Citations

Objectives: Intra-articular (IA) anesthetic injection is commonly performed as a diagnostic test in the setting of femoroacetabular impingement (FAI). Currently, there is a paucity of data correlating post-injection pain relief and outcomes after hip arthroscopy for FAI. The purpose of this study is to determine whether the amount of pain relief after IA injection predicts clinical and functional outcomes following hip arthroscopy. We hypothesize that increased pain relief (>50%) will correlate with better outcomes after surgery. Methods: The records of patients undergoing hip arthroscopy for FAI at our institution between April 2007 and April 2012 were reviewed. We identified patients who underwent IA injection and subsequent hip arthroscopy. Inclusion criteria were: ultrasound or fluoroscopic guided intra-articular anesthetic injection performed at our institution, prospectively documented pre- and post-injection Numerical Rating Scale (NRS) pain scores, no prior ipsilateral hip surgery, and minimum 1 year follow-up. Pre-operative radiographs were reviewed and degree of osteoarthritis was determined using the Tonnis classification system. Outcomes were assessed with Modified Harris Hip Score (MHHS) and Hip Outcome Score (HOS). Univariate and multivariate models were performed to assess whether percent pain relief correlated with outcome scores. Results: 99 hips in 96 patients met our inclusion criteria and included 71 females (74%) and 25 males (26%) with a mean age of 37.5 ± 14.0 years. 26 patients had Tonnis grade 0, 55 had grade 1, and 18 had grade 2 (0 grade 3). Mean pain relief after IA injection was 73.6 ± 36.1 (range 0-100) percent. 26 patients (26%) had ≤50% pain relief while 73 (74%) had >50% pain relief. Outcome scores were obtained at a mean 14.9 months. Mean MHHS, HOS-ADL, and HOS-Sport scores were 79.2 ± 17.3, 82.6 ± 17.3, and 67.4 ± 28.2, respectively. There was no statistical correlation between percent pain relief and MHHS, HOS-ADL, or HOS-Sport scores. There was no significant difference in outcome scores between those with ≤50% and >50% pain relief. While patients that received >50% pain relief by IA injection were more likely to achieve positive results (MHHS >70) with a likelihood ratio of 1.23 (95% CI 0.92-1.53), this was not significant. Multivariate regression analysis demonstrated no significant predictors of outcome, including age, gender, Tonnis grade, percent relief with IA injection, number of months postoperatively, or type of surgery. Conclusion: In patients undergoing hip arthroscopy for FAI, our data indicates that the amount of pain relief from IA injection is a poor predictor of short term outcome, even when adjusting for chondral degeneration. While anesthetic injections can be an important diagnostic tool in select patients, correlation of the clinical history, physical examination, and imaging findings are fundamental. In addition, outcome following hip arthroscopy remains multifactorial.

Objectives The aim was for the appointed committee of the Academy of Neurological Communication Disorders and Sciences to conduct a systematic review of published intervention studies of acquired apraxia of speech (AOS), updating the previous committee's review article from 2006. Method A systematic search of 11 databases identified 215 articles, with 26 meeting inclusion criteria of (a) stating intention to measure effects of treatment on AOS and (b) data representing treatment effects for at least 1 individual stated to have AOS. Results All studies involved within-participant experimental designs, with sample sizes of 1 to 44 (median = 1). Confidence in diagnosis was rated high to reasonable in 18 of 26 studies. Most studies (24/26) reported on articulatory–kinematic approaches; 2 applied rhythm/rate control methods. Six studies had sufficient experimental control for Class III rating according to the Clinical Practice Guidelines Process Manual (American Academy of Neurology, 2011), with 15 others satisfying all criteria for Class III except use of independent or objective outcome measurement. Conclusions The most important global clinical conclusion from this review is that the weight of evidence supports a strong effect for both articulatory–kinematic and rate/rhythm approaches to AOS treatment. The quantity of work, experimental rigor, and reporting of diagnostic criteria continue to improve and strengthen confidence in the corpus of research.

The present study examined the heme oxygenase (HO) system in an in vivo murine model of pathological shear stress induced by partial carotid artery ligation. In this model, along with upregulation of vasculopathic genes, HO-1 is induced in the endothelium and adventitia, whereas HO-2 is mainly upregulated in the endothelium. Within minutes of ligation, NF-κB, a transcription factor that upregulates vasculopathic genes and HO-1, is activated. Failure to express either HO-1 or HO-2 exaggerates the reduction in carotid blood flow and exacerbates vascular injury. After artery ligation, comparable induction of HO-2 occurred in HO-1+/+and HO-1−/−mice, whereas HO-1 induction was exaggerated in HO-2−/−mice compared with HO-2+/+mice. Upregulation of HO-1 by an adeno-associated viral vector increased vascular HO-1 expression and HO activity and augmented blood flow in both ligated and contralateral carotid arteries. Acute inhibition of HO activity decreased flow in the ligated carotid artery, whereas a product of HO, carbon monoxide (CO), delivered by CO-releasing molecule-3, increased carotid blood flow. In conclusion, in the partial carotid artery ligation model of pathological shear stress, this study provides the first demonstration of 1) upregulation and vasoprotective effects of HO-1 and HO-2 and the vasorelaxant effects of CO as well as 2) vascular upregulation of HO-1 in vivo by an adeno-associated viral vector that is attended by a salutary vascular response. Induction of HO-1 may reside in NF-κB activation, and, along with induced HO-2, such upregulation of HO-1 provides a countervailing vasoprotective response in pathological shear stress in vivo.

AimsEpithelioid haemangioendothelioma (EHE) is a malignant vascular neoplasm. Subsets have been characterized previously by translocations resulting in either WWTR1–CAMTA1 or YAP1–TFE3 fusion. We sought to develop molecular and immunohistochemical (IHC) assays to aid in the diagnosis and characterization of EHE.Methods and resultsFifty‐two formalin‐fixed, paraffin‐embedded (FFPE) cases diagnosed between 2002 and 2014 were retrieved from the pathology files of our institutions. Reverse transcription–polymerase chain reaction (RT–PCR) assays were optimized to detect WWTR1–CAMTA1 and YAP1–TFE3 fusion transcripts in FFPE tissue and transcription factor E3 (TFE3) protein accumulation was examined by immunohistochemistry (IHC). RNA was extracted from 33 adequate samples, with more recent cases providing a greater yield of high quality RNA. Fourteen of 18 informative cases were positive for WWTR1–CAMTA1 fusion transcripts, four of which showed higher‐grade cytological features termed by some as ‘malignant EHE’. Novel in‐frame fusion transcripts were identified in four cases by direct sequencing. IHC revealed variable nuclear TFE3 staining in six of 17 cases; three with patchy staining showed WWTR1–CAMTA1 fusion. One of 18 informative cases was positive for YAP1–TFE3 fusion and showed strong nuclear TFE3 staining by IHC.ConclusionsThis study confirms the high incidence of WWTR1–CAMTA1 and YAP1–TFE3 rearrangements in EHE and indicates that the staining pattern for TFE3 IHC is critical for specificity.

Background— Pathological processes underlying myxomatous mitral valve degeneration (MMVD) remain poorly understood. We sought to identify novel mechanisms contributing to the development of this condition. Methods and Results— Microarrays were used to measure gene expression in 11 myxomatous and 11 nonmyxomatous human mitral valves. Differential gene expression (thresholds P <0.05; fold-change >1.5) and pathway activation (Ingenuity) were confirmed using quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. Contributions of bone morphogenetic protein 4 and transforming growth factor (TGF)-β2 to differential gene expression were evaluated in vitro. Contributions of angiotensin II to differential pathway activation were examined in mice in vivo. A total of 2602 genes were differentially expressed between myxomatous and nonmyxomatous valves. Canonical TGF-β signaling was increased in MMVD because of increased ligand expression and derepression of SMA mothers against decapentaplegic 2/3 signaling and was confirmed with quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. Myxomatous valves demonstrated activation of canonical bone morphogenetic protein and Wnt/β-catenin signaling and upregulation of their common target runt-related transcription factor 2. Our data set provided transcriptional and immunohistochemical evidence for activated immune cell infiltration. In vitro treatment of mitral valve interstitial cells with TGF-β2 increased β-catenin signaling at mRNA and protein levels, suggesting interactions between TGF-β2 and Wnt signaling. In vivo infusion of mice with angiotensin II recaptured several changes in signaling pathways characteristic of human MMVD. Conclusions— These data support a new disease framework whereby activation of TGF-β2, bone morphogenetic protein 4, Wnt/β-catenin, or immune signaling plays major roles in the pathogenesis of MMVD. We propose these pathways act in a context-dependent manner to drive phenotypic changes that fundamentally differ from those observed in aortic valve disease and open novel avenues guiding future research into the pathogenesis of MMVD.