To ameliorate ischemia-induced graft injury, optimal organ preservation remains a critical hallmark event in solid organ transplantation. Although numerous preservation solutions are in use, they still have functional limitations. Here, we present a concise review of a modified Histidine-Tryptophan-Ketoglutarate (HTK) solution, named HTK-N. Its composition differs from standard HTK solution, carrying larger antioxidative capacity and providing inherent toxicity as well as improved tolerance to cold aiming to attenuate cold storage injury in organ transplantation. The amino acids glycine, alanine and arginine were supplemented, N-acetyl-histidine partially replaced histidine, and aspartate and lactobionate substituted chloride. Several in vitro studies confirmed the superiority of HTK-N in comparison to HTK, being tested in vivo in animal models for liver, kidney, pancreas, small bowel, heart and lung transplantation to adjust ingredients for required conditions, as well as to determine its innocuousness, applicability and potential advantages. HTK-N solution has proven to be advantageous especially in the preservation of liver and heart grafts in vivo and in vitro. Thus, ongoing clinical trials and further studies in large animal models and consequently in humans are inevitable to show its ability minimizing ischemia-induced graft injury in the sequel of organ transplantation.

Background and Purpose: New therapies for inflammatory bowel disease (IBD) are highly desirable. As apolipoprotein (apo)A‐I mimetic peptides are beneficial in several animal models of inflammation, we hypothesized that they might be effective at inhibiting murine colitis.Experimental Approach: Daily injections of 5A peptide, a synthetic bihelical apoA‐I mimetic dissolved in PBS, or PBS alone were administered to C57BL/6 mice fed 3% (w v^‐1) dextran sodium sulfate (DSS) in drinking water or healthy controls.Key Results: Daily treatment with 5A peptide potently restricted DSS‐induced inflammation, as indicated by improved disease activity indices and colon histology, as well as decreased intestinal tissue myeloperoxidase levels and plasma TNFα and IL‐6 concentrations. Additionally, plasma levels of monocyte chemoattractant protein‐1 and the monocyte expression of adhesion‐mediating molecule CD11b were down‐regulated, pro‐inflammatory CD11b⁺/Ly6c^high monocytes were decreased, and the number of intestinal monocytes was reduced in 5A peptide‐treated animals as determined by intravital macrophage‐related peptide‐8/14‐directed fluorescence‐mediated tomography and post‐mortem immunhistochemical F4/80 staining. Intravital fluorescence microscopy of colonic microvasculature demonstrated inhibitory effects of 5A peptide on leukocyte adhesion accompanied by reduced plasma levels of the soluble adhesion molecule sICAM‐1. In vitro 5A peptide reduced monocyte adhesion and transmigration in TNFα‐stimulated monolayers of human intestinal microvascular endothelial cells. Increased susceptibility to DSS‐induced inflammation was noted in apoA‐I^−/− mice.Conclusions and Implications: The 5A peptide is effective at ameliorating murine colitis by preventing intestinal monocyte infiltration and activation. These findings point to apoA‐I mimetics as a potential treatment approach for IBD.

Purpose: Modern oncological treatment algorithms require a central venous device in form of a totally implantable venous access port (TIVAP). While most commonly used techniques are surgical cutdown of the cephalic vein or percutaneous puncture of the subclavian vein, there are a relevant number of patients in which an additional strategy is needed. The aim of the current study is to present a surgical technique for TIVAP implantation via an open Seldinger approach of the internal jugular vein and to characterize risk factors, associated with primary failure as well as short- (< 30 days) and long-term (> 30 days) complications. Methods: A total of 500 patients were included and followed up for 12 months. Demographic and intraoperative data and short- as well as long-term complications were extracted. Primary endpoint was TIVAP removal due to complication. Logistic regression analysis was used to analyze associated risk factors. Results: Surgery was primarily successful in all cases, while success was defined as functional (positive aspiration and infusion test) TIVAP which was implanted via open Seldinger approach of the jugular vein at the intended site. TIVAP removal due to complications during the 1st year occurred in 28 cases (5.6%) while a total of 4 (0.8%) intraoperative complications were noted. Rates for short- and long-term complications were 0.8% and 6.6%, respectively. Conclusion: While the presented technique requires relatively long procedure times, it is a safe and reliable method for TIVAP implantation. Our results might help to further introduce the presented technique as a secondary approach in modern TIVAP surgery.

Background and Purpose: The lymphatic system maintains tissue homeostasis by unidirectional lymph flow, maintained by tonic and phasic contractions within subunits, ‘lymphangions’. Here we have studied the effects of the inflammatory cytokineIL‐1β on tonic contraction of rat mesenteric lymphatic muscle cells (RMLMC).Experimental Approach: We measuredIL‐1β in colon‐conditioned media (CM) from acute (AC‐CM, dextran sodium sulfate) and chronic (CC‐CM, T‐cell transfer) colitis‐induced mice and corresponding controls (Con‐AC/CC‐CM). We examined tonic contractility ofRMLMCin response toCM, the cytokines h‐IL‐1β or h‐TNF‐α (5, 10, 20 ng·mL⁻¹), with or withoutCOXinhibitors [TFAP(10⁻⁵ M), diclofenac (0.2 × 10⁻⁵ M)],PGE₂(10⁻⁵ M)],IL‐1‐receptor antagonist,Anakinra (5 μg·mL⁻¹), or a selective prostanoidEP₄receptor antagonist,GW627368X(10⁻⁶and 10⁻⁷ M).Key Results: Tonic contractility ofRMLMCwas reduced byAC‐ andCC‐CMcompared with corresponding control culture media,Con‐AC/CC‐CM.IL‐1β orTNF‐α was not found in Con‐AC/CC‐CM, but detected inAC‐ andCC‐CM. h‐IL‐1β concentration‐dependently decreasedRMLMCcontractility, whereas h‐TNF‐α showed no effect. Anakinra blocked h‐IL‐1β‐inducedRMLMCrelaxation, and withAC‐CM,restored contractility to RMLMC.IL‐1β increasedCOX‐2 protein andPGE₂production inRMLMC..PGE₂induced relaxations inRMLMC, comparable to h‐IL‐1β. Conversely,COX‐2 andEP₄receptor inhibition reversed relaxation induced byIL‐1β.Conclusions and Implications: TheIL‐1β‐induced decrease inRMLMCtonic contraction wasCOX‐2 dependent, and mediated byPGE₂. In experimental colitis,IL‐1β and tonic lymphatic contractility were causally related, as this cytokine was critical for the relaxation induced byAC‐CMand pharmacological blockade ofIL‐1β restored tonic contraction.

Sleep deprivation is a well-known risk factor for the performance of medical professionals. Solid organ transplantation (especially orthotopic liver transplantation (oLT)) appears to be vulnerable since it combines technically challenging operative procedures with an often unpredictable start time, frequently during the night. Aim of this study was to analyze whether night time oLT has an impact on one-year graft and patient survival. Deceased donor oLTs between 2006 and 2017 were retrospectively analyzed and stratified for recipients with a start time at day (8 a.m. and 6 p.m.) or at night (6 p.m. to 8 a.m.). We examined donor as well as recipient demographics and primary outcome measure was one-year patient and graft survival. 350 oLTs were conducted in the study period, 154 (44%) during daytime and 196 (56%) during nighttime. Donor and recipient variables were comparable. One-year patient survival (daytime 75.3% vs nighttime 76.5%, p = 0.85) as well as graft survival (daytime 69.5% vs nighttime 73.5%, p = 0.46) were similar between the two groups. Frequencies of reoperation (daytime 53.2% vs nighttime 55.1%, p = 0.74) were also not significantly different. Our retrospective single center data derived from a German transplant center within the Eurotransplant region provides evidence that oLT is a safe procedure irrespective of the starting time. Our data demonstrate that compared to daytime surgery nighttime liver transplantation is not associated with a greater risk of surgical complications. In addition, one-year graft and patient survival do not display inferior results in patients undergoing nighttime transplantation.

Background: Graft-versus-host disease following liver transplantation is a serious and usually fatal complication. Data identifying the risk factors and specifying the diagnosis and treatment options of the disease are scarce and contentious. Moreover, recommendations for therapeutic approaches are similarly sparse.Methods: A systematic review of the literature from 1988 to 2020 on graft-versus-host disease following liver transplantation was performed using the PubMed and MEDLINE databases. Medical subject headings, such as graft-versus-host disease and GvHD were used in combination with solid organ transplant, transplantation, or liver transplant. Following duplicate removal, 9298 articles were screened for suitability. A total of 238 full-text articles were analyzed for eligibility, resulting in 130 eligible articles for meta-analysis. Two hundred twenty-five patients developing graft-versus-host disease following liver transplantation reported herein were mainly published in case reports and case series.Results: Graft-versus-host disease occurred with an incidence of 1.2%. 85% developed following deceased donor liver transplant and 15% following living-related donor liver transplantation. The median follow-up period following liver transplantation was 84 days (interquartile range, 45–180). The median time from liver transplantation to graft-versus-host disease onset was 30 days (interquartile range, 21–42). The main clinical features included skin rash (59%), fever (43%), diarrhea (36%), and pancytopenia (30%). The overall mortality rate was 71%. Neither univariate (HR = 0.999; 95% CI, 0.493–2.023;p= 1.0) nor multivariate Cox regression analysis revealed a significant correlation between adaptation of immunosuppression and survival probability (HR = 1.475; 95% CI, 0.659–3.303;p= 0.3).Conclusions: This systematic review suggests that an increase in immunosuppressive regimen does not yield any survival benefit in patients suffering from graft-versus-host disease following liver transplantation.