Citations

AbstractIntroductionFor patients with catecholamine‐resistant vasoplegic syndrome (VS) during liver transplantation (LT), treatment with methylene blue (MB) and/or hydroxocobalamin (B12) has been an acceptable therapy. However, data on the effectiveness of B12 is limited to case reports and case series.MethodsWe retrospectively reviewed records of patients undergoing LT from January 2016 through March 2022. We identified patients with VS treated with vasopressors and MB, and abstracted hemodynamic parameters, vasopressor requirements, and B12 administration from the records. The primary aim was to describe the treatment efficacy of B12 for VS refractory to vasopressors and MB, measured as no vasopressor requirement at the conclusion of the surgery.ResultsOne hundred one patients received intraoperative VS treatment. For the 35 (34.7%) patients with successful VS treatment, 14 received MB only and 21 received both MB and B12. Of the 21 patients with VS resolution after receiving both MB and B12, 17 (89.5%) showed immediate, but transient, hemodynamic improvements at the time of MB administration and later showed sustained response to B12.ConclusionImmediate but transient hemodynamic response to MB in VS patients during LT supports the diagnosis of VS and should prompt B12 administration for sustained treatment response.

AbstractBackgroundPerturbations in immune pathways are strongly associated with Alzheimer’s disease. A positive association between autoimmune diseases and frontotemporal dementia has been reported. We explored whether early onset Alzheimer’s disease (EOAD) would associate with autoimmune diseases.MethodWe compared 313 patients with EOAD from the Mayo Clinic Florida, Alzheimer’s Disease Research Center (ADRC) Registry with matched cognitively normal controls (NC) based on age (+/‐ 2 years) and gender at 1:2 ratio. NC were derived from Mayo Clinic Biobank Project, Rochester (N = 313) and the Mayo Clinic Study of Aging (N = 313). Data abstraction was performed by trained statisticians using ICD 9&10 codes corresponding to 40 specified autoimmune diseases and/or documentation of specified immunomodulatory treatment. Data was also abstracted via retrospective record review. We further reviewed clinical records from EOAD patients with neuropathologically confirmed Alzheimer’s disease patients enrolled in the ADRC (n = 10). Each autoimmune disease type was compared between cases and controls using Fisher’s exact test. All tests were two‐sided with alpha level set at 0.05 for statistical significance. Continuous variables were summarized as median (range) while categorical variables were reported as frequency (percentage). The prevalence of autoimmune disease in the general population was based off Hayter & Cook, 2012 and Roberts & Erdei, 2020. All data abstraction was done blinded to the clinical diagnosis and baseline demographics.ResultAutoimmune disease history was abstracted from 949 patient records (313 EOAD, 10 pathologically‐confirmed EOAD, 626 NCI). The median age was 57 years‐old. (EOAD range 28,65 yrs.; NC 30,66 yrs.). Autoimmune thyroiditis (p = 0.0008), ulcerative colitis (p = 0.011, psoriasis (<0.0001), rheumatoid arthritis (p = 0.0005), and Raynaud’s syndrome (p = 0.0021) were less prevalent in patients with EOAD compared to NC. Furthermore, patients with EOAD had a lower prevalence of immune mediated hematologic disorders.ConclusionPatients with EOAD have a lower prevalence of autoimmune diseases than NC. Immune activation identified in early onset AD patients may be unrelated to autoimmunity. Findings should be explored in late onset AD patients.

Background: Depression is prevalent in almost half of patients with cardiovascular disease (CVD) and is associated with CVD and mortality. We used an artificial intelligence algorithm using ECG that predicts physiological age (ECG-Age) that has been linked to increased total and CVD mortality and CVD risk factors. We hypothesized that depressive symptoms would be associated with physiologic aging, as measured by AI-ECG Methods: A previously validated algorithm was applied to determine ECG-Age to 105,732 consecutive ECGs of individuals age ≥18 who sought care at Mayo Clinic between June 2019 and January 2022 and filled the Patient Health Questionnaire-9 (PHQ-9) within a month of ECG. PHQ-9 ascertains severity and frequency of depressive symptoms with values from 0 - 27 and were categorized as (None≤4, Mild 5-9, Moderate 10-14, Moderately severe 15-19 and Severe ≥20). Delta-Age was defined as ECG-Age minus chronological age and accelerated aging was defined as a Delta-Age >1SD above the mean. Logistic regression analyses associated PHQ-9 scores with positive Delta-Age while adjusting for CVD risk factors Results: Mean chronological age was 57±17 yr and mean ECG-Age 58±14 yr (R2 0.85, P < 0.0001), Delta-Age 0.71±9.40 yr, 58% women, average PHQ-9 5±6, 61% had none, 20% mild, 10 % moderate, 5%moderately severe and 4% had severe depressive symptoms. Delta-Age was 2.10 years higher in those with depressive symptoms, reflecting accelerated aging. Compared to those with no depressive symptoms, those with severe symptoms were 1.5 times more likely to have Delta-Age >1SD (OR 1.52 CI 95%1.73-1.33), independently of CV risk factors and the Charlson comorbidity index. Figure. There is significant attenuation of the association once accounting for age, sex and CVD risk factors Conclusions: Depressive symptoms are associated with physiologic aging, highlighting the role of depression in physiologic aging and the potential of preventive strategies in patients with depression and CVD

Introduction: Metabolically obese normal weight (MONW) refers to metabolic abnormalities despite normal body mass index (BMI). Hypothesis: Because obesity is generally defined by BMI, it is assumed that people with MONW do not have excessive adiposity but still have the metabolic dysregulation associated with adiposity. Methods: We included participants aged 20-65 of the National Health and Nutrition Examination Surveys from 1999-2006 and 2011-2018 with normal BMI (18.5-25 kg/m 2 ), fasting blood samples, and DEXA data. According to the AHA criteria, MONW was defined having ≥3 of the following criteria, besides a normal BMI: Hypertriglyceridemia (≥ 150 mg/dL) or treatment for elevated triglycerides; HDL cholesterol level < 40 mg/dL in men or <50 mg/dL in women or treatment for reduced HDL-C; elevated blood pressure (systolic ≥ 130 mmHg and/or diastolic ≥ 85 mmHg) or antihypertensive treatment or history of hypertension; elevated fasting plasma glucose ≥ 100 mg/dL or insulin/oral hypoglycemic treatment and central obesity by waist circumference (≥ 94 cm in men and ≥ 80 cm in women). High fat percentage was defined as ≥25% in men, ≥35% in women. Weighted logistic regression was performed to test the relation between MONW and high fat%, central obesity. Results: Of the 7,887 participants (53.6% men; mean age±SE was 39.23±0.24 years), 2433 (33.4%) had normal BMI included in the analysis. Among these, 148 had MONW (5%). Mean Fat% was 26.08±0.36% in those with MONW versus 21.90±0.17% in those without MONW for men, and 37.02±0.35% versus 33.31±0.21% for women. MONW subjects were 2.21 times more likely to have either central obesity or high fat % (OR 12.09, 95%CI: 6.18-23.67, p<0.01) and 2.18 times more likely to have high fat % (OR=2.84, 95%CI: 1.72-4.67, p<0.01) (see Figure). Conclusions: Most individuals with MONW have either increased fat content, central deposition of fat, or both. That highlights people with normal BMI may still have metabolic complications of adiposity.

Background: The role of body adiposity on metabolic dysregulation in subjects with normal body mass index (BMI) is still under debate with limited population-based evidence. Hypothesis: Body adiposity measured by dual x-ray absorptiometry (DEXA) is associated with metabolic disorders in normal-weight individuals. Methods: We evaluated a sample of adults aged 20-65 who underwent DEXA in the US National Health and Nutrition Examination Surveys from 1999-2006 and 2011-2018. We excluded those with history of cardiovascular disease, cancer, and chronic obstructive pulmonary disease. Weighted logistic regression was performed to test the association between body fat percentage (BF%) and metabolic disorders [e.g., insulin resistance (IR), metabolic syndrome (MS), dyslipidemia, type 2 diabetes mellitus (DM), hypertension]. Models were adjusted for potential confounders while considering complex survey design and were further stratified by sex and BF% as tertiles in normal-weight individuals. IR was tested as a secondary analysis to evaluate the effect on the predicted risk. Results: We included 20,613 individuals (51.5% men, 65.4% non-Hispanic whites), mean age ± SE was 39.42±0.22 years, and 6,424 were normal weight by BMI and represented our study sample. The overall BF% in these subjects measured by DEXA was 28.41±0.19%. In our cohort, metabolic disorders were prevalent in 2.1% to 40.4% of patients (Table 1). Every 10-unit % increase in total BF% was associated with a higher risk for IR, MS, dyslipidemia in the normal weight BMI group (Table 1). Metabolic disorders were associated with BF% tertiles (Figure 1). IR was significantly associated with body fat across all BF% tertiles for men and highest tertiles for women (Figure 2). Conclusion(s): Less than 1/3 of subjects in a representative national sample had a normal BMI. Even in these “normal weight” subjects, increases in body adiposity are significantly associated with increased cardiometabolic disease burden.

Introduction: NGS is increasingly being utilized to identify pathogenic somatic and targetable variants in patients with newly diagnosed AML and MDS. Patients with high-risk disease are typically recommended to undergo allo-HCT as consolidation, upon achieving morphological complete remission (CR). But, despite achieving hematologic CR, patients often have detectable somatic variants pre allo-HCT that predict for increased risk of disease relapse. Longitudinal monitoring of somatic variants via NGS at diagnosis, pre-allo-HCT and post allo-HCT can assist in prognostication and identify patients that remain at high risk of relapse despite allo-HCT. Methods: Patients with AML or MDS who underwent a first allo-HCT and completed NGS testing at day +100 between years 2016 to 2021 were identified from the transplant registry of Mayo Clinic in Florida. The primary aim of the study was to evaluate the prognostic impact of detectable variants via NGS at day +100 days post allo-HCT on the following outcomes: 1) overall survival (OS), 2) relapse, 3) progression-free survival (PFS), and 4) non-relapse mortality (NRM). Disease risk was assessed based on European Leukemia Network (ELN) 2022 risk classification for AML and Revised International Prognostic Scoring System (R-IPPS) for MDS. Baseline variables were compared between patients with and without mutation at day +100 days post allo-HCT using Wilcoxon rank sum test for continuous variables and Fisher's exact test for categorical variables. Kaplan-Meier (KM) method was used to estimate freedom from events at different time points and draw corresponding survival curves. Results: 105 patients who underwent allo-HCT for AML and MDS and completed NGS testing at day +100 were included in the study population. Median age of the study population was 63 years (22-74) and 58% were of the male gender. Median HCT comorbidity score (HCT-CI) and KPS Karnofsky performance score (KPS) were 3 (0-8) and 90 (60-100), respectively. Matched unrelated donor (50%) and peripheral blood stem cells (98%) were the most common donor and graft source, respectively. Median number of lines of therapy pre allo-HCT was 1(0-6) and 52 (50%) patients had detectable variants after completion of chemotherapy and prior to allo-HCT. Seventeen (16%) had detectable variants via NGS on day +100. Eleven (65%) of these 17 had variants pre-allo-HCT and amongst the 88 patients with no variants post allo-HCT, 41 (47%) had detectable variants pre allo-HCT. There was no significant difference in baseline characteristics between patients with detectable variants at day+100 versus those who did not except for a higher KPS in patients with no variants at Day +100 of 90 (60-100) vs. 80 (60-100) (p=0.003). At a median follow up of 1.4 years (0.1-5.5), presence of a variant at day +100 was associated with inferior 4-year OS (32% vs. 69%, p&lt;0.001) and higher relapse risk (64% vs. 23%, p&lt;0.001). In univariate models, a lower KPS and presence of variants post allo-HCT were significantly associated with inferior OS, high relapse risk and worse PFS. Presence of variants pre allo-HCT was associated with an inferior PFS but did not impact OS or relapse risk. In multivariate models, KPS remained significant for OS, PFS and NRM; presence of variants at day +100 post allo-HCT approached significance for OS (p=0.06) and PFS (p=0.08) and was significant for relapse risk (p=0.002) (Table1) (Figure 1). Data regarding longitudinal evolution of variants and impact of individual variants on long term outcomes will be included at the time of presentation. Conclusion: These results indicate that presence of detectable somatic variants at day +100 is associated with poor long-term outcomes and predicts for high risk of disease relapse. Longitudinal monitoring of somatic variants via NGS should be consistently incorporated in the management of patients with high-risk AML and MDS undergoing allo-HCT. Patients with detectable somatic variants post allo-HCT should be considered for additional intervention to mitigate relapse risk.

Background/Objective Few studies have investigated associations between rheumatologic serology patterns and different interstitial lung disease (ILD) patterns. Methods We present novel findings of a historic cohort study (n = 454) with data collected from 2011 to 2021 within our hospital system. In this institutional review board–approved study, data regarding rheumatologic serologies and ILD patterns were noted based on chart review in patients with scleroderma. The Kruskal-Wallis rank sum and χ 2 tests were used for statistical analysis. Results Results showed a statistically significant association between anti-U1 snRNP with lymphoid interstitial pneumonia, which has not been previously described. Conclusions We demonstrated novel serologic associations with ILD patterns, which have important clinical implications. More robust and high-powered studies are needed to elucidate the role of serologic testing and their association with ILD phenotypes.

Background: The gap between electrocardiogram (ECG) artificial intelligence-derived age (ECG-Age) and chronological age (Age-Gap) predicts cardiovascular (CV) comorbidities and mortality reflecting physiologic age. Adverse childhood experiences (ACEs) are traumatic and harmful events that impact adulthood CV outcomes. We hypothesized that ACEs would be associated with physiologic age as determined by the Age-Gap. Methods: We applied a previously validated ECG-Age algorithm to the ECGs of 1,988 consecutive individuals aged ≥18, that within 2 years completed an ACEs questionnaire as part of psychological evaluations for weight management. The ACE questionnaire assesses 3 psychosocial domains (i) childhood abuse (psychological, physical or sexual), (ii) household dysfunction (substance abuse, mental illness, female figure treated violently, criminal behavior and parental separation/divorce) and (iii) neglect (emotional or physical) before age 18; results ranged 0 to 10 and were categorized as burden (0, 1-3, and ≥4) and presence (abuse, household dysfunction, neglect). Age-Gap was operationalized as (≤mean or > mean) positive values reflect physiological aging. Logistic regression analyses tested the association between ACE and Age-Gap. Results: Mean ± SD chronological age was 49±13 yr, ECG-Age 54±12 yr, Age-Gap 4.26±8.95 yr,75% women, average ACE 2±2, 32% experienced 0, 44% 1-3, and 24% ≥4 ACEs. Age-Gap was 1.4 years higher in those who experienced at least 1 ACE. Compared to those who didn’t experience ACE those who faced 1-3 ACE were more likely to have an Age-Gap >mean (OR 1.28 95%CI 1.57-1.04) independent of sex and the age-adjusted Charlson comorbidity index Fig A. Also, they were more prone to experiencing neglect and household dysfunction Fig B. Conclusions: Age-gap was associated with ACEs burden and domains, underscoring the need to identify ACEs during clinical evaluations to prevent ACEs at the individual, family, and community levels.

OBJECTIVES: To systematically review literature describing the clinical presentation, risk factors, and treatment for dexmedetomidine withdrawal in the PICU (PROSPERO: CRD42022307178). DATA SOURCES: MEDLINE/PubMed, Cochrane, Web of Science, and Scopus databases were searched. STUDY SELECTION: Eligible studies were published from January 2000 to January 2022 and reported clinical data for patients younger than 21 years old following discontinuation of dexmedetomidine after greater than or equal to 24 hours of infusion. DATA EXTRACTION: Abstracts identified during an initial search were screened and data were manually abstracted after full-text review of eligible articles. The Newcastle-Ottawa Scale was used to assess study quality. Summary statistics were provided and Spearman rank correlation coefficient was used to identify relationships between covariates and withdrawal signs. A weighted prevalence for each withdrawal sign was generated using a random-effects model. DATA SYNTHESIS: Twenty-three studies (22 of which were retrospective cohort studies) containing 28 distinct cohorts were included. Median cumulative dexmedetomidine exposure by dose was 105.95 μg/kg (range, 30–232.7 μg/kg), median dexmedetomidine infusion duration was 131.75 hours (range, 20.5–525.6 hr). Weighted estimates for proportion (95% CI) of subjects experiencing withdrawal signs across all cohorts were: hypertension 0.34 (range, 0.0–0.92), tachycardia 0.26 (range, 0.0–0.87), and agitation 0.26 (range, 0.09–0.77). Meta-analysis revealed no correlation between dexmedetomidine exposure variables and withdrawal signs. A moderate negative monotonic relationship existed between the proportion of patients who had undergone cardiac surgery and the proportion experiencing hypertension (correlation coefficient, –0.47; p = 0.048) and tachycardia (correlation coefficient, –0.57; p = 0.008), indicating that in cohorts with a higher proportion of patients who were postcardiac surgery, there were fewer occurrences of hypertension and or tachycardia. CONCLUSIONS: On review of the 2000–2022 literature, dexmedetomidine withdrawal may be characterized by tachycardia, hypertension, or agitation, particularly with higher cumulative doses or prolonged durations. Since most studies included in the review were retrospective, prospective studies are needed to further clarify risk factors, establish diagnostic criteria, and identify optimal management strategies.

Introduction: This study evaluated patient preference of physician attire both before and after the coronavirus disease 2019 (COVID-19) global pandemic began. The primary outcome was patient preference of physician attire in 2017 compared to 2022 survey cohorts. Methods: An observational cross-sectional study performed at a single-site academic institution in the United States using patient survey materials. In total, 339 patients were included in the study, 161 from 2017 and 178 from 2022. Key Points: There was a statistically significant decrease in patient preference for formal attire in the clinical settings of primary care, hospital, and overall. Male patient preference for formal attire declined in primary care, emergency room, and overall; whereas female patient preference for formal attire declined in the hospital setting. For all genders, the odds ratio was statistically significantly lower in the settings of primary care clinic, hospital, and overall clinical settings. Conclusions: Patient preference for physicians wearing formal attire has decreased significantly since the COVID-19 global pandemic began.