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Introduction Colorectal cancer (CRC) is common among older patients, who face an increased risk of postoperative complications from malnutrition and systemic inflammation. The serum Albumin-Neutrophil-to-Lymphocyte Ratio Score (ANS), indicative of nutritional and inflammatory status, is a potential predictive tool in various cancers. This study evaluated the predictive value of preoperative ANS for postoperative survival and complications in older CRC patients. Methods We retrospectively analyzed 182 patients aged 65 and over who underwent curative-intent CRC surgery between 2018 and 2020 at a Taiwanese medical center. Based on pretreatment-ANS, patients were categorized into three groups: ANS 0, high albumin and low neutrophil-to-lymphocyte ratio (NLR); ANS 1, low albumin or high NLR; and ANS 2, low albumin and high NLR. Overall survival (OS), length of hospital stay (LOS), postoperative complications, and health-related quality of life (HRQoL) were analyzed and compared across groups. Results Patients in the ANS 2 group exhibited significantly poorer OS, with an adjusted hazard ratio of 2.90 (95% confidence interval [CI]:1.15-7.30, P = 0.024), compared to ANS 0. Additionally, they experienced a longer median LOS (14 vs 9 days, P < 0.001) and a higher risk of major postoperative complications (Odds ratio [OR] 3.74, 95% CI: 1.59-8.83, P = 0.003) and 30-day readmission rate (OR 5.04, 95% CI: 1.32-19.3, P = 0.018) than the ANS 0 group. ANS 2 patients reported worse HRQoL, particularly in mobility and maintaining purpose (P < 0.001 and P = 0.020, respectively), compared to ANS 0 patients. Conclusion Preoperative ANS significantly predicts survival, postoperative complications, and HRQoL in older CRC patients undergoing surgery, potentially guiding perioperative management.

John Luk and colleagues report the sequencing of 81 hepatitis B virus (HBV)-positive and 7 HBV-negative hepatocellular carcinomas and matched normal tissues. They confirm recurrent integration events of HBV at TERT and MLL4 and report recurrent events at the CCNE1 gene. To survey hepatitis B virus (HBV) integration in liver cancer genomes, we conducted massively parallel sequencing of 81 HBV-positive and 7 HBV-negative hepatocellular carcinomas (HCCs) and adjacent normal tissues. We found that HBV integration is observed more frequently in the tumors (86.4%) than in adjacent liver tissues (30.7%). Copy-number variations (CNVs) were significantly increased at HBV breakpoint locations where chromosomal instability was likely induced. Approximately 40% of HBV breakpoints within the HBV genome were located within a 1,800-bp region where the viral enhancer, X gene and core gene are located. We also identified recurrent HBV integration events (in ≥4 HCCs) that were validated by RNA sequencing (RNA-seq) and Sanger sequencing at the known and putative cancer-related TERT , MLL4 and CCNE1 genes, which showed upregulated gene expression in tumor versus normal tissue. We also report evidence that suggests that the number of HBV integrations is associated with patient survival.

Hospice care has a positive effect on medical costs. The correlation between survival time after receiving hospice care and medical costs has not been previously investigated in the literature on Taiwan. This study aimed to compare the differences in medical costs between traditional care and hospice care among end-of-life patients with cancer. Data from Taiwan's National Health Insurance program on all patients who had passed away between 2010 and 2013 were used. Those whose year of death was between 2010 and 2013 were defined as end-of-life patients. The patients were divided into two groups: traditional care and hospice care. We then analyzed the differences in end-of-life medical cost between the two groups. From 2010 to 2013, the proportion of patients receiving hospice care significantly increased from 22.2% to 41.30%. In the hospice group, compared with the traditional group, the proportions of hospital stays over 14 days and deaths in a hospital were significantly higher, but the proportions of outpatient clinic visits; emergency room admissions; intensive care unit admissions; use of ventilator; use of cardiopulmonary resuscitation; and use of hemodialysis, surgery, and chemotherapy were significantly lower. Total medical costs were significantly lower. A greater number of days of survival for end-of-life patients when receiving hospice care results in higher saved medical costs. Hospice care can effectively save a large amount of end-of-life medical costs, and more medical costs are saved when patients are referred to hospice care earlier.

Few studies comprehensively investigate factors associated with significant post-traumatic-stress-disorder (PTSD) symptoms among family members of ICU decedents. We aimed to identify factors associated with significant PTSD symptoms among bereaved ICU family members, focusing on those modifiable through high-quality end-of-life ICU care. A cohort study of 321 bereaved family members of critically ill patients assessed PTSD symptoms at 1, 3, 6, 13, 18, and 24 months postloss using the Impact of Event Scale-Revised (IES-R). Family-rated quality of dying and death (QODD) and ICU care satisfaction were assessed 1 month postloss using the ICU-QODD and Family Satisfaction in the ICU (FS-ICU) scales, respectively. Multivariable logistic regression with generalized estimating equations examined associations between significant PTSD symptoms and intrapersonal (demographics, vulnerabilities), interpersonal (perceived social support measured by the Medical Outcome Study Social Support Survey), bereavement-related (patient demographics, clinical characteristics), and death-circumstance (ICU-QODD and FS-ICU scores) factors identified from significant univariate analyses. Prevalence of significant PTSD symptoms decreased substantially over time (from 11.0 % at 1 month to 0 % at 24 months post loss). Financial insufficiency (adjusted odds ratio [AOR][95 % CI] = 3.281[1.306, 8.244]) and use of antidepressants in the year prior to the patient’s critical illness (AOR[95 % CI] = 6.406 [1.868, 21.967]) increased the likelihood of significant PTSD symptoms. Stronger family-perceived social support (AOR[95 % CI] = 0.964 [0.941, 0.988]) and higher family-judged patient QODD in ICUs (AOR[95 % CI] = 0.632 [0.435, 0.918]) lowered the odds of significant PTSD symptoms. Modifiable end-of-life ICU care factors, i.e. higher family-judged patient QODD and family-perceived social support, reduced bereaved ICU family members’ likelihood of significant PTSD symptoms. To reduce the likelihood of significant PTSD symptoms in bereaved family members, ICU clinicians should provide high-quality end-of-life care to improve patient QODD and leverage social support, particularly for at-risk groups with financial challenges or prior antidepressant use.

Pancreatic cancer is among the deadliest cancers, with a grim prognosis despite advances in treatment. We conducted a population‐based case–control study from Taiwan, linking Health and Welfare Data Science Center data to the Taiwan Cancer Registry, which offers a promising strategy for its treatment through drug repurposing. The study aims to identify the association of anti‐parkinsonian drugs with pancreatic cancer risk across different age groups. The analysis encompassed 18,921 pancreatic cancer cases and 75,684 matched controls, employing conditional logistic regression to assess the impact of anti‐parkinsonian drugs on the risk of pancreatic cancer. Key findings revealed a statistically significant association of the administration with specific anti‐parkinsonian medications, including anticholinergic agents, tertiary amines, dopa derivatives, and dopamine receptor agonists, with a reduction in pancreatic cancer risk. These associations were represented as adjusted odds ratios (aORs), ranging from 0.620 (95% CI 0.470–0.810) to 0.764 (95% CI 0.655–0.891). Further, age‐stratified analysis revealed variations in efficacy across different age groups. Anticholinergic agents and tertiary amines exhibited greater effectiveness in the 40–64‐year age group (aOR, 0.653; 95% CI, 0.489–0.872), whereas dopa derivatives and dopamine receptor agonists were particularly efficacious in the cohort aged ≥65 years (aOR, 0.728; 95% CI, 0.624–0.850 and aOR, 0.665; 95% CI, 0.494–0.894, respectively). Notably, specific drugs such as trihexyphenidyl, levodopa/dopa decarboxylase inhibitor (DDCI), and pramipexole demonstrated a significant decrease in cancer risk, especially in the elderly population. These preliminary findings can contribute to the possible therapeutic role of anti‐parkinsonian drugs in the treatment of pancreatic cancer. We conducted a population‐based case–control study from Taiwan, linking Health and Welfare Data Science Center data to the Taiwan Cancer Registry to evaluate the potential repurposing of anti‐parkinsonian drugs for pancreatic cancer treatment. The findings revealed a statistically significant association of the administration with specific anti‐parkinsonian medications, including anticholinergic agents, tertiary amines, dopa derivatives, and dopamine receptor agonists, with a reduction in pancreatic cancer risk. Further, age‐stratified analysis revealed differential efficacy across age groups.

Background/Objective Death in intensive care units (ICUs) may increase bereaved family members’ risk for posttraumatic stress disorder (PTSD). However, posttraumatic stress-related symptoms (hereafter as PTSD symptoms) and their precipitating factors were seldom examined among bereaved family members and primarily focused on associations between PTSD symptoms and patient/family characteristics. We aimed to investigate the course and predictors of clinically significant PTSD symptoms among family members of deceased ICU patients by focusing on modifiable quality indicators for end-of-life ICU care. Method In this longitudinal observational study, 319 family members of deceased ICU patients were consecutively recruited from medical ICUs from two Taiwanese medical centers. PTSD symptoms were assessed at 1, 3, 6, and 13 months post-loss using the Impact of Event Scale-Revised (IES-R). Family satisfaction with end-of-life care in ICUs was assessed at 1 month post-loss. End-of-life care received in ICUs was documented over the patient’s ICU stay. Predictors for developing clinically significant PTSD symptoms (IES-R score ≥ 33) were identified by multivariate logistic regression with generalized estimating equation modeling. Results The prevalence of clinically significant PTSD symptoms decreased significantly over time (from 11.0% at 1 month to 1.6% at 13 months post-loss). Longer ICU stays (adjusted odds ratio [95% confidence interval] = 1.036 [1.006, 1.066]), financial insufficiency (3.166 [1.159, 8.647]), and reported use of pain medications (3.408 [1.230, 9.441]) by family members were associated with a higher likelihood of clinically significant PTSD symptoms among family members during bereavement. Stronger perceived social support (0.937 [0.911, 0.965]) and having a Do-Not-Resuscitate (DNR) order issued before the patient’s death (0.073 [0.011, 0.490]) were associated with a lower likelihood of clinically significant PTSD symptoms. No significant association was observed for family members’ satisfaction with end-of-life care (0.988 [0.944, 1.034]) or decision-making in ICUs (0.980 [0.944, 1.018]). Conclusions The likelihood of clinically significant PTSD symptoms among family members decreased significantly over the first bereavement year and was lower when a DNR order was issued before death. Enhancing social support and facilitating a DNR order may reduce the trauma of ICU death of a beloved for family members at risk for developing clinically significant PTSD symptoms.

Introduction Nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) is an established second-line therapy for metastatic pancreatic ductal adenocarcinoma (PDAC). We previously developed a prognostic model (CGMH nomogram) to predict overall survival (OS) in patients receiving second-line chemotherapy before the nal-IRI + 5-FU/LV era. Herein, we aimed to validate the CGMH nomogram in a real-world cohort treated with nal-IRI plus 5-FU/LV, the current standard second-line treatment for metastatic PDAC. Methods A retrospective cohort of 148 patients with metastatic PDAC treated with second-line nal-IRI + 5-FU/LV was analyzed. Prognostic scores were assigned using the CGMH nomogram, with patients stratified into tertiles as good, intermediate, and poor prognostic groups. Predictive performance was assessed using the concordance index (c-index) and calibration plots. Results Our cohort had a median OS of 6.1 months. Patients in the good, intermediate, and poor prognostic groups had median OS of 8.7 (95% confidence interval [CI], 6.7-10.7), 5.7 (95% CI, 5.3-6.3), and 4.0 (95% CI, 2.8-5.2) months, respectively. Compared with the good group, intermediate and poor groups had hazard ratios of 1.99 (95% CI, 1.29-3.07, P = .002) and 3.18 (95% CI, 1.87-5.40, P < .001), respectively. The nomogram demonstrated strong predictive ability, with c-indices of 0.73 and 0.70 for 6- and 12-month OS predictions, respectively. Calibration plots displayed excellent agreement between predicted and observed survival. Conclusion The CGMH nomogram reliably predicted survival outcomes in nal-IRI + 5-FU/LV-treated patients with metastatic PDAC, and validation supported its use in clinical decision-making and personalized treatment planning. Plain Language Summary Why was the study done? For patients with metastatic pancreatic cancer, the combination of nal-IRI (nanoliposomal irinotecan) with 5-fluorouracil and leucovorin (5-FU/LV) is the standard second-line treatment. Predicting how long patients might survive with this treatment can help doctors personalize care. A tool called the CGMH nomogram was developed earlier to predict survival before this treatment became standard. This study tested whether the CGMH nomogram works well for patients receiving nal-IRI + 5-FU/LV. What did the researchers do? The researchers studied the medical records of 148 patients with metastatic pancreatic cancer treated with nal-IRI + 5-FU/LV. They used the CGMH nomogram to predict patients’ survival and divided them into three groups based on their predicted outcomes: good, intermediate, and poor prognosis. They then checked how accurate these predictions were by comparing them to the actual survival times. What did the researchers find? The average survival for all patients was about 6.1 months. Patients in the good prognosis group lived longer (8.7 months) than those in the intermediate (5.7 months) or poor (4.0 months) groups. The predictions made by the CGMH nomogram were very accurate, with strong agreement between predicted and actual survival outcomes. Statistical analyses confirmed that the nomogram is reliable for making predictions. What do the findings mean? The CGMH nomogram is a helpful tool for predicting survival in patients with advanced pancreatic cancer treated with nal-IRI + 5-FU/LV. It can guide doctors in making personalized treatment plans and support better decision-making for patients based on their expected outcomes.

Introduction The Cancer and Aging Research Group (CARG) model predicts chemotherapy-related toxicities in older patients; however, its applicability has not been validated in Taiwanese patients. This study aims to validate the CARG model in older Taiwanese patients with solid tumors. Methods Patients (N = 258) aged ≥65 years with solid tumors from a single medical center, slated for first-line chemotherapy, were recruited between 2018 and 2021, with follow-up until December 31, 2022. Patients were categorized into low- (N = 85), medium- (N = 117), and high- (N = 56) risk based on CARG. Validation of CARG involved receiver operating characteristic (ROC) curves. Individual CARG variables were analyzed using univariate analysis for their impact on toxicities and survival. Results Toxicities of grades ≥3 were 38.8%, 44.4%, and 67.9% (P = .001) in the three ascending risk groups, and there were significant differences in both hematological (P = .002) and non-hematological (P < .001) toxicities. ROC was 0.631 (95% CI: 0.562-0.700), indicating satisfactory discrimination. One-year overall survival rates were 88.7%, 79.7%, and 63.8%, respectively, in ascending-risk groups, with high-risk groups showing decreased survival (P = .002). In the multivariate analysis, decreased hemoglobin, history of falls, and inability to walk one block remained significantly associated with toxicity. For overall survival, the inability to take medications was the only independent predictor. Conclusion This prognostic study validated the CARG model in a heterogeneous solid tumor cohort in Taiwan. In addition to predicting both hematological and non-hematological toxicities, CARG could offer insights into patient survival among older individuals with cancer.

Background Colorectal cancer (CRC) predominantly affects older adults, whose treatment outcomes may be influenced by baseline health-related quality of life (HRQoL). This study aimed to identify predictors of poor preoperative HRQoL in older patients undergoing CRC surgery and to stratify them into risk groups. Methods We retrospectively analyzed data on patients aged ≥65 years who underwent radical CRC surgery at a single medical center in Taiwan (2016-2018). Preoperative HRQoL was assessed using the EORTC QLQ-ELD14 questionnaire and a comprehensive geriatric assessment. Patients were stratified into high or low HRQoL groups based on the median QLQ-ELD14 sum score. Logistic regression identified independent predictors of poor HRQoL, and recursive partitioning analysis (RPA) was applied for risk stratification. Results Among the 179 patients, the most distressing HRQoL domains were Burden of Disease, Maintaining Purpose, and Worries about Others. Independent predictors of poor HRQoL included female sex (adjusted odds ratio [OR] = 2.41, P = 0.029), frailty (adjusted OR = 1.53, P = 0.042), poor Eastern Cooperative Oncology Group (ECOG) performance status (adjusted OR = 2.19, P = 0.008), and lower educational attainment (adjusted OR = 0.23, P = 0.019). RPA identified five patient subgroups with distinct risk levels; frail female had the highest risk (71.4%), while fit patients with college education or higher had the lowest (9.5%). Conclusion Frailty, functional status, sex, and education level are key determinants of preoperative HRQoL in older patients with CRC. The RPA provides a simple tool to identify high-risk patients, allowing targeted preoperative interventions to optimize care and enhance surgical outcomes.

Background Bereaved people experience distinct trajectories of prolonged-grief-disorder (PGD) symptoms. A few studies from outside critical care investigated limited factors of PGD-symptom trajectories without a theoretical framework. We aimed to characterize factors associated with ICU bereaved surrogates’ PGD-symptom trajectories, drawing from the integrative framework of predictors for bereavement outcomes, emphasizing factors modifiable by ICU care. Methods Prospective cohort study of 291 family surrogates. Multinomial logistic regression was used to determine associations of three previously identified PGD-symptom trajectories (resilient [n = 242, 83.2%] as reference group, recovery [n = 35, 12.0%], and chronic [n = 14, 4.8%]) with risk factors. Factors included intrapersonal (demographics, personal vulnerabilities), interpersonal (perceived social support), bereavement-related (patient demographics, clinical characteristics, and patient-surrogate relationship), and death-circumstance (surrogate-perceived quality of patient dying and death [QODD] in ICUs classified as high, moderate, poor-to-uncertain, and worst QODD classes) factors. Results Most surrogates were female (59.1%), the patient’s adult child (54.0%), and about (standard deviation) 49.63 (12.53) years old. As surrogate age increased, recovery-trajectory membership decreased (adjusted odds ratio [95% confidence interval] = 0.918 [0.849, 0.993]) and chronic-trajectory membership increased (1.230 [1.010, 1.498]). Being married decreased membership in the recovery (0.186 [0.047, 0.729]) trajectory. Higher anxiety symptoms 1 month post loss increased membership in recovery (1.520 [1.256, 1.840]) and chronic (2.022 [1.444, 2.831]) trajectories. Spouses were more likely and adult–child surrogates were less likely than other relationships to be in the two more profound PGD-symptom trajectories. Membership in the chronic trajectory decreased (0.779 [0.614, 0.988]) as patient age increased. The poor-to-uncertain QODD class was associated with a nearly significant increase (4.342 [0.980, 19.248]) in membership in the recovery trajectory compared to the high QODD class. Conclusions Membership in the PGD-symptom trajectories was associated with factors modifiable by high-quality ICU care, including anxiety symptoms at early bereavement and surrogate-perceived QODD in the ICU. Clinicians should be sensitive to the psychological needs of at-risk family surrogates, provide high-quality end-of-life care to facilitate QODD, and promptly refer bereaved surrogates who suffer anxiety symptoms and profound and/or persistent PGD-symptoms for psychological support. Graphical abstract