What are the main factors affecting the outcome of tocilizumab therapy in COVID-19-induced cytokine release syndrome?

OBJECTIVE: Recommendations for the treatment of cytokine release syndrome/macrophage activation syndrome (MAS) associated with coronavirus disease-2019 (COVID-19) are still of poor quality. IL-6 is an important therapeutic target as a main mediator of cytokine storm. The aim of our study was to evaluate the tocilizumab (TCZ) efficacy and factors affecting the therapy outcome. METHODS: This retrospective study included 27 patients treated with TCZ for COVID-19-MAS. All patients in this study were treated with TCZ (intravenously, at a dose of 8 mg kg1 ) in addition to standard therapy. Clinical improvement (survival and decreased oxygen demand) on the 10-14th days and secondary infection rate were assessed. RESULTS: In our 27 treated patients, 14 (51.8%) received TCZ in the intensive care unit (ICU) and seven (25.9%) were need to invasive mechanical ventilation (IMV). Fifteen (55.6%) of these patients revealed a good clinical response (four patients discharge from the ICU and 11 patients who followed-up in nonICU beds showed a decrease in oxygen demand). TCZ was significantly less effective in patients having high Murray lung injury score, low PO2/FiO2 ratio, IMV, and ICU admission (P < .05). Severity of hypoxemia was found as a single independent risk factor in the multivariable analysis (P < .05). Secondary bacterial infections rate was significantly higher in intubated patients (P < .01) or treated in the ICU (P » .01). CONCLUSION: TCZ was showed limited efficacy for COVID-19-related MAS. The most important predictive indicator for therapy outcome was found as the severity of hypoxemia. In addition, IMV and/or ICU was associated with the poor outcome and high side effect. So, controlled trials are still needed to confirm the indications and timing of TCZ therapy.

Acute Kidney Injury After Pediatric Liver Transplantation.

BACKGROUND: The aim of the present study is to assess acute kidney injury (AKI) incidence according to the pRIFLE and AKIN criteria and to evaluate the risk factors for early developing AKI in postoperative intensive care unit after pediatric liver transplantation (LT). MATERIALS: After exclusion of retransplantations, 7 cadaveric and 44 living donors, totaling 51 pediatric LT patients that were performed between 2005 and 2017, were reviewed retrospectively. AKI was defined according to both pediatric RIFLE (Risk for renal dysfunction, Injury to the kidney, Failure of kidney function, Loss of kidney function, and End-stage renal disease) and Acute Kidney Injury Network (AKIN) criteria. Documented data were compared between AKI and non-AKI patients. RESULTS: AKI incidences were 17.6% by AKIN and 37.8% by pRIFLE criteria. AKIN-defined AKI group had statistically lower serum albumin level, higher serum sodium level, higher furosemide dose, and higher rate of red blood cell (RBC) transfusion than the non-AKI group (P = .02, P = .02, P = .01 and P = .04, respectively). AKI patients had significantly prolonged mechanical ventilation (P = .01) and hospital LOS (P = .02). The pRIFLE-defined AKI group had significantly lower serum albumin level, higher blood urea nitrogen (BUN) level, and higher ascites drained and also showed higher requirement for RBC and 20% human albumin transfusions than the non-AKI group (P = .02, P = .04, P: =.007, P = .02 and P = .05, respectively). CONCLUSION: We evaluated that hypoalbuminemia, high requirement for RBC and 20% human albumin transfusions, high serum sodium, high furosemide use, and high flow of ascites are risk factors for AKI and high BUN levels can be predictive for AKI in pediatric LT patients. The effect of AKI on outcome variables were prolonged mechanical ventilation and hospital LOS.

Impact of Cytokine Adsorption Treatment in Liver Failure.

Sepsis causes life-threatening organ dysfunction and is the leading cause of morbidity and mortality in critically ill patients worldwide. Mortality rate of sepsis is close to 30% to 50% despite better understanding of the pathophysiology of sepsis, and advances in antimicrobial therapy, resuscitation strategies, and mechanical ventilation. Liver failure is characterized by accumulation of potentially toxic substances in the systemic circulation of the patient. Toxic effects of these molecules can induce cellular injuries leading to multiorgan dysfunction. Hydrophobic unconjugated bilirubin and bile acids, hydrophilic conjugated bilirubin, and ammonium are the main toxins accumulated in liver failure. We carried out cytokine adsorbtion (CytoSorb) procedure with continuous venovenous hemodialysis in 12-hour sessions. The biochemical values of the patients before and after the use of the filter were recorded. The parameters compared were as follows: total bilirubin, direct bilirubin, C-reactive protein, leukocyte, neutrophil, alanine aminotransferase, aspartate aminotransferase, creatinine, colloid oncotic pressure, ammonia, gamma-glutamyl transferase, alkaline phosphatase, procalcitonin, hematocrit, hemoglobin, pH, albumin, international normalized ratio, fibrinogen, lactate dehydrogenase, platelet, temperature, changes in vasoactive medication requirement, temperature. According to these results, cytokine adsorption systems can be considered as an option to lower bilirubin levels in cases of liver failure. Its inability to lower ammonia level is considered a disadvantage compared with other bilirubin-lowering methods. Although further studies are needed to compare different methods, cytokine adsorption systems may be considered in treatment planning as it contributes to the treatment of sepsis and hyperbilirubinemia in liver failure patients with sepsis.

Scoring Systems and Postoperative Outcomes in Pediatric Liver Transplantation.

PURPOSE: The aim of this study is to investigate the effects of risk scores (Pediatric End-stage Liver Disease [PELD], Child-Turcotte-Pugh [CTP], and Pediatric Risk of Mortality [PRISM-III]) of pediatric liver transplant patients on the postoperative period. METHOD: Seven cadaveric and 45 living donors, totaling 52 pediatric liver transplantation (LT) patients, were reviewed retrospectively. PELD and CTP scores were calculated based on data at hospital admission. PRISM-III score was calculated from data during the first 24 hours of intensive care unit (ICU) admission. Hospital length of stay (LOS), ICU LOS, patients who developed acute kidney injury (AKI), requirement for inotropic-vasopressor therapy, hospital mortality, long-term mortality, duration of mechanical ventilation, metabolic disease, and demographic features were documented.For CTP score, class C was defined as high, and A and B as low. Cutoff values of PELD and PRISM-III scores were detected by using receiver operating characteristic curves. According to these cutoff values, patients were divided into 2 groups as high and low for each score. Documented data was analyzed and compared in groups for each score. RESULTS: Hospital LOS was significantly longer in the high-PELD (P = .01) and high-CTP (P = .01) groups. ICU LOS was significantly longer in the high-PRISM-III group (P = .01). Requirement for inotropic-vasopressor therapy was significantly higher in the high-PELD (P = .04) and high-CTP (P = .04) groups. CONCLUSION: Hemodynamic instability and long hospital LOS can be expected in pediatric post-LT patients with high PELD or CTP scores; there is also the risk that AKI maybe higher for high-PELD score patients. Unexpectedly, the PRISM-III score did not have any correlation with the severity of physiological condition and mortality.

Liver transplantation for homozygote familial hypercholesterolemia: the only curative treatment.

FH is an autosomal dominant genetic disorder characterized by increased TC and LDL level, which leads to xanthomas, atherosclerosis, and cardiac complications even in childhood. The treatment options are diet, medical treatment, lipid apheresis, and LT. The aim of our study was to analyze our data of patients with FH. Between 2004 and 2015, there were 51 patients who underwent pediatric LT at our center. All patients with FH were identified, and the data were retrospectively analyzed. There were eight patients with homozygous FH in the median age of 10 years (IQR 6-12) who underwent LT. The median pre-operative TC and LDL levels were 611 mg/dL (IQR: 460-844) and 574 mg/dL (IQR: 398-728) and decreased to normal levels 1 week after LT (TC: 193 mg/dL and LDL: 141 mg/dL). Two patients died two and 18 months after LT due to sudden cardiac arrest. Both patients were diagnosed with cardiovascular disease pre-operatively. The LT is the only curative treatment for this disease. To achieve an excellent outcome, it should be performed before the development of cardiovascular disease, because the regression of severe cardiovascular disease after transplantation is limited.