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Background: Progressive heart failure cardiogenic shock (HFCS) often requires escalation to temporary or durable mechanical circulatory support (MCS) as a bridge to transplant (BTT). Following the 2018 UNOS allocation changes, our center revised its BTT strategy to optimize support and shorten wait times. At our institution, the Impella 5.5 with SmartAssist via the axillary approach was selectively used for patients who remained refractory to guideline-directed medical therapy, failed single-inotrope therapy, and were not considered suitable durable LVAD candidates by our multidisciplinary heart team. We compared transplant-related outcomes of BTT patients supported with Impella 5.5 versus durable LVAD. Methods: We performed a single-center retrospective review of all heart and heart/kidney transplant candidates at Mayo Clinic Florida from October 2018 to February 2021. INTERMACS profile, baseline characteristics, and perioperative data were collected at the time of device implantation and throughout the transplant hospitalization. Results: A total of 87 heart and 4 heart–kidney transplants were completed. Forty-five patients (49%) required MCS as BTT: 27 (60%) with a durable LVAD and 18 (40%) with an Impella 5.5. All eighteen patients with Impella 5.5 as BTT (100%) were transplanted compared to nineteen patients with durable LVAD (70%), p = 0.001. The median time from listing to transplant was substantially shorter with Impella (32 vs. 696 days, p < 0.001), and this difference persisted across INTERMACS profiles. UNOS status at transplant was more urgent for Impella than LVAD (p < 0.001). Transplant surgery following Impella support required shorter cardiopulmonary bypass time (181 vs. 219 min, p < 0.001) and resulted in lower postoperative vasoactive-inotropic requirements (7.9 vs. 13, p = 0.003). No patients in the Impella group died or were delisted while awaiting transplant, whereas 5 LVAD patients (26%) died or were removed due to LVAD complications (p < 0.001). Conclusions: Our data demonstrates that the use of the Impella 5.5 as BTT was associated with significantly shorter waitlist time, higher transplantation rates, reduced perioperative morbidity, and lower postoperative vasoactive support compared with durable LVAD as BTT. These benefits were achieved despite a higher severity of illness at transplantation in the Impella cohort.

Background: HIV outcomes in people with HIV (PWH) are suboptimal and inequitably distributed in the United States. Long-acting injectable antiretroviral therapy (LAI-ART) has potential to make important contributions to improving HIV outcomes and quality of life for PWH. Methods: The SELIGO Study used a 1-time, 20-minute survey of 801 PWH from the Center for AIDS Research Network of Integrated Clinical Systems cohort in 3 US cities (Boston, MA; Chapel Hill, NC; San Diego, CA) that included 54 items. Using multinomial and binary logistic regression, we assessed factors associated with LAI-ART versus daily oral ART preferences. Results: Most participants were cisgender men (82.3%); 57.0% identified as racial and/or ethnic minorities; mean years of age, 52.2; mean years living with HIV, 18.1; 2.8% were using LAI-ART. Compared with daily oral ART, 56.9% preferred LAI-ART administered monthly, and 68.0% preferred LAI-ART administered every 2 months. Factors associated with greater odds of LAI-ART preference included medication/contraception injection experience, pill burden, no medication other than ART, 4 or more clinic visits per year, detectable viral load, reporting a higher number of HIV treatment considerations, and identifying as Black. Factors associated with decreased odds of LAI-ART preference included older age, identifying as neither gay nor straight, living > 1 hour from the clinic, and considerable/extreme needle fear. Conclusions: Findings demonstrate that although there is considerable interest in LAI-ART, HIV treatment modality preferences are multifaceted. Shared decision making can ensure that conversations about ART options consistently address specific factors across diverse groups to facilitate equitable LAI-ART uptake.

Background and Aims: Cholangiocarcinoma (CCA) is one of the most lethal cancers, characterized by molecular heterogeneity and treatment resistance. To uncover new biological signals and therapeutic opportunities, we employed multiomic characterization combined with machine learning. Approach and Results: We profiled all anatomical CCA subtypes using whole exome sequencing, mRNA sequencing, and proteome/phosphoproteome analysis. Integrative dimensional reduction revealed RNA, protein, and phosphoprotein features driving tumor heterogeneity, enabling clustering. Machine learning algorithms identified molecular features for each cluster and mapped external datasets and patient-derived xenograft (PDX) models onto these clusters. Kinase enrichment analysis highlighted targetable kinases active in each cluster. In vivo validation was performed in cluster-specific PDX models using the selective TNK1 inhibitor, TP-5801. We identified 3 molecular clusters with distinct pathway characterization: immunomodulatory (cluster 1), metabolic (cluster 2), and gene regulation/cellular fate (cluster 3). Cluster assignment was independent of anatomic subtype but correlated with overall survival following curative-intent resection. We also identified multiomic features and pathways linked to overall survival and lymph node metastases, crucial for patient treatment selection. Kinase enrichment analysis pinpointed TNK1 as a highly active kinase in the metabolic cluster. Treatment with TP-5801 significantly reduced tumor growth in a metabolic PDX model, but not in models representing the other clusters. Combining internal data with publicly available datasets, we identified the immunomodulatory cluster as most responsive to gemcitabine/cisplatin therapy, confirmed in vivo using cluster-specific PDX models. Conclusions: Integrated multiomic characterization provides translational insights by defining unique molecular subtypes associated both with therapeutic response and overall clinical outcomes. This approach identified TNK1 as a previously unrecognized therapeutic target in a defined subset of CCA tumors.

Background: In skeletally immature patients, alternative surgical approaches should be undertaken for the treatment of patellofemoral instability that respect the open physis. Remaining growth can be exploited for correction of genu valgum, a known anatomic risk factor of patellofemoral instability. Indications: A skeletally immature 14-year-old boy with bilateral genu valgum and patella alta presented with symptomatic, recurrent left knee patellar instability precluding sports participation and causing dysfunction in his activities of daily living. Technique Description: A midline approach to the knee was used. Medial patellofemoral ligament reconstruction (MPFL-R) was completed up until the point of femoral-sided allograft fixation. The socket for femoral-sided graft fixation was reamed with an all-epiphyseal technique. Next, growth modulation with temporary hemiepiphysiodesis of the medial distal femoral physis was undertaken with an 8-plate bilaterally. Patellar tendon shortening was completed. Femoral-sided graft fixation for the MPFL-R was then completed. Results: There were no acute complications associated with surgery. Surgical management led to resolution of the patient’s patellar instability. The patient is being followed for timing of hemiepiphysiodesis plate removal. Discussion/Conclusion: In skeletally immature patients, a physeal-sparing MPFL-R is a viable treatment option to address recurrent patellar instability. Other anatomic risk factors, such as genu valgum and patella alta, may be concomitantly addressed using techniques that are respective of the open physis. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Background: Despite its use in patients awaiting heart transplant (HT), the impact of continuous inotropic support on short-term complications and long-term transplant outcomes remains unclear. This study evaluated inotrope use at the time of HT on perioperative complications and post-transplant survival, comparing outcomes at 30 days, 1 year, and 10 years with mechanical circulatory support (MCS) strategies including ECMO, IABP, and VADs. Methods: A retrospective analysis of the United Network for Organ sharing (UNOS) registry was performed, stratifying patients based on bridge strategy at the time of transplant: inotropes, ECMO, IABP, or VADs. Baseline characteristics, perioperative complications, and 30-day, 1-year, and 10-year post-transplant survival outcomes were analyzed across groups. Survival was assessed using Kaplan–Meier and Cox proportional hazards models. Results: Among the 11,801 heart transplant patients included, 9330 were on inotropes, 372 were on ECMO, 1072 received an IABP, and 1027 had VADs. Inotrope-bridged patients had significantly lower 30-day and 1-year mortality rates compared to the ECMO, IABP, and VAD groups. They also experienced reduced incidences of post-transplant dialysis and stroke. At 10 years, the inotrope group demonstrated superior long-term survival, with significantly lower mortality risk compared to ECMO (HR: 1.81; CI: 1.49–2.20, p < 0.001), IABP (HR: 1.19; CI: 1.06–1.32, p = 0.005), and VAD (HR: 1.18; CI: 1.10–1.27, p < 0.001). Conclusions: Continuous use of inotropes after waitlisting is associated with lower short, intermediate, and long-term mortality and does not lead to worse outcomes compared to ECMO, IABP, and VAD support. When mechanical support is not an option, inotropic therapy remains a viable and effective strategy.

OBJECTIVE Anterior cervical discectomy and fusion (ACDF) is an established treatment for cervical degenerative disc disease; however, the procedure can cause loss of cervical spine range of motion and potentially accelerate adjacent segment degeneration. Cervical disc arthroplasty (CDA) seeks to preserve native motion of the cervical spine, which can theoretically reduce the incidence of adjacent level degeneration. The literature regarding the relative efficacy of ACDF versus CDA remains inconsistent. In this study, the authors investigate the difference in outcomes between ACDF and CDA and identify factors contributing to the heterogeneity in the literature. METHODS The Ovid, Embase, Scopus, Cochrane, and ClinicalTrials.gov databases were systematically searched from inception to September 5, 2023, for randomized controlled trials (RCTs) comparing ACDF and CDA for degenerative disc disease. Studies were extracted by two authors and verified by a third. Random-effects meta-analysis was performed. The primary outcome was the difference in clinical outcomes between the two surgical groups. The secondary outcomes were the differences in radiological outcomes, surgical characteristics, complication rates, and hospital lengths of stay. The study was registered with the International Prospective Register of Systematic Reviews (PROSPERO; registration no. CRD42023469204) and adhered to the PRISMA guidelines. RESULTS From 584 articles uploaded to the Covidence platform for screening, 35 studies derived from 25 RCTs were included in this systematic review and meta-analysis. A total of 4530 patients were treated with ACDF (2081) and CDA (2449). Forty-six percent of the patients (2063) were male, and the mean age of the study cohort was 45 ± 3 years. In terms of the primary outcome, CDA showed higher rates of neurological and overall success. Regarding the secondary outcomes, CDA demonstrated a significantly lower rate of adjacent level disease, higher rate of heterotopic ossification, and greater range of motion at the operated level. Additionally, CDA had lower rates of reoperation but significantly longer operative times than ACDF. The inclusion of myelopathic patients and variations in follow-up between the surgical groups contributed to the observed effect heterogeneity among studies. CONCLUSIONS In this study, CDA showed comparable or potentially greater success in overall and neurological outcomes, along with a lower incidence of adjacent level degeneration and reoperation rates but longer operative times.

ABSTRACT Objectives To explore the clinical impact of social determinants of health (SDoH) stress in bipolar disorder (BD) course of illness and to explore potential gender differences in SDoH stress endorsement. Methods 2280 individuals living with BD type I or II (62% women; 67.5% BD‐I) participating in the Mayo Clinic Bipolar Biobank who completed a questionnaire assessing positive and negative‐valent stressors in the 12 months prior to study enrollment were included for this analysis. Six negative stressors were used as proxies of SDoH. Generalized linear models were used to test the association between SDoH stressors and markers of illness severity as well as potential differences by sex by including an interaction term. Results After adjusting for age, sex, and recruitment site, SDoH‐related stressors were significantly associated with a more severe course of illness in both men and women. Except for unemployment rates, women reported more frequently SDoH‐related stress (i.e., lack of family support, financial problems, health coverage and access problems). Conclusions The study found significant gender differences in both the endorsement of specific SDoH stressors and in the prevalence of specific illness severity markers; however, it did not directly test the predictive relationship between gender differences in SDoH and illness severity markers. Future studies aiming to achieve health equity in mental health care should continue assessing social determinants of health stressors, incorporating a gender perspective to better understand their influence on bipolar disorder.

Importance Multiparametric magnetic resonance imaging (MRI), with or without prostate biopsy, has become the standard of care for diagnosing clinically significant prostate cancer. Resource capacity limits widespread adoption. Biparametric MRI, which omits the gadolinium contrast sequence, is a shorter and cheaper alternative offering time-saving capacity gains for health systems globally. Objective To assess whether biparametric MRI is noninferior to multiparametric MRI for diagnosis of clinically significant prostate cancer. Design, Setting, and Participants A prospective, multicenter, within-patient, noninferiority trial of biopsy-naive men from 22 centers (12 countries) with clinical suspicion of prostate cancer (elevated prostate-specific antigen [PSA] level and/or abnormal digital rectal examination findings) from April 2022 to September 2023, with the last follow-up conducted on December 3, 2024. Interventions Participants underwent multiparametric MRI, comprising T2-weighted, diffusion-weighted, and dynamic contrast–enhanced (DCE) sequences. Radiologists reported abbreviated biparametric MRI first (T2-weighted and diffusion-weighted), blinded to the DCE sequence. After unblinding, radiologists reported the full multiparametric MRI. Patients underwent a targeted biopsy with or without systematic biopsy if either biparametric MRI or multiparametric MRI was suggestive of clinically significant prostate cancer. Main outcomes and measures The primary outcome was the proportion of men with clinically significant prostate cancer. Secondary outcomes included the proportion of men with clinically insignificant cancer. The noninferiority margin was 5%. Results Of 555 men recruited, 490 were included for primary outcome analysis. Median age was 65 (IQR, 59-70) years and median PSA level was 5.6 (IQR, 4.4-8.0) ng/mL. The proportion of patients with abnormal digital rectal examination findings was 12.7%. Biparametric MRI was noninferior to multiparametric MRI, detecting clinically significant prostate cancer in 143 of 490 men (29.2%), compared with 145 of 490 men (29.6%) (difference, −0.4 [95% CI, −1.2 to 0.4] percentage points; P = .50). Biparametric MRI detected clinically insignificant cancer in 45 of 490 men (9.2%), compared with 47 of 490 men (9.6%) with the use of multiparametric MRI (difference, −0.4 [95% CI, −1.2 to 0.4] percentage points). Central quality control demonstrated that 99% of scans were of adequate diagnostic quality. Conclusion and relevance In men with suspected prostate cancer, provided image quality is adequate, an abbreviated biparametric MRI scan, with or without targeted biopsy, could become the new standard of care for prostate cancer diagnosis. With approximately 4 million prostate MRIs performed globally annually, adopting biparametric MRI could substantially increase scanner throughput and reduce costs worldwide. Trial registration ClinicalTrials.gov Identifier: NCT04571840