Citations

ABSTRACT Developing novel approaches to treat skeletal disorders requires an understanding of how critical molecular factors regulate osteoblast differentiation and bone remodeling. We have reported that (1) retinoic acid receptor-related orphan receptor beta (Rorβ) is upregulated in bone samples isolated from aged mice and humans in vivo; (2) Rorβ expression is inhibited during osteoblastic differentiation in vitro; and (3) genetic deletion of Rorβ in mice results in preservation of bone mass during aging. These data establish that Rorβ inhibits osteogenesis and that strict control of Rorβ expression is essential for bone homeostasis. Because microRNAs (miRNAs) are known to play important roles in the regulation of gene expression in bone, we explored whether a predicted subset of nine miRNAs regulates Rorβ expression during both osteoblast differentiation and aging. Mouse osteoblastic cells were differentiated in vitro and assayed for Rorβ and miRNA expression. As Rorβ levels declined with differentiation, the expression of many of these miRNAs, including miR-219a-5p, was increased. We further demonstrated that miR-219a-5p was decreased in bone samples from old (24-month) mice, as compared with young (6-month) mice, concomitant with increased Rorβ expression. Importantly, we also found that miR-219a-5p expression was decreased in aged human bone biopsies compared with young controls, demonstrating that this phenomenon also occurs in aging bone in humans. Inhibition of miR-219a-5p in mouse calvarial osteoblasts led to increased Rorβ expression and decreased alkaline phosphatase expression and activity, whereas a miR-219a-5p mimic decreased Rorβ expression and increased osteogenic activity. Finally, we demonstrated that miR-219a-5p physically interacts with Rorβ mRNA in osteoblasts, defining Rorβ as a true molecular target of miR-219a-5p. Overall, our findings demonstrate that miR-219a-5p is involved in the regulation of Rorβ in both mouse and human bone. © 2018 American Society for Bone and Mineral Research.

11559 Background: Paraneoplastic neurologic disease (PND) is an aberrant immune-mediated response against the nervous system triggered by occult malignancy. Given the rarity of this disease, a paucity of data exists describing breast cancer (BC)-related PND; thus, we sought to further examine this specific population of patients. Methods: Using an institution specific clinical search tool, we identified all patients at our institution from 1997-2016 with a diagnosis of BC-related PND, verified by an international expert. Retrospective review was used to record tumor and treatment factors associated with PND and BC. A descriptive analysis was performed of the characteristics associated with BC-related PND. Results: BC-related PND was diagnosed in 58 female patients. Average age at BC diagnosis was 54.0±10.3 years. Most had invasive cancer of Stage II or higher [Stage 0 (10.3%), I (10.3%), II (44.8%), III (13.8%), IV (6.9%), unknown (13.8%)]. Most patients were hormone receptor (HR)+ (63.8%), while 4 (6.9%) were HR-, and 17 (29.3%) were unknown. Of the 34 patients where Her2/neu (Her2) data was available, 7 (20.6%) were Her2+ and 27 (79.4%) were Her2-. The majority (62.1%) had neurological symptoms prior to BC, 5.2% were concurrent, and 32.7% developed PND after initial BC. The interquartile range for time from PND to BC diagnosis was -8.5 to 10.5 months. Of the 58 patients, 29 (50%) had autoantibodies detected: Purkinje Cell Cytoplasmic Autoantibody Type-1 (PCA-1[anti-Yo]) (10), amphiphysin-IgG (n = 9), Anti-Neuronal Nuclear Autoantibody Type-2 (ANNA-2[anti-Ri]) (n = 5), and other (n = 5). The most common syndromes were cerebellar ataxia (n = 14), myelopathy (n = 11), and myopathy (n = 11). Immunotherapy was used for PND in 53 of 58 (91.4%) patients; benefit from immunotherapy was assessed as complete 0 (0%), robust 11 (20.8%), mild to moderate 28 (52.8%), none 9 (17%), and indeterminate 5 (9.4%). Conclusions: BC-related PND is rare, with only 58 cases over 20 years at a large academic institution. Paraneoplastic symptoms often present prior to BC diagnosis and BC characteristics are typical of the general population. Over 75% of patients benefit from immunotherapy. These data may provide helpful information to providers treating this population of patients.

6512 Background: Cancer patients are nearly 3x more likely to declare bankruptcy than people without cancer. However, little is known about the dynamics of the healthcare provider/patient (pt) conversations around cost issues, the range of topics explored, and the factors that may influence them. We reviewed audio recordings of a cross-section of medical oncology conversations to determine frequency, patterns and attitudes of pts and providers on cost. Methods: We audio recorded conversations between 5/3/2012 & 11/20/2013 for adult patients with any solid tumor malignancy seen in an outpatient medical oncology clinic at one of three sites in the Upper Midwest and Southern California. Basic demographic variables were abstracted from chart review. Recordings were de-identified, reviewed and flagged for any mention of cost. We used descriptive statistics and inductive qualitative content coding methods to further characterize conversation themes. Results: Among 525 recordings, 151 (28%) contained any mention of cost. Median age (range) of pts was 58 years (22-93), and 75% Caucasian, 18% Hispanic, 5% Asian, and 1% Black. Average length of cost discussions was < 2 minutes, and pts usually initiated the discussion (106 /151). Among the 151 conversations, social service referrals were mentioned only 6 times (4%). Through qualitative analysis we identified several key topics: insurance coverage, disability, drug copays, and transportation. The recording dynamics most frequently displayed acknowledging but not taking action on the part of clinicians. Only 25% of clinicians behave confidently in how to address a patients cost concerns. Conclusions: In a diverse cross-section of oncology visits, cost comes up only 1/4 to 1/3 of the time and focuses on insurance coverage, disability and out of pocket drug costs. However clinicians often leave these issues unaddressed. Discussing financial burdens and identifying way to improve existing conversations will be important to mitigate additional financial distress. [Table: see text]

BACKGROUND: Excessive perioperative fluid administration likely increases postoperative cardiovascular, infectious, and GI complications. Early administration of diuretics after elective surgery facilitates rapid mobilization of excess fluid, potentially leading to decreased bowel edema, more rapid return of bowel function, and reduced length of hospital stay. OBJECTIVE: This study aimed to evaluate the benefit of early diuresis after elective colon and rectal surgery in the setting of an enhanced recovery after surgery practice. DESIGN: This was a prospective study. SETTINGS: The study was conducted at a quaternary referral center. PATIENTS: A randomized, open-label, parallel-group trial was conducted in patients undergoing elective colon and rectal surgery at a single quaternary referral center. INTERVENTION: The primary intervention was administration of intravenous furosemide plus enhanced recovery after surgery on postoperative day 1 and 2 versus enhanced recovery after surgery alone. MAIN OUTCOME MEASURES: The primary outcome was length of hospital stay. Secondary outcomes included 30-day readmission rate, time to stool output during hospitalization after surgery, and incidence of various complications within the first 48 hours of hospital stay. RESULTS: In total, 123 patients were randomly assigned to receive either furosemide plus enhanced recovery after surgery (n = 62) or enhanced recovery after surgery alone (n = 61). Groups were evenly matched at baseline. At interim analysis, length of hospital stay was not superior in the intervention group (80.6 vs 99.6 hours, p = 0.564). No significant difference was identified in the rates of nasogastric tube replacement (1.6% vs 9.7%, p = 0.125). Time to return of bowel function was significantly longer in the intervention group (45.4 vs 48.8 hours, p = 0.048). The decision was made to end the study early because the conditional power of the study favored futility. LIMITATIONS: This was a single-center study. CONCLUSIONS: Early administration of furosemide does not significantly reduce the length of hospital stay after elective colon and rectal surgery in the setting of enhanced recovery after surgery practice. See Video Abstract at http://links.lww.com/DCR/A714.

AimsRhabdomyosarcomas of bone are extremely rare, with fewer than 10 reported cases. A very rare subtype of spindle cell/sclerosing rhabdomyosarcoma harbouring a FUS–TFCP2 fusion and involving both soft tissue and bone locations has been reported very recently. We report only the fourth case of this unusual, clinically aggressive rhabdomyosarcoma.Material and resultsA previously well 72‐year‐old male presented with a destructive lesion of the mandible. Morphological and immunohistochemical study of a needle biopsy and the subsequent resection showed a spindle cell rhabdomyosarcoma. RNA‐seq, RT–PCR and FISH confirmed the presence of the FUS–TFCP2 fusion.ConclusionsSpindle cell rhabdomyosarcomas carrying the FUS–TFCP2 fusion are very rare rhabdomyosarcoma variants with osseous predilection. The classification and differential diagnosis of this unusual molecular variant of spindle cell/sclerosing rhabdomyosarcoma are discussed.

Phased sequencing identified the HLA‐C*07:607 allele in an African‐American patient and sibling donor.

Mycobacterial spindle cell pseudotumor (MSP) is a rare benign spindle cell lesion containing acid-fact mycobacteria. These lesions are most commonly identified in the lymph nodes, skin, spleen, or bone marrow of immunocompromised patients and only rarely involve the lungs. We report 3 cases of pulmonary MSP, which include 2 patients who are known to be HIV-positive. The histopathological diagnosis of MSP in the lung lends itself to many challenges due to its rare incidence and its spindled tumor-like appearance. The differential diagnosis is broad and includes both benign and malignant entities. We highlight the importance of the clinical context in which these lesions typically present and the morphologic spectrum of features seen, and we offer a practical approach to the workup of pulmonary mycobacterial pseudotumor. Appropriate recognition of this entity should lead to an accurate diagnosis of a treatable benign condition despite the clinical presentation often favoring malignancy.