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101.
Alastair Baker Nanda Kerkar Lora Todorova Binita M. Kamath Roderick H.J. Houwen 《Clinics and research in hepatology and gastroenterology》2019,43(1):20-36
Background and aims
Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of rare genetic disorders associated with bile acid secretion or transport defects. This is the first systematic review of the epidemiology, natural history and burden of PFIC.Methods
MEDLINE and Embase were searched for publications on PFIC prevalence, incidence or natural history, and the economic burden or health-related quality of life (HRQoL) of patients with PFIC. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.Results
Of 1269 records screened, 20 were eligible (epidemiology, 17; humanistic burden, 5; both, 2). Incidence of intrahepatic cholestasis, including but not limited to PFIC, was 1/18 000 live births in one study that did not use genetic testing. In two studies of infants and children (2–18 years) with cholestasis, 12–13% had genetically diagnosed PFIC. Of the three main PFIC subtypes, PFIC2 was the most common (21–91% of patients). Common symptoms (e.g. pruritus, jaundice, hepatomegaly, splenomegaly) generally appeared at about 3 months of age and tended to emerge earliest in patients with PFIC2. Patients reported that pruritus was often severe and led to dermal damage and reduced HRQoL. Disease progression led to complications including liver failure and hepatocellular carcinoma, with 20–83% of patients requiring liver transplantation. Mortality was 0–87% across 10 studies (treatment varied among studies), with a median age at death of ~4 years in one study.Conclusions
Patients with PFIC face debilitating symptoms and poor prognosis. Further research is needed to inform patient management and clinical trial design. Published data on the epidemiology and socioeconomic burden of PFIC is limited. 相似文献102.
Bradley Jerson Christine D'Urso Ronen Arnon Tamir Miloh Kishore Iyer Nanda Kerkar Rachel A. Annunziato 《Pediatric transplantation》2013,17(7):612-620
The purpose of this study was to examine the safety, feasibility, acceptability, and preliminary efficacy of a cross‐age peer mentoring program created to improve adherence and psychosocial outcomes for pediatric liver transplant recipients. Twenty‐two participants were assigned to a “mentor now” or “mentor later” waitlist control group. Tacrolimus SD, a validated measure of adherence, was assessed for six months pre‐ and post‐intervention for both groups. Self‐report measures of self‐management and HRQOL were completed at recruitment and three months after training. Participant report indicated the acceptability of the intervention. Clinically significant improvement in adherence was detected. No significant changes on the psychosocial outcome measures at follow‐up were observed. This study demonstrated that an outpatient‐based mentoring program is a safe, feasible, and acceptable option to incorporate within a pediatric liver transplant program with potential for promising application in other transplantation populations as well. These results also suggest that the program may have been associated with meaningful improvement in adherence, although further evaluation is warranted. 相似文献
103.
104.
Nanda Kerkar Steven Cohen Christina Dugan Raffaella A Morotti Robert G Phelps Betsy Herold Benjamin Shneider Sukru Emre 《Liver transplantation》2006,12(11):1705-1710
Coomb's positive autoimmune hemolytic anemia with giant cell hepatitis (GCH) is a rare cause of liver failure and is usually associated with poor prognosis. A child with liver kidney microsomal (LKM) antibody positivity underwent successful liver transplantation for liver failure secondary to GCH with Coomb's positive hemolytic anemia. Autoimmune neutropenia developed ten months after transplant. Four months later, pemphigoid skin lesions developed. The diagnosis of bullous pemphigoid (BP) was made on the basis of skin biopsy, direct and indirect immunofluorescence test results. Treatment was with immunosuppressants - prednisone and azathioprine/rapamycin, with addition of dapsone when lesions persisted. This child is unique in that his liver function and hemolytic anemia appeared to normalize after liver transplant, but neutropenia and BP both thought to be autoimmune in etiology, developed more than a year post-transplant. 相似文献
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106.
107.
Kerkar SP Sanchez-Perez L Yang S Borman ZA Muranski P Ji Y Chinnasamy D Kaiser AD Hinrichs CS Klebanoff CA Scott CD Gattinoni L Morgan RA Rosenberg SA Restifo NP 《Journal of immunotherapy (Hagerstown, Md. : 1997)》2011,34(4):343-352
T-cell receptor (TCR) gene therapy enables for the rapid creation of antigen-specific T cells from mice of any strain and represents a valuable tool for preclinical immunotherapy studies. Here, we describe the superiority of γ-retroviral vectors compared with lentiviral vectors for transduction of murine T cells and surprisingly illustrate robust gene-transfer into phenotypically naive/memory-stem cell like (TN/TSCM; CD62L(hi)/CD44(low)) and central memory (TCM; CD62L(hi)/CD44(hi)) CD8+ T cells using murine stem cell-based γ-retroviral vectors (MSGV1). We created MSGV1 vectors for a major histocompatibility complex-class I-restricted TCR specific for the melanocyte-differentiation antigen, glycoprotein 100 (MSGV1-pmel-1), and a major histocompatibility complex-class II-restricted TCR specific for tyrosinase-related protein-1 (MSGV1-TRP-1), and found that robust gene expression required codon optimization of TCR sequences for the pmel-1 TCR. To test for functionality, we adoptively transferred TCR-engineered T cells into mice bearing B16 melanomas and observed delayed growth of established tumors with pmel-1 TCR engineered CD8+ T cells and significant tumor regression with TRP-1 TCR transduced CD4 T cells. We simultaneously created lentiviral vectors encoding the pmel-1 TCR, but found that these vectors mediated low TCR expression in murine T cells, but robust gene expression in other murine and human cell lines. These results indicate that preclinical murine models of adoptive immunotherapies are more practical using γ-retroviral rather than lentiviral vectors. 相似文献
108.
Fenella Greig Robert Rapaport Genna Klein Gidon Akler Rachel Annunziato Tamir Miloh Ronen Arnon Sander Florman Nanda Kerkar 《Pediatric transplantation》2013,17(1):27-33
Greig F, Rapaport R, Klein G, Akler G, Annunziato R, Miloh T, Arnon R, Florman S, Kerkar N. Characteristics of diabetes after pediatric liver transplant. Abstract: Studies of DALT in pediatric recipients describe incidence and risk factors, but diagnostic criteria varied. This study reports characteristics and course of pediatric DALT by established diabetes criteria. Retrospective chart review of pediatric LT recipients evaluated for hyperglycemia (1/1/1997–12/30/2009) and matched, non‐diabetic controls. DALT: random blood glucose >11.1 mm , ≥2 times, with insulin treatment. DALT diagnosed in 8.0% (24/300) included 7/24 (29.2%) with severe hyperglycemia (>27.7 mm ), ketoacidosis in 2/24 (8.3%). At diagnosis, age was ≥11 yr old in 22/24 (91.7%); body mass was lean (BMIz ?0.2 ± 1.5). Mean blood glucose was 24.6 mm with negative diabetes autoantibodies (19/19) and elevated C‐peptide (2.3 nm ). DALT onset median 5.0 months included 29.1% >12 months. Insulin duration median 4.6 months included 41.7% >6 months. DALT resolved in 83.3% over 4.9 (0.9–9.1) yr. DALT differed from controls by increased preceding rejections, prednisolone dose, tacrolimus level, and triple immunosuppression (all p < 0.01). In conclusion, pediatric DALT occurred in non‐obese adolescents with insulin resistance, distinct from diabetes types 1 or 2. DALT was associated with preceding rejection and increased immunosuppression. Blood glucose monitoring, especially during increased immunosuppression following LT, could allow early diagnosis and reduce morbidity. 相似文献
109.
Kerkar SP Kemp CD Avital I 《HPB : the official journal of the International Hepato Pancreato Biliary Association》2010,12(9):589-596
Background
The 5-year survival of patients receiving standard-of-care chemotherapy for metastatic gastric cancer (MGC) to the liver is <2%. This review examines the published data on liver resections for MGC and analyses the rationale for potentially aggressive surgical management.Methods
A search of the PubMed and Scopus databases was used to identify studies published in English from 1990 to 2009 that reported on 10 or more patients who underwent liver resections for MGC. All available clinicopathologic data were analysed. In particular, we examined longterm survival and the characteristics of individuals surviving for >5 years.Results
Nineteen studies reported on 436 patients. Median 5-year survival was 26.5% (range: 0–60%). Overall, 13.4% (48/358) of patients were alive at 5 years and studies with extended follow-up reported that 4.0% (7/174) of patients survived for >10 years. Overall in-hospital mortality was 3.5% (12/340 patients); however, the median mortality rate across the studies was 0%. No prognostic factor was found to be consistently statistically significant across these small studies.Conclusions
Despite the limitations of any analysis of retrospective data for highly selected groups of patients, it would appear that liver resections combined with systemic therapy for MGC can result in prolonged survival. 相似文献110.