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

Ultrasound in augmented reality: a mixed-methods evaluation of head-mounted displays in image-guided interventions

Purpose: Augmented reality (AR) and head-mounted displays (HMD) in medical practice are current research topics. A commonly proposed use case of AR-HMDs is to display data in image-guided interventions. Although technical feasibility has been thoroughly shown, effects of AR-HMDs on interventions are not yet well researched, hampering clinical applicability. Therefore, the goal of this study is to better understand the benefits and limitations of this technology in ultrasound-guided interventions. Methods: We used an AR-HMD system (based on the first-generation Microsoft Hololens) which overlays live ultrasound images spatially correctly at the location of the ultrasound transducer. We chose ultrasound-guided needle placements as a representative task for image-guided interventions. To examine the effects of the AR-HMD, we used mixed methods and conducted two studies in a lab setting: (1) In a randomized crossover study, we asked participants to place needles into a training model and evaluated task duration and accuracy with the AR-HMD as compared to the standard procedure without visual overlay and (2) in a qualitative study, we analyzed the user experience with AR-HMD using think-aloud protocols during ultrasound examinations and semi-structured interviews after the task. Results: Participants (n = 20) placed needles more accurately (mean error of 7.4 mm vs. 4.9 mm, p = 0.022) but not significantly faster (mean task duration of 74.4 s vs. 66.4 s, p = 0.211) with the AR-HMD. All participants in the qualitative study (n = 6) reported limitations of and unfamiliarity with the AR-HMD, yet all but one also clearly noted benefits and/or that they would like to test the technology in practice. Conclusion: We present additional, though still preliminary, evidence that AR-HMDs provide benefits in image-guided procedures. Our data also contribute insights into potential causes underlying the benefits, such as improved spatial perception. Still, more comprehensive studies are needed to ascertain benefits for clinical applications and to clarify mechanisms underlying these benefits

Safety of intermittent Pringle maneuver during minimally invasive liver resection in patients with hepatocellular carcinoma with and without cirrhosis

Purpose: The aim of this study was to analyze the impact of minimally invasive intermittent Pringle maneuver (IPM) on postoperative outcomes in patients with hepatocellular carcinoma (HCC) and liver cirrhosis. Methods: In this retrospective cohort study, we evaluated the safety of IPM in patients with HCC who underwent minimally invasive liver resection during five years at our center. Factors influencing the use of IPM were examined in univariate and multivariate regression analysis. Cases with use of IPM (IPM) and those without use of IPM (no IPM) were then compared regarding intraoperative and postoperative outcomes after propensity score matching (PSM) for surgical difficulty. Results: One hundred fifty-one patients underwent liver resection for HCC at our center and met inclusion criteria. Of these, 73 patients (48%) received IPM with a median duration of 18 min (5-78). One hundred patients (66%) had confirmed liver cirrhosis. In multivariate analysis, patients with large tumors (>= 3 cm) and difficult tumor locations (segments VII or VIII) were more likely to undergo IPM (OR 1.176, p = 0.043, and OR 3.243, p = 0.001, respectively). After PSM, there were no differences in intraoperative blood transfusion or postoperative complication rates between the IPM and no IPM groups. Neither did we observe any differences in the subgroup analysis for cirrhotic patients. Postoperative serum liver function tests were not affected by the use of IPM. Conclusions: Based on our findings, we conclude that the use of IPM in minimally invasive liver resection is safe and feasible for patients with HCC, including those with compensated liver cirrhosis

CT fluoroscopy‐guided pancreas transplant biopsies: a retrospective evaluation of predictors of complications and success rates

To identify predictors of biopsy success and complications in CT-guided pancreas transplant (PTX) core biopsy. We retrospectively identified all CT fluoroscopy-guided PTX biopsies performed at our institution (2000-2017) and included 187 biopsies in 99 patients. Potential predictors related to patient characteristics (age, gender, body mass index (BMI), PTX age, PTX volume) and procedure characteristics (biopsy depth, needle size, access path, number of samples, interventionalist's experience) were correlated with biopsy success (sufficient tissue for histologic diagnosis) and the occurrence of complications. Biopsy success (72.2%) was more likely to be obtained in men [+25.3% (10.9, 39.7)] and when the intervention was performed by an experienced interventionalist [+27.2% (8.1, 46.2)]. Complications (5.9%) occurred more frequently in patients with higher PTX age [OR: 1.014 (1.002, 1.026)] and when many (3-4) tissue samples were obtained [+8.7% (-2.3, 19.7)]. Multivariable regression analysis confirmed male gender [OR: 3.741 (1.736, 8.059)] and high experience [OR: 2.923 (1.255, 6.808)] (biopsy success) as well as older PTX age [OR: 1.019 (1.002, 1.035)] and obtaining many samples [OR: 4.880 (1.240, 19.203)] (complications) as independent predictors. Our results suggest that CT-guided PTX biopsy should be performed by an experienced interventionalist to achieve higher success rates, and not more than two tissue samples should be obtained to reduce complications. Caution is in order in patients with older transplants because of higher complication rates

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

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

Biliary microbial patterns in primary sclerosing cholangitis are linked to poorer transplant-free survival

BACKGROUND: Factors that determine individual disease course of patients with primary sclerosing cholangitis (PSC) are poorly understood. Although an association between gut microbes and disease outcome has been suggested, little is known about the role of microbes in the biliary tract. METHODS: We analyzed microbial cultures from bile specimens obtained during routine endoscopic retrograde cholangiopancreatography (ERCP) and intraoperatively before liver transplantation in 114 patients with PSC in our tertiary academic center. The presence of bacterial and fungal species was correlated with clinical characteristics and outcome data. RESULTS: A total of 87 patients (76%) had positive bile culture results. The presence of concomitant inflammatory bowel disease (IBD) was associated with positive bile culture results in multivariate analysis (OR, 4.707; 95% CI, 1.688-13.128; p=0.003). Enterococcus spp. in the bile was associated with a more frequent occurrence of liver transplantation and/or death (OR, 2.778; 95% CI, 1.147-6.728; p=0.021) and recurrent (≥3) cholangitis episodes (OR, 2.839; 95% CI, 1.037-7.768; p=0.037). Biliary candidiasis was linked to a higher frequency of recurrent (≥3) cholangitis episodes (OR, 5.677; 95% CI, 1.940-16.616; p=0.001). Proton pump inhibitor intake conferred a clinical feature associated with biliary candidiasis in multivariate analysis (OR, 3.559; 95% CI, 1.275-9.937; p=0.016). CONCLUSIONS: Our data indicate that in patients with PSC, presence of Enterococcus spp. and Candida spp. in bile is associated with an adverse outcome. Concomitant IBD is linked to presence of microbes in bile, and proton pump inhibitor intake is a feature associated with biliary candidiasis in patients with PSC

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