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Key Points Nonimmunologic AKI-related rehospitalizations post–kidney transplant are associated with poorer long-term allograft and recipient outcomes. These data are not reported to United Network for Organ Sharing, and there are no datasets highlighting this important association; thus, our findings are valuable to clinicians. We hope to help the community create a cohort of higher risk transplant patients who need closer monitoring to potentially increase graft longevity Background AKI is associated with an increased risk of CKD and ESKD. However, only limited studies have investigated the effect of AKI episodes on kidney transplant outcomes. This study evaluated the effect of rehospitalization associated with nonimmunologic AKI on long-term outcomes. Data on rehospitalization with AKI after kidney transplant are not reported to United Network for Organ Sharing, and thus, there are no large datasets available to study this association. Methods We completed chart reviews of 989 deceased donor kidney transplant recipients transplanted from 2010 to 2014 at 13 transplant centers in the Deceased Donor Study Consortium. Rehospitalizations up to 5 years post-transplant were included. The cause of rehospitalizations was adjudicated by a transplant nephrologist on the basis of the discharge diagnosis. Primary outcomes were the effect of AKI-related rehospitalization on death-censored graft failure and all-cause mortality. We excluded rehospitalizations because of acute rejection from the primary analysis. The cohort was linked to data from Organ Procurement and Transplantation Network supplied by United Network for Organ Sharing. Time-varying cox-proportional hazard models were used to examine the association between rehospitalization and outcomes. Results We identified 200 (20%) recipients with at least one rehospitalization associated with AKI, 516 (52%) with rehospitalizations without AKI, and 273 (28%) without a rehospitalization post-transplant. Delayed graft function, donor age, and kidney donor profile index score differed between the three groups. We found a higher risk of death censored graft failure adjusted hazard ratio (aHR) 7.5 (95% confidence interval [CI], 4.0 to 13.8), all-cause graft failure aHR 6.7 (95% CI, 4.2 to 10.8), and all-cause mortality aHR 5.7 (95% CI, 2.7 to 11.8) for rehospitalizations associated with AKI compared with no rehospitalization. The non-AKI rehospitalizations also had significantly higher rates of measured outcomes; however, the associations were not as strong. Conclusions AKI rehospitalizations were associated with a significantly increased risk of poorer graft outcomes, and thus, closer follow-up of this high-risk group is warranted.

Abstract Growing evidence has demonstrated the clinical benefit of percutaneous left atrial appendage closure (LAAC) in patients with atrial fibrillation. Although procedural complication rates have declined with increasing experience, post-procedural device-related complications persist, impacting prognosis and reducing the long-term benefits of the procedure. Given the potential impact of these complications, surveillance imaging after LAAC is mandatory. Currently, different imaging modalities offer unique advantages to manage these complications which warrant a combined approach to optimize both short- and long-term follow-up. The aims of this review are to explore the distinct characteristics of each imaging modality, highlighting the primary findings to be assessed during follow-up imaging. Additionally, we propose an optimized clinical imaging surveillance roadmap from discharge to long-term follow-up.

Background Pilots face significant occupational risks affecting cardiometabolic health and are subject to regulatory health screenings. Cardiometabolic risk factors, cardiac screening findings and outcomes among pilots have not been well reported. Objectives This study aimed to investigate cardiac evaluations of asymptomatic aircraft pilots and the association between clinical risk factors and outcomes. Methods Asymptomatic aircraft pilots referred for cardiac assessment between January 1991 and May 2023 were studied. Baseline characteristics, cardiac test findings and outcomes were evaluated. Major adverse clinical event (MACE) was defined as death, myocardial infarction, stroke, major arrhythmia, heart failure event or cardiac-related hospitalisation and estimated using Kaplan-Meier methods. Significant valvular disease by echocardiography was defined as stenosis, regurgitation or prolapse of moderate severity or greater. Aortic dilation by transthoracic echocardiogram (TTE) was defined as measuring ≥40 mm in diameter. Results 212 pilots met eligibility criteria for the study. The majority were white (92.9%) and male (91%) with a mean age of 58.5±10.9 years. Mean body mass index was 27.8±4.8 with comorbid hyperlipidaemia (48%), hypertension (32%), prior cancer (27%), sleep apnoea (15%), arrhythmia (12%) and known coronary artery disease (6%). Imaging revealed significant valvular disease (2.4%) and dilated aortas (16%) based on TTEs. Functional cardiac testing performed showed mean functional aerobic capacity of 109±24.6% reaching 11.89±2.65 metabolic equivalents with <8% showing positive findings per EKG or wall motion abnormalities on exercise TTE. Six patients received coronary angiography based on clinical evaluation, with two undergoing percutaneous coronary intervention. Over a 32-year period with a median (range) follow-up of 5.15 (0.1, 31.82) years, MACE incidence was 15%. Conclusions Asymptomatic aircraft pilots have underlying cardiovascular risk factors but good overall functional capacity, long-term outcomes and life expectancy. Prevalence of cardiac structural findings like aortic dilatation warrants increased attention during examination of these patients.

Background Data on the safety profiles and clinical outcomes of patients with solid tumors and cardiac metastasis treated with immune checkpoint inhibitors (ICIs) are limited. Methods This is an international multicenter retrospective study of patients with cancer and cardiac metastasis at baseline. Patients who had received ≥1 dose of ICI were included. Treatment-related adverse events (trAEs) were graded per Common Terminology Criteria for Adverse Event V.5.0. Objective response rates (ORR) were evaluated by Response Evaluation Criteria in Solid Tumors V.1.1 when available. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Results Among 110 pts, median age at ICI initiation was 65 (IQR: 59–75). Median follow-up time since ICI initiation was 36 (95% CI: 26 to 51) months. Melanoma (38%, n=42) and non-small cell lung cancer (24%, n=26) were the most common. 68 (62%) patients received ICIs as first-line, and 29 (26%) patients were treated with combination anti-programmed death-1 and anti-cytotoxic T-lymphocyte antigen 4. The most common location of cardiac metastasis was in the atria (37%, n=41) and ventricles (35%, n=39). 15 patients (13.6%) had bilateral cardiac/pericardial metastasis, 44 (40%) had left-sided, and 43 (39.8%) had right-sided. At ICI initiation, 21% (n=23) had a cardiac thrombus. Cardiology referrals and cardiac MRIs at the time of cancer diagnosis were completed on 58 (53%) and 52 (47%) patients, respectively. Cardiac events occurred in 40 (36%) patients, including arrhythmias (n=14, 13%), arterial/venous emboli (n=4, 3.6%), and cardiac tamponade (n=3, 2.7%). 53 (47%) patients developed trAEs; most common were colitis/diarrhea (n=16, 15%), dermatitis (n=13, 12%), and hepatitis (n=9, 8.2%). ICI-related major cardiac trAEs occurred in 2 (1.8%) patients. 22 patients (20%) developed grade ≥3 trAE. Patients with multiple cardiac metastases had significantly lower responses to ICI-based regimens compared with patients with single cardiac metastasis (11% vs 63%, p=0.02). For melanoma, ORR, median PFS, and median OS were 38%, 9.0 months, and 28.9 months, respectively. 83% of patients with melanoma had concordant responses in overall disease burden and cardiac disease. 91 patients discontinued ICIs, and the main reason was progression or death in 55 (49%) patients. Conclusions Among patients with pre-existing cardiac metastasis, ICIs demonstrated meaningful clinical efficacy with no increase in safety signals. Most patients had concordant responses in the overall disease burden and cardiac mass. Multidisciplinary teams are crucial for the appropriate management of patients with cardiac metastasis.

Microglia actively survey the brain and dynamically interact with neurons to maintain brain homeostasis. Microglial Gi protein–coupled receptors (Gi-GPCRs) play a critical role in microglia-neuron communications. However, the impact of temporally activating microglial Gi signaling on microglial dynamics and neuronal activity in the homeostatic brain remains largely unknown. In this study, we used Gi-based designer receptors exclusively activated by designer drugs (Gi-DREADD) to selectively and temporally modulate microglial Gi signaling pathway. By integrating this chemogenetic approach with in vivo two-photon imaging, we observed that exogenous activation of microglial Gi signaling transiently inhibited microglial process dynamics, reduced neuronal activity, and impaired neuronal synchronization. These altered neuronal functions were associated with a decrease in interactions between microglia and neuron somata. Together, this study demonstrates that acute, exogenous activation of microglial Gi signaling regulates neuronal circuit function, offering a potential pharmacological target for the neuromodulation through microglia.

Background We tested whether biologic age, as estimated by deficits, functional impairments, or Age‐Gap or their combination, provide improved estimation of cause‐specific death as compared with chronological age. Methods Cardiovascular and noncardiovascular deficits, functional impairments, and Age‐Gap were prospectively collected in 535 patients aged ≥55 years undergoing percutaneous coronary interventions between August 1, 2014, and March 31, 2018. Age‐Gap was calculated as the difference between chronological age and age estimated by artificial intelligence ECG using a convolutional neural network. The full biological age model included deficits, functional impairments, and Age‐Gap >2 SD. A multivariable reduced model with the least number of variables was also created to provide a comparable C index to the full model. Results The average chronological age was 72.1±9.5 years, and there were 68% of men. During a median follow‐up of 2.61 years, 124 (23%) patients died. There was a modest correlation between Age‐Gap and biological age ( r =0.28 [95% CI, 0.20–0.35]; P <0.001). When modeled with chronologic age as a covariate, Age‐Gap predicted all‐cause (hazard ratio [HR], 1.07 [95% CI, 1.04–1.10]; P <0.001) and cardiovascular (HR, 1.07 [95% CI, 1.04–1.11]; P <0.001) mortality. As compared with chronological age, the full biological age model noted significant improvement in the prediction of long‐term overall (95% CI, 0.65–0.78), cardiovascular (95% CI, 0.69–0.77), and noncardiovascular (95% CI, 0.55–0.86) mortality. In the reduced models, most prognostic information for noncardiovascular mortality (C index: 0.79) was obtained by subjective difficulty in performing tasks, whereas the deficit‐based estimation predicted cardiovascular mortality (C index: 0.72). Conclusions Estimated biological age from deficits and functional impairments was superior to chronological age in predicting long‐term cause‐specific mortality following percutaneous coronary interventions.

AbstractA 60-year-old woman with chronic pain in the left long finger, occasionally involving the ring finger and intermittently extending to the hand, wrist, and distal forearm, was referred for radiographs and a triple-phase technetium-99m methylene diphosphonate bone scintigraphy to evaluate for possible complex regional pain syndrome. Initial radiographs were normal. A three-phase bone scan revealed focal radiotracer uptake at the distal aspect of the long finger during the blood pool phase only, with normal blood flow and delayed phases, suggesting a hypervascular soft tissue tumor. Follow-up magnetic resonance imaging showed a hypervascular nodule in the nail bed of the long finger. The lesion was surgically resected, and pathology results confirmed the diagnosis of a glomus tumor.

TPS294 Background: Approval of [ 177 Lu]Lu-PSMA-617 ( 177 Lu-PSMA-617) for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer, previously treated with androgen receptor pathway inhibitors and taxane-based chemotherapy, was based on the results of the Phase 3 VISION study (NCT03511664). It is important to further characterize long-term safety outcomes in 177 Lu-PSMA-617–treated patients, with particular regard to potential treatment-related risks. To this end, the long-term follow-up (LTFU) safety study (NCT05803941) has been established. Findings from the LTFU study will be crucial for assessing delayed toxicities for patients with PSMA-positive metastatic prostate cancer treated with 177 Lu-PSMA-617 globally. Methods: The LTFU study is a prospective, multi-center, non-EU post-authorization safety study. Patients who received ≥1 dose of 177 Lu-PSMA-617 within one of the prospective parent studies (Table 1) are eligible. Patients may enroll in the LTFU study after fulfilling the requirements of their corresponding parent study. The primary endpoint is the number and proportion of selected adverse events (AEs), including myelosuppression, xerostomia, renal failure, xerophthalmia, and second primary malignancies (eg, myelodysplastic syndrome or acute myeloid leukemia), other serious AEs, and changes in laboratory values. The secondary endpoint is the number and proportion of deaths. Following enrollment, patients will undergo assessments at baseline, and then every 6–8 months for up to 10 years after their first dose of 177 Lu-PSMA-617 or until death. At each visit, a review of selected treatment-related AEs (xerostomia, xerophthalmia, myelosuppression), any-cause AEs (renal toxicity, new diagnoses of second primary malignancies), and treatment-related serious AEs will be conducted. Physical and laboratory assessments, as well as details on concomitant medications and interventions, including anti-cancer therapies, will be collected. Patients may receive treatment with any medical intervention. Interim analyses are planned at 2 and 5 years post-study activation. Enrollment is ongoing (n=13). Clinical trial information: NCT05803941 . Parent studies of the long-term follow-up safety study. Trial Indication Phase N (all groups) ClinicalTrials.gov ID VISION (+sub-study) Post-taxane mCRPC 3 831 (+30) NCT03511664 PSMAfore Pre-taxane mCRPC 3 469 NCT04689828 PSMAddition mHSPC 3 1144 NCT04720157 177 Lu-PSMA-617 in patients with moderately or severely impaired, or normal renal function Post-taxane mCRPC 2 20 a NCT06004661 a Planned. mCRPC, metastatic castration-resistant prostate cancer; mHSPC, metastatic hormone-sensitive prostate cancer.

Background: Patients presenting with non-ST elevation myocardial infarction (NSTEMI) are often admitted to medical wards. We aimed to evaluate the impact of the admitting department on long-term outcomes. Methods: Patients admitted to a large tertiary center were categorized according to the admission ward, either the intensive cardiac care unit (ICCU) or internal medicine department (IMD). We compared major adverse cardiovascular events (MACEs), a composite of all-cause death, recurrent myocardial infarction (MI), and revascularization, along with the individual components of MACE, between the two groups during a long-term follow-up. Results: A total of 11,779 NSTEMI patients were included, with 4522 admitted to the ICCU and 7257 to the department of internal medicine. Patients admitted to the ICCU had lower systolic blood pressure, higher troponin levels and lower left ventricular ejection fraction (LVEF) compared to those in the IMD group, indicating greater initial clinical severity. Although patients admitted to the ICCU experienced a significantly higher rate of in-hospital complications, there were no significant differences in the incidence of in-hospital deaths between the two groups. During 5-year follow-up, NSTEMI patients initially admitted to the ICCU had significantly lower rates of mortality and MACEs. The estimated hazard ratio for 5-year MACE and 5-year mortality rates for NSTEMI patients admitted to the IMD vs. those admitted to the ICCU were 2.03 (95% CI, 1.04–3.34) and 2.5 (95% CI, 1.10–4.38), respectively. Conclusions: NSTEMI patients admitted to the ICCU experienced lower long-term mortality and MACE rates. These findings support the management of NSTEMI patients in cardiac wards and warrant further research into the reasons for the improved outcome.