Citations

BACKGROUND The use of Mohs micrographic surgery as a treatment for melanoma is rising, but the reliability of Mohs surgeons in assessing MART-1 melanoma en-face margins has not been evaluated. OBJECTIVE To evaluate interrater and intrarater reliability of Mohs surgeons in interpreting margins of early-stage melanoma. METHODS Twenty Mohs surgeons were asked to independently review images of frozen section MART-1 en-face peripheral margins of in situ or early-stage melanoma. Surgeons determined margins as positive or negative at initial evaluation and 6 weeks later. Primary outcomes were interrater and intrarater reliability. RESULTS Interrater agreement was 84.1% (95% confidence interval [CI]: 75.5%–92.8%) for assessment 1 and 87.5% (95% CI: 78.4%–96.4%) for assessment 2, with kappa values 0.68 (95% CI: 0.50–0.82) and 0.75 (95% CI: 0.57–0.88). Average intrarater percent agreement was 95.0% (95% CI: 70.6%–100.0%) with average kappa 0.90 (95% CI: 0.50–1.00). CONCLUSION Substantial interrater and nearly perfect intrarater agreement was identified among surgeons assessing melanoma margins utilizing MART-1 immunostaining, demonstrating consistent and reproducible assessment of melanoma margins during Mohs cases.

Abstract Next-generation sequencing has transformed cancer care by providing essential insights for diagnosis, prognosis, and treatment. However, variability in testing timing, reporting practices, and interpretation challenges limits its clinical impact. This article highlights key opportunities to optimize somatic reporting, emphasizing the importance of timely testing throughout the cancer care continuum to maximize the diagnostic and therapeutic relevance of findings. Technical factors such as test design, sequencing depth, and the use of liquid biopsy substantially influence result accuracy and interpretation, underscoring the need for careful integration with clinical history. Standardized reporting practices that clearly delineate diagnostic, prognostic, and therapeutic findings can enhance the clinical utility of next-generation sequencing results. Streamlined formats and curated clinical trial data further support actionable decision making. Additionally, direct patient engagement and education are essential for empowering patients to navigate genomic testing and make informed decisions about their care. By leveraging multidisciplinary tumor boards, decision-support tools, and emerging artificial intelligence technologies, clinicians can better navigate the complexities of somatic reports. Standardization and clarity in reporting are critical to advancing precision oncology, empowering providers and patients to make informed treatment decisions and improve outcomes.

Abstract Background: With over 1 billion individuals affected globally, obesity and obesity related diseases is now a leading cause of death. Metabolic and bariatric surgery (MBS) has emerged as a cornerstone intervention for severe obesity and its associated comorbidities. Despite its efficacy, postoperative care and follow-up after MBS remains highly variable worldwide. Objective: The PARTNER study aimed to evaluate global clinical practices in the postoperative management following MBS by surveying multidisciplinary healthcare professionals . Methods: This study was an international online survey conducted between October 2024 and January 2025. A multidisciplinary team developed the questionnaire based on existing literature and international guidelines. The survey assessed five domains: follow-up care, postoperative treatment, dietary management, patient support, and measurement of surgical outcomes. Responses were analysed descriptively. Results: A total of 262 responses were received from 62 countries. Most respondents were bariatric surgeons (72.1%) working in public healthcare systems (73.3%). While 78.7% reported conducting three-month postoperative reviews, only 23.7% offered indefinite follow-up. Hybrid models of care (virtual and in-person) were common (56.9%). VTE prophylaxis and postoperative PPI use were recommended by 64.1% and 84.3% respectively. Nearly all respondents (98.1%) provided dietary advice, with protein and micronutrient supplementation widely endorsed. Only 56.1% routinely referred patients for psychological follow-up. Definitions of surgical success and failure varied widely, with inconsistent objective outcome measures. Conclusion: The PARTNER study reveals significant international variation in postoperative management practices following MBS. These findings underscore the need for more standardized, evidence-based guidelines to improve long-term outcomes and equity of care worldwide.

Key Points This study demonstrates that peritoneal dialysis is a safe and feasible option for patients with autosomal dominant polycystic kidney disease, even with high cystic organ volumes. Larger organ volumes, including height-adjusted cumulative kidney and liver volume, were not associated with increased peritoneal dialysis–related complications. Background Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent genetic kidney disorder and the fourth leading cause of kidney failure. Peritoneal dialysis (PD), preferred for its home-based convenience and cost-effectiveness, is often underutilized in ADPKD because of concerns over enlarged kidneys and heightened risk of complications. Methods This retrospective cohort study used data from the Mayo Clinic Polycystic Kidney Disease Database to evaluate individuals with ADPKD undergoing PD. We analyzed demographics, clinical parameters, and PD-related parameters. Complications were correlated with kidney and liver volumes derived from pre-kidney failure imaging. Results A total of 155 individuals with ADPKD on PD were included, of whom 45.1% were male. The mean age at PD initiation was 54.3±12.8 years, and the mean body mass index was 28.0±7.0 kg/m 2 . The median duration of PD was 24.3 months (interquartile range [IQR], 10.7–43.1), with 21.9% transitioning to hemodialysis. The most common complications were abdominal hernias (30.3%) and peritonitis (23.9%), with a peritonitis rate of 0.11 episodes per patient-year. Imaging analyses performed on a subset of 50 patients showed a median height-adjusted total kidney liver volume of 2731.9 ml/m (IQR, 2102.5–3131.1) and a median height-adjusted total kidney volume of 1303.5 ml/m (IQR, 733.1–1829.4). Kaplan–Meier analysis demonstrated no differences in complications rates on the basis of height-adjusted total kidney liver volume or height-adjusted total kidney volume (above versus below median values) or body mass index categories. Multivariate Cox regression analysis revealed that higher height-adjusted cumulative organ volume was associated with a lower risk of PD-related complications (hazard ratio=0.56, P = 0.026). Conclusions PD is a safe and feasible treatment option for patients with ADPKD, with no increased risk of PD-related complications associated with larger height-adjusted cumulative organ volumes. Infectious complication rates in this cohort were within International Society of Peritoneal Dialysis guideline thresholds, further supporting the safety of PD in this population.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disorder. It is primarily caused by pathogenic variants in the PKD1 or PKD2 genes. This leads to the development of numerous kidney cysts, which can result in kidney enlargement and progression to kidney failure. Pain is a common symptom in ADPKD and can negatively affect quality of life (QOL). This pain is often due to the continuous growth of kidney and liver cysts or associated cystic complications. We present a case of a 29-year-old woman with ADPKD who experienced chronic, refractory right-sided flank pain that significantly affected her QOL. Her pain persisted despite taking daily multimodal analgesics and undergoing multiple invasive interventions. She had an unusual asymmetric disease with the right kidney accounting for only 24% of her kidney function. After exhausting all other pain control strategies, she underwent right nephrectomy and partial hepatectomy, which led to substantial improvement in pain and QOL. This review describes the causes, manifestations, and management strategies for abdominal and/or flank pain in ADPKD, including a practical stepwise algorithm to guide clinicians in managing pain and improve QOL of patients with ADPKD. Pain in ADPKD can either be acute or chronic and can lead to significant physical and psychologic distress. Effective pain management in ADPKD requires a multidisciplinary approach, incorporating both nonpharmacologic and pharmacologic interventions such as gabapentin or tolvaptan in select cases. Interventions considered in ADPKD pain control include cyst aspiration with sclerotherapy, celiac plexus blockade, spinal cord stimulation, renal denervation, or nephrectomy.

ABSTRACT Bipolar disorder’s (BD) clinical heterogeneity has an unresolved genetic basis. We meta-analyzed genome-wide association studies (GWAS) of 16 BD subphenotypes in 226,032 individuals from 57 cohorts (38,022 cases); 10 advanced to multivariate and multi-trait analyses. Four factors (compulsive, psychotic, dysregulated, internalizing) explained 82.8% of shared genetic variance. BD1 and BD2 loaded on distinct factors despite a high genetic correlation; 87.0% of common-factor loci were significant in neither subtype. Unipolar mania aligned with psychosis over internalizing, and was distinguishable from BD1, and rapid cycling showed heritable cross-domain liability. We identified 356 risk loci, 158 novel, including the first univariate-GWAS associations for psychosis, unipolar mania, rapid cycling and schizoaffective disorder—and 249 credible genes (89 high-confidence), 12 with approved-drug or clinical-phase annotations. Cell-type association showed a midbrain dopaminergic–GABAergic gradient along the psychotic factor. BD’s genetic architecture appears hierarchical—a general liability resolving into dimensions of course and comorbidity beyond diagnostic subtypes.

Abstract Aim Growing evidence suggests that immune/inflammatory pathways play a crucial role in the persistence of symptoms in diverticular disease (DD). We hypothesize that chronic diverticulitis triggers a self‐sustained inflammatory status which can be detected by measuring the levels of tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6). The aim of this study was to investigate the systemic levels of TNF‐α and IL‐6 before and after elective surgery in patients with DD, and their relationship with the gastrointestinal quality of life index (GIQLI) score. Method This prospective multicentric study enrolled patients from the Diverticular Disease Registry (DDR‐Trial, NCT04907383). All adult patients diagnosed with symptomatic uncomplicated diverticular disease (SUDD), uncomplicated recurrent diverticulitis (URD) and smouldering diverticulitis (SmD) between 1st December 2022 and 31st December 2023 were included in this study. Exclusion criteria were as follows: no surgery, a concurrent chronic immunomodulated systemic disease, a SARS‐CoV‐2‐positive test in the previous 12 months, a history of cancer in the previous 5 years, patients treated with immunomodulators, an American Society of Anesthesiologists category of class IV, and complicated acute diverticulitis. Results Seventy‐two patients were included: 52 (72%) with URD, 11 (15%) with SUDD, and nine (13%) with SmD. The median postsurgery – presurgery (Δ)IL‐6 and ΔTNF‐α levels were −16.8 and −17.3 pg/mL, respectively ( p < 0.001 for both; Wilcoxon test). Spearman correlation revealed a significant, negative association between the ΔGIQLI and the ΔIL‐6, as well as the ΔTNF‐α ( p < 0.001 for both). Greater reduction in the levels of IL‐6 and TNF‐α following surgery are associated with higher GIQLI scores postoperatively. Conclusion Patients with chronic diverticulitis may experience persistent systemic inflammation driven by a colonic trigger. Surgical removal of this trigger appears to enhance GIQLI outcomes reducing IL‐6 and TNF‐α across surgery.

e19033 Background: CLL tends to affect older individuals, and older patients often endure greater health disparities and treatment burdens that may impact their access to healthcare resources, adherence to treatment regimens and treatment outcomes (UN, Health Inequalities in Old Age). This study aimed to assess treatment utilization patterns, discontinuation, and healthcare resource utilization (HCRU) of 1L use of BTKi in CLL, focusing on older patients ≥65 years (yrs). Methods: A retrospective observational study using the Symphony Integrated Dataverse was conducted to identify adult CLL patients initiating a 1L BTKi (zanubrutinib [ZANU], acalabrutinib [ACA] or ibrutinib [IBR]) treatment regimen from 02/2022 and 09/2024 (index period). Patients were required to have ≥30 days of continuous enrollment in the pre- and post-index periods. Patients initiating a BTKi were further categorized by age at index date. Patient sociodemographic, clinical characteristics, and outcomes were reported in overall and older (≥65 yrs) CLL patients by each BTKi group. Treatment discontinuation rate was examined at 60, 90, 120, 150, 180, and 360 days, and by median time to discontinuation (TTD), estimated using the Kaplan-Meier method, censoring patients at the end of follow-up. HCRU (outpatient, inpatient, and other services) was evaluated during time on treatment and over the follow-up period and reported as per-patient-per-year (PPPY). Results: A total of 6,846 patients initiated a 1L BTKi (ZANU: n=1,853; ACA: 3,519; IBR: 1,474) for CLL during the index period. Patients receiving ZANU were older (mean age: 70.9 yrs; 78% ≥65 yrs) than those receiving ACA (69.4 yrs; 71% ≥65 yrs) and IBR (69.6 yrs; 73% ≥65 yrs). Payer type and geography were significantly different across each BTKi group ( p <.001). There were no significant differences across the BTKis regarding baseline comorbidities. ZANU patients had the longest estimated median TTD overall (ZANU: 18.9 months [m], ACA: 17.8 m, IBR: 14.5 m; p <.001) and in patients ≥65 yrs (ZANU: 17.2 m, ACA: 15.2 m, IBR: 12.6 m; p <.001). ZANU patients also had the lowest estimated discontinuation rates at 60- , 90-, 120-, 150-, 180-, and 360-days post BTKi initiation in the overall and ≥65 yrs groups. There were significant differences across the BTKi group for inpatient visits PPPY in all patients and ≥65 yrs with ZANU having the lowest visits of the BTKis (ZANU: 2.6, ACA: 3.6, IBR: 4.6; p =.029 and ZANU: 2.5, ACA: 4.3, IBR: 5.3; p =.004, respectively). Conclusions: This real-world study demonstrated that CLL patients treated with ZANU had longer TTD, lower discontinuation rates, and less HCRU than ACA and IBR across all patients and specifically in older patients ≥65 yrs. Further studies on long-term and clinical outcomes are warranted.