GSH Attenuates Organ Injury and Improves Function after Transplantation of Fatty Livers

Ischemia-reperfusion injury (IRI) is increased after transplantation of steatotic livers. Since those livers are increasingly used for transplantation, protective strategies must be developed. Reactive oxygen species (ROS) play a key role in hepatic IRI. In lean organs, glutathione (GSH) is an efficient scavenger of ROS, diminishing IRI. The aim of this study was to evaluate whether GSH also protects steatotic allografts from IRI following transplantation. Fatty or lean livers were explanted from 10-week-old obese or lean Zucker rats and preserved (obese 4 h, lean 24 h) in hypothermic University of Wisconsin solution. Arterialized liver transplantation was then performed in lean syngeneic Zucker rats. Recipients of fatty livers were treated with GSH (200 mu mol/h/kg) or saline during reperfusion (2 h, n = 5). Parameters of hepatocellular damage and bile flow were measured. Transplantation of steatotic livers enhanced early reperfusion injury compared to lean organs as measured by increased aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase plasma levels. Bile flow was also reduced in steatotic grafts. Intravenous administration of GSH effectively decreased liver damage in fatty allografts and resulted in improved bile flow. Intravenous application of GSH effectively reduces early IRI in steatotic allografts and improves recovery of these marginal donor organs following transplantation. Copyright (C) 2010 S. Karger AG, Base

Ex vivo machine perfusion: current applications and future directions in liver transplantation

Background: Liver transplantation is the only curative treatment option for end-stage liver disease; however, its use remains limited due to a shortage of suitable organs. In recent years, ex vivo liver machine perfusion has been introduced to liver transplantation, as a means to expand the donor organ pool. Purpose: To present a systematic review of prospective clinical studies on ex vivo liver machine perfusion, in order to assess current applications and highlight future directions. Methods: A systematic literature search of both PubMed and ISI web of science databases as well as the ClinicalTrials.gov registry was performed. Results: Twenty-one articles on prospective clinical trials on ex vivo liver machine perfusion were identified. Out of these, eight reported on hypothermic, eleven on normothermic, and two on sequential perfusion. These trials have demonstrated the safety and feasibility of ex vivo liver machine perfusion in both standard and expanded criteria donors. Currently, there are twelve studies enrolled in the clinicaltrials.gov registry, and these focus on use of ex vivo perfusion in extended criteria donors and declined organs. Conclusion: Ex vivo liver machine perfusion seems to be a suitable strategy to expand the donor pool for liver transplantation and holds promise as a platform for reconditioning diseased organs

Caspofungin for post solid organ transplant invasive fungal disease: results of a retrospective observational study

M. Winkler, J. Pratschke, U. Schulz, S. Zheng, M. Zhang, W. Li, M. Lu, D. Sgarabotto, G. Sganga, P. Kaskel, S. Chandwani, L. Ma, J. Petrovic, M. Shivaprakash. Caspofungin for post solid organ transplant invasive fungal disease: results of a retrospective observational study. Transpl Infect Dis 2010: 12: 230–237. All rights reserve

Postattenuation neurologic signs after surgical attenuation of congenital portosystemic shunts in dogs:A review

The development of postattenuation neurologic signs (PANS) is a poorly understood and potentially devastating complication after surgical attenuation of congenital portosystemic shunts in dogs. Postattenuation neurologic signs include seizures but also more subtle neurologic signs such as depression, behavioral changes, tremors, and twitching. They most commonly occur within 7 days postoperatively and are typically unrelated to hyperammonemia, hypoglycemia, or electrolyte disturbances. This narrative review summarizes the findings of 50 publications from 1988-2020 that report occurrence of PANS. While most published reports included only dogs affected by postattenuation seizures (PAS), others included dogs with any form of PANS. Overall, PANS (including PAS) affected 1.6%-27.3% of dogs, whereas incidence of PAS ranged from 0%-18.2%. The etiology of PANS remains unknown; however, several theories have been proposed. Risk factors include preoperative hepatic encephalopathy, increasing age, and possibly certain breeds and extrahepatic shunt morphology. There is increasing evidence that prophylactic antiepileptic drugs do not prevent PANS. Treatment is centered around controlling neurologic signs with antiepileptic drugs and providing supportive intensive care. The 30-day survival rate in studies that included a minimum of four dogs affected by PANS was 0%-100% (median, 50.0%) and 0%-75.0% (median, 37.5%) for those with PAS. Mortality associated with PANS was typically related to occurrence of generalized seizure activity. Prognostic factors positively associated with short-term survival included having a history of preoperative seizures and development of focal seizures only. If affected dogs survived to discharge, survival for several years was possible, and the majority of neurologic signs manifested as part of the phenomenon of PANS appeared to resolve

Tissue engineering for the diaphragm and its various therapeutic possibilities - a systematic review

Diaphragmatic impairments exhibit high morbidity as well as mortality while current treatment options remain unsatisfactory. Tissue engineering (TE) approaches have explored the generation of an optimal biocompatible scaffold for diaphragmatic repair through tissue decellularization or de novo construction, with or without the addition of cells. We conducted a systematic review on the current state of the art in diaphragmatic tissue engineering (DTE) and found 24 articles eligible for final synthesis. The included approaches studied decellularization-based graft generation (9) and de novo bioscaffold construction (9). Three studies focused on in vitro host-scaffold interaction with synthesized, recellularized grafts (2) and decellularized extracellular matrix scaffolds (1). Another three studies investigated evaluation tools for decellularization efficacy. Among all studies, recellularization was performed in both decellularization-based (4) and de novo generated scaffolds (4). De novo constructed biocomposites as well as decellularized and recellularized scaffolds induced pro-regenerative remodeling and recovery of diaphragmatic function in all examined animal models. Potential therapeutic applications comprise substance defects requiring patch repair, such as congenital diaphragmatic hernia, and functional diseases demanding an entire organ transplant, like muscular dystrophies or dysfunction after prolonged artificial respiration

Engineering an endocrine Neo-Pancreas by repopulation of a decellularized rat pancreas with islets of Langerhans

Decellularization of pancreata and repopulation of these non-immunogenic matrices with islets and endothelial cells could provide transplantable, endocrine Neo- Pancreata. In this study, rat pancreata were perfusion decellularized and repopulated with intact islets, comparing three perfusion routes (Artery, Portal Vein, Pancreatic Duct). Decellularization effectively removed all cellular components but conserved the pancreas specific extracellular matrix. Digital subtraction angiography of the matrices showed a conserved integrity of the decellularized vascular system but a contrast emersion into the parenchyma via the decellularized pancreatic duct. Islets infused via the pancreatic duct leaked from the ductular system into the peri- ductular decellularized space despite their magnitude. TUNEL staining and Glucose stimulated insulin secretion revealed that islets were viable and functional after the process. We present the first available protocol for perfusion decellularization of rat pancreata via three different perfusion routes. Furthermore, we provide first proof-of-concept for the repopulation of the decellularized rat pancreata with functional islets of Langerhans. The presented technique can serve as a bioengineering platform to generate implantable and functional endocrine Neo-Pancreata

The effect of prophylactic treatment with levetiracetam on the incidence of post-attenuation seizures in dogs undergoing surgical management of single congenital extrahepatic portosystemic shunts

Objectives: To report (1) the incidence of post-attenuation seizures (PAS) in dogs that underwent single congenital extrahepatic portosystemic shunt (cEHPSS) attenuation and (2) to compare incidence of PAS in dogs that either did or did not receive prophylactic treatment with levetiracetam (LEV).Study Design: Multi-institutional retrospective study.Sample Population: Nine-hundred-and-forty dogs.Methods: Medical records were reviewed to identify dogs that underwent surgical attenuation of a single cEHPSS from January 2005 through July 2017 and developed PAS within seven days postoperatively. Dogs were divided into three groups: no LEV (LEV-); LEV at >15mg/kg TID for >24 hours or a 60mg/kg intravenous loading dose preoperatively, followed by >15mg/kg TID postoperatively (LEV1); ); and LEV at less than 15mg/kg TID, for less than 24 hours preoperatively, or continued at less than 15mg/kg TID postoperatively (LEV2).Results: Nine-hundred-and-forty dogs were included. Seventy-five (8.0%) developed PAS. Incidence of PAS was 35/523 (6.7%), 21/188 (11.2%) and 19/228 (8.3%) in groups LEV-, LEV1 and LEV2, respectively. This difference was not statistically significant (p=0.14). No significant differences between groups of dogs that seized with respect to variables investigated were identified.Conclusions: The overall incidence of PAS was low (8%). Prophylactic treatment with LEV according to the protocols investigated in our study was not associated with a reduced incidence of PAS.Clinical Significance: Prophylactic treatment with LEV does not afford protection against development of PAS. Surgically treated dogs should continue to be monitored closely during the first seven days postoperatively for seizures

Improved survival in liver transplant recipients receiving prolonged-release tacrolimus in the European liver transplant registry

This study was a retrospective analysis of the European Liver Transplant Registry (ELTR) performed to compare long-term outcomes with prolonged-release tacrolimus versus tacrolimus BD in liver transplantation (January 2008-December 2012). Clinical efficacy measures included univariate and multivariate analyses of risk factors influencing graft and patient survival at 3 years posttransplant. Efficacy measures were repeated using propensity score-matching for baseline demographics. Patients with <1 month of follow-up were excluded from the analyses. In total, 4367 patients (prolonged-release tacrolimus: n = 528; BD: n = 3839) from 21 European centers were included. Tacrolimus BD treatment was significantly associated with inferior graft (risk ratio: 1.81; p = 0.001) and patient survival (risk ratio: 1.72; p = 0.004) in multivariate analyses. Similar analyses performed on the propensity score-matched patients confirmed the significant survival advantages observed in the prolonged-release tacrolimus- versus tacrolimus BD-treated group. This large retrospective analysis from the ELTR identified significant improvements in long-term graft and patient survival in patients treated with prolonged-release tacrolimus versus tacrolimus BD in primary liver transplant recipients over 3 years of treatment. However, as with any retrospective registry evaluation, there are a number of limitations that should be considered when interpreting these data

Flat feline faces: is brachycephaly associated with respiratory abnormalities in the domestic cat (Felis catus)?

There has been little research into brachycephalism and associated disorders in cats. A questionnaire aimed at cat owners was used to determine the relationship between feline facial conformation and owner-reported cat management requirements and respiratory abnormalities. Owner-submitted photographs of cats were used to develop novel measures of skull conformation. One thousand valid questionnaires were received. Within these there were 373 valid photographs that allowed measurement of muzzle ratio (M%) and 494 that allowed nose position ratio (NP%). The data included 239 cats for which both measurements were available. Owners reported lifestyle factors (e.g. feeding type, grooming routine, activity level), physical characteristics (e.g. hair length) and other health characteristics of their cat (e.g. tear staining, body condition score). A composite respiratory score (RS) was calculated for each cat using their owner’s assessment of respiratory noise whilst their cat was asleep and then breathing difficulty following activity. Multivariate analyses were carried out using linear models to explore the relationship between RS and facial conformation, and lifestyle risk factors. The results showed that reductions in NP% and M% were significantly associated with RS (P < 0.001 and P = 0.026, respectively) and that the relationship was significantly negatively correlated (r = -0.56, P < 0.001 for both). Respiratory score was also significantly associated with increased presence of tear staining (P < 0.001) and a sedentary lifestyle (P = 0.01). This study improves current knowledge concerning cats with breeding-related alterations in skull confirmation and indicates that brachycephalism may have negative respiratory implications for cat health and welfare, as has been previously shown in dogs

Moon phases and moon signs do not influence morbidity, mortality and long-term survival, after living donor kidney transplantation

Background: Approximately 11% of the German population are convinced that certain moon phases and moon signs may impact their health and the onset and clinical course of diseases. Before elective surgery, a considerable number of patients look to optimize the timing of the procedure based on the lunar cycle. Especially patients awaiting living donor kidney transplantation (LDKT) commonly look for an adjustment of the date of transplantation according to the moon calendar. This study therefore investigated the perioperative and long-term outcome of LDKT dependent on moon phases and zodiac signs. Methods: Patient data were prospectively collected in a continuously updated kidney transplant database. Two hundred and seventy-eight consecutive patients who underwent LDKT between 1994 and December 2009 were selected for the study and retrospectively assigned to the four moon phases (new-moon, waxing-moon, full-moon, and waning-moon) and the corresponding zodiac sign (moon sign Libra), based on the date of transplantation. Preexisting comorbidities, perioperative mortality, surgical outcome, and long-term survival data were analyzed. Results: Of all LDKT procedures, 11.9, 39.9, 11.5, and 36.5% were performed during the new, waxing, full, and waning moon, respectively, and 6.2% during the moon sign Libra, which is believed to interfere with renal surgery. Survival rates at 1, 5, and 10 years after transplantation were 98.9, 92, and 88.7% (patient survival) and 97.4, 91.6, and 80.6% (graft survival) without any differences between all groups of lunar phases and moon signs. Overall perioperative complications and early graft loss occurred in 21.2 and 1.4%, without statistical difference (p > 0.05) between groups. Conclusion: Moon phases and the moon sign Libra had no impact on early and long-term outcome measures following LDKT in our study. Thus, concerns of patients awaiting LDKT regarding the ideal time of surgery can be allayed, and surgery may be scheduled independently of the lunar phases