Bone marrow failure and developmental delay caused by mutations in poly(A)-specific ribonuclease (PARN).

Background: Deadenylation regulates RNA function and fate. Poly(A)-specific ribonuclease (PARN) is a deadenylase that processes mRNAs and non-coding RNA. Little is known about the biological significance of germline mutations in PARN.

Serum microRNA profiling to distinguish papillary thyroid cancer from benign thyroid masses.

Objectives: Papillary thyroid cancer (PTC) is increasing in incidence. Fine needle aspiration is the gold standard for diagnosis, but results can be indeterminate. Identifying tissue and serum biomarkers, like microRNA, is therefore desirable.

Renal function in patients with Wilms tumor.

Survival in patients with Wilms tumor (WT) is excellent compared with other pediatric malignancies and adult renal tumors. Treatment-related long-term morbidity and mortality in WT survivors is an area of increasing concern. Renal dysfunction is an example of one of the most feared long-term issues observed in these survivors.

Development of an internationally agreed minimal dataset for juvenile dermatomyositis (JDM) for clinical and research use.

Background: Juvenile dermatomyositis (JDM) is a rare autoimmune inflammatory disorder associated with significant morbidity and mortality. International collaboration is necessary to better understand the pathogenesis of the disease, response to treatment and long-term outcome. To aid international collaboration, it is essential to have a core set of data that all researchers and clinicians collect in a standardised way for clinical purposes and for research.

Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma.

Background: Elotuzumab, an immunostimulatory monoclonal antibody targeting signaling lymphocytic activation molecule F7 (SLAMF7), showed activity in combination with lenalidomide and dexamethasone in a phase 1b-2 study in patients with relapsed or refractory multiple myeloma.

Methods: In this phase 3 study, we randomly assigned patients to receive either elotuzumab plus lenalidomide and dexamethasone (elotuzumab group) or lenalidomide and dexamethasone alone (control group). Coprimary end points were progression-free survival and the overall response rate.

The Role of Metacognitive Reading Strategies, Metacognitive Study and Learning Strategies, and Behavioral Study and Learning Strategies in Predicting Academic Success in Students With and Without a History of Reading Difficulties.

We examined the self-reported use of reading, study, and learning strategies in university students with a history of reading difficulties (HRD; n = 77) and with no history of reading difficulties (NRD; n = 295). We examined both between-groups differences in strategy use and strategy use as a predictive measure of academic success. Participants completed online questionnaires regarding reading history and strategy use.

The risk and nature of flares in juvenile idiopathic arthritis: results from the ReACCh-Out cohort.

Objective: To describe probabilities and characteristics of disease flares in children with juvenile idiopathic arthritis (JIA) and to identify clinical features associated with an increased risk of flare.

Methods: We studied children in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) prospective inception cohort. A flare was defined as a recurrence of disease manifestations after attaining inactive disease and was called significant if it required intensification of treatment.

Effects of Adjuvant Sorafenib and Sunitinib on Cardiac Function in Renal Cell Carcinoma Patients without Overt Metastases: Results from ASSURE, ECOG 2805.

Purpose: Sunitinib and sorafenib are used widely in the treatment of renal cell carcinoma (RCC). These agents are associated with a significant incidence of cardiovascular (CV) dysfunction and left ventricular ejection fraction (LVEF) declines, observed largely in the metastatic setting. However, in the adjuvant population, the CV effects of these agents remain unknown.

Surgical treatment and reconstruction of nonmelanoma facial skin cancers.

Learning Objectives: After reading this article, the participant should be able to: (1) Identify the appropriate resection margins for common types of nonmelanoma skin cancer. (2) Discuss indications for secondary intention healing, skin grafting, and local flaps for reconstruction of facial skin cancer defects. (3) Describe at least one local flap for reconstruction of scalp, forehead, temple/cheek, periocular, nose, and lips.

Impact of the 2013 American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing of invasive breast carcinoma: a focus on tumours assessed as 'equivocal' for HER2 gene amplification by fluorescence in-situ hybridization.

Aims: The updated 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) human epidermal growth factor receptor 2 (HER2) testing guidelines include changes to HER2 in-situ hybridization (ISH) interpretation criteria. We conducted a retrospective review of a consecutive cohort of primary breast carcinomas to assess the impact of updated guidelines on HER2 classification and laboratory resource utilization, and to characterize the pathobiology of HER2 equivocal tumours.

Methods And Results: A total of 904 dual-probe HER2/chromosome enumeration probe (CEP17) FISH tests on invasive breast carcinomas were studied.

Ileitis associated with Meckel's diverticulum.

Aims: Histological features of chronic active ileitis in the small intestine neighbouring a Meckel's diverticulum raise the possibility of concurrent Crohn's disease. Several studies have reported a significant association between Meckel's diverticulum and Crohn's disease, whereas some case reports have proposed that the ileitis is attributable to acid-secreting gastric heterotopia. The aim of this study was to evaluate the incidence, histomorphology and clinical follow-up of Meckel's diverticulum-associated ileitis.

Gemcitabine/dexamethasone/cisplatin vs cytarabine/dexamethasone/cisplatin for relapsed or refractory aggressive-histology lymphoma: cost-utility analysis of NCIC CTG LY.12.

Background: The NCIC CTG LY.12 study showed that gemcitabine, dexamethasone, and cisplatin (GDP) were noninferior to dexamethasone, cytarabine, and cisplatin (DHAP) in patients with relapsed or refractory aggressive histology lymphoma prior to autologous stem cell transplantation. We conducted an economic evaluation from the perspective of the Canadian public healthcare system based on trial data.

Cutaneous manifestations of angioimmunoblastic T-cell lymphoma: clinical and pathological characteristics.

Angioimmunoblastic T-cell lymphoma (AITL), an uncommon variant of peripheral T-cell lymphoma, affects the skin in approximately 50% of cases. Its protean clinical and histopathological cutaneous manifestations pose a challenge in diagnosis, particularly when these precede the diagnosis of AITL on a lymph node biopsy. In this retrospective study, we compared 11 cases of AITL with cutaneous manifestations (mean age 67 years; male:female ratio 1:0.

Mood Disorders in Systemic Lupus Erythematosus: Results From an International Inception Cohort Study.

Objective: To examine the frequency, characteristics, and outcome of mood disorders, as well as clinical and autoantibody associations, in a multiethnic/racial, prospective inception cohort of patients with systemic lupus erythematosus (SLE).

Methods: Patients were assessed annually for mood disorders (4 types, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) and 18 other neuropsychiatric events. Global disease activity scores (SLE Disease Activity Index 2000 [SLEDAI-2K]), damage scores (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI]), and Short Form 36 subscales, mental and physical component summary scores were collected.

Exit competencies in pathology and laboratory medicine for graduating medical students: the Canadian approach.

Physicians in every medical and surgical field must be able to use pathology concepts and skills in their practice: for example, they must order and interpret the correct laboratory tests, they must use their understanding of pathogenesis to diagnose and treat, and they must work with the laboratory to care for their patients. These important concepts and skills may be ignored by medical schools and even national/international organizations setting graduation expectations for medical students. There is an evolving international consensus about the importance of exit competencies for medical school graduates, which define the measurable or observable behaviors each graduate must be able to demonstrate.

Generalized Multinucleate Cell Angiohistiocytoma.

Background: There are less than 100 cases of multinucleate cell angiohistiocytoma (MCA) currently reported in the literature. It occurs as a localized, asymptomatic, benign proliferation of the skin, characterized histologically by irregular multinucleate cells. Due to its novelty, the etiology of the disease and treatment options are still under investigation.

Adolescent immunization - Protecting youth and preparing them for a healthy future.

Adolescence is a period of profound biological, physical, intellectual and neuro-cognitive growth and development, during which new social roles and responsibilities are acquired. Vaccination has the potential to avert acute and chronic illness during this period and to decrease the risk of illness, disability, and cancer in adult life. Here, the vaccines recommended for adolescents are reviewed, and the essential role of health care providers in providing education to adolescents about immunization is highlighted.

Plasma pro-surfactant protein B and lung function decline in smokers.

Plasma pro-surfactant protein B (pro-SFTPB) levels have recently been shown to predict the development of lung cancer in current and ex-smokers, but the ability of pro-SFTPB to predict measures of chronic obstructive pulmonary disease (COPD) severity is unknown. We evaluated the performance characteristics of pro-SFTPB as a biomarker of lung function decline in a population of current and ex-smokers. Plasma pro-SFTPB levels were measured in 2503 current and ex-smokers enrolled in the Pan-Canadian Early Detection of Lung Cancer Study.

Outcomes of invasive meningococcal disease in adults and children in Canada between 2002 and 2011: a prospective cohort study.

Background: Neisseria meningitidis causes 500 000 cases of septicemia and meningitis worldwide annually, with approximately 200 cases in Canada each year. Previous studies describe a case-fatality rate of 5%-15% and up to 20% of survivors suffering from long-term disability.

Methods: This study was performed in Canada between 2002 and 2011; the study area included >50% of the country's population.