Recent Publications by CFE Educators

OBJECTIVE

To examine associations of HLA class I and class II alleles with ankylosing spondylitis (AS) in three cohorts of patients of European, Asian and African ancestry.

METHODS

HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 and HLA-DPB1 alleles were genotyped in 1948 unrelated white and 67 African-American patients with AS from the Prospective Study of Outcomes in Ankylosing Spondylitis cohort, the North American Spondylitis Consortium and Australo-Anglo-American Spondyloarthritis Consortium, 990 white and 245 African-American Controls and HLA-B alleles in 442 Han Chinese patients with AS and 346 controls from Shanghai and Gansu, China. In addition to the case:control analyses, -negative patients with AS were analysed separately, and logistic regression and 'relative predispositional effects' (RPE) analyses were carried out to control for the major effect of on disease susceptibility.

RESULTS

Although numerous associations were seen between HLA alleles and AS in whites, among HLA-B*27-negative patients with AS , positive associations were seen with and and negative associations with and . Additional associations with and (B60) were observed via RPE analysis, which excludes the alleles. The increased frequency of and decreased frequency of was also seen in Han Chinese and African-Americans with AS. was decreased in whites with acute anterior uveitis.

CONCLUSIONS

These data, analysing the largest number of patients with AS examined to date in three ethnic groups, confirm that other HLA class I and II alleles other than HLA-B*27 to be operative in AS predisposition.

Fast-spiking (FS) neurons can fire action potentials (APs) up to 1,000 Hz and play key roles in vital functions such as sound location, motor coordination, and cognition. Here we report that the concerted actions of Kv3 voltage-gated K (Kv) and Na (Nav) channels are sufficient and necessary for inducing and maintaining FS. Voltage-clamp analysis revealed a robust correlation between the Kv3/Nav current ratio and FS. Expressing Kv3 channels alone could convert ∼30%-60% slow-spiking (SS) neurons to FS in culture. In contrast, co-expression of either Nav1.2 or Nav1.6 together with Kv3.1 or Kv3.3, but not alone or with Kv1.2, converted SS to FS with 100% efficiency. Furthermore, RNA-sequencing-based genome-wide analysis revealed that the Kv3/Nav ratio and Kv3 expression levels strongly correlated with the maximal AP frequencies. Therefore, FS is established by the properly balanced activities of Kv3 and Nav channels and could be further fine-tuned by channel biophysical features and localization patterns.

OBJECTIVES

Prophylactic femoral neck fixation may be performed in the setting of geriatric diaphyseal femur fracture, pathologic or impending atypical femur fractures. Fixation constructs often utilize cephalomedullary implants with one or two proximal interlocking screws into the femoral head/neck. Variations in proximal femoral anatomy and implant design can interfere with the placement of two screws in the femoral head and neck. Our objective was to assess the strength of piriformis entry reconstruction implants with one versus two proximal interlock screws for prophylactic femoral neck fixation.

METHODS

Thirty fourth generation synthetic femur models were separated into 5 groups. The control group was an intact femur, and the second group was an intact femur with an entry hole in the piriformis fossa. The remaining groups had an intramedullary nail placed with either 0, 1, or 2 screws placed into the femoral head and neck. Each femur was mechanically loaded along the mechanical axis through the femoral head. Load to failure and failure displacement were recorded.

RESULTS

Mean load to failure was 5583 ± 543 N in the intact femur. Constructs with 2 screws had a significantly higher mean load to failure (3223 ± 474 N) compared to one screw constructs (2368 ± 280 N). All of the experimental groups remained significantly lower than the intact femur model (p  0.05).

CONCLUSION

Our results demonstrate that piriformis entry reconstruction implants have a significantly lower load to failure compared to an intact femur irrespective of screw construct. Further studies are needed to investigate this potential iatrogenic weakening.

OBJECTIVE

To examine the prevalence of ultrarapid metabolizers of codeine among children in an ethnically diverse urban community.

STUDY DESIGN

Cross-sectional study.

SETTING

A tertiary care academic children's hospital in the Bronx, New York.

SUBJECTS AND METHODS

In total, 256 children with nonsyndromic congenital sensorineural hearing loss were analyzed. DNA was assessed for 63 previously described single-nucleotide polymorphisms (SNPs) and copy number variants (CNVs) known to alter the function and expression of the CYP2D6 gene primarily responsible for codeine metabolism. The rate of CYP2D6 metabolism was predicted based on participants' haplotype.

RESULTS

Ethnic distribution in the study subjects paralleled recent local census data, with the largest portion (115 children, 45.8%) identified as Hispanic or Latino. A total of 154 children (80.6%) had a haplotype that corresponds to extensive codeine metabolism, 18 children (9.42%) were identified as ultrarapid metabolizers (UMs), and 16 children (8.37%) were intermediate metabolizers. Only 3 children in our cohort (1.57%) were poor metabolizers. Patients identifying as Caucasian or Hispanic had an elevated incidence of UMs (11.3% and 11.2%, respectively) with extensive variability within subpopulations.

CONCLUSIONS

The clinically significant rate of ultrarapid metabolizers reinforces safety concerns regarding the use of codeine and related opiates. A patient-targeted approach using pharmacogenomics may mitigate adverse effects by individualizing the selection and dosing of these analgesics.

BACKGROUND

Automated cardiac image interpretation has the potential to transform clinical practice in multiple ways, including enabling serial assessment of cardiac function by nonexperts in primary care and rural settings. We hypothesized that advances in computer vision could enable building a fully automated, scalable analysis pipeline for echocardiogram interpretation, including (1) view identification, (2) image segmentation, (3) quantification of structure and function, and (4) disease detection.

METHODS

Using 14 035 echocardiograms spanning a 10-year period, we trained and evaluated convolutional neural network models for multiple tasks, including automated identification of 23 viewpoints and segmentation of cardiac chambers across 5 common views. The segmentation output was used to quantify chamber volumes and left ventricular mass, determine ejection fraction, and facilitate automated determination of longitudinal strain through speckle tracking. Results were evaluated through comparison to manual segmentation and measurements from 8666 echocardiograms obtained during the routine clinical workflow. Finally, we developed models to detect 3 diseases: hypertrophic cardiomyopathy, cardiac amyloid, and pulmonary arterial hypertension.

RESULTS

Convolutional neural networks accurately identified views (eg, 96% for parasternal long axis), including flagging partially obscured cardiac chambers, and enabled the segmentation of individual cardiac chambers. The resulting cardiac structure measurements agreed with study report values (eg, median absolute deviations of 15% to 17% of observed values for left ventricular mass, left ventricular diastolic volume, and left atrial volume). In terms of function, we computed automated ejection fraction and longitudinal strain measurements (within 2 cohorts), which agreed with commercial software-derived values (for ejection fraction, median absolute deviation=9.7% of observed, N=6407 studies; for strain, median absolute deviation=7.5%, n=419, and 9.0%, n=110) and demonstrated applicability to serial monitoring of patients with breast cancer for trastuzumab cardiotoxicity. Overall, we found automated measurements to be comparable or superior to manual measurements across 11 internal consistency metrics (eg, the correlation of left atrial and ventricular volumes). Finally, we trained convolutional neural networks to detect hypertrophic cardiomyopathy, cardiac amyloidosis, and pulmonary arterial hypertension with C statistics of 0.93, 0.87, and 0.85, respectively.

CONCLUSIONS

Our pipeline lays the groundwork for using automated interpretation to support serial patient tracking and scalable analysis of millions of echocardiograms archived within healthcare systems.

BACKGROUND

Multi-institutional data describing remedial parathyroidectomy compared with index parathyroidectomy are scarce.

METHODS

Using data in the Collaborative Endocrine Surgery Quality Improvement Program (2014-2017), baseline characteristics and outcomes of patients undergoing remedial parathyroidectomy versus index parathyroidectomy were examined using bivariate and multivariate methods. Rates of hypercalcemia and hypocalcemia at ≥ 180 days were assessed.

RESULTS

Among 6,795 patients, 367 (5.4%) underwent remedial parathyroidectomy. A single localization study was done in 24.8% versus 26.9% of remedial parathyroidectomy versus index parathyroidectomy (P = .37). Patients undergoing remedial parathyroidectomy had higher rates of preoperative laryngoscopy (45.5% versus 6.2%, P .001), intraoperative nerve monitoring (57.5% versus 34.5%, P .001), and 50% drop in hyperparathyroidism than those undergoing index parathyroidectomy (9.6% versus 3.3%, P .001). Among patients with ≥ 180 days follow-up, none of the remedial parathyroidectomy versus three index parathyroidectomy patients (0.3%) had vocal cord dysfunction. Hypercalcemia rates for remedial parathyroidectomy and index parathyroidectomy were 10.5% versus 5.0 (P = .07), and hypocalcemia rates were 10.5% versus 2.4% (P .001). After multivariate adjustment, failure to cure was 4.0 times more likely in remedial parathyroidectomy than index parathyroidectomy (P .001).

CONCLUSION

This is the first multi-institutional examination of remedial parathyroidectomy outcomes in the Collaborative Endocrine Surgery Quality Improvement Program. Nerve injury rates are low; high rates of hypercalcemia and hypocalcemia suggest potential opportunities to refine the preoperative and intraoperative management of patients undergoing remedial parathyroidectomy.

The association between coding variants in the melanocortin 4 receptor gene (MC4R) and binge eating disorder (BED) in patients with obesity is controversial. Two independent reviewers systematically searched MEDLINE, Embase, PsycINFO, BIOSIS Previews, Web of Science Core Collection and Google Scholar up to February 2018, using terms describing the MC4R gene and BED. Six of 103 identified references were included. Studies examined associations between at least one coding variant/mutation in MC4R and BED and screened for BED as per the Diagnostic and Statistical Manual of Mental Disorders. Risk of bias was assessed using a modified version of the Q-Genie tool, and overall quality of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation guidance. Meta-analysis was conducted via logistic regression models. A positive association between gain-of-function (GOF) variants in the MC4R and BED was observed (odds ratio [OR] = 3.05; 95% confidence interval [CI]: 1.82, 5.04; p = 1.7 × 10 ), while no association was detected between loss-of-function (LOF) mutations and BED (OR = 1.50; 95% CI: 0.73, 2.96; p = 0.25). Similar results were found after accounting for study quality (GOF variants: OR = 3.15; 95% CI: 1.76, 5.66; p = 1.1 × 10 ; LOF mutations: OR = 1.50; 95% CI: 0.73, 2.97; p = 0.25). Our systematic review and meta-analysis provides evidence that GOF variants as opposed to LOF mutations in MC4R are associated with BED in subjects with obesity.

INTRODUCTION

The University of California San Francisco Fresno Department of Emergency Medicine provides base hospital support for the Sequoia and Kings Canyon National Parks (SEKI) emergency medical services (EMS) system. This descriptive epidemiologic study reports reasons the park EMS system is used and interventions provided, detailing the nature of patient encounters, type and frequency of injuries and interventions, reasons for base hospital contact, and patient dispositions.

METHODS

Patient charts for all EMS encounters in SEKI from 2011 to 2013 were included, and relevant data were extracted by a single reviewer.

RESULTS

Of the 704 charts reviewed, 570 (81%) were frontcountry patient encounters (within 1.6 km [1 mi] of a paved road); 100 (14%) were backcountry; and 34 (5%) occurred in undefined locations. Regarding sex and age, 58% of patients were men; 22% were younger than 18 y, and 15% were 65 y or older. More than 80% of calls occurred during the months of June through August. The most common complaints were extremity trauma (24%), torso trauma (13%), and lacerations (9%). Almost 50% of patients were transferred to a higher level of care. Medications were administered to 37% of patients, with oxygen being the most common. Procedures were performed 49% of the time, primarily intravenous access and splinting. Base hospital contact was made 38% of the time, most commonly (54%) for advice regarding disposition.

CONCLUSIONS

SEKI EMS providers encounter a wide variety of patients in various settings, including the backcountry. Resource allocation, training, and protocol development should be tailored to meet their needs.