Rachel M. Cymerman

Catastrophic failure after open reduction internal fixation of femoral neck fractures with a novel locking plate implant.

Objectives: To determine if the use of a novel proximal femoral locking plate could reduce the incidence of femoral neck shortening and improve clinical outcomes after open reduction internal fixation (ORIF) for femoral neck fractures as compared with historical controls. Design: Single surgeon, retrospective case–control study. Setting: Academic level I trauma center. Patients/Participants: Twenty-one femoral neck fractures treated with the posterolateral femoral locking plate (Synthes, Inc, Paoli, PA) were eligible for inclusion. Eighteen met inclusion/exclusion criteria with a mean follow-up of 16 months. Intervention: ORIF of femoral neck fracture with the posterolateral femoral locking plate. This consists of a side plate with multiple locking screws directed into the femoral head at converging/diverging angles and a single shaft screw. Intraoperative compression was achieved with partially threaded screws before locking screw insertion. Main Outcome Measurements: Maintenance of reduction was assessed by comparing immediate postoperative and final follow-up radiographs. Clinical outcome was assessed with Harris Hip Scores after 1 year. Complications and secondary operations were noted. Results: Seven (36.8%) of 18 patients experienced catastrophic failure. Five of these patients required total hip replacement, whereas the remaining 2 died before further treatment. The remaining 11 patients (61.1%) achieved bony union; the average displacement of the center of the head did not differ when compared with historical controls (0.78 mm inferiorly, 1.62 mm medially, and 2.4 degrees of increased varus vs. 0.86 mm, 1.23 mm, and 0.6 degree). Complications in this group include 1 instance of screw fracture, 2 total hip replacements, and a peri-implant subtrochanteric femur fracture. The average patient age and proportion of displaced fractures did not differ between the historical control and experimental groups. Fracture displacement was strongly associated with catastrophic failure in the experimental group only. Average Harris Hip Scores was significantly worse compared with that of historical controls (67.9 vs. 84.7, P = 0.05). Conclusions: ORIF of femoral neck fractures using a locking plate construct yielded unacceptably poor outcomes in this patient population. We hypothesize that the stiffness of this construct prevents any fracture site micromotion, placing the mechanical burden on the implant, which can result in failure at the bone–screw interface or fatigue failure of the implant itself. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Treatment of olecranon fractures with 2.4- and 2.7-mm plating techniques.

Objectives: To evaluate the outcomes of olecranon fractures treated with 2.4- and 2.7-mm plate constructs. Design: Retrospective Case Series. Setting: One-level 1 trauma center and 1 tertiary care hospital. Patients: Thirty-five consecutive patients meeting inclusion criteria. Intervention: A 2.7- or 2.4-mm reconstruction plate was placed on the dorsal ulnar cortex and contoured to allow passage of either a 2.7- or 3.5-mm intramedullary screw. In 9 patients, additional plates were required to control comminution. Available computed tomographic (CT) scans were evaluated for the presence of comminution. Main Outcome Measurements: Average Disabilities of the Arm, Shoulder, and Hand (DASH) and Mayo Elbow Performance Score (MEPS). Results: All fractures were united. Average extension deficit was 4.2 degrees, and average flexion angle was 137.4 degrees. Outcome scores were completed by 94% (33/35) of study patients. Average DASH score was 6.6, and average MEPS score was 94.5. Implants were removed in 18 patients. In the cohort of patients with CT scans, 6 of the 7 fractures thought to be simple on plain film analysis were found to have occult comminution on CT scan. Conclusions: Comminution should be considered in all olecranon fractures, even when plain films display simple patterns; although this did not affect treatment in this series of plated patients, it may be important if selecting tension band wiring. Fixation with 2.4- and 2.7-mm plates addresses comminution in olecranon fractures, avoiding the pitfalls of tension band wiring. In patients with completed outcome scores, 97% (32/33) reported their outcomes as good or excellent according to the MEPS. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Covert spatial attention is functionally intact in amblyopic human adults

Certain abnormalities in behavioral performance and neural signaling have been attributed to a deficit of visual attention in amblyopia, a neurodevelopmental disorder characterized by a diverse array of visual deficits following abnormal binocular childhood experience. Critically, most have inferred attentions role in their task without explicitly manipulating and measuring its effects against a baseline condition. Here, we directly investigate whether human amblyopic adults benefit from covert spatial attention—the selective processing of visual information in the absence of eye movements—to the same degree as neurotypical observers. We manipulated both involuntary (Experiment 1) and voluntary (Experiment 2) attention during an orientation discrimination task for which the effects of covert spatial attention have been well established in neurotypical and special populations. In both experiments, attention significantly improved accuracy and decreased reaction times to a similar extent (a) between the eyes of the amblyopic adults and (b) between the amblyopes and their age- and gender-matched controls. Moreover, deployment of voluntary attention away from the target location significantly impaired task performance (Experiment 2). The magnitudes of the involuntary and voluntary attention benefits did not correlate with amblyopic depth or severity. Both groups of observers showed canonical performance fields (better performance along the horizontal than vertical meridian and at the lower than upper vertical meridian) and similar effects of attention across locations. Despite their characteristic low-level vision impairments, covert spatial attention remains functionally intact in human amblyopic adults.

Intramedullary Allograft Fibula as a Reduction and Fixation Tool for Treatment of Complex Proximal Humerus Fractures with Diaphyseal Extension.

Summary: In this study, we present a novel technique for reduction and fixation of complex, unstable proximal humerus fractures with diaphyseal extension with the assistance of fibula allograft. We treated 14 patients using this technique since 2009 and found that it improves the reduction and enhances fixation while making the surgical procedure technically more manageable, and allows for early postoperative motion. In the first part of this study, we describe in detail the indications and surgical technique applied to these fractures. In the second part, we review the clinical and radiographic outcomes of these patients. Using this new technique, we have achieved an excellent union rate with minimal incidence of complications when treating these challenging fractures.

Comparison of Supination External Rotation Type IV Ankle Fractures in Geriatric Versus Nongeriatric Populations

Background: Geriatric patients’ (defined as those older than 65 years old) inherent comorbidities, functional limitations, and bone quality present obstacles to successful clinical outcomes for operatively treated supination external rotation (SER) ankle fractures. We retrospectively reviewed a prospectively collected series of SER injuries between 2004 and 2010. This is a comparison of the radiographic and clinical outcomes of our geriatric (27 patients) and nongeriatric (81 patients) populations. We hypothesized that geriatric patients would have worse outcomes when compared to nongeriatric patients. Methods: All SER ankle fractures (176) treated by a single surgeon were enrolled in a prospective database. All patients fulfilled inclusion criteria (108) consisting of 1 year of having clinical follow-up, postoperative radiographs, and Foot & Ankle Outcome Scores (FAOS). The primary outcome evaluated was functional outcome as exhibited by the FAOS. The secondary outcomes included adequacy of reduction, loss of reduction, postoperative complications (wound complications, infection, pain-driven hardware removal), and range of motion. Results: Despite significantly higher rates of diabetes (P < .001) and peripheral vascular disease (P < .001), there were statistically significantly better FAOS outcomes in the symptoms subcategory among the geriatric population. There was no significant difference in the articular reduction, syndesmotic reduction, wound complications, postoperative infections, or range of motion between these groups. Conclusion: Geriatric patients exhibited equivalent complication rates, radiographic outcomes, and functional outcomes compared to nongeriatric patients in this series. Anatomic fixation and soft tissue management counter the inherent risks of operative intervention in geriatric populations that report higher rates of comorbidities. This study supports aggressive fracture- and ligament-specific operative intervention in geriatric patients presenting with unstable SER injuries. Level of Evidence: Level III, retrospective case control study of prospectively collected data.

Coronary Artery Disease and Reticular Macular Disease, a Subphenotype of Early Age-Related Macular Degeneration

ABSTRACT Purpose: Reticular macular disease (RMD) is the highest risk form of early age-related macular degeneration and also specifically confers decreased longevity. However, because RMD requires advanced retinal imaging for adequate detection of its characteristic subretinal drusenoid deposits (SDD), it has not yet been completely studied with respect to coronary artery disease (CAD), the leading cause of death in the developed world. Because CAD appears in middle age, our purpose was to screen patients aged 45–80 years, documented either with or without CAD, to determine if CAD is associated with RMD. Design: A prospective cohort study of patients with documented CAD status and no known retinal disease in a clinical practice setting at one institution. Subjects and Controls: A number of 76 eyes from 38 consecutive patients (23 with documented CAD, 15 controls documented without CAD; 47.4% female; mean age 66.7 years). Methods: Patients were imaged with near-infrared reflectance/spectral domain optical coherence tomography and assessed in masked fashion by two graders for the presence of SDD lesions of RMD and soft drusen. Main Outcome Measures: Presence or absence of RMD/SDD and soft drusen. Results: RMD was more frequent in patients with CAD versus those without (Relative Risk [RR] = 2.1, CI = 1.08–3.95, P = 0.03). There was no association of CAD with soft drusen. Conclusions: A specific relationship between CAD and RMD suggests common systemic causes for both and warrants further study.

Vulvar infections: beyond sexually transmitted infections

The vulva is an under‐studied area of the female genitourinary tract which is prone to maceration, overgrowth of organisms, and atypical presentations of common dermatologic conditions. In current practice, dermatologists must recognize and manage vulvar infections and infestations beyond the more commonly recognized sexually transmitted infections. Herein, this article reviews the literature on a selection of under‐recognized viral, bacterial, fungal, and parasitic vulvar infections and infestations.

Examining the scalp for melanoma? Try a blow dryer

CLINICAL CHALLENGE The incidence of scalp melanomas has been increasing with that of melanoma overall, and scalp melanomas carry a higher mortality rate than melanomas on other locations, including nearby areas of the head and neck. It has been suggested that the lower survival rates are a result of the inherent difficulties in identifying early-stage melanomas on the scalp. Although the importance of early detection of scalp melanomas cannot be overstated, the scalp examination itself is considered one of the most time-consuming elements of the complete skin examination.

Abstract 4627: A novel computational re-analysis of published GWAS data suggests new risk loci for melanoma susceptibility

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Purpose: Multiple melanoma GWAS have identified significant associations between single nucleotide polymorphisms (SNPs) and melanoma. As multiple variants within a given genetic locus may contribute to disease risk in different individuals, a novel computational approach to analyzing GWAS data by ‘wide-locus’ region has been shown to increase analytical power, and, in other diseases, has led to the discovery of new susceptibility loci. To date, this approach has not been applied to the study of germline genetic risk factors for melanoma. We applied this method to publically available melanoma GWAS data to identify novel germline risk factors for melanoma. Methods: We re-analyzed data from the M.D. Anderson Cancer Center melanoma GWAS study (dbGap accession: phs000187.v1.p1). In the original study, 1,977 cases and 1,047 controls of European ancestry were genotyped on an Illumina OMNI1-Quad chip. We age-matched cases and controls using “age-censoring” to account for differences in melanoma risk across different age groups. Biostatistical analysis of ‘wide-loci’ was performed across all SNPs to evaluate risk loci based on the influence of neighboring SNPs. The re-analysis was performed by individuals blinded to specific results of the original study. Genome-wide significance for each wide locus was based on number of regions examined, and was set at p<10−6.16. Results: Using the ‘wide-locus’ approach, we identified 21 risk loci on 16 chromosomes that met genome-wide significance. Firstly, we replicated all of the genome-wide significant findings of the original, single-SNP analysis, identifying specific SNPs at HERC2 and wide loci at MC1R and AFG3L1 that met genome-wide significance. Secondly, we identified additional SNPs not replicated to genome-wide significance in the original analysis but previously discovered in other populations. These additional SNPs reside in the MC1R, OCA2, CPNE7, DBNDD1, and AFG3L1 loci. Finally, we identified 15 new candidate loci meeting genome-wide significance, with the most significant findings located at KLK12 (associated with carcinogenesis in other cancers), PDE8 (involved with cAMP intra-cellular signaling and immune activation), and LY86 (involved in immune cell activation). Conclusion: Applying ‘wide-locus’-based statistical analysis to melanoma GWAS data replicated the findings of prior single-SNP analyses and identified multiple, new candidate risk loci worthy of further investigation. Citation Format: Rachel M. Cymerman, Benedetta Bigio, Martin P. Seybold, David Polsky, Knut M. Wittkowski. A novel computational re-analysis of published GWAS data suggests new risk loci for melanoma susceptibility. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4627. doi:10.1158/1538-7445.AM2015-4627

Abstract 4628: Analysis of melanoma GWAS data suggests specific risk loci influencing age of onset of melanoma

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Introduction/Purpose: The average age of diagnosis of melanoma is younger than that of other major cancers. In addition, melanoma is the second most common cancer among individuals in their 20s. Analyzing GWAS data by ‘wide-locus region’ (i.e. analyzing multiple nearby single nucleotide polymorphisms (SNPs) together) increases statistical power compared to single-SNP analyses. This approach has uncovered new associations in GWAS data for diseases other than melanoma. By applying wide-locus analysis to GWAS data from melanoma cases, we aimed to discover common genetic risk variants related to age of melanoma onset. Procedures: We re-analyzed data from the 1977 melanoma cases of European ancestry made available by the MD Anderson Cancer Center study (accession: phs000187.v1.p1). Patients were genotyped on the Illumina OMNI1-Quad chip. Biostatistical analysis was performed from a window moving across the whole genome using u-statistics for multivariate, genetically structured wide-locus data to derive genetic risk scores to determine if any gene regions were associated with age of onset in melanoma patients. This statistical approach resulted in a genome-wide significance level of p<10−5.64. Results: Common variants in several genes were associated with melanoma age-of-onset at the level of genome-wide significance. The most significant functional risk loci were located at DLEU1 (p<10−6.75), NRP1 (p<10−6.66), PTPN11P (p<10−6.49) and BAT1/ATP6/NFKBIL (p<10−6.41). Of note, none of these risk loci have been shown to be associated with risk of developing melanoma overall, or longevity in prior GWAS. The NRP1 and PTPN11P genes have been linked to the RAS pathway, an important driver of melanoma pathogenesis. Conclusions: Our analysis revealed novel associations between several common genetic variants and earlier age of melanoma diagnosis. Some of these loci interact with the RAS pathway. Additional studies of common genetic variants and age of cancer diagnosis using this approach may reveal similar findings in other melanoma cohorts and possibly other cancer types. Citation Format: Rachel M. Cymerman, Benedetta Bigio, Martin P. Seybold, David Polsky, Knut M. Wittkowski. Analysis of melanoma GWAS data suggests specific risk loci influencing age of onset of melanoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4628. doi:10.1158/1538-7445.AM2015-4628