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Cystathionine-b-synthase (CBS) deficiency is a human genetic disease causing homocystinuria, thrombosis, mental retardation, and a suite of other devastating manifestations. Early detection coupled with dietary modification greatly reduces pathology, but the response to treatment differs with the allele of CBS. A better understanding of the relationship between allelic variants and protein function will improve both diagnosis and treatment. To this end, we tested the function of 84 CBS alleles previously sequenced from patients with homocystinuria by ortholog replacement in Saccharomyces cerevisiae. Within this clinically associated set, 15% of variant alleles were indistinguishable from the predominant CBS allele in function, suggesting enzymatic activity was retained. An additional 37% of the alleles were partially functional or could be rescued by cofactor supplementation in the growth medium. This large class included alleles rescued by elevated levels of the cofactor vitamin B6, but also alleles rescued by elevated heme, a second CBS cofactor. Measurement of the metabolite levels in CBS-substituted yeast grown with different B6 levels using LC-MS revealed changes in metabolism that propagated beyond the substrate and product of CBS. Production of the critical antioxidant glutathione through the CBS pathway was greatly decreased when CBS function was restricted through genetic, cofactor, or substrate restriction, a metabolic consequence with implications for treatment.T HE first complete human genome sequence seeded the defining challenge of human genetics for the foreseeable future: interpreting the impact of variations in the sequences of individual human genomes. Comparative genome sequencing reveals an average of one single-nucleotide change per 1200 bp between any two individuals. In the absence of strong Mendelian inheritance and linkage, confirming that any human genotype actually caused a phenotype is a significant challenge given the approximately 3 million genetic variants per person. Indeed, 4000 traits of medical interest show evidence for inheritance but lack a clear determinant (Online Mendelian Inheritance in Man 2012). Next-generation sequencing within small pedigrees (Ng et al. 2010a,b;Fan et al. 2011), or a more narrowly defined clinical phenotype (Schubert et al. 1997), can sometimes disentangle the underlying contribution of a gene to disease. In this work we have taken an approach that complements both increased sequencing capacity and expanded phenotypic description. We used surrogate genetics to assay directly the function of allelic variants and then evaluate their potential contribution to phenotypes of clinical importance.Homocystinuria, elevated levels of the sulfur-containing metabolite homocystine in the urine, illustrates several Reference numbers for publicly available data; GenBank: L14577.1 (CBS); dbSNP: rs17849313 (A69P), rs2229413 (P70L), rs11700812 (R369P); SGD: YGR155W (CYS4) and YDR232W (HEM1 challenges inherent to elucidating the molecular bases of human geneti...

OBJECTIVEIntraoperative local steroid application has been theorized to reduce swelling and improve swallowing in the immediate period following anterior cervical discectomy and fusion (ACDF). Therefore, the purpose of this study was to quantify the impact of intraoperative local steroid application on patient-reported swallow function and swelling after ACDF.METHODSA prospective, randomized single-blind controlled trial was conducted. A priori power analysis determined that 104 subjects were needed to detect an 8-point difference in the Quality of Life in Swallowing Disorders (SWAL-QOL) questionnaire score. One hundred four patients undergoing 1- to 3-level ACDF procedures for degenerative spinal pathology were randomized to Depo-Medrol (DEPO) or no Depo-Medrol (NODEPO) cohorts. Prior to surgical closure, patients received 1 ml of either Depo-Medrol (DEPO) or saline (NODEPO) applied to a Gelfoam carrier at the surgical site. Patients were blinded to the application of steroid or saline following surgery. The SWAL-QOL questionnaire was administered both pre- and postoperatively. A ratio of the prevertebral swelling distance to the anteroposterior diameter of each vertebral body level was calculated at the involved levels ± 1 level by using pre- and postoperative lateral radiographs. The ratios of all levels were averaged and multiplied by 100 to obtain a swelling index. An air index was calculated in the same manner but using the tracheal air window diameter in place of the prevertebral swelling distance. Statistical analysis was performed using the Student t-test and chi-square analysis. Statistical significance was set at p < 0.05.RESULTSOf the 104 patients, 55 (52.9%) were randomized to the DEPO cohort and 49 (47.1%) to the NODEPO group. No differences in baseline patient demographics or preoperative characteristics were demonstrated between the two cohorts. Similarly, estimated blood loss and length of hospitalization did not differ between the cohorts. Neither was there a difference in the mean change in the scaled total SWAL-QOL score, swelling index, and air index between the groups at any time point. Furthermore, no complications were observed in either group (retropharyngeal abscess or esophageal perforation).CONCLUSIONSThe results of this prospective, randomized single-blind study did not demonstrate an impact of local intraoperative steroid application on patient-reported swallowing function or swelling following ACDF. Neither did the administration of Depo-Medrol lead to an earlier hospital discharge than that in the NODEPO cohort. These results suggest that intraoperative local steroid administration may not provide an additional benefit to patients undergoing ACDF procedures.■ CLASSIFICATION OF EVIDENCE Type of question: therapeutic; study design: randomized controlled trial; evidence: Class I.Clinical trial registration no.: NCT03311425 (clinicaltrials.gov)

Intraoperative imaging is vital for accurate placement of instrumentation in spine surgery. However, the use of biplanar fluoroscopy and other intraoperative imaging modalities is associated with the risk of significant radiation exposure in the patient, surgeon, and surgical staff. Radiation exposure in the form of ionizing radiation can lead to cellular damage via the induction of DNA lesions and the production of reactive oxygen species. These effects often result in cell death or genomic instability, leading to various radiation-associated pathologies including an increased risk of malignancy. In attempts to reduce radiation-associated health risks, radiation safety has become an important topic in the medical field. All practitioners, regardless of practice setting, can practice radiation safety techniques including shielding and distance to reduce radiation exposure. Additionally, optimization of fluoroscopic settings and techniques can be used as an effective method of radiation dose reduction. New imaging modalities and spinal navigation systems have also been developed in an effort to replace conventional fluoroscopy and reduce radiation doses. These modalities include Isocentric Three-Dimensional C-Arms, O-Arms, and intraoperative magnetic resonance imaging. While this influx of new technology has advanced radiation safety within the field of spine surgery, more work is still required to overcome specific limitations involving increased costs and inadequate training.

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Introduction: Social media represents a novel platform for patient-physician interaction. Although social media utilization patterns have been analyzed in other fields, no such study has been performed in shoulder and elbow specialists. Methods: The membership database of the society of the American Shoulder and Elbow Surgeons was queried. Online searches were performed to identify if each surgeon had professional profiles on popular social media platforms. A social media score was then calculated, defined as the number of active accounts. Statistical analysis was used to test for associations between demographics and social media utilization. Results: Six hundred seventy-six surgeons were analyzed. The average social media score was 1.61. The most highly used platform was LinkedIn (61%). The least used platform was Instagram (5% active, 11% total). Female surgeons were more likely to use Instagram than men (12.5% versus 4.9%). Academic surgeons were more likely to use ResearchGate (46.5% versus 33.3%), whereas private practice surgeons were more likely to have a website (19.9% versus 11.7%). Practitioners from the South had the lowest social media utilization. Conclusions: Shoulder and elbow surgeons underuse social media. As the influence of social media continues to grow, it will be important for surgeons to implement social media within their practices.

OBJECTIVEGiven the increasing prevalence of obesity, more patients with a high body mass index (BMI) will require surgical treatment for degenerative spinal disease. In previous investigations of lumbar spine pathology, obesity has been associated with worsened postoperative outcomes and increased costs. However, few studies have examined the association between BMI and postoperative outcomes following anterior cervical discectomy and fusion (ACDF) procedures. Thus, the purpose of this study was to compare surgical outcomes, postoperative narcotics consumption, complications, and hospital costs among BMI stratifications for patients who have undergone primary 1- to 2-level ACDF procedures.METHODSThe authors retrospectively reviewed a prospectively maintained surgical database of patients who had undergone primary 1- to 2-level ACDF for degenerative spinal pathology between 2008 and 2015. Patients were stratified by BMI as follows: normal weight (< 25.0 kg/m2), overweight (25.0–29.9 kg/m2), obese I (30.0–34.9 kg/m2), or obese II–III (≥ 35.0 kg/m2). Differences in patient demographics and preoperative characteristics were compared across the BMI cohorts using 1-way ANOVA or chi-square analysis. Multivariate linear or Poisson regression with robust error variance was used to determine the presence of an association between BMI category and narcotics utilization, improvement in visual analog scale (VAS) scores, incidence of complications, arthrodesis rates, reoperation rates, and hospital costs. Regression analyses were controlled for preoperative demographic and procedural characteristics.RESULTSTwo hundred seventy-seven patients were included in the analysis, of whom 20.9% (n = 58) were normal weight, 37.5% (n = 104) were overweight, 24.9% (n = 69) were obese I, and 16.6% (n = 46) were obese II–III. A higher BMI was associated with an older age (p = 0.049) and increased comorbidity burden (p = 0.001). No differences in sex, smoking status, insurance type, diagnosis, presence of neuropathy, or preoperative VAS pain scores were found among the BMI cohorts (p > 0.05). No significant differences were found among these cohorts as regards operative time, intraoperative blood loss, length of hospital stay, and number of operative levels (p > 0.05). Additionally, no significant differences in postoperative narcotics consumption, VAS score improvement, complication rates, arthrodesis rates, reoperation rates, or total direct costs existed across BMI stratifications (p > 0.05).CONCLUSIONSPatients with a higher BMI demonstrated surgical outcomes, narcotics consumption, and hospital costs comparable to those of patients with a lower BMI. Thus, ACDF procedures are both safe and effective for all patients across the entire BMI spectrum. Patients should be counseled to expect similar rates of postoperative complications and eventual clinical improvement regardless of their BMI.