Tocilizumab reduces COVID-19 mortality and pathology in a dose and timing-dependent fashion: a multi-centric study.

Life-threatening COVID-19 is associated with strong inflammation, where an IL-6-driven cytokine storm appears to be a cornerstone for enhanced pathology. Nonetheless, the specific inhibition of such pathway has shown mixed outcomes. This could be due to variations in the dose of tocilizumab used, the stage in which the drug is administered or the severity of disease presentation. Thus, we performed a retrospective multicentric study in 140 patients with moderate to critical COVID-19, 79 of which received tocilizumab in variable standard doses (< 400 mg, 400-800 mg or > 800 mg), either at the viral (1-7 days post-symptom onset), early inflammatory (8-15) or late inflammatory (16 or more) stages, and compared it with standard treated patients. Mortality, reduced respiratory support requirements and pathology markers were measured. Tocilizumab significantly reduced the respiratory support requirements (OR 2.71, CI 1.37-4.85 at 95%) and inflammatory markers (OR 4.82, CI 1.4-15.8) of all patients, but mortality was only reduced (4.1% vs 25.7%, p = 0.03) when the drug was administered at the early inflammatory stage and in doses ranging 400-800 mg in severely-ill patients. Despite the apparent inability of Tocilizumab to prevent the progression of COVID-19 into a critical presentation, severely-ill patients may be benefited by its use in the early inflammatory stage and moderate doses.

Low serum albumin is not a contraindication for early iatrogenic bile duct injury repair.

UNLABELLED: Most iatrogenic bile duct injuries are recognized in the early postoperative period (first 48 hours). These patients usually have additional complications such as a suboptimal hydroelectrolitic status, subhepatic collections, external biliary fistula and malnutrition. In these circumstances, besides the elevation of bilirubin and transaminases associated with the injury, hypoalbuminemia is frequently encountered. The timing for repair is decided according to the condition of each patient. We report the impact of preoperative abnormal low serum albumin levels on the results of biliary tract reconstruction after a iatrogenic biliary lesion. METHOD: Patients who underwent biliary reconstruction in our center from 1998 to 2002 were analyzed. Only patients with complex injuries (Strasberg E, Bismuth III-IV, Stewart-Way III) were included. Major postoperative complications were recorded and correlated with preoperative liver function tests. RESULTS: Seventy seven patients were analyzed. In 41 cases, the injury was a consequence of a laparoscopic operation. All patients were treated by a Roux-en-Y hepatojejunostomy. No operative mortality was recorded. The most frequent postoperative complications were postoperative biliary fistula (8/77-9%, p < 0.017) and subhepatic collections (9/77-9%, p < 0.39). All fistulae closed spontaneously and the subhepatic collections were drained. Overall, complications were more common in the group with hypoalbuminemia (p < 0.002). CONCLUSION: Early repair is indicated if there is no systemic contraindication (sepsis, multiple organic failure, electrolytic imbalance). Abnormalities in the liver function tests, particularly a low serum albumin, should not delay the operation. Although significantly more postoperative complications are observed in an early repair, long-term results are comparable to those of an elective repair.