Wendy L. Parker

ALK1 opposes ALK5/Smad3 signaling and expression of extracellular matrix components in human chondrocytes.

Introduction: TGF‐β is a multifunctional regulator of chondrocyte proliferation, differentiation, and extracellular matrix production. Dysregulation of TGF‐β action has been implicated in cartilage diseases such as osteoarthritis. TGF‐β signaling is transduced through a pair of transmembrane serine/threonine kinases, known as the type I (ALK5) and type II receptors. However, recent studies on endothelial cells have identified ALK1 as a second type I TGF‐β receptor and have shown that ALK1 and ALK5 have opposing functions in these cells. Here we examined ALK1 expression and its regulation of TGF‐β signaling and responses in human chondrocytes.

Endoglin differentially regulates TGF-β-induced Smad2/3 and Smad1/5 signalling and its expression correlates with extracellular matrix production and cellular differentiation state in human chondrocytes

OBJECTIVE Transforming growth factor-β (TGF-β) plays a critical role in cartilage homeostasis and deregulation of its signalling is implicated in osteoarthritis (OA). TGF-β isoforms signal through a pair of transmembrane serine/threonine kinases known as the type I and type II TGF-β receptors. Endoglin is a TGF-β co-receptor that binds TGF-β with high affinity in the presence of the type II TGF-β receptor. We have previously shown that endoglin is expressed in human chondrocytes and that it forms a complex with the TGF-β signalling receptors. However, the functional significance of endoglin expression in chondrocytes is unknown. Our objective was to determine whether endoglin regulates TGF-β/Smad signalling and extracellular matrix (ECM) production in human chondrocytes and whether its expression varies with chondrocyte differentiation state. METHOD Endoglin function was determined by overexpression or antisense morpholino/siRNA knockdown of endoglin in human chondrocytes and measuring TGF-β-induced Smad phosphorylation, transcriptional activity and ECM production. Alterations in endoglin expression levels were determined during subculture-induced dedifferentiation of human chondrocytes and in normal vs OA cartilage samples. RESULTS Endoglin enhances TGF-β1-induced Smad1/5 phosphorylation and inhibits TGF-β1-induced Smad2 phosphorylation, Smad3-driven transcriptional activity and ECM production in human chondrocytes. In addition, the enhancing effect of endoglin siRNA knockdown on TGF-β1-induced Smad3-driven transcription is reversed by ALK1 overexpression. Furthermore, endoglin levels are increased in chondrocytes following subculture-induced dedifferentiation and in OA cartilage as compared to normal cartilage. CONCLUSION Together, our results suggest that endoglin regulates the balance between TGF-β/ALK1/Smad1/5 and ALK5/Smad2/3 signalling and ECM production in human chondrocytes and that endoglin may represent a marker for chondrocyte phenotype.

Endoglin Is Expressed on Human Chondrocytes and Forms a Heteromeric Complex With Betaglycan in a Ligand and Type II TGFβ Receptor Independent Manner

Previous work has implicated transforming growth factor β (TGFβ) as an essential mediator of cartilage repair and TGFβ signaling as a requirement for the maintenance of articular cartilage in vivo. However, the mechanisms regulating TGFβ action in chondrocytes are poorly understood. Endoglin, an accessory receptor of the TGFβ receptor superfamily, is highly expressed on endothelial cells and has been shown to potently modulate TGFβ responses. It is not known whether chondrocytes express endoglin or whether it modulates TGFβ signaling in these cells. In this study, we show that endoglin is expressed on human chondrocytes at levels comparable with endothelial cells and that it forms higher order complexes with the types I and II TGFβ receptors. More importantly, we show that endoglin forms a heteromeric complex with betaglycan on these cells at endogenous receptor concentrations and ratios. Endoglin complexes with betaglycan in a ligand‐independent and ‐dependent manner as indicated by co‐immunoprecipitation in the absence of TGFβ and after affinity labeling with radiolabeled TGFβ, respectively. Also, the endoglin‐betaglycan association can occur independently of the type II TGFβ receptor. These findings, taken together with the available evidence that endoglin and betaglycan are potent modulators of TGFβ signal transduction, imply that the complex formation between endoglin and betaglycan may be of critical significance in the regulation of TGFβ signaling in chondrocytes.

Effect of treatment delay on mandibular fracture infection rate.

Background: The incidence of infection secondary to mandibular fractures ranges from 0 to 30 percent, resulting in significant sequelae. Unlike other variables that may influence infection, delayed repair is often unavoidable. The objective of this study was to accurately identify the effect of treatment delay on mandibular fracture infection rate by adjusting for confounders, thus providing strong evidence for preoperative management of these patients. Methods: A retrospective review of mandibular fracture patients treated at the Montreal General Hospital was performed. Length of time delay between injury and operative intervention (≤72 hours and >72 hours) and presence of infection were noted. Logistic regression was used to analyze the effect of treatment delay on infection, after adjustment for covariates. Results: One hundred seventy-seven patients fulfilled the selection criteria and had complete records. The overall incidence of infection was 14 percent (95 percent confidence interval, 8.8 to 18.8 percent). Multiple logistic regression showed no evidence (odds ratio, 2.96; 95 percent confidence interval, 0.87 to 10.1) (p = 0.08) that treatment delay of more than 72 hours is a significant predictor of infection. The incidence of nonunion was 36 percent in the infection group (95 percent confidence interval, 17.2 to 54.8 percent) and 0 percent in the no-infection group. Conclusions: Infections following mandibular fractures frequently require extended treatment and significantly increase costs. These results show that delay of mandibular fracture treatment greater than 72 hours does not significantly increase infection risk. Repair should occur promptly after the injury. If that is not possible, the standard patient management should not be altered, as the benefits of doing so are unproven.

Large Area Local Anesthesia (LALA) in Submuscular Breast Augmentation

BACKGROUND Large area local anesthesia (LALA) has been recommended for decreasing localized pain and shortening discharge time after breast augmentation surgery. However, quantifiable, objective outcome data for evaluation of the effectiveness of LALA in aesthetic plastic surgery procedures have not yet been reported. OBJECTIVE We conducted a retrospective patient chart review to determine whether irrigation of the submuscular pocket with bupivacaine in retropectoral breast augmentation procedures quantifiably alters the patients postoperative course with respect to narcotic requirement, nausea and vomiting, and time to discharge. The findings were evaluated in the context of a critical review of the literature dealing with pain management after breast augmentation, and in particular with the use of LALA. METHODS All procedures were performed by the senior author in a private surgical facility. All patients received an identical general anesthetic plus local infiltration of incisions with 1% lidocaine with epinephrine. An inframammary approach was used in all cases; retropectoral dissection was performed with electrocautery dissection followed by hemostasis. In one cohort of patients the submuscular pocket was irrigated with 10 mL of 0.125% bupivacaine before dissection of the contralateral side; in a second control cohort it was not. Postoperative care was the same for both groups. RESULTS We found a trend toward decreased nausea and vomiting and narcotic use, and a statistically significant decrease in time to discharge, for the cohort that received intraoperative bupivacaine irrigation. CONCLUSIONS LALA is an effective means to decrease recovery time and possibly postoperative pain, nausea and vomiting, and narcotic requirements. Because evidence-based medicine is the surest basis for clinical decisions, evaluation of LALA as well as other treatment modalities should include quantifiable outcome measures.

Objective interpretation of surgical outcomes: is there a need for standardizing digital images in the plastic surgery literature?

Background: Subjective interpretation of preoperative and postoperative photographs is heavily relied on for evaluating standards of care. For preoperative and postoperative digital images to accurately reflect surgical outcomes, image characteristics, other than acquisition, must be rigidly standardized. The authors investigated, using objective methodology, the consistency of published images within the plastic surgery literature. Methods: A panel reviewed four plastic surgery journals (Aesthetic Plastic Surgery, Aesthetic Surgery Journal, Plastic and Reconstructive Surgery, and the British Journal of Plastic Surgery), with 100 consecutive, color, digital, paired preoperative and postoperative images per journal compared. Image characteristics, including color, brightness, contrast, resolution, view, zoom, size, image labeling, background, patient clothing, accessories, makeup/tan, facial expression, and hairstyle, were objectively assessed using a five-point Likert scale; mean values were tabulated and compared among journals; and statistical significance was determined (p < 0.05). Results: The most consistent characteristics among journals included labeling (4.782) and size (4.867), in contrast to clothing (3.097) and hairstyle (3.724) (p < 0.001). Much variability was also present in color, brightness, and view. Plastic and Reconstructive Surgery and American Aesthetic Plastic Surgery were the two most consistent journals when all image characteristics were combined, scoring 4.6 and 4.5, respectively (p ≤ 0.01). Conclusions: Standardization of photographic images is essential in plastic surgery for validity of results. Overall, the authors have demonstrated that much variability exists for all image characteristics between preoperative and postoperative images. Many are crucial to the evaluation of the surgical outcome depicted. In a specialty with a dramatically increasing trend toward communication by means of digital imaging, an effort toward standardization is essential.

First carpal-metacarpal joint dislocation and trapezial fracture treated with external fixation in an adolescent.

The intrinsic joint stability of the first carpal-metacarpal joint (CMC) makes dislocation a rare injury with fewer than 40 cases described. The degree to which supporting ligaments have been disrupted is reflected clinically by a spectrum of joint stability. Close review of radiographs and an attentive physical examination are necessary to make the diagnosis. Acute treatment has consisted of closed or open reduction with K-wires for stabilization or casting with failures leading to chronic joint instability and the need for soft tissue tendon suspension to maintain joint alignment. We present the case of a 12-year-old boy with a complete first CMC dislocation and trapezial fracture treated with closed reduction and external fixation. At a 3-year follow-up, our patient demonstrates excellent range of motion, strength, and no joint instability without functional limitations. We suggest that external fixation be added to the armamentarium for managing these difficult injuries especially in the pediatric population where interference with growth plates is not ideal.

Evidence-based medicine: thumb carpometacarpal arthroplasty.

Learning Objectives: After studying this article, the participant should be able to: 1. Recount the epidemiology of basilar joint arthritis. 2. Understand how the anatomy and kinematics of this joint contribute to the development of the disease process. 3. Combine patient history, clinical examination, and radiographic findings to formulate a diagnosis and staging of the arthritis. 4. Incorporate conservative management into the patient treatment plan to aid in determining a patient’s surgical candidacy. 5. Comprehend the basic principles of available surgical options, potential complications, and evidence pertaining to surgical outcome. Summary: This article has been prepared to accompany practice-based assessment with ongoing surgical education for the Maintenance of Certification for the American Board of Plastic Surgery. It is structured for physicians to comparatively evaluate their care of a patient with arthritis of the thumb carpometacarpal joint.

Desmoid tumor of the hand: a case report.

SUMMARY Extra-abdominal desmoid tumors are extremely rare in the hand. These tumors do not metastasize; however, they are potentially locally invasive and have extremely high local recurrence rates after surgical excision with reports of up to 78% recurrence, specifically in the hand. We describe the first case of a desmoid tumor originating from the extensor mechanism of a digit and discuss our treatment approach. In addition, a literature review performed shows a male predominance of desmoid tumors in the hand in the 30- to 50-year-old age group. Current evidence supports aggressive early wide surgical excision and reconstruction to preserve function.

Management of Zygomatic Fractures: A National Survey.

Introduction:Repair of zygomatic fractures can be classified into the early closed reduction or the more recent open reduction and rigid internal fixation (ORIF) methods. Surgical training and literature advocate ORIF, but the actual frequency of the different techniques in clinical practice is unknown. The purpose of this study was to determine the current trends in the management of zygomatic fractures among US surgeons and elucidate their influences. Methods:A 10-question survey was developed and distributed to over 16,000 practicing US facial trauma surgeons, including plastic surgeons (PS), oral and maxillofacial surgeons (OMFS), and otorhinolaryngologists (ENT). The survey queried training background, zygoma fracture treatment preferences, and rationale. Responses were tabulated and both univariate and bivariate statistical analyses completed. Results:One thousand six hundred eleven (10%) total responses were received. Zygomatic fractures are treated most commonly by OMFS (61%), then PS (20%) and ENT (19%), with 71% of repairs being performed in private practice. Open reduction and rigid internal fixation is the most common treatment modality (81%), with most surgeons using 2 to 3 sites for exposure, reduction, and fixation with titanium miniplates (70%). Thirty-five percent of surgeons perform routine orbital floor exploration. Forty-three percent quoted training and 32% reported accuracy of repair as the primary reason for choosing ORIF. Conclusions:This is the largest reported survey on the repair of zygoma fractures. The response rate suggests dominance of OMFS in zygoma fracture care, an area pioneered by PS. Evolution of technique is also evident by predominance of ORIF with emphasis of multiple points of exposure, reduction, and fixation with rigid hardware.