Search

Non‐alcoholic fatty liver disease (NAFLD) is an increasing problem in pediatrics with limited treatment options. We prospectively assessed outcomes in patients managed in a hepatology clinic (HC) alone vs. those managed in combination with a multidisciplinary weight management program (MWMP). We describe each group's readiness to change at the time of NAFLD diagnosis. Patients diagnosed with NAFLD were given a modified Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES) at enrollment (T1) to assess readiness to change. They were then followed at 3–9 months (T2) and at 10–15 months (T3). Linear mixed models were used to evaluate changes in body mass index (BMI), BMI z‐score, and transaminases over time and between the two groups. There were no significant treatment group main effects or treatment × time interactions for our primary end points for HC alone (n = 75) or with MWMP (n = 18). There was a significant main effect for time for BMI z‐score, with BMI z‐scores declining on average by 0.0568 (P = 0.004) from visit to visit. Low SOCRATES subscales scores in HC alone (n = 33) or with MWMP (n = 4) suggested a patient population with low recognition of disease and likelihood of taking steps for change. Patients with obesity and NAFLD had low scores on all three SOCRATES subscales. Despite this, both groups had improvement in BMI z‐score without significant difference between the two treatment groups in other primary end points. Further study is needed to identify the most effective patient selection and treatment strategies for pediatric patients with NAFLD, including pharmacotherapy and surgery. [ABSTRACT FROM AUTHOR]

Background: Variation in IS exists among pediatric liver transplant centers. While individual centers may publish their practice paradigms, current data on practices as a whole are lacking. This study sought to ascertain the IS protocols of pediatric liver transplant centers within the SPLIT to better understand variability and similarities among peer institutions. Methods: A 27‐item questionnaire was developed within the SPLIT Quality Improvement and Clinical Care Committee. The survey collected data regarding center demographics, IS practices, and treatment of acute cellular rejection. Results: Twenty‐eight (64%) SPLIT centers responded with 22 (79%) centers performing more than 10 transplants per year and 17 (61%) following more than 100 post‐transplant recipients. All centers use a written protocol, and 25 (89%) have a dedicated transplant pharmacist/PharmD. Twenty‐five (89%) centers use steroids for induction alone or in combination with thymoglobulin/interleukin‐2 antibodies. All centers use tacrolimus for initial maintenance therapy. Most centers have specialized protocols for ABO‐incompatible transplants, recipients with renal dysfunction, autoimmune liver diseases, and liver tumors. Treatment of rejection varied but was associated with escalation in IS. Conclusion: IS practices among pediatric liver transplant centers are similar including the use of written protocols, pharmacy involvement, steroids for induction, tacrolimus as initial IS, tacrolimus reduction/delay for renal dysfunction, and escalation of IS with rejection severity. However, other IS practices show wide variability including treatment for ABO‐incompatible grafts and presumed rejection. This study serves as a foundation to guide prospective research linking IS practice to outcomes to determine best practice. [ABSTRACT FROM AUTHOR]

Background Lifetime risk of thyroid cancer associated with FAP has been reported as 1-2%. The mean age at diagnosis of thyroid carcinoma in FAP has been reported at 28 years. The aims of this paper are to better understand gene mutations associated with thyroid cancer and refine surveillance recommendations for patients with FAP. Methods We performed a search in Pubmed, Ovid Medline and Embase with the terms ('Thyroid Gland'[Mesh] OR 'Thyroid Neoplasms'[Mesh]) AND 'Adenomatous Polyposis Coli'[Meshdenomatous Polyposis Coli'[Mesh] to identify subjects with thyroid cancer and FAP. As a reference group for APC mutations in the unselected FAP population, we used the UMD-APC database referenced in the Orphanet portal, which includes APC mutation data on 2040 individuals with FAP. Results There were 115 reported cases of thyroid cancer in patients with FAP (95 female: 11 male) with an average age of 29.2 years. Gene mutation testing results were reported in 48 patients. On comparing the prevalence of APC mutation in the population of FAP patients with thyroid cancer and the prevalence of the same mutation in the reference population an increased odds ratio was evident in individuals harboring an APC mutation at codon 1061 (OR: CI 4.1: 1.7-8.9). Analysis of the prevalence of thyroid cancer in individuals with FAP segregated by the region of the gene affected shows an increased risk of thyroid cancer in individuals harboring mutations proximal to codon 512 (OR 2.6, p 0.0099). Conclusions There is increased risk for thyroid cancer in individuals with APC mutations at the 5' end (proximal to codon 528) along with the established high risk group harboring mutation at codon 1061. It is suggested that these patients might benefit from directed surveillance by annual ultrasound from age 18 years onwards. Keywords: Thyroid cancer, Familial adenomatous polyposis, FAP, Adenomatous polyposis gene mutation, APC, Papillary thyroid carcinoma, Author(s): Seth Septer[sup.1] , Voytek Slowik[sup.2] , Ryan Morgan[sup.4] , Hongying Dai[sup.3] and Thomas Attard[sup.1] Introduction Familial Adenomatous Polyposis (FAP) is an autosomal dominant syndrome with a predisposition for colorectal [...]

Autoimmune enteropathy (AIE) is a rare clinical condition characterized by intractable diarrhea of early childhood. While AIE can featureboth simple Mendelian inheritance or a complex multifactorial pattern, the pathogenesis remains unclear in many cases. This is important for providing anaccurate recurrence risk as affected individuals survive until adulthood and have children. Here, we describe a father and son with AIE who had clinicallydistinct courses. Exome sequencing has revealed a novel missense variant, c.2147C>T; (p.Thr716Met) in the signal transducer and activator of transcription3 gene (STAT3) in both the father and son, consistent with autosomal dominant inheritance. STAT3 regulates immune reactions, and mutations in thisgene have previously been associated with autoimmunity and Hyper IgE syndrome, but not AIE. Further studies are needed to assess the functional effectof this variant as it relates to the phenotype. [ABSTRACT FROM AUTHOR]

Background: One of the major issues in the field of acute liver failure (ALF) is the lack of reliable biomarkers that predict outcome. Many cases present with very limited treatment options and prognostic indicators are invaluable. We tested whether leukocyte cell derived chemotaxin 2 can be used as a prognostic biomarker to predict patient survival either alone or in combination with other routine clinical parameters., Methods: Serum samples and associated clinical data from came from two independent sources, the Acute Liver Failure Study Group (ALFSG) registry and the University of Kansas Medical Center. We analyzed a total of 61 cases, each with individual time points collected over a period of 0 to 7 days after hospital admission. Analysis was developed to compare responses in survivors vs. non-survivors., Results: The data indicate that survivors had significantly lower serum levels of leukocyte cell derived chemotaxin 2 compared to non-survivors (P=0.03). Further, it was able to predict patient survival when taken together with either international normalized ratio (INR) alone (71% concordance) or INR and bilirubin (76% concordance) or INR and serum albumin (77% concordance). Furthermore, when we analyzed data for each day, serum Lect2 and INR taken together were able to predict survival at day three after hospital admission with 86.3% concordance., Conclusions: These studies have revealed test batteries consisting of easily available serum tests that are concordant with survival status of ALF patients early during the clinical course., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.