Citations

ABSTRACTBackgroundAlternate complement dysregulation postrenal transplantation can result in thrombotic microangiopathy (TMA). There is a scarcity of data regarding outcomes based on the timing of TMA post‐transplant, coupled with a lack of follow‐up biopsy findings post TMA diagnosis. This study aims to assess allograft and patient outcomes in individuals developing early TMA, defined within 4 months post‐transplantation, and explore any differences in follow‐up surveillance biopsies compared to a non‐TMA group.DesignThis is a single center retrospective study between January 1, 2002 and October 10, 2019. Patients who developed TMA within 4 months post‐transplantation were compared to a propensity matched non‐TMA group.ResultsThirty‐one patients developed TMA within 4 months of renal transplantation. Index TMA biopsy featured noticeable glomerular, and vascular lesions along with acute tubular injury. Four‐month surveillance biopsy showed significant glomerulitis, transplant glomerulopathy and chronic interstitial fibrosis as compared to non‐TMA group. However, at 1 year, these differences were no longer significant. There was no significant difference in patient survival (TMA vs. non‐TMA,p = 0.083); however, death censored graft survival was significantly lower in the TMA group (p < 0.001). TMA patients had a significantly lower estimated glomerular filtration rate at 4 months and at 1 year as compared to the non‐TMA group.ConclusionEarly onset TMA post renal transplant leads to decreased renal function and lower graft survival. Early recognition and prompt treatment may help in reducing the adverse outcomes.

Abstract BACKGROUND H3K27-altered diffuse midline glioma (DMG) is a devastating pediatric brainstem tumor that affects 200-300 individuals in the US per year. Median survival is 9-11 months, and there are virtually no long-term survivors. Despite decades of clinical trials, radiation therapy remains standard of care, extending survival by 2-3 months. Elucidating the mechanisms that drive H3K27-altered DMG pathogenesis in order to uncover therapeutic vulnerabilities is of critical importance. Recent studies implicate MALT1 as a potential therapeutic target in gliomas. MALT1 is the effector molecule of the CARMA-BCL10-MALT1 (CBM) signalosome, a cytoplasmic protein complex that drives downstream pro-survival transcriptional activity. MALT1, which possesses scaffolding and protease functions, promotes cell viability, proliferation, and migration/invasion in multiple cancer types. We aim to evaluate the hypotheses that MALT1 promotes DMG cancer cell proliferation and migration and that MALT1 inhibition will abrogate tumor progression. METHODS/RESULTS We screened a panel of cells including astrocytes, neural stem cells, and DMG cell lines by Western blot and found that CBM complex members BCL10 and MALT1 are present in all cells tested. We next demonstrated that MALT1 is proteolytically active in DMG cell lines SF8628 and HSJD-DIPG-007. Specifically, we showed cleavage of the MALT1 protease substrate HOIL, which was abrogated by treatment with the MALT1 protease inhibitor MLT-748. We next generated multiple dox-inducible MALT1 shRNA DMG cell lines to assess the impact of MALT1 deficiency on DMG biology. Thus far, we find that shRNA knockdown of MALT1 does not impact SF8628 cell proliferation. CONCLUSIONS MALT1 is expressed and proteolytically active in DMG cells. Initial studies show that MALT1 knockdown does not affect proliferation of SF8628 cells. We will next evaluate the effect of MALT1 knockdown on proliferation of additional DMG cell lines, as well as the impact on other malignant features of DMG cells including migration/invasion.

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.

AbstractBackgroundUniversal skin cancer screening for the Latino population is impractical.ObjectivesWe focused on melanoma education by conducting an online education campaign and collected baseline, postintervention, and 3‐month follow‐up surveys to assess sun‐protective behaviors.MethodsParticipants were recruited through (1) social media ads and (2) emails sent to Mayo Clinic Latino patients.ResultsTotal social media impressions were 508,442 and 413,007 in Spanish and English, respectively. There were 18,790 and 11,731 clicks for the Spanish and English ads, respectively, resulting in 175 baseline survey responses. From email distribution, 4151 emails translated to 219 baseline participants. Of the 394 patients who participated in the baseline survey, 89 completed the postintervention survey, and 57 completed the 3‐month follow‐up survey (28 from social media and 29 Mayo Clinic patients). Social media provides a unique opportunity for the medical community to promote melanoma education, distribute content quickly, and provide medical education in disparate healthcare areas. Our Spanish ad click‐through rate was 3.70% compared to 2.84% for English. The click‐to‐action rate was 0.57%, and the baseline‐to‐completion rate was 16.00%.ConclusionsOur study suggests social media could be a unique tool for distributing melanoma educational materials to Latino populations. The click‐through rates for this study were several‐fold higher than other studies' reported click‐through rates (0.4%–0.93%). It is important to develop melanoma educational materials that are culturally relevant and focused on Latino populations that can provide persistent improvements in mitigating melanoma risk behaviors such as sunscreen application and self‐skin examinations.

Introduction: Recent studies report similar outcomes with antiplatelet drugs and intravenous thrombolysis (IVT) in patients with minor nondisabling ischemic stroke. These patients still meet emergent triage criteria and can increase the burden on stroke systems through prehospital stroke activation. Prehospital large vessel occlusion (LVO) scales can improve triage of LVO patients but have not been evaluated as tools to predict IVT administration. We sought to determine if common LVO scales can predict IVT use in a large academic telestroke practice. Methods: This retrospective study included all video telestroke consults performed in a large academic telestroke network from 2019-2020. Patients were excluded if they were on anticoagulation, presented beyond 4.5 hours from last known well, or family declined IVT due to goals of care. We recorded presenting NIHSS and IVT recommendations. NIHSS was used to calculate 7 LVO scales (RACE, G-FAST, FAST-ED, VAN, PASS, 3I-SS, and C-STAT). Scale performance was assessed by calculating area under curve (AUC) and compared to NIHSS total score using the DeLong test. Youden cutpoint was established for each scale and subsequently used to calculate sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy. Results: A total of 513 patients were included; 205/513 (40%) were recommended IVT. Median (IQR) NIHSS was 1 (0-3) in non-IVT patients and 6 (4-11) in IVT patients. The RACE and G-FAST scales were noninferior to the NIHSS in predicting IVT recommendation (Table 1). Conclusion: The RACE and G-FAST scales may be useful triage tools to identify patients needing emergent stroke evaluation for consideration of IVT.

Introduction: Telestroke enables timely and remote evaluation of patients with acute stroke syndromes. However, stroke mimics represent more than 30% of this population. Given the resources required for management of suspected acute ischemic stroke, several scales have been developed to help identify stroke mimics. Our objective was to externally validate four mimic scales (Khan Score [KS], TeleStroke Mimic Score [TS], simplified FABS [sFABS], and FABS) in a large, academic telestroke network. Methods: This is a retrospective, IRB exempt study of all patients who presented with suspected acute stroke syndromes and underwent video evaluation between 2019-2020 at a large academic telestroke network. Detailed chart review was conducted to extract both the variables needed to apply the mimic scales the final diagnosis confirmed by final imaging and discharge diagnosis (cerebral ischemic vs stroke mimic). Overall score performance was assessed by calculating area under curve (AUC). Youden cutpoint was established for each scale and used to calculate sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy. Results: A total of 1043 patients were included in the final analysis. Final diagnosis of cerebral ischemia was made in 662/1043 patients (63.5%) and stroke mimic was diagnosed in 381/1043 patients (36.5%). To predict stroke mimic, TS had the highest AUC (68.3) and PPV (73%); KS had the highest accuracy (68.6%), sensitivity (86.6%) and NPV (61.5%); and FABS had the highest specificity (54.8%) (Table 1). Conclusions: While each scale offers unique strengths, none was able to identify stroke mimics effectively enough to confidently apply in clinical practice. There remains need for significant clinical judgment to determine the likelihood of stroke mimic at presentation.