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Diffuse B-cell lymphomas are the most prevalent canine hematologic malignancies, and their clinical presentation resembles that of human B-cell non-Hodgkin lymphomas (NHLs). However, a lack of a clear subtyping framework perpetuates imprecise treatment approaches that fail to address mechanisms of therapy resistance. Here, we employed deep phenotyping via serial sampling and longitudinal transcriptomics to evaluate intratumoral composition and therapy response in a 6-year-old neutered male goldendoodle with stage 5A marginal zone lymphoma (MZL). Following sequential treatment consisting of a single IV dose of oncolytic vesicular stomatitis virotherapy (VSV) and standard CHOP chemotherapy 30 days later, we performed scRNAseq on seven serial lymph node biopsies and spatial sequencing on a resection taken 10 days post-VSV treatment. B cells (>90%) comprised three transcriptionally distinct and temporally stable subpopulations, with specific copy number profiles and robust spatial organization despite disrupted lymph node architecture. Analysis across subpopulations revealed downregulation of the quiescence program including KLF2, suggesting similarity to KLF2-deficient human MZL. While VSV successfully reached target B cells, downstream transcriptional responses were predominantly localized to the T-cell compartment. T cells (≤6%) showed increased proliferation and upregulation of cytotoxicity markers post-VSV administration, enriching for leukocyte-mediated cytotoxicity pathways consistent with an anti-viral immune response. Ultimately, these results provide an in vivo proof-of-concept for the treatment paradigm in canine lymphoma, while emphasizing the need for improved subtyping frameworks and multidimensional treatment strategies targeting intratumoral heterogeneity.

Objective To assess the effect of Moses™ 2.0 (Lumenis Be Ltd., Yokneam Illit, Israel; Boston Scientific, Marlborough, MA, USA) for lithotripsy of renal stones of 8–20 mm in diameter on operative time, surgeon workload, and retropulsion. Subjects/Patients and Methods In our multicentre, randomised, double‐blind clinical trial, patients were randomised 1:1 to standard or Moses 2.0 laser lithotripsy and stratified by stone size. Patients and surgeons were blinded to laser modality. Primary outcomes were total operative time as well as surgeon workload assessed by the National Aeronautics and Space Administration‐Task Load Index (NASA‐TLX). Secondary outcomes were stone retropulsion evaluated by blinded video review and postoperative clinical outcomes. Linear regression modelling was used for analysis. Results A total of 153 patients (79 Standard, 74 Moses 2.0) with similar clinical, stone, and operative characteristics were evaluated. There was no significant difference in operative times between the Standard and Moses 2.0 groups ( P = 0.73). Moses 2.0 was associated with lower effort, frustration, mental, physical, and temporal workload, as well as higher rated overall performance compared to the standard laser. Video review demonstrated no difference in rates of retropulsion ( P = 0.13). Complication rates (Standard: 13%; Moses 2.0: 10%) and stone‐free rates (Standard: 51%; Moses: 2.0 55%) were comparable. Conclusion Our study evaluated the impact of Moses 2.0 technology on high‐powered renal stone dusting, constituting the largest double‐blind trial of its kind to date. There was insufficient evidence to suggest any difference in operative times or clinical outcomes when using Moses 2.0 compared to standard laser lithotripsy. Moses 2.0 was associated with reduced surgeon workload, which has implicit impact on surgeon wellness.

Purpose To assess the reliability, predictability, and discriminative capacity of 3 anatomic measurements, tibial tubercle‐trochlear groove (TT‐TG), tibial tubercle‐posterior cruciate ligament, and patellar tendon‐lateral trochlear ridge (PT‐LTR), where PT‐LTR may offer a complementary approach to assessing recurrent patellofemoral instability (PFI) risk. Methods Patients diagnosed with PFI before primary patellofemoral stabilization surgery at a single institution between 2022 and 2024 were included. A control group without PFI was propensity matched 1:1 for age, sex, and laterality. Magnetic resonance images were evaluated to measure TT‐TG, tibial tubercle‐posterior cruciate ligament, and PT‐LTR. A priori power analysis determined the cohort size. Statistical analyses compared differences between the PFI and control groups with Student t‐tests, receiver operating characteristic analyses, and area under the curve with resultant sensitivity, specificity, and an optimal cutoff. Results Patients included 50 knees with PFI (28 women, 22 men; mean age 18 ± 5 years). The control group included 50 knees (27 women, 23 men; mean age 18 ± 4 years). Excellent inter‐ and intra‐rater reliability (intraclass correlation coefficient > 0.7) was shown for TT‐TG and PT‐LTR in the PFI and control groups. The distances for TT‐TG, tibial tubercle‐posterior cruciate ligament, and PT‐LTR were significant predictors ( P ≤ .025) of PFI. The average PT‐LTR distance difference for the PFI and control groups was 7.0 mm ( P < .001). PT‐LTR showed an area under the curve of 0.80 and, when ≥4.6 mm, was 66% sensitive and 92% specific for PFI. Conclusions The PT‐LTR distance is a reliable and discriminative metric for identifying PFI in both pediatric and adult populations. A PT‐LTR cutoff value of 4.6 mm showed diagnostic discrimination and substantially high specificity for recurrent PFI, indicating strong ability to identify patients with instability. Level of Evidence Level III, retrospective case control study.

Abstract Meniscus surgery remains one of the most common orthopedic procedures worldwide. Successful meniscus repair requires A natomic reduction, B iologic preparation and augmentation, C ircumferential compression (ABCs), and an optimized rehabilitation protocol. Rehabilitation after surgery is critical for optimizing outcomes, yet the ideal approach remains controversial. A recent international European Union‐United States consensus task force developed recommendations for rehabilitation meniscal surgery. The group concluded that rehabilitation after meniscal repair and reconstruction should progress according to both time‐ and criterion‐based milestones. In practice, 2 rehabilitation pathways are utilized after meniscal repair: a standard protocol for biomechanically stable repairs that tolerate some weight‐bearing in full extension and a complex protocol for repairs requiring greater protection. Standard meniscal repairs (i.e., vertical longitudinal) are biomechanically stable and treated with moderate protection. During the first 4 weeks, patients are restricted to 0° to 90° of knee range of motion, partial weight‐bearing with crutches, and full knee extension during ambulation. Between weeks 4 and 8, patients progress to weight‐bearing as tolerated while avoiding loaded knee flexion beyond 90° until week 16, with emphasis on gait normalization and strengthening. From weeks 8 to 16, aerobic conditioning and strengthening continue. Pending surgeon clearance, return to running begins at week 12, plyometric exercises at week 14, and return to sport at 4 to 8 months. Complex meniscal repairs (e.g., radial or root tears) require a protective rehabilitation approach. During weeks 0 to 6, range of motion is restricted to 0° to 90° with toe‐touch weight‐bearing and full knee extension during ambulation. Range of motion and weight‐bearing progress from weeks 6 to 12, while loaded flexion beyond 90° remains restricted until week 16. Between weeks 12 and 18, aerobic conditioning and strengthening continue. Pending surgeon clearance, running begins at week 14, plyometrics at week 16, and return to sport typically occurs at 6 to 9 months.

Abstract Medial meniscus posterior root repair improves symptoms and function, but repair alone does not normalize gait. In the referenced study, patients who underwent repair achieved an acceptable symptom state more often than those with an unrepaired tear (71.4%‐81.0% vs 10.5%‐26.3%). Gait mechanics moved toward normal but did not reach it: compared with controls, the tear group differed significantly in midstance knee extension and terminal‐stance knee adduction moment, with the repair group falling at an intermediate level. Varus thrust and reduced internal rotation persisted in both groups despite only modest differences in static mechanical alignment. This underscores that dynamic gait assessment, not a static radiograph, is beneficial to fully assess the effect of root repair. Restoration of full extension and objectively confirmed quadriceps recovery may be essential to closing this gap and to long‐term chondroprotection. This raises a rehabilitation paradox: prolonged protection safeguards healing but may potentiate quadriceps inhibition and persistent gait dysfunction. Earlier controlled weightbearing, potentially supported by meniscal centralization with multiple fixation points, warrants a prospective study. Root preservation should extend beyond fixation alone to include gait restoration, extrusion control, and long‐term joint protection.

Purpose To evaluate implantation rates, time to implantation, and predictors of implantation following matrix‐induced autologous chondrocyte implantation (MACI) biopsy for knee chondral defects. Methods Patients undergoing MACI biopsy or implantation for symptomatic knee chondral defects from 2017 to 2024 at a single institution were reviewed. At a minimum 1‐year follow‐up, the decision to proceed with implantation, recurrent symptoms, complications, and reoperations were assessed. Kaplan‐Meier analysis estimated time to implantation, and multivariable logistic regression identified predictors of MACI implantation. Results A total of 208 knees in 202 patients (mean age 28.0 ± 10.9 years, range 11‐59) underwent MACI biopsy for 243 chondral defects (patella [38%], femoral condyle [34%], and trochlea [26%]). At a mean follow‐up of 4.3 years (range 1.0‐8.3), 64 knees (31%) proceeded to second‐stage MACI implantation. Among 144 knees not implanted, 87 (60%) reported symptom improvement, and 26 (18%) had persistent symptoms. The remaining 22% did not undergo implantation due to another cartilage procedure, insurance denial, or pending scheduling. Patients who underwent biopsy at the home institution had a shorter time from biopsy to implantation compared with those biopsied at outside institutions (6.1 vs 13.1 months, P = .001). Median time to implantation was 9.4 months (95% confidence level: 7.2‐12.2) for home biopsies. Lower body mass index was associated with progression to implantation after adjusting for covariates (odds ratios 0.92, P = .019). Patients implanted within 4 months had larger chondral defects (4.0 vs 3.0 cm 2 , P = .045). At a mean 4.1‐year follow‐up, 6 patients (8%) experienced postoperative complications, including 3 (4%) who required revision chondroplasty. Conclusions MACI biopsy for knee chondral defects resulted in approximately one‐third of patients proceeding to MACI implantation, at a median of 9.4 months after biopsy. Lower body mass index was associated with higher likelihood of progression to implantation, larger chondral defects with earlier implantation, and among patients who did not proceed to implantation, approximately 60% reported symptom improvement following concomitant chondroplasty at the time of biopsy. Level of Evidence Level IV, retrospective case series.

PURPOSE Detection of bone marrow disease has been a major component of rhabdomyosarcoma (RMS) staging with bilateral bone marrow aspirates/biopsies (BMAB) from the iliac crests considered the diagnostic gold standard. This study's goal was to determine if 2- 18 F-labeled fluorodeoxyglucose positron emission tomography/computed tomography ([ 18 F]FDG PET/CT) or PET/magnetic resonance imaging (MRI) may replace BMAB in RMS staging. METHODS Patients were recruited in Europe and North America. Medical records, FDG PET/CT or FDG PET/MRI (PET), and BMAB reports were collected retrospectively. Images were re-reviewed by nuclear medicine physicians at the patients' home institutions if PET reports indicated increased FDG uptake at bone/bone marrow sites or if tumor cells were detected in bone marrow samples. RESULTS PET imaging and BMAB were performed before chemotherapy and tumor resection in 301 patients with FDG-avid RMS. Bone marrow metastases were detected by PET and BMAB in 54, by PET only in 24, and by BMAB only in one of 301 patients with FDG-avid primary tumors. Absence of bone marrow metastases was confirmed by PET and BMAB in 222 of 301 patients. These observations translated into 98% sensitivity and 90% specificity for PET in detecting bone marrow metastases when BMAB was considered as gold standard. FDG-avid marrow disease was patchy (1-5 foci) in one third of cases. Patients with marrow disease indicated by PET and BMAB had more FDG-avid bone marrow foci, more metastatic sites, and lower survival than those with marrow disease indicated by PET only, suggesting more advanced disease stages. CONCLUSION Bone marrow sampling may be omitted in patients without evidence of FDG-avid bone marrow disease by PET. If there are FDG-avid bone marrow lesions, further investigation by MRI and/or biopsy should be considered.

ABSTRACT Background and Objectives Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal, but the contribution of nonbiological factors to long‐term survival is unclear. We evaluated demographic, socioeconomic, clinical, treatment, and care‐delivery factors associated with 3‐year survival and whether these associations persisted at 5 years. Methods National Cancer Database patients with stage I–III PDAC diagnosed from 2012 to 2022 were analyzed using multivariable logistic regression adjusted for treatment pathway. Results Among 57,053 patients, 51,071 were eligible for a 3‐year analysis, and 12,205 (23.9%) survived. Compared with chemotherapy alone, surgery with chemotherapy (OR, 7.12; 95% CI, 6.64–7.63) and surgery alone (OR, 3.84; 95% CI, 3.49–4.23) had the strongest associations with survival. Younger age, lower comorbidity, Asian race, Spanish/Hispanic ethnicity, private insurance, lower grade, body or tail location, and lower nodal burden were independently associated with survival. Black race and treatment timing were not significant after adjustment. Findings were directionally consistent at 5 years. Conclusion Demographic, socioeconomic, and clinical factors independently influence 3‐year survival in PDAC. These findings underscore the need to complement biologic and therapeutic advances with structural interventions, such as insurance expansion and improved access to high‐quality centers, to mitigate disparities and improve outcomes in this highly lethal cancer.

Background: Dancers are at risk of femoroacetabular impingement (FAI) owing to supraphysiologic range of motion and associated demands placed on their hips. There remains a paucity of literature on midterm outcomes in dancers who undergo primary arthroscopy and labral repair for FAI. Purpose: To determine the rate of return to dance and patient-reported outcome measures in competitive dancers after hip arthroscopy with labral repair for FAI with minimum 2-year follow-up. Study Design: Case series; Level of evidence, 4. Methods: This study included dancers with FAI undergoing primary hip arthroscopy with labral repair from 2010 to 2022. Patient-reported outcome measures were collected at 2-year minimum follow-up: modified Harris Hip Score (overall, activities of daily living, gait, pain), Hip Outcome Score (activities of daily living, sports-specific subscale), Tegner Activity Scale, visual analog scale for pain, and surgery satisfaction. Patients were evaluated for preoperative radiographic measurements, postoperative return to sport, and revision surgery. Return to dance was evaluated. Results: Thirty-seven dancers were followed for a mean 7.4 years (range, 3.2-12.2) postoperatively (36 female and 1 male; mean ± SD age, 21 ± 7 years; mean body mass index, 23.3 ± 4.5). All outcome scores significantly improved postoperatively as compared with preoperatively ( P ≤ .037). Twenty dancers (71%) returned to dance. Of those who returned to dance, 17 (85%) returned to sport at the same or higher level as compared with the preoperative level. At final follow-up, 45% of dancers who initially returned to dance continued to dance. Of the dancers who no longer participated in dance at final follow-up, 7 (65%) quit dancing for nonhip-related reasons. Mean surgery satisfaction (0-10) at final follow-up was 7.1. Four patients (10%) underwent revision hip arthroscopy with revision labral repair. Conclusion: Hip arthroscopy with labral repair in dancers results in sustained improvements in function and pain at minimum 2-year follow-up. Most dancers return to their prior levels of dance, and nearly half remain active several years later. Notably, discontinuation of dance was often unrelated to hip symptoms, underscoring the importance of counseling patients on clinical and lifestyle factors influencing return to sport.

Polycythemia vera is characterized by erythrocytosis and increased risk of thrombosis. Sapablursen is an antisense oligonucleotide that suppresses transmembrane serine protease 6 (TMPRSS6), increases hepcidin production, and reduces iron availability for erythropoiesis. IMPRSSION; an ongoing phase 2a, randomized, open-label study includes patients meeting 2016 WHO criteria for polycythemia vera, requiring ≥3 phlebotomies within 6 months of screening and ≥1 phlebotomy within the last 12 weeks. Cohort A (120 or 80 mg) and Cohort B (40 mg) received sapablursen subcutaneously once every 4 weeks (Q4W). The primary efficacy endpoint was the reduction in phlebotomy frequency from baseline to weeks 17-37 in patients who received ≥1 dose. Forty-nine patients received ≥1 sapablursen dose (median age 61 years; 82% male). The baseline mean±SD weekly phlebotomy rate was 0.15±0.07 in Cohort A; 0.17±0.07 in Cohort B and was reduced by -0.10 (95%CI, -0.13, -0.07; n=32;p&lt;0.0001) in Cohort A; -0.10 (95%CI, -0.14, -0.06; n=17;p=0.0001) in Cohort B. Sapablursen reduced the median (IQR) number of phlebotomies from 5.0 (3.0-6.0,Cohort A; 3.5-6.5,Cohort B) at baseline (26-weeks) to 0 (0-1.0) in the efficacy evaluation window (20-weeks) in Cohort A and 1.5 (0-2.5) in Cohort B. Most adverse events were mild or moderate; anemia and fatigue were most common. The mean change in MPN-SAF-TSS at week 37 was -6.21 points (95%CI: -10.56, -1.85, p=0.0052) in Cohort A; -2.71 points in Cohort B (95% CI: -8.33, 2.91, p=0.34). Sapablursen reduced phlebotomy need, improved symptoms, and was safe and well-tolerated in patients with polycythemia vera. (Funded by Ionis Pharmaceuticals; ClinicalTrials.gov: NCT05143957)