Efficacy and safety of Link Natural Sudarshana, an Ayurvedic herbal preparation in COVID-19 patients: A phase II multicenter double-blind randomized placebo-controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: In vitro and in vivo studies have shown anti-viral and immunomodulatory actions in components of many traditional medicines. Various constituents of traditional medicines have been found to be effective against coronavirus disease (COVID-19) in several clinical trials and in-silico studies. Sudarshana cúrna, a polyherbal Ayurvedic medicine, has been used over thousands of years for a variety of infectious fevers. AIMS OF THE STUDY: This study aimed to evaluate the efficacy and safety of Link Natural Sudarshana (LNS) tablets, in patients with COVID 19 disease. LNS is a polyherbal preparation comprising 49 medicinal plants included in the Sudarshana cúrna. MATERIALS AND METHODS: A randomized parallel-group double-blind placebo-controlled multi-center phase II clinical trial was conducted in patients with mild to moderate COVID-19 disease. They were randomly allocated to intervention and control groups. The intervention group received LNS tablets whereas the control group received placebo tablets for 10 days or until the patient was discharged from the hospital. All patients received standard symptomatic treatment. The primary outcome, a reduction in mean log viral load was assessed at day 5 of treatment. The secondary outcomes, clinical progression and safety, were assessed by, monitoring changes in symptoms daily on a Likert scale ranging from 1 to 4 and laboratory tests respectively. RESULTS: A total of 171 patients (treatment group 83, control group 88) completed the trial. There were no significant differences between the baseline status of the two groups except that body mass index was significantly higher in the placebo group. The mean log viral load reduction at day 5 was higher in the treatment group (2.20 ± 1.67) compared to the placebo group (1.93 ± 1.80), with a mean difference of -0.278. This difference was not statistically significant at the 5% significant level. Reduction of mean cumulative symptom score, which included 16 symptoms graded according to severity, was higher in the treatment group compared to the placebo group. This difference was not statistically significant. None of the study participants developed hypoxia. Among the 7 lymphopenia patients in the placebo group, 3 continued to have lymphopenia at day 10, whereas 9 lymphopenia patients in the treatment group, reverted to normal counts. C reactive proteins (CRP) showed a greater reduction in the treatment group. None reported adverse effects. No significant changes occurred in hematological and biochemical parameters that assessed safety. CONCLUSIONS: LNS is safe to use in COVID-19 patients and accelerated the decline in viral load, relieved symptoms, reduced CRP levels and reversed lymphopenia earlier, when compared to the placebo.

Case Report: A Case of Acute Intravascular Hemolysis in Dengue Fever.

Acute intravascular hemolysis (AIH) with hemoglobinuria is a rare complication of dengue viral infection. Review of the literature revealed only one report of AIH as a complication of dengue fever (DF). We report a case of AIH with massive hemoglobinuria in a 17-year-old Sri Lankan male, in the febrile phase of DF. This unusual and rare complication warranted forced diuresis, to prevent acute kidney injury. This was a departure from the recommended fluid therapy for DF.

Native Valve Streptococcus bovis Endocarditis and Refractory Transfusion Dependent Iron Deficiency Anaemia Associated with Concomitant Carcinoma of the Colon: A Case Report and Review of the Literature.

Streptococcus bovis is found as a commensal organism in human gut and may become opportunistically pathogenic. Infective endocarditis is one of the commonest modes of presentation of this infection. The association between Streptococcus bovis endocarditis and colorectal cancer is well recognized. We report a case of Streptococcus bovis endocarditis along with a refractory iron deficiency anaemia associated with concomitant carcinoma of ascending colon in a 63-year-old male. Cooccurrence of these two conditions may cause a challenge in the management. Considering the strong association of colon cancer with Streptococcus bovis endocarditis, a detailed screening colonoscopy is mandatory following the diagnosis of the latter.

A hypothetical intervention to reduce plasma leakage in dengue haemorrhagic fever.

Plasma leakage from increased vascular permeability, if left unattended, will lead to intravascular volume depletion. The ensuing tissue hypoperfusion and the consequent life-threatening complications may have a fatal outcome in dengue haemorrhagic fever (DHF). Although an accurately calculated volume of fluid infused during the critical phase of plasma leakage can prevent such an eventuality, the practical difficulties in its execution with properly-timed adjustments to the fluid infusion rate and the aggressive monitoring needed during this phase of the illness can limit the expected benefits of an exclusively fluid-based regime. An intervention to reduce plasma leakage in DHF complementing the standard fluid regime conceivably would improve the outcome. It is my hypothesis that fresh frozen plasma (FFP) by Fc receptor blockade and the associated reduction in immune-enhanced viral replication could reduce cytokine-mediated increase in vascular permeability. Additionally, albumin in FFP, by adhering to the glycocalyx, could further compromise fluid fluxes during the critical phase of DHF. However, this hypothesis needs to be tested by a randomized controlled study.

Management dilemmas in the treatment of dengue fever.

This paper is aimed at highlighting some of the dilemmas faced by clinicians in the management of adultpatients with dengue and my views in resolving these issues.Even though early diagnosis and prompt fluid therapy are central to reduce morbidity and mortality indengue, achieving these goals are contentious issues and are often hampered by the limited access to expensive laboratory data in most developing countries which would enable a rapid and accurate diagnosis. My viewpoint on overcoming these dilemmas is to make an early diagnosis on the clinical features, and apply clinical predictors of disease severity in selecting patients for interventions. In thisregard, diffuse blanching erythema in a patient with features of a viral fever during dengue epidemicswould suffice to diagnose and treat the patient as a dengue case. Laboratory confirmatory data areexpensive, not readily available and could delay treatment. Fluid therapy and intervention modalitiesfor thrombocytopaenia should be judged clinically on an individual basis rather than the blind, strictadherence to theoretical fluid regimens with the potential risk of fluid overloading. Capillary refill time,pulse pressure, cervical lymphadenopathy, and changes in the sensorium are useful clinical parameters for selection of patients for intervention as well as subtle adjustments and termination of fluid therapy.A practically feasible step-wise approach to dengue management is described in this paper.