Citations

Abstract A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of “heterozygote advantage” regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06–1.60; OR MZL = 1.45, 95% CI = 1.12–1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24–3.55; OR MZL = 2.10, 95% CI = 0.99–4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes. Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma. Cancer Res; 78(14); 4086–96. ©2018 AACR.

Background In addition to its fundamental functions in mediating the survival, proliferation, and migration of keratinocytes, increasing evidence suggests that the amphiregulin-epidermal growth factor receptor pathway has a major impact on cutaneous inflammation. Transgenic expression of amphiregulin in the epidermis of mice induces skin pathology with striking phenotypic similarity to that of psoriasis. Prominent T-cell and dendritic cell infiltrates are observed in the lesional skin from these mice. Objective In this study, we aimed to identify more fully the effect of amphiregulin on keratinocytes and T cells during cutaneous inflammation through examining relevant cytokines in the lesional skin as well as in human keratinocyte culture. Methods Using a multicytokine enzyme-linked immunosorbent assay, we found that amphiregulin directly induces the production of monocyte chemoattractant protein-1, interleukin-α, and interleukin-8 from keratinocytes in vitro. In addition, we examined the cutaneous expression of T-cell cytokines in amphiregulin transgenic mice compared with wild-type mice using quantitative polymerase chain reaction, which demonstrated upregulation of interferon-γ, vascular endothelial growth factor, and interleukin-4 in amphiregulin transgenic mice. Results and Conclusion Our study suggested that amphiregulin in the epidermis not only induces keratinocyte proliferation but also induces T-cell activation through a complex circuit of proinflammatory cytokines. Elucidating the role of amphiregulin on the generation, interactions, and balance among T-cell subsets will advance the understanding of psoriasis pathogenesis.

Abstract The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician/advanced practice provider and the microbiologists who provide enormous value to the healthcare team. This document, developed by experts in laboratory and adult and pediatric clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. This document presents a system-based approach rather than specimen-based approach, and includes bloodstream and cardiovascular system infections, central nervous system infections, ocular infections, soft tissue infections of the head and neck, upper and lower respiratory infections, infections of the gastrointestinal tract, intra-abdominal infections, bone and joint infections, urinary tract infections, genital infections, and other skin and soft tissue infections; or into etiologic agent groups, including arthropod-borne infections, viral syndromes, and blood and tissue parasite infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also emphasized. There is intentional redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a guidance for physicians in choosing tests that will aid them to quickly and accurately diagnose infectious diseases in their patients.

INTRODUCTION: Obesity is associated with postnatal depression; however, the prevalence of postnatal depression in women after bariatric surgery has not been further evaluated. METHODS: For this observational investigation, women, ages 18-45 years, with pregnancy from 1989-2015 and bariatric surgery were identified using the Olmsted County Rochester Epidemiology Project and ICD-9 codes. Those with surgery after pregnancy and/or without permission to use their records were excluded. Charts were reviewed for maternal and infant characteristics and outcomes. Postnatal depression was identified from a positive screen, referral for mood disorder, antidepressant medication increase, suicidality, or provider diagnosis from delivery to 12 months postpartum. RESULTS: Ninety-one women with pregnancy >23 weeks after surgery and available data were reviewed. The average body mass index at time of surgery was 47±8.6 kg/m2 (N=88) and at time of pregnancy 32±6.6 kg/m2 (N=89). The average age at surgery was 29±4.1 years and at delivery 33±4.4 years. Roux-en-Y gastric bypass was the most common surgery (N=70, 77%). Pregnancy outcomes included: 14% preterm deliveries (<37 weeks, N=13), 67% vaginal deliveries (N=61), no stillbirths, and 97% singleton deliveries (N=88). Mean singleton birthweight was 3225 grams (±471, N=86). Postnatal depression was noted in 38% of women (N=35), which is significantly higher than that for obese women in general (13-18%) when a 1-sample proportion test is conducted for comparison (38%vs18%, p <0.0001). CONCLUSION: Postnatal depression may be increased in women with a history of bariatric surgery. Further investigation is needed, but particular care should be taken to screen and diagnose these high-risk women.

Summary Ketogenic dietary therapies ( KDTs ) are established, effective nonpharmacologic treatments for intractable childhood epilepsy. For many years KDTs were implemented differently throughout the world due to lack of consistent protocols. In 2009, an expert consensus guideline for the management of children on KDT was published, focusing on topics of patient selection, pre‐ KDT counseling and evaluation, diet choice and attributes, implementation, supplementation, follow‐up, side events, and KDT discontinuation. It has been helpful in outlining a state‐of‐the‐art protocol, standardizing KDT for multicenter clinical trials, and identifying areas of controversy and uncertainty for future research. Now one decade later, the organizers and authors of this guideline present a revised version with additional authors, in order to include recent research, especially regarding other dietary treatments, clarifying indications for use, side effects during initiation and ongoing use, value of supplements, and methods of KDT discontinuation. In addition, authors completed a survey of their institution's practices, which was compared to responses from the original consensus survey, to show trends in management over the last 10 years.

Key Points PRS, based on the known CLL loci, predicts CLL risk with high discrimination. This PRS predicts risk of monoclonal B-cell lymphocytosis, a precursor to CLL and a condition that has clinical impact beyond risk for CLL.

ObjectiveDue to an aging population, increasing prevalence of rheumatic disease, and a growing supply and demand gap of rheumatology providers, innovative solutions are needed to meet the needs of persons with rheumatic conditions. Nurse practitioners (NPs) and physician assistants (PAs) have been identified as a group of health professionals who could help address the workforce shortage. The Executive Committee of the Association of Rheumatology Health Professionals (ARHP), a division of the American College of Rheumatology (ACR), charged a task force to facilitate the preparation of NPs/PAs to work in a rheumatology practice setting.MethodsThe task force, consisting of private practice and academic rheumatologists, and NPs and PAs, from both adult and pediatric settings, conducted a needs assessment survey of current NPs and PAs to identify mechanisms for acquiring rheumatology knowledge. Through face‐to‐face and webinar meetings, and incorporating stakeholder feedback, the task force designed a rheumatology curriculum outline to enrich the training of new NPs and PAs joining rheumatology practice.ResultsInformed by the needs assessment data and stakeholders, an NP/PA rheumatology curriculum outline was developed and endorsed by the ACR Board of Directors for use by community‐based and academic rheumatology practices, whether pediatric or adult, who desire to add NPs and PAs to their practice setting.ConclusionAs rheumatology is facing workforce shortages, the ACR/ARHP rheumatology curriculum outline can be utilized to train NPs and PAs and create more efficient integration of NPs and PAs into rheumatology practice.

Background Primary prevention implantable cardioverter‐defibrillators (ICDs) reduce mortality in selected patients with left ventricular systolic dysfunction by delivering therapies (antitachycardia pacing or shocks) to terminate potentially lethal arrhythmias; inappropriate therapies also occur. We assessed device therapies among adults receiving primary prevention ICDs in 7 healthcare systems. Methods and Results We linked medical record data, adjudicated device therapies, and the National Cardiovascular Data Registry ICD Registry. Survival analysis evaluated therapy probability and predictors after ICD implant from 2006 to 2009, with attention to Centers for Medicare and Medicaid Services Coverage With Evidence Development subgroups: left ventricular ejection fraction, 31% to 35%; nonischemic cardiomyopathy <9 months’ duration; and New York Heart Association class IV heart failure with cardiac resynchronization therapy defibrillator. Among 2540 patients, 35% were <65 years old, 26% were women, and 59% were white. During 27 (median) months, 738 (29%) received ≥1 therapy. Three‐year therapy risk was 36% (appropriate, 24%; inappropriate, 12%). Appropriate therapy was more common in men (adjusted hazard ratio [HR], 1.84; 95% confidence interval [CI], 1.43–2.35). Inappropriate therapy was more common in patients with atrial fibrillation (adjusted HR, 2.20; 95% CI, 1.68–2.87), but less common among patients ≥65 years old versus younger (adjusted HR, 0.72; 95% CI, 0.54–0.95) and in recent implants (eg, in 2009 versus 2006; adjusted HR, 0.66; 95% CI, 0.46–0.95). In Centers for Medicare and Medicaid Services Coverage With Evidence Development analysis, inappropriate therapy was less common with cardiac resynchronization therapy defibrillator versus single chamber (adjusted HR, 0.55; 95% CI, 0.36–0.84); therapy risk did not otherwise differ for Centers for Medicare and Medicaid Services Coverage With Evidence Development subgroups. Conclusions In this community cohort of primary prevention patients receiving ICD, therapy delivery varied across demographic and clinical characteristics, but did not differ meaningfully for Centers for Medicare and Medicaid Services Coverage With Evidence Development subgroups.