Citations

Background Cancers persist despite expression of immunogenic neoantigens and ongoing antitumor immune responses. While some occult tumors likely are cleared by effective antitumor immune responses, the targeted antigens are not easily identifiable as those tumors spontaneously disappear. Methods We used mouse models with a defined antigenic protein mimicking tumor-specific neoantigens to address the nature of these spontaneous anti-tumor immune responses. Results BALB/c (H-2d ) mice challenged with BALB/c breast tumors expressing the rat-erbB2 oncoprotein succumb to their tumors despite ongoing immune responses targeting tumor-specific model antigens. Meanwhile, congenic BALB.B (H-2b ) and H-2d/H-2b F1 hybrid mice spontaneously eliminate genetically matched tumors in a major histocompatibility complex (MHC)-II dependent manner. Adoptive transfer and immune cell depletion strategies revealed CD4+ T cells and CD20+ B cells are crucial mediators of the protective response in H-2b mice. Furthermore, passive transfer of immune serum from mice rejecting their tumors confers resistance in tumor antigen-tolerant animals with an inversely proportional relationship between tumor outgrowth and the amount of rat-erbB2 specific antibody present in tumor-bearing mice. Introduction of the rat-erb2 ectodomain into other H-2b tumor models also promotes their spontaneous tumor rejection. Notably, the tumor microenvironments differ in rat-erbB2+ tumor-bearing BALB.B and BALB/c mice at the time of fate decision in the models reflecting the differences between effective and ineffective tumor immune responses. Conclusions We find that the effective antitumor immunity targeting neoantigens in these breast cancer models is determined by MHC-II-restricted presentation of optimal cancer-associated antigens. These responses are dependent on CD4+ T cells, B cells, and antigen-specific antibodies.

Background: Various medial patellofemoral ligament (MPFL) reconstruction techniques have been developed to minimize risks to the physis in skeletally immature patients. Purpose: To examine outcomes of MPFL reconstruction (MPFLR) based on fixation technique in skeletally immature patients. Study Design: Systematic review; Level of evidence, 4. Methods: PubMed, Scopus, Ovid, Cochrane Library, and CINAHL databases were searched for the literature on outcomes of MPFLR in the pediatric population, utilizing various anatomic and nonanatomic techniques. Primary outcomes were postoperative redislocation rates, return-to-sports (RTS) rates, and patient-reported outcomes (PROs). Moreover, outcomes involving sequela of growth plate disturbance were collected. Results: The final analysis included 17 studies—2 using sling-based techniques, 3 using surface-based techniques, 5 using soft tissue realignments, and 7 utilizing transosseous femoral fixations. Higher rates of postoperative redislocation were found in the sling-based (14.8%) and distal soft tissue realignment using semitendinosus tenodesis (38%) techniques, while lower rates were noted with surface-based (1.3%) and transosseous (3.4%) techniques. For PROs, there were large amounts of heterogeneity among studies, but all reported postoperative improvements, with more positive PROs generally seen in anatomic reconstructions. The RTS rate was 100% for surface-based techniques, 79.4% for distal soft tissue realignments, 79.5% for soft tissue realignment techniques, and 83.2% for transosseous techniques. No negative outcomes as a sequela of growth plate disturbance were reported. Conclusion: Nonanatomic techniques—such as sling-based and distal soft tissue realignment techniques—have higher rates of redislocation and lower RTS rates in skeletally immature patients undergoing MPFLR. Surface-based and transosseous tunnel-based techniques were shown to have lower redislocation and higher RTS rates. Clinical Relevance: This review provides insight into the most appropriate surgical management of patellar instability in patients with open growth plates.

Background: Benefits of hospice care, such as improvement in quality of life and reduced costs, depend on duration of enrollment in hospice services, making timely hospice referral essential. Patient-, provider-, and system-level factors associated with hospice referral timing and length of stay (LOS) are unclear. 1 – 6 Objective: To review existing hospice referral patterns to identify patient- and system-level factors associated with hospice LOS. Methods: We performed a retrospective review of all adult patients referred from our institution (located in Rochester, Minnesota, USA) to a nonprofit hospice agency between 2013 and 2017. The primary dependent variable was hospice LOS. Patient-level variables included demographic characteristics, place of residence, and hospice diagnosis. System-level variables included referral setting and provider-specific variables, such as title and gender. Statistical analyses were performed using multivariate logistic regression. Results: A total of 2072 patients were referred to hospice during the study period. Patient-level factors associated with LOS included hospice diagnosis and place of residence. Patients referred for cancer had a higher odds of a long LOS, while patients from long-term care facilities had a higher odds of a short LOS. System-level factors associated with LOS included provider gender and title. Referral by a female provider or by a physician, rather than an advanced practice provider, was associated with a lower odds of a short LOS. Conclusion: Based on a review of hospice referral patterns, the integration of hospice care into subspecialty practices, long-term care facilities, and advanced practice education could be an effective strategy to improve hospice LOS.

Background and Aims: Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) prevent fibrosis progression in a preclinical model of steatotic liver disease. Our objective was to assess the impact of ACEi/ARB use on clinical outcomes in patients with metabolic dysfunction–associated steatotic liver diseases. Approach and Results: Using TriNetX, a nationwide database, we identified all patients with metabolic dysfunction–associated steatotic liver diseases from January 1, 2011, to December 31, 2019. Using a target trial emulation framework, ACEi/ARB users were matched with calcium channel blocker (CCB) users using propensity score matching (PSM). Patients were followed up to 10 years after the index date. Cox proportional hazards regression was used to determine the risk of mortality, major adverse liver outcomes, major adverse cardiac events, and incident cancers. Of the 35,988 eligible patients, 28,423 were ACEi/ARB users, and 7565 were CCB users. After PSM, 7238 pairs were well-balanced. ACEi/ARB use was associated with a significantly decreased mortality risk (HR: 0.59, 95% CI: 0.51–0.68). ACEi/ARB was associated with a significantly reduced risk of developing major adverse liver outcomes (HR: 0.70, 95% CI: 0.61–0.80), including ascites (HR: 0.78, 95% CI: 0.63–0.98) and HE (HR: 0.67, 95% CI: 0.57–0.78). ACEi/ARB use was also associated with a lower risk of major adverse cardiac events (HR: 0.82, 95% CI: 0.76–0.90) but not incident cancer (HR: 0.97, 95% CI: 0.86-1.10) compared with CCB. Conclusions: ACEi/ARB use in patients with metabolic dysfunction–associated steatotic liver diseases was associated with a reduced risk of mortality, major adverse liver outcomes, and major adverse cardiac events compared with CCB use. A large prospective study is needed for external validation.

Abstract Background Adults with congenital heart disease (ACHD) frequently experience gaps in lifelong ACHD specialty care, leading to preventable complications, hospitalizations, and premature mortality. However, effective, scalable, accessible, and sustainable strategies to reduce these gaps are lacking. Digital health offers potential solutions but requires a rigorous scientific approach in its design to address the needs of the target population. Objective To describe the development of a theory-based, community co-designed digital health intervention to improve lifelong ACHD care. Methods We integrated theory-based behavioral frameworks, semi-structured qualitative interviews with patients and clinicians, and a community-engaged approach to develop a digital health intervention for ACHD. The primary behavioral target was completing an ACHD specialist appointment. We conducted Capability, Opportunity, Motivation, and Behavior (COM-B)-guided semi-structured interviews with ACHD patients and clinicians to identify barriers to specialized care amenable to a digital intervention and patient-centered goals for the digital tool. The community partners helped develop key intervention objectives, create a theory-driven framework, and specify how each intervention component targets specific COM-B barriers. Results We interviewed 54 participants (37 ACHD patients and 17 clinicians) and engaged 21 community partners representing 4 advocacy organizations. Design objectives emphasized addressing patient loneliness, ensuring accessibility and credibility, and enabling scalability while centering patient perspectives. Participants identified four priorities: providing credible resources, uplifting patient voices, customizing to patient needs, and centering positivity and joy. The digital tool, named by community partners as Empower My Congenital Heart (EMCH), was designed within the web- and mobile-based, Apple- and Android-compatible, Eureka Digital Research platform (University of California, San Francisco). Key intervention components included educational modules, peer support, appointment planning nudges, and a digital medical passport. The EMCH’s theory-driven framework specifies how each intervention component targets specific COM-B barriers to specialized ACHD care. Conclusions The theory-driven, community co-designed EMCH digital tool is a rapidly scalable approach to improve guideline-recommended specialized ACHD care. Future studies will evaluate the acceptability, feasibility, effectiveness, and implementation outcomes to provide insight into a novel tool to reduce preventable morbidity and mortality in ACHD. Trial Registration The National Clinical Trial number for this study is NCT06581484 .

Spatial heterogeneity of liver viscoelasticity, measured at three-dimensional vector MR elastography, positively correlated with metabolic dysfunction–associated steatotic liver disease progression.

Abstract Purpose: 1) To report the clinical outcomes and reoperation rates of arthro- and endo-scopic iliopsoas release at short-term follow-up following ipsilateral total hip arthroplasty from two separate medical institutions, and 2) to evaluate whether demographic and radiographic parameters are associated with postoperative patient reported outcomes. Methods: Patients with iliopsoas tendinitis in the setting of prior THA that underwent arthroscopic iliopsoas fractional lengthening from 1988 – 2023 were reviewed at two academic institutions. Patients were included if they had minimum 12-month follow-up and were evaluated for preoperative anterior acetabular component overhang, surgery satisfaction, postoperative subjective hip flexion strength and anterior groin pain improvement, modified Harris Hip Score (mHHS), Single Assessment Numeric Evaluation (SANE) score, Tegner activity scale, visual analog scale (VAS), and revision hip arthroplasty. Results: Sixty hips in 58 patients (19 males, 39 females) were followed for a mean of 39.3 (12.0-105.9) months postoperatively. 77% of patients reported feeling “much” or “slightly better”, 75% reported improved anterior groin pain, and 60% reported improved subjective hip flexion strength. Surgery satisfaction was 7.2 ± 3.3 (scale of 0 to 10). Mean postoperative mHHS, VAS pain at rest, VAS pain with use, and SANE scores were 73.9 ± 19.4, 1.3 ± 2.4, 3.8 ± 2.9, and 71.9 ± 21.9 respectively. Preoperative anterior acetabular component overhang was 3.3 ± 6.5 mm and didn’t significantly correlate with postoperative PROs (p ≥ 0.45). Tegner score improved to 2.9 ± 1.4 from 2.5 ± 1.7 preoperatively (p = 0.0253). Three patients underwent revision arthroplasty at a mean of 25.3 (11.6 – 40.4) months postoperatively, with an acetabular component revision rate of 3.3%. Conclusions: Satisfactory outcomes and low revision arthroplasty rates were observed in patients undergoing arthroscopic iliopsoas lengthening following THA. There was no statistically significant relationship between anterior acetabular component overhang and final PROs. Level of Evidence: IV; Retrospective Case Series

Background and Aims: Immunotherapy has emerged as an effective treatment for advanced HCC. We aimed to investigate the real-world effectiveness of immunotherapy compared to lenvatinib in HCC. Approach and Results: From the TriNetX database, we used a target trial emulation framework and identified patients with HCC who received first-line treatment with immunotherapy (atezolizumab/bevacizumab or tremelimumab/durvalumab) or lenvatinib between or between August 2018 and December 2023. OS was compared using Kaplan-Meier analysis and Cox proportional hazards regression. After propensity score matching, 1203 patients were included in each group. Immunotherapy was associated with improved OS versus lenvatinib (median survival: 545 vs. 425 d; HR: 0.86, 95% CI: 0.76–0.97). Regarding treatment type, atezolizumab plus bevacizumab showed improved survival compared to lenvatinib (n=1070 in each group; HR: 0.87, 95% CI: 0.77–0.99), while the point estimate favored durvalumab plus tremelimumab versus lenvatinib (HR: 0.81, 95% CI: 0.59–1.12), though this difference was not statistically significant, likely due to small sample size. Regarding etiology, immunotherapy had improved OS compared to lenvatinib in viral hepatitis (n=510 in each group; HR: 0.74, 95% CI: 0.61–0.89) and alcohol-associated liver disease (n=190 in each group; HR: 0.65, 95% CI: 0.49–0.87), but not in metabolic dysfunction–associated steatotic liver diseases (n=156 in each group; HR: 0.96, 95% CI: 0.70–1.31). Conclusions: In this real-world analysis, immunotherapy was associated with improved OS compared to lenvatinib in advanced HCC, with consistent benefit across most subgroups. These findings support the use of immunotherapy as a first-line treatment for advanced HCC.