Citations

Abstract Context Lipodystrophy syndromes are rare disorders characterized by deficient adipose tissue, leading to insulin resistance, dyslipidemia, and organ system abnormalities. Objective Our goal was to develop a lipodystrophy severity score (LDS) to holistically capture the diverse manifestations of lipodystrophy into a numerical score to aid in prediction of clinical outcomes and/or treatment impact. Design An 8-domain LDS was developed by 8 disease experts in consultation with patient organizations. The LDS was rated for feasibility and content validity by 28 additional clinicians and 9 patient representatives. LDS was compared to the Clinical Global Impression (CGI) of severity for 20 putative patient profiles, each at 2 different time points, and by comparing change in LDS to global impression of change. For external validation, LDS was calculated in 2 cohorts of patients with lipodystrophy treated with metreleptin. Results LDS domains include Diabetes/Insulin Resistance, Microvascular Complications of Diabetes, Lipids, Cardiovascular, Liver, Kidney, Reproductive, and Other. Each domain is assessed by 1 or more questions assessing both lifetime and recent complications of lipodystrophy. The LDS had high content validity and feasibility and high reliability by intraclass correlation coefficients (>0.95). Global and domain-specific LDS were strongly correlated with CGI, as were changes in scores across visits (R = 0.79-0.99, P < .001 for all). In generalized lipodystrophy, metreleptin significantly reduced LDS (from 46 to 26 at 12 months, P < .001). The reductions were smaller in partial lipodystrophy (from 65 to 61 at 12 months, P = .04). Conclusion The LDS can reflect the severity of diverse manifestations of lipodystrophy and monitor changes following interventions.

Background: Latinas with mammographic dense breasts are at increased risk of breast cancer. This randomized controlled trial tests the effectiveness of three breast density (BD) educational approaches on adherence to subsequent mammography screening among Latinas receiving care at a Federally Qualified Health Center (FQHC). Measure(s): Adherence was ascertained using electronic health record and survey responses. Kaplan–Meier estimates of the time to subsequent mammogram were used to obtain adherence rates at 1- and 2-years post baseline mammogram. Cox modeling assessed whether adherence differed by patient characteristics or group assignment. Results: This analysis was limited to Latinas enrolled between October 27, 2016, and December 21, 2018 ( n = 946; 66.1% <50 years of age, 53.5% with dense breasts). Adherence rates at 1 year was 24.8% increasing to 51.7% by year 2. Latinas randomized to the Promotora + brochure + letter arm (hazard ratio [HR]: 1.09 [95% confidence interval [95% CI] 0.87 to 1.36]) or brochure + letter (HR: 1.03 [95% CI 0.82 to 1.29]) arm were not more likely to be adherent to subsequent mammography compared to the letter only arm ( p = 0.76) . Adjusting for age and study group, having more prior mammograms, being “extremely likely” to get an annual mammogram, and having more confidence to get an annual mammogram at baseline were significant drivers of subsequent adherence. Conclusion: Informational interventions targeting BD education alone are unlikely to significantly improve adherence to subsequent mammography among Latinas receiving care in FQHCs.

Abstract Purpose: Digital proteomic profiling was performed to identify spatial context in relationship to patient response and survival after anti–PD-1 therapy in metastatic colorectal cancer. Experimental Design: Primary colorectal cancers with deficient mismatch repair from patients treated with anti–PD-1 antibodies were analyzed (N = 30) using digital spatial profiling (GeoMx nCounter). At the invasive margin, 71 proteins were profiled in 10 regions of interest/slide that were segmented into 3 compartments labeled with pan-cytokeratin (epithelia), CD45 (stromal cells), and SYTO13 (nuclei). In an independent cohort (n = 13), digital spatial profiling data and single-cell transcriptomic data were analyzed. Differential protein abundance, after Benjamini–Hochberg correction, was examined by clinical response and progression-free survival (PFS) using multivariable Cox regression. Results: Protein abundance varied significantly between epithelial and stromal compartments. Nonresponders to anti–PD-1 showed higher fibronectin and smooth muscle actin abundance in the epithelial compartment that was associated with significantly shorter PFS (adjusted HR: 6.49 and 4.52, respectively; P &lt; 0.05). In CD45+ stroma, increased expression of proteins related to T cells (CD3 and CD4), NK cells (CD56), antigen presentation (CD40), immune activation (CD27, ICOS), and apoptosis (GZMA) were found in responders (vs nonresponders) to anti–PD-1; each marker was significantly associated with longer patient PFS (0.02 &lt; adjusted HR &lt; 0.17; P &lt; 0.05). In a separate cohort, consistent results by compartment were found for fibronectin and CD56. Gene expression data revealed that fibronectin and smooth muscle actin were primarily derived from cancer-associated fibroblasts. Conclusions: Spatially resolved protein profiles within microenvironments of deficient mismatch repair colorectal cancers can influence patient response and survival after anti–PD-1, highlighting their potential clinical significance.

Background Left ventricular diastolic dysfunction (LVDD) predicts mortality in patients in cardiac intensive care units. An artificial intelligence enhanced ECG (AIECG) algorithm can predict LVDD and mortality in general populations but has not been examined in cardiac intensive care units. Methods This historical cohort study included consecutive adults admitted to Mayo Clinic cardiac intensive care unit from 2007 to 2018 with an admission AIECG. The AIECG assigned the LVDD grade (0–3). Medial mitral E/e' ratio >15 on transthoracic echocardiogram (TTE) defined elevated filling pressures. In‐hospital and 1‐year mortality was evaluated, before and after multivariable adjustment. Results We included 11 868 patients (median age 69.5 years, 37.7% female); 48% had heart failure and 44% had acute coronary syndromes. AIECG LVDD grade was 0 (normal), 33%; 1, 7%; 2, 39%; and 3, 21%. In‐hospital and 1‐year mortality increased in each higher AIECG LVDD grade. After adjustment, each higher AIECG LVDD grade was associated with higher in‐hospital (adjusted odds ratio [OR], 1.22 [95% CI, 1.13–1.32]) and 1‐year mortality (adjusted hazard ratio [HR], 1.23 [95% CI, 1.19–1.29]); this persisted after adjustment for TTE measurements. Patients with grade 2 or 3 LVDD by AIECG and medial mitral E/e' ratio >15 by TTE had the highest in‐hospital (adjusted OR, 2.54 [95% CI, 1.69–3.88]) and 1‐year (adjusted HR, 2.03 [95% CI, 1.65–2.48]) mortality, whereas patients meeting either of these criteria had similar, elevated mortality. Conclusions The AIECG LVDD grade was strongly associated with in‐hospital and 1‐year mortality in patients in cardiac intensive care units, even after adjusting for clinical variables and TTE measurements. Patients with concordant AIECG and TTE for elevated filling pressures were at highest risk.

Background Although intravenous thrombolysis (IVT) is safe and effective in populations with general stroke, its impact on cervical artery dissection–related acute ischemic stroke (CeAD‐AIS) remains unclear. This retrospective study used the National Inpatient Sample to compare outcomes in patients with CeAD‐AIS treated with and without IVT. Methods We included adult patients with concurrent CeAD and AIS diagnoses ( International Classification of Diseases, Tenth Revision [ ICD‐10 ], codes) hospitalized from 2016 to 2019. The primary outcome was home discharge; safety outcomes included inpatient death and intracerebral hemorrhage. We performed survey‐weighted multivariable logistic regressions comparing IVT versus no IVT, followed by interaction analyses to examine effect modifications based on age, medical history, stroke severity, carotid artery involvement, and endovascular treatment. Results Between 2016 and 2019, 1360 (12.1%) of 11 285 patients with CeAD‐AIS received IVT. IVT‐treated patients had higher median National Institutes of Health Stroke Scale scores (median [interquartile range], 8 [4–17] versus 3 [1–11]; P <0.001). Adjusted analyses showed IVT was associated with higher odds of home discharge (adjusted odds ratio [OR], 1.40 [95% CI, 1.01–1.92]; P =0.042), but not with inpatient death (adjusted OR, 1.29 [95% CI, 0.76–2.20]; P =0.347) or intracerebral hemorrhage (adjusted OR, 0.69 [95% CI, 0.32–1.48]; P =0.341). Stroke severity ( P for interaction=0.001) and carotid artery involvement ( P for interaction=0.021) significantly modified IVT's effect on home discharge, with IVT being associated with an increased likelihood of home discharge in patients with moderate to severe strokes (National Institutes of Health Stroke Scale score >4) and carotid artery involvement. Conclusions IVT improves the likelihood of home discharge in patients with CeAD‐AIS without increasing the risk of inpatient death or intracerebral hemorrhage.

ABSTRACTIntroduction/AimsHealthcare utilization and costs in myotonic dystrophy (DM) are not well understood. This study describes the burden of DM and its associated costs.MethodsWe performed a retrospective study using data from a large U.S. administrative claims database to identify commercially insured individuals with DM and compared healthcare utilization and cost with a matched cohort. Analyses were performed between the cohorts with ≥ 3 years of insured follow‐up.ResultsWe identified 1182 DM individuals with coverage at least 3 year prior and 3 years following an index DM diagnosis from January 1, 2009 to December 31, 2018. Compared to controls, DM individuals were 3.7 times more likely to be hospitalized (p < 0.0001), 2.4 times more likely to visit an emergency department (p < 0.0001), and had twice as many outpatient visits (p < 0.0001) in the first year post‐diagnosis, with similar utilization at 2‐ and 3‐years post‐diagnosis. Annual mean costs were 3.9 times higher for health plan paid costs (p < 0.0001) and 2.6 times higher for patient‐paid costs (p < 0.0001) for DM individuals than controls in the first year post‐diagnosis, with similar costs at 2‐ and 3‐years post‐diagnosis. Factors associated with higher costs included the need for durable medical equipment, including gait aids or respiratory support devices.DiscussionIndividuals with DM experience significantly higher healthcare utilization and associated healthcare costs than controls of similar age, sex, race, and census region. The findings show the high clinical and economic burden of DM, highlighting the importance of improving cost‐effective care delivery in this population.

Abstract Background: Self-efficacy theory proposes that confidence to engage in a health behavior is associated with engaging in that specific behavior. Most research examining self-efficacy has been conducted with white young adult populations. This secondary analysis examined the association of self-efficacy (i.e., confidence) for healthy eating and physical activity in two immigrant communities. Methods: At enrollment into the Healthy Immigrant Community study, a clinical weight management and cardiovascular risk reduction intervention set in southeastern [state], 475 participants completed assessments about their confidence for healthy eating and physical activity. Measurements also included self-reports of dietary quality and intake, physical activity, quality of life, and biometric assessments. Study materials were available in English, Spanish, and Somali. Results In total, 450 adults (Hispanic/Latinx = 267; Somali = 183) completed measures at baseline and were included for analysis. Their average age was 45 years (range 18–87) and 59% were female. Confidence for healthy eating was significantly associated with self-report of eating healthy snacks ( p = < 0.0001) and less consumption of high-calorie drinks ( p = 0.02) and regular soda ( p = < 0.0001). Confidence to be physically active was significantly associated with more self-reported physical activity ( p = < 0.01). Conclusions Confidence to eat healthy and be physically active appears to be associated with having a healthier diet and higher levels of physical activity. Given the large sample size and strength of the associations, it also appears that the theoretical model of self-efficacy can be effectively measured and applied within these immigrant populations. Self-efficacy theory may be useful in understanding potential mediating mechanisms when designing future interventions with immigrant communities. ClinicalTrials.gov registration: NCT05136339; April 23, 2022

INTRODUCTION: Abdominal bloating is a difficult symptom to treat. Hypnotherapy and diaphragmatic intervention have separately shown benefit on bloating in prior work but have not been united into a single intervention. We aimed to obtain data on the potential therapeutic impact of a novel audio-recorded bloating treatment for bloating integrating hypnosis and diaphragmatic breathing, with proposed synergistic effect. METHODS: Patients with nonorganic bowel disorders with predominant bloating symptoms completed a digitally delivered 7-session audio-recorded hypnotherapy program without clinician involvement. The intervention combined bloating-targeted hypnotic suggestions and guided diaphragmatic breathing delivered under hypnosis, and was supplemented with interval self-guided breathing exercises. Participants completed online REDCap assessments at baseline, midtreatment, at end of treatment, and 3-month follow-up, evaluating symptom severity, gastrointestinal symptom-specific anxiety, overall anxiety/depression, and quality of life. Outcomes were assessed in an intention-to-treat manner with repeated measures analysis of variances (ANOVAs) with Bonferroni-adjusted pairwise post hoc tests. RESULTS: Of 23 patients who started treatment, 22 (95.6%) completed follow-up. Bloating severity on Irritable Bowel Syndrome-Symptom Severity Scale and Patient Assessment of Upper Gastrointestinal Symptom Severity Index showed reduction in bloating with large effect sizes (Cohen d of ∼0.8) at the end of treatment, as did Visceral Sensitivity Index bloating-related anxiety. At the end of treatment, 16 patients (69.6%) were Irritable Bowel Syndrome-Symptom Severity Scale treatment responders (≥30% symptom reduction) on bloating and 17 (73.9%) on overall bowel symptom severity. Anxiety, depression, and quality-of-life scores were unchanged. Outcome measures were fully maintained at the 3-month follow-up. DISCUSSION: Results suggest the therapeutic utility of a new cost-effective self-administered bloating intervention. A randomized controlled trial is planned to confirm these therapeutic effects.

ABSTRACTSeveral dynamic models predict mortality and corticosteroid response in alcohol‐associated hepatitis (AH), yet no consensus exists on the most effective model. This study aimed to assess predictive models for corticosteroid response and short‐term mortality in severe AH within a global cohort. We conducted a multi‐national study of patients with severe AH treated with corticosteroids for at least 7 days, enrolled between 2009 and 2019. Dynamic models—Lille‐4, Lille‐7, trajectory of serum bilirubin (TSB), and neutrophil‐to‐lymphocyte ratio (NLR)—were used to estimate 30‐ and 90‐day mortality. Lille‐7 demonstrated the highest accuracy for both 30‐ and 90‐day mortality.