Melatonin for the Treatment of Sepsis: The Scientific Rationale

Sepsis affects 30 million people worldwide, leading to 6 million deaths every year (WHO), and despite decades of research, novel initiatives are drastically needed. According to the current literature, oxidative imbalance and mitochondrial dysfunction are common features of septic patients that can cause multiorgan failure and death. Melatonin, alongside its traditionally accepted role as the master hormonal regulator of the circadian rhythm, is a promising adjunctive drug for sepsis through its anti-inflammatory, antiapoptotic and powerful antioxidant properties. Several animal models of sepsis have demonstrated that melatonin can prevent multiorgan dysfunction and improve survival through restoring mitochondrial electron transport chain (ETC) function, inhibiting nitric oxide synthesis and reducing cytokine production. The purpose of this article is to review the current evidence for the role of melatonin in sepsis, review its pharmacokinetic profile and virtual absence of side effects. While clinical data is limited, we propose the adjunctive use of melatonin is patients with severe sepsis and septic shock

Quercetin and Vitamin C: An Experimental, Synergistic Therapy for the Prevention and Treatment of SARS-CoV-2 Related Disease (COVID-19)

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) represents an emergent global threat which is straining worldwide healthcare capacity. As of May 27th, the disease caused by SARS-CoV-2 (COVID-19) has resulted in more than 340,000 deaths worldwide, with 100,000 deaths in the US alone. It is imperative to study and develop pharmacological treatments suitable for the prevention and treatment of COVID-19. Ascorbic acid is a crucial vitamin necessary for the correct functioning of the immune system. It plays a role in stress response and has shown promising results when administered to the critically ill. Quercetin is a well-known flavonoid whose antiviral properties have been investigated in numerous studies. There is evidence that vitamin C and quercetin co-administration exerts a synergistic antiviral action due to overlapping antiviral and immunomodulatory properties and the capacity of ascorbate to recycle quercetin, increasing its efficacy. Safe, cheap interventions which have a sound biological rationale should be prioritized for experimental use in the current context of a global health pandemic. We present the current evidence for the use of vitamin C and quercetin both for prophylaxis in high-risk populations and for the treatment of COVID-19 patients as an adjunct to promising pharmacological agents such as Remdesivir or convalescent plasma

Tricuspid Regurgitation in Acute Heart Failure: Predicting Outcome Using Novel Quantitative Echocardiography Techniques

Background: The prognostic impact of tricuspid regurgitation (TR) in acute heart failure (AHF) remains uncertain. Methods: We retrospectively assessed 418 consecutive AHF patients who underwent comprehensive echocardiographic assessment within 24 h of study recruitment. TR was quantitatively assessed with 3 guideline-directed measures: regurgitant volumes (RgVol), effective regurgitant orifice area (ERO) and vena contracta (VC) diameter. Disproportionate TR was assessed by the ratio of the VC diameter to the tricuspid annulus diameter (VC/TA) ≥ 0.24. Results: The prevalence of significant (i.e., >mild) TR differed when various standard assessment parameters were applied to quantification: RgVol 50.3% (173/344), ERO 75.6% (260/344) and VC diameter 94.6% (335/354). None were able to delineate those at excess risk of all-cause 2-year mortality using guideline-directed cut-offs of mild, moderate and severe TR. Using a cut-off of VC/TA ≥ 0.24, we identified that 36.9% (130/352) had “disproportionate” TR. Disproportionate TR was associated with an excess risk of mortality at 2 years compared to proportionate TR; HR 1.48 (95% CI 1.06–2.06 [p = 0.02]) which was not significant on multivariate assessment (p = 0.94). Conclusions: TR was not associated with outcome in AHF using guideline measures. A new assessment of “Disproportionate” TR carries a higher risk than proportionate TR but was not related to outcome based on multivariate analysis. Further research is needed to quantify TR more effectively to identify cut-offs for future guidelines and disproportionate TR may be an important part of Heart Failure 2.0