Citations

SummaryBackgroundCoeliac disease (CD), characterised by the presence of villous atrophy (VA) in the small intestine, is associated with increased mortality, but it is unknown if mortality is influenced by mucosal recovery.AimsTo determine whether persistent VA is associated with mortality in CD.MethodsThrough biopsy reports from all pathology departments (n = 28) in Sweden, we identified 7648 individuals with CD (defined as VA) who had undergone a follow‐up biopsy within 5 years following diagnosis. We used Cox regression to examine mortality according to follow‐up biopsy.ResultsThe mean age of CD diagnosis was 28.4; 63% were female; and the median follow‐up after diagnosis was 11.5 years. The overall mortality rate of patients who underwent follow‐up biopsy was lower than that of those who did not undergo follow‐up biopsy (Hazard Ratio 0.88, 95% CI: 0.80–0.96). Of the 7648 patients who underwent follow‐up biopsy, persistent VA was present in 3317 (43%). There were 606 (8%) deaths. Patients with persistent VA were not at increased risk of death compared with those with mucosal healing (HR: 1.01; 95% CI: 0.86–1.19). Mortality was not increased in children with persistent VA (HR: 1.09 95% CI: 0.37–3.16) or adults (HR 1.00 95% CI: 0.85–1.18), including adults older than age 50 years (HR: 0.96 95% CI: 0.80–1.14).ConclusionsPersistent villous atrophy is not associated with increased mortality in coeliac disease. While a follow‐up biopsy will allow detection of refractory disease in symptomatic patients, in the select population of patients who undergo repeat biopsy, persistent villous atrophy is not useful in predicting future mortality.

Background: A breast cancer diagnosis can entail numerous physical and psychosocial challenges. Yoga practice (YP) may contribute to improved well-being for these patients. Primary Study Objective: Investigate feasibility and impact of YP on quality of life (QoL), mood, fatigue, and perceived stress immediately after breast cancer diagnosis. Methods: Thirty women were randomly assigned to a yoga group (YG) or control group (CG) immediately after cancer diagnosis. Setting: Pilot study conducted at an academic medical center breast clinic. Participant(s): Females (N = 30) who received a biopsy-proven breast cancer diagnosis without metastatic disease. Intervention (YG): One individual YP session at baseline, then 2 individual and 8 weekly group sessions followed by weekly gentle yoga at home (DVD). Questionnaires and saliva samples (ie, cortisol) completed at baseline and 12 weeks postdiagnosis. Results: Both groups reported significant improvements in QoL postintervention but with no significant difference between groups. Emotional well-being, mood-related tension-anxiety, depression-dejection, and confusion-bewilderment scores improved for both groups, and cortisol and cortisone levels decreased. Lumpectomies were prevalent with YG (67%) and CG (47%). YP was rated as “very effective,” providing relaxation (85%), stress relief (69%), and reduced muscle tension/general feeling of wellness (each 62%). Conclusion: Feasibility of YP immediately after breast cancer diagnosis was good. Improvement in emotional well-being, anxiety, depression, and levels of confusion was found in both groups. To our knowledge, this is the first study examining the impact of YP immediately after breast cancer diagnosis. Further research in this area is warranted.

Menopausal hormone treatment (MHT) may limit progression of cardiovascular disease (CVD) but poses a thrombosis risk. To test targeted candidate gene variation for association with subclinical CVD defined by carotid artery intima-media thickness (CIMT) and coronary artery calcification (CAC), 610 women participating in the Kronos Early Estrogen Prevention Study (KEEPS), a clinical trial of MHT to prevent progression of CVD, were genotyped for 13,229 single nucleotide polymorphisms (SNPs) within 764 genes from anticoagulant, procoagulant, fibrinolytic, or innate immunity pathways. According to linear regression, proportion of European ancestry correlated negatively, but age at enrollment and pulse pressure correlated positively with CIMT. Adjusting for these variables, two SNPs, one on chromosome 2 for MAP4K4 gene (rs2236935, β = 0.037, P value = 2.36 × 10−06) and one on chromosome 5 for IL5 gene (rs739318, β = 0.051, P value = 5.02 × 10−05), associated positively with CIMT; two SNPs on chromosome 17 for CCL5 (rs4796119, β = −0.043, P value = 3.59 × 10−05; rs2291299, β = −0.032, P value = 5.59 × 10−05) correlated negatively with CIMT; only rs2236935 remained significant after correcting for multiple testing. Using logistic regression, when we adjusted for waist circumference, two SNPs (rs11465886, IRAK2, chromosome 3, OR = 3.91, P value = 1.10 × 10−04; and rs17751769, SERPINA1, chromosome 14, OR = 1.96, P value = 2.42 × 10−04) associated positively with a CAC score of >0 Agatston unit; one SNP (rs630014, ABO, OR = 0.51, P value = 2.51 × 10−04) associated negatively; none remained significant after correcting for multiple testing. Whether these SNPs associate with CIMT and CAC in women randomized to MHT remains to be determined.

Background— Giant cell myocarditis (GCM) typically causes fulminant heart failure, arrhythmias, or heart block, necessitating aggressive immunosuppression, ventricular assist device insertion, or cardiac transplantation. We describe a novel variant of GCM, primarily involving the atria, that displays distinctive clinical features and follows a more benign course than ventricular GCM. Methods and Results— We identified 6 patients (median age 67.5 years, 4 male) with atrial GCM in our pathology consultation practices from 2010 to 2012. Clinical history, imaging, and pathology materials were reviewed. Clinically, 4 patients had atrial fibrillation, 1 had acute heart failure, and 1 had incidental disease at autopsy. Among the 5 living patients, echocardiography revealed severe atrial dilatation (5 cases), mitral/tricuspid regurgitation (5), atrial mural thrombus (3), atrial wall thickening (2), and atrial hypokinesis (2). Ventricular function was preserved in all 5. Histological review of surgically resected atria showed giant cell and lymphocytic infiltrates, lymphocytic myocarditis-like foci, cardiomyocyte necrosis, and cardiomyocyte hypertrophy in all cases. Other features included interstitial fibrosis (5), poorly-formed granulomas (4), eosinophils (4), neutrophils (1), and vasculitis (1). Treatment consisted of steroids and cyclosporine (1), pacemaker placement for sick sinus syndrome (1), and supportive care (3). All 5 living patients returned to baseline exercise tolerance after 6 to 16 weeks of follow-up. Conclusions— Atrial GCM represents a distinct clinicopathologic entity with a more favorable prognosis than classic ventricular GCM. This disorder should be included in the differential diagnosis of atrial dilatation, particularly when associated with atrial wall thickening. The utility of immunomodulatory therapy for this condition remains unknown.

Abstract Diffuse idiopathic skeletal hyperostosis (DISH) is a noninflammatory spondyloarthropathy, characterized by ectopic calcification of spinal tissues. Symptoms include spine pain and stiffness, and in severe cases dysphagia and spinal cord compression. The etiology of DISH is unknown and there are no specific treatments. Recent studies have suggested a role for purine metabolism in the regulation of biomineralization. Equilibrative nucleoside transporter 1 (ENT1) transfers hydrophilic nucleosides, such as adenosine, across the plasma membrane. In mice lacking ENT1, we observed the development of calcified lesions resembling DISH. By 12 months of age, ENT1–/– mice exhibited signs of spine stiffness, hind limb dysfunction, and paralysis. Micro–computed tomography (µCT) revealed ectopic mineralization of paraspinal tissues in the cervical-thoracic region at 2 months of age, which extended to the lumbar and caudal regions with advancing age. Energy-dispersive X-ray microanalysis of lesions revealed a high content of calcium and phosphorus with a ratio similar to that of cortical bone. At 12 months of age, histological examination of ENT1–/– mice revealed large, irregular accumulations of eosinophilic material in paraspinal ligaments and entheses, intervertebral discs, and sternocostal articulations. There was no evidence of mineralization in appendicular joints or blood vessels, indicating specificity for the axial skeleton. Plasma adenosine levels were significantly greater in ENT1–/– mice than in wild-type, consistent with loss of ENT1—a primary adenosine uptake pathway. There was a significant reduction in the expression of Enpp1, Ank, and Alpl in intervertebral discs from ENT1–/– mice compared to wild-type mice. Elevated plasma levels of inorganic pyrophosphate in ENT1–/– mice indicated generalized disruption of pyrophosphate homeostasis. This is the first report of a role for ENT1 in regulating the calcification of soft tissues. Moreover, ENT1–/– mice may be a useful model for investigating pathogenesis and evaluating therapeutics for the prevention of mineralization in DISH and related disorders. © 2013 American Society for Bone and Mineral Research.

Background. Acute kidney injury (AKI) is a frequent complication of critically ill patients. The impact of different risk factors associated with this entity in the ICU setting is unknown.Objectives. The purpose of this research was to assess the risk factors associated with the development of AKI in critically ill patients by meta-analyses of observational studies.Data Extraction. Two reviewers independently and in duplicate used a standardized form to collect data from published reports. Authors were contacted for missing data. The Newcastle-Ottawa scale assessed study quality.Data Synthesis. Data from 31 diverse studies that enrolled 504,535 critically ill individuals from a wide variety of ICUs were included. Separate random-effects meta-analyses demonstrated a significantly increased risk of AKI with older age, diabetes, hypertension, higher baseline creatinine, heart failure, sepsis/systemic inflammatory response syndrome, use of nephrotoxic drugs, higher severity of disease scores, use of vasopressors/inotropes, high risk surgery, emergency surgery, use of intra-aortic balloon pump, and longer time in cardiopulmonary bypass pump.Conclusion. The best available evidence suggests an association of AKI with 13 different risk factors in subjects admitted to the ICU. Predictive models for identification of high risk individuals for developing AKI in all types of ICU are required.

The development of pharmacologic agents for the prevention of breast cancer is a significant milestone in medical and laboratory research. Despite these advances, the endorsement of preventive options has become challenging and complex, as physicians are expected to counsel and tailor their recommendations using a personalized approach taking into account medical comorbidities, degree of risk and patient preferences. This article provides a comprehensive overview of the major breast cancer prevention trials, review of the pharmacologic options available for breast cancer prevention, and strategies for integrating chemoprevention of breast cancer in high-risk women into clinical practice.