Citations

Abstract Introduction: Monitoring minimal residual disease (MRD) is critical in multiple myeloma (MM) to predict outcomes and guide therapy. Traditional bone marrow (BM) aspirates for MRD detection are invasive and limited by sample quality. We therefore explored cell-free DNA (cfDNA) fragmentation as a less invasive alternative for MRD detection. Methods: We performed 30-40X whole-genome sequencing (WGS) on peripheral blood cfDNA from 45 MM patients, collecting baseline (n = 45) and follow-up samples (n = 98) from eight Canadian sites (M4 and IMMAGINE studies) and one U.S. site (SPORE study), plus 25 healthy controls. Samples were collected post-induction therapy (n = 13), 100 days post-autologous stem cell transplantation (ACST, n = 36), and during maintenance therapy (n = 49). Multiparameter flow cytometry (MFC) MRD testing was conducted on 77 samples. We evaluated insert size metrics and MM-specific chromatin accessibility (from Ordoñez et al., 2020) using Griffin (described in Doebley et al., 2022). Results: Baseline samples had a higher proportion of short fragments (20-150 bp) than follow-up samples (p = 0.0037) and healthy controls (p = 0.019). A fragment score (FS) based on weighted fragment distribution (per Vessies et al., 2022) was highest at baseline (mean = -0.384), followed by MRD-positive (mean = -0.495) and MRD-negative (mean = -0.550) samples. MRD-negative FS was lower than baseline samples (p < 0.001) but higher than healthy controls (mean = -0.639; p = 0.016). Baseline samples had lower coverage at MM-specific chromatin regions than MRD timepoints (p < 0.05; baseline mean = 0.982; MRD-positive = 0.989; MRD-negative = 0.994; healthy = 0.993), suggesting higher transcriptional activity pre-treatment. MRD-negative samples had higher coverage than MRD-positive cases (p < 0.01). Using logistic regression, we assessed the predictive performance of FS and coverage at MM-specific sites. FS alone achieved an AUC of 0.632 (sensitivity [SN] 39.4%, specificity [SP] 92.1%, accuracy [AC] 67.6%). Coverage yielded an AUC of 0.681 (SN 75.8%, SP 60.5%, AC 67.6%). Combining FS and coverage at MM sites improved performance (AUC = 0.734; SN 48.5%, SP 92.1%, AC 71.8%). We next evaluated whether adjusting the BM tumor cell percentage cutoff by MFC could improve performance. At 0.017% (1 in 5, 789 cells) for MRD positivity, the combined model’s accuracy reached 83% with an AUC of 0.757 (SN 17%, SP 97%). Conclusions: cfDNA fragmentomic analysis achieved high specificity (92-97%) in detecting MRD, providing a less invasive alternative to facilitate serial monitoring. While sensitivity remains an area for improvement, the high specificity of cfDNA makes it valuable for confirming MRD negativity and reducing invasive procedures. Future efforts aim to enhance sensitivity by integrating additional fragmentomic features. Citation Format: Dor D. Abelman, Jenna Eagles, Aimee Wong, Saumil Shah, Stephanie Pedersen, Stephenie Prokopec, David S. Scott, Sarah Bridges, Darrell White, Irwindeep Sandhu, Kevin Song, Esteban Braggio, Alli Murugesan, Anthony Reiman, Suzanne Trudel, Trevor J. Pugh. Tumor-independent monitoring of minimal residual disease in multiple myeloma using cfDNA fragmentomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3250.

Background: Mandible contour significantly influences facial appearance, framing the lower facial silhouette. Redefining mandibular contour is key for facial and neck rejuvenation. Yet, there is limited facial aging research across different lifespans and sexes. Here, we utilize artificial intelligence and advanced 3-dimensional (3D) analysis to elucidate mandibular aging patterns in male and female subjects. Methods: A retrospective analysis of facial computed tomography scans in White patients was conducted, categorizing subjects into 3 age groups (20–79 y) and stratifying them by sex. Artificial intelligence–assisted segmentation into 3D mandibles was done in Mimics v.25, and statistical shape modeling was used to create an average mandible for each group. Volume and linear measurements were assessed via 3D overlays. Results: Analysis of 280 mandibles demonstrated statistically significant aging changes in both sexes. Ramus height showed a marked decrease with age, by approximately 5.3 mm in women and 4.2 mm in men (P < 0.001). Interrami and intercondylar widths increased by a mean of 4–5 mm (P < 0.01). Women exhibited an increase in mandibular angle (P < 0.01), and bony resorption over the chin compared to men, who exhibited concentrated bone resorption at the gonion projection. Conclusions: Mandibular aging, independent of tooth loss, exhibits specific bone remodeling patterns by sex. Posteriorly, mandibular widths increase in both sexes, whereas ramus height decreases. Women experience more resorption at the anterior alveolar surface and chin than men. Statistical shape modeling effectively visualizes these patterns on a population level, bridging the gap between traditional aging research and current understanding.

This case series examines long-term outcomes for 2 aquaporin-4-IgG (AQP4-IgG)–positive patients with neuromyelitis optica spectrum disorder (NMOSD) who underwent autologous hematopoietic stem cell transplantation with a nonmyeloablative conditioning regimen and rituximab.

Hypertrophic olivary degeneration (HOD) is a rare condition characterized by degeneration and hypertrophy of the inferior olivary nucleus (ION) in the brainstem. This case report presents a 39-year-old woman with HOD undergoing left total shoulder arthroplasty. Despite long-standing concerns about regional anesthesia in patients with central nervous system disorders, an interscalene catheter was placed using ultrasound and nerve stimulation guidance. The patient experienced effective analgesia without new neurologic deficits. This report highlights the safe use of regional anesthesia in patients with HOD and underscores the need for individualized anesthetic management and further research to establish clear guidelines.

Background: Pediatric thumb ulnar collateral ligament (UCL) injuries usually have osseous involvement presenting as a Salter-Harris III avulsion fracture from the base of the proximal phalanx. There is limited guidance about when surgical or non-surgical treatment is more appropriate. Methods: Patients with thumb bony UCL injuries who presented to a large pediatric hospital between 2007 and 2017 were retrospectively identified. Demographics, fracture pattern, treatment, clinical course, and outcomes were collected. Radiographic measurements included size and displacement of fracture fragment as a percentage of the proximal phalanx base articular surface. A classification system was developed incorporating clinical stability of the metacarpophalangeal joint and quantity of displacement. Results: Sixty-five patients were included (47 males and 18 females). The mean age at time of injury was 14.8 SD 1.9 yrs old. 46 (71%) injuries occurred during sporting activities. 50 (77%) patients underwent nonsurgical management with immobilization, and 15 (23%) patients were treated surgically with open reduction internal fixation. For patients treated surgically, the mean fragment size was 28.2% SD 6.8% of the articular surface compared to 14.3% SD 12.5% of those treated non-surgically (P<0.0001). The mean fracture displacement for surgically treated patients was 32.7% SD 19.0% compared to 11.4% SD 7.3% of those treated non-surgically (P<0.0001). Overall, 100% of patients reported they were able to return to their previous level of activity. Conclusion: Many pediatric thumb bony UCL injuries can be treated non-surgically. A classification system based upon joint stability and fracture displacement may help guide appropriate management of these injuries.

Objective: Review the current literature for available treatments for acute cholecystitis (AC) in nonsurgical candidates and provide guidelines for the management of these patients. Background: Cholecystectomy is the gold-standard treatment modality for AC. A considerable number of patients who are not eligible for surgery are managed by percutaneous and endoscopic techniques. There is recent data regarding endoscopic ultrasound-guided gallbladder drainage and emerging percutaneous approaches to address cholelithiasis and remove drains. Methods: An expert panel of surgeons, gastroenterologists, and interventional radiologists reviewed the current literature and provided recommendations for AC management in nonsurgical candidates. Recommendations were based on relevant evidence, with quality and strength assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Results: Percutaneous cholecystostomy is advised for patients ineligible for lumen-apposing metal stent (LAMS) or with reversible conditions, aiming to bridge to cholecystectomy. The optimal timing of cholecystectomy after percutaneous cholecystostomy remains unclear. In cases where surgery is not feasible, potential definitive treatments such as percutaneous cholecystolithotripsy/lithectomy and cholecystoduodenal stenting should be considered. For calculous AC, endoscopic ultrasound-guided gallbladder drainage with LAMS is recommended as a therapy for never-surgical candidates if they are eligible for monitored anesthesia care or general anesthesia and there is institutional expertise and minimal intervening ascites. Conclusions: The management of AC in nonsurgical candidates remains a challenge, with institutional protocols varying based on physician preferences and expertise. The proposed protocol integrates percutaneous and endoscopic approaches and emphasizes the need for multidisciplinary collaboration. Further research is required to evaluate these evolving management techniques, as the current literature is limited.