Citations

Since the discovery of the first psychoactive medications, their psychiatric and medical uses have overlapped. Designating a medication psychiatric or psychotropic is thus arbitrary, based on its most common usage, but labeling it so obscures the full range of its pharmacologic activity and clinical utility. Psychotropic medications (PMs) are frequently used to treat medical conditions or symptoms in the areas of neurology (e.g., migraine, seizure disorder), dermatology (e.g., itching), gastroenterology, and chronic pain, among many others. It is important for both primary care and specialty physicians to be aware of the potential non-psychiatric indications for the use of common PMs such as antidepressants, antipsychotics, and anxiolytics. This review examines the potential benefits and risks of PMs when used for non-psychiatric indications, highlighting how their pharmacologic effects on neurotransmitters contribute to both therapeutic outcomes and adverse effects. It also provides guiding principles for prescribers, including the importance of adjusting doses based on the specific indication, monitoring for harmful side effects, considering age-related factors, and addressing the risks associated with polypharmacy.

Background and objective: Heart failure (HF) is associated with high morbidity, mortality, and healthcare costs. Its prevalence continues to rise, particularly in the context of ageing populations and increasing rates of metabolic comorbidities such as type 2 diabetes and obesity. We aimed to assess the therapeutic potential of repurposing PPARα agonists for the treatment of HF. Method: We conducted a comprehensive literature review to evaluate preclinical and clinical evidence investigating the potential of PPARα agonist drugs in reducing HF. We did not apply any restrictions on the study design. Results: The current body of evidence consists of preclinical mechanistic studies, emerging pharmacogenetic data, and post hoc analyses of large randomised clinical trials (RCTs) that included HF endpoints. No dedicated, HF-specific RCTs of PPARα agonists were identified. These studies support the hypothesis that PPARα agonists may link metabolic modulation with cardiac remodelling. Preclinical models demonstrate potential therapeutic benefits, such as enhanced myocardial energy metabolism and attenuation of fibrosis and inflammation, as well as context-dependent risks, including possible deleterious effects in advanced HF or off-target mechanisms. Prior failures of fibrates to improve cardiovascular outcomes in some trials and concerns in PPARα-deficient states underscore the complexity of metabolic therapies in HF. These findings support a more stratified, phenotype-driven approach to therapy. RCTs specifically designed to evaluate HF outcomes are essential to clarify whether PPARα agonists can complement established neurohormonal treatments, particularly in the context of the rising burden of HFpEF associated with obesity and type 2 diabetes. Conclusions: PPARα agonists represent a promising class within the emerging therapeutic framework of metabolic heart failure. They are inexpensive, generally well tolerated, and address several pathophysiological mechanisms of HF. Preliminary evidence suggests that fenofibrate may delay or prevent HF in high-risk diabetic populations. However, rigorous, dedicated trials are needed to establish their clinical utility.

BACKGROUND: The purpose of this study was to assess the feasibility and prognostic value of cardiac output (CO) reserve assessment using exercise echocardiography in Fontan patients. We hypothesized that adults with Fontan palliation had lower CO reserve compared with controls, and impaired CO reserve was associated with greater congestion (NT-proBNP [N-terminal pro-B-type natriuretic peptide]) and cardiovascular events (death/transplant/heart failure hospitalization) in Fontan patients. METHODS: Thirty-seven Fontan patients and 61 controls underwent exercise echocardiography using a supine cycle ergometer. Doppler-derived CO and oxygen consumption (VO 2 ) were assessed at rest and every stage of exercise. CO reserve was calculated as ∆CO/Watt (∆CO/W) and ∆CO/∆VO 2 . RESULTS: Assessment of CO reserve was feasible in 95% of the Fontan group with modest reproducibility. Although both groups had similar CO at rest, the Fontan group had lower CO reserve with exercise as evidenced by lower ∆CO/W ratio (46±17 versus 57±19 mL/W; P <0.001) and lower ∆CO/∆VO 2 ratio (4.48±1.02 versus 5.37±2.18 mL/mL; P =0.03). There was a correlation between ∆CO/W ratio and log NT-proBNP (r=0.65; P <0.001), and between ∆CO/∆VO 2 ratio and log NT-proBNP (r=0.53; P =0.009). Impaired CO reserve was associated with congestion and cardiovascular events and provided improved prognostication (higher area under the curve and C statistics) above conventional echocardiographic indices and treadmill peak VO 2 . CONCLUSIONS: Patients with Fontan palliation had lower CO reserve, and impaired CO reserve was associated with congestion and cardiovascular events. Further studies are required to determine whether cardiac interventions can improve CO reserve and whether changes in CO reserve can be used as a surrogate end point for therapeutic response.

Chronic pain affects nearly 100 million adults in the U.S., yet few novel therapeutics have emerged in recent decades. P2X4 receptor (P2X4R), implicated in pain signaling, represents a promising target. We evaluated a humanized single-chain variable fragment (hscFv) targeting P2X4R for its ability to reduce ATP-induced currents and modulate excitability in human dorsal root ganglion (hDRG) neurons. Voltage-clamp recordings confirmed that human P2X4R (hP2X4R) hscFv significantly reduced ATP-evoked currents in HEK-293T cells expressing human P2X4, likely by relocalization of the receptor to the perinuclear region after hscFv treatment. Immunohistochemistry and transcriptomic analyses demonstrated widespread P2X4R ( P2RX4 ) expression across hDRG neuronal subtypes in both male and female donors. Current-clamp recordings revealed that hP2X4R hscFv selectively increased action potential (AP) threshold in multi-firing hDRG neurons, without affecting single-firing neurons. Spontaneous activity at rest and depolarizing spontaneous fluctuation (DSF) amplitude were also reduced. Analysis confirmed consistent effects of hP2X4R hscFv on excitability parameters. These findings suggest that hP2X4 hscFv exerts modest but targeted effects on human sensory neurons, supporting its potential as a novel therapeutic for chronic pain.

Abstract The practice of formally documenting radiologic and pathologic concordance after percutaneous breast biopsies was instituted more than 20 years ago. There are several ways in which this can be done, but in many practices the performing radiologist independently compares the imaging findings with the pathology report to determine concordance. However, some studies show that a multidisciplinary review of breast biopsy results can maximize cancer detection, identify discordant cases in a timely manner, decrease imaging follow-up, and avoid unnecessary surgical intervention. This article will propose a practical method to establish a formal radiology-pathology conference in which percutaneous breast biopsies are reviewed with multidisciplinary input to increase efficiency and improve patient care. With the wide implementation of digital radiologic imaging and digital pathology evaluation plus the recent adoption of virtual meeting platforms, a successful radiology-pathology conference can be implemented in nearly any practice setting. Case examples will be presented demonstrating the utility of such a conference.

Abstract Aims Our aim was to assess the clinical and prognostic significance of the left ventricular (LV) hypercontractile phenotype (HP) in hypertrophic cardiomyopathy (HCM), which until now remains unclear. Methods and results We enrolled 1533 HCM patients (age 51 ± 15 years, 965 males, 63%) with ejection fraction (EF) ≥ 50%, referred for rest transthoracic echocardiography (TTE) in 27 laboratories from 13 countries. Two-dimensional volumetric TTE assessment included LV outflow tract gradient (LVOTG), LV EF, and LV force (systolic blood pressure + LVOTG/ESV, mmHg/mL). HP was defined as the highest quartile of the force (&gt; 7.32 mmHg/mL). Survival analysis was performed in a subset of 1200 patients with follow-up information. Compared with non-HP patients, HP showed higher heart rate (72 ± 14 vs. 67 ± 14 beats per minute, P &lt; 0.001), lower stroke volume (50 ± 22 vs. 67 ± 22 mL, P &lt; 0.001), larger left atrial volume index (44 ± 16 vs. 40 ± 16 mL/m2, P = 0.011) and higher coronary flow velocity in the mid-distal left anterior descending artery (n = 325, 41 ± 12 vs. 37 ± 14 cm/s, P = 0.021). Force was moderately related to LV EF (r = 0.48, P &lt; 0.001) and weakly to LVOTG (r = 0.36, P &lt; 0.001). During a median follow-up of 87 months (interquartile range 45–143 months), 131 all-cause deaths occurred. At multivariable Cox analysis, a force &gt; 7.32 mmHg (the fourth quartile for analyzed patients) was associated with a hazard ratio of 1.44 (95% Confidence intervals 1.00–2.07) for all-cause death, independently of LVOTG and LV EF. Conclusion HP in HCM is associated with a disadvantageous systemic, cardiac and coronary hemodynamic profile as well as lower survival in the long-term.