Citations

Abstract Introduction: Next generation of Theranostics studies are looking at novel combinations with radiation sensitizers to enhance PRRT’s efficacy. Here, we present safety and efficacy data from a multi-center phase 1 study of a [¹⁷⁷Lu]lutetium-dotatate -triapine combination in patients with GEP-NETs. Methods: The study consisted of two phases (dose escalation and expansion) administering the recommended phase 2 doses (RP2D) for the two agents. All patients received 200 mCi of [¹⁷⁷Lu]lutetium-dotatate on day 1 of four 8-week cycles, in combination with oral triapine administered at assigned dose levels (100 mg, 150 mg or 200mg) from days 1 to 14 of each cycle. Results: A total of 31 (A: 15 ; B: 16 ) patients received treatment. Nine patients experienced dose-limiting toxicities; Grade 3 anemia (n=1), Grade 5 cardiac arrest (n=1), and Grade 4 neutropenia (n=7). Based on the overall safety and pharmacokinetics data, a [¹⁷⁷Lu]lutetium-dotatate (200 mCi) plus triapine (150 mg) dose was selected as the RP2D for the expansion phase. Grade ≥3 treatment related adverse events were observed in 77% patients: anemia (23%), nausea and vomiting (3% ), lymphopenia ( 58%), neutropenia ( 35%) and leukopenia ( 39%). The majority of cytopenias were transient and resolved within two weeks. Among the 28 evaluable patients, the objective response rate (ORR) was 21.4% and the median progression-free survival (mPFS) has not been reached (median follow-up period: 23.7 months). Conclusions: The combination of [¹⁷⁷Lu]lutetium-dotatate (200 mCi) and oral triapine (150 mg D1-14) was well tolerated and demonstrated preliminary activity in patients with well-differentiated GEP-NETs. (NCT04234568).

Background Randomized trials have shown equivocal outcomes between a direct aspiration as first-pass technique (ADAPT) and stent retriever (SR) stroke thrombectomy, yet whether specific patient subgroups benefit differentially from one technique over the other remains unknown. Methods In this retrospective multicenter cohort study, patients with large vessel occlusion were included, and those who underwent ADAPT versus SR first-pass thrombectomy (either as standalone or combined with aspiration) were compared. The primary outcome was a composite of first-pass effect (FPE, modified Thrombolysis In Cerebral Infarction (mTICI) 2c or better with one attempt) with no symptomatic intracranial hemorrhage (sICH). A causal forest model was used to estimate the conditional average treatment effect (CATE) for each patient, with larger CATEs indicating that ADAPT is expected to be more advantageous. Patients were stratified by CATEs, and outcomes were compared between treatment groups. Results Among 6700 included patients, ADAPT (n=3695, 55%) was associated with a higher rate of FPE with no sICH (39.9% vs 26.9%; adjusted OR (aOR) 2.07, 95% CI 1.77 to 2.41, P<0.001). The causal forest identified significant treatment effect heterogeneity (interaction P<0.001), where ADAPT was more advantageous in more recent years and among patients with M1 occlusions presenting in earlier time windows. Low-CATE patients showed no statistically significant difference between techniques (aOR 0.91, 95% CI 0.57 to 1.45, P=0.70), while medium- and high-CATE patients demonstrated progressively larger ADAPT advantages (aOR 2.06, 95% CI 1.67 to 2.55, and aOR 2.99, 95% CI 2.24 to 3.98, respectively, both P<0.001). Conclusions ADAPT may be superior to SR for a majority of patients, particularly in recent years, and among patients with M1 occlusions presenting in earlier time windows.

ABSTRACT Purpose Despite 5‐year survival rates of over 90% among children and adolescents/young adults (CAYAs) with classic Hodgkin lymphoma (cHL), 15%–20% relapse after frontline therapy. Prior analysis of frontline Children's Oncology Group (COG) clinical trials demonstrated that, despite similar rates of relapse, non‐Hispanic Black (NHB) and Hispanic (vs. non‐Hispanic White [NHW]) patients experienced higher post‐relapse mortality. It is unknown whether post‐relapse disparities persist when second‐line treatment is delivered in a cooperative group trial setting. We examined overall survival (OS) by race and ethnicity in CAYAs enrolled in COG trials for relapsed/refractory (r/r) cHL. Methods A pooled analysis of individual‐level data from CAYAs (≤ 29 years) receiving therapy for r/r cHL on COG clinical trials (2001–2016) was conducted. The Kaplan–Meier method estimated 3‐year OS by racial and ethnic groups. Cox regression models examined associations of race and ethnicity and OS, adjusted for age, insurance, first versus ≥2 relapse, and time from initial diagnosis to relapse trial enrollment. Results Among 175 CAYAs treated on COG trials for r/r cHL (5.7% Asian or Pacific Islander, 14.9% Hispanic, 14.3% NHB, 61.7% NHW, 3.4% other), at median follow‐up of 4.9 years, 3‐year OS was 82.1% (95% confidence interval [CI], 75.3%–87.1%) and did not differ by race and ethnicity ( p = 0.36). In multivariable analyses, shorter time from diagnosis to relapse trial enrollment ( p = 0.01) and ≥2 relapses (vs. first, p = 0.004) conferred worse OS, with no significant effect of race and ethnicity ( p = 0.43). Conclusion Post‐relapse survival did not differ by race and ethnicity among CAYAs enrolled in COG trials for r/r cHL, suggesting access to clinical trials may mitigate OS disparities.

Abstract Purpose The female waist and torso remain fundamental aesthetic elements in body contouring, yet empirical data describing public preferences for waist-to-hip ratio (WHR) and abdominal muscle definition are limited. Misalignment between patient perceptions and actual aesthetic preferences may influence body dissatisfaction, drive unnecessary procedures, and shape unrealistic surgical goals. This study aimed to (1) evaluate how females perceive their own waist shape and ideal appearance using standardized manipulated images, (2) quantify male preferences for female WHR and abdominal definition, and (3) assess the discrepancy between what women believe men find attractive and men’s actual preferences. Methods An anonymous online survey was distributed internationally and collected 900 responses from adult participants. Two digitally manipulated, standardized female torso images were created: one varying waist-to-hip ratio across five levels (WHR 0.60 to 0.80) and one varying abdominal muscle definition. Male participants rated which WHR and abdominal definition they found most attractive. Female participants reported (1) which WHR and definition most resembled their current appearance, (2) which represented their ideal, and (3) which they believed men found most attractive. Additional demographic and body image variables were collected. Descriptive statistics were generated, and comparative analyses (chi-square tests) were conducted to evaluate differences in preference distributions and female perception versus male reality. Results A total of 900 respondents participated, including 41% men and 59% women. Male respondents showed a clear preference for smaller waist-to-hip ratios (WHR). The lowest WHR (0.60) was the most frequently selected option (38%), with steadily decreasing selections as WHR increased. Men also most preferred mild abdominal definition (Option B). Female responses revealed notable perception gaps: women most often perceived themselves as having midrange WHRs (0.70) but selected lower WHRs (0.65) as ideal, and they substantially overestimated men’s preference for the smallest WHR. Subgroup analyses showed that male WHR preferences varied significantly by continent (p &lt; 0.05), with Europe, North and South America favoring smaller WHRs, while Africa, Australia, and Asia preferred larger ones. Higher male physical activity was associated with selecting smaller WHRs (r = –0.220, p &lt; 0.05) and slightly greater abdominal definition (r = 0.169, p &lt; 0.05). Social media use did not influence male preferences. Among women, physical activity strongly predicted desired abdominal muscularity (r = 0.236, p &lt; 0.05) but not ideal WHR. Perceived social media influence significantly shaped ideal WHR (r = 0.202, p &lt; 0.05), such that women who reported more negative influence selected smaller, more exaggerated WHRs. Time spent on social media did not significantly affect female aesthetic preferences. Conclusion This study provides quantitative evidence describing public preferences for female waist and torso aesthetics, revealing important divergences between perception and reality. Men strongly prefer smaller waist-to-hip ratios and mild abdominal definition, but not to the extreme levels that women commonly assume. Women’s own ideal waist shape aligns directionally with male preferences, yet women significantly overestimate the degree to which men favor the smallest possible WHR. This misperception may contribute to body dissatisfaction, drive interest in unnecessary procedures, or set unrealistic surgical expectations. For aesthetic surgeons, these findings highlight the need for patient-centered counseling that addresses perception gaps, corrects inaccurate beliefs about male preferences, and reinforces natural, proportionate outcomes rather than extreme contouring. The data support a trend toward moderate enhancement rather than highly exaggerated WHR reduction or aggressive abdominal definition in female body contouring. Incorporating these insights may improve patient satisfaction, promote psychological well-being, and guide surgical planning grounded in evidence-based aesthetics.

Background The management of osteochondral lesions of the talus (OLT) is challenging, with 2 main options being conservative and surgical management. Orthobiologic therapies come to bridge the gap between these 2 options; however, inconsistencies in indication, composition, and heterogeneous evidence limit clinical decision-making. To address these challenges, 3 International Congress Meetings on Cartilage Repair of the Ankle were convened in Pittsburgh, USA (2017), Dublin, Ireland (2019), and New York, USA (2025) to establish agreement on the role of conservative management and injectable orthobiologic strategies in the treatment of OLT. Methods Seventy-five multidisciplinary experts from over 25 countries and 1 territory participated in a structured Delphi-based consensus process. Blinded surveys, structured questionnaires, and in-person discussions were used to develop and refine statements, supported by literature review and graded evidence (A1–E). Consensus strength was defined as consensus (51%-74%), strong consensus (75%-99%), or unanimous (100%) Results In total, 29 consensus statements were achieved across the 3 meetings. Strong agreement was reached regarding indications and expected outcomes of conservative management, including the role of immobilization and appropriate timing for surgical intervention. Orthobiologic injections, including platelet-rich plasma, concentrated bone marrow aspirate, and hyaluronic acid, were considered appropriate in select patients with persistent symptoms, although no superiority was demonstrated among formulations, preparation methods, or injection strategies. When used as adjuncts to surgical procedures, orthobiologics may improve radiological outcomes, with limited evidence for improvement in clinical outcomes. Technical considerations, including preferred harvest sites and a lack of standardized preparation protocols, were identified, along with key principles for patient counseling Conclusion These international consensus statements establish a standardized framework for the conservative management and use of injectable orthobiologic therapies in OLT. By clarifying indications, technical considerations, and current limitations, this work aims to improve consistency in clinical practice, guide treatment decision-making, and inform future research.

Introduction: Limited research explores dermoscopy use among physician associates (PAs), outside of one prior study examining dermoscopy in PA student education. This study sought to investigate dermoscopy use among practicing PAs and its impact on their overall diagnostic confidence, including in darker skin tones, when differentiating between benign and malignant skin lesions. Methods: An anonymous survey was developed in 2023 with input from experts in dermoscopy and survey creation to assess PA confidence in skin lesion evaluation as well as PA dermoscopy knowledge and use, perceptions, barriers to use, and prior education. The dermoscopy survey was included as an optional module in the 2024 American Academy of Physician Associates (AAPA) Salary Survey. Results: Of 3,174 invited PAs, 995 (31.4%) responded. Most had never used dermoscopy in practice (81%) but knew or recognized the term (71%). A majority (53%) believed PAs should be trained in dermoscopy during PA school, and 26% reported no interest in future dermoscopy use. Dermatology PAs reported more frequent dermoscopy use and generally greater confidence in evaluating skin lesions, both overall and in darker skin tones, than PAs in other specialties. PAs in surgical (OR=0.2, 95% CI 0.1-0.6) and medical (OR=0.3, 95% CI 0.2-0.5) subspecialties were less likely to use dermoscopy at least annually compared with PAs in primary care. PAs in rural areas were more likely to feel confident in differentiating skin lesions than those in urban areas (OR 2.9, 95% CI 1.7-5.0). Conclusion: Dermoscopy use is associated with higher overall skin lesion assessment confidence. Wider adoption, especially outside dermatology, requires training, increased advocacy, and expanded education.

BACKGROUND: Primary aldosteronism (PA) is a common and treatable cause of hypertension, yet data on the durability of medical treatment response beyond the first year are limited. Using the PA medical treatment outcomes framework, we evaluated long-term biochemical and clinical outcomes and factors associated with treatment response. METHODS: We conducted an international, multicenter, observational cohort study across 27 centers on 4 continents. Adults with PA treated with mineralocorticoid receptor antagonists and/or epithelial sodium channel blockers between 2016 and 2021 were included if follow-up data were available at ≥12 months. Biochemical and clinical responses were classified as complete, partial, or absent using PA medical treatment outcomes criteria. Ordinal logistic regression identified determinants of a favorable treatment response. RESULTS: The cohort included 1292 patients (47.5% women, mean age 52 years) with a median follow-up of 34 months (interquartile range, 21–51). At ≥12 months, 58.3% achieved a complete biochemical response, and 20.8% achieved a complete clinical response, with only 5% showing no response. Determinants of a favorable biochemical response included lower aldosterone and lateralization index, and higher renin and potassium levels at baseline. In those taking spironolactone, a higher daily dose was also associated with a favorable biochemical response. Determinants of a favorable clinical response included female sex, lower body mass index, shorter duration of hypertension, and absence of hypertension-mediated organ damage. CONCLUSIONS: Targeted medical therapy for PA can deliver sustained biochemical and clinical benefits. Early disease detection and adequate dose titration are highly actionable determinants of long-term treatment success.

Abstract Background Ultrasound (US)‐guided hydrodissection is a minimally invasive treatment for cubital tunnel syndrome (CuTS) with promising early results. However, data on patient‐perceived outcomes, durability of relief, and impact on surgical need remain limited. Objective To assess the effectiveness of US‐guided cubital tunnel hydrodissection in improving CuTS symptoms via patient‐centered outcomes. Design Retrospective chart review with cross‐sectional telephone follow‐up. Setting Quaternary medical center multidisciplinary outpatient hand clinic. Participants Seventeen patients (19 arms) with clinical CuTS who received US‐guided hydrodissection from one physician. Interventions Patients were contacted by telephone for cross‐sectional outcome assessment. Main Outcome Measures Patient‐reported improvements in weakness, paresthesias, and/or pain, percent pain relief, symptom improvement duration, adverse events, and Patient Global Impression of Change (PGIC) scores. Results At mean 7 ± 5 month follow‐up, improvement in weakness, paresthesia, and pain was reported in 12 (63%) extremities (95% confidence interval [CI] 41%–85%; p < .001) . Pain relief ≥50% occurred in 12 (63%) and ≥75% in 8 (42%) extremities, with mean duration 4 months. PGIC scores showed 14 (74%; 95% CI 54%–94%; p < .001) at least “minimally improved” and 8 (42%) (95% CI 20%–64%; p < .001) “much improved.” No adverse events occurred. Two patients without improvement underwent surgical decompression with anterior transposition at 1 and 3 months after hydrodissection, achieving 90%–100% pain relief and “much or very much improved” PGIC scores. Of 19 extremities, 7 (37%) were McGowan Grade I and 12 (63%) Grade II; none were Grade III. Grade II extremities showed significantly greater overall symptom relief ( p = .004) and pain relief ≥50% ( p = .004). PGIC scores did not differ significantly between grades (both p > .062). Conclusion US‐guided cubital tunnel hydrodissection was associated with meaningful symptom improvement and no adverse events. Limitations include small sample size, no control group, single operator, and potentially time‐limited relief. The procedure appears safe and a potential nonoperative treatment option.

ABSTRACT Purpose We studied histologic Ewing sarcoma (ES) tumor response at local control surgery to explore associations between histologic response and chemotherapy practice changes over time and confirm its prognostic significance in the modern era. Methods We reviewed clinical data for 126 patients with ES treated at Mayo Clinic from 1977 to 2022, analyzing the percentage necrosis as a prognostic factor across chemotherapy regimens (including modern interval‐compressed VDC‐IE). Results In the historical cohort, 5‐year event‐free survival (EFS) and overall survival (OS) for patients with ≤5% versus greater than 5% viable tumor were 76% versus 59% ( p = 0.01) and 83% versus 62% ( p = 0.01). Review of 104 specimens by two pathologists identified the percentage remaining viable tumor as more reproducible than the percentage necrosis and/or fibrosis. On multivariable analysis of patients with localized disease ( n = 87), pelvic tumors and greater than 5% viable tumor remained independent risk factors for poor survival (EFS: hazard ratio [HR] 3.1, p < 0.01; OS: HR 2.1, p = 0.048). The modern cohort consisted of 22 patients. No patients with tumor size less than 8 cm at diagnosis and 100% necrosis after surgery had events; four of seven with tumors greater than 8 cm had events despite 100% necrosis. Conclusions Our results validate the historical threshold of greater than 5% viable tumor with older chemotherapy regimens but not with modern interval‐compressed VDC‐IE. In addition, inter‐rater reliability for the percentage viable is more reproducible than the percentage necrosis. Although numbers are small, tumors less than 8 cm with no viable tumor appear to be a favorable subgroup and suggest risk stratification using a combination of tumor size and any viable tumor should be evaluated in ES.