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.

Objective: To evaluate the efficacy of regional anesthesia (RA) in enabling arteriovenous fistula (AVF) creation in patients with small-caliber veins who would typically receive arteriovenous grafts (AVG), and to compare access outcomes between AVF and AVG cohorts. Methods: We conducted a retrospective analysis of a prospectively maintained database from 2018 through 2024 involving patients with chronic kidney disease (CKD) requiring access creation. Eligible patients were those aged 18 years or older with inadequate veins for AVF creation based on initial ultrasound vein mapping. All patients underwent RA prior to the access creation and had a repeated intraoperative vein mapping at least 30 min after RA. Patients whose veins were sufficiently dilated and met the criteria for AVF creation underwent AVF formation; otherwise, an AVG was created. Outcomes included access maturation, patency rates, access failure, abandonment, and mortality. Statistical analysis was performed using R software, with significance set at p < 0.05. Results: Of the 106 patients, 67 (63.2%) underwent AVF creation post-RA due to sufficient vein dilation, while 39 (36.8%) received AVGs. Baseline vein diameters and comorbidities were comparable between groups. AVF maturation was achieved in 83.6% of AVF patients, with longer times to successful cannulation compared to AVG (median 187.0 vs 80.0 days, p = 0.037). Kaplan-Meier analysis revealed no difference in primary patency ( p = 0.97), but AVF patients had superior primary assisted ( p = 0.015) and secondary patency ( p = 0.033), and lower access failure rates ( p = 0.034) compared to AVG patients. Access abandonment and mortality rates did not differ significantly between groups. Conclusions: RA-induced venodilation enables the use of veins previously deemed inadequate for AVF creation, leading to improved access outcomes compared to AVG placement. Implementing RA may increase AVF utilization and enhance patient outcomes in hemodialysis access surgery.

ABSTRACT Newly diagnosed patients with non‐Hodgkin lymphoma (NHL) often have a history of other diseases, and these comorbidities can impact patient treatment and management options, as well as overall survival (OS). We developed the Lymphoma Epidemiology of Outcomes (LEO) comorbidity index (LCI) as a sum of 10 comorbidities adapted from the Self‐Report‐Generated Charlson Comorbidity Index (SRG‐CCI) for use in the LEO cohort, a national prospective study of newly diagnosed NHL. Of the 5502 participants with self‐reported comorbidity data, 3107 (56.4%) were male and the mean age at diagnosis was 60.9 years (range, 18–99 years). The LCI ranged from 0 to 6, with 48.6% having 0, 30.2% having 1, 21.2% having 2 or more comorbidities. With a median follow‐up of 62.4 months among surviving participants, 2099 patients had an event and 1219 died. Continuous LCI similarly predicted both 1‐year mortality (c‐statistic = 0.654) and OS (c‐statistic = 0.655), while it showed a weaker but still statistically significant predictive ability for lymphoma‐specific (c‐statistics = 0.617) and event‐free (c‐statistic = 0.574) survival. Participants with 1 (HR = 1.21, 95% CI 1.05–1.39) and 2+ (HR = 1.80, 95% CI 1.56–2.08) comorbidities had inferior OS compared to those with no comorbidities after adjustment for age and sex (c‐statistic = 0.654), and performance strengthened after adjustment for the International Prognostic Index (c‐statistic = 0.672). LCI predicted OS most strongly in marginal zone (c‐statistics = 0.748) and weakest in T‐cell (c‐statistic = 0.579) lymphoma. The cumulative incidence of death due to lymphoma, lymphoma treatment, and other causes all increased with increasing comorbidities, with the greatest increase observed for death due to other causes. The LCI performs comparable to other published comorbidity indices, supporting its use in the LEO cohort to better model real‐world outcomes and more generally providing an approach to implementing comorbidity indices in cancer survivorship cohorts.

Abstract In recent years, various tracking technologies that work independently of imaging systems have been proposed to automate, simplify, and enhance various tasks in the brachytherapy treatment workflow. These tasks, critical to the overall accuracy of the therapeutic dose delivery, include applicator, catheter and needle insertion guidance, and reconstruction as well as transfer tube connection in afterloading technique. Task Group 317 was established as a joint American Association of Physicists in Medicine (AAPM) and European Society for Radiotherapy and Oncology (ESTRO) committee to review: the current state‐of‐the‐art scientific literature as it pertains to tracking technology in the field of brachytherapy; the benefits and issues related to the use of the technology for automated reconstruction of brachytherapy implants, quality control (QC) tasks such as channel path and tip reconstruction, and real‐time guidance tasks; their limitations, in particular in the clinical environment and, finally, to develop recommendations related to commissioning, quality assurance (QA) and clinical use. The Task Group has looked in detail at key tracking technologies in advanced brachytherapy applications: infrared, electromagnetic, fiber optic shape sensing (fiber Bragg grating), and active radiofrequency coil tracking. For each, the performance and accuracy in well‐controlled conditions as well as in clinically relevant environments are provided. Guidelines for clinical implementations, including target accuracy and performance needed for critical tasks, are summarized. Risk‐based analysis is discussed in the context of an electromagnetic‐based tracking system used as part of a clinical trial. The report concludes with the essential elements of an effective quality management program dedicated to the advanced features enabled by the above‐described technology.

Introduction: Percutaneous nephrolithotomy (PCNL) has been a mainstay treatment for large stone burdens since the 1980s, historically offering improved stone-free rates over retrograde intrarenal surgery (RIRS). Gaining optimal access into the renal collecting system can be challenging, requiring advanced skills or interventional radiology assistance. The learning curve for fluoroscopic and ultrasonography access can be steep, with only a minority of PCNL access performed by urologists in the United States. This study compares robotic-assisted electromagnetic (EM) guidance to traditional fluoroscopy for obtaining percutaneous renal access between cohorts of novice and expert urologists. Methods: Ten novices and five expert urologists used robotic-assisted EM guidance to obtain access in a modified supine position compared with using fluoroscopy in a traditional prone position in human cadavers. Primary success was defined as papillary access. Performance metrics, including number of puncture attempts, time to access, radiation exposure, and participant confidence, were compared between novices and experts. Results: Robotic-assisted EM guidance improved success rates for both novices (100% vs 70%) and experts (93% vs 87%) compared with fluoroscopy. Novices showed greater accuracy using robotic assistance (97% vs 37%). The number of insertion attempts decreased with robotic guidance for both groups (novices: 3.42 ± 0.44 vs 1.47 ± 0.19; experts: 2.13 ± 0.36 vs 1.40 ± 0.24; p < 0.002). EM guidance ( p < 0.05) and experience ( p < 0.05) significantly reduced the time from needle insertion to access (novices: 12.86 ± 2.41 minutes vs 4.49 ± 0.96 minutes; experts: 4.90 ± 1.40 minutes vs 4.09 ± 1.12 minutes). Radiation exposure was notably lower with EM guidance (novices, 1.12 ± 0.17 mGy vs 4.86 ± 0.70 mGy; experts, 0.69 ± 0.12 mGy vs 4.11 ± 1.21 mGy; p < 0.001). Novices felt more confident (5[3–5] vs 2[1–4], p < 0.001) and at ease (5[3–5] vs 2.75[1–3], p < 0.001) with EM guidance. Conclusion: Robotic-assisted EM guidance improves percutaneous access success, reduces attempts and radiation exposure, and enhances novice confidence and accuracy. This technology could enable urologists to more effectively and safely perform PCNL, especially for less experienced practitioners.

Importance Annual rates of first intracranial hemorrhage (ICH) from unruptured brain arteriovenous malformations (AVMs) are often quoted as 2% to 4% in clinical practice. Precise estimates and risk factors are unavailable to inform treatment decisions. Objective To provide estimates of rates and risk factors for first ICH in a large cohort study of unruptured brain AVMs. Design, Setting, and Participants The Multicenter Arteriovenous Malformation Research Study (MARS) included data from 9 cohorts, each contributing 100 or more unruptured brain AVMs. The study was conducted from 2017 to 2023 with retrospective and prospective data collection for existing cohorts and/or new recruitment. This was an international study (2 population-based and 7 referral-based cohorts) that included participants diagnosed with an unruptured brain AVM. Exposures Demographic, clinical, and angiographic characteristics. Main Outcome and Measure The primary outcome was time to first ICH after diagnosis of unruptured brain AVM. Data were collected using standardized definitions; missing data were imputed. Cox regression analysis was performed, censoring at first brain AVM treatment, death, or last visit, and allowing baseline hazards to vary by cohort. Results A total of 3225 individuals were eligible for participation in this study. After 195 exclusions, 3030 participants (median [IQR] age, 38 [25-50] years; 1524 female [50.3%]) were included. Among 2989 participants with unruptured brain AVMs, 1333 (45%) presented with seizure. The median (IQR) maximal brain AVM diameter was 3.1 (2.2-4.4) cm, 248 of 2466 AVMs (10%) had exclusively deep venous drainage, 297 of 2690 (11%) were in supratentorial deep or cerebellar locations, and 457 of 2440 (19%) had associated arterial aneurysms. First ICH occurred in 159 participants over 11 339 person-years of follow-up for an ICH rate of 1.40 (95% CI, 1.20-1.64) per 100 person-years. Significant independent risk factors included (1) increasing age category at diagnosis (hazard ratio [HR], 0.87; 95% CI, 0.53-1.41 for those aged 20 to 39 years; HR, 1.23; 95% CI, 0.74-2.04 for those aged 40 to 59 years; and HR, 2.01; 95% CI, 1.14-3.57 for those aged 60 years vs younger than 20 years; P = .008), (2) presence of associated aneurysms (HR, 1.66; 95% CI, 1.06-2.59; P = .03), and (3) cerebellar or supratentorial deep location (HR, 1.87; 95% CI, 1.16-3.00; P = .01). Conclusions and Relevance The annual ICH rate from unruptured brain AVM was lower than that commonly cited in clinical practice. Increasing age, associated arterial aneurysms, and cerebellar or supratentorial deep brain AVM location were associated with risk of first ICH. These results may be used to counsel patients about the natural history of unruptured brain AVMs.

Abstract The Fracture Nonunion Symposium presented at the 2024 Orthopaedic Trauma Association Basic Science Focus Forum featured invited speakers who discussed current perspectives on this topic. Clinical approaches, diagnostic advancements, basic science perspectives, and novel treatment strategies were discussed. This symposium was curated to highlight this common and challenging clinical problem faced by orthopaedic and musculoskeletal practitioners from around the globe.

Background: Evaluation of otolaryngology resident technical performance has historically relied on subjective perioperative feedback. Despite various assessment tools attempting to provide consistent surgical skill evaluations, current methods remain inherently subjective. Aim: This proof-of-concept pilot study aimed to assess if a 3-dimensional surgical navigation system could capture objective surgical data during endoscopic sinus surgery (ESS). A secondary aim was to analyze if there were any differences between novice and practiced trainees. Methods: Otolaryngology residents performed supervised ESS on patients while their instrument (microdebrider, suction) motion was recorded using a TruDi ® Navigation System. Prior to the surgery, surgical landmarks were defined with sensory beacons in the navigation system using the patient’s preoperative computed tomography (CT) scan. Metrics included time to reach beacons, number of alerts at each beacon, and instrument speed. Results: Fifteen otolaryngology residents performed 87 ESS. The navigation system successfully obtained “time to reach sinus X” data for 64% of sinuses/ case, velocity data in 93% of cases, and number of beacon “alerts” per minute in 93% of cases. We found a significant difference between PGY 3 residents and PGY 4/PGY5 residents in the number of sphenoid sinus alerts per minute ( P = .01) and the percentage of cases in which the resident accessed the maxillary sinus via the natural os ( P < .001). Impact: This study demonstrates the feasibility of collecting objective, navigation-based intraoperative metrics during live surgery and is a first step toward building a comprehensive objective assessment tool in ESS. We hope this report encourages further research into this technology’s application in objective resident skill assessment and correlation with concurrent faculty assessments.

Abstract BRCA-associated homologous recombination deficiency (HRD) is present in ~ 50% of high-grade serous carcinomas (HGSC) and predicts sensitivity to platinum-based therapy. However, there is little understanding of why some patients with BRCA-deficient tumors experience unexpectedly poor outcomes. We profiled 154 tumors, enriched for patients with BRCA-deficient tumors that experienced short overall survival (≤ 3 years, n = 42), using whole-genome, transcriptome, and methylation analyses. All but one BRCA-deficient tumor exceeded an accepted HRD genomic scarring threshold. However, patients with BRCA1-deficient HGSC with a more elevated HRD score survived significantly longer. Patients with BRCA2-deficient HGSC and loss of NF1 survived twice as long as those without NF1 loss, whereas PIK3CA or RAD21 amplification defined BRCA2-deficient HGSC with exceptionally short survival. BRCA1-deficient tumors in short survivors had evidence of immunosuppressive c-kit signaling and EMT. In a large HGSC cohort (n = 1,389) including 282 individuals with pathogenic germline BRCA variants (gBRCApv), the location of the mutation within functional domains stratified clinical outcomes. Notably, residual disease after primary surgery had limited prognostic effect in gBRCApv-carriers compared to non-carriers. Our findings indicate that tumor HR proficiency in the context of therapy response and survival is not a binary property, and highlight genomic and immune modifiers of outcomes in BRCA-deficient HGSC.

Abstract BACKGROUND Mirdametinib is the first FDA-approved MEK1/2 inhibitor for both adults and children (≥2 years) with NF1 who have symptomatic PN not amenable to complete resection. We report updated results from the LTFU phase of the pivotal, phase 2b ReNeu trial (NCT03962543) evaluating the efficacy and safety of mirdametinib. MATERIALS AND METHODS In ReNeu, mirdametinib capsules or tablets for oral suspension (2 mg/m2 BID, max 4 mg BID) are administered in 3-weeks-on/1-week-off 28-day cycles. Following the 24-cycle (~2 years) treatment phase, patients could continue mirdametinib in an optional LTFU phase. These analyses are inclusive of the treatment and LTFU phases (data cutoff: June 12, 2024; an additional 9 months of cumulative data following the primary analysis). Exploratory analyses reported here included confirmed objective response rate (ORR; proportion of patients with ≥20% reduction of target PN volume from baseline on consecutive MRI scans within 2 to 6 months, assessed by blinded independent central review), duration of response (DoR), change from baseline in target PN volume, and safety. RESULTS Fifty-eight adults and 56 children were dosed with mirdametinib. Median (range) duration of mirdametinib treatment was 21.8 (0.4, 54.4) months in adults and 25.4 (1.6, 48.5) months in children. Among LTFU-eligible patients, 26/31 (84%) adults and 32/37 (86%) children entered the LTFU. Confirmed ORR was 47% (27/58; 95% CI, 33%, 60%) in adults and 55% (31/56; 95% CI, 42%, 69%) in children. Of patients with a confirmed objective response, 18 adults and 19 children achieved a deep response (best target PN volume reduction from baseline of &gt;50%). Median (range) best percentage change from baseline in target PN volume was -41% (-90%, 13%) in adults and -43% (-98%, 48%) in children. Median DoR was not reached. Treatment-related adverse events (TRAEs) in ≥25% of patients were dermatitis acneiform, diarrhoea, nausea, and vomiting in adults, and diarrhoea, dermatitis acneiform, and paronychia in children. Grade ≥3 TRAEs occurred in 17% of adults and 25% of children. Dose interruptions, dose reductions, and discontinuations due to TRAEs occurred in 9%, 17%, and 22%, respectively, of adults, and in 14%, 14%, and 9%, respectively, of children. CONCLUSIONS An increase in confirmed ORR was observed with longer duration of mirdametinib treatment, with additional deep responses achieved in both adults and children with NF1-PN. Mirdametinib continued to be well tolerated with a manageable safety profile and no new safety signals identified in the LTFU phase. SUPPORTED BY SpringWorks Therapeutics, Inc.