IntroductionSnakebite envenoming (SBE) results in over 500 000 deaths or disabling injuries annually. Varespladib methyl, an oral inhibitor of secretory phospholipase A2, is a nearly ubiquitous component of snake venoms. We conducted a phase II clinical trial to assess efficacy and safety of oral varespladib methyl in patients bitten by venomous snakes.MethodsThis double-blind, randomised, placebo-controlled trial enrolled patients in emergency departments in India and the USA. Patients with SBE were randomly assigned (1:1) to receive varespladib methyl or placebo two times per day for 1 week. All patients received standard of care, including antivenom. The primary outcome was change in the composite Snakebite Severity Score (SSS) measuring the severity of envenoming, from baseline to the average composite SSS at 6 and 9 hours.ResultsAmong 95 patients randomised August 2021 through November 2022, the most common snakebites were from Russell’s vipers (n=29), copperheads (n=18) and rattlesnakes (n=14). The SSS improved from baseline to the average at 6 and 9 hours by 1.1 (95% CI, 0.7 to 1.6) in the varespladib group versus 1.5 (95% CI, 1.0 to 2.0) in the placebo group (difference −0.4, 95% CI, −0.8 to 0.1, p=0.13). While key secondary outcomes were not statistically different by treatment group, benefit was seen in the prespecified subgroup initiating study drug within 5 hours of bite (n=37). For this early treatment group, clinically important differences were observed for illness severity over the first week, patient-reported function on days 3 and 7 and complete recovery. No death or treatment emergent serious adverse event occurred.ConclusionFor emergency department treatment of snakebites, the addition of varespladib to antivenom did not find evidence of difference for the primary outcome based on the SSS. A potentially promising signal of benefit was observed in patients initiating treatment within 5 hours of snakebite.

Mixed Cryoglobulinemia (MC) is a rare disorder and often causes diagnostic dilemma. Cryoglobulinemia is of 3 types according to Brouet Classification. Types 2 and 3 are known as MC as type 2 is a mixture of polyclonal IgG and monoclonal IgM associated with viral infection and type 3 consists of polyclonal IgG, associated with systemic lupus erythematosus. Cryoglobulins must be differentiated from cryofibrinogen which precipitates only in plasma and not in serum. Immune complex deposition leads to cryoglobulinemic vasculitis. Females are more commonly affected that males. The case presented here, had recurrent episodes of anemia, painful rashes, pedal swelling with subsequent renal dysfunction which ultimately responded to intravenous steroids and rituximab. Hepatitis C Virus (HCV) infection was ruled out twice during the hospital visits. Skin biopsy and bone marrow biopsy and detection of cryoglobulins clinched the diagnosis. The importance of the case lies in the fact that MC, though a rare disorder, should not be missed in the diagnosis and it should be remembered that HCV negative cryoglobulinemic vasculitis has poor prognosis and may be refractory to treatment.

INTRODUCTION:Renal dysfunction is common in chronic liver disease. The cause of this renal dysfunction is either multi-organ involvement in acute conditions or secondary to advanced liver disease.OBJECTIVES:The study was undertaken to assess the renal function in chronic liver diseases and find out the association of alteration of renal function with gradation of liver disease. (assessed by child-pugh criteria) and to find out the association of alteration of renal function among the cases of chronic liver disease of different aetiology.MATERIALS AND METHODS:This cross-sectional, observational study was undertaken in Department of General Medicine, Calcutta National Medical College & Hospital, Kolkata during March 2012 to July 2013 with 50 admitted patients of chronic liver disease after considering the exclusion criteria. The patients were interviewed with a pre-designed and pre-tested schedule, examined clinically, followed by some laboratory investigations relevant to diagnose the aetiology of chronic liver disease, and to assess the severity of liver and renal dysfunction. Data was analysed by standard statistical method.RESULTS:Eighty six percent of the patients were male and the mean age of study population was 43.58 y, 68% patients suffered from alcoholic liver disease, followed by 14% patients had chronic Hepatitis-B, 10% patients developed acute kidney injury, 20% had hepato renal syndrome and 14% had IgA deposition. The distribution of serum urea and creatinine across the categories of Child Pugh classification tested by Mann-Whitney test and the distribution was statistically significant.CONCLUSION:The present study has found significant association between severity of liver dysfunction and certain parameters of renal dysfunction.

Neurological complications may occur with the Plasmodium falciparum infection. However, the association of neurological manifestations with vivax malaria remains doubtful. Of late, there are isolated case reports/studies which have implicated P. vivax in the pathogenesis of severe malaria which is characterized by the features of different organ dysfunctions, which were previously thought to be caused by P. falciparum alone. Though several case studies have mentioned the association of the P. vivax infection with cerebral malaria, a causal correlation has yet to be established. Dorsal cord myelitis (which leads to paraplegia) during the febrile illness, is rarely described in association with vivax malaria, though there are reports on the Post Malaria Neurological Syndrome (PMNS) and acute disseminated encephalomyelitis following vivax malaria. We are reporting a case of P. Vivax malaria which presented with myelitis, which responded well to the antimalarial treatment.