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Objective: Management of emergency care Background: Liver transplantation is a life-saving intervention for patients with a diagnosis of acute liver failure or endstage liver disease. Despite advances in surgical techniques and immunosuppressive therapies, primary nonfunction remains a concern, often necessitating retransplantation. In these scenarios, the anhepatic state, achieved through total hepatectomy with a temporary portacaval shunt, serves as a bridge to retransplantation. However, the challenge lies in the uncertain survival period and several potential complications associated with this procedure. Case Report: We present a case of a 35-year-old male patient with autoimmune hepatitis who underwent liver transplantation from a deceased donor. Seven days later, he experienced acute liver failure, leading to an urgent listing for retransplantation. To prevent the intense systemic inflammatory response, the patient underwent a total hepatectomy with a temporary portacaval shunt while awaiting another graft and endured a 57-h anhepatic state. On day 17 following retransplantation, he had cerebral death due to a hemorrhagic stroke. Conclusions: This case underscores one of the most prolonged periods of anhepatic state as a bridge to retransplantation, highlighting the complexities associated with this technique. The challenges include sepsis, hypotension, coagulopathy, metabolic acidosis, renal failure, electrolyte disturbances, hypoglycemia, and hypothermia. Vigilant monitoring and careful management are crucial to improve patient outcomes. Further research is needed to optimize the duration of the anhepatic state and minimize complications for liver transplantation recipients. [ABSTRACT FROM AUTHOR]

Congenital absence of the portal vein (CAPV) is a rare venous malformation in which mesenteric venous blood drains directly into systemic circulation. Herein, we report a case of pediatric deceased donor liver transplantation (DDLT) for symptomatic CAPV with whole liver graft from a hepatitis B surface antigen (HBsAg)-positive donor. A 4-year-old boy suffered from CAPV and secondary portal hypertension. He was also diagnosed with DiGeorge syndrome and heart anomalies. After waiting for 4 months, a 5-year-old donor weighing 19 kg with positive HBsAg was allocated to this 4-year-old patient weighing 15 kg. Recipient operation was performed according to the standard procedures of pediatric DDLT. Portal vein reconstruction was performed using interposition of a vascular homograft conduit to the superior mesenteric vein-splenic vein confluence. The patient recovered uneventfully from DDLT. He has been administered with lamivudine to prevent hepatitis B virus infection. This patient has been doing well for 5 years after DDLT without growth retardation. In conclusion, CAPV patients can have various vascular anomalies, thus combined vascular anomalies should be thoroughly assessed before and during liver transplantation operation. The most effective reconstruction techniques should be used to achieve satisfactory results following liver transplantation.

Purpose: Ex vivo hepatectomy is the incorporation of liver transplant techniques in the non-transplant setting, providing opportunity for locally advanced tumors found conventionally unresectable. Because the procedure is rare and reports in the literature are limited, we sought to perform a systematic review and meta-analysis investigating technical variations of ex vivo hepatectomies. Methods: In the literature, there is a split in those performing the procedure between venovenous bypass (VVB) and temporary portacaval shunts (PCS). Of the 253 articles identified on the topic of ex vivo resection, 37 had sufficient data to be included in our review. Results: The majority of these procedures were performed for hepatic alveolar echinococcosis (69%) followed by primary and secondary hepatic malignancies. In 18 series, VVB was used, and in 18, a temporary PCS was performed. Comparing these two groups, intraoperative variables and morbidity were not statistically different, with a cumulative trend in favor of PCS. Ninety-day mortality was significantly lower in the PCS group compared to the VVB group (p=0.03). Conclusion: In order to better elucidate these differences between technical approaches, a registry and consensus statement are needed. [ABSTRACT FROM AUTHOR]

ImportanceBleeding esophageal varices has been studied extensively, but bleeding gastric varices (BGV) has received much less investigation. However, BGV has been reported in ≤ 30% of patients with acute variceal bleeding. In our studies of 1,836 bleeding cirrhotics, 12.7% were bleeding from gastric varices. BGV mortality rate of 45-55% has been reported. The BGV literature has mainly involved retrospective case reports, often with short-term follow-up.ObjectiveWe sought to describe the results of a prospective, randomized, controlled trial (RCT) in unselected, consecutive patients with BGV comparing endoscopic therapy (ET) with portacaval shunt (PCS; n = 518), and later comparing emergency transjugular intrahepatic portosystemic shunt (TIPS) with emergency portacaval shunt (EPCS; n = 70).Design, setting, and participantsInitially, our RCT involved 518 patients with BGV comparing ET with direct PCS regarding control of bleeding, mortality rate, and disability. When entry of patients ended, the RCT was expanded to compare emergency TIPS with EPCS (n = 70). This RCT of BGV was separate from our other RCTs of bleeding esophageal varices.InterventionsInitially, ET was compared with PCS. In the second part of our RCT, emergency TIPS was compared with emergency PCS (EPCS).Main outcome measuresOutcomes were survival, control of bleeding, portal-systemic encephalopathy (PSE), quality of life, and direct costs of care. In the RCT of ET versus PCS, 28 and 30%, respectively, were in Child class C. In the expanded RCT of TIPS versus EPCS, 40 and 41%, respectively, were in Child class C. Permanent control of BGV was achieved in 97-100% of patients treated by emergency or elective PCS, compared with 27-29% by ET. TIPS was even less effective, achieving long-term control of BGV in only 6%. Survival rates after PCS were greater at all time intervals and in all Child classes (P < .001). Repeated episodes of PSE occurred in 50% of TIPS patients, 16-17% treated by ET, and 8-11% treated by PCS. Shunt stenosis or occlusion occurred in 67% of TIPS patients, in contrast with 0-2% of PCS patients.ConclusionThese results support the conclusion that PCS is uniformly effective, whereas ET and TIPS are not very effective.

Purpose: This study evaluated a novel magnetic compression technique (magnamosis) for creating a portacaval shunt in a canine model of portal hypertension, relative to traditional manual suture.Methods: Portal hypertension was induced in 18 dogs by partial ligation of the portal vein (baseline). Six weeks later, extrahepatic portacaval shunt implantation was performed with either magnetic anastomosis rings, or traditional manual suture (n = 9, each). The two groups were compared for operative time, portal vein pressure, and serum biochemical indices. Twenty-four weeks post-implantation, the established anastomoses were evaluated by color Doppler imaging, venography, and gross and microscopic histological examinations.Results: Anastomotic leakage did not occur in either group. The operative time to complete the anastomosis for magnamosis (4.12 ± 1.04 min) was significantly less than that needed for manual suture (24.47 ± 4.89 min, P < 0.01). The portal vein pressure in the magnamosis group was more stable than that in the manual suture group. The blood ammonia level at the end of the 24-week post-implantation observation period was significantly lower in the magnamosis group than in the manual suture group. Gross and microscopic histological examinations revealed that better smoothness and continuity of the vascular intima had been achieved via magnamosis than with manual suture.Conclusion: Magnamosis was superior to manual suture for the creation of a portacaval shunt in this canine model of portal hypertension. [ABSTRACT FROM AUTHOR]

The cerebellum is critical for controlling motor and non-motor functions via cerebellar circuit that is composed of defined cell types, which approximately account for more than half of neurons in mammals. The molecular mechanisms controlling developmental progression and maturation processes of various cerebellar cell types need systematic investigation. Here, we analyzed transcriptome profiles of 21119 single cells of the postnatal mouse cerebellum and identified eight main cell clusters. Functional annotation of differentially expressed genes revealed trajectory hierarchies of granule cells (GCs) at various states and implied roles of mitochondrion and ATPases in the maturation of Purkinje cells (PCs), the sole output cells of the cerebellar cortex. Furthermore, we analyzed gene expression patterns and co-expression networks of 28 ataxia risk genes, and found that most of them are related with biological process of mitochondrion and around half of them are enriched in PCs. Our results also suggested core transcription factors that are correlated with interneuron differentiation and characteristics for the expression of secretory proteins in glia cells, which may participate in neuronal modulation. Thus, this study presents a systematic landscape of cerebellar gene expression in defined cell types and a general gene expression framework for cerebellar development and dysfunction. [ABSTRACT FROM AUTHOR]

Background: The purpose of this article was to clarify the optimal management concerning transjugular intrahepatic portosystemic shunts (TIPSs) and surgical shunting in treating portal hypertension. Methods: All databases, including CBM, CNKI, WFPD, Medline, EMBASE, PubMed and Cochrane up to February 2014, were searched for randomized controlled trials (RCTs) comparing TIPS with surgical shunting. Four RCTs, which were extracted by two independent investigators and were evaluated in postoperative complications, mortality, 2- and 5-year survival, hospital stay, operating time and hospitalization charges. Results: The morbidity in variceal rehemorrhage was significantly higher in TIPS than in surgical shunts (odds ratio [OR] = 7.45, 95% confidence interval[CI]: (3.93-14.15), P < 0.00001), the same outcomes were seen in shunt stenosis (OR = 20.01, 95% CI: (6.67-59.99), P < 0.000001) and in hepatic encephalopathy (OR = 2.50, 95% CI: (1.63-3.84), P < 0.0001). Significantly better 2-year survival (OR = 0.66; 95% CI: (0.44-0.98), P = 0.04) and 5-year survival (OR = 0.44; 95% CI: (0.30-0.66), P < 0.00001) were seen in patients undergoing surgical shunting compared with TIPS. Conclusions: Compared with TIPS, postoperative complications and survival after surgical shunting were superior for patients with portal hypertension. Application of surgical shunting was recommended for patients rather than TIPS.

Ammonia is neurotoxic, and chronic hyperammonemia is thought to be a major contributing factor to hepatic encephalopathy in patients with liver disease. Portacaval shunting of rats is used as an animal model to study the detrimental metabolic effects of elevated ammonia levels on body tissues, particularly brain and testes that are deleteriously targeted by high blood ammonia. In normal adult rats, the initial uptake of label (expressed as relative concentration) in these organs was relatively low following a bolus intravenous injection of [N]ammonia compared with lungs, kidneys, liver, and some other organs. The objective of the present study was to determine the distribution of label following intravenous administration of [N]ammonia among 14 organs in portacaval-shunted rats at 12 weeks after shunt construction. At an early time point (12 s) following administration of [N]ammonia the relative concentration of label was highest in lung with lower, but still appreciable relative concentrations in kidney and heart. Clearance of N from blood and kidney tended to be slower in portacaval-shunted rats versus normal rats during the 2-10 min interval after the injection. At later times post injection, brain and testes tended to have higher-than-normal N levels, whereas many other tissues had similar levels in both groups. Thus, reduced removal of ammonia from circulating blood by the liver diverts more ammonia to extrahepatic tissues, including brain and testes, and alters the nitrogen homeostasis in these tissues. These results emphasize the importance of treatment paradigms designed to reduce blood ammonia levels in patients with liver disease. [ABSTRACT FROM AUTHOR]

Paul and Pammi's combined research career of 60 plus years focused on preventive vaccine against schistosomiasis. Worm migration studies in rats using 75SE-methionine labeled cercariae and analyzed by autoradiography demonstrated that resistance to reinfection (R/R) requires host immune response resulting in worm death. In permissive hosts, anti eggs immunity causes inflammation leading to host death, whereas in non-permissive hosts this is not the case due to reduced egg burdens. Pathology caused by the presence of eggs & inflammatory debris due to immune attack on worms is important for vaccine design! Protective immune responses are perhaps induced when naïve hosts are vaccinated with either schistosome-derived molecules or attenuated cercariae as suggested by the induction of protective anti-parasite antibodies and monoclonal antibodies. Others and we have used such findings of successful immunizations with schistosome-derived molecules and evidence of R/R in primary hosts as the criteria for embarking on a research career to develop anti schistosome vaccine. However, these immunological strategies rarely produce 85-90% R/R as is achievable by portal-caval shunting. Alternatively induction of anti-schistosoma immunity induces portacaval shunting? However, this has not been tested but seems highly unlikely. Pammi identified a tegumental glycoprotein Sm25 as a candidate vaccine antigen. Differential screening with sera from twice-infected rats, protective (F2x) from Fisher vs.non protective (W2x) from Wistar Furth rats was used and corresponding gene (GP22) cloned. Codons 43-182 amplified by PCR and cloned in pET 15b bacterial expression system. Recombinant protein r140, in combination with different adjuvants was tested for its vaccination potential in mice. Despite high titre anti-r140 antibodies with protective isotypes that detected a 25kDa surface antigen, no protection against subsequent cercarial challenge nor any effect on liver eggs yield was observed.

Introduction: Congenital portosystemic shunts constitute a rare disorder in childhood with a wide spectrum of symptoms and signs, one of which may be cyanosis. Case Presentation: We describe for the first time in Iran a 9-year-old boy with a portacaval shunt presenting with cyanosis. He was diagnosed, managed, and treated successfully. The postoperative period was complicated by portal vein thrombosis, which wasgradually resolved with appropriate treatment. Conclusions: Cyanosis is one of the hallmarks of cardiopulmonary disease; however, as was the case in our patient, a secondary cause of pulmonary disease should be considered. The portacaval shunt is a rare but important cause of cyanosis and should be considered in all patients in whom cyanosis is unexplained.

Worm transplantation studies show that physiological and reproductive status of the worm is influenced by the microenvironment of the host and critical for vaccine design. Worm migration studies in rats with 75Se-methionine labeled cercariae demonstrated that resistance to reinfection (R/R) requires a host immune response resulting in worm death. In permissive hosts, inflammation due to anti eggs immunity leads to host death, whereas in non-permissive hosts this is not the case due to reduced egg burdens. Eggs-induced pathology and inflammatory debris resulting from immune attack on worms are important for vaccine design. Protective immune responses are perhaps induced when naïve hosts are vaccinated with either schistosome-derived molecules or attenuated cercariae as suggested by the induction of protective anti-parasite antibodies and monoclonals. However, these immunological strategies rarely produce 85-90% R/R as is achievable by portal-caval shunting. Alternatively, induction of anti-schistosoma immunity may induce portacaval shunting, seems highly unlikely although not yet tested. Differential screening with sera from twice-infected rats, protective (F2x) from Fisher vs. non-protective (W2x) from Wistar-Furth rats, was used to identify candidate vaccine antigens. [ABSTRACT FROM AUTHOR]

Portacaval shunting is a model for hepatic encephalopathy that causes chronic hyperammonemia, disruption of metabolic, signaling, and neurotransmitter systems, and progressive morphological changes. Exposure of cultured cells to ammonia raises intralysosomal pH and inhibits proteolysis, and the present study tested the hypothesis that proteolytic capacity is diminished in portacaval-shunted rats. Proteins were labeled in vivo with tracer doses of diisopropylfluorophosphate (DFP) and clearance of label was assayed. This approach labeled proteins independent of protein synthesis, which is reported to be altered in shunted rats, and avoided complications arising from re-utilization of labeled amino acids that causes underestimation of degradation rate. Characterization of DFP labeling showed that protein labeling was fast, about 50 % of the label was released during a 24 h interval, labeling by DFP metabolites was negligible, inhibition of brain acetylcholinesterase was not detectable, and labeling by [H]- and [C]DFP was equivalent. To assay degradative capacity, proteins were first labeled with [H]DFP, followed by labeling with [C]DFP that was given 24 or 72 h later. The H/C ratio in each animal was used as a relative measure of removal of H-labeled proteins. H/C ratios were generally significantly higher in portacaval-shunted rats than in controls, consistent with reduced proteolytic capacity. Assays of amino acid incorporation into brain protein generally replicated literature reports, supporting the conclusion that protein synthesis unlikely to be markedly inhibited and amino acid recycling influences calculated protein synthesis rates in shunted rats. Therapeutic strategies to reduce ammonia level would help normalize lysosomal functions and protein and lipid turnover. [ABSTRACT FROM AUTHOR]

Background & Aims The pathogenesis of hepatic encephalopathy ( HE) is multifactorial and often associated with the development of brain oedema. In addition to ammonia playing a central role, systemic oxidative stress is believed to aggravate the neuropsychological effects of ammonia in patients with chronic liver disease ( CLD). The aim of this study was to (i) induce systemic oxidative stress in hyperammonaemic portacaval anastomosed ( PCA) rats by inhibiting the antioxidant glutathione using Dimethyl maleate ( DEM) and (ii) investigate whether a synergistic relationship between ammonia and oxidative stress contributes to the pathogenesis of brain oedema in CLD. Methods Four-week PCA and sham-operated rats received DEM (0.4-4 mg/kg/day) for the last 10 days before sacrifice when oxidative stress markers [reactive oxygen species ( ROS) and malondialdehyde ( MDA)] were assessed in blood and frontal cortex. Brain water content was measured using a specific gravimetric technique. Results Dimethyl maleate induced an increase in ROS and MDA in the blood, but not in the brain, of the PCA rats, compared with non-treated PCA rats. This was accompanied with an increase in brain water content ( PCA+ DEM: 78.45 ± 0.13% vs. PCA: 77.38 ± 0.11%, P < 0.001). Higher doses of DEM induced systemic oxidative stress in sham-operated controls, but brain oedema did not develop. Conclusions Dimethyl maleate provoked systemic, not central, oxidative stress in PCA rats, resulting in the development of brain oedema. Independently, hyperammonaemia and systemic oxidative stress do not precipitate brain oedema; therefore, our findings sustain that a synergistic effect between hyperammonaemia and systemic oxidative stress is responsible for the development of brain oedema in HE. [ABSTRACT FROM AUTHOR]