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Melanocortins play a fundamental role in several basic functions of the organism (sexual activity, feeding, inflammation and immune responses, pain sensitivity, response to stressful situations, motivation, attention, learning, and memory). Moreover, a large body of animal data, some of which were also confirmed in humans, unequivocally show that melanocortins also have impressive therapeutic effects in several pathological conditions that are the leading cause of mortality and disability worldwide (hemorrhagic, or anyway hypovolemic, shock; septic shock; respiratory arrest; cardiac arrest; ischemia- and ischemia/reperfusion-induced damage of the brain, heart, intestine, and other organs; traumatic injury of brain, spinal cord, and peripheral nerves; neuropathic pain; toxic neuropathies; gouty arthritis; etc.). Recent data obtained in animal models seem to moreover confirm previous hypotheses and preliminary data concerning the neurotrophic activity of melanocortins in neurodegenerative diseases, in particular Alzheimer’s disease. Our aim was (i) to critically reconsider the established extrahormonal effects of melanocortins (on sexual activity, feeding, inflammation, tissue hypoperfusion, and traumatic damage of central and peripheral nervous system) at the light of recent findings, (ii) to review the most recent advancements, particularly on the effects of melanocortins in models of neurodegenerative diseases, (iii) to discuss the reasons that support the introduction into clinical practice of melanocortins as life-saving agents in shock conditions and that suggest to verify in clinical setting the impressive results steadily obtained with melanocortins in different animal models of tissue ischemia and ischemia/reperfusion, and finally, (iv) to mention the advisable developments, particularly in terms of selectivity of action and of effects.

Background: Undifferentiated shock is recognized as a criticality state that is transitional in immune-mediated topology for casual risk of lethal microcirculatory dysfunction. This was a sensitivity analysis of a drug (tetracosactide; TCS10) targeting melanocortin receptors (MCRs) in a phase 3 randomized controlled trial to improve cardiovascular surgical rescue outcome by reversing mortality and hemostatic disorders., Methods: Sensitivity analysis was based on a randomized, two-arm, multicenter, double-blind, controlled trial. The Naïve Bayes classifier was performed by density-based sensitivity index for principal strata as proportional hazard model of 30-day surgical risk mortality according to European System for Cardiac Operative Risk Evaluation inputs-outputs in 100 consecutive cases (from August to September 2013 from Emilia Romagna region, Italy). Patients included an agent-based TCS10 group (10 mg, single intravenous bolus before surgery; n = 56) and control group (n = 44) and the association with cytokines, lactate, and bleeding-blood transfusion episodes with the prior-risk log-odds for mortality rate in time-to-event was analyzed., Results: Thirty-day mortality was significantly improved in the TCS10 group vs. control group (0 vs. 8 deaths, P < 0.0001). Baseline levels of interleukin (IL)-6, IL-10, and lactate were associated with bleeding episodes, independent of TCS10 treatment [odds ratio (OR) = 1.90, 95% confidence interval (CI) 1.39-2.79; OR = 1.53, 95%CI 1.17-2.12; and OR = 2.92, 95%CI 1.40-6.66, respectively], while baseline level of Fms-like tyrosine kinase 3 ligand (Flt3L) was associated with lower bleeding rates in TCS10-treated patients (OR = 0.31, 95%CI 0.11-0.90, P = 0.03). For every 8 TCS10-treated patients, 1 bleeding case was avoided. Blood transfusion episodes were significantly reduced in the TCS10 group compared to the control group (OR = 0.32, 95%CI 0.14-0.73, P = 0.01). For every 4 TCS10-treated patients, 1 transfusion case was avoided., Conclusions: Sensitivity index underlines the quality target product profile of TCS10 in the runway of emergency casualty care. To introduce the technology readiness level in real-life critically ill patients, further large-scale studies are required., Trial Registration: European Union Drug Regulating Authorities Clinical Trials Database (EudraCT Number: 2007-006445-41 )., (© 2024. The Author(s).)

Purulent pericarditis is rare and usually associated with pneumonia, bacteremia, immunosuppression, and thoracic surgery. A timely diagnostic pericardiocentesis with dedicated maneuvers to improve the effectiveness of drainage and pericardial fibrinolytic rinsing can improve prognosis and prevent a surgical pericardiectomy. Imaging offers useful clues for a more aggressive approach.

Objective: The purpose of this study was to review the risk-benefit ratio of mitral valve repair in patients with severe mitral regurgitation and no or mild symptoms., Methods: From January 1989 to December 1994, 584 patients were operated on for mitral regurgitation. Of these, 175 patients were in New York Heart Association class I or II with grade 3 to 4 isolated chronic mitral regurgitation. They comprise our study population. Mean age was 51.3 +/- 14.3 years. Principal causes of mitral regurgitation were degenerative in 128 (73%) and rheumatic in 26 patients (15%). Leaflet prolapse was the mechanism responsible for regurgitation in 152 patients (86%). Mitral valve repair was performed in 174 patients, and one patient required initial valve replacement. Mean follow-up was 34.3 +/- 18.8 months., Results: Three patients died, for an overall mortality of 1.7%. Five patients were reoperated on, for an actuarial freedom from reoperation of 97.0% +/- 0.8% at 5 years. Actuarial freedom from thromboembolism and endocarditis was 96.3% +/- 1.7% and 99.4% +/- 0.6%, respectively, for an event-free survival of 91.0% +/- 2.0% at 5 years. Left atrial diameter decreased from 54.3 +/- 11.6 mm to 43.6 +/- 10.5 mm (p < 0.001). Left ventricular end-systolic and end-diastolic diameters decreased from 40.0 +/- 6.8 mm and 64.8 +/- 7.0 mm to 34.6 +/- 6.7 mm (p < 0.001) and 52.7 +/- 7.4 mm (p < 0.001), respectively. Mean residual mitral regurgitation was 0.44 +/- 0.6., Conclusion: Mitral valve repair for chronic mitral regurgitation in patients having mild or no symptoms was performed with low mortality and morbidity, good valve function, and preserved late left ventricular performance. Early repair may be advocated on the basis of severity of regurgitation and valve repairability, regardless of symptoms.

Tricuspid valve incompetence from ruptured papillary muscle or chordae as a result of nonpenetrating trauma is uncommon. Blunt trauma causing partial detachment of a leaflet from the annulus is very rare. We report the case of a young adult involved in a car accident who had these findings. Operative repair with resuture of the leaflet to the annulus and annuloplasty using a Carpentier ring resulted in complete recovery.

A new technique for constructing a pulmonary valve from the wall of the pulmonary artery is described. Hemodynamic studies conducted following this procedure demonstrated no systolic gradient and good diastolic competence. A long-term study of this procedure is needed to determine whether or not the technique has clinical applicability.