Citations

ABSTRACT Background and Aims It remains unclear whether different factors influence 30‐ and 90‐day readmission rates. We identified predictors of 90‐day mortality in a global cohort of hospitalised patients with cirrhosis. Methods Variables associated with 30‐ and 90‐day post‐discharge readmission, liver transplantation (LT), and mortality were compared in prospectively enrolled, non‐electively hospitalised adult patients with cirrhosis. Results We enrolled 4208 patients from 125 centres across 37 countries. Alcohol‐related liver disease was the most common aetiology of cirrhosis (40%), followed by hepatitis B virus infection (21%); 47% were readmitted, 8% received liver transplantation (LT), and 23% died within 90 days post‐discharge. In multivariable analysis, country income was significantly associated with both 30‐ and 90‐day readmission rates, the receipt of LT, and mortality within 30 and 90 days post‐discharge (all p ‐values < 0.001). Independent predictors of higher rates of 30‐ and 90‐day readmissions, respectively, were disease severity ( p < 0.001, p = 0.003), prior ascites ( p = 0.025, p = 0.016), prior hospitalisation ( p < 0.001), hyponatremia ( p < 0.001, p = 0.008), and in‐hospital vasopressor use ( p = 0.002, p = 0.011). Prior variceal bleeding independently predicted higher 90‐day readmission rates, whereas age, disease severity, mechanical ventilation, and in‐hospital vasopressor use (all, p < 0.001) increased odds of 30‐ and 90‐day post‐discharge death. Additionally, admission ( p = 0.011) and nosocomial ( p = 0.022) infections increased the odds of 90‐day post‐discharge death. Conclusion In a global cohort of hospitalised patients with cirrhosis, patients in high‐income countries exhibited the highest rates of 30‐ and 90‐day readmission, alongside lower mortality rates and a higher incidence of LT. Variables that predict 30‐day readmission also predicted 90‐day readmission. Understanding these disparities is essential for achieving health equity.

BACKGROUND: Anthracyclines are a widely used and effective class of chemotherapy. However, a major limitation for their use is cardiotoxicity, manifesting as systolic dysfunction, congestive heart failure, and arrhythmias. The objective of this study was to identify genes and genetic risk variants for doxorubicin-induced arrhythmia. METHODS: We performed genome-wide association studies and meta-analysis across 2 independent nonoverlapping, genetically homogenous data sets from the Molecular Epidemiology Resource (cases N=77, controls N=1184) and Tapestry (cases N=13, controls N=172). Doxorubicin-related arrhythmia was the primary cardiac outcome, followed by investigation of a broader phenotype of cardiac events. Effects of doxorubicin on top-associated genes were assessed by quantitative polymerase chain reaction on RNA extracted from human cardiomyocytes following treatment with doxorubicin and by echocardiography in a zebrafish model of doxorubicin-induced cardiomyopathy. RESULTS: In the meta-analysis, rs12151014 at the KCTD15 locus was associated with doxorubicin-related arrhythmia at the genome-wide significance (minor allele frequency in Molecular Epidemiology Resource cases 0.195 versus 0.069 in controls; Tapestry cases 0.192 versus 0.079 in controls) P =9.01×10 −9 ; odds ratio, 3.61. MMP 16 rs1094199 was associated with the broader phenotype of arrhythmia and heart failure (minor allele frequency in Molecular Epidemiology Resource cases 0.079 versus 0.019 in controls; Tapestry cases 0.038 versus 0.015) P =1.98×10 − 8 ; odds ratio=6.15. In human cardiomyocytes, MMP16 and KCTD15 gene expression was significantly downregulated by doxorubicin, and in a zebrafish MMP16 knockout was protective of doxorubicin-induced decline in left ventricular ejection fraction. CONCLUSIONS: Genetic variants at KCTD15 and MMP16 are associated with doxorubicin-related arrhythmia and cardiac events. MMP16 is a potential cardioprotective therapeutic target.

ABSTRACT HLA‐DPA1*01:49 is characterised by a single nucleotide substitution in codon 119 in exon 3.

Introduction Immigrants of African Descent (IAD) are a subset of the population in the United States with unique healthcare needs and experiences driving health disparities, including inadequate access to healthcare for cancer prevention and control. This study reports the impact of a Cancer advocacy program in IAD communities, using the training of trainers approach. Methods IAD from different organizations were invited to undergo cancer advocacy training organized by Inclusive Cancer Care Research Equity and Mayo Clinic Comprehensive Cancer Center as Master trainers on colorectal, breast, and prostate cancers. Participation was through in-person training and Zoom sessions. Our team communicated with participants frequently via email to provide support and updates. The Master trainers led cancer awareness programs within their communities during the second phase of the program. Results Participants included two breast cancer survivors, three prostate cancer survivors, six cancer caregivers, and 19 community advocates. There were 19 advocate-led cancer risk reduction and research participation events, reaching 2045 community members, and 875 were navigated to research. Community responses showed that 96% found the information given at the Master Trainer-led event was very useful, 46% promised to seek more cancer information, and 17% agreed to volunteer to become a cancer advocate. The insights from this study suggested that the train-the-trainers’ approach was efficient in ensuring community ownership of cancer advocacy. Conclusion IAD can be trained to effectively lead advocacy programs in immigrant communities, using the train-the-trainer approach. Future studies should establish the feasibility of sustaining community outreach and research navigation in IAD communities to improve cancer prevention and cancer care outcomes in this population.

Abstract Effector gene expression in CD8+ T cells is tightly controlled at the epigenetic and transcriptional levels; however, crucial regulatory signals remain incompletely understood. In this study, we identify dual specificity phosphatase 2 (DUSP2) as a key epigenetic modulator of effector CD8+ T-cell state, by elucidating inhibition of BAF-mediated chromatin opening by DUSP2. Induced downregulation of DUSP2 in human CD8+ T cells enhances cytotoxicity and effector phenotypes by increasing chromatin accessibility through upregulation of BAF subunits, such as SMARCA4, and permitting binding of ETS1 to BAF subunit gene loci and those essential for effector programs. These findings uncover a previously unrecognized role of DUSP2 in the management of the chromatin landscape in effector CD8+ T cells and the epigenetic fine-tuning of their functionality, highlighting DUSP2 as a promising therapeutic target for T cell–based immunotherapy.

Aim: Despite advances with immune checkpoint inhibitor (ICI)-based regimens in the past decade, patients with metastatic urothelial cancer (mUC) face a poor prognosis with few approved options. Platinum-based chemotherapy with paclitaxel and carboplatin (TC) +/– ICI may be a feasible choice. Methods: We generated an IRB-approved, HIPAA-compliant retrospective database of patients at Mayo Clinic Cancer Center with mUC who started TC +/– ICI after disease progression on ICI from January 2018 through December 2024. Baseline demographics, clinicopathologic features, and treatment outcomes were extracted from the electronic health record. Kaplan-Meier method was used to calculate median duration of response (DOR), progression-free survival (PFS) and overall survival (OS). Results: There were 32 patients who fit inclusion criteria, including 31 patients who had disease progression on ICI in the metastatic setting and 1 patient who developed metastatic disease on adjuvant nivolumab. Patients received a median of 4 cycles (range 1–14) of TC over median 12 weeks (range 3–53). Overall, 81% of patients received TC concurrently with an ICI, and 28% continued maintenance ICI after TC discontinuation (at the treating oncologist’s discretion due to adequate response or toxicity). The best objective response rate was 41% and disease control rate was 75%, with median DOR of 4.8 months (IQR 2.7–10.4), median PFS of 4.6 months (IQR 3.3–10.2), and median OS of 9.4 months (IQR 6.3–15.9). Some patients in this series had very durable responses with PFS > 12 months and OS > 24 months. TC +/– ICI was overall well tolerated with expected type and severity of adverse events. Conclusions: Strategies to overcome ICI resistance are needed, and TC +/– ICI after disease progression on an ICI shows promising tolerability and efficacy in this setting for patients with mUC. Our series was notable for some patients having a durable response. Validation in larger cohorts is warranted.

OBJECTIVE Ganglioneuromas (GNs) are rare benign tumors arising from sympathetic neural crest derivatives, with limited large-scale data guiding management. The objective of this study was to characterize the clinical presentation, imaging features, surgical management, and long-term outcomes of patients with GN treated at a single institution over a 30-year period. METHODS The authors conducted a retrospective review of all patients diagnosed with GN between 1995 and 2025 at a single institution. Clinical data, imaging characteristics, operative details, perioperative complications, and long-term outcomes were abstracted. RESULTS A total of 101 patients (62.3% female, mean age 26.9 ± 15.9 years) were identified. Tumors most commonly arose in the retroperitoneum (n = 46, 45.5%), thoracic paraspinal/mediastinal region (n = 33, 32.7%), presacral space (n = 18, 17.8%), and cervical region (n = 4, 4%). The mean tumor dimensions on MRI were 8.5 ± 3.8 × 6.6 ± 3.2 × 5.8 ± 3.7 cm. Most lesions (72%) were incidental findings. Seventy patients underwent 72 surgeries, of which 69.4% had preoperative biopsy confirmation. Gross-total resection (GTR) was achieved in 73.6% of cases (53/72) and subtotal resection (STR) was performed in 26.4% (19/72). Short-term postoperative complications occurred in 43.1% of cases, most commonly neurological deficits (22.2%). The mean hospital length of stay was 4.6 ± 3.7 days. At the final follow-up (mean duration 33.8 ± 42.6 months), 46.5% of patients were stable, 42.3% had improved, and 11.3% had worsened from baseline. Two patients experienced recurrence (2.9%, 2/70). No malignant transformations were observed. Thirty-one patients were managed with observation (mean age 32.3 ± 17.7 years; mean follow-up duration 90.9 ± 151 months). Observation was chosen primarily due to proximity to major vascular or neural structures (74.2%). No patient in the observation group developed new symptoms, and 2 tumors exhibited minimal interval growth (0.08–0.17 cm/year). CONCLUSIONS GNs demonstrate indolent behavior, low recurrence rates, and no observed malignant transformation in this large cohort. GTR is achievable in most cases, but STR provides excellent long-term control when required to avoid morbidity. Observation is safe for asymptomatic tumors, particularly when adjacent to critical structures, with no growth observed on long-term follow-up, except for minimal growth in few cases. These findings support an individualized, risk-based approach to management.

OBJECTIVE This study examines the recovery rates of patients who experience postoperative dysphagia within 1 month following cervical spine surgery. METHODS Data from a prospectively maintained multi-institutional quality registry were retrospectively analyzed. Eating Assessment Tool-10 (EAT-10) questionnaire scores were collected at baseline and 1, 3, and 12 months postoperatively, with total scores ≥ 3 indicating dysphagia. Patients were grouped by whether they reported baseline dysphagia to assess the impact of baseline dysphagia on recovery. Recovery was defined as resolution of postoperative dysphagia and not reporting the condition at any follow-up time point. Patients were excluded from the recovery model if they did not report dysphagia within 1 month of surgery. Recovery to baseline was defined as reporting a postoperative EAT-10 score equal to or less than the baseline score at subsequent time points. Patients were excluded from the recovery-to-baseline model if they did not report EAT-10 scores within 1 month of surgery that were worse than their baseline score. Survival curves were generated for both models. RESULTS Of the 2003 patients in the registry, 627 met inclusion criteria for the recovery curve and 714 for the recovery-to-baseline curve. Of the patients without baseline dysphagia, 498 developed new postoperative dysphagia within 1 month, with cumulative recovery probabilities of 39.5% by 3 months and 59.1% by 12 months after cervical spine surgery. Furthermore, of the patients without baseline dysphagia, 73.5% (175/238) who reported no dysphagia at 3 months and 32.5% (68/209) who reported no dysphagia at 12 months experienced long-term recovery. Eighty patients with baseline dysphagia reported worse EAT-10 scores within 1 month, with cumulative probabilities of improvement to baseline or below of 37.7% by 3 months and 54.1% by 12 months. Patients with baseline dysphagia were significantly less likely to recover than patients without baseline dysphagia (hazard ratio [HR] 0.37, 95% CI 0.26–0.53; p < 0.001) but significantly more likely to recover to baseline (HR 1.45, 95% CI 1.05–2.00; p = 0.025). CONCLUSIONS Patients who develop postoperative dysphagia within 1 month of cervical spine surgery generally see symptomatic improvement over time. This analysis may aid in clinical decision-making when informing patients about the risk of developing postoperative dysphagia and the recovery rate of this surgical complication.