Although it is well established that hepatic macrophages play a crucial role in the development of liver fibrosis, the underlying mechanisms remain largely elusive. Moreover, it is not known whether other mononuclear phagocytes such as dendritic cells contribute to hepatic stellate cell (HSC) activation and liver fibrosis. Here we show for the first time that hepatic macrophages enhance myofibroblast survival in an NF-κB-dependent manner, and thereby promote liver fibrosis. Microarray and pathway analysis revealed no induction of HSC activation pathways by hepatic macrophages but a profound activation of the nuclear factor-kappa B (NF-κB) pathway in HSCs. Conversely, depletion of mononuclear phagocytes during fibrogenesis in vivo resulted in suppressed NF-κB activation in HSCs. Macrophage-induced activation of NF-κB in HSC in vitro and in vivo was mediated by IL-1 and TNF. Notably, IL-1 and TNF did not promote HSC activation but promoted survival of activated HSC in vitro and in vivo and thereby increased liver fibrosis, as demonstrated by neutralization in co-culture experiments, and genetic ablation of IL-1 and TNF receptor in vivo. Co-culture and in vivo ablation experiments revealed only a minor contribution to NF-κB activation in HSCs by dendritic cells, and no contribution of dendritic cells to liver fibrosis development, respectively.
Conclusion
Promotion of NF-κB-dependent myofibroblast survival by macrophages but not dendritic cells provides a novel link between inflammation and fibrosis.
Although the overall morbidity did increase with age, it was still less when compared to that of historical groups with traditional care. Therefore, multimodal perioperative rehabilitation should be recommended for the elderly.
Aim: Multimodal perioperative rehabilitation in patients undergoing curative conventional colonic resection for cancer has not yet been studied in a multicenter setting. In 2005, a nationwide quality assurance program was initiated in Germany in an unselected patient population. Methods: The prospective multicenter data collection includes patients from 24 German hospitals. All hospitals had established ‘fast-track’ rehabilitation as the standard perioperative treatment in elective colonic resection, and all patients entered the registry. Results: 748 of 2,047 fast-track patients (36.5%) underwent open resection of colonic cancer. The median age of the 380 female and 368 male patients was 71 (26–96) years. Compliance was high for epidural analgesia (89%), systemic basic nonopioid analgesia (93%), ‘restrictive’ intraoperative intravenous fluids (81%), oral feeding (73%) and enforced mobilization (84%) on the day of surgery. Surgical complications were diagnosed in 20%, general morbidity occurred in only 13% of all patients, and 3 patients (0.4%) died in the early postoperative period. Readmission within 30 days of discharge was necessary in 27 patients (4%). Conclusions: Compliance with fast-track measures was high, and general morbidity was low in a population of patients undergoing multimodal perioperative rehabilitation for conventional colonic cancer resection.
Appendix strangulation caused by an incisional trocar site hernia following laparoscopy is an extremely rare entity. A 63-year-old man was admitted to our department with continuous abdominal pain and irreducible minimal swelling in the right abdomen. His surgical history was significant for rectal cancer one year previously. The patient had undergone a laparoscopic low anterior rectal resection with construction of a protective temporary end ileostomy (pT1, pN0, G2, M0). The ileostomy was reversed 3 months after initial surgery. An incarcerated herniation was diagnosed. Subsequent surgery surprisingly revealed that the right lower trocar point incisional hernia contained a strangulated appendix. Routine appendectomy was performed and the hernias were repaired using a typical sublay technique.
Background/Aim: Chemotherapy can induce serious leukopenia. The aim of our study was to investigate the effects on leukopoiesis when the antineoplastic agent taurolidine (TRD) is administered by a bolus injection or during repetitive treatment (21 cycles) over 7 days in rats. Methods: Rats were intravenously treated with a single injection (A) or by a 7-day treatment (B) with increasing doses of TRD versus control (isotone sodium) in a standardized animal model. Hematological adverse effects on leukopoiesis were analyzed in peripheral blood. Results: (A) Neither the highest TRD concentration (3%) nor 1 or 2% caused a significant difference between the control and TRD groups (p > 0.085) in the perioperative course after bolus administration. (B) The administration of TRD 3% led to a slight change of granulocyte and monocyte counts compared to the control group particularly on postoperative day 7, but this difference was not significant. In both protocols a slight postoperative increase in leukocytes was observed. Conclusion: We report that TRD administered intravenously in an antitumor dose does not affect leukopoiesis in rats. Thus, the agent offers a promising and safe means in cancer treatment. The effects are currently investigated in incurable cancer patients.
The main objective of this case‐cohort‐type observational study conducted at different Surgical Departments of the Charité‐Universitätsmedizin in Berlin was to evaluate the sequential use concept first described by Systagenix Wound Management in 2007. Fifty‐two patients with different wound healing by secondary intention were treated for 7 weeks at the Charité‐Universitätsmedizin in Berlin. A multidisciplinary team worked together to reach consensus in wound assessment; in classification of infection status according to the criteria described by European Wound Management Association (EWMA); in treatment protocol and on dressings to be used to ‘cover’ wounds. Before dressing application, all wounds were cleaned from debris. Following the sequential use concept, wounds classified as stages 2 and 3 were dressed with SILVERCEL® and TIELLE® or TIELLE PLUS® to ‘clean’ the wounds. After 2–3 weeks, treatment was changed to PROMOGRAN PRISMA® and TIELLE® to ‘close and cover’ wounds, thus providing optimal wound healing. Wounds classified as non infected were dressed with PROMOGRAN PRISMA® and TIELLE® during the complete treatment period. Patients were asked to evaluate the treatment using a simplified questionnaire developed at the Charité‐Universitätsmedizin in Berlin. Wounds comprised 37 surgical procedures, 8 chronic mixed ulcer, 4 pressure sores, 1 diabetic foot ulcer, 1 venous leg ulcer, and 1 mixed arterial/venous ulcer. At baseline, 12 wounds were classified as stage 3, 38 wounds as stage 2 and 2 wounds as stage 1. After 7 weeks of treatment, all patients showed a positive clinical response to the sequential use treatment. Results of wound size showed a high significant progression of wound healing expressed with a profound reduction of wound area (P in all measurements <0·001, chi‐square test) and improved granulation. This study summarises the clinical experiences derived from the evaluation of the sequential use concept in the daily clinical practice of wound treatment. On the basis of the wound healing results, patients' evaluation of treatment and the clinicians' and staff experiences, this concept was implemented at different Surgical Departments of the Charité‐Universitätsmedizin in Berlin.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.