Nevin Manimala

Cancers (Basel). 2025 Apr 1;17(7):1200. doi: 10.3390/cancers17071200.

ABSTRACT

BACKGROUND: The relationship between body composition and bladder cancer outcomes is complex. While a higher body mass index (BMI) has been associated with an increased risk of bladder cancer development, its impact on survival outcomes is less clear. This study aimed to explore the association between BMI, survival, health-related quality of life, and the performance of ADLs in a cohort of older patients with bladder cancer.

METHODS: Data were obtained from the Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey, including patients diagnosed with bladder cancer who had recorded BMI values. Analysis of variance was used to assess the association between BMI categories and patient demographics as well as cancer/treatment characteristics. Generalized linear models examined the impact of BMI on health-related quality of life, as measured by the physical and mental component summary scores when controlling for confounding variables. Kaplan-Meier survival curves across BMI categories were compared using log-rank tests.

RESULTS: The final cohort consisted of 8013 patients (age ≥ 65) with a mean age of 77.7 ± 7.1 years, the majority of whom were White (85.6%) and male (74.8%). We observed no significant association between BMI and cancer/treatment characteristics. The severely obese subgroup had the highest rate of disability in performing ADLs (18.3%) followed by the underweight subgroup (10.3%). Overweight patients exhibited the highest physical and mental component summary scores, indicating better health-related quality of life. BMI was a significant predictor of overall survival, with overweight, obese, and severely obese patients demonstrating improved survival compared to those with healthy or underweight BMI. These findings remained statistically significant in multivariable analysis.

CONCLUSIONS: Our findings suggest a dual role of BMI in older patients with bladder cancer: higher BMI provides a survival advantage and, to an extent, a QoL advantage. At the same time, severe obesity did lead to the lowest QoL despite improved survival outcomes. These results underscore the complex interplay between BMI, survival, and QoL in this bladder cancer population.

PMID:40227765 | DOI:10.3390/cancers17071200

Cancers (Basel). 2025 Apr 1;17(7):1199. doi: 10.3390/cancers17071199.

ABSTRACT

Background/Objectives: Proliferative verrucous leukoplakia (PVL) is an oral disorder with the greatest degree of malignant transformation. However, it is relatively rare. This study compared the clinical characteristics of patients with oral squamous cell carcinoma (OSCC) who had and had not been previously diagnosed with PVL. Methods: This case control study compared the clinical characteristics of patients classified as early (T1 and T2) or advanced (T3 and T4) OSCC according to the T size of the Tumor, Node, Metastasis (TNM) classification, including age, gender, location, and clinical type of oral squamous cell carcinoma. The analysis involved 140 patients. Group 1: 50 OSCC patients with PVL (OSCC-PVL) and Group 2: 90 OSCC patients without PVL (OSCC-noPVL). Results: The patients with OSCC-PVL were younger than those with OSCC-noPVL, but this did not reach statistical significance. Regarding patient gender, those with OSCC-PVL were much more frequently female (70%), while OSCC-noPVL was more prevalent in men (65.5%) (p < 0.01). There were also significant differences in the oral locations between the two groups: the gingiva was most prevalent in OSCC-PVL and the tongue in OSCC-noPVL. Erythroleukoplastic forms were significantly more common in OSCC-PVL (30% vs. 7.7%), while ulcerated forms were more frequent in OSCC-noPVL (63.3% vs. 42%). Finally, early T stages were much more prevalent in our patients with OSCC-PVL. Conclusions: We found that OSCC preceded by PVL was much more frequent in women, had less aggressive clinical forms, and had significantly more frequent early T stages than in OSCC-noPVL.

PMID:40227760 | DOI:10.3390/cancers17071199

Cancers (Basel). 2025 Mar 31;17(7):1182. doi: 10.3390/cancers17071182.

ABSTRACT

BACKGROUND: Peripherally Inserted Central Catheters (PICCs) and midline catheters are crucial for chemotherapy and supportive care in cancer patients. Their use requires ongoing monitoring to prevent late complications such as infections, dislodgements, and replacements. The COVID-19 pandemic challenged healthcare systems, potentially increasing these complications due to reduced outpatient services and limited specialized personnel.

OBJECTIVES: This study compared the incidence of late complications associated with PICCs and midline catheters in cancer patients during and after the COVID-19 pandemic.

METHODS: A retrospective observational study was conducted at a Cancer Center in Italy from March 2020 to April 2024. Catheter-related complications were divided into two cohorts: during the pandemic (March 2020-March 2022) and post-pandemic (April 2022-April 2024). The primary outcome was the incidence of late complications requiring device removal, categorized as infections, dislodgements, and replacements. Statistical analyses included the Chi-squared test for categorical variables and the Kruskal-Wallis test for continuous variables.

RESULTS: Of 4104 PICC and midline catheter placements, 2291 removals were recorded, with 550 (24%) due to late complications-404 during the pandemic and 146 post-pandemic (p < 0.001). Suspected infections were the most frequent complication, significantly higher during the pandemic (p < 0.001). Dislodgements and replacements also decreased markedly post-pandemic. Limited outpatient services and disrupted healthcare workflows likely contributed to higher complication rates during the pandemic.

CONCLUSIONS: The COVID-19 pandemic negatively impacted catheter management in cancer patients, increasing late complications. The post-pandemic decline highlights the importance of consistent care, infection prevention, remote monitoring, and stronger healthcare resilience to reduce risks in future crises.

PMID:40227726 | DOI:10.3390/cancers17071182

JAMA Neurol. 2025 Apr 14. doi: 10.1001/jamaneurol.2025.0465. Online ahead of print.

ABSTRACT

IMPORTANCE: Poststroke epilepsy (PSE) is a major complication among young adults and is associated with problems with functional recovery and daily life. Although scores have been developed to predict risk of PSE, they have not been validated among patients with stroke at a young age.

OBJECTIVES: To investigate both the risk of and risk factors for PSE at a young age and validate current PSE risk scores among a cohort of young adults.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from ODYSSEY (Observational Dutch Young Symptomatic Stroke Study), a prospective cohort study conducted among 17 hospitals in the Netherlands between May 27, 2013, and March 3, 2021, with follow-up until February 28, 2024. Participants included 1388 consecutive patients aged 18 to 49 years with neuroimaging-proven ischemic stroke or intracerebral hemorrhage (ICH) and without a history of epilepsy. Statistical analysis took place between June and August 2024.

EXPOSURE: First-ever neuroimaging-proven ischemic stroke or ICH.

MAIN OUTCOMES AND MEASURES: Poststroke epilepsy was defined as at least 1 remote symptomatic seizure (>7 days). Cumulative incidence functions were used to calculate the 5-year risk of PSE. Fine-Gray regression models were used to identify risk factors associated with PSE (age, sex, clinical stroke, and neuroimaging variables). The performances of the SeLECT (severity of stroke, large-artery atherosclerosis, early seizure, cortical involvement, and territory of middle cerebral artery) 2.0 risk score (for ischemic stroke) and the CAVE (cortical involvement, age, bleeding volume, and early seizure) risk score (for ICH) were assessed with C statistics and calibration bar plots.

RESULTS: This study included 1388 patients (ischemic stroke, 1231 [88.7%]; ICH, 157 [11.3%]; median age, 44.1 years [IQR, 38.0-47.4 years]; 736 men [53.0%]; median follow-up, 5.3 years [IQR, 3.4-7.4 years]), of whom 57 (4.1%) developed PSE. The 5-year cumulative risk of PSE was 3.7% (95% CI, 0.2%-4.8%) after ischemic stroke and 7.6% (95% CI, 3.5%-11.8%) after ICH. Factors associated with PSE after ischemic stroke were an acute symptomatic seizure (<7 days) (hazard ratio [HR], 10.83 [95% CI, 2.05-57.07]; P = .005) and cortical involvement (HR, 5.35 [95% CI, 1.85-15.49]; P = .002). The only factor associated with PSE after ICH was cortical involvement (HR, 8.20 [95% CI, 2.22-30.25]; P = .002). The C statistic was 0.78 (95% CI, 0.71-0.84) for the SeLECT 2.0 risk score and 0.83 (95% CI, 0.76-0.90) for the CAVE risk score, and calibration was good for both scores.

CONCLUSION: This study suggests that the risk of PSE among young adults is relatively low and that the factors that were associated with PSE were similar to variables included in the existing risk scores, which can therefore also be applied for young adults after stroke. Future clinical trials should investigate the optimal primary and secondary prophylaxis for patients at high risk.

PMID:40227717 | DOI:10.1001/jamaneurol.2025.0465

Cancers (Basel). 2025 Mar 30;17(7):1162. doi: 10.3390/cancers17071162.

ABSTRACT

OBJECTIVES: This study investigates the association between microsatellite instability (MSI) and the risk of occult lymph node metastases (LNMs) in patients with early-stage endometrial cancer (EC) who showed no evidence of nodal involvement on preoperative imaging.

METHODS: A retrospective multicenter cohort study was conducted, including 237 patients with EC who underwent primary staging surgery between January 2022 and October 2024. The patients were stratified into two groups based on MSI status. The primary outcome was the prevalence of occult LNMs. Statistical analyses included univariate and multivariate logistic regression models, adjusting for potential confounders such as tumor grading and lymphovascular space invasion (LVSI). The significance of the models was assessed using the maximum likelihood method and Bayesian Information Criterion (BIC). Measures to reduce bias included blinding the data analyst, standardization of histopathological evaluation, and exclusion of patients with genetic conditions predisposing to MSI.

RESULTS: The MSI group had a significantly higher incidence of occult LNMs compared to the MSS group (19% vs. 6.7%, p = 0.005). The multivariate analysis confirmed MSI as an independent risk factor for LNMs (OR = 1.105, 95% CI 1.016-1.202, p = 0.020). The sub-analysis showed that loss of MLH1/PMS2 or both MLH1/PMS2 and MSH2/MSH6 heterodimers further increased LNMs risk, independently from other risk factors.

CONCLUSIONS: MSI is independently associated with a higher risk of occult LNMs in early-stage EC, suggesting a potential role for MSI profiling in refining lymph node staging strategies. Future prospective studies should assess the prognostic impact of this association and its implications for surgical decision-making.

PMID:40227711 | DOI:10.3390/cancers17071162

Cancers (Basel). 2025 Mar 31;17(7):1171. doi: 10.3390/cancers17071171.

ABSTRACT

BACKGROUND/OBJECTIVES: Obstruction of the biliary duct may be caused by various conditions ranging from chronic inflammation to neoplasia, including cholangiocarcinoma (CCA). While the definite histological diagnosis of intrahepatic lesions is relatively straightforward, the diagnostic workup of biliary duct stenosis can be challenging, despite the availability of novel tools for intraductal diagnosis. This proof-of-principle study aimed to investigate whether microRNAs (miRNAs) from bile duct stents may be used as biomarkers to differentiate between various bile duct diseases.

METHODS: For this purpose, we included 100 patients with one or more bile duct stents for various reasons, including malignant disease (n = 40), stenosis due to liver transplantation or surgery (n = 60), and cholangitis (n = 42). During endoscopic retrograde cholangiography, the stents were collected, and miRNA analyses were performed to evaluate miR-16, miR-21, and miR-223.

RESULTS: All studied miRNAs were successfully detected from the specimens obtained from the bile duct stents and were comparable in different stents from the same subjects. Following normalization, significant increases in miR-16, -21, and -223 levels were identified in patients with cholangitis compared to specimens from a non-inflammatory cohort. However, when comparing the data from patients in the malignant and non-malignant cohorts, the individual levels of miR-16, miR-21, and miR-223 showed high variation, without reaching a statistically significant difference.

CONCLUSIONS: In summary, bile duct stents can be considered as potential sources of intraductal biomarkers, specifically miRNAs. Further profiling and validation analyses are necessary to identify the most appropriate miRNA targets for differentiating bile duct diseases.

PMID:40227700 | DOI:10.3390/cancers17071171

JAMA Netw Open. 2025 Apr 1;8(4):e254675. doi: 10.1001/jamanetworkopen.2025.4675.

ABSTRACT

IMPORTANCE: Head and neck cancer (HNC) epidemiology varies geographically, and rural populations (typically less affluent) may face barriers accessing cancer care, which could lead to worse outcomes.

OBJECTIVE: To compare health care resource use between patients with HNC living in urban and rural areas.

DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study in Alberta, Canada. Participants were adult patients (aged ≥18 years) diagnosed with HNC with at least 1 year of posttreatment follow-up between January 2012 and September 2020. Data were analyzed from August to September 2024.

EXPOSURE: Rural location of residence at HNC diagnosis, defined using the forward sortation area of the patients’ postal code.

MAIN OUTCOMES AND MEASURES: The primary outcomes were health care resource use and patient care trajectories, including hospital length of stay, 30-day hospital readmissions, emergency department visits, time from diagnosis to first treatment, first type of practitioner seen after hospital discharge, and most common practitioner-to-practitioner transitions.

RESULTS: The cohort included 2189 patients with a median (IQR) age of 63 (55-71) years, who were mostly men (1557 patients [71.1%]) with stage IV cancer (1149 patients [52.5%]) of the tongue (640 patients [29.2%]), of which 375 (17.1%) lived in a rural area. There was no difference in cumulative hospital length of stay between urban and rural patients; however, male patients living in rural areas had a longer surgical hospital length of stay than male patients living in urban areas (incidence rate ratio, 1.24; 95% CI, 1.03-1.50). Patients living in rural areas had more 30-day hospital readmissions (63 patients [16.8%] vs 183 patients [10.1%]) and emergency department visits (median [IQR], 8 [3-17] vs 4 [2-9]) than their urban counterparts. Time to first treatment was longer in patients living in rural areas compared with patients living in urban areas (median [IQR], 64 [46-95] days vs 57 [40-84] days). Patients living in rural areas without comorbid conditions had greater odds of being discharged directly to the care of a general practitioner after a hospital stay than urban patients (odds ratio, 1.97; 95% CI, 1.23-3.15).

CONCLUSIONS AND RELEVANCE: In this cohort study of patients with HNC, living in rural areas was associated with higher health care resource use than patients living in urban areas. Recommendations specific to patients with HNC living in rural areas may be warranted given these differences.

PMID:40227686 | DOI:10.1001/jamanetworkopen.2025.4675

JAMA Netw Open. 2025 Apr 1;8(4):e254682. doi: 10.1001/jamanetworkopen.2025.4682.

ABSTRACT

IMPORTANCE: Pancreas cancer is the seventh leading cause of cancer death and colorectal cancer is the second leading cause of cancer death worldwide, with increasing incidence for both, particularly in younger age cohorts.

OBJECTIVE: To report updated incidence trends for pancreas and colorectal adenocarcinomas in the US, with the specific intent of examining the annual percentage changes (APCs) in younger age groups.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from the Surveillance, Epidemiology, and End Results database to examine incidence trends from 2000 to 2021. Individuals with pancreatic and colorectal adenocarcinoma were included. Data through 2021 were released on April 17, 2024. Data analysis occurred from December 4, 2024, to February 1, 2025.

MAIN OUTCOMES AND MEASURES: Yearly incidence rates were obtained for pancreatic and colorectal adenocarcinoma. Temporal trends of pancreas adenocarcinoma incidence rates by covariates were measured by APC and 95% CIs.

RESULTS: From 2000 to 2021, 275 273 cases of pancreas adenocarcinoma were identified (142 633 male patients [51.8%]; 239 840 patients [87.1%] aged ≥55 years). The APC for pancreatic adenocarcinoma was 4.35 (95% CI, 2.03 to 6.73) in the group aged 15 to 34 years, which was statistically significantly higher than the APCs of 1.74 (95% CI, 1.59 to 1.89) (P = .007) for the group aged 55 years and older and 1.54 (95% CI, 1.18 to 1.90) (P = .004) for the group aged 35 to 54 years. A total of 1 215 200 cases of colorectal cancer were identified (641 776 male patients [52.8%]; 976 716 patients [80.4%] aged ≥55 years). The APC for colorectal adenocarcinoma was -3.31 (95% CI, -3.54 to -3.08) for the group aged 55 years and older, which was statistically significantly lower than the APCs of 1.75 (95% CI, 1.08 to 2.42) (P = .001) for the group aged 15 to 34 years and 0.78 (95% CI, 0.51 to 1.06) (P = .002) for the group aged 35 to 54 years.

CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that the incidence of pancreatic adenocarcinoma has increased among all age groups, whereas that of colorectal adenocarcinoma has increased among younger age groups. Clinicians should be aware of this trend when evaluating younger patients with relevant symptoms.

PMID:40227685 | DOI:10.1001/jamanetworkopen.2025.4682

JAMA Netw Open. 2025 Apr 1;8(4):e254740. doi: 10.1001/jamanetworkopen.2025.4740.

ABSTRACT

IMPORTANCE: In the era of sodium-glucose cotransporter 2 (SGLT2) inhibitors, population-wide screening for chronic kidney disease (CKD) may provide good value, yet implications across racial and ethnic groups are unknown.

OBJECTIVE: To evaluate the health outcomes, costs, and cost-effectiveness of population-wide CKD screening for 4 racial and ethnic groups.

DESIGN, SETTING, AND PARTICIPANTS: In this cost-effectiveness analysis, a decision-analytic Markov model was separately calibrated to simulate CKD progression among simulated cohorts of US Hispanic adults, non-Hispanic Black adults, non-Hispanic White adults, and adults who belong to additional racial and ethnic groups (ie, Asian and multiracial individuals and those self-reporting other race and ethnicity). Effectiveness of SGLT2 inhibitors was derived from the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease trial. Mortality, quality-of-life weights, and cost estimates were obtained from published cohort studies, randomized clinical trials, and Centers for Medicare & Medicaid Services data. Analyses were conducted from January 1, 2023, to November 6, 2024.

EXPOSURES: One-time or periodic (every 10 or 5 years) screening for albuminuria, initiated between age 35 and 75 years, with and without addition of SGLT2 inhibitors to angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker therapy for CKD.

MAIN OUTCOMES AND MEASURES: Lifetime cumulative incidence of kidney failure requiring kidney replacement therapy (KRT); discounted life-years (LYs), quality-adjusted LYs (QALYs), lifetime health care costs (in 2024 US dollars), and incremental cost-effectiveness ratios.

RESULTS: Under the status quo, non-Hispanic Black adults aged 35 years had the highest lifetime incidence of kidney failure requiring KRT (6.2% [95% UI, 2.8%-10.6%]) compared with Hispanic adults (3.6% [95% UI, 1.1%-6.7%]), non-Hispanic White adults (2.3% [95% UI, 0.4%-5.2%]), and adults from additional racial and ethnic groups (3.3% [95% UI, 1.2%-6.5%]). Screening every 5 years from ages 55 to 75 years combined with SGLT2 inhibitors reduced incidence of KRT and increased LYs across all racial and ethnic groups, with the largest average changes observed for non-Hispanic Black adults (0.8-percentage point decrease and 0.19-year increase). Every 5-year screening from age 55 to 75 years cost $99 100/QALY gained for the overall population and less than $150 000/QALY gained across racial and ethnic groups, with the lowest cost observed for non-Hispanic Black adults ($73 400/QALY gained). Screening starting at age 35 years was only cost-effective for non-Hispanic Black adults ($115 000/QALY gained).

CONCLUSIONS AND RELEVANCE: In this cost-effectiveness analysis, population-wide screening for CKD from ages 55 to 75 years was projected to improve population health, was cost-effective, and reduced disparities across 4 racial and ethnic groups. Starting population-wide screening at younger ages was projected to further benefit non-Hispanic Black adults.

PMID:40227684 | DOI:10.1001/jamanetworkopen.2025.4740

JAMA Netw Open. 2025 Apr 1;8(4):e254751. doi: 10.1001/jamanetworkopen.2025.4751.

ABSTRACT

IMPORTANCE: Multiple sclerosis (MS) is an immune-mediated neurological disorder that affects 2.4 million people worldwide, and up to 60% experience anxiety.

OBJECTIVE: To investigate whether anxiety in MS is associated with white matter lesion burden in the uncinate fasciculus (UF).

DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective case-control study of participants aged 18 years or older diagnosed with MS by an MS specialist and identified from the electronic medical record at a single-center academic medical specialty MS clinic in Pennsylvania. Participants received research-quality 3-Tesla magnetic resonance neuroimaging as part of MS clinical care from January 6, 2010, to February 14, 2018. After excluding participants with poor image quality, participants were stratified into 3 groups naturally balanced in age and sex: (1) MS without anxiety, (2) MS with mild anxiety, and (3) MS with severe anxiety. Analyses were performed from June 1 to September 30, 2024.

EXPOSURE: Anxiety diagnosis and anxiolytic medication.

MAIN OUTCOMES AND MEASURES: Main outcomes were whether patients with severe anxiety had greater lesion burden in the UF than those without anxiety and whether higher anxiety severity was associated with greater UF lesion burden. Generalized additive models were used, with the burden of lesions (eg, proportion of fascicle impacted) within the UF as the outcome measure and sex, spline of age, and total brain volume as covariates.

RESULTS: Among 372 patients with MS (mean [SD] age, 47.7 [11.4] years; 296 [80%] female), after anxiety phenotype stratification, 99 (27%) had no anxiety (mean [SD] age, 49.4 [11.7] years; 74 [75%] female), 249 (67%) had mild anxiety (mean [SD] age, 47.1 [11.1] years; 203 [82%] female), and 24 (6%) had severe anxiety (mean [SD] age, 47.0 [12.2] years; 19 [79%] female). UF burden was higher in patients with severe anxiety compared with no anxiety (T = 2.01 [P = .047]; Cohen f2, 0.19 [95% CI, 0.08-0.52]). Additionally, higher mean UF burden was associated with higher severity of anxiety (T = 2.09 [P = .04]; Cohen f2, 0.10 [95% CI, 0.05-0.21]).

CONCLUSIONS AND RELEVANCE: In this case-control study of UF lesion burden and anxiety in MS, overall lesion burden in the UF was associated with the presence and severity of anxiety. Future studies linking white matter lesion burden in the UF with treatment prognosis are warranted.

PMID:40227683 | DOI:10.1001/jamanetworkopen.2025.4751