Anchored multiplex PCR for targeted next-generation sequencing reveals recurrent and novel USP6 fusions and upregulation of USP6 expression in aneurysmal bone cyst.

Primary aneurysmal bone cyst (ABC) is a neoplastic process due to recurrent translocations involving the USP6 gene. By fluorescence in situ hybridization, up to 69% of primary ABCs harbored USP6 translocations; no USP6 translocation was found in secondary ABC or giant cell tumor of bone (GCT). GCT can recur locally, metastasize to the lungs in some cases, and rarely undergo malignant transformation. Differentiating primary ABC from its mimics is important for treatment and prognosis. We evaluated USP6 fusion and expression in 13 cases of primary and 1 case of secondary ABC, and 9 cases of GCT using nucleic acid extracted from formalin-fixed, paraffin-embedded tissue and a next generation sequencing (NGS)-based assay. USP6 fusions including 7 novel fusions and USP6 transcripts were identified in all 13 primary ABCs. Nine cases with strong evidence of fusions showed high levels of USP6 transcripts by reverse transcription-PCR (RT-PCR). The remaining four had no detectable USP6 expression by a first-round of RT-PCR but the presence of USP6 transcripts was identified by a second-round, nested PCR. The major fusions were confirmed by RT-PCR followed by Sanger sequencing. No USP6 fusion or transcript was detected in any of the GCTs or the case of secondary ABC by NGS or by two rounds of PCR. All USP6 translocations resulted in fusion of the entire USP6 coding sequence with promoters of the fusion gene leading to upregulation of USP6 transcription, which is likely the underlying mechanism for ABC oncogenesis. © 2016 Wiley Periodicals, Inc.

Challenges and opportunities in creating a deprescribing program in the emergency department: A qualitative study.

BACKGROUND: As the population of older adults increases, appropriate deprescribing becomes increasingly important for emergency geriatric care. Older adults represent the sickest patients with chronic medical conditions, and they are often exposed to high-risk medications. We need to provide an evidence-based, standardized deprescribing program in the acute care setting, yet the evidence base is lacking and standardized medication programs are needed. METHODS: We conducted a qualitative study with the goal to understand the perspective of healthcare workers, patients, and caregivers on deprescribing high-risk medications in the context of emergency care practices, provider preferences, and practice variability, along with the facilitators and barriers to an effective deprescribing program in the emergency department (ED). To ensure rich, contextual data, the study utilized two qualitative methods: (1) a focus group with physicians, advanced practice providers, nurses, pharmacists, and geriatricians involved in care of older adults and their prescriptions in the acute care setting; (2) semi-structured interviews with patients and caregivers involved in treatment and emergency care. Transcriptions were coded using thematic content analysis, and the principal investigator (S.L.) and trained research staff categorized each code into themes. RESULTS: Data collection from a focus group with healthcare workers (n = 8) and semi-structured interviews with patients and caregivers (n = 20) provided evidence of a potentially promising ED medication program, aligned with the vision of comprehensive care of older adults, that can be used to evaluate practices and develop interventions. We identified four themes: (1) Challenges in medication history taking, (2) missed opportunities in identifying high-risk medications, (3) facilitators and barriers to deprescribing recommendations, and (4) how to coordinate deprescribing recommendations. CONCLUSIONS: Our focus group and semi-structured interviews resulted in a framework for an ED medication program to screen, identify, and deprescribe high-risk medications for older adults and coordinate their care with primary care providers.