Citations

BACKGROUND Cutaneous lichen planus (LP) is a recalcitrant, difficult-to-treat, inflammatory skin disease characterized by pruritic, flat-topped, violaceous papules on the skin. Baricitinib is an oral Janus kinase (JAK) 1/2 inhibitor that interrupts the signaling pathway of IFN-γ, a cytokine implicated in the pathogenesis of LP. METHODS In this phase II trial, 12 patients with cutaneous LP received 2 mg daily baricitinib for 16 weeks, accompanied by in-depth spatial, single-cell, and bulk transcriptomic profiling of pre- and posttreatment samples. RESULTS An early and sustained clinical response was seen, with 83.3% of patients responsive at week 16. Our molecular data identified a unique, oligoclonal IFN-γ, CD8 + , and CXCL13 + cytotoxic T cell population in LP skin and demonstrated a rapid decrease in IFN signature within 2 weeks of treatment, most prominently in the basal layer of the epidermis. CONCLUSION This study demonstrates the efficacy and molecular mechanisms of JAK inhibition in LP. TRIAL REGISTRATION NCT05188521 FUNDING Eli Lilly, Appignani Benefactor Funds, 5P30AR075043, Mayo Clinic Clinical Trials Stimulus Funds.

SUMMARY Goal While studies have examined quality and health outcomes related to the Centers for Medicare & Medicaid Services’ (CMS’s) Hospital Value-Based Purchasing (HVBP) Program, a significant gap exists in the literature regarding the relationship between pay-for-performance initiatives and hospital financial performance in the program’s Efficiency and Cost Reduction domain. This study examined the association between hospitals’ cost inefficiency and participation in the HVBP Program by estimating the probability and magnitude of improvement or achievement in the program’s Efficiency and Cost Reduction domain. Methods The 2014–2019 Efficiency and Cost Reduction domain data were obtained from CMS and merged with the American Hospital Association’s Annual Survey Database. We conducted a zero-inflated negative binomial regression to account for the excessive number of zeros in the data. Principal Findings The negative binomial component of the model assessed the magnitude of the impact on the Efficiency and Cost Reduction improvement from each covariate, while the zero-inflated component assessed the odds of being in the “certain-zero” group, meaning no chance to improve or achieve. Hospital ownership, location, size, safety-net status, percentage of Medicare patients, and the number of registered nurses per bed were statistically significant. Additionally, the Herfindahl-Hirschman Index and teaching status significantly influenced efficiency performance. Practical Applications Changes in hospital performance in this domain exist and have evolved. Hospitals might be at a disadvantage with this performance measure because of their inherent organizational structure. The HVBP Program may not provide clear enough direction or actionable incentive to address the needs of stakeholders influenced primarily by measures of Medicare spending per beneficiary. This study’s findings hold practical value for policymakers, healthcare administrators, and researchers. Policymakers can use this information to tailor future pay-for-performance programs and effectively allocate resources. Healthcare administrators can identify areas for improvement and benchmark their performance against similar institutions. Researchers can explore the program’s long-term sustainability and investigate cost drivers within different hospital groups. By understanding the link between hospital characteristics and cost reduction, all stakeholders can contribute to a more efficient healthcare system.

BACKGROUND: The ability to predict recovery of left ventricular ejection fraction (LVEF) in response to guideline-directed therapy among patients with nonischemic cardiomyopathy is desired. We sought to determine whether left ventricular endocardial unipolar voltage measured during invasive electroanatomic mapping could be used to predict LVEF recovery among those with recent-onset nonischemic cardiomyopathy. METHODS: We analyzed the left ventricular voltage maps of patients included in the eMAP trial (Electrogram-Guided Myocardial Advanced Phenotyping; NCT03293381), a prospective, nonrandomized, interventional trial conducted at 2 institutions between 2017 and 2020. Patients had recent-onset nonischemic cardiomyopathy defined by LVEF ≤45% and development of symptoms or signs of heart failure within the past 6 months. Detailed voltage maps of the left ventricular endocardium were generated using the Carto electroanatomic mapping system. Abnormal unipolar amplitude was defined as <8.27 mV. The primary end point was recovery of LVEF (Recovery) defined by a 1-year LVEF ≥50% or ≥45% with ≥10% increase from baseline. RESULTS: Of the 29 enrolled patients (median age, 49 years [25th percentile, 39; 75th percentile, 59], 8 females [27.6%]), LVEF recovered in 13 (44.8%) by 1-year follow-up. The percentage of total endocardial surface area with unipolar voltage abnormality (AUA) was significantly lower among Recovery patients than No Recovery patients (18.2% [25th percentile, 6.4; 75th percentile, 22.4] versus 80.0% [25th percentile, 29.5; 75th percentile, 90.9]; P =0.004). Percent AUA was associated with lower likelihood of Recovery (odds ratio, 0.64 per 10% increase in AUA; 95% CI, 0.47–0.88; P =0.006). A 28% cutoff value for percent AUA was 92% sensitive and 75% specific with an area under the receiver operating characteristic curve of 0.81 (95% CI, 0.63–0.99; P =0.001) for predicting recovery versus no recovery. The majority of patients (12 of 13; 92.3%) with a percent AUA >28% did not recover. CONCLUSIONS: Left ventricular unipolar voltage abnormality is a potent predictor of LVEF recovery among patients recently diagnosed with nonischemic cardiomyopathy. Detailed left ventricular unipolar voltage mapping could therefore be used as a valuable prognostic tool in guiding treatment decisions.

Background: As machine learning becomes increasingly utilized in orthopaedic clinical research, the application of machine learning methodology to cohort data from the Multicenter ACL Revision Study (MARS) presents a valuable opportunity to translate data into patient-specific insights. Purpose: To apply novel machine learning methodology to MARS cohort data to determine a predictive model of revision anterior cruciate ligament reconstruction (rACLR) graft failure and features most predictive of failure. Study Design: Cohort study; Level of evidence, 3. Methods: The authors prospectively recruited patients undergoing rACLR from the MARS cohort and obtained preoperative radiographs, surgeon-reported intraoperative findings, and 2- and 6-year follow-up data on patient-reported outcomes, additional surgeries, and graft failure. Machine learning models including logistic regression (LR), XGBoost, gradient boosting (GB), random forest (RF), and a validated ensemble algorithm (AutoPrognosis) were built to predict graft failure by 6 years postoperatively. Validated performance metrics and feature importance measures were used to evaluate model performance. Results: The cohort included 960 patients who completed 6-year follow-up, with 5.7% (n = 55) experiencing graft failure. AutoPrognosis demonstrated the highest discriminative power (model area under the receiver operating characteristic curve: AutoPrognosis, 0.703; RF, 0.618; GB, 0.660; XGBoost, 0.680; LR, 0.592), with well-calibrated scores (model Brier score: AutoPrognosis, 0.053; RF, 0.054; GB, 0.057; XGBoost, 0.058; LR, 0.111). The most important features for AutoPrognosis model performance were prior compromised femoral and tibial tunnels (placement and size) and allograft graft type used in current rACLR. Conclusion: The present study demonstrated the ability of the novel AutoPrognosis machine learning model to best predict the risk of graft failure in patients undergoing rACLR at 6 years postoperatively with moderate predictive ability. Femoral and tibial tunnel size and position in prior ACLR and allograft use in current rACLR were all risk factors for rACLR failure in the context of the AutoPrognosis model. This study describes a unique model that can be externally validated with larger data sets and contribute toward the creation of a robust rACLR bedside risk calculator in future studies. Registration: NCT00625885 (ClinicalTrials.gov identifier).

BACKGROUND: Studies in the past have demonstrated an association between sarcoidosis and pulmonary embolism but little is known about its impact, especially in young adults. We aim to determine the burden and impact of pulmonary embolism (PE) in young adults hospitalized with sarcoidosis. METHOD: The study investigates the prevalence and consequences of PE in young adults aged 18-44 years hospitalized with sarcoidosis using data from the National Inpatient Sample (2016-2020) with relevant ICD-10 codes. This study aims to address the primary outcomes of the burden and trends of PE and its associated impact on in-hospital mortality. Additionally, it explores secondary outcomes such as healthcare resource utilization and discharge patterns. RESULT: Among 50,385 young adults (median age 37 years) hospitalized with sarcoidosis, 1120 had PE, showing a linear increase from 2% in 2016 to 2.9% (p<0.001) in 2020. Sarcoidosis-PE+ group, predominantly in young blacks, exhibited a higher prevalence of comorbidities such as obesity, smoking, drug use, peripheral vascular disease, hypothyroidism, and prior history of VTE. In contrast, the sarcoidosis-PE- group had a higher prevalence of diabetes (with/without chronic complication), hyperlipidemia, and chronic pulmonary disease. Multivariable regression analysis adjusted for all potential sociodemographic and comorbid variables showed higher odds of all-cause mortality (OR: 2.92, 95% CI: 1.18-7.24, p <0.02) in the sarcoidosis-PE+ group as compared to sarcoidosis-PE- group. The sarcoidosis-PE+ group also had higher hospital costs and length of stay. CONCLUSION: The higher odds of in-hospital mortality with an increased length of stay and hospital cost observed in the sarcoidosis-PE+ group highlight the often underreported complications of sarcoidosis, particularly in a younger demographic. The relevance of this study stems from its potential to uncover trends that could lead to improved diagnostic and therapeutic strategies.

Background: Sleep disordered breathing (SDB) is frequently observed in patients with cardiovascular disease, and is associated with intermittent hypoxia, sympathetic activation, oxidative stress, and endothelial dysfunction, all of which may facilitate the development and progression of cardiovascular disease. Objectives: We sought to determine the prevalence, subtypes, and clinical implications of comorbid SDB in patients with hypertrophic cardiomyopathy (HCM). Methods: In this prospective observational study, patients with HCM without prior diagnosis of SDB were recruited to undergo inpatient polysomnography between May 1 st 2018 and October 31 st 2022. Electrocardiographic and echocardiographic parameters, cardiac biomarkers, and symptoms were comparatively assessed in patients with and without comorbid SDB. Patients were assessed for the development of major adverse cardiovascular events (MACE) during follow-up (median 29, range 3-57 months). Results Among 154 participants, 91 (59.1%) were diagnosed with SDB of whom 38 (41.8%) had mild, 22 (24.2%) moderate, 18 (19.8%) severe obstructive sleep apnea, and 13 (14.3%) had central sleep apnea. SDB was associated with greater left ventricular mass (median [IQR]) (128 [107, 161] vs. 109 [96, 134] g/m 2 , p =0.034) and E/e’ ratio (12.5 [10, 15] vs. 10.0 [8.3, 14.5], p =0.039). Patients with HCM over the age of 50 years, with body mass index ≥ 30kg/m 2 , who described their sleep as “poor” were at particularly high risk of having comorbid SDB, as were those who were diabetic, hypertensive, or described greater exertional limitation (NYHA Class ≥II 53% vs. 27%, p =0.005). Importantly, subjects with SDB had elevated baseline Troponin T levels (14 ng/L vs 11 ng/L, p =0.030), and further substantial overnight troponin increases following untreated apneic sleep (2.1ng/L vs 0.2ng/L, p =0.009). Finally, patients with comorbid SDB experienced a significantly higher proportion of incident adverse cardiovascular events (MACE hazard ratio 5.3, 95% CI, 1.6, 17.2, p =0.006) than those without SDB. Conclusions: We report a particularly high burden of previously undiagnosed SDB in patients with HCM, particularly in older, heavier, male patients. Undiagnosed SDB in HCM is not benign and is associated with symptom progression, comorbidity, and a poorer prognosis, particularly in the case of central sleep apnea. These important new findings provide rationale for heightened vigilance and routine screening for SDB in patients with HCM.

Introduction: Ebstein's anomaly (EA) is associated with ECG signature of right bundle branch block (RBBB). Patients with EA also have high incidence of accessory pathways (AP) and it has been hypothesized that the absence of RBBB on ECG may be associated with a higher prevalence of AP. This study aims to assess the prevalence of RBBB in patients with EA and examine the correlation between its absence and the presence of AP. Methods: Adults (age>18 years) with EA, identified using the Mayo Adult Congenital Heart Disease registry, were divided into 3 groups based on the QRS morphology of their first ECG. Those with prior AP ablation were excluded. The demographic characteristics, baseline ECG data, echocardiographic parameters and EP study data were retrospectively collected and compared between the three groups using Chi-square or ANOVA test as appropriate. Results: Of 596 patients with EA, 358(60.06%) patients had a RBBB, bifascicular block or an incomplete RBBB (group1) ; 18 (3.02%) patients had either a LBBB , ventricular pre-excitation, isolated left anterior or posterior fascicular block (group 2); and 220 (36.92%) patients had normal QRS (group 3). The characteristics of these groups are compared in the table. Patients with RBBB had larger RV size, reduced RV systolic function and higher likelihood of tricuspid valve surgery. EP study was performed in 51 (14%), 3 (17%) and 51 (23%) patients in groups 1, 2,and 3 respectively. One or more APs were noted in 11/51 (22%) and 14/51 (30%) patients with RBBB and normal QRS respectively (p=0.18). Additionally, in patients who did not undergo an EP study, supraventricular tachycardia was documented in 39/307 (13%), 2/15(13%) and 13/169 patients (8%) in group 1,2 and 3 respectively during followup . Conclusion: In a large cohort of adults with EA in a tertiary referral center, greater than one-third of patients had a normal QRS complex without RBBB. However, EP study did not reveal a significant difference in the prevalence of accessory pathways between patients with and without RBBB. In EA, the absence of RBBB may not increase the risk of an underlying accessory pathway.