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Early effects of renal replacement therapy on cardiovascular comorbidity in children with end-stage kidney disease: findings from the 4C-T Study.

Wed, 09/20/2017 - 12:45
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Early effects of renal replacement therapy on cardiovascular comorbidity in children with end-stage kidney disease: findings from the 4C-T Study.

Transplantation. 2017 Sep 18;:

Authors: Schmidt BMW, Sugianto RI, Thurn D, Azukaitis K, Bayazit AK, Canpolat N, Eroglu AG, Caliskan S, Doyon A, Duzova A, Karagoz T, Anarat A, Deveci M, Mir S, Ranchin B, Shroff R, Baskin E, Litwin M, Özcakar ZB, Büscher R, Soylemezoglu O, Dusek J, Kemper M, Matteucci MC, Habbig S, Laube G, Wühl E, Querfeld U, Sander A, Schaefer F, Melk A, 4C Study Consortium

Abstract
BACKGROUND: The early impact of renal transplantation on subclinical cardiovascular measures in pediatric patients has not been widely investigated. This analysis is performed for pediatric patients participating in the prospective 4C study and focuses on the early effects of RRT modality on cardiovascular comorbidity in patients receiving a preemptive transplant or started on dialysis.
METHODS: We compared measures indicating subclinical cardiovascular organ damage (aortal pulse wave velocity, carotid intima media thickness, left ventricular mass index) and evaluated cardiovascular risk factors in 166 pediatric patients before and 6 to 18 months after start of RRT (n=76 transplantation, n=90 dialysis).
RESULTS: RRT modality had a significant impact on the change in arterial structure and function: compared to dialysis treatment, transplantation was independently associated with decreases in pulse wave velocity (ß=-0.67; p<0.001) and intima media thickness (ß=-0.40; p=0.008). Independent of RRT modality, an increase in pulse wave velocity was associated with an increase in diastolic blood pressure (ß=0.31; p<0.001). Increasing intima media thickness was associated with a larger increase in body mass index (ß=0.26; p=0.003) and the use of antihypertensive agents after RRT (ß=0.41; p=0.007). Changes in left ventricular mass index were associated with changes in systolic blood pressure (ß=1.47; p=0.01).
CONCLUSIONS: In comparison with initiating dialysis, preemptive transplantation prevented further deterioration of the subclinical vascular organ damage early after transplantation. Classical cardiovascular risk factors such as hypertension and obesity are of major importance for the development of cardiovascular organ damage after renal transplantation.

PMID: 28926375 [PubMed - as supplied by publisher]

Environmental peer pressure: CD4+ T cell help in tolerance and transplantation.

Wed, 09/20/2017 - 12:45
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Environmental peer pressure: CD4+ T cell help in tolerance and transplantation.

Liver Transpl. 2017 Sep 19;:

Authors: Tedesco D, Grakoui A

Abstract
The liver participates in a multitude of metabolic functions that are critical for sustaining human life. Despite constant encounters with antigenic-rich intestinal blood, oxidative stress and metabolic intermediates, there is no appreciable immune response. Interestingly, patients undergoing orthotopic liver transplantation benefit from a high rate of graft acceptance in comparison to other solid organ transplant recipients. In fact, co-transplantation of a donor liver in tandem with a rejection-prone graft increases the likelihood of graft acceptance. A variety of players may account for this phenomenon including the interaction of intrahepatic antigen presenting cells with CD4+ T cells and the preferential induction of Foxp3 expression on CD4+ T cells following injurious stimuli. Ineffective insult management can cause chronic liver disease, which manifests systemically as: antibody mediated disorders, ineffective antiviral and antibacterial immunity, and gastrointestinal disorders. These sequelae share the requirement of CD4+ T cell help to coordinate aberrant immune responses. In this review, we will focus on CD4+ T cell help due to the shared requirements in hepatic tolerance and coordination of extrahepatic immune responses. Overall, intrahepatic deviations from steady state can have deleterious systemic immune outcomes, and highlight the liver's remarkable capacity to maintain a balance between tolerance and inflammatory response while simultaneously being inundated with a panoply of antigenic stimuli. This article is protected by copyright. All rights reserved.

PMID: 28926189 [PubMed - as supplied by publisher]

Excellent outcomes in combined liver-kidney transplantation: Impact of KDPI and delayed kidney transplantation.

Wed, 09/20/2017 - 12:45
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Excellent outcomes in combined liver-kidney transplantation: Impact of KDPI and delayed kidney transplantation.

Liver Transpl. 2017 Sep 19;:

Authors: Ekser B, Mangus RS, Kubal CA, Powelson JA, Fridell JA, Goggins WC

Abstract
The positive impact of delayed kidney transplantation (KT) on patient survival for combined liver-KT (CLKT) has already been demonstrated by our group. The purpose of this study is to identify whether the quality of the kidneys (based on KDPI) or the delayed approach KT contributes to improved patient survival. 130 CLKT were performed between 2002-2015; 69 with simultaneous KT (Group S) and 61 with delayed KT (Group D) (performed as a second operation with a mean cold ischemia time [CIT] of 50±15h). All patients were categorized according to the KDPI score; 1-33%, 34-66%, and 67-99%. Recipient and donor characteristics were comparable within Groups S and D. Transplant outcomes were comparable within Groups S and D, including liver and kidney CIT, warm ischemia time, and delayed graft function. Lower KDPI kidneys (<34%) were associated with increased patient survival in both groups. Combination of delayed KT and KDPI 1-33% resulted in 100% patient survival at 3-years. These results support that delayed KT in CLKT improves patient survival. The combination of delayed KT and low KDPI offers excellent patient survival up to 3-years. Improved outcomes in the delayed KT group including high KDPI kidneys supports expansion of the donor pool with the use of more ECD and DCD kidneys. This article is protected by copyright. All rights reserved.

PMID: 28926173 [PubMed - as supplied by publisher]

Biliary Reconstructive techniques and associated anatomic variants in adult living donor liver transplants: The A2ALL experience.

Wed, 09/20/2017 - 12:45
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Biliary Reconstructive techniques and associated anatomic variants in adult living donor liver transplants: The A2ALL experience.

Liver Transpl. 2017 Sep 19;:

Authors: Baker TB, Zimmerman MA, Goodrich NP, Samstein B, Pomfret EA, Pomposelli JJ, Gillespie BW, Berg CL, Emond JC, Merion RM

Abstract
INTRODUCTION: Living donor liver transplantation (LDLT) is a technically demanding endeavor, requiring command of the complex anatomy of partial liver grafts. We examined the influence of anatomic variation and reconstruction technique on surgical outcomes and graft survival in the nine-center A2ALL Study.
METHODS: Data from 272 adult LDLT recipients (2011-2015) included details on anatomic characteristics and types of intraoperative biliary reconstruction. Associations were tested between reconstruction technique and complications, which included first biliary complication ([BC]; leak, stricture, or biloma) and first vascular complication (hepatic artery thrombosis [HAT] or portal vein thrombosis [PVT]). Time to patient death, graft failure, and complications were estimated using Kaplan-Meier curves and tested with log-rank tests.
RESULTS: Median post-transplant follow-up was 1.2 years. Associations were found between the type of biliary reconstruction and the incidence of vascular complication (p=0.034) and BC (p=0.053). Recipients with Roux-en-Y hepatico-jejunostomy had the highest probability of vascular complication. Recipients with biliary reconstruction involving the use of high biliary radicals on the recipient duct had the highest likelihood of developing BC (56% by one year) compared to duct-to-duct (42% by one year).
CONCLUSION: The varied surgical approaches in the A2ALL centers offer a novel opportunity to compare disparate LDLT approaches. The choice to use higher biliary radicals on the recipient duct for reconstruction was associated with more BC, possibly secondary to devascularization and ischemia. The use of Roux-en-Y biliary reconstruction was associated with vascular complications (HAT and PVT). These results can be used to guide biliary reconstruction decisions in the setting of anatomic variants and inform further improvements in LDLT reconstructions. Ultimately, this information may contribute to a lower incidence of technical complications after LDLT. This article is protected by copyright. All rights reserved.

PMID: 28926171 [PubMed - as supplied by publisher]

Clostridium difficile Infection in Intestinal Transplant Recipients.

Wed, 09/20/2017 - 12:45
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Clostridium difficile Infection in Intestinal Transplant Recipients.

Transpl Int. 2017 Sep 19;:

Authors: Goldenberg V, Berbel A, Camargo JF, Simkins J

Abstract
Clostridium difficile infection (CDI) is a common complication among solid organ transplant (SOT) recipients with an estimated incidence of 7-31% for lung recipients, 8-15% for heart, 3-19% for liver, 9% for intestinal, 4-16% for kidney and 2-8% for pancreas-kidney recipients (1) and it is associated with increased mortality (2). There is limited data on CDI in intestinal transplant (ITx) recipients. This is a retrospective study that was conducted at Jackson Memorial Hospital, a 1558-licensed bed tertiary care teaching hospital. Our study was approved by the Institutional Review Board of University of Miami. This article is protected by copyright. All rights reserved.

PMID: 28926130 [PubMed - as supplied by publisher]

Decreasing incidence of cancer after liver transplantation - A Nordic population-based study over three decades.

Wed, 09/20/2017 - 12:45
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Decreasing incidence of cancer after liver transplantation - A Nordic population-based study over three decades.

Am J Transplant. 2017 Sep 19;:

Authors: Nordin A, Åberg F, Pukkala E, Pedersen CR, Storm HH, Rasmussen A, Bennet W, Olausson M, Wilczek H, Ericzon BG, Tretli S, Line PD, Karlsen TH, Boberg KM, Isoniemi H

Abstract
Cancer remains one of the most serious long-term complications after liver transplantation (LT). Data for all adult LT patients between 1982 and 2013 was extracted from the Nordic Liver Transplant Registry. Through linkage with respective national cancer-registry data, we calculated standardized incidence ratios (SIRs) based on country, sex, calendar time, and age-specific incidence rates. Altogether 461 cancers were observed in 424 individuals out the 4246 LT patients during a mean 6.6-year follow-up. The overall SIR was 2.22 (95%CI 2.02-2.43). SIRs were especially increased for colorectal cancer in recipients with PSC (4.04) and for lung cancer in recipients with alcoholic liver disease (4.96). A decrease in the SIR for cancers occurring within 10 years post-LT was observed from the 1980s: 4.53 (95%CI 2.47-7.60), the 1990s: 3.17 (95%CI 2.70-3.71), to the 2000s: 1.76 (95%CI 1.51-2.05). This was observed across age- and indication-groups. The sequential decrease for the SIR of non-Hodgkin lymphoma was 25.0 - 12.9 - 7.53, and for non-melanoma skin cancer 80.0 - 29.7 - 10.4. Cancer risk after LT was found to be decreasing over time, especially for those cancers that are strongly associated with immunosuppression. Whether immunosuppression minimization contributed to this decrease merits further study. This article is protected by copyright. All rights reserved.

PMID: 28925583 [PubMed - as supplied by publisher]

mHealth Application Areas and Technology Combinations*. A Comparison of Literature from High and Low/Middle Income Countries.

Wed, 09/20/2017 - 12:45
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mHealth Application Areas and Technology Combinations*. A Comparison of Literature from High and Low/Middle Income Countries.

Methods Inf Med. 2017 Aug 08;56(7):e105-e122

Authors: Abaza H, Marschollek M

Abstract
BACKGROUND: With the continuous and enormous spread of mobile technologies, mHealth has evolved as a new subfield of eHealth. While eHealth is broadly focused on information and communication technologies, mHealth seeks to explore more into mobile devices and wireless communication. Since mobile phone penetration has exceeded other infrastructure in low and middle-income countries (LMICs), mHealth is seen as a promising component to provide pervasive and patient-centered care.
OBJECTIVES: The aim of our research work for this paper is to examine the mHealth literature to identify application areas, target diseases, and mHealth service and technology types that are most appropriate for LMICs.
METHODS: Based on the 2011 WHO mHealth report, a combination of search terms, all including the word "mHealth", was identified. A literature review was conducted by searching the PubMed and IEEE Xplore databases. Articles were included if they were published in English, covered an mHealth solution/ intervention, involved the use of a mobile communication device, and included a pilot evaluation study. Articles were excluded if they did not provide sufficient detail on the solution covered or did not focus on clinical efficacy/effectiveness. Cross-referencing was also performed on included articles.
RESULTS: 842 articles were retrieved and analyzed, 255 of which met the inclusion criteria. North America had the highest number of applications (n=74) followed by Europe (n=50), Asia (n=44), Africa (n=25), and Australia (n=9). The Middle East (n=5) and South America (n=3) had the least number of studies. The majority of solutions addressed diabetes (n=51), obesity (n=25), CVDs (n=24), HIV (n=18), mental health (n=16), health behaviors (n=16), and maternal and child's health (MCH) (n=11). Fewer solutions addressed asthma (n=7), cancer (n=5), family health planning (n=5), TB (n=3), malaria (n=2), chronic obtrusive pulmonary disease (COPD) (n=2), vision care (n=2), and dermatology (n=2). Other solutions targeted stroke, dental health, hepatitis vaccination, cold and flu, ED prescribed antibiotics, iodine deficiency, and liver transplantation (n=1 each). The remainder of solutions (n=14) did not focus on a certain disease. Most applications fell in the areas of health monitoring and surveillance (n=93) and health promotion and raising awareness (n=88). Fewer solutions addressed the areas of communication and reporting (n=11), data collection (n=6), telemedicine (n=5), emergency medical care (n=3), point of care support (n=2), and decision support (n=2). The majority of solutions used SMS messaging (n=94) or mobile apps (n=71). Fewer used IVR/phone calls (n=8), mobile website/email (n=5), videoconferencing (n=2), MMS (n=2), or video (n=1) or voice messages (n=1). Studies were mostly RCTs, with the majority suffering from small sample sizes and short study durations. Problems addressed by solutions included travel distance for reporting, self-management and disease monitoring, and treatment/medication adherence.
CONCLUSIONS: SMS and app solutions are the most common forms of mHealth applications. SMS solutions are prevalent in both high and LMICs while app solutions are mostly used in high income countries. Common application areas include health promotion and raising awareness using SMS and health monitoring and surveillance using mobile apps. Remaining application areas are rarely addressed. Diabetes is the most commonly targeted medical condition, yet remains deficient in LMICs.

PMID: 28925418 [PubMed - in process]

Optimizing hepatic venous outflow reconstruction for hepatic vein stenosis with indwelling stent in living donor liver retransplantation.

Wed, 09/20/2017 - 12:45
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Optimizing hepatic venous outflow reconstruction for hepatic vein stenosis with indwelling stent in living donor liver retransplantation.

Pediatr Transplant. 2017 Sep 18;:

Authors: Shigeta T, Sakamoto S, Sasaki K, Uchida H, Narumoto S, Fukuda A, Kasahara M

Abstract
The patient was a boy of 7 years and 5 months of age, who underwent LDLT for acute liver failure at 10 months of age. HV stent placement was performed 8 months after LDLT because of intractable HV stenosis. At 7 years of age, his liver function deteriorated due to chronic rejection. The patient therefore underwent living donor liver retransplantation from his father. The HV was transected with the stent in situ. The IVC was resected due to stenosis. The pericardial cavity was opened and detached around the IVC to elongate the IVC. The divided ends of the IVC were joined by suturing to the posterior wall of the IVC. A new triangular orifice was made by adding an incision on the anterior wall of the IVC. The graft HV was then anastomosed to the new orifice with continuous sutures in the posterior wall and interrupted sutures in the anterior wall using 5-0 non-absorbable sutures. Doppler ultrasound showed a triphasic waveform. We successfully performed HV reconstruction without a vascular graft. This is a feasible procedure for overcoming HV stenosis in LDLT patients with an indwelling stent.

PMID: 28925086 [PubMed - as supplied by publisher]

When and how can nephrologists treat hepatitis C virus infection in dialysis patients?

Wed, 09/20/2017 - 12:45
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When and how can nephrologists treat hepatitis C virus infection in dialysis patients?

Semin Dial. 2017 Sep 18;:

Authors: Davis MI, Chute DF, Chung RT, Sise ME

Abstract
Hepatitis C virus (HCV) infection, a major cause of end-stage liver disease, is a common comorbidity in patients on dialysis and causes increased morbidity and mortality. Historically HCV has been extremely difficult to cure with interferon and ribavirin-based therapies, which are also associated with significant side effects, and few dialysis patients ever received HCV treatment. However, in the last 4 years, interferon-free direct-acting antiviral therapies have been approved, and several combinations have been studied in dialysis patients. A recently approved, pan-genotypic, direct-acting antiviral regimen, glecaprevir and pibrentasvir, may simplify prescribing. The simplicity of these new therapies, with few side effects, makes it possible for nephrologists to treat HCV infection in their patients on dialysis. We review the workflow and motivation behind nephrology-led management of HCV infection. We highlight the importance of identifying which patients need referral to a hepatologist or HCV specialist prior to treatment and which can be managed by their nephrologist. Nephrologist involvement would lead to improved access to treatment and ensure that appropriate patients are referred for HCV treatment. In this paper, we review the background of HCV infection, its effect on dialysis patients, and impact on kidney transplantation. In addition, we outline the therapy options for each genotype of HCV, and we discuss the benefits and barriers to nephrology-led HCV treatment.

PMID: 28925068 [PubMed - as supplied by publisher]

Extracorporeal Membrane Oxygenation Can Save Lives in Children With Heart or Lung Failure After Liver Transplantation.

Wed, 09/20/2017 - 12:45
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Extracorporeal Membrane Oxygenation Can Save Lives in Children With Heart or Lung Failure After Liver Transplantation.

Artif Organs. 2017 Sep;41(9):862-865

Authors: Jean S, Chardot C, Oualha M, Capito C, Bustarret O, Pouard P, Renolleau S, Lacaille F, Dupic L

Abstract
The risk of cardiac or lung failure after liver transplantation (LT) is significant. In rare cases, the usual intensive care techniques fail to maintain organ oxygenation with a risk of multiorgan dysfunction. Although extracorporeal membrane oxygenation (ECMO) is a difficult and risky procedure, it can be proposed as life-saving. Four children with either acute pulmonary (three) or cardiac (one) failure after LT, and the criteria that decided the use of ECMO (level of ventilation and results, dosage of inotropic drugs, cardiac ultrasound, blood lactate) were retrospectively reported. These patients, 1-11 years old, were treated with either veno-arterial (three) or veno-venous (one) ECMO. Two experienced a full recovery, with 3 and 6 years of follow-up. Two died of systemic inflammatory response syndrome (SIRS) due to ECMO, and relapse of heart failure due to the underlying disease. Although our patients' survival was only 50%, we showed that ECMO can be useful in children after LT. It should be considered before the development of irreversible multiorgan failure.

PMID: 28925053 [PubMed - in process]

Assessing the Non-tumorous Liver: Implications for Patient Management and Surgical Therapy.

Wed, 09/20/2017 - 12:45
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Assessing the Non-tumorous Liver: Implications for Patient Management and Surgical Therapy.

J Gastrointest Surg. 2017 Sep 18;:

Authors: Pandey P, Pandey A, Dillhoff M, Schmidt C, Kamel IR, Pawlik TM

Abstract
INTRODUCTION: Hepatic resection is performed for various benign and malignant liver tumors. Over the last several decades, there have been improvements in the surgical technique and postoperative care of patients undergoing liver surgery. Despite this, liver failure following an extended hepatic resection remains a critical potential postoperative complication. Patients with underlying parenchymal liver diseases are at particular risk of liver failure due to impaired liver regeneration with an associated mortality risk as high as 60 to 90%. In addition, live donor liver transplantation requires a thorough presurgical assessment of the donor liver to minimize the risk of postoperative complications.
RESULTS AND CONCLUSION: Recently, cross-sectional imaging assessment of diffuse liver diseases has gained momentum due to its ability to provide both anatomical and functional assessments of normal and abnormal tissues. Various imaging techniques are being employed to assess diffuse liver diseases including magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound (US). MRI has the ability to detect abnormal intracellular and molecular processes and tissue architecture. CT has a high spatial resolution, while US provides real-time imaging, is inexpensive, and readily available. We herein review current state-of-the-art techniques to assess the underlying non-tumorous liver. Specifically, we summarize current approaches to evaluating diffuse liver diseases including fatty liver alcoholic or non-alcoholic (NAFLD, AFLD), hepatic fibrosis (HF), and iron deposition (ID) with a focus on advanced imaging techniques for non-invasive assessment along with their implications for patient management. In addition, the role of and techniques to assess hepatic volume in hepatic surgery are discussed.

PMID: 28924922 [PubMed - as supplied by publisher]

Cystic Presentation of Hepatic Schistosomiasis.

Wed, 09/20/2017 - 12:45
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Cystic Presentation of Hepatic Schistosomiasis.

Indian J Pediatr. 2017 Sep 19;:

Authors: Sood V, Chaudhari SR, Borle D, Sureka B, Bihari C, Kumar S

PMID: 28924731 [PubMed - as supplied by publisher]

Alcoholic liver disease is a strong predictor of colorectal polyps in liver transplant recipients.

Wed, 09/20/2017 - 12:45
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Alcoholic liver disease is a strong predictor of colorectal polyps in liver transplant recipients.

Endosc Int Open. 2017 Sep;5(9):E918-E923

Authors: Ma AT, Therrien A, Giard JM, von Renteln D, Bouin M

Abstract
BACKGROUND AND AIMS:  Colorectal cancer (CRC) is associated with a significantly reduced survival rate in transplant recipients. The prevalence and risk factors of CRC and of colorectal polyps after orthotopic liver transplant (OLT) remain unclear. The study aim was to determine the prevalence of colorectal polyps in OLT recipients. A secondary objective was to explore possible risk factors of polyps.
PATIENTS AND MATERIALS:  This was a retrospective single center study of all OLT recipients transplanted between 2007 and 2009. All patients who underwent a colonoscopy 5 ± 5 years after OLT were included. The outcome was colorectal polyps, as identified on colonoscopy. A logistic regression model was performed to identify potential predictors of polyps.
RESULTS:  Of 164 OLT recipients, 80 were included in this study. Polyps were diagnosed in 37 % of patients before transplant and in 33 % afterwards. With regard to post-transplant lesions, 22 % were advanced adenomas or cancerous. In the regression analysis, the odds of post-transplant polyps were 11 times higher in patients with alcoholic liver disease (OR 11.3, 95 %CI 3.2 - 39.4; P  < 0.001).
CONCLUSION:  Patients with end-stage liver disease may be at high risk of colorectal polyps before and after liver transplant, and screening should be continued in both contexts. Those with alcoholic liver disease are particularly at risk for post-OLT polyps and may benefit from more intensive screening.

PMID: 28924600 [PubMed]

Development of a Valid and Reliable Questionnaire to Identify Professional Opinion Regarding Organ Transplantation System.

Wed, 09/20/2017 - 12:45
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Development of a Valid and Reliable Questionnaire to Identify Professional Opinion Regarding Organ Transplantation System.

Int J Organ Transplant Med. 2017;8(3):146-156

Authors: Sah B, Ayer A, Yadav BN, Jha S, Yadav SK

Abstract
BACKGROUND: Currently, the Nepalese law permits organ donation by an individual who falls into the category of a "close relative" of the recipient. There is a need for expansion of the live organ donor pool beside close relatives. Different systems of organ transplantation are followed by several countries and the professional opinions that underpin these systems need to be studied.
OBJECTIVE: To generate a questionnaire related to different organ transplant systems and validate it so that it can be used to collect mass professional opinions.
METHODS: Item generation, item reduction, item scaling, and pretesting were used to develop a questionnaire. The final version of the questionnaire was reviewed by experts for its content validity and then was used twice for participants at a 20-day interval to calculate Cronbach's alpha for testing its internal consistency and Intra-class correlation for testing its test and retest reliability.
RESULTS: The questionnaire was found to be valid and reliable with an overall Cronbach's alpha of 0.701. Intra-class correlation scores for each question in both test and retest were correlated.
CONCLUSION: A valid and reliable questionnaire was developed that can be used to collect mass professional opinions to assist policy makers to establish a better organ transplant system.

PMID: 28924463 [PubMed]

Occult Hepatitis Infection in Transfusion Medicine: Screening Policy and Assessment of Current Use of Anti-HBc Testing.

Wed, 09/20/2017 - 12:45
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Occult Hepatitis Infection in Transfusion Medicine: Screening Policy and Assessment of Current Use of Anti-HBc Testing.

Transfus Med Hemother. 2017 Aug;44(4):263-272

Authors: Esposito A, Sabia C, Iannone C, Nicoletti GF, Sommese L, Napoli C

Abstract
HBV still represents a global risk factor in transfusion medicine. The residual risk of HBV is not limited to pre-seroconversion window period but it extends to donors with occult HBV infection (OBI) characterized by the presence of HBV DNA in liver and by the absence of the virus surface antigen. Each country developed an appropriate blood screening policy according to local HBV prevalence, yields of infectious units per different screening methods and cost-effectiveness. We underline the need of maintaining a high level of attention for OBI carrier identification in all blood banks worldwide where the screening procedures are generally based on a combination of both serological markers and nucleic acid amplification test. In this context, markers such as hepatitis B surface antibodies and hepatitis B core antibodies (anti-HBc) might be useful, although the use of this latter is highly debated and still controversial. Our aim is to give an overview on the relevant diagnostic approaches for the routine screening for HBV focusing on the feasibility of anti-HBc testing as precautionary measure in preventing OBI transmission worldwide. In our tailored algorithm, the loss of about 1% of 'anti-HBc only' donors, does not significantly affect the blood supply while improving recipient safety.

PMID: 28924431 [PubMed]

An expanded role for heterozygous mutations of ABCB4, ABCB11, ATP8B1, ABCC2 and TJP2 in intrahepatic cholestasis of pregnancy.

Wed, 09/20/2017 - 12:45
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An expanded role for heterozygous mutations of ABCB4, ABCB11, ATP8B1, ABCC2 and TJP2 in intrahepatic cholestasis of pregnancy.

Sci Rep. 2017 Sep 18;7(1):11823

Authors: Dixon PH, Sambrotta M, Chambers J, Taylor-Harris P, Syngelaki A, Nicolaides K, Knisely AS, Thompson RJ, Williamson C

Abstract
Intrahepatic cholestasis of pregnancy (ICP) affects 1/140 UK pregnancies; with pruritus, hepatic impairment and elevated serum bile acids. Severe disease is complicated by spontaneous preterm delivery and stillbirth. Previous studies have reported mutations in hepatocellular transporters (ABCB4, ABCB11). High throughput sequencing in 147 patients was performed in the transporters ABCB4, ABCB11, ATP8B1, ABCC2 and tight junction protein 2 (TJP2). Twenty-six potentially damaging variants were identified with the following predicted protein changes: Twelve ABCB4 mutations - Arg47Gln, Met113Val, Glu161Gly, Thr175Ala, Glu528Glyfs*6, Arg590Gln, Ala601Ser, Glu884Ter, Gly722Ala, Tyr775Met (x2), Trp854Ter. Four potential ABCB11 mutations - Glu297Gly (x3) and a donor splice site mutation (intron 19). Five potential ATP8B1 mutations - Asn45Thr (x3), and two others, Glu114Gln and Lys203Glu. Two ABCC2 mutations - Glu1352Ala and a duplication (exons 24 and 25). Three potential mutations were identified in TJP2; Thr62Met (x2) and Thr626Ser. No patient harboured more than one mutation. All were heterozygous. An additional 545 cases were screened for the potential recurrent mutations of ATP8B1 (Asn45Thr) and TJP2 (Thr62Met) identifying three further occurrences of Asn45Thr. This study has expanded known mutations in ABCB4 and ABCB11 and identified roles in ICP for mutations in ATP8B1 and ABCC2. Possible novel mutations in TJP2 were also discovered.

PMID: 28924228 [PubMed - in process]

Associations between Voriconazole Therapeutic Drug Monitoring, Toxicity and outcome in Liver Transplant Patients; an Observational Study.

Wed, 09/20/2017 - 12:45
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Associations between Voriconazole Therapeutic Drug Monitoring, Toxicity and outcome in Liver Transplant Patients; an Observational Study.

Antimicrob Agents Chemother. 2017 Sep 18;:

Authors: Hashemizadeh Z, Badiee P, Malekhoseini SA, Raeisi Shahraki H, Geramizadeh B, Montaseri H

Abstract
The aim of this study was to investigate the variability of voriconazole plasma level and its relationship with clinical outcomes and adverse events, among liver transplant recipients to optimize the efficacy and safety of their treatment. Liver transplant recipients treated with voriconazole were included and voriconazole trough levels were quantified by the validated high-performance liquid chromatography method. Cytochrome P450 genotypes of CYP2C19 were evaluated in allograft liver tissues. A total of 832 voriconazole trough levels from 104 patients were measured. Proven, probable and possible invasive fungal infections were reported in (8/104, 7.7%), (42/104, 40.4%), and (54/104, 51.9%) patients, respectively. ROC curve analysis indicated that trough concentration ≥1.3 μg/ml minimized the incidence of treatment failure (95% CI 0.68-0.91; P < 0.001), and < 5.3 μg/ml minimized the incidence of any adverse events (95% CI 0.83-0.97; P < 0.001). Voriconazole trough levels were significantly higher in heterozygous extensive metabolizers, poor metabolizers and co-administration with proton pump inhibitors. In ultra-rapid metabolizers, oral administration of voriconazole and concomitant use of glucocorticoids, voriconazole blood concentrations were significantly reduced. Furthermore, there was no statistically significant association of patients' age, weight, gender, co-administration of tacrolimus and cyclosporine with voriconazole trough level. In conclusion, the results of our analysis indicated large inter and intra-individual variabilities of voriconazole concentrations in liver transplant recipients. Voriconazole trough concentrations between ≥1.3 μg/ml and < 5.3 μg/ml are optimal for treatment and minimize adverse events. Optimizing drug efficacy and safety need rational doses for voriconazole therapy.

PMID: 28923870 [PubMed - as supplied by publisher]

Case Report of Extensive Isolated Spontaneous Celiac Trunk Dissection After Liver Transplantation.

Wed, 09/20/2017 - 12:45
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Case Report of Extensive Isolated Spontaneous Celiac Trunk Dissection After Liver Transplantation.

Transplant Proc. 2017 Oct;49(8):1956-1959

Authors: Iwaki K, Yagi S, Iida T, Ogawa E, Masano Y, Tajima T, Okumura S, Yamamoto G, Kamo N, Taura K, Kaido T, Uemoto S

Abstract
Arterial dissection is a rare complication after liver transplantation (LT). We report a case of extensive isolated spontaneous celiac trunk dissection (ISCTD) up to the proper hepatic artery, left gastric artery, and splenic artery after living donor liver transplantation. A 48-year-old woman with cryptogenic liver cirrhosis underwent living donor liver transplantation. Intraoperative and postoperative Doppler ultrasound revealed sufficient flow in the hepatic artery, portal vein, and hepatic vein. On postoperative day (POD) 10, Doppler ultrasound showed reduction of hepatic arterial flow. On POD 16, a contrast-enhanced computed tomography scan showed that the ISCTD extended to the proper hepatic artery, left gastric artery, and splenic artery with an entry tear on the proximal side of the celiac trunk. Although the computed tomography scan showed ischemia of a small part of the liver, blood flow to the liver was kept to some extent. Because all false lumens were occluded by thrombi and the liver enzyme levels normalized, we chose conservative therapy with antiplatelet agents. The patient was discharged on POD 53. She remains well without any liver dysfunction after 18 months with reduction in all false lumens and a patent hepatic artery. Several cases of ISCTD have been reported apart from LT, most of which were treated with conservative therapy. We conclude that conservative therapy could be the first choice in ISCTD even after LT.

PMID: 28923654 [PubMed - in process]

Effects of the Mammalian Target of Rapamycin Inhibitor Everolimus on Hepatitis C Virus Replication In Vitro and In Vivo.

Wed, 09/20/2017 - 12:45
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Effects of the Mammalian Target of Rapamycin Inhibitor Everolimus on Hepatitis C Virus Replication In Vitro and In Vivo.

Transplant Proc. 2017 Oct;49(8):1947-1955

Authors: Frey A, Ecker EM, Piras-Straub K, Walker A, Hofmann TG, Timm J, Singer BB, Gerken G, Herzer K

Abstract
BACKGROUND: The influence of immunosuppressants on hepatitis C virus (HCV) re-infection after liver transplantation, particularly mammalian target of rapamycin inhibitors, remains unclear. The aim of our study was to analyze the influence of everolimus (EVR) on HCV replication activity in the context of underlying molecular mechanisms, with focus on the pro-myelocytic leukemia protein (PML).
METHODS: HCV viral load was recorded in 40 patients with post-transplant HCV re-infection before and 8 weeks after introduction of EVR. An HCV cell culture replicon system for genotype (GT) 1b, GT2b, and GT3a was used to compare the influence of EVR on HCV replication for the respective genotypes in vitro. Fluorescence-activated cell-sorting analysis was used to test for effects on cell proliferation. PML expression was silenced with the use of small hairpin RNA constructs, and PML expression was quantified by means of quantitative real-time polymerase chain reaction.
RESULTS: In patients with HCV, the viral load of GT1a and GT1b was hardly affected by EVR, whereas the viral load was reduced in patients with GT2a (P ≤ .0001) or GT3 infection (P ≤ .05). In vitro EVR impairs HCV replication activity of GT2a and GT3a up to 60% (P ≤ .0005), whereas in GT1b cells, HCV replication activity is increased by 50% (P ≤ .005). Replicon cell viability was not impaired. HCV replication activity is impaired in the absence of PML, which can be reversed by overexpression of PML isoforms. Furthermore, in the absence of PML, the effect of EVR on HCV replication activity is nearly abrogated.
CONCLUSIONS: The mammalian target of rapamycin inhibitor EVR influences HCV replication via PML. The herein presented results suggest a genotype-dependent benefit for an EVR-based immunosuppressive regimen in patients with GT2a or GT3 re-infection after liver transplantation.

PMID: 28923653 [PubMed - in process]

Simultaneous Kidney-Pancreas Transplantation With an Original "Transverse Pancreas" Technique: Initial 9 Years' Experience With 56 Cases.

Wed, 09/20/2017 - 12:45
Related Articles

Simultaneous Kidney-Pancreas Transplantation With an Original "Transverse Pancreas" Technique: Initial 9 Years' Experience With 56 Cases.

Transplant Proc. 2017 Oct;49(8):1879-1882

Authors: Paulino J, Martins A, Vigia E, Marcelino P, Nobre AM, Bicho L, Filipe E, Barroso E

Abstract
An innovative technique for pancreas transplantation is described. The main aspect consists of the horizontal positioning of the pancreas, which allows a better venous outflow, thus preventing thrombosis and graft loss. The program of pancreas transplantation in this national reference center for pancreatic and liver surgery was started in 2007; the initial results were considered poor, resulting in the loss of half of the grafts due to venous thrombosis. After analyzing the possible causes, this technique was proposed and successfully implemented, reducing the postoperative complications, particularly the problem of venous thrombosis. A detailed description of the new surgical technique is provided. The main clinical and demographic characteristics of the 56 patients who underwent the surgery are analyzed. The incidence of venous thrombosis was 5.3% (3 patients) and graft loss was 3.5% (2 patients). Due to the good results, this technique became the standard surgery for transplantation of the pancreas in our center. The technique proved to be safe and successful. Due to the unique pancreas graft implantation, we called it "transverse pancreas surgery."

PMID: 28923641 [PubMed - in process]

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