Drug Discovery in Liver Disease Using Kinome Profiling.

The liver is one of the most important organs, playing critical roles in maintaining biochemical homeostasis. Accordingly, disease of the liver is often debilitating and responsible for untold human misery. As biochemical nexus, with kinases being master regulators of cellular biochemistry, targeting kinase enzymes is an obvious avenue for treating liver disease. Development of such therapy, however, is hampered by the technical difficulty of obtaining comprehensive insight into hepatic kinase activity, a problem further compounded by the often unique aspects of hepatic kinase activities, which makes extrapolations from other systems difficult. This consideration prompted us to review the current state of the art with respect to kinome profiling approaches towards the hepatic kinome. We observe that currently four different approaches are available, all showing significant promise. Hence we postulate that insight into the hepatic kinome will quickly increase, leading to rational kinase-targeted therapy for different liver diseases.

Case Report: Comparison of Plasma Metagenomics to Bacterial PCR in a Case of Prosthetic Valve Endocarditis.

Molecular assays for infectious diseases have emerged as important clinical decision-making tools. Unbiased, metagenomic next-generation sequencing is a novel approach holding promise to detect pathogens missed by conventional modalities and to deconvolute admixed nucleic acid sequences from polymicrobial infections in order to identify constituent pathogens. Recent studies have raised concerns about the clinical impact of metagenomics assays and whether their expense is justified. Here, we report a case of polyclonal Streptococcus cristatus endocarditis in a 14-year-old woman with a history of Tetralogy of Fallot. Three sets of admission blood cultures and a commercial plasma metagenomics assay were negative for pathogens, despite persistent vegetations observed on the valve during a later procedure. Multiple strains of Streptococcus cristatus were identified from the explanted valve by amplicon-based 16S rRNA sequencing, confirming the patient had received appropriate antibiotic therapy. This case highlights limitations in the use and interpretation of clinical metagenomics for infectious disease diagnosis and indicates that the clinical yield of these tools may depend upon infection type and anatomic location.

Replacement of Vena Cava up to the Right Atrium during Living Donor Liver Transplantation for Echinococcus alveolaris.

Management of advanced stage of Echinococcus alveolaris is a very difficult procedure. Surgical treatment like resection and liver transplantation is accepted procedure nowadays. Here we presented a case report of Echinococcus alveolaris which invaded the inferior vena cava up to the right atrium and surrounding tissues. This patient underwent living donor liver transplantation with replacement of inferior vena cava up to the right atrium with cryopreserved cadaveric aortic graft. This procedure is very difficult but it is a life-saving chance for patients in advanced cases of Echinococcus alveolaris.

Intrarectal negative pressure system in the management of open abdomen with colorectal fistula: A case report.

INTRODUCTION: To present the management of open abdomen with colorectal fistula by application of intrarectal negative pressure system (NPS) in addition to abdominal NPS. PRESENTATION OF CASE: Twenty-year old man had a history of injuries by a close-range gunshot to the abdomen eight days ago and he had been treated by bowel repairs, resections, jejunal anastomosis and Hartman's procedure. He was referred to our center after deterioration, evisceration with open abdomen and enteric fistula in septic shock. There were edematous, fibrinous bowels and large multiple fistulas from the edematous rectal stump. APACHE II, Mannheim Peritoneal Index and Björck scores were 18, 33 and 3, respectively (expected mortality 100%). After intensive care for 5 days, he was treated by abdominal and intrarectal NPS. NPS repeated for 5 times and the fistula was recovered on day 18 completely. Fascial closure was facilitated with a dynamic abdominal closure system (ABRA) and he was discharged on day 33 uneventfully. There was no herniation and any other problem after 12 months follow-up. DISCUSSION: Management of fistula in OA can be extremely challenging. Floating stoma, fistula VAC, nipple VAC, ring and silo VAC, fistula intubation systems are used for isolation of the enteric effluent from OA. Several biologic dressings such as acellular dermal matrix, pedicled flaps have been used to seal the fistula opening with various success. Resection of the involved enteric loop and a new anastomosis of the intestine is very hard and rarely possible. In all of these reports, usually patients are left to heal with a giant hernia. In contrast to this, there is no hernia in our case during one year follow up period. CONCLUSION: Combination of intra and extra luminal negative pressure systems and ABRA is a safe and successful method to manage open abdomen with colorectal fistula.

Living donor liver transplantation with replacement of vena cava for Echinococcus alveolaris: A case report.

INTRODUCTION: There is no medical treatment for alveolar echinococceal disease (AED) of liver till now. Curative surgical resection is optimal treatment but in most advanced cases curative resection can't be done. Liver transplantation is accepted treatment option for advanced AED. AED in some case invade surrounding tissue especially inferior vena cava (IVC). Advanced AED with invasion to IVC can be treated with deceased liver transplantation. Although living donor liver transplantation is very difficult to perform in patients with advanced AED with resected IVC, it come into consideration, since there is very few cadaveric liver. PRESENTATION OF CASE: Here we present a case with advanced stage of AED of liver which cause portal hypertension and cholestasis. AED invaded surrounding tissue, right diaphragm, both lobes of liver and retrohepatic part of IVC. Invasion of IVC forced us to make resection of IVC and reconstruction with cryopreserved venous graft to reestablish blood flow. After that a living donor liver transplantation was done. DISCUSSION: Curative surgery is the first-choice option in all operable patients with AED of liver. Advanced stage of AED like chronic jaundice, liver abscess, sepsis, repeated attacks of cholangitis, portal hypertension, and Budd-Chiari syndrome may be an indication for liver transplantation. In some advanced stage AED during transplantation replacement of retrohepatic part of IVC could be done with artificial vascular graft, cadaveric aortic and caval vein graft. CONCLUSION: Although living donor liver transplantation with replacement of IVC is a very difficult operation, it should be considered in the management of advanced AED of liver with IVC invasion because of the rarity of deceased liver.