Clinical outcome of patients with rheumatic tricuspid valve disease: matched cohort study.

Rheumatic heart disease (RHD) is still a major health problem, especially in low- to mid-income countries, leading premature deaths owing to valvular disease. Although left-sided valvular involvement is most commonly seen in RHD, the tricuspid valve can also be affected. However, there is a lack of information about the prognostic value of primary tricuspid valve (TV) disease in RHD. This study aimed to determine the impact of TV disease on clinical outcome in RHD. This prospective study enrolled patients with rheumatic mitral valve disease (MVD) referred to a tertiary center for management of heart valve disease. Primary rheumatic TV disease was defined by echocardiographic features including thickening of leaflets associated with some degree of restricted mobility. Patients with rheumatic TV disease were matched to patients with MVD using 1:1 genetic matching algorithm that maximized balance of baseline covariates prior to exploring outcome differences. The main outcome was either need for MV replacement or death. Among 694 patients eligible for the study, age of 47 ± 13 years, 84% female, 39 patients (5.6%) had rheumatic TV disease. After excluding patients with incomplete data, 33 patients with TV disease were matched to 33 controls based on age, right-sided heart failure, atrial fibrillation, and MV area. During a mean follow-up of 42 months (median 28, IQR 8 to 71 months), 32 patients (48.5%) experienced adverse events, including 6 cardiovascular deaths and 26 patients who underwent surgery for mitral valve replacement. The adjusted analysis demonstrated a significant association between TV disease and the outcome, with a hazard ratio (HR) of 3.386 (95% CI 1.559-7.353; P = 0.002) in the genetic matched cohort with balance on baseline covariates of interest. The model exhibited good discriminative ability, as indicated by a C-statistic of 0.837. In patients with rheumatic mitral valve disease, rheumatic TV disease significantly increased risk of adverse events compared with matched controls. The involvement of TV may express overall disease severity that adversely affects clinical outcome.

Potential Biomarkers of impulsivity in mild traumatic brain injury: A pilot study.

Very few studies have investigated cognition and impulsivity following mild traumatic brain injury (mTBI) in the general population. Furthermore, the neurobiological mechanisms underlying post-TBI neurobehavioral syndromes are complex and remain to be fully clarified. Herein, we took advantage of machine learning based-modeling to investigate potential biomarkers of mTBI-associated impulsivity. Twenty-one mTBI patients were assessed within one-month post-TBI and their data were compared to 19 healthy controls on measures of impulsivity (Barratt Impulsiveness Scale - BIS), executive functioning, episodic memory, self-report cognitive failures and blood biomarkers of inflammation, vascular and neuronal damage. mTBI patients were significantly more impulsive than controls in BIS total and subscales. Serum levels of sCD40L, Cathepsin D, IL-4, Neuropilin-1, IFN-α2, and Copeptin were associated with impulsivity in mTBI patients. Besides showing that mTBI are associated with impulsivity in non-military people, we unveiled different pathophysiological pathways potentially implicated in mTBI-related impulsivity.

Inflammasome activation and assembly in Huntington's disease.

Huntington's disease (HD) is a rare neurodegenerative disease characterized by motor, cognitive, and psychiatric symptoms. Inflammasomes are multiprotein complexes capable of sensing pathogen-associated and damage-associated molecular patterns, triggering innate immune pathways. Activation of inflammasomes results in a pro-inflammatory cascade involving, among other molecules, caspases and interleukins. NLRP3 (nucleotide-binding domain, leucine-rich-repeat containing family, pyrin domain-containing 3) is the most studied inflammasome complex, and its activation results in caspase-1 mediated cleavage of the pro-interleukins IL-1ß and IL-18 into their mature forms, also inducing a gasdermin D mediated form of pro-inflammatory cell death, i.e. pyroptosis. Accumulating evidence has implicated NLRP3 inflammasome complex in neurodegenerative diseases. The evidence in HD is still scant and mostly derived from pre-clinical studies. This review aims to present the available evidence on NLRP3 inflammasome activation in HD and to discuss whether targeting this innate immune system complex might be a promising therapeutic strategy to alleviate its symptoms.