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PurposeTo investigate the use of magnetic resonance elastography (MRE) in the quantitative assessment of pulmonary fibrosis by comparing quantitative shear stiffness measurements of lung parenchyma in patients diagnosed with fibrotic interstitial lung disease (ILD) and healthy controls.Materials and MethodsA 1.5T spin‐echo, echo planar imaging MRE (SE‐EPI MRE) pulse sequence was utilized to assess absolute lung shear stiffness in 15 patients with diagnosed ILD and in 11 healthy controls. Data were collected at residual volume (RV) and total lung capacity (TLC). Spirometry data were obtained immediately prior to scanning. To test for statistical significance between RV and TLC shear stiffness estimates a two‐sample t‐test was performed. To assess variability within individual subject shear stiffness estimates, the intraclass correlation coefficient (ICC) and Krippendorff's alpha were calculated.ResultsPatients with ILD exhibited an average (±1 standard deviation) shear stiffness of 2.74 (±0.896) kPa at TLC and 1.32 (±0.300) kPa at RV. The corresponding values for healthy individuals were 1.33 (±0.195) kPa and 0.849 (±0.250) kPa, respectively. The difference in shear stiffness between RV and TLC was statistically significant (P < 0.001). At TLC, the ICC and alpha values were 0.909 and 0.887, respectively. At RV, the ICC and alpha values were 0.852 and 0.862, respectively.ConclusionIn subjects with known fibrotic interstitial lung disease, parenchymal shear stiffness is increased when compared to normal controls at both RV and TLC, with TLC demonstrating the most significant difference. MRE‐derived parenchymal shear stiffness is a promising new noninvasive imaging‐based biomarker of interstitial lung disease.Level of Evidence: 1Technical Efficacy: Stage 2J. MAGN. RESON. IMAGING 2017;46:365–374

ObjectiveTo explore gout self‐management and associated challenges and solutions in African Americans.MethodsWe conducted semistructured interviews with 35 African American veterans with gout, who received health care at Birmingham or Philadelphia Veterans Affairs (VA) medical centers, had filled urate‐lowering therapy (ULT; most commonly allopurinol) for at least 6 months, and had a ULT medication possession ratio ≥80%. The interview protocol was constructed to explore key concepts related to gout self‐management, including initial diagnosis of gout, beginning medical care for gout, the course of the gout, ULT medication adherence, dietary strategies, comorbidity and side effects, and social support.ResultsThirty‐five African American male veterans with gout who had ≥80% ULT adherence (most commonly, allopurinol) were interviewed at Birmingham (n = 18) or Philadelphia (n = 17) VA medical centers. Mean age was 65 years, mean body mass index was 31.9 kg/m2, 97% had hypertension, 23% had coronary artery disease, and 31% had renal failure. The main themes motivating African American veterans to better gout self‐management were fear of pain, adherence to medications, self‐discipline, lifestyle changes, information gathering, and developing a positive outlook. Birmingham participants more frequently revealed skipping gout medications. More Philadelphia participants discussed lifestyle/diet changes to prevent gout flares, indicated limiting social activities that involved drinking, and sought more information about gout self‐management from health care providers and internet sources.ConclusionIdentified themes, including cultural differences by site, led to the development of a patient‐centered intervention to improve gout self‐management in African American men with gout.

Abstract Background Tube thoracostomy (TT) can be an effective therapy for thoracic pathologies. Ineffective placement of TT is common and associated with significant complications. Complications require additional interventions to repair damaged tissues or replace dysfunctional TT. We hypothesize that complicated TT insertion increases cost to the hospital system. Methods Adult trauma patients requiring TT at a level 1 trauma center (2012–2013) were reviewed. Intraoperative or image‐guided TT placements were excluded. Baseline demographics and TT insertion cost (normalized and assigned by hospital billing records) were recorded. Costs included initial TT equipment, radiographs, and subsequent operative or radiologic intervention to correct TT complications. Complications were categorized using previously validated method. Secondary outcomes included: number of TT inserted, number of chest radiographs performed, and TT dwell time utilizing a standardized TT discontinuation protocol. Results A total of 154 patients with 246 TT were included. Ninety TT (37%) had complication. Complication categories are postremoval ( n = 15, 16.7%), insertional ( n = 13, 14.4%), positional ( n = 62, 68.9%). Overall median complicated TT cost was 9 times greater than uncomplicated TT insertion, p = 0.001. Insertional complications median cost 21 times greater than an uncomplicated, due to operative and radiologic interventions ( p = 0.0001). Positional and postremoval complication rates increased median cost by 3 times compared to uncomplicated TT ( p = 0.03). Operative or radiologic interventions ( n = 10) were performed for organ injury or uncontrolled hemo‐/pneumothorax. Increased dwell time median [IQR] was associated with complicated TT compared to uncomplicated 3 [1–5] versus 2 [1–3], p = 0.01. Conclusion TT is a common procedure. TT complications are often considered benign. However, patients with a complicated TT insertion, especially related to insertional subtypes, have markedly increased hospitalization costs due to need for operative or radiologic repair. Level of evidence Level V—retrospective study. Study type This is a retrospective single‐institution study.

Current treatment regimens for gastric cancer are not adequate. Cancer stem cells (CSCs) may be a key driving factor for growth and metastasis of this tumor type. In contrast to the conventional clonal evolution hypothesis, CSCs can initiate tumor formation, self‐renew, and differentiate into tumor‐propagating cells. Because gastric cancer can originate from CSCs, it is necessary to review current targets of signaling pathways for CSCs in gastric cancer that are being studied in clinical trials. These pathways are known to regulate the self‐renewal and differentiation process in gastric CSCs. A better understanding of the clinical results of trials that target gastric CSCs will lead to better outcomes for patients with gastric cancer. Cancer 2017;123:1303–1312. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society . This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Peak oxygen uptake (peak V ˙ O 2 ) measured by clinical exercise testing is the benchmark for aerobic fitness. Aerobic fitness, estimated from maximal treadmill exercise, is a predictor of mortality in adults. Peak V ˙ O 2 was shown to predict longevity in patients aged 7–35 years with cystic fibrosis over 25 years ago. A surge of exercise studies in young adults with congenital heart disease over the past decade has revealed significant prognostic information. Three years ago, the first clinical trial in children with pulmonary arterial hypertension used peak V ˙ O 2 as an endpoint that likewise delivered clinically relevant data. Cardiopulmonary exercise testing provides clinicians with biomarkers and clinical outcomes, and researchers with novel insights into fundamental biological mechanisms reflecting an integrated physiological response hidden at rest. Momentum from these pioneering observations in multiple disease states should impel clinicians to employ similar methods in other patient populations; e.g., sickle cell disease. Advances in pediatric exercise science will elucidate new pathways that may identify novel biomarkers. Our initial aim of this essay is to highlight the clinical relevance of exercise testing to determine peak V ˙ O 2 , and thereby convince clinicians of its merit, stimulating future clinical investigators to broaden the application of exercise testing in pediatrics.

ObjectiveHuman adipose‐derived mesenchymal stem cells (ADSCs) were used to rehabilitate bone damaged by osteoradionecrosis (ORN) in an established animal model.Study DesignProspective animal study.SettingAcademic department laboratory.Subjects and MethodsAfter institutional review board and Institutional Animal Care and Use Committee approval, 24 athymic nude rats were divided into 5 groups: 4 groups irradiated (20 Gy) by brachytherapy catheter placed at the left hemimandible and 1 mock irradiation control (n = 4). For all groups, ORN was initiated by extraction of the central molar 1 week later. After 28 days, animals (n = 5/group) received injection at the extraction site with saline (SAL), ADSCs, platelet‐rich plasma and collagen (PRP/COL), or ADSCs + PRP/COL. Rats were sacrificed 28 days later and their mandibles harvested for histopathology analysis (osteoblasts, osteoclasts, and fibrosis) and bone volume measurement using 3‐dimensional micro–computed tomography.ResultsAll but 1 rat survived the experiment period (23/24). Radiographic and histological analysis revealed 60% bone loss in the SAL group compared with the nonirradiated control. Injection of ADSCs increased jaw region bone volume by up to 36% (P <. 01). All experimental groups (ADSC, PRP/COL, and ADSC + PRP/COL) showed dramatically decreased osteoclast counts (P <. 001) while injection of PRP/COL with or without ADSCs increased osteoblasts. Increased fibrosis was observed after ADSC injection (P <. 05).ConclusionThe application of human ADSCs to an induced mandibular osteoradionecrosis model in athymic rats results in increased deposition or preservation of bone, demonstrated both histologically and radiographically. This offers an encouraging possible treatment option for translational research in this difficult disease.

We describe a novel technique to minimize total body contrast exposure during endovascular angiography. A patient with severe renal impairment and history of contrast-induced nephropathy was referred for subclavian artery intervention. Angiography and intervention was performed via transfemoral access, while a transradial sheathless-guiding catheter was used to aspirate injected contrast/blood mix from the downstream axillary artery. Semiquantitative analysis indicated approximately 50% of the injected contrast was retrieved. Adaptation of this simple strategy could be considered for selected coronary, lower extremity, and carotid procedures, using contrast removal techniques from the coronary sinus, femoral, and jugular veins.

Significance Antigen recognition by the immune system triggers rapid, specific, and protective responses, which are counterbalanced by inhibitory checkpoints to minimize potentially harmful immunity. The programmed death-1/ programmed death ligand-1 (PD-1/PD-L1) checkpoint is overreactive in cancer patients, curbing antitumor immunity. Whether a failing PD-1/PD-L1 checkpoint contributes to spontaneous autoimmune disease in humans is unknown. Here, we found that in patients with the autoimmune vasculitis giant cell arteritis, antigen-presenting cells provide insufficient negative signaling; unleashing highly activated T cells to infiltrate and damage the walls of large arteries. Thus, immunoinhibitory signals protect large arteries against inflammatory attack and checkpoint activation may be a suitable strategy to treat autoimmune vasculitis.

Abstract Background: Epigenetic disturbances are crucial in cancer initiation, potentially with pleiotropic effects, and may be influenced by the genetic background. Methods: In a subsets (ASSET) meta-analytic approach, we investigated associations of genetic variants related to epigenetic mechanisms with risks of breast, lung, colorectal, ovarian and prostate carcinomas using 51,724 cases and 52,001 controls. False discovery rate–corrected P values (q values &lt; 0.05) were considered statistically significant. Results: Among 162,887 imputed or genotyped variants in 555 candidate genes, SNPs in eight genes were associated with risk of more than one cancer type. For example, variants in BABAM1 were confirmed as a susceptibility locus for squamous cell lung, overall breast, estrogen receptor (ER)–negative breast, and overall prostate, and overall serous ovarian cancer; the most significant variant was rs4808076 [OR = 1.14; 95% confidence interval (CI) = 1.10–1.19; q = 6.87 × 10−5]. DPF1 rs12611084 was inversely associated with ER-negative breast, endometrioid ovarian, and overall and aggressive prostate cancer risk (OR = 0.93; 95% CI = 0.91–0.96; q = 0.005). Variants in L3MBTL3 were associated with colorectal, overall breast, ER-negative breast, clear cell ovarian, and overall and aggressive prostate cancer risk (e.g., rs9388766: OR = 1.06; 95% CI = 1.03–1.08; q = 0.02). Variants in TET2 were significantly associated with overall breast, overall prostate, overall ovarian, and endometrioid ovarian cancer risk, with rs62331150 showing bidirectional effects. Analyses of subpathways did not reveal gene subsets that contributed disproportionately to susceptibility. Conclusions: Functional and correlative studies are now needed to elucidate the potential links between germline genotype, epigenetic function, and cancer etiology. Impact: This approach provides novel insight into possible pleiotropic effects of genes involved in epigenetic processes. Cancer Epidemiol Biomarkers Prev; 26(6); 816–25. ©2017 AACR.