Citations

Background: Pancreas transplantation is a crucial surgical intervention for managing diabetes, but it faces challenges such as its invasive nature, stringent patient selection criteria, organ scarcity, and centralized expertise. Despite the steadily increasing number of pancreas transplants in the United States, there is a need to understand global trends in interest to increase awareness of and participation in pancreas and islet cell transplantation. Methods: We analyzed Google Search trends for “Pancreas Transplantation” and “Islet Cell Transplantation” from 2004 to 14 November 2023, assessing variations in search interest over time and across geographical locations. The Augmented Dickey–Fuller (ADF) test was used to determine the stationarity of the trends (p < 0.05). Results: Search interest for “Pancreas Transplantation” varied from its 2004 baseline, with a general decline in peak interest over time. The lowest interest was in December 2010, with a slight increase by November 2023. Ecuador, Kuwait, and Saudi Arabia showed the highest search interest. “Islet Cell Transplantation” had its lowest interest in December 2016 and a more pronounced decline over time, with Poland, China, and South Korea having the highest search volumes. In the U.S., “Pancreas Transplantation” ranked 4th in interest, while “Islet Cell Transplantation” ranked 11th. The ADF test confirmed the stationarity of the search trends for both procedures. Conclusions: “Pancreas Transplantation” and “Islet Cell Transplantation” showed initial peaks in search interest followed by a general downtrend. The stationary search trends suggest a lack of significant fluctuations or cyclical variations. These findings highlight the need for enhanced educational initiatives to increase the understanding and awareness of these critical transplant procedures among the public and professionals.

Background. Predicting long-term mortality postkidney transplantation (KT) using baseline clinical data presents significant challenges. This study aims to evaluate the predictive power of artificial intelligence (AI)-enabled analysis of preoperative electrocardiograms (ECGs) in forecasting long-term mortality following KT. Methods. We analyzed preoperative ECGs from KT recipients at three Mayo Clinic sites (Minnesota, Florida, and Arizona) between January 1, 2006, and July 30, 2021. The study involved 6 validated AI algorithms, each trained to predict future development of atrial fibrillation, aortic stenosis, low ejection fraction, hypertrophic cardiomyopathy, amyloid heart disease, and biological age. These algorithms’ outputs based on a single preoperative ECG were correlated with patient mortality data. Results. Among 6504 KT recipients included in the study, 1764 (27.1%) died within a median follow-up of 5.7 y (interquartile range: 3.00–9.29 y). All AI-ECG algorithms were independently associated with long-term all-cause mortality (P < 0.001). Notably, few patients had a clinical cardiac diagnosis at the time of transplant, indicating that AI-ECG scores were predictive even in asymptomatic patients. When adjusted for multiple clinical factors such as recipient age, diabetes, and pretransplant dialysis, AI algorithms for atrial fibrillation and aortic stenosis remained independently associated with long-term mortality. These algorithms also improved the C-statistic for predicting overall (C = 0.74) and cardiac-related deaths (C = 0.751). Conclusions. The findings suggest that AI-enabled preoperative ECG analysis can be a valuable tool in predicting long-term mortality following KT and could aid in identifying patients who may benefit from enhanced cardiac monitoring because of increased risk.

Importance West Nile virus (WNV) is the leading cause of human arboviral disease in the US, peaking during summer. The incidence of WNV, including its neuroinvasive form (NWNV), is increasing, largely due to the expanding distribution of its vector, the Culex mosquito, and climatic changes causing heavy monsoon rains. However, the distinct characteristics and outcomes of NWNV in individuals who are immunosuppressed (IS) and individuals who are not IS remain underexplored. Objective To describe and compare clinical and radiographic features, treatment responses, and outcomes of NWNV infection in individuals who are IS and those who are not IS. Design, Setting, and Participants This retrospective cohort study used data from the Mayo Clinic Hospital system collected from July 2006 to December 2021. Participants were adult patients (age ≥18 years) with established diagnosis of NWNV infection. Data were analyzed from May 12, 2020, to July 20, 2023. Exposure Immunosuppresion. Main Outcomes and Measures Outcomes of interest were clinical and radiographic features and 90-day mortality among patients with and without IS. Results Of 115 participants with NWNV infection (mean [SD] age, 64 [16] years; 75 [66%] male) enrolled, 72 (63%) were not IS and 43 (37%) were IS. Neurologic manifestations were meningoencephalitis (98 patients [85%]), encephalitis (10 patients [9%]), and myeloradiculitis (7 patients [6%]). Patients without IS, compared with those with IS, more frequently reported headache (45 patients [63%] vs 18 patients [42%]) and myalgias (32 patients [44%] vs 9 patients [21%]). In contrast, patients with IS, compared with those without, had higher rates of altered mental status (33 patients [77%] vs 41 patients [57%]) and myoclonus (8 patients [19%] vs 8 patients [4%]). Magnetic resonance imaging revealed more frequent thalamic T2 fluid-attenuated inversion recovery hyperintensities in individuals with IS than those without (4 patients [11%] vs 0 patients). Individuals with IS had more severe disease requiring higher rates of intensive care unit admission (26 patients [61%] vs 24 patients [33%]) and mechanical ventilation (24 patients [56%] vs 22 patients [31%]). The 90-day all-cause mortality rate was higher in the patients with IS compared with patients without IS (12 patients [28%] vs 5 patients [7%]), and this difference in mortality persisted after adjusting for Glasgow Coma Scale score (adjusted hazard ratio, 2.22; 95% CI, 1.07-4.27; P = .03). Individuals with IS were more likely to receive intravenous immunoglobulin than individuals without IS (12 individuals [17%] vs 24 individuals [56%]), but its use was not associated with survival (hazard ratio, 1.24; 95% CI, 0.50-3.09; P = .64). Conclusions and Relevance In this cohort study of individuals with NWNV infection, individuals with IS had a higher risk of disease complications and poor outcomes than individuals without IS, highlighting the need for innovative and effective therapies to improve outcomes in this high-risk population.

Abstract Cytotoxic CD8+ T cells play a key role in response to anti-PD-1/PD-L1 immune checkpoint inhibitors (ICI) therapy. However, the exact effector molecules that are regulated by PD-1 signals in cytotoxic CD8+ T cells have not been completely defined. Lack of this knowledge is a crucial problem in addressing how to overcome the low clinical response rate to ICI therapy. When exploring why certain patients not responding to ICI therapy, we found non-responders did not have an elevated NKG7 expression in CD8+ T cells as responders to ICI therapy. The difference in NKG7 expression in CD8+ T cells between non-responders and responders to anti-PD-1 therapy prompted us to investigate the potential role of PD-1 signaling in regulating NKG7 expression. To that end, we generated a CD8+ T cell-specific Pdcd1 conditional knockout mice (CD8 E8ICre-Pdcd1fl/fl, also known as CD8-PD-1 cKO) where Pdcd1 is deleted after thymic selection of single positive CD8+ T cells. We observed a delayed tumor growth and prolonged survival in CD8-PD-1 cKO mice compared to control mice after B16-OVA melanoma tumor challenge. On Day 12, when the CD8-PD-1 cKO mice demonstrated their ability to control tumor growth, we conducted single cell RNA sequencing on isolated tumor infiltrating CD8+ T cells, revealing a significant increase of Nkg7 expression in effector CD8+ T cells in the Pdcd1 deficient CD8+ T cells compared to the control wild type T cells. Pdcd1-deficient effector CD8+ T cells also had increased expression of genes linked to NFAT/Calcineurin signaling pathway including Nfatc1, S100a4, Tbet and Tox, suggesting Nkg7 could be regulated by Pdcd1 via the NFAT pathway. To determine the impact of increased NKG7 expression in CD8+ T cells, we used OVA protein as a surrogate tumor antigen in vaccination. We found a complete B16-OVA tumor rejection in CD8-PD-1 cKO mice compared to control mice when tumor cells were injected on day 7 after vaccination with OVA protein and poly (I:C) (as an adjuvant), but only a partial rejection on day 21. The CD8-PD-1 cKO mice that were tumor-free for 30-40 days rejected 2nd tumor challenge with B16-OVA tumors. This long-term protection is tumor antigen (OVA) specific because these mice did not reject B16F10 tumor cells that do not express OVA antigen. We also found effector memory CD8+ T cells with high cytotoxicity increased in the spleen of CD8-PD-1 cKO mice after OVA antigen immunization compared to control. In conclusion, we found NKG7 is one of the effector molecules in cytotoxic CD8+ T cells, which can be regulated by PD-1 signals through NFAT signaling. Targeting the PD-1-NFAT pathway may be a new option to overcome low responses of T cells to ICI therapy in treatment of refractory cancer. Citation Format: Zhiming Mao, Joanina Gicobi, Jacob Hirdler, Xin Liu, Michelle Hsu, Emilia Dellacecca, Wenjing Zhang, Fabrice Lucien-Matteoni, Hai dong. PD-1 signals regulate NKG7 that is required for CD8+ T cells to sustain cytotoxicity and durable antitumor memory responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3979.

PURPOSE Improving care transitions for patients with cancer discharged from the hospital is considered an important component of quality care. Digital monitoring has the potential to better the delivery of transitional care through improved patient-provider communication and enhanced symptom management. However, remote patient monitoring (RPM) interventions have not been widely implemented for oncology patients after discharge, an innovative setting in which to apply this technology. METHODS We implemented a RPM intervention which identifies medical oncology patients at discharge, monitors their symptoms for 10 days, and intervenes as necessary to manage symptoms. We evaluated the feasibility (>50% patient engagement with symptom assessment), appropriateness (symptom alerts), and acceptability (net promoter score >0.7) of the intervention and the initial effect on acute care visits and return on investment. RESULTS During the study period, January 1, 2021, to December 31, 2022, we evaluated 2,257 medical oncology discharges representing 1,857 unique patients. We found that 65.9% of patients discharged (N = 1,489) completed at least one symptom assessment postdischarge and of them, 45.5% (n = 678) generated a severe symptom alert that we helped to manage. Patients expressed high satisfaction with the intervention with a net promoter score of 84%. In preliminary analysis of patients with GI malignancies (n = 449), we found a nonsignificant decrease in 30-day readmissions for the intervention cohort (n = 269) by 5.8% as compared with the control (n = 180; from 33.3% to 27.5%; P = .22). CONCLUSION Digital transitional care management was feasible and demonstrated that patients transitioning from the hospital to home have a substantial symptom burden. The intervention was associated with high patient satisfaction but will require further refinement and evaluation to increase its impact on 30-day readmission.