Citations

Abstract Marginal zone lymphomas (MZL) are a group of indolent non-Hodgkin's B-cell lymphomas (NHL) comprising extranodal MZL of mucosa-associated lymphoid tissue (MALT) type, splenic MZL and nodal MZL. MZL comprises 7-12% of adult NHLs. The genetic etiology of MZL is poorly understood. To better understand the genetic risk factors for MZL, we conducted the first genome-wide association study (GWAS) of this lymphoid malignancy. The GWAS included 824 MZL cases and 6,220 controls of European ancestry from 22 studies of NHL. Genotyping was carried out at the Cancer Genomics Research Laboratory (CGR) of NCI using Illumina Human OmniExpress arrays. Standard genotyping quality controls were performed. Imputation of common SNPs was performed using IMPUTE2 software and 1000 Genomes Project release version 3 data. Association testing was subsequently performed using SNPTEST, assuming a log-additive genetic model adjusting for age, gender and three significant eigenvectors. We identified one locus at 6p21.32 within the HLA class II region that attained genome-wide significance (P<5x10-8). When a small number of additional cases (n=58) and controls (n=66) genotyped using Taqman assays were included, rs9461741 (BTNL2) was associated with an increased risk of MZL (per-allele odds ratio = 2.38, 95% confidence interval: 1.74-3.24; P=4.32x10-8). Other SNPs at the 6p21.32 locus were also highly associated with MZL, suggesting that this is unlikely to be a chance finding. Promising signals yet to be confirmed were also observed on chromosomes 3 and 14. The BTNL2 protein has extracellular immunoglobulin domains and is expressed in multiple tissues including various immune organs and the gut and it inhibits T-cell activation. Genetic variability at BTNL2 has been associated with inflammatory and infectious phenotypes, highlighting the importance of this locus for immune diseases. In conclusion, findings from this GWAS identify the HLA class II region as an important susceptibility locus for MZL. Citation Format: Joseph Vijai, Zhaoming Wang, Sonja I. Berndt, Susan L. Slager, James R. Cerhan, Christine Skibola, Sophia S. Wang, Angela R. Brooks-Wilson, Silvia de Sanjose, Paige M. Bracci, Mads Melbye, Bengt Glimelius, Rebecca D. Jackson, Wendy Cozen, Nikolaus Becker, Lauren R. Teras, John J. Spinelli, Jenny Turner, Qing Lan, Mark P. Purdue, Kimberly A. Bertrand, Kenneth Offit, Paolo Vineis, Brian K. Link, Graham G. Giles, Anne Zelenuich-Jacquotte, Alain Monnereau, Maria Grazia Ennas, Demetrius Albanes, Laurie Burdett, Nathaniel Rothman, Stephen J. Chanock, Alexandra Nieters, On behalf of the NHL GWAS Consortium. A genome-wide association study suggests evidence of variants at 6p21.32 associated with marginal zone lymphoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5071. doi:10.1158/1538-7445.AM2014-5071

Child-health research initiative enables rapid response to opportunities for participation in multicenter pediatric clinical trials.

BACKGROUNDThe current study was performed to determine whether patient characteristics, including race/ethnicity, were associated with patient‐reported care coordination for patients with colorectal cancer (CRC) who were treated in the Veterans Affairs (VA) health care system, with the goal of better understanding potential goals of quality improvement efforts aimed at improving coordination.METHODSThe nationwide Cancer Care Assessment and Responsive Evaluation Studies survey involved VA patients with CRC who were diagnosed in 2008 (response rate, 67%). The survey included a 4‐item scale of patient‐reported frequency (“never,” “sometimes,” “usually,” and “always”) of care coordination activities (scale score range, 1‐4). Among 913 patients with CRC who provided information regarding care coordination, demographics, and symptoms, multivariable logistic regression was used to examine odds of patients reporting optimal care coordination.RESULTSVA patients with CRC were found to report high levels of care coordination (mean scale score, 3.50 [standard deviation, 0.61]). Approximately 85% of patients reported a high level of coordination, including the 43% reporting optimal/highest‐level coordination. There was no difference observed in the odds of reporting optimal coordination by race/ethnicity. Patients with early‐stage disease (odds ratio [OR], 0.60; 95% confidence interval [95% CI], 0.45‐0.81), greater pain (OR, 0.97 for a 1‐point increase in pain scale; 95% CI, 0.96‐0.99), and greater levels of depression (OR, 0.97 for a 1‐point increase in depression scale; 95% CI, 0.96‐0.99) were less likely to report optimal coordination.CONCLUSIONSPatients with CRC in the VA reported high levels of care coordination. Unlike what has been reported in settings outside the VA, there appears to be no racial/ethnic disparity in reported coordination. However, challenges remain in ensuring coordination of care for patients with less advanced disease and a high symptom burden. Cancer 2015;121:2207–2213. © 2015 American Cancer Society.

A 29-year-old male patient with a functioning pituitary macroadenoma is discussed. The pituitary mass was detected by MRI after the patient presented with sudden onset of headache, suggestive of an apoplectic event. The headache resolved with analgesic medications. Within a follow-up period of one week, the pituitary mass had spontaneously regressed to nearly half its original size without any therapy. The patient never reported any visual complaints and displayed no signs of hypopituitarism. Elevated prolactin levels were present. Seven weeks after the initial event, the pituitary mass showed continued regression on MRI. Prolactin levels remained elevated. This case provides a unique look at the rapid spontaneous regression of mass effect that may occur following apoplexy of a pituitary adenoma.

Objective The aim of this study was to define health care providers’ perceptions toward prone patient positioning for spine surgery using the Jackson Table, which has not been hitherto explored. Methods We analyzed open-ended questionnaire data and interviews conducted with the spine surgical team regarding the current process of spinal positioning/repositioning using the Jackson Table. Participants were asked to provide an open-ended explanation as to whether they think the current process of spinal positioning/repositioning is safe for the staff or patients. Follow-up qualitative interviews were conducted with 11 of the participants to gain an in-depth understanding of the challenges and safety issues related to prone patient positioning. Results Data analysis resulted in 6 main categories: general challenges with patient positioning, role-specific challenges, challenges with the Jackson Table and the “sandwich” mechanism, safety concerns for patients, safety concerns for the medical staff, and recommendations for best practices. Conclusions This study is relevant to everyday practice for spinal surgical team members and advances our understanding of how surgical teams qualitatively view the current process of patient positioning for spinal surgery. Providers recommended best practices for using the Jackson Table, which can be achieved through standardized practice for transfer of patients, educational tools, and checklists for equipment before patient transfer and positioning. This research has identified several important practice opportunities for improving provider and patient safety in spine surgery.

Aims and ObjectivesThis paper explores patients' perspectives on infection prevention and control.BackgroundHealthcare‐associated infections are the most frequent adverse event experienced by patients. Reduction strategies have predominantly addressed front‐line clinicians' practices; patients' roles have been less explored.DesignVideo‐reflexive ethnography.MethodsFieldwork undertaken at a large metropolitan hospital in Australia involved 300 hours of ethnographic observations, including 11 hours of video footage. This paper focuses on eight occasions, where video footage was shown back to patients in one‐on‐one reflexive sessions.FindingsViewing and discussing video footage of clinical care enabled patients to become articulate about infection risks, and to identify their own roles in reducing transmission. Barriers to detailed understandings of preventative practices and their roles included lack of conversation between patients and clinicians about infection prevention and control, and being ignored or contradicted when challenging perceived suboptimal practice. It became evident that to compensate for clinicians' lack of engagement around infection control, participants had developed a range of strategies, of variable effectiveness, to protect themselves and others. Finally, the reflexive process engendered closer scrutiny and a more critical attitude to infection control that increased patients' sense of agency.ConclusionThis study found that patients actively contribute to their own safety. Their success, however, depends on the quality of patient–provider relationships and conversations. Rather than treating patients as passive recipients of infection control practices, clinicians can support and engage with patients' contributions towards achieving safer care.Relevance to clinical practiceThis study suggests that if clinicians seek to reduce infection rates, they must start to consider patients as active contributors to infection control. Clinicians can engage patients in conversations about practices and pay attention to patient feedback about infection risk. This will broaden clinicians' understandings of infection control risks and behaviours, and assist them to support appropriate patient self‐care behaviour.

AbstractGuanine‐adenine‐thymine‐adenine 2 (GATA2) mutated disorders include the recently described MonoMAC syndrome (Monocytopenia and Mycobacterium avium complex infections), DCML (dendritic cell, monocyte, and lymphocyte deficiency), familial MDS/AML (myelodysplastic syndrome/acute myeloid leukemia) (myeloid neoplasms), congenital neutropenia, congenital lymphedema (Emberger's syndrome), sensorineural deafness, viral warts, and a spectrum of aggressive infections seen across all age groups. While considerable efforts have been made to identify the mutations that characterize this disorder, pathogenesis remains a work in progress with less than 100 patients described in current literature. Varying clinical presentations offer diagnostic challenges. Allogeneic stem cell transplant remains the treatment of choice. Morbidity, mortality, and social costs due to the familial nature of the disease are considerable. We describe our experience with the disorder in three affected families and a comprehensive review of current literature.

Background and Purpose— The relationships between cerebrovascular lesions visible on imaging and cognition are complex. We explored the possibility that the cerebral cortical volume mediated these relationships. Methods— Total of 1906 nondemented participants (59% women; 25% African–American; mean age, 76.6 years) in the Atherosclerosis Risk in Communities (ARIC) study underwent cognitive assessments, risk factor assessments, and quantitative MRI for white matter hyperintensities (WMH) and infarcts. The Freesurfer imaging analysis pipeline was used to determine regional cerebral volumes. We examined the associations of cognitive domain outcomes with cerebral volumes (hippocampus and separate groups of posterior and frontal cortical regions of interest) and cerebrovascular imaging features (presence of large or small cortical/subcortical infarcts and WMH volume). We performed mediation pathway analyses to assess the hypothesis that hippocampal and cortical volumes mediated the associations between cerebrovascular imaging features and cognition. Results— In unmediated analyses, WMH and infarcts were both associated with worse psychomotor speed/executive function. In mediation analyses, WMH and infarct associations on psychomotor speed/executive function were significantly attenuated, but not abolished, by the inclusion of the posterior cortical regions of interest volume in the models, and the infarcts on psychomotor speed/executive function association were attenuated, but not abolished, by inclusion of the frontal cortical regions of interest volume. Conclusions— Both WMH and infarcts were associated with cortical volume, and both lesions were also associated with cognitive performance, implying shared pathophysiological mechanisms. Although cross-sectional, our findings suggest that WMH and infarcts could be proxies for clinically covert processes that directly damage cortical regions. Microinfarcts are 1 candidate for such a clinically covert process.

Dynamic QT Interval Monitoring Post‐LCSDBackgroundVideoscopic left cardiac sympathetic denervation (LCSD) is an adjunct therapy for reduction of arrhythmia‐induced events in patients with long‐QT syndrome (LQTS). LCSD reduces LQTS‐triggered breakthrough cardiac events. The temporal effects of QTc changes post‐LCSD have not been studied.MethodsWe utilized continuous QTc monitoring on 72 patients with LQTS. We evaluated acute and long‐term QTc changes in comparison to 12‐lead ECG‐derived QTc values prior to surgery, 24 hours postsurgery, and at follow up ≥3 months.ResultsSeventy‐two patients underwent LCSD at our institution (46% male, mean age at LCSD was 14 ± 10 years). The mean baseline, pre‐LCSD QTc was 505 ± 56 ms, which had decreased significantly at ≥3 months post‐LCSD to 491 ± 40 ms (P = 0.001). QTc monitoring revealed that the majority of the cohort (53/72; 74%) had a transient increase >30 ms in QTc from baseline, with an average maximum increase of 72 ± 30 ms. Resolution within 10 ms of baseline or less occurred in 57% (30/53) at 24 hours post‐LCSD.ConclusionsAlthough LQTS patients may have a paradoxically increased QTc post‐LCSD, the effects are transient in most patients. Importantly, no patients experienced any arrhythmias in the postoperative setting related to this transient rise in QTc.