Citations

AbstractBackgroundPresymptomatic C9orf72 expansion carriers show regions of low local gyrification index (lGI) as early as their thirties (Caverzasi et al. JNNP 2019) and regions of gyrification decline have been reported (van Veenhuijzen et al. Ann Neurol 2022). These findings raise the question as to whether abnormal gyrification represents a neurodevelopmental difference or early neurodegeneration in frontotemporal lobar degeneration (FTLD) mutation carriers. Yet, previous studies focusing on young adults is lacking and no study has explored gyrification in the two other common FTLD mutations, GRN and MAPT. Here, we analyzed lGI in young adult presymptomatic FTLD mutation carriers.MethodLGI quantifies buried cortex within the sulcal folds compared to the visible cortex on the outer surface, with larger values indicating more folding (Schaer et al. IEEE trans med imaging 2008). Mean lGI values, as measured by a parcel‐wise analysis implemented in FreeSurfer v.6.0, were compared between 31 presymptomatic (preSx) carriers (12 C9orf72, 13 MAPT, 6 GRN, mean age: 25.2 ± 3.91 years) and 28 demographically‐matched healthy controls (HC: mean age: 25.6 ± 3.8 years). We used ANCOVA to compare all presymptomatic carriers combined (preSxAll) and HC to identify regions with significant lGI differences regressing age, sex, education, handedness, total intracranial volume and scanner type as nuisance covariates. Significant group differences were analyzed by Dunnett’s post‐hoc tests between each mutation subgroup and HC (p<0.05).ResultCompared to HC, preSxAll had higher mean gyrification in the right caudal (F = 5.07, p = 0.03) and rostral anterior cingulate (F = 6.22, p = 0.17), and lower lGI in the left middle temporal gyrus (F = 4.22, p = 0.046). Within these regions, post‐hoc analyses showed that preSx GRN had greater gyrification in the right caudal anterior cingulate (t = 2.57, p = 0.039, 95% CI = [0.005, 0.248]) and preSx C9orf72 had lower lGI in the left middle temporal gyrus (t = ‐3.14, p = 0.009, 95% CI = [‐0.37, ‐0.04]) vs. HC.ConclusionYoung adult FTLD mutation carriers displayed higher gyrification in the right anterior cingulate and lower gyrification in the left middle temporal gyrus compared to HC. Future studies in children will confirm the extent to which these gyrification abnormalities represent neurodevelopmental differences.

Abstract Background The efficacy and safety of collagenase Clostridium histolyticum (CCH) have been demonstrated in the treatment of men with Peyronie’s disease (PD); however, the pivotal clinical trials excluded men with ventral penile curvature. Aim The study sought to evaluate outcomes of CCH treatment in men with ventral curvatures secondary to PD. Methods Men with PD treated with CCH were identified from a prospective database. Patients received up to 4 series of CCH injections using a progressively modified protocol over time. Results were compared between those with baseline ventral vs nonventral penile curvatures. Outcomes Changes in penile curvature, Peyronie’s Disease Questionnaire scores, International Index of Erectile Function scores, nonstandardized assessments, and adverse events. Results A total of 560 men with PD (85 ventral curvature, 475 nonventral curvature) were included in the analysis. Baseline median curvature was 60.0° (interquartile range, 48.8°-75.0°) in the ventral cohort and 65.0° (interquartile range, 45.0°-80.0°) in the nonventral cohort. Median change from baseline penile curvature was −25.0° in the ventral cohort vs −24.0° in the nonventral cohort (P = .08, between-group comparison), which corresponded to curvature reductions of 44.7% and 33.6%, respectively (P = .03). In the subset of patients who completed CCH treatment (ie, received 8 injections or discontinued early because of patient satisfaction with curvature reduction), median change from baseline was −35.0° in the ventral cohort vs −25.0° in the nonventral cohort (P &lt; .05); median percent improvement was 48.3% and 37.5%, respectively (P = .11). Median change from baseline in Peyronie’s Disease Questionnaire and International Index of Erectile Function domain scores and adverse events were similar between cohorts, with the exception of possibly higher hematoma rates in the nonventral group (50% vs 37%; P = .05). No urethral injuries were sustained in either cohort. Clinical Implications Data support the use of CCH for the treatment of ventral as well as nonventral penile curvatures in men with PD. Strengths and Limitations Study strengths are the inclusion of a general clinical population of men with PD, the prospective design, and the relatively large series of men with ventral curvature. Limitations include the single-center and observational nature of the study. Conclusion CCH was safe and effective in the treatment of both ventral and nonventral penile curvatures in men with PD.

Abstract Background Diagnosis of breast cancer in young women has been shown to affect their decision‐making with regard to fertility and family planning. Limited data are available from populations across the U.S. regarding this issue; thus, we sought to describe fertility concerns and efforts to preserve fertility in a national clinical trial population of young breast cancer patients. Methods The young and strong study was a cluster‐randomized controlled trial testing an intervention program for young women with breast cancer. Patients were surveyed within 3 months after diagnosis and at 3, 6, and 12 months after. Surveys asked about sociodemographics, psychosocial domains, fertility concerns, and fertility preservation strategies. Univariable and multivariable models were used to investigate sociodemographic, clinical, and psychosocial predictors of fertility concerns. Results Of 467 women from 54 clinical sites across the U.S. (14 academic, 40 community), 419 were evaluable regarding fertility concerns. Median age was 40 years (range 22–45), 11% were Black, 6% Hispanic, and 75% had children. Tumor stage was I (35%), II (51%), or III (14%); 82% received chemotherapy. At time of the treatment decision, 133 (32%) participants had fertility concerns, among whom 47% indicated this affected their treatment decisions. Sixty percent of participants reported having discussed fertility with their physician. Twenty percent of those with fertility concerns used fertility preservation strategies. History of difficulty becoming pregnant and younger age were associated with higher odds of fertility concerns in multivariable modeling. Conclusion Many young women with newly diagnosed breast cancer are concerned about fertility in a way that impacts their treatment decisions. Concerns were discussed, but few used fertility preservation strategies. These findings have implications for counseling young patients.

Aim: Studies in the past have linked obesity as a risk factor for atrial fibrillation (AF). However, there is a paucity of data on this influence in young adult males. This meta-analysis aims to evaluate and stratify the association between BMI and AF among young men. Methods: PubMed, Scopus, and Google Scholar databases were systematically reviewed for studies reporting long term-incidence of atrial fibrillation in young male adults (18-49 years) with obesity (BMI>30 kg/m 2 ), and overweight BMI (BMI 20-25 kg/m 2 ). Random effects models were used for the meta-analyses and subgroup analyses. I 2 statistics were used to identify (>50%) heterogeneity. A sensitivity analysis was performed using leave-one-out method. Results: Six studies with a total of 21,856,538 individuals were screened, out of which 6,732,531 young males with higher BMI and obesity were evaluated for the risk of Atrial fibrillation for a median follow-up duration of 6.3 years (3.3 - 29 years range). South Korean and Japanese studies together constituted 99.86% of the study population. Most commonly associated comorbidities were hypertension, diabetes mellitus type 2, dyslipidemia and smoking. The unadjusted HR showed a significant association between overweight (BMI 25-30) [OR:1.42, (95%CI:1.28-1.58, I 2 : 75.86%; p< 0.01] and obesity (BMI >30) and AF [OR: 2.02, (95%CI: 1.77-2.29, I 2 :64.3%; p=0.02] in young adult males. After multivariable analysis, the association remained significant for overweight [OR:1.22, 95%CI: 1.14-1.32, I 2 : 82.74%; p< 0.01] and obesity [OR:1.48, 95%CI: 1.29-1.71, I 2 : 90.43%; p< 0.01]. Sensitivity analysis indicated that no single study unduly influenced the pooled estimates. Conclusion: This meta-analysis revealed that higher BMI (overweight and obese) in young males is associated with an increased long-term risk of AF over a median follow-up duration of 6.3 years.

Introduction and Importance: While the use of vaping has increased significantly among young individuals, the effects of the various vape aerosol chemical contents on cardiac electrophysiological dynamics remain unknown. Case Presentation: A 22-year-old female with a history of energy vaping but no significant past medical history presented with cardiac arrest. Found to have no pulse, CPR was started and initial rhythm of ventricular tachycardia was obtained. Shock was administered with follow-up rhythm of ventricular fibrillation. Patient was shocked again and entered atrial fibrillation with rapid ventricular response. She later cardioverted into sinus tachycardia and was intubated. Transthoracic echocardiogram showed normal ejection fraction but was otherwise unremarkable. Patient was extubated on day four of hospitalization. Left heart catheterization and cardiac MRI were completely unremarkable. Toxicology, urine analysis, and troponins were all negative. Patient was discharged with metoprolol tartrate, and a life-vest with outpatient follow-ups for possible implantable cardioverter-defibrillator placement in the setting of negative work up for sudden cardiac arrest. Clinical Discussion: Vaping-induced sudden cardiac arrest may be attributed to a reduction in cardiac repolarization reserve. Exposure to vegetable glycerin and propylene glycol, substances present in nearly all vape products, have been found to incite arrhythmias and disrupt cardiac conduction in animals. Acrolein,a byproduct of glycerin, has also been found to induce arrhythmias due to autonomic dysfunction. Increased prevalence of ventricular arrhythmias have also been noted with exposure to aerosols containing nicotine-free propylene glycol (PG).This likely stems from the impact of PG aerosols on the transient outward potassium current, which plays a significant role in early cardiac repolarization. Conclusion: The effects of inhaling vape aerosols remain not fully understood. While there is a perceived notion that nicotine-free aerosols may not be harmful, that remains unclear.Further studies should be conducted to evaluate for pro-arrhythmogenic effects and autonomic dysfunction from the various chemical substances present in vape aerosols.

Introduction: Long-term outcomes of young patients with chest pain and normal epicardial coronary arteries (NECA) in angiography remain understudied. Methods: We conducted a prospective study in a tertiary heart hospital between 2004-2020, enrolling men<45 and women<55 years presenting with symptoms or objective findings of coronary artery disease (CAD) and confirmed NECA in angiography. Patients with cardiomyopathy, coronary anomaly, and significant valvular, renal, pulmonary, or liver diseases were excluded. The primary outcome was MACCE, defined as the composite of death, CCU admission (for MI or unstable angina), stroke, and revascularization. Follow-ups were done every 5 years using a standardized questionnaire and a committee of experts reviewed all the events. Expected age and sex-adjusted mortality rates were estimated using national data. The association between exposures and MACCE was studied using multivariable Cox-proportional hazard models. Results: 1257 patients, 340 (27.05%) men (38.34±5.46 years), and 917 (72.95%) women (48.41±4.94 years) were included. 698 (55.53%) had acute and 559 (44.47%) had chronic symptoms. Over the median 9.4 (8.5-11.0) years of follow-up, 134 (10.66%) events happened. CCU admission (6.33%) was the most common event (Figure). The 10-year mortality rate (per 100,000-person-years) was 265 for men and 174 for women, which were 1.6 and 2.5 times higher than the age-sex-matched rate of the normal population, respectively. Diabetes, hypertension, and presenting with acute symptoms were associated with higher MACCE with the hazard ratios (95% CI) of 1.87 (1.05-3.31, P:0.03), 1.72 (1.13-2.61, P:0.01), and 1.56 (1.03-2.36, P:0.04), respectively. During follow-up, 192 (15.27%) repeated angiographies were done and 19.8% developed obstructive CAD. Conclusions: In young patients with chest pain and NECA, approximately 10% experienced MACCE during a 10-year follow-up, and the mortality is higher than expected.

Background: Limited research has focused on the rising incidence of major adverse cardiac and cerebrovascular events (MACCE) among young women (aged 18-44) with at least one traditional cardiovascular disease risk factor (CVD), especially in rural hospital settings. We aimed to address this research gap by providing insights into the burden of CVD in this population. Methods: Using data from the National Inpatient Sample (2019), we identified young women (aged 18-44) with at least one cardiovascular risk factor admitted to rural hospitals. Baseline demographics, comorbidities, and outcomes were assessed, including MACCE and all-cause mortality. Multivariable logistic regression was performed, adjusting for age, race, income, and comorbidities. Results: Among 179,410 young women, MACCE occurred in 2,455 individuals (1.4%), with varying rates among racial groups: whites (1.2%), blacks (2.4%), Hispanics (1.3%), Asian or Pacific Islanders (API) (2%), Native Americans (NA) (1.6%), and others (1%). All-cause mortality was observed in 385 women (0.2%), with rates of 0.2% for whites and 0.4% for blacks. Blacks had twice the event rates of MACCE, and all-cause mortality compared to whites. Comorbidities and substance abuse were associated with MACCE (P<0.001). In higher-income households, multivariable analysis adjusted for confounders revealed significantly higher odds of MACCE in blacks (OR 1.23, 95% CI 0.11-14.08), API (OR 4.48, 95% CI 1.06-18.93), and NA (OR 10.22, 95% CI 1.03-101.50) compared to whites. In contrast, mortality rates were lower for Hispanics than whites (OR 0.24, 95% CI 0.02-3.80) (all p < 0.001) (Table 1). Conclusion: In higher-income households, greater odds of MACCE were noted among blacks, API, and NA compared to whites. Future research should focus on understanding factors contributing to these disparities and developing interventions to prioritize equitable healthcare access for rural women across diverse ethnic and income classes.

Background: The impact of computer ECG interpretation (CEI) on medical professionals’ performance is understudied. This study aims to assess the interpretation proficiency of diverse medical professionals with and without access to CEI reports. Methods: Medical professionals from diverse backgrounds interpreted 60 12-lead ECGs with urgent and non-urgent findings. The interpretation process involved two interpretation phases: (i) 30 ECGs with clinical statements and (ii) the same 30 ECGs and clinical statements in random order along with a CEI report. Diagnostic performance was evaluated based on interpretation accuracy, time per ECG, and self-reported confidence (rated 0 [not confident], 1 [somewhat confident], or 2 [confident]). Results: Among 892 participants, there were 44 (4.9%) primary care physicians, 123 (13.8%) cardiology fellows-in-training, 259 (29.0%) resident physicians, 137 (15.4%) medical students, 56 (6.3%) advanced practice providers, 82 (9.2%) nurses, and 191 (21.4%) allied health professionals. The inclusion of the CEI significantly improved interpretation accuracy by 15.1% (95% CI, 14.3 to 16.0; P<0.001), reduced interpretation time by 52 seconds (95% CI, -56 to -48; P<0.001), and increased confidence by 0.06 (95% CI, 0.03 to 0.09; P=0.003) (Table 1) . Conclusions: CEI integration improves ECG interpretation accuracy, efficiency, and confidence across medical professionals. Nevertheless, even with CEI, significant gaps in ECG interpretation proficiency remain.

Background: Accurate ECG interpretation is vital, but variations in skills exist among healthcare professionals. This study aims to identify factors contributing to ECG interpretation proficiency. Methods: Survey data and ECG test scores from participants in the EDUCATE Trial were analyzed. The dependent variable was the test score for interpreting 30 12-lead ECGs. Independent variables included non-modifiable factors (physician status, clinical experience, patient care impact) and modifiable factors (weekly interpretations, training hours, expert supervision frequency). Bivariate and multivariate analyses generated the Comprehensive Model (all factors) and Actionable Model (modifiable factors only). Results: Among 1206 participants, there were 72 (6.0%) primary care physicians, 146 (12.1%) cardiology fellows-in-training, 353 (29.3%) resident physicians, 182 (15.1%) medical students, 84 (7.0%) advanced practice providers, 120 (9.9%) nurses, and 249 (20.7%) allied health professionals. Physicians accounted for 571 (47.3%) of participants, while 453 (37.6%) were non-physicians. Bivariate analysis showed associations between test scores and multiple variables (Table 1) . In the Comprehensive Model, scores were independently associated with weekly interpretations (9.9 score increase; 95% CI 7.9-11.8; P<0.001), physician status (9.0 score increase; 95% CI 7.2-10.8; P<0.001), and training hours (5.7 score increase; 95% CI 3.7-7.6; P<0.001). In the Actionable Model, scores were independently associated with weekly interpretations (12.0 score increase; 95% CI, 10.0-14.0; P<0.001) and training hours (4.7 score increase; 95% CI 2.6-6.7; P<0.001). The Comprehensive and Actionable Models accounted for 18.7% and 12.3% of the variance in test scores, respectively. Conclusions: Being a physician is a non-modifiable predictor, while training and regular practice are modifiable predictors of ECG interpretation performance.

Introduction: Cardiac sarcoidosis (CS) results in HFrEF, but its natural history and response to GDMT remains uncertain. Methods: We queried a registry of 631 CS patients evaluated at our institution to identify those with LVEF < 35% on TTE within 30 d of diagnosis and a follow-up TTE 12-18 months later (external CS diagnoses were excluded). Demographics, LVEF, NT-proBNP, GDMT, immunosuppression, CIED, and outcomes (hyperkalemia, LVAD/transplant, CV hospitalization, death) were recorded. Results: Overall, 25/631 (4%) of CS patients had an LVEF <35% at initial presentation (36% female, 84% white; median age of 58 y; probable/not biopsy-proven CS in 52%). Mean baseline LVEF was 27% (σ=7%), NT-proBNP 1736 pg/mL (n=11), potassium 4.3 mEq/L (n=18), and median NYHA Class II (54%). Patients were on a mean 1.7 GDMT agents at CS diagnosis (Figure). Most were treated with immunosuppression (88%) for mean 0.75 y, usually prednisone (88%, mean 16 mg daily) and fewer with mycophenolate (32%, mean 1875 mg daily), methotrexate (28%, mean 18mg weekly), or TNF-α inhibitor (4%). 64% were on trimethoprim-sulfamethoxazole prophylaxis. At follow-up (median 317 d), 3 patients (12%) required LVAD and 1 (4%) required heart transplant. Mean LVEF improved to 37% (excluding LVAD/transplant, σ=11%, p=0.001). CIED prevalence increased from 48 to 81% (p=0.03). Overall GDMT did not change (mean 2.0 agents, p=0.2) and only beta-blocker dose changed (64 to 138 mg mean daily metoprolol equivalents). Potassium did not change (p=0.4) and hyperkalemic events were infrequent (16%). No patients died, but unplanned hospitalization occurred in 36% of patients. Conclusions: CS patients with HFrEF are usually on partial GDMT at diagnosis, presumably due to earlier recognition of HFrEF, but intensification of GDMT may be limited. Despite improved LVEF which may be due to GDMT, immunosuppression, and/or CIED, over 1/3 patients were hospitalized within 18 mo, highlighting the high-risk profile of HFrEF in CS.