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Introduction: Leptospirosis is an important zoonotic disease commonly found in tropical or sub-tropical countries. The most severe form is Weil's syndrome which presents with jaundice, renal failure, and bleeding diatheses. Although jaundice occurs in 38% of patients with leptospirosis, no studies in Asia have focused on the liver biochemical profile of these patients. Characterization of liver biochemical profile and ultrasonographic findings may shed more light on the disease process. Identification of liver biochemical parameters that portend a poor prognosis may also allow for early aggressive intervention. Objective: To describe the liver biochemical profile and liver ultrasonographic findings in adult patients with laboratory-confirmed leptospirosis, admitted at a tertiary hospital in Manila, Philippines. The association of clinical and laboratory features with clinical outcomes (i.e., severe liver injury, Weil's syndrome, and mortality) was also investigated. Methods: This retrospective cross-sectional study reviewed all available cases of adult patients with laboratory-confirmed leptospirosis admitted in the Philippine General Hospital from January 2009 to August 2018. The clinical features, liver biochemical profiles, and ultrasound findings were recorded and analyzed. Comparison between the means of each group based on clinical outcome (i.e., mortality, Weil's syndrome) was done via Students' t-test for continuous variables, and calculation of the Odds Ratio for categorical variables. Results: Total and direct bilirubin levels were elevated in patients with leptospirosis compared to serum amino-transferases and alkaline phosphatase levels which were only mildly elevated. Abdominal ultrasound showed typically un-enlarged livers with normal parenchymal echogenicity, normal spleens, and non-dilated biliary trees. Dyspnea was associated with an increased odds for mortality. Although jaundice was present in 39.5% of patients and significantly associated with severe liver injury, this was not associated with mortality. Liver biochemical test values did not differ among patients who expired and those who survived to discharge. The presence of myalgia and abdominal pain increased the odds for Weil's syndrome. Conclusion: To date, no local studies have fully described the liver biochemical profile of patients with leptospirosis. Our findings are compatible with previous studies showing that leptospirosis typically presents with predominantly elevated direct bilirubin from cholestasis and systemic infection. Contrary to previous literature, however, our study found no association between jaundice and mortality.
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Background: Severe and critical COVID-19 disease is characterized by hyperinflammation involving pro-inflammatory cytokines, particularly IL-6. Tocilizumab is a monoclonal antibody that blocks IL-6 receptors. Objectives: This study evaluated the efficacy of tocilizumab in Filipino patients with severe to critical COVID-19 disease. Methods: This phase 3 randomized double-blind trial, included patients hospitalized for severe or critical COVID-19 in a 1:1 ratio to receive either tocilizumab plus local standard of care or placebo plus standard of care. Patients were eligible for a repeat IV infusion within 24-48 hours if they deteriorated or did not improve. Treatment success or clinical improvement was defined as at least two categories of improvement from baseline in the WHO 7-point Ordinal Scale of patient status, in an intention-to-treat manner. Results: Forty-nine (49) patients were randomized in the tocilizumab arm and 49 in the placebo arm. There was no significant difference in age, comorbidities, COVID-19 severity, need for mechanical ventilation, presence of acute respiratory distress syndrome, or biomarker levels between groups. Use of adjunctive therapy was similar between groups, with corticosteroid used in 91.8% in tocilizumab group and 81.6% in the placebo group, while remdesivir was used in 98% of participants in both groups.There was no significant difference between groups in terms of treatment success in both the intention-to-treat analysis (relative risk=1.05, 95% CI: 0.85-1.30) and per-protocol analysis (relative risk=0.98, 95% CI: 0.80 to 1.21). There was no significant difference in time to improvement of at least two categories relative to baseline on the 7-point Ordinal Scale of clinical status. Conclusion: The use of tocilizumab on top of standard of care in the management of patients with severe to critical COVID-19 did not result in significant improvement as defined by the WHO 7-point Ordinal Scale of patient status, nor in significant improvement in incidence of mechanical ventilation, incidence of ICU admission, length of ICU stay, and mortality rate.