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Introduction: Therapy of proliferative lupus nephritis (PLN) is yet to be optimized. Standard of care for induction consists of intravenous (IV) cyclophosphamide (CYC) and steroids, which shows an improved outcome, but end-stage renal disease (ESRD) progression, increased mortality, and therapy-related adverse effects remain a major concern. The other treatment reported to induce early remission was the multitarget therapy comprising tacrolimus, mycophenolate, and steroid, but infections were high in the multitarget therapy. Considering azathioprine as a potentially safer and effective alternative anti-B-cell therapy, modified multitarget therapy (MMTT) was planned replacing mycophenolate with azathioprine. Material and Methods: A single-center, 24-week, open-label, randomized controlled trial comprising adults of age 18-65 years with biopsy-proven PLN was carried out. The intervention groups were 1) MMTT: tacrolimus 0.075 mg/kg/day and azathioprine 2 mg/kg/day and 2) IV CYC group with a starting dose of 0.75 (adjusted to 0.5-1.0) g/m² every 4 weeks for 6 months. Both groups received 3 days of pulse methylprednisolone followed by a tapering course of oral prednisone therapy. Results: Among 100 randomized patients, 48 were in MMTT arm and 52 were in IV CYC arm. At the end of 24 weeks, overall remission (complete and partial) was comparable in both the arms: MMTT (86.36%) and IV CYC (87.75%). There was comparable proteinuria reduction and systemic lupus erythematosus disease activity index (SLEDAI) score improvement with recovery of complement level C3 in both groups. Major adverse events were numerically more in the IV CYC group, including one death from pneumonia. Conclusion: The MMTT arm is as effective as IV CYC in improving short-term outcome in PLN, with a comparable safety profile. [ABSTRACT FROM AUTHOR]

Background: Recent studies suggest that hydrocortisone, Vitamin C, and thiamine alone or in combination may improve the clinical outcomes of patients with septic shock. The aim of this study is the effects of this combination therapy on clinical outcome and sepsis biomarkers in patients with septic shock. Materials and Methods: Fifty-eight consecutive patients suffering septic shock were randomly assigned into two groups receiving the combination therapy of hydrocortisone (50 mg/6 h, intravenously), Vitamin C (1.5 g/6 h in 100 ml normal saline or DW5%, intravenously), and thiamine (200 mg/12 h in 50 ml normal saline or DW5%, intravenously) or placebo for up to 4 days. Results: The decline in procalcitonin, lactate, and leukocyte count 72 h after the initiation of treatment was significantly greater in the intervention as compared to the control group. The intervention group has a significantly lower sequential organ failure assessment score 72 h after treatment (P < 0.001). The mean duration of vasopressor dependency was shorter in the intervention group (P = 0.039). In-hospital death occurred in 10.3% of the patients who received combination therapy and 37.9% in the control group (P = 0.014). Conclusion: The administration of the triple combination of hydrocortisone, thiamine, and Vitamin C appeared to be effective in improving the clinical outcomes of patients with septic shock and of reducing vasopressor requirements with a significant increase in the rate of improvement of sepsis biomarkers. [ABSTRACT FROM AUTHOR]