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Abstract Background Identification of individuals at increased risk for synucleinopathies is becoming more feasible with advances in biomarkers. However, the ethical and practical aspects of communicating disease risk remain unresolved, particularly across diagnostic groups and cultural contexts. Objectives We aimed to evaluate attitudes toward disclosure of future synucleinopathy risk among individuals with isolated/idiopathic REM sleep behavior disorder (iRBD), as well as in individuals who developed Parkinson's disease (PD), or multiple system atrophy (MSA), in a large non‐Western registry. Methods This nationwide survey study included participants from 28 movement disorders and sleep centers across Türkiye. Questionnaires assessing attitudes toward risk disclosure, additional testing, and clinical trial participation were administered face‐to‐face. Responses were analyzed using contingency tables and regression models. Results are reported following the Consensus‐Based Checklist for Reporting of Survey Studies (CROSS) guideline. Results Among 1385 participants (1039 PD, 107 MSA, 239 iRBD), individuals with iRBD showed the highest support for risk disclosure (88.3%), exceeding PD (64.4%) and MSA (51.9%). Approval declined modestly (3–8%) when framed within the absence of disease‐modifying treatment. iRBD participants were more willing for additional testing but less willing to join clinical trials (31.8%) than PD (45.3%) or MSA (48%). MSA patients expressed the greatest concern about psychological impact. Male sex had more favorable views on disclosure and trial participation, while younger and better‐educated participants favored additional testing. Conclusions Attitudes toward risk disclosure differ markedly across the synucleinopathy spectrum and demographic characteristics. Culturally informed and diagnosis‐specific disclosure strategies will be essential for trial recruitment and patient‐centered care.

We provide the first longitudinal and most comprehensive analysis of the intrarenal microvasculature in a slowly progressive model of autosomal dominant polycystic kidney disease (ADPKD) and integrate the findings with studies in a young cohort of individuals with ADPKD. We identified vasculature-related pathways that could be targeted for therapeutic interventions and contribute promising, noninvasive biomarkers in patients with ADPKD. Alterations of the intrarenal microcirculation may affect drug delivery; a better understanding of its longitudinal changes may aid in treatment management.

ABSTRACTObjectiveTo conduct an economic evaluation of a group mindfulness program compared to an education support program for breast cancer survivors (BCS).MethodsThe cost‐utility analysis (cost per quality‐adjusted life year [QALY]) was performed from a single‐center randomized controlled trial in the United States. Data from 181 BCS were included in the analysis (91 from the mindfulness‐based stress reduction for breast cancer, MBSR(BC) and 90 from the Breast Cancer Education Support, (BCES)). Analyses were conducted from two perspectives: societal and healthcare system. The EuroQol EQ‐5D‐5L was used to measure quality of life and the Client Service Receipt Inventory (CSRI) was used to measure health services utilization from baseline through 26 weeks. The impact of MBSR(BC) on health services utilization and costs was estimated with generalized linear models.ResultsIn the reference case analyses (societal perspective), the average total cost in the MBSR(BC) group was $5744 compared with $6140 in the BCES group. At the end of follow‐up, the MBSR(BC) group dominated BCES in terms of Incremental Cost Utility Ratio (ICUR), with MBSR(BC) providing an incremental cost of −$541 (95% CI: −$3400, $2318) and a 0.021 QALY (95% CI: −0.014, 0.055). Net monetary benefit (NMB) analysis showed that MBSR(BC) has a higher probability of achieving positive NMB across a range of possible societal willingness‐to‐pay for improving quality of life.ConclusionsOur findings suggest that MBSR(BC) is likely to be cost‐effective for breast cancer survivors over 6 months. Cost savings primarily resulted from reduced ER and hospital admissions and tests.

Abstract Background Catheter ablation for atrial fibrillation (AF) improves quality of life and lowers cardiovascular adverse events. However, AF recurrence rates remain high - thus the need for better or improved predictors of AF recurrence. The role of left atrial (LA) stiffness remains unclear, as prior findings were controversial. Purpose To explore the relationship between a noninvasive LA stiffness index (LAstiffn) and AF recurrence after catheter ablation. Methods We analyzed a prospectively recruited cohort of patients who underwent catheter ablation for AF, were in sinus rhythm at 3 months post-ablation, had no significant (< moderate) valvular disease, and had LA volumes and LA diastolic function prospectively measured. LAStiffn was calculated as (E/e’)/LA emptying fraction (LAEF) ratio (abnormal defined as >15/45≈0.3). Outcome endpoint was the first documented AF/atrial flutter episode, lasting >30s, beyond 3 months post ablation (end of blanking period). Results A total of 589 patients were studied (mean age 60±10 years; 75% men; 50% with persistent AF; Table 1). At 3 months post-ablation, mean LAVI(Left atrial volume index) was 36±10 mL/m2 and LAstiffn 0.32±0.22. LAstiffn tended to be higher in older patients, in females, and patients with persistent AF and comorbidities (hypertension, congestive heart failure, coronary artery disease, CHA2DS2-VASc score ≥2, etc). At multivariable regression analysis, LAstiffn correlated with LV size and mass, degree of mitral/tricuspid regurgitation, and right ventricular systolic pressure. At 1 year, 3 years, and 8 years follow up, AF recurred in 118, 191, and 347 patients, respectively. At univariate Cox proportional hazards regression analysis, LAstiffn index >0.3 was significantly associated with AF recurrence at 1 year (log-rank P=.0005), 3 years (P=.0002), and 8 years follow up (P<.0001; Figure). In multivariate analysis including all clinical and laboratory factors with P<.10 in univariate analysis, LAstiffn >0.3 remained an independent factor for AF recurrence only at 3-years (adjusted HR 1.40 [1.03-1.91], P=.03) and 8 years follow up (adjusted HR 1.65 [1.29-2.13], P<.0001) after adjustment for age, sex, type of AF (persistent/paroxysmal), LA volume index (LAVi), obstructive sleep apnea, and prior pacemaker/ICD implantation (best independent factors); P=.14 at 1 year follow up. In ROC analysis, LAstiffn (AUC 0.61, P=.001) performed slightly better than LA deformation LAEF (AUC 0.59, P=.002) or E/e’ (AUC 0.58, P=.03), though with modest sensitivity/specificity (58%/62%). Conclusions LAstiffn may reflect LA myopathy that is likely due to the cumulative effects of comorbidities, diastolic dysfunction, and intrinsic LA tissue remodeling. LA stiffening may be a substrate facilitating redevelopment of AF, thus patients with increased LAstiffn may need more frequent monitoring to prevent/treat AF recurrence earlier.

Introduction: The Mindfulness-Based Stress Reduction program for breast cancer survivors (MBSR [BCs]) is a stress-reducing program designed to increase cognitive functioning through four meditational practices. This randomized clinical trial aimed to determine if improvements in cognitive functioning and perceived cognitive abilities achieved from the MBSR(BC) were mediated through increased mindfulness, decreased rumination, and decreased perceived stress. Methods: Breast cancer survivors (BCSs) who met inclusion criteria of stage I, II, or III BC and received either chemotherapy (CT) or both CT and radiation were randomized to either the 6-week MBSR(BC), or Breast Cancer Education Support (BCES) program, or to a usual care (UC) regimen. Analysis of covariance was first implemented to identify potential mediators, followed by a formal mediational analysis to evaluate the effects of MBSR(BC) on 6-, 12-, and 26-week outcomes. Results: After consent, 212 BCS were randomized to MBSR(BC) ( n = 91), BCES ( n = 90), or UC ( n = 31). The mean age was 56.5 and the majority of the BCS, 73.1%, were White and non-Hispanic. Results showed increases in “observing” as part of mindfulness as a potential mediator of MBSR(BC) effects on impairments on quality of life and logical memory at 6 months relative to UC. No mediation effects were identified for outcomes measured at 6 or 12 weeks and also when MBSR(BC) was compared with the BCES program. Discussion: These results partially supported our hypothesis that improvement in cognitive functioning would occur through increased mindfulness. Although few mediating relationships were identified, results showed a relationship between mindfulness and cognitive functioning. Both mediating relationships occurred through increases in “observing,” a subconcept of “mindfulness,” when compared to the MBSR(BC) with UC at 6 months. This study shows that mediators may help “optimize” clinical therapeutic treatment effects, thus contributing to the advancement of science. Trial Registration: ClinicalTrials.gov, www.ClinicalTrials.gov . Registration Number: NCT02786797.

Introduction: An elevated blood pressure (mean arterial pressure, MAP) response to exercise is an independent predictor of hypertension (HTN) development. HTN is highly prevalent in postmenopausal females. Postmenopausal, compared to premenopausal, females have a higher MAP at rest and during exercise primarily due to higher systemic vascular resistance (SVR). Studies using small muscle mass exercise have suggested that postmenopausal females have augmented increases in MAP from rest to exercise. However, it is unclear if postmenopausal females have augmented MAP responses from rest to exercise during whole-body exercise. Hypothesis: We hypothesized that postmenopausal females would have greater increases in MAP and smaller decreases in SVR from rest to peak exercise than premenopausal females. Methods: Normotensive premenopausal (n=16; age: 30±7 yrs; BMI: 23±4 kg/m 2 ) and postmenopausal (n=14; age: 57±7 yrs; BMI: 27±4 kg/m 2 ) female participants performed an incremental cycling test until task failure. Blood pressure was measured by manual sphygmomanometry, cardiac output (Q) via open-circuit acetylene wash-in technique, and SVR was calculated. Data are reported at rest and peak oxygen uptake (VO 2 ). Data are also reported as % change from rest to VO 2 peak. Results: Postmenopausal females had higher MAP and SVR at rest and at VO 2 peak than premenopausal females (all, p<0.05). Postmenopausal, compared to premenopausal, females had lower Q at VO 2 peak commensurate with the lower achieved VO 2 peak (p<0.01). Resting MAP was positively related to MAP at VO 2 peak in postmenopausal females (r=0.85, p<0.01), but not premenopausal females (p=0.22). % change in MAP from rest to VO 2 peak was not different between groups (Post: 18±8 vs. Pre: 18±9%) (p=0.94). However, postmenopausal females had smaller % decreases in SVR from rest to VO 2 peak (Post: -44±7 vs. Pre: -54±8%) and smaller % increases in Q compared to premenopausal females (Post: 113±31 vs. Pre: 162±50%) (both, p<0.01). Conclusion: Our findings indicate that postmenopausal and premenopausal females have similar increases in MAP from rest to VO 2 peak; however, the mechanisms contributing to the MAP response differed by menopausal status. Postmenopausal females relied on smaller decreases in SVR, whereas premenopausal females had greater increases in Q. These findings provide important insight into the mechanisms contributing to the clinically relevant higher MAP response during exercise in postmenopausal females.

Background Genetics may influence symptoms experienced by breast cancer survivors (BCS) by moderating the effects of stress-reducing interventions, including the Mindfulness-Based Stress Reduction (MBSR(BC)) program, to reduce symptom severity. As part of a larger clinical trial, the aim of this study was to evaluate genetic variants as moderators of MBSR(BC) on improvements among BCS in cognitive functioning and symptoms. Methods BCS ( n = 128) were randomized to MBSR(BC) or the Breast Cancer Education Support Program. Objective neuropsychological and subjective measures of cognitive performance, and psychological and physical symptoms were collected at baseline, 6, 12, and 26 weeks. Linear mixed models were implemented to identify MBSR(BC)’s effects over time. A total of 22 single nucleotide polymorphisms (SNPs) from 20 genes known to be related to these symptoms were investigated using genomic DNA. These SNPs were tested as moderators of MBSR(BC) program effects. Results Results showed MBSR(BC) participants experienced significantly greater benefits in cognitive functioning, however, the level of benefit varied based on one’s genetic profile. Effects sizes, consistency across similar measures were investigated. Among 22 candidate SNPs, rs4680 in COMT, rs1800497 in ANKK1, and rs6277 in DRD2 demonstrated the strongest, most consistent positive effects in moderating MBSR(BC)’s impact on cognitive outcomes. Conclusions Although the effects were small, this translational research may potentially identify BCS with genotypes that would be most influenced by the MBSR(BC) program. These results may be used to develop personalized intervention programs tailored to the genetic profile of each breast cancer survivor who received chemotherapy or chemotherapy and radiation. Trial Registration ClinicalTrials.gov, https://www.ClinicalTrials.gov Registration Number: NCT02786797.

Pheochromocytomas are rare neuroendocrine tumors characterised by the secretion of catecholamines and their metabolites. While some patients may be asymptomatic, they can also present with various symptoms including hypertensive crisis, headaches, palpitations, diaphoresis or other signs of catecholamine toxicity. Adrenal haemorrhage, though rare, is a potentially fatal complication that is often diagnosed during autopsy. In all patients with suspected pheochromocytoma, regardless of whether haemorrhagic conversion has occurred, prompt diagnosis is imperative. Early identification allows for the timely initiation of treatment, preventing potentially life-threatening complications. This case report details the haemorrhagic conversion of an undiagnosed pheochromocytoma in a female patient in her 30s.

Introduction: The Mindfulness-Based Stress Reduction (MBSR) Program for breast cancer survivors (BCS) is designed to enhance cognitive training through formal and informal meditational practices. This randomized clinical trial (RCT) aimed to evaluate if BCS assigned to either the MBSR(BC), Breast Cancer Education Support (BCES), or Usual Care (UC) regimens experienced greater improvements at 6, 12, and 26 weeks on objective and subjective cognitive performance. Methods: BCS ( n = 212) randomized to a three-group RCT: MBSR(BC) ( n = 91), BCES ( n = 90), or UC ( n = 31) were assessed on cognitive performance and symptoms at baseline, 6, 12, and 26 weeks. Linear mixed models were fit to evaluate the effects of the MBSR(BC) program, hypothesizing ordered effect improvements: (MBSR[BC] highest, BCES intermediate, UC lowest) along with baseline characteristics evaluated as moderators. Results: Of the BCS (mean age of 57), 73% were White, and non-Hispanic, and 77% received both chemotherapy (CT) and radiation. Cognitive performance improved in all groups. Although there were no statistically significant between-group differences in cognitive outcomes, significant symptom reductions occurred for the MBSR(BC) group ( p = 0.003). Within-group effect size analysis at 26 weeks showed substantial improvements in all three groups (effect sizes >0.50) in subjective impairments and quality of life (effect size >0.50) and objective measures of cognitive performance. MBSR(BC) showed the largest within-group effect size in the reduction of fatigue (effect size = 0.81). Effect sizes occurred in the hypothesized direction for 10 of the 18 outcomes. Discussion: Although the MBSR(BC) program did not show significant differences in cognitive performance compared with BCES and UC, all groups improved and reductions in fatigue were beneficial for MBSR(BC). Results suggest that cognitive performance may improve after CT over time considering one’s natural history. Furthermore, BCS enrolled in RCTs may be more motivated to improve their health status (NCT02786797).