Sarcoidosis presenting as granulomatous myositis in a 16-year-old adolescent

BACKGROUND: Sarcoidosis is a multi-system disease characterized by the presence of non-caseating epithelioid granulomas in affected tissues, including skeletal muscle. These organized collections of immune cells have important pathophysiologic action including cytokine production leading to inflammation as well as enzymatic conversion of cholecalciferol to calcitriol via 1-α hydroxylase. There are limited reports of isolated granulomatous myositis causing hypercalcemia in pediatric patients. Our patient uniquely presented with symptoms from hypercalcemia and renal insufficiency caused by an overwhelming burden of granulomatous myositis in her lower extremities, but was otherwise asymptomatic. CASE PRESENTATION: A 16 year old Caucasian female presented with protracted symptoms of fatigue, nausea and prominent weight loss with laboratory evidence of hypercalcemia and renal insufficiency. She lacked clinical and physical findings of arthritis, weakness, rash, uveitis, fever, lymphadenopathy or respiratory symptoms. After extensive negative investigations, re-examination yielded subtle soft tissue changes in her lower extremities, with striking MRI findings of extensive myositis without correlative weakness or serum enzyme elevation. Biopsy showed the presence of non-caseating epithelioid granulomas and calcium oxalate crystals. The patient responded well to prednisone and methotrexate but relapsed with weaning of steroids. She reachieved remission with addition of adalimumab. CONCLUSIONS: Sarcoidosis should be considered in patients presenting with symptomatic hypercalcemia with no apparent causes and negative routine workup. The absences of decreased muscle strength or elevated muscle enzymes do not preclude the diagnosis of granulomatous myositis

Uncertainty as a Key Influence in the Decision To Admit Patients with Transient Ischemic Attack

Background Patients with transient ischemic attacks (TIA) are at high risk of subsequent vascular events. Hospitalization improves quality of care, yet admission rates for TIA patients vary considerably. Objectives We sought to identify factors associated with the decision to admit patents with TIA. Design We conducted a secondary analysis of a prior study’s data including semi-structured interviews, administrative data, and chart review. Participants We interviewed multidisciplinary clinical staff involved with TIA care. Administrative data included information for TIA patients in emergency departments or inpatient settings at VA medical centers (VAMCs) for fiscal years (FY) 2011 and 2014. Chart reviews were conducted on a subset of patients from 12 VAMCs in FY 2011. Approach For the qualitative data, we focused on interviewees’ responses to the prompt: “Tell me what influences you in the decision to or not to admit TIA patients.” We used administrative data to identify admission rates and chart review data to identify ABCD2 scores (a tool to classify stroke risk after TIA). Key Results Providers’ decisions to admit TIA patients were related to uncertainty in several domains: lack of a facility TIA-specific policy, inconsistent use of ABCD2 score, and concerns about facilities’ ability to complete a timely workup. There was a disconnect between staff perceptions about TIA admission and facility admission rates. According to chart review data, staff at facilities with higher admission rates in FY 2011 reported consistent reliance on ABCD2 scores and related guidelines in admission decision-making. Conclusions Many factors contributed to decisions regarding admitting a patient with TIA; however, clinicians’ uncertainty appeared to be a key driver. Further quality improvement interventions for TIA care should focus on facility adoption of TIA protocols to address uncertainty in TIA admission decision-making and to standardize timely evaluation of TIA patients and delivery of secondary prevention strategies

Ribonucleoprotein Purification and Characterization Using RNA Mango

The characterization of RNA–protein complexes (RNPs) is a difficult but increasingly important problem in modern biology. By combining the compact RNA Mango aptamer with a fluorogenic thiazole orange desthiobiotin (TO1-Dtb or TO3-Dtb) ligand, we have created an RNA tagging system that simplifies the purification and subsequent characterization of endogenous RNPs. Mango-tagged RNP complexes can be immobilized on a streptavidin solid support and recovered in their native state by the addition of free biotin. Furthermore, Mango-based RNP purification can be adapted to different scales of RNP isolation ranging from pull-down assays to the isolation of large amounts of biochemically defined cellular RNPs. We have incorporated the Mango aptamer into the S. cerevisiae U1 small nuclear RNA (snRNA), shown that the Mango-snRNA is functional in cells, and used the aptamer to pull down a U1 snRNA-associated protein. To demonstrate large-scale isolation of RNPs, we purified and characterized bacterial RNA polymerase holoenzyme (HE) in complex with a Mango-containing 6S RNA. We were able to use the combination of a red-shifted TO3-Dtb ligand and eGFP-tagged HE to follow the binding and release of the 6S RNA by two-color native gel analysis as well as by single-molecule fluorescence cross-correlation spectroscopy. Together these experiments demonstrate how the Mango aptamer in conjunction with simple derivatives of its flurophore ligands enables the purification and characterization of endogenous cellular RNPs in vitro