Citations

AbstractBackgroundOvarian juvenile granulosa cell tumors (juvGCT) are rare sex cord‐stromal tumors that occur primarily in children and adolescents. This study summarizes the clinical presentation and outcomes of patients with juvGCT.MethodsPatients were enrolled in the International Ovarian and Testicular Stromal Tumor and/or International Pleuropulmonary Blastoma/DICER1 Registries. Available medical records were abstracted, and pathology was centrally reviewed. Surgical staging was classified using the 2014 International Federation of Gynecology and Obstetrics (FIGO) criteria.ResultsIn total, 70 patients with juvGCT enrolled and were diagnosed between 2001 and 2024; most patients (81%, 57 of 70) presented with FIGO stage I disease. Adjuvant chemotherapy was given in 30% (21 of 70); all regimens were platinum‐based. Three‐year event‐free survival among patients with stage IA tumors was 80.2% (95% confidence interval [CI], 62.4%–100.0%), IC1 was 87.4 (95% CI, 72.4%–100.0%), IC2‐IC3 was 63.6% (95% CI, 40.7%–99.5%), and II‐IV was 48% (95% CI, 24.6%–93.8%). Of the patients with recurrent juvGCT with known mitotic index (MI), all had MI greater than 19 mitoses per 10 high power fields (HPF) at diagnosis.ConclusionOutcomes were worse for patients with FIGO stage ≥IC2 disease and for tumors with >19 mitoses per 10 HPF. Given the prognostic significance of MI, the authors strongly recommend the assessment of MI for all juvGCTs. More information about tumor biology is critical to identify which patients may benefit from adjuvant chemotherapy and to facilitate the development of novel therapies.

Abstract As obesity is increasing in prevalence and its associated morbidity and mortality are escalating worldwide, medications like tirzepatide are frequently used for weight loss benefits in patients without diabetes. Tirzepatide has rarely been associated with acute pancreatitis, but there are no reported cases of fulminant, necrotizing pancreatitis resulting in fatality. We present a case of fatal, fulminant, necrotizing pancreatitis in a 64-year-old low-risk female patient with recent tirzepatide initiation. Prior to starting this medication, a case-by-case risk benefit analysis should be performed for each patient. The importance of this should be emphasized by making necrotizing pancreatitis a boxed warning for tirzepatide.

Abstract Background Central sleep apnea (CSA) is characterized by recurrent central apneas during sleep and obstructive sleep apnea (OSA) is characterized by recurrent apneas during sleep due to upper airway obstruction. While OSA may be treated surgically, soft tissue surgery is not considered for treatment of CSA. Case Presentation We present the case of a patient with severe CSA with an Apnea/Hypopnea Index (AHI) of 122 and a central apnea index (CAI) of 74 who experienced complete resolution of CSA following tonsillectomy and expansion pharyngoplasty. Conclusions Although there is significant overlap between OSA and CSA, this is the first report of resolution of CSA following soft tissue surgical intervention in an adult. This suggests an unusual underlying pathophysiology, possibly post-arousal in nature.

Abstract The range of Babesia microti (Franca, 1910)-infected ticks is expanding, resulting in locally acquired human babesiosis cases occurring in new areas: Maryland (2009), the District of Columbia (2013), Virginia (2016), and West Virginia (2017). We collected host-seeking ticks from old fields, ecotones, forested habitats and animal hosts in Delaware, Maryland, and Virginia, 2010 to 2024. Ixodes scapularis Say, the tick vector of babesiosis, was captured in all 3 states. PCR revealed B. microti in 2.7% (36/1310) of I. scapularis, with site prevalence ranging from <1% to 12.5% infected. The first B. microti-positive I. scapularis was collected in Northampton County, Virginia, 2012. Of the B. microti-infected ticks, 50% (18/36) were coinfected with Borrelia burgdorferi and one was triple-infected with B. microti, B. burgdorferi, and Anaplasma phagocytophilum. We collected Ixodes keiransi Beati, Nava, Venzal, and Guglielmone ticks from Delaware and Virginia. We found B. microti and B. burgdorferi in those from Virginia, and B. burgdorferi in ticks from a shrew in Delaware. To our knowledge, this is the first report of B. microti and B. burgdorferi-positive I. keiransi from Virginia, and the first report of B. burgdorferi-positive I. keiransi from Delaware. Ixodes keiransi ticks rarely bite humans but are involved in the maintenance and spread of pathogens when sympatric with I. scapularis. We tested a subset of both tick species for Babesia duncani; none were positive. Jurisdictions in the southern mid-Atlantic region should expect babesiosis cases, and Lyme disease and anaplasmosis coinfections, and healthcare providers should consider these tick-borne infections as part of the differential diagnosis.

Abstract Recurrence after surgery remains a major cause of failure in head and neck squamous cell carcinoma (HNSCC), particularly for HPV-negative patients whose 2-year failure rate is > 50%. There is unmet need for an accurate diagnostic test that predicts risk of recurrence prior to adjuvant therapy selection. We evaluated ctDNA in lymphatic exudate (“lymph”) collected via surgical drains at 24 hours to detect molecular residual disease (MRD) and compared its performance to plasma and adverse pathology features. Lymph, plasma and blood were collected from 76 HPV- HNSCC patients 24 hours after surgery. Tumor tissue was collected at surgery. 73 patients passed QC. Samples were sequenced using a 699-gene custom panel to a median of 6322x (lymph and plasma cfDNA) or 533x (tumor and blood genomic DNA). Tumor variants were directly genotyped in lymph and plasma using a tumor-informed pipeline. MRD status was determined using a calibrated cutoff based on mean variant allele fraction. Wilcoxon signed-rank test was used for comparisons. Kaplan-Meier estimator with log-rank test and Cox proportional hazards model were used for survival analysis. We previously demonstrated that 24 hour postoperative lymph ctDNA detects recurrence in HPV(-) HNSCC across two independent multi-site cohorts and by orthogonal sequencing approaches (sensitivity (SN) = 72%, specificity (SP) = 65%, p = 0.003, hazard ratio (HR) = 3.1, n = 73). When compared to other data available at this early time point (pathology and 24 hour postoperative plasma), lymph ctDNA outperformed each for recurrence detection (extranodal extension (ENE, p = 0.30), lymphovascular invasion (p = 0.02), perineural invasion (p = 0.38), positive lymph nodes (p = 0.03), plasma (p = 0.8)). We next evaluated lymph ctDNA in a critical subpopulation: patients considered intermediate risk by pathology (negative for ENE or margins but with one or more other adverse pathologic feature). Current NCCN guidelines recommend radiotherapy and to “consider systemic therapy” for these patients. Lymph ctDNA accurately stratified recurrence in this group with high sensitivity (SN = 88%, SP = 69%; P = 0.013, HR = 9.1, n = 24). Within this cohort, 77% of patients who received RT alone and later recurred were positive for lymph ctDNA at 24 hours, suggesting an opportunity to use molecular data in concert with pathology to identify patients who may benefit from adjuvant treatment intensification. Postoperative lymph represents a novel proximal analyte for MRD detection in HPV- HNSCC designed specifically for use in the immediate post-surgical window when adjuvant therapy decisions must be made. Lymph ctDNA is significantly associated with recurrence and outperforms both time-matched plasma and pathology. Accurate MRD identification at this early timepoint has the potential to augment traditional pathology and personalize adjuvant treatment paradigms in HPV-negative HNSCC. Citation Format: Seka Lazare, Zhuosheng Gu, Noah Earland, Adam Harmon, Maciej Pacula, Megan Long, Ashley Tellis, Damion Whitfield, Adam Benson, Lucien Khalil, Robert L. Ferris, Marra Francis, Aadel A. Chaudhuri, Jose P. Zevallos, Wendy Winckler. Postoperative lymphatic exudate in HPV-negative head and neck cancer detects recurrence prior to adjuvant treatment decisions [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 1946.

Abstract Hospital medicine (HM), a well‐established clinical specialty, requires clarity of research priorities to identify target areas for investment in HM research infrastructure and activities. The Society of Hospital Medicine's Research Committee developed a 20‐item survey and used purposeful sampling of US hospitalist leaders to prioritize primary research topic domains and subdomains. Respondents were asked to rank their HM research priorities using a scale (1 [highest] to 8 [lowest]). Of 239 surveys distributed, 81 (34%) responded. Respondents were predominantly White (53%) and from academic institutions (57%). “ Overall, 46% of respondents were male and 33% were female. ” Top‐ranked research domains were innovation in care delivery (median 2, IQR 1,3), value‐based care (median 3.5, IQR 2,6), and health disparities (median 4, IQR 2,5). This survey identified top HM research priorities including systems‐based topics and health disparities, aligning with HM's identity as a specialty focused on improving systems of care and inequities in care.

Experimental analyses of knee joint contractures have traditionally utilized a 6-month rabbit model as the gold standard. However, this model is time-intensive and costly. The purpose of this study was to develop an abbreviated rabbit model of knee contractures and compare it to the well-established longer model. Twenty female New Zealand White rabbits were divided into two equal groups and prospectively studied to assess knee passive extension angles (PEA), contracture angles (CA), and terminal posterior capsular stiffness. Experimental knees were immobilized for either 4 weeks ( n = 10) with an 8-week remobilization period in the abbreviated model (i.e., 3 months) or for 8 weeks ( n = 10) with a 16-week remobilization period in the standard model (i.e., 6 months). PEAs were assessed at remobilization and several time points using differing vertical forces. At sacrifice, terminal biomechanical data were collected to assess posterior capsular stiffness. Analysis of PEAs in live animals at each torque value and time point demonstrated increased PEAs and decreased CAs in the 3-month abbreviated model as compared to the 6-month standard model. At sacrifice, biomechanical analysis demonstrated that the posterior capsules of the 3-month experimental limbs were significantly more stiff than the contralateral limb (2.4 vs. 0.05 Ncm/°, p < 0.0001), but significantly less stiff compared to the 6-month experimental limbs (2.4 vs. 4.7 Ncm/°, p < 0.0001). Our study suggests that the 6-month standard rabbit knee model of arthrofibrosis should continue to be used in the laboratory assessment of arthrofibrosis. However, the abbreviated model may be beneficial under selected experimental conditions.

AimsTo evaluate the role of autophagy in primary knee fibroblasts undergoing myofibroblast differentiation as an in vitro model of arthrofibrosis, a complication after total knee arthroplasty characterized by aberrant intra-articular scar tissue formation and limited range of motion.MethodsWe conducted a therapeutic screen of autophagic-modulating therapies in primary human knee fibroblasts undergoing transforming growth factor-beta 1 (TGF-β1)-mediated myofibroblast differentiation. Autophagy was induced pharmacologically with rapamycin or by amino acid deprivation. Picrosirius red staining was performed to quantify collagen deposition. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were conducted to evaluate fibrotic gene expression levels.ResultsRapamycin, an mTOR complex 1 (mTORC1) inhibitor and autophagy inducer, reduced TGF-β1-mediated collagen deposition. Interestingly, we simultaneously report that myofibrogenic genes, including ACTA2, were highly upregulated following rapamycin-TGF-β1 treatment. When autophagy was induced through amino acid deprivation, we demonstrated suppressed extracellular matrix levels, fibrotic gene expression (e.g. ACTA2), and SMAD2 phosphorylation levels in TGF-β1-stimulated fibroblasts.ConclusionOur findings demonstrate that the induction of cellular autophagy suppresses TGF-β1-induced collagen deposition in primary human knee fibroblasts. Taken together, these data suggest that cellular autophagy may be prophylactic against the pathogenesis of arthrofibrosis.Cite this article: Bone Joint Res 2025;14(4):328–337.