Citations

Background Transplantation using hearts obtained through donation after circulatory death (DCD) is increasing, but data on recipient renal outcomes are limited. Methods and Results Patients at a single institution who underwent heart transplantation using organs procured through DCD or donation after brain death (DBD) from April 2016 to August 2022 were included in this retrospective cohort study. Hemodynamic measures were collected via right heart catheterization performed 1 week after transplantation. Posttransplantation renal outcomes included estimated glomerular filtration rate at 1 week, 4 weeks, and 16 weeks, and the incidence of acute kidney injury (AKI) and renal replacement therapy within 1 week. The analysis included 225 patients (55 recipients of DCD). Baseline characteristics were comparable between recipients of DCD and DBD. Renal outcomes within 1 week posttransplantation in recipients of DCD were similar to recipients of DBD, including percent change in estimated glomerular filtration rate (−37.9% [−58.6 to −6.2] versus −31.9% [−52.4 to −9.9]; P =0.91), incidence of AKI (47.3% versus 46.5%; P >0.99) and incidence of renal replacement therapy (3.6% versus 4.7%; P >0.99). Recipients of DCD with AKI within 1 week (“early AKI”) did not recover to baseline estimated glomerular filtration rate (75.8 [60.2–91.3] mL/min per 1.73 m 2 ) by week 16 (59.3 [46.9–73.6] mL/min per 1.73 m 2 ; P =0.002), whereas recipients without early AKI exhibited comparable estimated glomerular filtration rate to baseline by week 4 (84.5 [70.8–98.5] mL/min per 1.73 m 2 ; P =0.084). Similar trends were observed in recipients of DBD. Conclusions Recipients of DCD demonstrated similar renal outcomes compared with recipients of DBD, supporting the ongoing use of DCD transplantation. Early AKI was associated with persistent renal dysfunction for recipients of both DCD and DBD.

BACKGROUND: Sugammadex, aprepitant, and fosaprepitant are increasingly used perioperatively. These medications may interfere with the effectiveness of hormonal contraception. This study assessed anesthesia providers’ use of sugammadex and aprepitant, their knowledge of interactions with hormonal birth control, and patient counseling practices to identify possible knowledge gaps or opportunities for practice improvement. METHODS: In January 2023, an electronic survey was distributed to all anesthesia providers at Mayo Clinic sites (Mayo Clinic Rochester, Mayo Clinic Arizona, Mayo Clinic Florida, and Mayo Clinic Health System hospitals). The survey included 32 questions assessing providers’ use of sugammadex and aprepitant, their knowledge of the medications’ interactions with hormonal contraceptives (HC), their perceptions regarding education of these interactions during training, and their perioperative patient counseling practices. The collected data were analyzed using descriptive statistics. RESULTS: A total of 337 of 1092 (31%) providers completed the survey. While almost all respondents (324; 96%) knew that sugammadex may interfere with oral contraceptive effectiveness, only 158 (47%) knew about aprepitant’s potential contraceptive interference. Only 176 providers (52%) knew the recommended duration for alternative contraceptive methods after use after sugammadex, and 119 providers (35%) knew the recommended duration after aprepitant exposure. Most respondents considered the interference of these perioperative drugs with HCs to be clinically relevant (sugammadex, 217, 64%; aprepitant, 191, 58%). Despite the common belief that the decision between these medications and alternatives should be shared between provider and patient, most providers reported rarely engaging in such shared decision-making (SDM) in practice. Most providers recognized the need for preoperative discussions on sugammadex (280, 83%) and aprepitant (257, 76%), yet 184 providers (73%) never or rarely discussed contraception use before surgery for aprepitant, and 135 (36%) never or rarely did so for sugammadex. Lastly, many providers believed that the interference between sugammadex, aprepitant, and HC was poorly taught during training. CONCLUSIONS: The results of this study highlight the need for increased education and awareness among anesthesia providers regarding drug interactions with HCs during the perioperative period. To facilitate SDM, it is imperative that providers discuss alternative medications and the potential need for additional contraception methods after drug administration and communicate the risks with patients preoperatively to enable informed and SDM. The patient’s preferences should be accounted for, especially if they are unwilling or unable to use an alternative contraceptive for 7 to 30 days, thereby avoiding the complexities and burdens of altering birth control methods.

Abstract Background Hypomagnesemia has been correlated with inferior outcomes in patients with large B cell lymphoma (LBCL) undergoing stem cell transplants. As T-cell and myeloid cell dysfunction have been associated with low magnesium conditions, we investigated whether serum magnesium (Mg) levels could predict clinical outcomes in LBCL patients who received chimeric antigen receptor T-cell therapy. Methods Patients with LBCL who received axi-cel under the ZUMA-1 trial or as FDA approved therapy at Mayo Clinic were examined. Serum samples were obtained at specified time points and cytokine analysis was performed. Single cell RNA sequencing was performed on peripheral blood mononuclear cells. The Student T-test, Kruskal Wallis, or Fisher's Exact Tests were used to compare differences in demographics across Mg levels. Survival curves were plotted using the Kaplan-Meier methodology and compared using the Wilcoxon test. Results We found that hypomagnesemia before lymphodepletion chemotherapy predicted for inferior progression-free and overall survival in the pivotal study ZUMA-1 (NCT02348216). These results were validated in an independent cohort of LBCL patients receiving axicabtagene ciloleucel (axi-cel) at Mayo Clinic. Hypomagnesemia correlated with increased inflammatory serum markers and cytokine levels including ferritin, IL-6, IL1Ra, IL-8, and MIP1a. scRNAseq analysis unveiled altered immune interactions between monocytes and T cells with a concordant immune suppressive transcriptome. Conclusions Hypomagnesemia at the time of CAR-T infusion associates with an unfavorable inflammatory profile and decreased response and survival in LBCL patients receiving axi-cel. These findings suggest a potentially actionable prognostic factor for patients with large cell lymphoma undergoing CAR-T.

Abstract Accumulating evidence suggests dysregulated immune checkpoint (IC) signaling can exacerbate COVID-19 severity, but the role of these molecules in the pathogenesis of fatal COVID-19-related diffuse alveolar damage (DAD) remains elusive. Understanding how IC proteins influence acute lung injury due to COVID-19 can provide insights into potential therapeutic strategies to modulate immune responses and improve patient outcomes. Here, in a single-center autopsy cohort, we determined the cellular localization of ICs in lung tissue from cases of fatal COVID-19, DAD-comparators, and non-fibrotic controls by using immunohistochemistry, and investigated their association with clinical outcomes. We expanded our findings by performing analyses of publicly available single-cell RNA sequencing datasets from patients with fatal COVID-19 and non-fibrotic controls. We demonstrated the presence of protein-protein interaction networks of ICs in the lung cellular niche by performing transcriptomic profiling of lung tissue-derived RNA counts from patients with fatal COVID-19. Further, we leveraged data from the largest international, multi-center COVID-19 autopsy cohort and validated that, among patients with fatal COVID-19, those with higher PD-L1/CD274 expression in lung endothelial cells had more rapid clinical deterioration. Lastly, in a cohort of individuals with early COVID-19, IC plasma protein levels were elevated in those with persistent SARS-CoV-2 RNAemia and adverse clinical outcomes. Collectively, our data provide unique pathological insights into the role of IC dysregulation and differential disease severity in COVID-19.

Abstract Background THES is a rare autosomal recessive syndromic enteropathy caused by pathogenic variants in two genes, the Tetratricopeptide Repeat Domain 37 (TTC37) and Ski2 Like RNA Helicase (SKIV2L), that encode components of the human SKI complex involved in RNA degradation. This disease is characterized by several clinical features with variable penetrance including intractable congenital diarrhea, wooly hair abnormalities, intrauterine growth restriction, facial dysmorphism, immune dysfunction, liver abnormalities, and skin hyperpigmentation. Hypogammaglobulinemia with low IgG and normal to low IgM levels have been described in these cases which may require intravenous immunoglobulin (IVIG) replacement therapy. Some cases have a reduced population of switched memory B cells, T cells with reduced IFN-γ secretion, and hyporesponsive NK cells. Our patient is a 4-year-old female reported to have a homozygous TTC37 mutation with clinical manifestations of TPN dependence, liver fibrosis with portal hypertension, splenomegaly, developmental delay, thrombocytopenia and anemia requiring transfusion, and a history of hypogammaglobinemia requiring IVIG replacement. Patient would go on to develop elevated immunoglobin levels leading to additional testing described below. Methods Serum total protein analysis performed using the using Siemens Atellica CH Total Protein II test (Weichselbaum method using biuret reagent). Serum immunoglobin (IgA, IgG and IgG), IgG subclass, and kappa/lambda free light chain level analysis performed by turbidimetric photometry assay using a Binding Site Optilite analyzer. Serum protein electrophoresis and immunotyping performed using CAPILLARYS 2 capillary zone electrophoresis and immunosubtraction with antisera. Serum protein immunofixation performed using Sebia Hydrasys 2 with Hydragel 9 IF Maxi kit. Confirmation and final determination of serum immunoproteins performed at our reference laboratory using MASS-FIX (MALDI-TOF MS) matrix-assisted laser desorption/ionization-time of flight mass spectrometry after patient serum applied to 5 separate immunoaffinity resins specific to immunoglobulin G, A, M, K, and L for purification. Results Initial testing showed a broadly migrating beta-gamma region IgG kappa monotypic restriction measuring 1.7 g/dL, with predominantly kappa subtraction and trivial lambda subtraction by immunosubtraction; serum free kappa/lambda light chain ratio was increased at 22.94. Serum immunoglobins and free light chains measured (mg/dL): IgA 738 (15 - 160), IgM 48 (50 - 240), IgG 2,805 (405 - 1,160), free kappa 20.42 (0.33 - 1.94), and free lambda 0.89 (0.57 - 2.63). IgG subclasses measured (mg/dL): IgG1 533 (320 - 950), IgG2 174 (50 - 340), IgG3 16.9 (10.0 - 120.0), IgG4 1,221.1 (2.0 - 110.0). Additional serum protein values included (g/dL): total protein 8.10 (6.00 - 8.30), albumin 2.97 (3.43 - 4.84), alpha-1 0.32 (0.21 - 0.44), alpha-2 0.52 (0.54 - 0.97), beta globulin 3.42 (0.65 - 1.03), and gamma globulin 0.87 (0.70 - 2.30). The polyclonal nature of the IgG4 spike was later demonstrated by the MASS-FIX mass spectrograph. Conclusions MASS-FIX is a useful addition to the toolset used in the diagnosis of possible monoclonal gammopathies and protein disorders, especially where broad monotypic restrictions are observed or in patients with abnormal presentations for monoclonal gammopathies. Using current standard techniques, the above case could have been incorrectly classified as a monoclonal process resulting in unnecessary cost and incorrect treatment.

ImportancePatients with atrial fibrillation (AF) who have ischemic stroke despite taking oral anticoagulation therapy (OAT) have a very high risk of recurrence. Left atrial appendage occlusion (LAAO) is a mechanical stroke prevention strategy that may provide additional protection in patients with thromboembolic events under OAT.ObjectiveTo compare percutaneous LAAO with continuing OAT alone regarding stroke prevention in patients with AF who had a thromboembolic event despite taking OAT.Design, Setting, and ParticipantsThis cohort study was a propensity score–matched comparison of the STR-OAC LAAO cohort, an international collaboration of 21 sites combining patients from multiple prospective registries of patients who underwent LAAO between 2010 and 2022. STR-OAC LAAO cohort patients who had follow-up longer than 3 months were propensity score–matched to a previously published control cohort comprising patients from an established international collaboration of investigator-initiated prospective studies. This control cohort included patients with nonvalvular AF, recent ischemic stroke or transient ischemic attack, and follow-up longer than 3 months who were taking OAT before the index event. Analyses were adjusted for imbalances in gender, age, hypertension, diabetes, and CHA2 DS2-VASc score.ExposureLeft atrial appendage occlusion vs continuation of oral anticoagulation therapy alone (control group).Main Outcomes and MeasuresThe primary outcome was time to first ischemic stroke.ResultsFour hundred thirty-three patients from the STR-OAC LAAO cohort (mean [SD] age, 72 [9] years; 171 [39%] females and 262 [61%] males; mean [SD] CHA2 DS2-VASc score, 5.0 [1.6]) were matched to 433 of 1140 patients (38%) from the control group. During 2-year follow-up, 50 patients experienced ischemic stroke: an annualized event rate of 2.8% per patient-year in the STR-OAC LAAO group vs 8.9% per patient-year in the control group. Left atrial appendage occlusion was associated with a lower risk of ischemic stroke (hazard ratio, 0.33; 95% CI, 0.19-0.58; P < .001) compared with the control group. After LAAO, OAT was discontinued in 290 patients (67%), and the remaining 143 patients (33%) continued OAT after LAAO as an adjunctive therapy.Conclusions and RelevanceIn patients with nonvalvular AF and a prior thromboembolic event despite taking OAT, LAAO was associated with a lower risk of ischemic stroke compared with continued OAT alone. Randomized clinical trial data are needed to confirm that LAAO may be a promising treatment option for this population with a very high risk of stroke.

Abstract Introduction: The Community Engagement Internal Medicine Residents Rotation (IMRR) connects Mayo Clinic Florida (MCF) medical professionals to partners in the Florida catchment area to better understand administrative operations, the referral processes of these organizations and how best they fit the needs of the communities they serve. The goal is to give residents exposure to a more diverse population including rural, Black and Hispanic/Latin as well as connecting them with partners where community- based research is conducted. This IMRR is also designed to encourage cancer-focused community based research (CBR). We learned that the lack of patient diversity at MCF was a drawback to resident recruitment and developing an interest in cancer focused health disparities research. We agreed to assist in this potential solution to the diversity deficit. Methods: The goal for the elective is to provide senior residents with an introduction to community engagement and cancer focused community engaged research. The elective consists of one week of didactics and one of experiential learning. The first week includes an introduction to cancer health disparities in our catchment areas and how to conduct cancer focused CBR. During the second week, residents interact with community partners focused on providing care and cancer education to those who otherwise may not have access to resources. Strategically, these partners are those with whom we are engaged in cancer research initiatives. Internal Medicine Residents (IMR) complete visitation paperwork that included Background Screenings and Sovereign Immunity Contracts. We limit the number of IMR to two in order to accommodate some of the smaller community clinic spaces. IMR visit community partners for no less than a half day each and at the end of the rotation they debrief and complete rotation evaluations. Data: Rotation evaluations aggregated to date indicate 91.67% of IMR feel the rotation meets the goals and objectives. In addition, evaluation comments indicate an improved understanding of population health as well as community resources for improved health and wellness in underserved populations. Anecdotal comments also show evidence of increased understanding of cancer focused CBR and cancer related health disparities. Conclusion: IMMR through community outreach and engagement visits have increased understanding of how partners address varying cancer burden needs. The IMRR has increased residents’ awareness of how environment impacts access to healthcare and improved cost-conscious ordering and treatment plans (medications). IMR better understand the significance of how social determinants of health (SDOH) resources impact community. IMR are better equipped to help patients and their families navigate to additional SDOH solutions and are familiar with the referral process for community safety net resources. The offer of this type of IMRR has enhanced recruitment to MCF training programs and significantly increased IM and fellow participation in cancer focused CBR initiatives and studies. Citation Format: Monica Albertie, Chelsea Reeves, Noreen Stephenson, Folakemi Odedina. Mayo Clinic Cancer Comprehensive Center Community Outreach and Engagement Internal Medicine Residents Rotations [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B035.

Abstract The Cancer Advocacy Training Program aimed to enhance participants' knowledge, skills, and confidence in cancer advocacy, particularly addressing disparities in cancer health outcomes. This evaluation assesses the program's impact through pre- and post-training survey comparisons. The program included 25 participants from various states and focused on comprehensive training. Surveys measured changes in knowledge, attitudes, self-perceived skills, and confidence. Results showed that accurate identification of cancer's main categories increased from 83% to 96%, and awareness of the NCI's mammogram recommendations rose from 70% to 96%. Recognition of the root causes of health disparities remained at 100%, and belief in the inclusivity of cancer advocacy roles was consistently high. Understanding of trust dynamics in advocacy increased by 50%, and recognition of essential political advocacy components improved by 14%. Specific learning outcomes indicated consistent identification of research advocates, a 23% increase in knowledge of strategic funding sources, a 31% improvement in understanding health communication audiences, a 19% rise in awareness of patient advocacy benefits, and a 13% increase in comprehension of informed consent. Confidence in advocacy skills also saw significant improvements. "Extremely confident" participants increased to 33% in problem-solving, adaptability, and communication with stakeholders. Confidence in fundraising and partnership building rose to 19%, evaluation of advocacy outcomes to 24%, identifying key issues to 29%, presentation skills to 33%, and using digital tools to 29%. Self-efficacy results demonstrated notable gains: confidence in solving difficult problems related to cancer advocacy increased with participants reporting "extremely confident" rising from 11% to 33%. Confidence in adaptability under stress improved significantly, with "extremely confident" participants rising from 11% to 33%. Effective communication with stakeholders saw a significant increase, with "extremely confident" participants rising from 17% to 33%. Fundraising and partnership-building confidence increased from 6% to 19%, and confidence in evaluating advocacy outcomes improved, with "extremely confident" participants rising from 6% to 24%. The program effectively enhanced participants' knowledge, attitudes, and advocacy skills, integrating theoretical and practical learning. Gains in confidence across problem-solving, adaptability, and communication skills underline the program's success in preparing participants for real-world advocacy. Participant feedback confirmed the program's relevance and efficacy, suggesting future iterations should emphasize diversity in advocacy and deepen content on key topics. This program serves as a valuable model for empowering cancer advocates and addresses the critical need for targeted training to reduce cancer health disparities. Citation Format: Manisha Salinas, Monica Albertie. Empowering cancer advocates: Evaluating the impact of a comprehensive training program [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B112.

Purpose of review The use of implantable medical devices (IMDs) continues to increase with estimates that 10% of the American population will have an IMD in their lifetime. IMDs require special considerations for management in the perioperative period to ensure optimal patient care and patient safety. This review summarizes the current perioperative considerations for IMDs. Recent findings This review summarizes perioperative recommendations for spinal cord stimulators, deep brain stimulators, peripheral nerve stimulators, vagus nerve stimulators, muscle stimulators, intrathecal drug delivery systems, implantable infusion pumps, artificial pancreas devices, continuous glucose monitors, and cochlear implants. There are multiple publications and guidelines regarding the perioperative considerations of cardiac implantable electronic devices; thus, this review excludes those devices. This review includes recommendations on management of the device perioperatively, the potential complications, and postoperative care of the device. Summary There are very few guidelines regarding the perioperative management of IMDs. Given the significant impact that these devices have on patient care and safety, evidence-based guidelines should be established.