Citations

Objective: We aim to identify the spectrum of etiologies of steatosis in pediatric liver biopsies. Methods: Information was collected from 155 children with steatosis on liver biopsy, including anthropometrics, laboratory, and radiologic data. Biopsies were reviewed by a liver pathologist. Results: The 4 major diagnoses associated with hepatic steatosis were nonalcoholic fatty liver disease (37%), metabolic disease (9%), oncologic disease (8%) and viral hepatitis (7%). Patients with nonalcoholic fatty liver disease were older ( P = .0001) and more likely to have a body mass index z score >2 ( P < .0001). Patients with a metabolic diagnosis were younger ( P = .0002). Radiologic imaging of the liver yielded normal results in 44 of 108 of children (30%); 7 of these had >66% macrovesicular fatty change on biopsy, and 3 had severe fibrosis/cirrhosis. Conclusions: The range of causes of steatosis in pediatric liver biopsies is broad. Not all patients, even with advanced liver disease, had abnormalities with liver imaging, emphasizing the role for liver biopsy in certain cases.

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.

We report a case of sinonasal phosphaturic mesenchymal tumor (PMT) and conduct a systematic review of the literature to highlight a unique paraneoplastic syndrome associated with PMT. We used English language publications from Medline and Cochrane databases (1970–2013) as data sources. A systematic review of the literature was conducted. All reported cases of head and neck PMTs were included. The presence or absence of the associated paraneoplastic syndrome was noted. We found 33 cases of PMT in the head and neck reported in the literature, 17 of which occurred in the sinonasal area. Approximately 5% of all PMTs are located in the head and neck. Just greater than half are concentrated in the sinonasal area, and the remaining involve various bony and soft tissue structures of the head and neck. PMT is sometimes associated with a paraneoplastic syndrome of tumor-induced (oncogenic) osteomalacia (TIO) causing bone pain, muscle weakness, and pathologic fractures. We present the 18th reported case of sinonasal PMT. A smooth mucosa-covered midline intraseptal mass filling the posterior nasal cavity with destruction and erosion of the skull base was found in an adult male. The patient underwent successful endoscopic resection with wide negative margins and is without recurrence at 24-month follow-up. PMT is a benign, locally aggressive tumor with rare malignant transformation. Knowledge of the bony invasion and destruction caused by this tumor is essential in planning surgical resection with wide negative margins. Familiarity with the associated TIO is essential to investigate for and manage any associated bony morbidity.

AbstractBackgroundLate‐onset Alzheimer's disease (AD) is heritable with 20 genes showing genome‐wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis.MethodsThe ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain.ResultsALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 × 10−12 after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 × 10−11), cholesterol transport (P = 2.96 × 10−9), and proteasome‐ubiquitin activity (P = 1.34 × 10−6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002–.05).ConclusionsThe immune response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.

Significance Long noncoding RNAs (lncRNAs) are involved in numerous biological roles including epigenetic regulation, apoptosis, and cell cycle. Whereas lncRNAs contribute to epigenetic gene regulation, metastasis, and prognosis in solid tumors, their role in acute myeloid leukemia (AML) has not been hitherto reported. Here, we show that lncRNA expression profiles are associated with recurrent mutations, clinical features, and outcome in AML. A fraction of these lncRNAs may have a functional role in leukemogenesis. Furthermore, lncRNAs could be used as biomarkers for outcome in AML. The identification of patients likely to achieve complete remission with standard therapy alone, based on lncRNA expression, is a significant advance potentially sparing such patients from other toxicities and focusing investigational approaches on postremission studies.

Background: As heart failure often follows an unpredictable clinical trajectory, there has been an impetus to promote iterative patient-provider discussions regarding prognosis and preferences for end-of-life care. Aim: To examine clinicians’ practices, expectations, and personal level of confidence in discussing goals of care and providing end-of-life care to their patients with heart failure. Design: Multi-site clinician survey. Setting and Participants: Physicians, nurse practitioners, and physician assistants at Mayo Clinic (Rochester, Minnesota, USA) and its surrounding health system were asked to participate in an electronic survey in October 2013. Tertiary Care Cardiology, Community Cardiology, and Primary Care clinicians were surveyed. Results: A total of 95 clinicians participated (52.5% response rate). Only 12% of clinicians reported having annual end-of-life discussions as advocated by the American Heart Association. In total, 52% of clinicians hesitated to discuss end-of-life care citing provider discomfort (11%), perception of patient (21%) or family (12%) unreadiness, fear of destroying hope (9%), or lack of time (8%). Tertiary and Community Cardiology clinicians (66%) attributed responsibility for end-of-life discussions to the heart failure cardiologist, while 66% of Primary Care clinicians felt it was their responsibility. Overall, 30% of clinicians reported a low or very low level of confidence in one or more of the following: initiating prognosis or end-of-life discussions, enrolling patients in hospice, or providing end-of-life care. Most clinicians expressed interest in further skills acquisition. Conclusion: Clinicians vary in their views and approaches to end-of-life discussions and care. Some lack confidence and most are interested in further skills acquisition.