drei Jahrzehnte monozentrischer Erfahrung

Background: Hepatitis C viral infection had been the leading indication for liver transplantation for many years. Post-transplant survival was decisively influenced by recurrent hepatitis following graft fibrosis, cirrhosis and graft failure. In an era of great achievements in antiviral treatment the course of this disease and pre- und posttransplant path changed completely. In this study three decades of Hepatitis C related liver failure and consecutive liver transplantation is reviewed. Methods: We compared n = 529 patients who underwent liver transplantation due to a Hepatitis C associated liver failure between 1989 and 2017 at the Charité Berlin. The data is analyzed regarding demographics, inflammation, fibrosis, HCV-genotyp, antiviral treatment, retransplantation, HCV-recurrence and survival. Results: Significant improvement in the therapeutic success of the antiviral therapy (p < 0.01) of the interferon-free treatment regimens over previous treatment approaches is demonstrated. In addition, a significantly faster fibrosis progression (p = 0.01) of the natural course of Hepatitis C can be shown in contrast to fibrosis development under a drug therapy. HCV recurrence after liver transplantation declines from 100% to 0% per annum over the three decades (p < 0.01). Furthermore, it can be shown that advanced early fibrosis/inflammation as well as drug therapy, the presence of hepatocellular carcinoma and the HCV genotype 1b have a significant impact on survival. Conclusion: In this study, the development and the different epochs of drug treatment before and after transplantation for HCV-associated liver disease are reviewed. The different phases range from an incurable disease with liver transplantation as the final treatment option with modest results, to the safe and low-risk drug treatment of Hepatitis C with implications for the necessity of liver transplantation and the postoperative course.Die Hepatitis-C-Infektion war über einen langen Zeitraum, aufgrund der fehlenden medikamentösen Behandlungsmöglichkeiten, die führende Indikation zur Lebertransplantation. Der postoperative Verlauf war gekennzeichnet durch eine Rekurrenz der Grunderkrankung mit entsprechender Entwicklung einer fortgeschrittenen Fibrose bzw. Zirrhose bis hin zum Transplantatversagen. In einer Ära der großen medizinischen Entwicklungen hat sich die HCV-Therapie von einer wenig effektiven, mit schweren Nebenwirkungen behafteten zu einer sicheren und nebenwirkungsarmen Behandlungsmethode entwickelt. In dieser Untersuchung werden drei Jahrzehnte der Lebertransplantation aufgrund eines Hepatitis-C-assoziierten-Leberversagens ausgewertet und die entscheidenden Entwicklungsschritte rausgearbeitet. Methodik: Es werden n = 529 Hepatitis-C-positive Patienten nach Lebertransplantation zwischen 1989 und 2017 an der Charité Berlin eingeschlossen und bezüglich demografischer Daten, Inflammation, Fibrose, HCV-Genotyp, antiviraler Therapie, Retransplantation, HCV-Rekurrenz und Überleben untersucht. Ergebnisse: Es wird eine signifikante Verbesserung des Therapieerfolges der antiviralen Therapie (p < 0.01) der interferonfreien Therapieregime gegenüber früherer Behandlungsansätze nachgewiesen. Die Progression der Fibrose verläuft unter Einsatz einer antiviralen Medikation signifikant langsamer. Die HCV-Rekurrenz nach Lebertransplantation entwickelt sich im Laufe der drei Jahrzehnte von 100 % auf 0 % pro Jahr (p < 0.01). Weiterhin kann verdeutlicht werden, dass eine fortgeschrittene, frühe Fibrose/Inflammation, die medikamentöse Therapie, das Vorliegen eines Hepatozellulären Karzinoms sowie der HCV-Genotyp 1b signifikanten Einfluss auf das Überleben haben. Der Allokationsmodus hingegen hat einen nachrangigen Einfluss. Schlussfolgerung: In dieser Untersuchung können die Entwicklung sowie die verschiedenen Epochen der medikamentösen Behandlung der HCV-assoziierten Lebertransplantation aufgearbeitet werden. Die unterschiedlichen Phasen reichen von einer nicht heilbaren Erkrankung mit der Lebertransplantation als Endglied der Behandlungskette mit mäßigen Ergebnissen bis hin zur sicher und nebenwirkungsarm zu behandelnden Infektionserkrankung mit Auswirkung auf die Notwendigkeit der Lebertransplantation und auf den postoperativen Verlauf

Infections in Burn Patients: A Retrospective View over Seven Years

Backgroundand objectives: Burn patients represent a challenging cohort because the injuries entail a vulnerability to colonisation by microorganisms. The ensuing infections can lead to serious complications and, in many cases, to the death of the burn patient. Surgical intervention and wound dressings, as well as antibiotic treatment, are crucial for optimising the treatment of the patient. Materialand Methods: In this retrospective analysis, we analysed the treatment course, antibiotic therapy, and general complications of 252 burn patients with second- or third-degree burns over a time span of 7 years. Results: Patients who developed infections tended to have, on average, a higher total body surface area (TBSA), higher abbreviated burn severity index (ABSI) scores, and longer hospital stays. Patients who were admitted to the burn unit after 2006 had significantly shorter stays in the burn unit. TBSA and ABSI scores were lower in the patient cohort admitted after 2006. Patients exhibiting a TBSA greater than 30% had significantly longer hospital stays and antibiotic treatment periods. TBSA and ABSI scores were significantly higher in patients who died. The results of binary logistic regression indicate that a higher ABSI score increases the odds ratio of developing an infection. Bacteria number had no significant effect on the odds of patient death but positively influenced the odds ratio of developing an infection. TBSA was negatively associated with the risk of developing an infection and was an insignificant predictor of mortality. Conclusions: To gauge the optimal treatment for a burn patient, it is crucial for practitioners to correctly select, dose, and time antibiotics for the patient. Monitoring bacterial colonisation is vital to nip rising infection in the bud and ensure the correct antibiotic selection. This will help prevent the development of multi-resistant bacteria

Wnt Pathway in Bone Repair and Regeneration – What Do We Know So Far

Wnt signaling plays a central regulatory role across a remarkably diverse range of functions during embryonic development, including those involved in the formation of bone and cartilage. Wnt signaling continues to play a critical role in adult osteogenic differentiation of mesenchymal stem cells. Disruptions in this highly-conserved and complex system leads to various pathological conditions, including impaired bone healing, autoimmune diseases and malignant degeneration. For reconstructive surgeons, critically sized skeletal defects represent a major challenge. These are frequently associated with significant morbidity in both the recipient and donor sites. The Wnt pathway is an attractive therapeutic target with the potential to directly modulate stem cells responsible for skeletal tissue regeneration and promote bone growth, suggesting that Wnt factors could be used to promote bone healing after trauma. This review summarizes our current understanding of the essential role of the Wnt pathway in bone regeneration and repair