Cystoid Macular Edema Arising 10 Years After Cessation of Pentosan Polysulfate Sodium Successfully Treated With Bevacizumab.

Purpose: To describe a patient initially diagnosed with age-related macular degeneration (AMD) who was ultimately determined to have progressing pentosan polysulfate sodium (PPS)-associated maculopathy leading to secondary cystoid macular edema (CME) 10 years after cessation of PPS. Methods: An interventional case report is presented. Results: A 57-year-old woman diagnosed with AMD presented with unilateral worsening vision and metamorphopsia from CME. A detailed history showed a 3-year course of PPS, which had been discontinued 10 years previously. This led to the diagnosis of PPS-associated maculopathy. After topical NSAID and corticosteroid treatment failed, intravitreal bevacizumab resolved the symptoms. CME developed in the fellow eye 5 months later and also responded to bevacizumab. Conclusions: This case emphasizes the importance of a thorough review of past medication and medical histories in patients with pigmentary retinopathy and supports the use of antivascular endothelial growth factor therapy as an option to treat CME secondary to PPS-associated maculopathy.

MCUB Regulates the Molecular Composition of the Mitochondrial Calcium Uniporter Channel to Limit Mitochondrial Calcium Overload During Stress.

BACKGROUND: The mitochondrial calcium uniporter (mtCU) is an ≈700-kD multisubunit channel residing in the inner mitochondrial membrane required for mitochondrial Ca2+ (mCa2+) uptake. Here, we detail the contribution of MCUB, a paralog of the pore-forming subunit MCU, in mtCU regulation and function and for the first time investigate the relevance of MCUB to cardiac physiology. METHODS: We created a stable MCUB knockout cell line (MCUB-/-) using CRISPR-Cas9n technology and generated a cardiac-specific, tamoxifen-inducible MCUB mutant mouse (CAG-CAT-MCUB x MCM; MCUB-Tg) for in vivo assessment of cardiac physiology and response to ischemia/reperfusion injury. Live-cell imaging and high-resolution spectrofluorometery were used to determine intracellular Ca2+ exchange and size-exclusion chromatography; blue native page and immunoprecipitation studies were used to determine the molecular function and impact of MCUB on the high-molecular-weight mtCU complex. RESULTS: Using genetic gain- and loss-of-function approaches, we show that MCUB expression displaces MCU from the functional mtCU complex and thereby decreases the association of mitochondrial calcium uptake 1 and 2 (MICU1/2) to alter channel gating. These molecular changes decrease MICU1/2-dependent cooperative activation of the mtCU, thereby decreasing mCa2+ uptake. Furthermore, we show that MCUB incorporation into the mtCU is a stress-responsive mechanism to limit mCa2+ overload during cardiac injury. Indeed, overexpression of MCUB is sufficient to decrease infarct size after ischemia/reperfusion injury. However, MCUB incorporation into the mtCU does come at a cost; acute decreases in mCa2+ uptake impair mitochondrial energetics and contractile function. CONCLUSIONS: We detail a new regulatory mechanism to modulate mtCU function and mCa2+ uptake. Our results suggest that MCUB-dependent changes in mtCU stoichiometry are a prominent regulatory mechanism to modulate mCa2+ uptake and cellular physiology.

Epidemiologic dynamics contributing to pediatric wrist fractures in the United States.

BACKGROUND: The purpose of this study was to explore and evaluate national trends and factors contributing to pediatric wrist fractures. METHODS: Over a 16-year period from January 1998 to December 2013, we identified and reviewed patients aged 0-17 years old with the primary diagnosis of wrist fracture, as evaluated in US EDs and chronicled by the National Electronic Injury Surveillance System (NEISS) database of the US Consumer Product Safety Commission. We conducted descriptive epidemiologic, bivariate, and chi-square analyses. Patients were categorized into age-defined subgroups and further stratified by sex, race, location, and consumer product/activity associated with injury. RESULTS: There were 53,265 children evaluated in NEISS EDs (national estimate, 1,908,904) with wrist fractures from 1998 to 2013. Mean age was 10.9 years, with 64 % males and 36 % females. The most common locations of injury were place of recreation/sports, home, and school. The top five consumer-product-related injuries were associated with bicycles, football, playground activities, basketball, and soccer. The highest subgroup associations were with beds (0-12 months), stairs (13-36 months), playgrounds (3-5 and 6-10 years), and football (11-17 years). The greatest increase in fractures occurred between ages 0-12 and 13-36 months, with the second-largest increase between ages 3-5 and 6-10. CONCLUSIONS: It is essential to develop injury prevention and safety strategies as well as identify individual risk factors for fracture, including activity, sex, and key age transitions. Surveillance is imperative to advance our understanding of these fractures, and in the future may facilitate development of research prediction tools to anticipate or prevent injury.

2013 Subtalar Arthroereisis Survey: The Current Practice Patterns of Members of the AOFAS.

BACKGROUND: Subtalar arthroereisis (SA) has been a procedure used for the correction of painful flexible flatfoot deformity in adults and children. Clinical studies of patients who had a SA are sparse and with mixed results and variable indications. The purpose of this study was to determine the current practice among orthopaedic foot and ankle specialists regarding SA. METHODS: Web-based questionnaires were e-mailed to members of the American Orthopaedic Foot and Ankle Society (AOFAS). Requested information included demographics and practice patterns in regard to performing SA surgery. A total of 572 respondents completed the survey (32% response rate). RESULTS: A total of 273 respondents (48%) have performed SA. Of this group, 187 respondents (69%) still perform this procedure (33% of total respondents currently perform SA). Of the respondents, 401 (70%) practice in the United States, 40% have performed SA, and 60% of those still perform this procedure. Of non-US respondents, 66% have performed SA, and 80% of those still perform it. The most common US indications are painful congenital flatfoot, posterior tibial tendon dysfunction, and flatfoot associated with accessory navicular. CONCLUSION: Many doctors have performed SA, and a significant number no longer perform this procedure for various reasons. A greater percentage of non-US practitioners have performed and continue to perform SA than their counterparts in the United States. There is a common list of surgical indications. Most doctors who still perform this procedure have removed the implants, commonly for pain. SA is still being performed in the United States and throughout the world.