Colitis Following Initiation of Sofosbuvir and Simeprevir for Genotype 1 Hepatitis C.

Sofosbuvir and simeprevir are used for the treatment of chronic hepatitis C (HCV) genotype 1. Both drugs have been well-tolerated, with diarrhea noted in 6% cases with sofosbuvir, 16% with sofosbuvir plus simeprevir, and 0% with simeprevir. No prior reports exist of colitis secondary to either drug or their combination. We report a patient with no prior history of inflammatory bowel disease who developed significant bloody diarrhea within 2 weeks of sofosbuvir/simeprevir initiation. Colonoscopy and biopsy confirmed pancolitis, which responded to mesalamine and completion of sofosbuvir/simeprevir

Contiguous Deletion of the X-Linked Adrenoleukodystrophy Gene (ABCD1) and DXS1357E: A Novel Neonatal Phenotype Similar to Peroxisomal Biogenesis Disorders

X-linked adrenoleukodystrophy (X-ALD) results from mutations in ABCD1. ABCD1 resides on Xq28 and encodes an integral peroxisomal membrane protein (ALD protein [ALDP]) that is of unknown function and that belongs to the ATP-binding cassette–transporter superfamily. Individuals with ABCD1 mutations accumulate very-long-chain fatty acids (VLCFA) (carbon length >22). Childhood cerebral X-ALD is the most devastating form of the disease. These children have the earliest onset (age 7.2 ± 1.7 years) among the clinical phenotypes for ABCD1 mutations, but onset does not occur at <3 years of age. Individuals with either peroxisomal biogenesis disorders (PBD) or single-enzyme deficiencies (SED) in the peroxisomal β-oxidation pathway—disorders such as acyl CoA oxidase deficiency and bifunctional protein deficiency—also accumulate VLCFA, but they present during the neonatal period. Until now, it has been possible to distinguish unequivocally between individuals with these autosomal recessively inherited syndromes and individuals with ABCD1 mutations, on the basis of the clinical presentation and measurement of other biochemical markers. We have identified three newborn boys who had clinical symptoms and initial biochemical results consistent with PBD or SED. In further study, however, we showed that they lacked ALDP, and we identified deletions that extended into the promoter region of ABCD1 and the neighboring gene, DXS1357E. Mutations in DXS1357E and the ABCD1 promoter region have not been described previously. We propose that the term “contiguous ABCD1 DXS1357E deletion syndrome” (CADDS) be used to identify this new contiguous-gene syndrome. The three patients with CADDS who are described here have important implications for genetic counseling, because individuals with CADDS may previously have been misdiagnosed as having an autosomal recessive PBD or SE

Cancer and Leukemia Group B Pathology Committee Guidelines for Tissue Microarray Construction Representing Multicenter Prospective Clinical Trial Tissues

Practice-changing evidence requires confirmation, preferably in multi-institutional clinical trials. The collection of tissue within such trials has enabled biomarker studies and evaluation of companion diagnostic tests. Tissue microarrays (TMAs) have become a standard approach in many cooperative oncology groups. A principal goal is to maximize the number of assays with this precious tissue. However, production strategies for these arrays have not been standardized, possibly decreasing the value of the study. In this article, members of the Cancer and Leukemia Group B Pathology Committee relay our experiences as array facility directors and propose guidelines regarding the production of high-quality TMAs for cooperative group studies. We also discuss statistical issues arising from having a proportion of patients available for TMAs and the possibility that patients with TMAs fail to represent the greater study population