Citations

Purpose Enhancer of zeste homolog 2 (EZH2), a chromatin remodeler, is implicated in the pathogenesis of clear cell renal cell carcinoma (ccRCC). However, the effect of EZH2 on outcomes in localized ccRCC is unclear, and molecular biomarkers are not currently integrated into prognostic models or adjuvant therapy trials. Methods We performed Cox regression to evaluate the association of tumor-based EZH2 gene and protein expression with survival in three independent cohorts: a cohort from The Cancer Genome Atlas (n = 532), a cohort from University of Texas Southwestern Medical Center (n = 122), and a cohort from Mayo Clinic (n = 1,338). Analyses were adjusted for the prognostic stage, size, grade, and necrosis (SSIGN) score as well as within low-, intermediate-, and high-risk SSIGN groups. Results Patients in The Cancer Genome Atlas cohort with EZH2-high gene expression were 1.5 times more likely to experience overall death than patients with EZH2-low expression (95% CI, 1.1 to 2.3; P = .028). Patients in the University of Texas Southwestern Medical Center cohort with EZH2-high protein expression were two times more likely to experience overall death than patients with EZH2-low expression (95% CI, 1.1 to 4.4; P = .034). Similarly, patients in the Mayo Clinic cohort with EZH2-high protein expression were 1.4 times more likely to experience overall death (95% CI, 1.2 to 1.7; P < .001). Patients in the Mayo Clinic cohort with EZH2-high protein expression were nearly two times more likely to experience RCC-specific death (95% CI, 1.5 to 2.6; P < .001); EZH2 protein expression was particularly prognostic among patients with low-risk SSIGN tumors (HR, 6.1; 95% CI, 3.4 to 11.1; P < .001). Conclusion EZH2 expression accurately predicts risk of RCC death beyond existing clinicopathologic models, particularly in low- and intermediate-risk SSIGN tumors. Further studies are required to incorporate molecular biomarkers into surveillance guidelines and adjuvant clinical trials.

* Preclinical animal studies have demonstrated that vascularized bone grafts increase blood flow, maintain patent pedicles, provide immediate structural integrity, hypertrophy in response to mechanical stress, and deliver proper environments for healing in challenging situations. * The absolute indications for vascularized bone graft as borne out by high-quality studies have yet to be defined. Currently, the literature suggests varying success rates for difficult reconstructive problems requiring additional biological and structural properties offered only by vascularized bone-grafting. * Orthopaedic reconstructive challenges can be met with a variety of options, including pedicled and free vascularized bone grafts.

Objective: To examine the distribution of clinic and operative pathology in a tertiary care laryngology practice. Methods: Probability density and cumulative distribution analyses (Pareto analysis) was used to rank order laryngeal conditions seen in an outpatient tertiary care laryngology practice and those requiring surgical intervention during a 3-year period. Results: Among 3783 new clinic consultations and 1380 operative procedures, voice disorders were the most common primary diagnostic category seen in clinic (n = 3223), followed by airway (n = 374) and swallowing (n = 186) disorders. Within the voice strata, the most common primary ICD-9 code used was dysphonia (41%), followed by unilateral vocal fold paralysis (UVFP) (9%) and cough (7%). Among new voice patients, 45% were found to have a structural abnormality. The most common surgical indications were laryngotracheal stenosis (37%), followed by recurrent respiratory papillomatosis (18%) and UVFP (17%). Conclusions: Nearly 55% of patients presenting to a tertiary referral laryngology practice did not have an identifiable structural abnormality in the larynx on direct or indirect examination. The distribution of ICD-9 codes requiring surgical intervention was disparate from that seen in clinic. Application of the Pareto principle may improve resource allocation in laryngology, but these initial results require confirmation across multiple institutions.

Background: Multi-ligament knee injury (MLKI) associated with knee dislocation can result in vascular injury. The purpose of this study was to compare knee function after MLKI between patients with a vascular injury requiring popliteal artery bypass grafting and patients without vascular involvement. Additionally, factors associated with poor knee function in patients who had MLKI with vascular injury were evaluated. Methods: This retrospective study identified patients with an MLKI between 1992 and 2014. Each patient who had a concomitant vascular injury requiring bypass grafting (vascular cohort, n = 16; mean age, 30.3 years) was matched to 2 patients without a vascular injury (control cohort, n = 32; mean age, 31.4 years) on the basis of age, knee dislocation (KD) grade, and peroneal nerve status. Fifteen patients in the vascular cohort and 26 patients in the control cohort had an isolated knee injury. Functional outcomes were assessed with physical examination of range of motion and ligamentous stability as well as patient-reported outcome scores. Results: The vascular cohort had a mean Lysholm score of 62.5 points (range, 16 to 100 points) and a mean International Knee Documentation Committee (IKDC) score of 59.7 points (range, 14.9 to 100 points) at a mean (and standard deviation) of 8.3 ± 5.0 years after surgery. The control cohort had a mean Lysholm score of 86.4 points (range, 51.0 to 100.0 points) and a mean IKDC score of 83.8 points (range, 35.6 to 100.0 points) at a mean of 6.0 ± 4.0 years. The vascular cohort had significantly lower Lysholm (p = 0.001) and IKDC (p = 0.002) scores than the control cohort. A body mass index (BMI) of >30 kg/m 2 was predictive of lower IKDC (p = 0.0009) and Lysholm (p = 0.0008) scores. Conclusions: Patients who sustain an MLKI with an associated popliteal artery injury requiring bypass grafting have significantly lower knee function scores than patients without vascular involvement. This information can be used to help counsel patients with combined multiple ligament and popliteal artery injuries. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Purpose The relationship between syringomyelia and presyrinx, characterized by edema in the spinal cord, has not been firmly established. Patients with syringomyelia have abnormal spinal canal tapering that alters cerebrospinal fluid flow dynamics, but taper ratios in presyrinx have never been reported. We tested the hypothesis that presyrinx patients have abnormal spinal canal tapering. Materials and methods At six medical institutions, investigators searched the PACS system for patients with Chiari I and spinal cord edema unassociated with tumor, trauma, or other evident cause. In each case taper ratios were calculated for C1 to C4 and C4 to C7. In two age- and gender-matched control groups, Chiari I patients with no syringomyelia and patients with normal MR scans, the same measurements were made. Differences between groups were tested for statistical significance with t tests. Results The study enrolled 21 presyrinx patients and equal numbers of matched Chiari I and normal controls. C4 to C7 taper ratios were positive and steeper in presyrinx patients than in the normal controls ( p = 0.04). The upper cervical spine, C1 to C4, tapered negatively in cases and controls without significant differences between the groups. The difference in degree of tonsillar herniation was statistically significant between presyrinx patients and Chiari I controls ( p = 0.01). Conclusions Presyrinx patients have greater than normal positive tapering in the lower cervical spine and greater degree of tonsillar herniation than the controls.

We previously reported an extremely rare case of follicular dendritic cell sarcoma (FDCS) presented as a thyroid mass. Given the rarity of this disease, there are no personalized and molecularly targeted treatment options due to the lack of knowledge in the genomic makeup of the tumor. A 44-year-old white woman was diagnosed with an extranodal FDCS in thyroid. The patient underwent a total thyroidectomy, central compartment dissection, parathyroid re-implantation, and adjuvant radiation therapy. Tumor DNA sequencing of 236 genes by FoundationOne panel found truncating mutations in PTEN and missense mutations in RET and TP53. However, patient-matched germline DNA was not sequenced which is critical for identification of true somatic mutations. Furthermore, the FoundationOne panel doesn't measure genomic rearrangements which have been shown to be abundant in sarcomas and are associated with sarcoma tumorigenesis and progression. In the current study, we carried out comprehensive genomic sequencing of the tumor, adjacent normal tissues, and patient-matched blood, in an effort to understand the genomic makeup of this rare extranodal FDCS and to identify potential therapeutic targets. Eighty-one somatic point mutations were identified in tumor but not in adjacent normal tissues or blood. A clonal truncating mutation in the CLTCL1 gene, which stabilizes the mitotic spindle, was likely a driver mutation of tumorigenesis and could explain the extensive copy number aberrations (CNAs) and genomic rearrangements in the tumor including a chr15/chr17 local chromothripsis resulted in 6 expressed fusion genes. The fusion gene HDGFRP3→SHC4 led to a 200-fold increase in the expression of oncogene SHC4 which is a potential target of the commercial drug Dasatinib. Missense mutations in ATM and splice-site mutation in VEGFR1 were also detected in addition to the TP53 missense mutation reported by FoundationOne.

BackgroundThere is lack of evidence of the impact of varying season on heart failure (HF) hospitalization outcomes in the U.S.HypothesisHF hospitalization outcomes exhibit significant seasonal variation in the U.S.MethodsUsing data from the National Inpatient Sample (2011‐2013), seasonal variation was classified based on meteorological classification of Northern Hemisphere–Spring, Summer, Fall, & Winter–and analysis was conducted via multivariable‐adjusted mixed‐effect model.ResultsAn estimated 2.8 million adults were hospitalized for HF in the U.S. from 2011 to 2013. Of all hospitalizations, admissions were highest in Winter (27%), followed by Spring (26%), Fall (24%), and Summer (23%). The overall mortality rate was 3.1%. Compared with Spring, there was significantly lower mortality in Summer (odds ratio [OR]: 0.95, 95% CI: 0.91‐0.99) and Fall (OR: 0.94, 95% CI: 0.89‐0.98), but the highest mortality was in Winter (OR: 1.06, 95% CI: 1.02‐1.11). In addition, mean length of stay and median cost of hospitalization were highest in Winter (5.3 days, USD7459, respectively) and lowest in Summer (5.1 days, USD7181, respectively). However, age and sex differences existed (e.g. seasonal variation in inpatient mortality was only significant for patients age ≥65 years, and, comparedwith the Spring season, males had higher risk of inpatient mortality in Winter (OR: 1.10, 95% CI: 1.04‐1.17) and females had lower risk of inpatient mortality in Summer (OR: 0.94, 95% CI: 0.88‐1.00) and Fall (OR: 0.92, 95% CI: 0.87‐0.98).ConclusionsAmong HF patients in the U.S., hospitalization outcomes were worse in Winter but better in Summer.

The purpose was to determine if smartphone photography is a reliable tool in measuring wrist movement. Smartphones were used to take digital photos of both wrists in 32 normal participants (64 wrists) at extremes of wrist motion. The smartphone measurements were compared with clinical goniometry measurements. There was a very high correlation between the clinical goniometry and smartphone measurements, as the concordance coefficients were high for radial deviation, ulnar deviation, wrist extension and wrist flexion. The Pearson coefficients also demonstrated the high precision of the smartphone measurements. The Bland–Altman plots demonstrated 29–31 of 32 smartphone measurements were within the 95% confidence interval of the clinical measurements for all positions of the wrists. There was high reliability between the photography taken by the volunteer and researcher, as well as high inter-observer reliability. Smartphone digital photography is a reliable and accurate tool for measuring wrist range of motion. Level of evidence: II