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Plans for $22.5M nursing home, pediatric heart transplant program denied by state

MedWorm Heart Transplant - Mon, 02/19/2018 - 13:36
Arnold Palmer Medical Center's $1.5 million plan gets turned down. (Source: bizjournals.com Health Care:Pharmaceuticals headlines)

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Categories: Publications

Recipient characteristics and morbidity and mortality after liver transplantation.

PubMed Kidney Transplant - Sun, 02/18/2018 - 13:45
Related Articles

Recipient characteristics and morbidity and mortality after liver transplantation.

J Hepatol. 2018 Feb 14;:

Authors: Asrani SK, Saracino G, O'Leary JG, Gonzales S, Kim P, McKenna G, Klintmalm G, Trotter J

Abstract
BACKGROUND: Over the last decade, liver transplantation of sicker, older non-hepatitis C cirrhotics with multiple co-morbidities has increased in the United States.
METHODS: We sought to identify a parsimonious set of recipient factors among HCV negative adult transplant recipients associated with significant morbidity and mortality within 5 years after liver transplantation using national (n=31,829, 2002-2015) and center specific data. Coefficients of relevant recipient factors were converted to weighted points and scaled from 0-5. Recipient factors associated with graft failure included: ventilator support (5 pts; HR 1.59, 95% CI 1.48-1.72); recipient age >60 years (3 pts; HR 1.29, 95% CI 1.23-1.36); hemodialysis (3 pts; HR 1.26, 95% CI 1.16-1.37); diabetes (2 pts; HR 1.20, 95% CI 1.14-1.27); or serum creatinine ≥1.5mg/dL without hemodialysis (2 pts; HR 1.15, 95% CI 1.09-1.22).
RESULTS: Graft survival within 5 years based on points (any combination) was 77.2% (0-4), 69.1% (5-8) and 57.9% (>8). In recipients with > 8 points, graft survival was 42% (MELD<25) and 50% (MELD 25-35) in recipients receiving donors with donor risk index >1.7. In center specific data within the first year, subjects with ≥ 5 points (vs. 0-4) had longer hospitalization (11 vs. 8 days, p<0.01), higher admissions for rehabilitation (12.3% versus 2.7%, p<0.01), and higher incidence of cardiac disease (14.2% vs. 5.3%, p<0.01) and stage 3 chronic kidney disease (78.6% vs. 39.5%, p=0.03) within 5 years.
CONCLUSION: The impact of co-morbidities in a MELD based organ allocation system needs to be reassessed. The proposed clinical tool may be helpful for center specific assessment of risk of graft failure in non HCV patients and discussion regarding relevant morbidity in selected subsets.
LAY SUMMARY: Over the last decade, liver transplantation of sicker, older patient with multiple co-morbidities has increased. In this study, we show that a set of recipient factors (recipient age>60 years, ventilator status, diabetes, hemodialysis and creatinine>1.5mg/dL) can help identify patients that may not do well after transplant. Transplanting sicker organs in patients with certain combinations of these characteristics further leads to lower survival.

PMID: 29454069 [PubMed - as supplied by publisher]

Estimated GFR in stable older kidney transplant recipients - are present algorithms valid? A national cross-sectional cohort study.

PubMed Kidney Transplant - Sun, 02/18/2018 - 13:45
Related Articles

Estimated GFR in stable older kidney transplant recipients - are present algorithms valid? A national cross-sectional cohort study.

Transpl Int. 2018 Feb 17;:

Authors: Heldal K, Midtvedt K, Hartmann A, Reisaeter AV, Heldal TF, Bergan S, Salvador CL, Åsberg A

Abstract
Several equations have been developed for estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease (CKD), but none were developed based on data from elderly kidney transplant recipients (KTR). The primary aim of this study was to evaluate different creatinine based equations in stable elderly KTR. A national cross-sectional study was performed using data from 263 consecutive kidney transplant recipients 60 years or older who performed a routine GFR measurement one year after engraftment. GFR was measured by iohexol clearance calculation based on two samples. eGFR was calculated from a range of different creatinine based equations using information obtained at the time of GFR measurement. Bias, precision, and accuracy were evaluated for each equation. All equations apart from Nankivell had accuracy > 80%. The BIS1, FAS, LMRCR and Cockcroft & Gault equations in recipients older than 70 years and the FAS, LMRCR and MDRD in recipients 60-69 years old had non-significant bias. The CKD-EPI had significant bias in both groups. If one should choose a single equation for follow-up of individual CKD progression in all recipients ≥ 60 years, the FAS or LMRCR equations are probably the best alternatives. This article is protected by copyright. All rights reserved.

PMID: 29453878 [PubMed - as supplied by publisher]

Immune System and Kidney Transplantation.

PubMed Kidney Transplant - Sun, 02/18/2018 - 13:45
Related Articles

Immune System and Kidney Transplantation.

JNMA J Nepal Med Assoc. 2017 Oct-Dec;56(208):482-486

Authors: Shrestha BM

Abstract
The immune system recognises a transplanted kidney as foreign body and mounts immune response through cellular and humoral mechanisms leading to acute or chronic rejection, which ultimately results in graft loss. Over the last five decades, there have been significant advances in the understanding of the immune responses to transplanted organs in both experimental and clinical transplant settings. Modulation of the immune response by using immunosuppressive agents has led to successful outcomes after kidney transplantation. The paper provides an overview of the general organisation and function of human immune system, immune response to kidney transplantation, and the current practice of immunosuppressive therapy in kidney transplantation in the United Kingdom.

PMID: 29453486 [PubMed - in process]

Coronary artery disease in heart transplantation: new concepts for an old disease.

PubMed Lung Transplant - Sun, 02/18/2018 - 13:45
Related Articles

Coronary artery disease in heart transplantation: new concepts for an old disease.

Transpl Int. 2018 Feb 17;:

Authors: Langstraat M, Musters KJS, Manintveld O, Masetti M, Potena L

Abstract
BACKGROUND: Cardiac allograft vasculopathy (CAV) remains one of the main long-term complications after heart transplantation. We performed a systematic review focused on articles published in the previous 6 years to reappraise the novel evidences supporting risk-factors, pathology, prevention and treatment of CAV.
METHODS: We identified a search string for a literature search on PubMed. We excluded articles specifically focused on diagnosis/biomarkers/imaging only or complications of other diseases.
RESULTS: We included 98 studies out of our search. 48 Articles describe risk factors for CAV, 13 pathology, 24 prevention and 13 treatment of CAV.
DISCUSSION: While confirming known concepts, we found supportive evidence that CAV pathophysiology may vary according to the time post-transplant and the prevalence of metabolic vs. immune-mediated risk factors. Selective revascularization of focal lesions in patients with CAV may result in some clinical benefit, but CAV prevention, rather than treatment, by controlling risk factors and by using targeted immunosuppressive therapies is the most evidence-based approach to reduce disease progression. This article is protected by copyright. All rights reserved.

PMID: 29453887 [PubMed - as supplied by publisher]

Examining the Incidence and Presentation of Melanoma in the Cardiothoracic Transplant Population.

PubMed Lung Transplant - Sun, 02/18/2018 - 13:45
Related Articles

Examining the Incidence and Presentation of Melanoma in the Cardiothoracic Transplant Population.

JAMA Dermatol. 2018 Feb 16;:

Authors: Puza CJ, Cardones AR, Mosca PJ

Abstract
Importance: The immunosuppression vital to maintaining transplanted organs comes with an increased incidence of cutaneous neoplasms. Understanding the genesis of malignant melanoma (MM) in transplant subpopulations is necessary for adequate disease surveillance.
Objective: To determine the incidence and timing of presentation of MM in the cardiothoracic (heart and/or lung) transplant (CTT) population.
Design, Setting, and Participants: This was a retrospective cohort study of 1164 patients who underwent a CTT from 2001 through 2016 with a median follow-up time of 4.3 years. The study was performed at a single academic, tertiary referral center. The retrospective database was used to identify 1164 patients who underwent a CTT at Duke University Hospital from 2001 to 2016. Ten patients were excluded from the study owing to a history of MM, resulting in 1154 patients in the study. Five patients who developed MM after CTT were identified.
Exposures: Exposures included tacrolimus, prednisone, and mycophenolate mofetil.
Main Outcomes and Measures: The primary outcome measurement was the MM incidence. Secondary outcomes included time to diagnosis and survival.
Results: Five of 1154 patients who underwent a CTT (0.4%) developed biopsy-proven MM at a median follow-up time of 4.3 years after transplantation at a median age of 64.5 years (range, 31.0-74.0 years). Of the 1154 patients, 923 (80%) were men. Their mean (SD) age range was 63.8 years (27.2-68.2 years). Four patients (80%) presented with stage I disease while 1 (20%) presented with stage IV disease at a median time of 2.5 years (range, 0.1-5.3 years) after transplant compared with a median time of 6.2 years (range, 0.9-8.7 years) in Duke University's renal transplant population at a median follow-up time of 6.6 years. Two patients died after transplant, 1 owing to complications of the transplant and 1 owing to metastatic MM.
Conclusions and Relevance: Representing one of the largest reported studies of patients with CTT developing MM, our findings suggest that the CTT population experiences an incidence of MM similar to that of other solid organ transplant recipients and with a median of 2.5 years from transplant to melanoma diagnosis. While the small scale of our study prevents far-reaching conclusions, further study is warranted to better understand the incidence, timing, and clinical ramifications of melanomagenesis in the CTT population.

PMID: 29453871 [PubMed - as supplied by publisher]

Human neutrophils can mimic myeloid-derived suppressor cells (PMN-MDSC) and suppress microbead or lectin-induced T cell proliferation through artefactual mechanisms.

PubMed Lung Transplant - Sun, 02/18/2018 - 13:45
Related Articles

Human neutrophils can mimic myeloid-derived suppressor cells (PMN-MDSC) and suppress microbead or lectin-induced T cell proliferation through artefactual mechanisms.

Sci Rep. 2018 Feb 16;8(1):3135

Authors: Negorev D, Beier UH, Zhang T, Quatromoni JG, Bhojnagarwala P, Albelda SM, Singhal S, Eruslanov E, Lohoff FW, Levine MH, Diamond JM, Christie JD, Hancock WW, Akimova T

Abstract
We report that human conventional CD15+ neutrophils can be isolated in the peripheral blood mononuclear cell (PBMC) layer during Ficoll gradient separation, and that they can impair T cell proliferation in vitro without concomitant neutrophil activation and killing. This effect was observed in a total of 92 patients with organ transplants, lung cancer or anxiety/depression, and in 18 healthy donors. Although such features are typically associated in the literature with the presence of certain myeloid-derived suppressor cell (PMN-MDSC) populations, we found that commercial centrifuge tubes that contained membranes or gels for PBMC isolation led to up to 70% PBMC contamination by CD15+ neutrophils, with subsequent suppressive effects in certain cellular assays. In particular, the suppressive activity of human MDSC should not be evaluated using lectin or microbead stimulation, whereas assays involving soluble or plate-bound antibodies or MLR are unaffected. We conclude that CD15+ neutrophil contamination, and associated effects on suppressor assays, can lead to significant artefacts in studies of human PMN-MDSC.

PMID: 29453429 [PubMed - in process]

The management of antibodies in heart transplantation: An ISHLT consensus document.

PubMed Lung Transplant - Sun, 02/18/2018 - 13:45
Related Articles

The management of antibodies in heart transplantation: An ISHLT consensus document.

J Heart Lung Transplant. 2018 Jan 31;:

Authors: Kobashigawa J, Colvin M, Potena L, Dragun D, Crespo-Leiro MG, Delgado JF, Olymbios M, Parameshwar J, Patel J, Reed E, Reinsmoen N, Rodriguez ER, Ross H, Starling RC, Tyan D, Urschel S, Zuckermann A

Abstract
Despite the successes from refined peri-operative management techniques and immunosuppressive therapies, antibodies remain a serious cause of morbidity and mortality for patients both before and after heart transplantation. Patients awaiting transplant who possess antibodies against human leukocyte antigen are disadvantaged by having to wait longer to receive an organ from a suitably matched donor. The number of pre-sensitized patients has been increasing, a trend that is likely due to the increased use of mechanical circulatory support devices. Even patients who are not pre-sensitized can go on to produce donor-specific antibodies after transplant, which are associated with worse outcomes. The difficulty in managing antibodies is uncertainty over which antibodies are of clinical relevance, which patients to treat, and which treatments are most effective and safe. There is a distinct lack of data from prospective trials. An international consensus conference was organized and attended by 103 participants from 75 centers to debate contentious issues, determine the best practices, and formulate ideas for future research on antibodies. Prominent experts presented state-of-the-art talks on antibodies, which were followed by group discussions, and then, finally, a reconvened session to establish consensus where possible. Herein we address the discussion, consensus points, and research ideas.

PMID: 29452978 [PubMed - as supplied by publisher]

Differential role of gpaB and sidA gene expressions in relation to virulence in Aspergillus species from patients with invasive aspergillosis.

PubMed Lung Transplant - Sun, 02/18/2018 - 13:45
Related Articles

Differential role of gpaB and sidA gene expressions in relation to virulence in Aspergillus species from patients with invasive aspergillosis.

Braz J Microbiol. 2018 Feb 03;:

Authors: Ghods N, Falahati M, Roudbary M, Farahyar S, Shamaei M, Pourabdollah M, Seif F

Abstract
The virulence genes in invasive aspergillosis (IA) have not been analyzed adequately. The present study was designed to evaluate the expression of gpaB and sidA genes, which are important virulence genes in Aspergillus spp. from bronchoalveolar lavage (BAL) samples. Direct examination and culture on Czapek Agar and Sabouraud Dextrose Agar media were performed for 600 BAL specimens isolated from patients with possible aspergillosis. A Galactomannan ELISA assay was also carried out. The expression levels of the gpaB and sidA genes in isolates were analyzed using quantitative real-time PCR (qRT-PCR). We identified 2 species, including Aspergillus flavus (A. flavus) and Aspergillus fumigatus (A. fumigatus) in 25 positive samples for invasive aspergillosis as validated using GM-ELISA. A. flavus is the main pathogen threatening transplant recipients and cancer patients worldwide. In this study, A. flavus had low levels of the gpaB gene expression compared to A. fumigatus (p=0.006). The highest sidA expression was detected in transplant recipients (p=0.05). There was no significant correlation between sidA expression and underlying disease (p=0.15). The sidA and gpaB gene expression patterns may provide evidence that these virulence genes play important roles in the pathogenicity of Aspergillus isolates; however, there are several regulatory genes responsible for the unexpressed sidA and gpaB genes in the isolates.

PMID: 29452846 [PubMed - as supplied by publisher]

Donor and recipient P450 gene polymorphisms influence individual pharmacological effects of tacrolimus in Chinese liver transplantation patients.

PubMed Liver Transplant - Sun, 02/18/2018 - 13:45
Related Articles

Donor and recipient P450 gene polymorphisms influence individual pharmacological effects of tacrolimus in Chinese liver transplantation patients.

Int Immunopharmacol. 2018 Feb 14;57:18-24

Authors: Liu J, Ouyang Y, Chen D, Yao B, Lin D, Li Z, Zang Y, Liu H, Fu X

Abstract
The immunosuppressant drug tacrolimus (Tac) used for the prevention of immunological rejection is a metabolic substrate of cytochrome P450 enzymes. This study was designed to evaluate the short-term and long-term potential influence of single-nucleotide polymorphisms (SNPs) in CYP450 genes of liver transplant (LT) recipients as well as the donors on individual pharmacological effects of Tac and to guide individualized-medication from the perspective of pharmacogenomics. Twenty-one SNPs of the CYP450 gene were genotyped for both recipients and donors in 373 LT patients receiving Tac-based immunosuppressants. The Tac concentration/dosage ratio (C/D) was evaluated from the initial medication until one year after LT. The C/D ratio was significantly higher when the donor and/or recipient genotype of CYP3A5 rs776746 was G/G or rs15524 was T/T or rs4646450 was C/C all through one year after transplantation. Comparing the effect of donor gene variants of rs776746, rs15524, and rs4646450 on Tac C/D ratios with the recipients, statistically significant differences were found between the donor T/T group and the recipient T/T group in rs15524 at 1 month and 6 months, and at 6 months, the donor C/C group differed from the recipient C/C group in rs4646450. In conclusion, rs776746, rs15524, and rs4646450 of CYP3A5 had a significant influence on Tac pharmacological effects for both the initial use and long-term use. The donor liver genotype and the recipient intestine genotype contribute almost equally in the short-term, but the donor genotype had a greater effect than the recipient genotype at 6 months. Personalized Tac treatment after LT should be based on the CYP3A5 genotype.

PMID: 29454235 [PubMed - as supplied by publisher]

Nanofibrous PLGA Electrospun Scaffolds Modified with Type I Collagen Influence Hepatocyte Function and Support Viability In Vitro.

PubMed Liver Transplant - Sun, 02/18/2018 - 13:45
Related Articles

Nanofibrous PLGA Electrospun Scaffolds Modified with Type I Collagen Influence Hepatocyte Function and Support Viability In Vitro.

Acta Biomater. 2018 Feb 14;:

Authors: Brown JH, Das P, DiVito MD, Ivancic D, Poh Tan L, Wertheim JA

Abstract
A major challenge of maintaining primary hepatocytes in vitro is progressive loss of hepatocyte-specific functions, such as protein synthesis and cytochrome P450 (CYP450) catalytic activity. We developed a three-dimensional (3D) nanofibrous scaffold made from poly(L-lactide-co-glycolide) (PLGA) polymer using a newlyoptimizedwet electrospinning techniquethat resulted in a highly porous structure that accommodated inclusion of primary human hepatocytes. Extracellular matrix (ECM) proteins (type I collagen or fibronectin) at varying concentrations were chemically linked to electrospun PLGA using amine coupling to develop an in vitro culture system containing the minimal essential ECM components of the liver micro-environment that preserve hepatocyte function in vitro. Cell-laden nanofiber scaffolds were tested in vitro to maintain hepatocyte function over a two-week period. Incorporation of type I collagen onto PLGA scaffolds (PLGA-Chigh: 100 µg/mL) led to 10-fold greater albumin secretion, 4-fold higher urea synthesis, and elevated transcription of hepatocyte-specific CYP450 genes (CYP3A4, 3.5-fold increase and CYP2C9, 3-fold increase) in primary human hepatocytes compared to the same cells grown within unmodified PLGA scaffolds over two weeks. These indices, measured using collagen-bonded scaffolds, were also higher than scaffolds coupled to fibronectin or an ECM control sandwich culture composed of type I collagen and Matrigel. Induction of CYP2C9 activity was also higher in these same type I collagen PLGA scaffolds compared to other ECM-modified or unmodified PLGA constructs and was equivalent to the ECM control at 7 days. Together, we demonstrate a minimalist ECM-based 3D synthetic scaffold that accommodates primary human hepatocyte inclusion into the matrix, maintains long-term in vitro survival and stimulates function, which can be attributed to coupling of type I collagen.
STATEMENT OF SIGNIFICANCE: Culturing primary hepatocytes within a three-dimensional (3D) structure that mimics the natural liver environment is a promising strategy for extending the function and viability of hepatocytes in vitro. In the present study we generate porous PLGA nanofibers, that are chemically modified with extracellular matrix proteins, to serve as 3D scaffolds for the in vitro culture of primary human hepatocytes. Our findings demonstrate that the use of ECM proteins, especially type I collagen, in a porous 3D environment helps to improve the synthetic function of primary hepatocytes over time. We believe the work presented within will provide insights to readers for drug toxicity and tissue engineering applications.

PMID: 29454157 [PubMed - as supplied by publisher]

Quantitative Imaging Features and Postoperative Hepatic Insufficiency: A Multi-Institutional Expanded Cohort.

PubMed Liver Transplant - Sun, 02/18/2018 - 13:45
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Quantitative Imaging Features and Postoperative Hepatic Insufficiency: A Multi-Institutional Expanded Cohort.

J Am Coll Surg. 2018 Feb 14;:

Authors: Pak LM, Chakraborty J, Gonen M, Chapman WC, Do RK, Koerkamp BG, Verhoef K, Lee SY, Massani M, van der Stok EP, Simpson AL, Memorial Sloan Kettering Cancer Center Hepatopancreatobiliary Service

Abstract
BACKGROUND: Post-hepatectomy liver insufficiency (PHLI) is a significant cause of morbidity and mortality after liver resection. Quantitative imaging analysis using CT scans measures variations in pixel intensity related to perfusion. A preliminary study demonstrated a correlation between quantitative imaging features of the future liver remnant (FLR) parenchyma from preoperative CT scans and PHLI. The objective of the present study was to explore the potential application of quantitative imaging analysis in PHLI in an expanded, multi-institutional cohort.
STUDY DESIGN: Patients were retrospectively identified from five high-volume academic centers that developed PHLI after major hepatectomy and were matched to control patients without PHLI (by extent of resection, pre-operative chemotherapy treatment, age (±5 years), and sex). Quantitative imaging features were extracted from the FLR in the preoperative CT scan, and the most discriminatory features were identified using conditional logistic regression. %RLV was defined as follows: (FLR volume)/(total liver volume)x100. Significant clinical and imaging features were combined in a multivariate analysis using conditional logistic regression.
RESULTS: From 2000 to 2015, 74 patients with PHLI and 74 matched controls were identified. The most common indications for surgery were colorectal liver metastases (53%), hepatocellular carcinoma (37%), and cholangiocarcinoma (9%). Two CT imaging features (FD1_4: image complexity; ACM1_10: spatial distribution of pixel intensity) were strongly associated with PHLI and remained associated with PHLI on multivariate analysis (p=0.018 and p=0.023, respectively), independent of clinical variables, including preoperative bilirubin and %RLV.
CONCLUSIONS: Quantitative imaging features are independently associated with PHLI and are a promising preoperative risk stratification tool.

PMID: 29454098 [PubMed - as supplied by publisher]

Recipient characteristics and morbidity and mortality after liver transplantation.

PubMed Liver Transplant - Sun, 02/18/2018 - 13:45
Related Articles

Recipient characteristics and morbidity and mortality after liver transplantation.

J Hepatol. 2018 Feb 14;:

Authors: Asrani SK, Saracino G, O'Leary JG, Gonzales S, Kim P, McKenna G, Klintmalm G, Trotter J

Abstract
BACKGROUND: Over the last decade, liver transplantation of sicker, older non-hepatitis C cirrhotics with multiple co-morbidities has increased in the United States.
METHODS: We sought to identify a parsimonious set of recipient factors among HCV negative adult transplant recipients associated with significant morbidity and mortality within 5 years after liver transplantation using national (n=31,829, 2002-2015) and center specific data. Coefficients of relevant recipient factors were converted to weighted points and scaled from 0-5. Recipient factors associated with graft failure included: ventilator support (5 pts; HR 1.59, 95% CI 1.48-1.72); recipient age >60 years (3 pts; HR 1.29, 95% CI 1.23-1.36); hemodialysis (3 pts; HR 1.26, 95% CI 1.16-1.37); diabetes (2 pts; HR 1.20, 95% CI 1.14-1.27); or serum creatinine ≥1.5mg/dL without hemodialysis (2 pts; HR 1.15, 95% CI 1.09-1.22).
RESULTS: Graft survival within 5 years based on points (any combination) was 77.2% (0-4), 69.1% (5-8) and 57.9% (>8). In recipients with > 8 points, graft survival was 42% (MELD<25) and 50% (MELD 25-35) in recipients receiving donors with donor risk index >1.7. In center specific data within the first year, subjects with ≥ 5 points (vs. 0-4) had longer hospitalization (11 vs. 8 days, p<0.01), higher admissions for rehabilitation (12.3% versus 2.7%, p<0.01), and higher incidence of cardiac disease (14.2% vs. 5.3%, p<0.01) and stage 3 chronic kidney disease (78.6% vs. 39.5%, p=0.03) within 5 years.
CONCLUSION: The impact of co-morbidities in a MELD based organ allocation system needs to be reassessed. The proposed clinical tool may be helpful for center specific assessment of risk of graft failure in non HCV patients and discussion regarding relevant morbidity in selected subsets.
LAY SUMMARY: Over the last decade, liver transplantation of sicker, older patient with multiple co-morbidities has increased. In this study, we show that a set of recipient factors (recipient age>60 years, ventilator status, diabetes, hemodialysis and creatinine>1.5mg/dL) can help identify patients that may not do well after transplant. Transplanting sicker organs in patients with certain combinations of these characteristics further leads to lower survival.

PMID: 29454069 [PubMed - as supplied by publisher]

Living-donor liver transplantation for mild Zellweger spectrum disorder: Up to 17 years follow-up.

PubMed Liver Transplant - Sun, 02/18/2018 - 13:45
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Living-donor liver transplantation for mild Zellweger spectrum disorder: Up to 17 years follow-up.

Pediatr Transplant. 2018 Feb 16;:

Authors: Demaret T, Varma S, Stephenne X, Smets F, Scheers I, Wanders R, Van Maldergem L, Reding R, Sokal E

Abstract
Mild Zellweger spectrum disorder, also described as Infantile Refsum disease, is attributable to mutations in PEX genes. Its clinical course is characterized by progressive hearing and vision loss, and neurodevelopmental regression. Supportive management is currently considered the standard of care, as no treatment has shown clinical benefits. LT was shown to correct levels of circulating toxic metabolites, partly responsible for chronic neurological impairment. Of three patients having undergone LT for mild ZSD, one died after LT, while the other two displayed significant neurodevelopmental improvement on both the long-term (17 years post-LT) and short-term (9 months post-LT) follow-up. We documented a sustained improvement of biochemical functions, with a complete normalization of plasma phytanic, pristanic, and pipecolic acid levels. This was associated with stabilization of hearing and visual functions, and improved neurodevelopmental status, which has enabled the older patient to lead a relatively autonomous lifestyle on the long term. The psychomotor acquisitions have been markedly improved as compared to their affected siblings, who did not undergo LT and exhibited a poor neurological outcome with severe disabilities. We speculate that LT performed before the onset of severe sensorineural defects in mild ZSD enables partial metabolic remission and improved long-term clinical outcomes.

PMID: 29453832 [PubMed - as supplied by publisher]

Proposal for new selection criteria considering pre-transplant muscularity and visceral adiposity in living donor liver transplantation.

PubMed Liver Transplant - Sun, 02/18/2018 - 13:45
Related Articles

Proposal for new selection criteria considering pre-transplant muscularity and visceral adiposity in living donor liver transplantation.

J Cachexia Sarcopenia Muscle. 2018 Feb 17;:

Authors: Hamaguchi Y, Kaido T, Okumura S, Kobayashi A, Shirai H, Yao S, Yagi S, Kamo N, Okajima H, Uemoto S

Abstract
BACKGROUND: The significance of pre-operative body composition has recently attracted much attention in various diseases. However, cut-off values for these parameters remain undetermined, and these factors are not currently included in selection criteria for recipients of living donor liver transplantation (LDLT).
METHODS: Using computed tomography of 657 donors for LDLT, skeletal muscle mass, muscle quality, and visceral adiposity were evaluated by using skeletal muscle mass index (SMI), intramuscular adipose tissue content (IMAC), and visceral-to-subcutaneous adipose tissue area ratio (VSR). Sex-specific cut-offs for SMI, IMAC, and VSR were determined, and correlations with outcomes after LDLT in 277 recipients were examined with the aim of establishing new selection criteria for LDLT.
RESULTS: On the basis of younger donor data, we determined sex-specific cut-off values for low SMI, high IMAC, and high VSR (mean ± 2 standard deviations). Patients with all three factors showed the lowest survival rate after LDLT (1 year survival rate, 41.2%; P < 0.001). On multivariate analysis, low SMI (P = 0.002), high IMAC (P = 0.002), and high VSR (P = 0.001) were identified as independent risk factors for mortality after LDLT. Based on these findings, we have excluded patients showing all three factors (low SMI, high IMAC, and high VSR) as candidates for LDLT since October 2016.
CONCLUSIONS: Using cut-off values determined from healthy donors, we have established new selection criteria for LDLT including body composition, which should improve post-transplant outcomes.

PMID: 29453829 [PubMed - as supplied by publisher]

Unusual spontaneous porto-systemic shunt: The importance of diagnosing non-anatomical porto-systemic shunts to improve portal flow in pediatric living-related liver transplantation. Case report.

PubMed Liver Transplant - Sun, 02/18/2018 - 13:45
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Unusual spontaneous porto-systemic shunt: The importance of diagnosing non-anatomical porto-systemic shunts to improve portal flow in pediatric living-related liver transplantation. Case report.

Pediatr Transplant. 2018 Feb 16;:

Authors: Rubio JS, Rumbo C, Farinelli PA, Aguirre N, Ramisch DA, Paladini H, D Angelo P, Barros Schelotto P, Gondolesi GE

Abstract
Collateral circulation secondary to liver cirrhosis may cause the development of large PSSs that may steal flow from the main portal circulation. It is important to identify these shunts prior to, or during the transplant surgery because they might cause an insufficient portal flow to the implanted graft. There are few reports of "steal flow syndrome" cases in pediatrics, even in biliary atresia patients that may have portal hypoplasia as an associated malformation. We present a 12-month-old female who received an uneventful LDLT from her mother, and the GRWR was 4.8. During the early post-operative period, she became hemodynamically unstable, developed ascites, and altered LFT. The post-operative ultrasound identified reversed portal flow, finding a non-anatomical PSS. A 3D CT scan confirmed the presence of a mesocaval shunt through the territory of the right gonadal vein, draining into the right iliac vein, with no portal inflow into the liver. The patient was re-operated, and the shunt was ligated. An intraoperative Doppler ultrasound showed adequate portal inflow after the procedure; the patient evolved satisfactorily and was discharged home on day number 49. The aim was to report a case of post-operative steal syndrome in a pediatric recipient due to a mesocaval shunt not diagnosed during the pretransplant evaluation.

PMID: 29453782 [PubMed - as supplied by publisher]

Primary sclerosing cholangitis.

PubMed Liver Transplant - Sun, 02/18/2018 - 13:45
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Primary sclerosing cholangitis.

Lancet. 2018 Feb 13;:

Authors: Dyson JK, Beuers U, Jones DEJ, Lohse AW, Hudson M

Abstract
Primary sclerosing cholangitis is a rare, chronic cholestatic liver disease characterised by intrahepatic or extrahepatic stricturing, or both, with bile duct fibrosis. Inflammation and fibrosis of bile ducts and the liver are followed by impaired bile formation or flow and progressive liver dysfunction. Patients might be asymptomatic at presentation or might have pruritus, fatigue, right upper quadrant pain, recurrent cholangitis, or sequelae of portal hypertension. The key diagnostic elements are cholestatic liver biochemistry and bile duct stricturing on cholangiography. Genetic and environmental factors are important in the cause of the disease, with the intestinal microbiome increasingly thought to play a pathogenetic role. Approximately 70% of patients have concurrent inflammatory bowel disease and patients require colonoscopic screening and surveillance. Primary sclerosing cholangitis is associated with increased malignancy risk and surveillance strategies for early cholangiocarcinoma detection are limited. No single drug has been proven to improve transplant-free survival. Liver transplantation is effective for advanced disease but at least 25% of patients develop recurrent disease in the graft.

PMID: 29452711 [PubMed - as supplied by publisher]

Extraordinary disease-free survival in a rare malignant extrarenal rhabdoid tumor: a case report and review of the literature.

PubMed Liver Transplant - Sun, 02/18/2018 - 13:45
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Extraordinary disease-free survival in a rare malignant extrarenal rhabdoid tumor: a case report and review of the literature.

J Med Case Rep. 2018 Feb 17;12(1):39

Authors: D'Amico F, Bertacco A, Cesari M, Mescoli C, Caturegli G, Gondolesi G, Cillo U

Abstract
BACKGROUND: Malignant extrarenal rhabdoid tumor of the gastrointestinal tract is rarely reported in the literature. It is characterized by poor prognosis and aggressive metastatic features. A literature review evidenced only 19 cases, with poor outcome.
CASE PRESENTATION: We report a case of a colonic "pure" malignant extrarenal rhabdoid tumor with metastatic nodes in a 65-year-old Caucasian man. He was treated surgically with no recurrence, no adjuvant chemotherapy, and with 4-year survival without disease at the time of the submission of this article.
CONCLUSIONS: We present an extraordinary case of long-term survival due to the extended surgical treatment. We believe that the absence of organ metastasis at presentation is a positive prognostic factor, although pathology confirmed node involvement (13/38 positive) on microscopy.

PMID: 29452605 [PubMed - in process]

Coronary artery disease in heart transplantation: new concepts for an old disease.

PubMed Heart Transplant - Sun, 02/18/2018 - 13:45
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Coronary artery disease in heart transplantation: new concepts for an old disease.

Transpl Int. 2018 Feb 17;:

Authors: Langstraat M, Musters KJS, Manintveld O, Masetti M, Potena L

Abstract
BACKGROUND: Cardiac allograft vasculopathy (CAV) remains one of the main long-term complications after heart transplantation. We performed a systematic review focused on articles published in the previous 6 years to reappraise the novel evidences supporting risk-factors, pathology, prevention and treatment of CAV.
METHODS: We identified a search string for a literature search on PubMed. We excluded articles specifically focused on diagnosis/biomarkers/imaging only or complications of other diseases.
RESULTS: We included 98 studies out of our search. 48 Articles describe risk factors for CAV, 13 pathology, 24 prevention and 13 treatment of CAV.
DISCUSSION: While confirming known concepts, we found supportive evidence that CAV pathophysiology may vary according to the time post-transplant and the prevalence of metabolic vs. immune-mediated risk factors. Selective revascularization of focal lesions in patients with CAV may result in some clinical benefit, but CAV prevention, rather than treatment, by controlling risk factors and by using targeted immunosuppressive therapies is the most evidence-based approach to reduce disease progression. This article is protected by copyright. All rights reserved.

PMID: 29453887 [PubMed - as supplied by publisher]

Examining the Incidence and Presentation of Melanoma in the Cardiothoracic Transplant Population.

PubMed Heart Transplant - Sun, 02/18/2018 - 13:45
Related Articles

Examining the Incidence and Presentation of Melanoma in the Cardiothoracic Transplant Population.

JAMA Dermatol. 2018 Feb 16;:

Authors: Puza CJ, Cardones AR, Mosca PJ

Abstract
Importance: The immunosuppression vital to maintaining transplanted organs comes with an increased incidence of cutaneous neoplasms. Understanding the genesis of malignant melanoma (MM) in transplant subpopulations is necessary for adequate disease surveillance.
Objective: To determine the incidence and timing of presentation of MM in the cardiothoracic (heart and/or lung) transplant (CTT) population.
Design, Setting, and Participants: This was a retrospective cohort study of 1164 patients who underwent a CTT from 2001 through 2016 with a median follow-up time of 4.3 years. The study was performed at a single academic, tertiary referral center. The retrospective database was used to identify 1164 patients who underwent a CTT at Duke University Hospital from 2001 to 2016. Ten patients were excluded from the study owing to a history of MM, resulting in 1154 patients in the study. Five patients who developed MM after CTT were identified.
Exposures: Exposures included tacrolimus, prednisone, and mycophenolate mofetil.
Main Outcomes and Measures: The primary outcome measurement was the MM incidence. Secondary outcomes included time to diagnosis and survival.
Results: Five of 1154 patients who underwent a CTT (0.4%) developed biopsy-proven MM at a median follow-up time of 4.3 years after transplantation at a median age of 64.5 years (range, 31.0-74.0 years). Of the 1154 patients, 923 (80%) were men. Their mean (SD) age range was 63.8 years (27.2-68.2 years). Four patients (80%) presented with stage I disease while 1 (20%) presented with stage IV disease at a median time of 2.5 years (range, 0.1-5.3 years) after transplant compared with a median time of 6.2 years (range, 0.9-8.7 years) in Duke University's renal transplant population at a median follow-up time of 6.6 years. Two patients died after transplant, 1 owing to complications of the transplant and 1 owing to metastatic MM.
Conclusions and Relevance: Representing one of the largest reported studies of patients with CTT developing MM, our findings suggest that the CTT population experiences an incidence of MM similar to that of other solid organ transplant recipients and with a median of 2.5 years from transplant to melanoma diagnosis. While the small scale of our study prevents far-reaching conclusions, further study is warranted to better understand the incidence, timing, and clinical ramifications of melanomagenesis in the CTT population.

PMID: 29453871 [PubMed - as supplied by publisher]

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