Low-Dose Naltrexone for Pruritus in Systemic Sclerosis

Pruritus is a common symptom in systemic sclerosis (SSc), an autoimmune disease which causes fibrosis and vasculopathy in skin, lung, and gastrointestinal tract (GIT). Unfortunately, pruritus has limited treatment options in this disease. Pilot trials of low-dose naltrexone hydrochloride (LDN) for pruritus, pain, and quality of life (QOL) in other GIT diseases have been successful. In this case series we report three patients that had significant improvement in pruritus and total GIT symptoms as measured by the 10-point faces scale and the University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 (UCLA SCTC GIT 2.0) questionnaire. This small case series suggests LDN may be an effective, highly tolerable, and inexpensive treatment for pruritus and GIT symptoms in SSc

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Treatment and chemoprevention of NSAID-associated gastrointestinal complications

Edward J Frech1,2, Mae F Go1,21GI Section, George E Wahlen Department of Veterans Affairs Medical Center; 2Division of Gastroenterology, University of Utah School of Medicine, Salt Lake City, Utah, USAAbstract: The use of non-steroidal anti-inflammatory drugs has become ubiquitous worldwide and remains a common source of gastrointestinal morbidity. Antisecretory medications, particularly proton pump inhibitors, are effective in the treatment and prevention of NSAID-related gastrointestinal complications, including peptic ulcer disease and non-ulcer dyspepsia. A careful assessment of patients’ risk factors for developing NSAID-related gastrointestinal complications should be undertaken prior to initiation of any NSAIDs. Patients who are considered at risk for developing gastrointestinal complications should receive concurrent antisecretory medical therapy to minimize the risk for GI complications.Keywords: NSAIDs, peptic ulcer disease, gastrointestinal prophylaxi

Generation of a core set of items to develop classification criteria for Scleroderma renal crisis using consensus methodology

Objective: To generate a core set of items to develop classification criteria for scleroderma renal crisis (SRC) using consensus methodology. Methods: An international, multidisciplinary panel of experts was invited to participate in a 3-round Delphi exercise developed using a survey based on items identified by a scoping review. In round 1, participants were asked to identify omissions and clarify ambiguities regarding the items in the survey. In round 2, participants were asked to rate the validity and feasibility of the items using Likert-type scales ranging from 1 to 9 (where 1 = very invalid/unfeasible, 5 = uncertain, and 9 = very valid/feasible). In round 3, participants reviewed the results and comments from round 2 and were asked to provide final ratings. Items rated as highly valid and feasible (median scores ≥7 for each) in round 3 were selected as the provisional core set of items. A consensus meeting using a nominal group technique was conducted to further reduce the core set of items. Results: Ninety-nine experts from 16 countries participated in the Delphi exercise. Of the 31 items in the survey, consensus was achieved on 13, in the categories hypertension, renal insufficiency, proteinuria, and hemolysis. Eleven experts took part in the nominal group technique discussion, where consensus was achieved in 5 domains: blood pressure, acute kidney injury, microangiopathic hemolytic anemia, target organ dysfunction, and renal histopathology. Conclusion: A core set of items that characterize SRC was identified using consensus methodology. This core set will be used in future data-driven phases of this project to develop classification criteria for SRC. © 2019, American College of Rheumatolog

Perspectives on Strengthening Cancer Research and Control in Latin America Through Partnerships and Diplomacy: Experience of the National Cancer Institute’s Center for Global Health

According to the Pan American Health Organization, noncommunicable diseases, including cancer, are the leading causes of preventable and premature death in the Americas. Governments and health care systems in Latin America face numerous challenges as a result of increasing morbidity and mortality from cancer. Multiple international organizations have recognized the need for collaborative action on and technical support for cancer research and control in Latin America. The Center for Global Health at the US National Cancer Institute (NCI-CGH) is one entity among many that are working in the region and has sought to develop a strategy for working in Latin America that draws on and expands the collaborative potential of engaged, skilled, and diverse partners. NCI-CGH has worked toward developing and implementing initiatives in collaboration with global partners that share the common objectives of building a global cancer research community and translating research results into evidence-informed policy and practice. Both objectives are complementary and synergistic and are additionally supported by an overarching strategic framework that is focused on partnerships and science diplomacy. This work highlights the overall strategy for NCI-CGH engagement in Latin America through partnerships and diplomacy, and highlights selected collaborative efforts that are aimed at improving cancer outcomes in the region