Citations

Abstract Stress injuries of the lunate are rare and have been occasionally described in tennis players. Previously reported cases typically involve bone marrow edema or incomplete stress reactions. We report two elite tennis players presenting with advanced lunate stress fractures that were initially interpreted as Kienböck disease. A retrospective review was performed of patients presenting with lunate fractures in association with competitive tennis playing. Presenting symptoms, imaging studies, treatment, and outcomes were evaluated. Healing was assessed on serial computed tomography (CT) scans by the treating surgeon and was defined as osseous continuity across the fracture site on sagittal and axial slices. A literature review was performed of the world English literature. Magnetic resonance imaging (MRI) demonstrated lunate abnormalities in both athletes. CT imaging revealed a distinct fracture line involving the dorsal aspect of the lunate with associated fragment sclerosis. Conservative management failed to resolve symptoms. Surgical treatment consisted of fragment excision in one case and internal fixation in the other. Both patients returned to play. Lunate stress fractures should be considered in tennis players presenting with long-standing dorsal wrist pain. These lesions may mimic Kienböck disease on MRI, and CT can provide valuable information for diagnostic confirmation in advanced stages. Conservative treatment may be inadequate to return patients to competitive tennis. IV.

ABSTRACT Studies in humans and murine models have pointed towards a possible link between metabolic syndrome, which shows insulin resistance and metabolic dysregulation, and Alzheimer’s disease (AD) pathology marked by amyloid-beta (Aβ) accumulation at the BBB and hypometabolism in the brain. Yet, the underlying biological mechanisms by which metabolic syndrome affects these pathological changes in AD brain remain unknown. We hypothesized that insulin resistance is responsible for alterations in blood-brain barrier (BBB) transport of Aβ peptides and glucose. This hypothesis was tested by employing radiolabeled tracers ( 125 I-Aβ40, 125 I-Aβ42, and 18 F-FDG) in high-fat diet (HFD)-fed mouse models that manifest metabolic syndrome. Further, we assessed alterations in the expression of various molecular mediators within the brain microcapillaries harvested from both low-fat diet (LFD)-fed and HFD-fed mice. As expected, our studies show that HFD- fed mice developed peripheral insulin resistance and obesity. In addition, HFD-fed mice demonstrated an increase in the influx rate of Aβ peptides and a reduction in 18 F-FDG (a glucose surrogate) influx rate at the BBB compared to LFD-fed mice. These transport changes are associated with increase in the BBB endothelial expression of RAGE (receptor to traffic Aβ from plasma-to-brain) and a reduction of GLUT1 (glucose transporter) expression in HFD-fed mice compared to LFD-fed mice. Moreover, disruption in insulin signaling, as indicated by reduced pAKT and pERK expression, was observed in HFD-fed mice. Inhibiting AKT or ERK phosphorylation with specific inhibitors resulted in similar changes in Aβ and glucose uptake in polarized BBB endothelial cell monolayers in vitro. These results indicate that HFD induced metabolic syndrome may lead to BBB dysfunction, characterized by increased plasma-to-brain Aβ trafficking and diminished glucose transport at the BBB, thereby aggravating the expression of AD pathological hallmarks.

Primary mediastinal B-cell lymphoma (PMBCL) is a rare form of large B-cell lymphoma (LBCL) with around 90% of patients cured with frontline treatment. For relapsed or refractory (R/R) disease, the optimal treatment is unclear. CD19 chimeric antigen receptor-T cell (CAR-T) has been established as the preferred second line (2L) treatment for primary refractory or early relapsing LBCL based on the overall survival benefits observed in the landmark phase III trials. However, PMBCL patients were underrepresented on these pivotal studies. This study evaluated outcomes of 252 patients treated with 2L therapies for R/R PMBCL at 14 US institutions between 2001 and 2025. Platinum-based salvage with intent to proceed to high dose therapy and autologous stem cell transplant (HDT/ASCT) (platinum cohort) and CD19 CAR-T (CAR-T cohort) were given as 2L therapy in the real-world setting in 157 and 26 patients, respectively. Overall response rate (ORR), complete response (CR) rate and median progression-free survival (PFS) were significantly higher in the CAR-T cohort compared with the platinum cohort (ORR: 91.3% vs 44.2%, p <0.001; CR 65.2% vs 14.7%, p<0.001; median PFS not reached vs 3.5 months, hazard ratio (HR) 0.28, 95% CI 0.15-0.54, p=0.001). No significant difference was observed in overall survival. This study demonstrated superior response rate and PFS of CD19 CAR-T over platinum-based salvage with intent to proceed to HDT/ASCT as 2L treatment for R/R PMBCL.

Myeloproliferative neoplasm (MPN) patients are at risk of splanchnic vein thromboses (SVT). Prior studies have failed to demonstrate a benefit of hydroxyurea therapy in preventing recurrent thrombosis after SVT, but are limited by small sample sizes and inability to account for starting, stopping, or switching of cytoreductive therapies. To better assess the impact of cytoreductive therapy on thrombosis recurrence, we performed a retrospective cohort study of MPN-SVT patients from the international GASTRO-MPN Consortium, treating cytoreductive therapy as a time-dependent covariate. We identified 757 patients, of which 43% were treated with cytoreductive therapy. During a median follow-up of 7.4 years, 256 patients (34%) had thrombosis recurrence; 145 (19%) had SVT extension/recurrence/TIPS thrombosis, 138 (18%) an thrombosis recurrence outside the splanchnic bed (74% were venous). Additionally, 262 patients (35%) experienced clinically relevant bleeding and 170 (22%) died. After adjusting for age, sex, prior thrombosis, timing of MPN diagnosis relative to SVT, anticoagulation initiation within 30 days of SVT diagnosis, MPN type, JAK2 status, other cancers and cirrhosis, cytoreductive therapy was associated with a decreased risk of recurrent thrombosis (HR 0.67 95%CI 0.50-0.89, p=0.01). This was driven by a lower risk of SVT extension/recurrence (HR 0.62 95%CI 0.42-0.90, p=0.01) but not by extra-splanchnic thrombosis recurrence (HR 0.97 95%CI 0.72-1.30, p=0.82). In a subgroup of patients without erythrocytosis/thrombocytosis at initial SVT (n=275), cytoreductive therapy was associated with a HR 0.65 (95%CI 0.40-1.07, p=0.09) for recurrent thrombosis. These data support the use of cytoreductive therapy in MPN-SVT patients to prevent recurrent thrombosis, particularly SVT extension/recurrence.

PURPOSE EA1181 (ClinicalTrials.gov identifier: NCT04266249 ) is a single-arm trial evaluating neoadjuvant taxane, trastuzumab, and pertuzumab (THP) in patients with clinical stage II/IIIa human epidermal growth factor receptor 2 (HER2)–positive breast cancer. This report focuses on the secondary end points of pathologic complete response (pCR) rates and associated factors. The primary end point—3-year recurrence-free survival among patients achieving a pCR (ypT0/Tis, ypN0)—will be reported when data mature. METHODS Patients received four cycles of trastuzumab and pertuzumab (HP) with either once per week paclitaxel (12 weeks) or docetaxel (every 3 weeks for four cycles), followed by surgery. Clinicopathologic characteristics were assessed in all patients. The HER2DX pCR score was determined using diagnostic biopsy samples in a representative subset. Logistic regression models identified factors associated with pCR. RESULTS A total of 2,175 patients were enrolled (781 HER2+/estrogen receptor‑negative [ER–]; 1,394 HER2+/ER+). Of 2,141 patients who initiated THP, the overall pCR rate was 43.8%: 63.7% in HER2+/ER– and 32.4% in HER2+/ER+ tumors. Higher pCR rates were observed in tumors that were ER-negative or low ER expressing, progesterone receptor-negative or low expressing, HER2 immunohistochemistry (IHC) 3+, and in patients treated with once per week paclitaxel. T3 disease was associated with a lower pCR rate in HER2+/ER– tumors; otherwise, tumor (T) and nodal (N) stage did not significantly affect pCR. Among 569 patients assessed for HER2DX pCR scores, a high score was independently associated with higher pCR rates, after adjustment for clinicopathologic variables. CONCLUSION Neoadjuvant THP achieved pCR in nearly two-thirds of patients with HER2+/ER– and one third with HER2+/ER+ breast cancer. Low hormone receptor expression, HER2 IHC 3+ status, once per week paclitaxel use, and a high HER2DX pCR score were independent predictors of pCR. These findings should help optimize risk stratification and treatment personalization for patients with HER2-positive breast cancer.

Background Advanced chronic kidney disease (CKD) complicates anticoagulant treatment because thromboembolic and bleeding risks compete. We compared treatment outcomes for apixaban and rivaroxaban in adults with atrial fibrillation (AF) and stage 4/5 CKD. Methods Deidentified TriNetX records for patients treated with apixaban (n=49,698) and rivaroxaban (n=2660) underwent 1:1 propensity score matching (demographics, medications, procedures, laboratory values); 2533 matched pairs were identified (absolute standardized mean difference <0.10, indicating adequate balance). The smaller rivaroxaban cohort constrained matching; findings apply only to the matched population. Outcomes were assessed at 1, 3, and 5 years. Myocardial infarction (MI) findings were exploratory. P values were not adjusted for multiplicity. Results Gastrointestinal bleeding was lower for apixaban vs rivaroxaban (5-year: 9.3% vs 10.9%; relative risk [RR], 0.86; 95% CI, 0.71-1.02; P=.09). Cerebrovascular events were significantly higher for apixaban vs rivaroxaban at 3 years only (9.8% vs 7.9%; RR, 1.24; 95% CI, 1.01-1.53; P=.04); this association may reflect chance. Cerebral infarction was significantly higher for apixaban vs rivaroxaban at 1 year (3.0% vs 1.8%; RR, 1.61; 95% CI, 1.09-2.37; P=.02) and attenuated at 3 and 5 years. Rates of MI were nominally higher in the apixaban group. Five-year mortality risk was significantly lower for apixaban vs rivaroxaban (33.3% vs 36.1%; RR, 0.92; 95% CI, 0.86-0.10; P=.04) but differences in time-to-event survival were not significant. Conclusion Apixaban did not have greater bleeding risk than rivaroxaban and may be associated with lower gastrointestinal bleeding, a finding that requires further study. Isolated cerebrovascular, MI, and mortality findings require cautious interpretation. A mortality advantage for either drug was not established.

ABSTRACT A previously healthy 29-year-old man presented with abdominal pain and was found to have a liver mass with periductal infiltration and a stricture of the common bile duct, concerning for cholangiocarcinoma. Hepatic function panel disclosed alanine transaminase 293 U/L, aspartate aminotransferase 122 U/L, γ-glutamyl transferase 2019 U/L, normal total bilirubin, carcinoembryonic antigen, and carbohydrate antigen 19-9. Biopsy established the diagnosis of diffuse large B-cell lymphoma, with no underlying hepatic disease. He was started on polatuzumab-rituximab-cyclophosphamide-doxorubicin-prednisone chemotherapy and achieved complete tumor response. This case highlights the importance of a thorough evaluation of liver tumors and the critical role of tissue diagnosis.

Background Pericarditis may be associated with significant morbidity and mortality and can be a clinically challenging entity to diagnose. There is a clinical need for automated artificial intelligence (AI) algorithms to act as a screening aid to assist with the early and accurate detection of pericarditis. Methods We developed p-Cal, a browser-based pericarditis risk calculator that fuses the patient clinical data and 12-lead ECG image to estimate risk for pericarditis. The ECG encoder was designed based on a pretrained MedCLIP Vision Transformer and random forest classifier was used for the clinical tabular data. These two modalities were fused at the decision-level using a meta classifier. Model reasoning for both modalities was assessed using advanced explainable AI techniques—attention maps from the transformer model were used to interpret ECG images, while SHapley Additive exPlanations (SHAP) force plots were applied to analyse the tabular data. Results A total of 6508 patients (mean age 54.8±16.1 years, 50.9% female) were used for training and internal validation of the AI model, of whom 902 patients had a confirmed diagnosis of pericarditis (13.8%) and the remainder were normal controls. On 1302 hold-out test patients, the Fusion Model demonstrated the best discriminatory performance, achieving an area under the curve (AUC) of 0.89, which surpassed the ECG (AUC = 0.85) and the clinical data only models (AUC = 0.74) performance. On external validation in the Medical Information Mart for Intensive Care (MIMIC) Database, the fusion model achieved an AUC of 0.81. Conclusion A late fusion AI model integrating tabular clinical electronic medical record data and ECG signal has robust predictive capability for pericarditis as a screening tool.

This slideshow presentation provides a practical image-based road map to essential spinal and pelvic radiographic measurements, with stepwise instructions and reference values, for assessment and management of spinal disorders.