

PurposeTo investigate the effectiveness of neoadjuvant therapy and lymph node dissection(LND) on overall survival (OS) in patients with stage III/IV gallbladder cancer without distant metastases.MethodsData from 101 patients who received neoadjuvant therapy followed by surgery combined with adjuvant chemotherapy, and 1412 patients who received direct surgical treatment followed by adjuvant chemotherapy, were collected from the SEER database from 2004 to 2020. Patients were divided into group A (neoadjuvant therapy) and group B (direct surgery) based on the treatment modality. A total of 202 cases were obtained after propensity score matching, with 101 cases in each group (A and B). Cox unifactorial and multifactorial analyses were performed to identify independent risk factors for patients with advanced cholecystic carcinoma, and the Kaplan-Meier method was used to analyze overall survival (OS). The Cox proportional hazards model was used to investigate the effect of different subgroups on OS in both patient groups. Further survival analyses were conducted to determine whether lymph node dissection(LND) was beneficial for patients receiving neoadjuvant therapy for gallbladder cancer.ResultsCox univariate analysis showed that marital status, AJCC stage, number of LND, tumor size, and treatment modality were associated with OS (P&amp;lt;0.05). Cox multifactorial regression analysis indicated that AJCC stage, LND, tumor size, and treatment modality were independent risk factors for OS in patients with non-metastatic advanced gallbladder cancer (P&amp;lt;0.05). Survival curves demonstrated that the OS in group A was longer than in group B (median OS: 30 months vs. 14 months, P&amp;lt;0.001). Subgroup analysis indicated that neoadjuvant therapy had a consistent effect on the OS of patients with advanced gallbladder cancer, improving both survival time and outcomes. Survival curves indicated that lymph node dissection was not significant in group A patients (p&amp;gt;0.05) but was significant in group B (p&amp;lt;0.05).ConclusionNeoadjuvant therapy can improve the OS of patients with non-metastatic stage III/IV gallbladder cancer and is an independent risk factor affecting prognosis; however, the significance of lymph node dissection in these patients still needs further study.