Citations

Ventricular arrhythmias after electrical cardioversion for AF are rare. Most of these arrhythmias are related to QT prolongation, resulting from marked and sudden slowing of heart rates, treatment with Class III antiarrhythmic drugs or other QT-prolonging medications, and the ventricular repolarisation remodelling effect of electrical cardioversion. A case of polymorphic ventricular tachycardia post-cardioversion of rapid AF in a patient with tachycardia-induced cardiomyopathy and the use of amiodarone is reported.

Abstract Description Background Glutamic acid decarboxylase 65 (GAD65) antibodies are found in patients with stiff-person syndrome (SPS), cerebellar ataxia (CA), epilepsy and type-I diabetes (T1D). Given the intracellular localization of the antigenic target, a direct pathogenic role for GAD65 antibody (GAD65Ab) is unlikely. Methods PBMC-derived dendritic cells (DCs) from GAD65Ab+ patients with SPS (n = 6), epilepsy (n = 4), CA (n = 5), or T1D (n = 4) were pulsed with full-length GAD65 proteins or with 15-mer peptides from GAD65. T cell activation, exhaustion, and cytotoxicity were measured via cytometric bead array, FluoroSpot, flow cytometry, and live cell imaging. Results CD8+ T cells from patients with GAD65Ab-associated neurological disorders (AD) were activated by exposure to DCs pulsed with full-length GAD65 (p < 0.01 vs unstimulated, Mann-Whitney test; n = 16). We found 3 peptides of interest that caused a 10-30% increase in activated CD8+ T cells in GAD65AbAD patients, as assessed by surface CD69+ labeling. Using NetMHCpan4.2, we identified 8 different 9-mer peptides with high predicted affinity for HLA-C*03:03/04 and HLA-C*07:01/02. Two of these peptides showed high binding to HLA-C and subsequently demonstrated tetramer labeling of CD8+ T cells in GAD65AbAD patients. Conclusions We demonstrated that both full-length GAD65 protein and specific GAD peptides activated CD8+ T cells derived from patients with GAD65AbAD, indicating a potential pathogenic role for these effectors in these disorders. Funding Sources Support from Aditxt Immune Health Project (EU CT number: 2023-504798-19-00) and the Center for MS and Autoimmune Neurology in Mayo Clinic. Topic Categories Neuroimmunology (NEUR)

Abstract Description Background Castration-resistant prostate cancers (CRPC) do not respond to immunotherapy.1,2 Prostate cancer-derived immune factors (IF) like sPD-L1 drive immunosuppression and resistance.3 Circulating tumor-reactive T cells (TTR; CD8+CD11ahigh) and other immune subsets predict progression-free survival in oligometastatic CRPC after radiotherapy.4 A better understanding of the levels and changes in IF in CRPC—a tumor immune “circulome”—may lead to better immunotherapeutic approaches. Methods 79 men with oligometastatic castration-resistant prostate cancer were treated with radiation and blood was collected before and after treatment (NCT02816983). Peripheral blood mononuclear cells (PBMC) were subjected to immunophenotyping, and plasma was subjected to the Olink Explore panel assay measuring levels of 5,416 IFs using a proximity extension assay technology. Results High baseline soluble levels of PD-L1, PD-L2, TIM-3, and other selected immunotherapy-related IFs predicted inferior outcomes, including overall survival. Conversely, high soluble CTLA-4 levels strongly predicted superior outcomes (p < 0.0001). These results additionally correlated with changes in circulating tumor-reactive (TTR) T cells in these patients. Discussion IF influence systemic immunity in CRPC. These results suggest a multifactorial mechanism by which prostate cancers drive systemic immunosuppression and resistance to immunotherapy. Ongoing efforts to address IFs may help overcome CRPC immunotherapy resistance.5 Funding Sources Department of Defense HT9425-24-1-0622, An Atlas of the Tumor Immune Circulome (PI: Orme) Prostate Cancer Foundation Young Investigator Award (PI: Orme) National Cancer Institute K12 CA90628-23 (PI: Orme) Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)

Abstract Description This study dissects mechanisms of spontaneous tumor rejection leading to better understanding of successful immune responses to cancer. Cancers persist despite expression of tumor-specific neoantigens promoting ongoing anti-tumor immune responses. While some occult tumor cells likely are cleared by effective anti-tumor immune responses, the targeted antigens are not easily identifiable as those cells spontaneously disappear. Congenic mouse breast carcinoma models expressing a defined protein mimicking neoantigens were used to dissect the protective spontaneous immune response. BALB/c (MHC H-2d) mice challenged with BALB/c breast tumors expressing the rat-erbB2 oncoprotein succumb to their tumors despite demonstrated tumor immunogenicity, mimicking known patient responses to cancer. Meanwhile, H-2b positive BALB.B and H-2d/H-2b F1 hybrid mice spontaneously eliminate genetically matched tumors in an MHC-II dependent manner. CD4+ T-cells and B-cells or the rat-erbB2-specific antibodies they produce are crucial mediators of this protective response. Differences in the tumor microenvironments in rat-erbB2+ tumor-bearing BALB.B and BALB/c mice at the time of fate decision in the models reflect the differences between effective and ineffective anti-tumor immunity. Identifying the nature of the optimal MHC-II antigens, how they activate protective CD4+ T-cells, and the interactions that promote protective antibodies will better inform future cancer therapies. Funding Sources Bernie Fineman Research Fund Mayo Clinic Center for Biomedical Discovery Mayo Clinic Department of Immunology Mayo Clinic Graduate School of Biomedical Sciences NIH Traning Grant 5 R25 GM 55252 Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)

Background: Injury to the medial ulnar collateral ligament (MUCL) is a common setback for throwing athletes, often requiring reconstruction with 12 to 18 months of rehabilitation. The authors previously described a more anatomic technique with improved mechanical strength as compared with the docking technique, which may allow for an accelerated return to sport. Purpose: To evaluate return-to-sport rates, time to return to sport, and the effect on the functional performance of amateur and professional throwing athletes who underwent anatomic MUCL reconstruction with suture tape augmentation. Study Design: Case series; Level of evidence, 4. Methods: A retrospective case series was performed including baseball players who underwent anatomic MUCL reconstruction with suture tape augmentation by a single surgeon from 2018 to 2022. Inclusion criteria consisted of a minimum 2-year follow-up, participation in baseball, and utilization of autograft (palmaris longus or gracilis). Patients who underwent previous MUCL reconstruction were excluded from the study. All patients initially followed an accelerated rehabilitation protocol. Outcome measures were collected, including Kerlan-Jobe Orthopaedic Clinic (KJOC), Single Assessment Numeric Evaluation (SANE), and Conway-Jobe scores, as well as throwing metrics such as ball velocity and spin rate. Results: Thirty-four baseball players (mean ± SD age, 21 ± 3 years) underwent primary MUCL reconstruction. Time of final follow-up was 36.1 ± 10.3 months. Of these, 16 were professional athletes and 18 were amateur. All throwers returned to live gameplay at a mean 10.1 ± 2.0 months after reconstruction (professional, 10.6 ± 2.3; amateur, 9.7 ± 1.8). Furthermore, 97% (94% professional, 100% amateur) advanced through the accelerated postoperative protocol without issues, and 91% (88% professional, 94% amateur) returned to the same role and 85% (75% professional, 94% amateur) to the same level of play. Professional postinjury KJOC scores improved from 42.6 ± 16 to 87.5 ± 8.3 and SANE scores from 25.0 ± 11.2 to 95.6 ± 4.2. Amateur postinjury KJOC scores improved from 35.6 ± 10.7 to 90.9 ± 8.6 and SANE scores from 57.5 ± 16.9 to 95.2 ± 7.2. No significant difference was identified in preinjury versus postreconstruction throwing velocity, ball spin rate, or horizontal/vertical ball movement. The overall failure rate was 2.9%, with 1 professional pitcher requiring revision for graft rupture at 3 years postoperatively. Conclusion: Anatomic reconstruction of the MUCL with suture tape is a viable option for MUCL injuries, allowing an expedited return to sport at 10.1 ± 2.0 months (professional, 10.6 ± 2.3; amateur, 9.7 ± 1.8) in baseball players, with a low failure rate.

After successfully implementing an acute care telemedicine program internally, health care institutions often consider expanding and scaling services externally beyond the initial organizational network. This report outlines important considerations when expanding acute care telemedicine services externally, including cultural alignment and agility, practice context, staffing models, telemedicine technology selection, interrelated services, legal and compliance considerations, quality assurance, risk management, financing, and integration with medical education. These factors may inform program leaders of major planning considerations, potential barriers, and could influence strategic planning. Prospectively identifying and resolving challenges prior to contracting with new external sites will facilitate smooth, successful implementation and high utilization of the acute care telemedicine service.

Importance Treatment for cognitive dysfunction due to postacute sequelae of long COVID (ie, symptoms of fatigue, malaise, weakness, confusion that persist beyond 12 weeks after an initial COVID infection) remains a significant unmet need. Objective To test evidence-based rehabilitation strategies for improving cognitive symptoms in persons with long COVID. Design, Setting, and Participants This was a 5-arm, multicenter, randomized clinical trial of 3 remotely delivered interventions conducted between August 17, 2023, and June 10, 2024. The study took place at 22 trial sites and included the screening of individuals with cognitive long COVID. Interventions Participants were randomized to 1 of 5 arms: adaptive computerized cognitive training (BrainHQ [Posit Science]), cognitive-behavioral rehabilitation involving both group and individual counseling sessions (PASC-Cognitive Recovery [PASC-CoRE]) paired with BrainHQ, and transcranial direct current stimulation (tDCS) paired with BrainHQ. Two comparator arms were included as follows: unstructured computer puzzles and games (active comparator) and sham tDCS paired with BrainHQ. The interventions occurred 5 times per week over 10 weeks. Main Outcomes and Measures Cognitive and behavioral in-person assessments were performed at baseline, midintervention, at the end of intervention, and 3 months after the end of the intervention. The primary outcome measure was the modified Everyday Cognition Scale 2 (ECog2) completed at the end of the intervention compared to the baseline visit based on participant self-report looking back over the prior 7 days. Results A total of 378 individuals were screened, from which there were 328 participants (median [IQR] age, 48.0 [37.0-58.0] years; 241 female [73.5%]; race: 15 Asian [4.6%], 47 Black [14.3%], and 235 White [71.6%]; ethnicity: 52 Hispanic [15.9%]). None of the 3 active interventions demonstrated benefits on the modified ECog2 in the intention-to-treat population by the end of the intervention period. The adjusted differences in mean change were 0.0 (95% CI, −0.2 to 0.2) for BrainHQ vs active comparator, 0.1 (95% CI, −0.1 to 0.3) for PASC-CoRE + BrainHQ vs active comparator, 0.0 (95% CI, −0.2 to 0.2) for tDCS-active + BrainHQ vs tDCS-sham + BrainHQ, and 0.1 (95% CI, −0.1 to 0.3) for PASC-CoRE + BrainHQ vs BrainHQ alone. Secondary participant-reported outcomes and neuropsychological tests showed no differential benefits for any treatment arm. All 5 arms demonstrated some improvements over time on the modified ECog2 and on secondary outcomes. There were no serious adverse events attributable to the interventions. Conclusions and Relevance This phase 2 randomized clinical trial failed to demonstrate differential benefits for online cognitive training, a structured cognitive rehabilitation program, and tDCS for cognitive long COVID. Trial Registration ClinicalTrials.gov Identifier: NCT05965739 .