Technical Note: Novel Use of CytoSorb™ Haemadsorption to Provide Wound Healing Support in Case of Severe Burn Trauma via Reduction of Hyperbilirubinaemia

Hyperbilirubinaemia has been shown to compromise wound healing in severely burned patients. The therapy options for patients with impairment of wound healing and subsequent severe liver dysfunction are limited. A novel extracorporeal treatment, CytoSorb® (CytoSorbents Corp, USA), is a whole blood adsorber composed of highly biocompatible and porous polystyrene divinylbenzene copolymer beads covered in a polyvinylpyrrolidone coating. It is capable of extracting mainly hydrophobic middle-sized (up to 55 kDa) molecules from blood via size exclusion, including cytokines and bilirubin. We performed therapy with CytoSorb® on a severely burned (48% Total Body Surface Area-TBSA) patient with secondary sclerosing cholangitis (SCC) to promote the wound healing process by reducing bilirubin concentrations and to bridge the time to spontaneous liver regeneration or eventually to liver transplantation after two skin transplantations had failed to provide wound closure. In the first 6 days the cartridge was changed on a daily basis and later after every 2–4 days. The therapy with six adsorbers decreased a total bilirubin concentration from 14.02 to 4.29 mg/dl. By maintaining a stable bilirubin concentration under 5 mg/dl, debridement of abdomen and upper extremities with autologous skin grafting and, 4 weeks later, autologous skin grafting of the back from scrotum and lower extremities were performed successfully. After wound healing had been achieved, the CytoSorb therapy was discontinued after 57 days and 27 adsorber changes. CytoSorb therapy can be a promising support of wound and skin graft healing in patients with severe burns and liver dysfunction due to a significant reduction of total bilirubin concentration.

Association of Serum Total Bilirubin Concentration with Telomere Length: The National Health and Nutrition Examination Survey

Introduction. Mildly increased bilirubin concentration has a protective effect on oxidative stress–related diseases. However, it remains unknown whether elevated circulating bilirubin is associated with longer telomere length. The aim of this cross-sectional study was to examine the association between total bilirubin concentration and telomere length. Methods. We used the data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. The multivariable linear regression model was used to examine the association between total bilirubin concentration and telomere length. The nonlinear relationship was analyzed using a generalized additive model with the smoothing plot. Results. A total of 7818 participants with a mean age of 49.20 ± 18.82 years were included. Compared with the lowest concentration of total bilirubin (Q1), the highest quartile of total bilirubin concentration was associated with longer telomere length in male ( β = 0.04 , 95 CI%: 0.00, 0.07, P = 0.024 ) and female ( β = 0.04 , 95 CI%: 0.02, 0.04, P = 0.002 ). Furthermore, an inverted U-shaped relationship between total bilirubin and telomere length was found. On the left of turning points ( total bilirubin < 0.5 mg / dL ), total bilirubin concentration was positively associated with telomere length ( β = 0.23 , 95 CI%: 0.14, 0.32, P < 0.001 ). However, the association between total bilirubin concentration and telomere length was not significant ( β = 0.01 , 95% CI: -0.01, 0.04, P = 0.346 ) above the turning point. Conclusion. This is the first evidence based on a nationally representative survey demonstrating a positive and nonlinear association between total bilirubin concentration and telomere length. Future large-scale prospective studies are warranted to confirm our findings.

Bilirubin monitoring – future prospects

Monitoring of bilirubin concentration is essential during early neonatal life. According to the American Academy of Pediatrics Clinical Practice Guideline, the total serum bilirubin or transcutaneous bilirubin level should be measured in each infant in the first 24 hours of life. The concentration of bilirubin has been measured for 150 years. During that time the analytical methods for its determination have been significantly improved, the nomenclature of bilirubin has been also unified, but it is still unknown what concentration of bilirubin cause a life-threatening encephalopathy in the newborn. Under the current recommendations, clinical decisions to introduce phototherapy in the treatment of newborns’ hyperbilirubinemia are based on total bilirubin concentration, which is determined on biochemical analyzers and point of care testing systems. However, it is not always possible to predict encephalopathy based on the total bilirubin level. Probably in the future, as the availability of routine methods for the determination of unconjugated, free bilirubin becomes more available, measurement of “free” bilirubin will improve risk assessment for bilirubin neurotoxicity.

Serum Concentration of Fluoride in Patients with Alcoholic Liver Cirrhosis from the Lublin Region in Eastern Poland

In view of previous reports, it is important to determine the relationship between liver function and the level of fluoride in the serum. The aim of this study was to investigate serum concentrations of fluoride in 72 patients with alcoholic liver cirrhosis, living in the region of Lublin (Eastern Poland) divided based on the severity of disease according to the Child-Turcotte-Pugh criteria. Higher plasma fluoride concentrations were associated with changes in liver related parameters. In all groups of analyzed patients with different stages of alcoholic liver cirrhosis, elevated levels of plasma fluoride and increased activities of both alanine aminotransferase (ALT) and total bilirubin concentration were shown.

Zinc Oxide Nanoparticles Alleviate Cyclophosphamide Induced Hepatotoxicity in Male Albino Rats

Background: Cyclophosphamide (CP) is a potent anticancer agent. Its clinical use is restricted because of its marked organ toxicity associated with increased oxidative stress and inflammation. Zinc oxide nanoparticles (nZnO) are one of the most abundantly used nanomaterials in consumer products and biomedical applications. Objectives: The aim of the present study was to evaluate the ameliorative effect of Zn-O nano-particles on hepatotoxicity induced by cyclophosphamide in male albino rats. Materials and Methods: Twenty four adult male rats (Sprague Dawley) were grouped randomly into four groups of six rats each. Group I. Control group: Received 0.2 ml saline /day i.p. injection for 14 days (day by day), group II (CP group): Received CP 20 mg/kg/day body weight (b.w.) day by day for 14 days by intraperitoneal injection, Group III (nZnO group): Received nZnO (5 mg/kg)/day b.w., intraperitoneally for 14 days. Group IV (CP + ZnO NPs group): Received nZnO group: Received nZnO (5 mg/kg/day) b.w., intraperitoneally for 14 days, plus CP 20 mg/kg/day body weight (b.w.) day by day for 14 days by intraperitoneal injection. At the end of the experimental period, rats were anesthetized using light ether. Blood and liver samples were taken and prepared for biochemical measurements and histological examination. Results: Serum total proteins, albumin, and globulin levels, were reduced in CP group when compared with the control group. In CP-animals treated with nZnO, these parameters were improved when compared with the CP-treated. A significant elevation in ALT, AST, ALP activities and total bilirubin concentration were observed after CP treatment as compared to vehicle treatment. Co administration of Pretreatment and nZnO with CP were reduced the enzyme activities and total bilirubin concentration significantly, as compared to CP-treated animals. Photomicrograph section of liver of nZnO-treated group showing hepatic lobule and hepatocytes surrounding a central vein and normal sinusoid. Liver of CP treated group reveals lobular infiltrate by chronic inflammatory cells congested hepatic sinusoids containing red blood cells with hepatocytes disarray and cloudy swelling, increased sinusoidal Kupffer cells, and hepatocytes with inculpated or triple nucleated. Photomicrograph of the section of liver of nZnO and CP combination group showed, decrease of the inflammation and infiltration of the portal area. Conclusion: It can be concluded that CP induced hepatotoxicity. Treatment of rats with zinc oxide nano-particles and CP together ameliorated the toxicity induced by CP. These results may provide further visions into proper treatment of patients by improving side effects of chemotherapy. However further studies are necessary to establish optimal doses of nZnO and receive the best safety profile.