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Individuals with inflammatory bowel disease (IBD) experience overlooked deficits in objectively measured cognitive functioning; however, there is limited knowledge about self-reported cognitive symptoms in this group. Sleep characteristics, such as insomnia, poor sleep quality, or fragmented sleep, may be key modifiable factors that are associated with cognitive symptoms among individuals with IBD. This study aimed to describe cognitive symptoms and examine the relationship between these symptoms and sleep characteristics among adults with IBD. We conducted a descriptive, cross-sectional study using the Pittsburgh Sleep Quality Index, wrist actigraphy, the Insomnia Severity Index, and the FACT-Cog Perceived Cognitive Impairments subscale. Bivariate statistics were used to evaluate relationships between variables. The sample included 83 participants (mean age 40.44 years [standard deviation 10.7], 71% female). Over 77% ( n = 60) had poor self-reported sleep quality, and 69.5% ( n = 57) had clinically meaningful insomnia. The most frequently reported cognitive symptoms (experienced two or more times a week) were trouble concentrating (51.3%), forgetting names (43.8%), forgetting intended tasks (38.9%), and slow thinking (37.6%). Insomnia severity was moderately correlated with three out of the four most common cognitive symptoms (trouble concentrating: r s = .51, p < .01; forgetting intended tasks: r s = .38, p < .01; slow thinking: r s = .46, p < .01). Future research is needed to examine relationships between objective cognitive measures and sleep characteristics and to test the effects of insomnia treatment on daytime cognitive symptoms in this complex patient population.

While the clinical focus on the sentinel lymph node biopsy (SLNB) is the presence of intra- or extra-nodal metastases, preclinical studies suggest that tumor-draining SLNB-associated vascular architecture and adhesion properties are altered regardless of SLNB positivity. Human intravital microscopy (HIVM) has defined blood vessel abnormalities that may impact lymphocyte adhesion and systemic drug delivery at primary melanoma sites. In this pilot study of HIVM during melanoma SLNB, we sought to determine the feasibility of obtaining HIVM observations of SLNB-associated vessels. We successfully performed HIVM in all 20 SLNB patients, and 7 were found to have nodal micrometastases by standard pathology. HIVM was capable of identifying both functional and non-functional SLNB-associated vessels based on the presence or absence of fluorescent dye uptake, respectively. Comparing vessel characteristics as a secondary exploratory objective, no statistically significant differences were noted in the diameter, flow rate, functionality, or shear stress of SLNB-associated blood vessels between positive and negative SLNBs, which may likely have been a reflection of the minimal disease burden. Nonetheless, these initial observations provide the framework to optimize future trials of HIVM in cancer patients.

INTRODUCTION: Long-term data are needed for offspring exposed in utero to medications for inflammatory bowel disease (IBD). METHODS: We used a prospective cohort of pregnant women with IBD and their offspring (Pregnancy in IBD and Neonatal Outcomes) to compare rates of serious infection, congenital malformations, and developmental delay by medication exposures. RESULTS: We included 438 offspring with at least 4 years of follow-up. No differences in adverse outcomes were observed by medication. Preterm birth, but not specific drug exposure, was associated with infection risk. Breastfeeding was not associated with serious infection differences. DISCUSSION: These findings support the use of effective IBD therapies throughout pregnancy.

Background Tricuspid regurgitation (TR) is a common valvular disorder that can affect patients’ quality of life and survival. The impact of TR etiology on overall survival and the associated risk factors in each subgroup are not well studied. Methods Multisite, retrospective study evaluating survival based on TR etiology using Kaplan–Meier and Cox regression models. Stepwise approach was used to define TR etiology (≥moderate): primary (PTR; presence of a primary valvular pathology), lead associated (LTR; lead interfering with closure), and secondary TR (STR) in the setting of left‐sided valvular disease, left ventricular disease, other causes of pulmonary hypertension, right ventricular disease, and atrial secondary TR. Results A total of 12 899 patients were included (3% PTR, 90% STR, 7% LTR). The mean age was 68±14, 73±13, and 71±13 years, respectively (44%–55% female patients). Adjusting for age, sex, and TR severity, patients with PTR had better overall survival (PTR: reference; STR hazard ratio [HR], 1.4 [1.2–1.6], LTR HR, 1.5 [1.1–1.7]). On multivariable Cox regression, the Tricuspid Regurgitation Impact on Outcomes score was associated with mortality across all groups ( P <0.05 for all). In addition, other risk factors associated with worse outcomes included pulmonary hypertension and ≥moderate right ventricular enlargement in PTR; left‐sided valvular disease, pulmonary hypertension, and ≥moderate right ventricular dysfunction in STR; and left ventricular disease and ≥moderate right ventricular dysfunction in LTR. Conclusions Patients with PTR have better survival than STR and LTR. Tricuspid Regurgitation Impact on Outcomes score was associated with mortality across etiologies, whereas other risk factors are etiology specific. Improved risk profiling may enhance patient selection, treatment decisions, and outcomes.

Importance There is a need for greater recognition of clinical psychopharmacology endpoints, including instances where specific psychotropic medications may become unnecessary, redundant, contradictory, or otherwise inappropriate and therefore merit deprescribing. Objective To address circumstances warranting psychotropic medication deprescribing. Evidence Review The American Society of Clinical Psychopharmacology convened a panel of 45 international psychopharmacology experts who developed and completed a multiround Delphi survey and conducted a focused literature review between January and May of 2025, in order to identify areas of consensus or disagreement on key aspects of the deprescribing of psychotropic medications. These included collaborative risk-benefit assessments with patients; pharmacokinetic and pharmacodynamic factors; pharmacogenomics; distinguishing redundant or conflictual from complementary mechanisms of action; managing adverse effects; assuring medication adherence; drug tolerance or tachyphylaxis; medication misuse; and the psychological context and ramifications of deprescribing. Findings Consensus was achieved on 44 of 50 final Delphi statements (88%). Panelists unanimously agreed that components of a pharmacotherapy regimen should undergo periodic review to ensure that treatments target relevant symptoms and have favorable risk-benefit ratios. Key points of consensus were that deprescribing: (1) should not occur without first assessing medication adherence; (2) merits consideration if less than partial therapeutic response is apparent, or if treatment goals have been reached and relapse prevention is not a long-term objective; (3) involves psychological ramifications that warrant attention; (4) should be followed by close clinical monitoring; and (5) risk-benefit decisions should ideally involve active patient participation within a shared decision-making model. Conclusions and Relevance Through this Consensus Statement, the Task Force identified circumstances in which the selective elimination of certain psychotropic medications may be clinically indicated. Empirical trials are needed to assess the implementation of deprescribing protocols and gauge their safe, effective, and acceptable outcomes.

Abstract Background Exercise stress echocardiography (ESE) is recommended in patients with mitral regurgitation (MR) when resting echocardiographic findings and symptoms do not align. However, the role of MR assessment in patients undergoing ESE for any indication remains uncertain. Purpose This study aimed to investigate whether the assessment of MR during ESE provides prognostic value beyond the evaluation of inducible regional wall motion abnormalities (RWMA) in patients undergoing ESE for any clinical indication, including suspected coronary artery disease (CAD). Methods Data were analyzed from a large multicenter and multinational prospective study. Current analysis included patients who underwent ESE for any indication and had MR (from 0= absent, to 3= severe) assessed at rest and peak exercise with an integrated qualitative, semi-quantitative, and (in selected cases) quantitative assessment. The primary endpoint was all-cause mortality. Results Of 1,351 included patients (age 56±16 years; 66% women; 30% with known CAD). MR score increased during exercise (rest=0.74±0.7 vs. peak=0.89±0.8, p&lt;0.001), with severe MR present in 2% of patients at rest and 7% at peak ESE. Patients with severe MR during exercise (n=96, Group 1) compared to those with non-severe MR during exercise (n=1255, Group 2) showed more B-lines, lower left ventricular contractile and chronotropic reserve, and trend (p=0.09) to more frequent decrease in ejection fraction during ESE (Table 1). After a median follow-up of 2.1 years (IQR 1.0–6.9), 99 patients (7%) had died. Severe MR at rest was associated with increased mortality (log-rank p&lt;0.001). Patients with severe MR at peak ESE had a higher risk of death compared to the other patients (log-rank p 0.035) (Figure 1). After adjusting for age, CAD, and inducible RWMA, severe MR with exercise remained strongly associated with an increased risk of death (adjusted-HR: 2.2, 95%CI 1.3-3.8, p=0.002). Similar results were seen with further adjustment for rest MR severity (adjusted-HR:1.9, 95%CI 1.02-3.5, p=0.004). Conclusion Patients, with and without CAD, with severe MR during ESE have greater functional impairment expressed by more pulmonary congestion, blunted heart rate reserve, and lower left ventricular contractile reserve. The assessment of MR during ESE provides significant prognostic information, independent of resting RWMA or inducible ischemia. Incorporating MR evaluation into routine ESE protocols may improve clinical decision-making and patient outcomes.Fig 1 Survival by MR at peak exercise Table 1

Abstract Background Chronotropic incompetence (CI) is a biomarker of cardiac autonomic dysfunction. Aim To assess the risk stratification value of CI during physical or pharmacological stress echocardiography in patients with chronic coronary syndromes. Methods In a prospective, multicenter, international, observational study design, we enrolled 13,445 patients with known or suspected chronic coronary syndromes who underwent stress echo in 19 sites from 10 countries using either exercise (n=2,594), dobutamine (n=2,440), or dipyridamole (n=8,411). Heart rate was automatically measured from the 1-lead ECG in the echo monitor. We considered CI as failure to reach 85% of the maximal predicted (220-age) heart rate for exercise and dobutamine, and heart rate reserve (peak/rest heart rate) &lt;1.22 (&lt;1.17 in permanent atrial fibrillation) for dipyridamole. All-cause death was the outcome measure. Results Heart rate reserve was available in all patients; there was no extra imaging or analysis time, and no intra- and inter-observer variability. CI was observed in 5,045 patients (38%); abnormal regional wall motion abnormality in 1,648 (13%). Over a median follow-up time of 3.5 years, there were 2,426 (18%) deaths. The 10-year mortality was 39% in patients with and 21% in patients without CI (p&lt;0.0001). CI was associated with a significant (p&lt;0.0001) increase in 10-year mortality in all age groups ranging from &lt;54 years to &gt;75 years. In addition, it was associated with increased mortality (p&lt;0.0001) irrespective of β-blocker use (Figure). Cox multivariable analysis revealed that CI was a significant predictor of mortality (HR 1.60, 95% confidence interval 1.47-1.74; p&lt;0.0001) together with age, male sex, diabetes mellitus, ejection fraction, and resting heart rate. Conclusion In patients with chronic coronary syndromes, CI during physical or pharmacological stress is a simple, inexpensive, quantitative, and objective predictor of survival.

Abstract Background Inducible ST-segment depression during stress echocardiography (SE) is associated with a higher risk in patients with inducible regional wall motion abnormality (RWMA). Objective To assess ST segment elevation's prevalence and functional correlates during SE. Methods ECG response was analyzed in 1712 patients (age 63±12 years; 1011 men, 59%) undergoing SE for chronic coronary syndromes (CCS) prospectively recruited at 39 laboratories. Among the patients analyzed, 1286 (75%) performed SE with exercise, 306 (18%) with dobutamine and 120 (7%) with a vasodilator. ECG response was considered abnormal in case of ST-segment shift &gt;1.0 mm from baseline at 80 ms from the J point developed in ≥2 contiguous leads during SE. The stress to rest (∆) change in the wall motion score index (WMSI) was assessed in all patients. Coronary angiography was available in 765 patients. Major adverse cardiac events (MACE) were the outcome measure in 746 patients with follow-up information. Results No significant ST segment shift was observed in 1000 patients (58%, Group 1), ST-segment depression occurred in 609 patients (35.5%, Group 2), and ST-segment elevation in 103 patients (6%, Group 3). ST-segment elevation occurred in 66/1286 patients (5.2%) with exercise, 30/306 with dobutamine (10%), and 7/120 with vasodilators (6%, p = ns vs. exercise and p&lt;0.01 vs. dobutamine). The prevalence of stress-induced RMWA was higher in Group 2 (38.1%) compared to Group 3 (33%) and Group 1 (11.9%. P&lt; 0.001 vs. Groups 2 and 3); however, the ΔWMSI was more pronounced in Group 3 compared to Group 2 and Group 1 (p = ns vs. Group 2 and p&lt;0.001 vs. Group 1). (Figure, left panel). Non-significant CAD (defined as coronary stenosis &lt;50% on coronary angiography) was more prevalent in Group 1 (36%) and 3 (40%) compared to Group 2 (17.5%, p&lt;0.01 vs. Group 1 and 3). . During a median follow-up of 387 days (IQ range 314-603 days), 150 events occurred in 112 patients: 14 all-cause deaths, 39 acute myocardial infarctions, 19 atrial fibrillations, 34 late coronary revascularizations, and 44 acute heart failure hospitalizations. The exposure-adjusted event rate was the lowest in Group 1 compared to Groups 2 and 3 (Figure, right panel). Conclusion In all-comers with CCS, the electrocardiographic pattern of ST-segment elevation is not rare, more frequent with dobutamine, associated with more stress-to-rest change in RWMA and more events despite less extensive underlying anatomic CAD. The paradox of more ischemia with less coronary stenosis is consistent with a coronary vasospastic origin as an important yet frequently overlooked cause of stress-induced ST segment elevation.Figure