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The head and face are prone to injury in bicycle accidents and helmets are proven to be helpful in decreasing injuries to some extent. The aim of this study was to determine whether certain craniomaxillofacial regions are at increased risk of injury (fracture) during bicycle accidents among helmeted cyclists.This retrospective cohort study was conducted using data from the National Electronic Injury Surveillance System (NEISS). Data concerning craniomaxillofacial injuries as a result of cycling accidents between 2019 and 2020 were reviewed. The primary predictor variables were the craniomaxillofacial region and a craniofacial bone. The co-variates included patient characteristics (age, gender, race) and injury characteristics (location, season). The primary outcome variable was a fracture. Logistic regression was used to determine any independent risk factors for a fracture.Five hundred patients reported helmet use at the time of injury. Fractures of the face region were 75 times (p .01) more likely than the head region. No particular craniofacial bone was at greater risk of fracture relative to the maxilla. Adults (OR 24.0, p .01) and seniors (OR 38.6, p .01) were each at greater risk for fracture relative to children.The facial region was at increased risk of fracture relative to the head during a bicycle accident. Adults and seniors were at increased risk of suffering craniofacial fractures relative to children.

Background: Thromboembolism-associated stroke is the most feared complication of Atrial fibrillation (AF). Percutaneous left atrial appendage closure (pLAAC) is indicated for stroke prevention in patients with AF who can’t tolerate long-term anticoagulation. We aim to study gender differences in peri-procedural and readmissions outcomes in pLAAC patients. Methods: Using the national readmission database from January 2016 to December 2018, AF patients undergoing the pLAAC procedure were identified. We used multivariate logistic regression analyses and time-to-event Cox regression analyses to conduct the study. Propensity matching with the Greedy method was done for the accuracy of results. Result: 28,819 patients were included in our study. Among them 11,946 (41.5%) were women and 16,873 (58.6%) were men. The mean age of overall population was 76.1 ± 8.5 years, with women ~ 1 year older than men. The overall rate of complications was higher in women (8.6% vs 6.6%, P

Background Osteocutaneous fibula free flap (OCFFF) donor sites are often covered with skin grafts, with an additional donor site, more postoperative care, and increased cost. The authors examine posterior tibial artery (PTA) based pedicled propeller flaps (PPF) as an alternative for OCFFF donor site coverage. Patients and methods Retrospective review of 16 consecutive patients from 30 to 79 years old, who underwent OCFFF reconstruction of head and neck defects (11 mandibular, 5 maxillary), with the closure of donor site with PPF based on a perforator from PTA. Mean donor site defect measured 12.9 × 5.1 cm, PPF was an elliptical design, and rotated 180 degrees in a propeller fashion, to cover donor site defect. Visual analog scale (VAS) was used to assess esthetic results, functional outcomes assessed using mobility and range of motion (ROM), and secondary complications including infections, hematomas, and seromas were recorded. Follow-up period was noted in months postoperatively. Other information collected included underlying head and neck pathology. Results Average dimension of PPF measured 13.9 × 4.1 cm. Successful closure of donor site defects in 14 of 16 patients, with two flaps having partial necrosis, one requiring a secondary skin graft. Follow-up was 6 to 10 months, esthetic results with mean VAS 8.8 of 10, full ROM, and mobility noted. No secondary complications were observed. The most common pathology noted was squamous cell carcinoma (6 of 16 patients). Conclusion PPFs based on the soleus branch of the PTA represent an excellent alternative to skin grafts for the closure of OCFFF donor site defects.

Osteoclasts play key roles in bone remodeling and pathologic osteolytic disorders such as inflammation, infection, bone implant loosening, rheumatoid arthritis, metastatic bone cancers, and pathological fractures. Osteoclasts are formed by the fusion of monocytes in response to receptor activators of NF-κB-ligand (RANKL) and macrophage colony stimulating factor 1 (M-CSF). Calreticulin (CRT), a commonly known intracellular protein as a calcium-binding chaperone, has an unexpectedly robust anti-osteoclastogenic effect when its recombinant form is applied to osteoclast precursors in vitro or at the site of bone inflammation externally in vivo. Externally applied Calreticulin was internalized inside the cells. It inhibited key pro-osteoclastogenic transcription factors such as c-Fos and nuclear factor of activated T cells, cytoplasmic 1 (NFATc1)-in osteoclast precursor cells that were treated with RANKL in vitro. Recombinant human Calreticulin (rhCRT) inhibited lipopolysaccharide (LPS)-induced inflammatory osteoclastogenesis in the mouse calvarial bone in vivo. Cathepsin K molecular imaging verified decreased Cathepsin K activity when rhCalreticulin was applied at the site of LPS application in vivo. Recombinant forms of intracellular proteins or their derivatives may act as novel extracellular therapeutic agents. We anticipate our findings to be a starting point in unraveling hidden extracellular functions of other intracellular proteins in different cell types of many organs for new therapeutic opportunities. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2658-2666, 2017.

Objective Evaluate if vascular normalization with an antiangiogenic monoclonal antibody improves detection of melanoma using fluorescently labeled antibody-based imaging. Study Design Preclinical. Methods Panitumumab and control IgG were covalently linked to a near-infrared fluorescent probe (IRDye800CW). Immunodeficient mice with ear xenografts of melanoma cell lines (A375 and SKMEL5) were systemically injected (200 μg, tail vein) with either IgG-IRDye800CW, panitumumab-IRDye800CW, or a combination (bevacizumab [5mg/kg], administered 72 hours prepanitumumab-IRDye800CW) (n = 5). Primary tumors were imaged with open-field (LUNA, Novadaq, Toronto, Ontario, Canada) and closed-field (Pearl, LI-COR Biosciences, Lincoln, NB) imaging devices. Postresection, the concentration of labeled antibody within the tumor (μg/g) was calculated using normalized standards. Results The mean fluorescence within the melanoma tumors was greater for the combination group compared to panitumumab alone for both cell lines (P < 0.001). The tumor-to-background ratio (TBR) for the A375 tumors was greater for the combination (3.4–7.1) compared to the panitumumab alone (3.2–5.0) (P = 0.04). The TBR for SKMEL5 tumors was greater for the combination (2.4–6.0) compared to the panitumumab alone (2.2–3.9) (P = 0.02). Within A375 tumors, the concentration was lower for panitumumab (0.51 μg/g) compared to combination group (0.68 μg/g) (P = 0.036). Within SKMEL5 tumors, the concentration was lower for panitumumab (0.0.17 μg/g) compared to combination group (0.35 μg/g) (P = 0.048). Residual tumor (1.0–0.2 mg) could be differentiated from background in both panitumumab and combination groups. For both cell lines, panitumumab and combination groups had greater mean fluorescence of the tumor compared to control IgG. Conclusion The addition of antiangiogenic therapy improves uptake of fluorescently labeled monoclonal antibodies within melanoma tumors. Clinical translation could improve detection of melanoma intraoperatively, reducing positive margins and sparing normal tissue. Level of Evidence N/A. Laryngoscope, 2016

The osteoclast is an integral cell of bone resorption. Since osteolytic disorders hinge on the function and dysfunction of the osteoclast, understanding osteoclast biology is fundamental to designing new therapies that curb osteolytic disorders. The identification and study of lysosomal proteases, such as cathepsins, have shed light on mechanisms of bone resorption. For example, Cathepsin K has already been identified as a collagen degradation protease produced by mature osteoclasts with high activity in the acidic osteoclast resorption pits. Delving into the mechanisms of cathepsins and other osteoclast related compounds provides new targets to explore in osteoclast biology. Through our anti-osteoclastogenic compound screening experiments we encountered a modified version of the Cathepsin B inhibitor CA-074: the cell membrane-permeable CA-074Me (L-3-trans-(Propylcarbamoyl) oxirane-2-carbonyl]-L-isoleucyl-L-proline Methyl Ester). Here we confirm that CA-074Me inhibits osteoclastogenesis in vivo and in vitro in a dose-dependent manner. However, Cathepsin B knockout mice exhibited unaltered osteoclastogenesis, suggesting a more complicated mechanism of action than Cathepsin B inhibition. We found that CA-074Me exerts its osteoclastogenic effect within 24 h of osteoclastogenesis stimulation by suppression of c-FOS and NFATc1 pathways.

BACKGROUND PSA is a biomarker for diagnosis and management of prostate cancer. PSA is known to have anti-tumorigenic activities, however, the physiological role of PSA in prostate tumor progression is not well understood. METHODS Five candidate peptides identified based upon computer modeling of the PSA crystal structure and hydrophobicity were synthesized at >95% purity. The peptides in a linear form, and a constrained form forced by a di-sulfide bond joining the two ends of the peptide, were investigated for anti-angiogenic activity in HUVEC. RESULTS None of the five PSA-mimetic peptides exhibited PSA-like serine protease activity. Two of the peptides demonstrated significant anti-angiogenic activity in HUVEC based on (i) inhibition of cell migration and invasion; (ii) inhibition of tube formation in Matrigel; (iii) anti-angiogenic activity in a sprouting assay; and (iv) altered expression of pro- and anti-angiogenic growth factors. Constrained PSA-mimetic peptides had greater anti-angiogenic activity than the corresponding linearized form. Complexing of PSA with ACT eliminated PSA enzymatic activity and reduced anti-angiogenic activity. In contrast, ACT had no effect on the anti-angiogenic effects of the linear or constrained PSA-mimetic peptides. Modeling of the ACT-PSA complex demonstrated ACT sterically blocks the anti-angiogenic activity of the two bioactive peptides. CONCLUSIONS The interaction of a hydrophilic domain on the surface of the PSA molecule with a target on the cell membrane of prostate endothelial and epithelial cells was responsible for the anti-angiogenic or anti-tumorigenic activity of PSA: enzymatic activity was not associated with anti-angiogenic effects. Furthermore, since PSA and ACT are both expressed within the human prostate tissue microenvironment, the balance of their expression may represent a mechanism for endogenous regulation of tissue angiogenesis. Prostate 75:1285–1299, 2015. © 2015 Wiley Periodicals, Inc.

Despite advancements in multimodality chemotherapy, conventional cytotoxic treatments still remain ineffective for a subset of patients with aggressive metastatic or multifocal osteosarcoma. It has been shown that pERK1/2 inhibition enhances chemosensitivity to doxorubicin and promotes osteosarcoma cell death in vivo and in vitro. One of the pro-apoptotic mechanisms is upregulation of Bim by pERK1/2 inhibitors. To this end, we examined proteomic changes of 143B human osteosarcoma cells with and without treatment of PD98059, pERK1/2 inhibitor. Specifically, we identified 14-3-3ϵ protein as a potential mediator of Bim expression in response to inhibition of pERK1/2. We hypothesized that 14-3-3ϵ mediates upregulation of Bim expression after pERK1/2 inhibition. We examined the expression of Bim after silencing 14-3-3ϵ using siRNA. The 14-3-3ϵ gene silencing resulted in downregulation of Bim expression after PD98059 treatment. These data indicate that 14-3-3ϵ is required for Bim expression and that it has an anti-cancer effect under pERK1/2 inhibition in 143B cells. By playing an essential role upstream of Bim, 14-3-3ϵ may potentially be a coadjuvant factor synergizing the effect of pERK1/2 inhibitors in addition to conventional cytotoxic agents for more effective osteosarcoma treatments.

Objectives/Hypothesis: Medical imaging techniques have continually improved. However, measuring esthetic outcomes using conventional two-dimensional photography has inherent limitations visualizing in three dimensions such as the face. Study Design: This study used three-dimensional imaging to visualize facial images preoperatively and postoperatively in patients undergoing Contour threadlift procedures. Methods: In patients undergoing Contour threadlift placement for midfacial rejuvenation, we prospectively imaged and photographed patients preoperatively and postoperatively. From three-dimensional images, we measured three-axis vector movement of the facial soft tissue in millimeters. Three control subjects (n = 6, bilateral sides) who had not undergone any procedure were a control group to confirm stability of the images over time. Patients also completed a questionnaire regarding their results and overall experience. Results: We studied 6 (n = 12, bilateral procedures) undergoing Contour thread placement. Analyzed images revealed a trend of midface soft tissue flattening of nasolabial contour over 3 months. Average nasolabial flattening or tightening was 2.3 mm (P > .05) in the Contour patient group. The flattening of the midfacial region returned to baseline postprocedure at 90 days. Three-dimensional imaging for the control subjects demonstrate less than 0.2 mm change (P < .05) in the nasolabial region weekly over a period of 3 weeks. Conclusions: After 3 months, patients undergoing Contour thread placement had three-dimensional imaging measurements suggesting a return to baseline values. Three-dimensional imaging may increase accuracy in quantifying change after surgery specifically with contour differences; film and digital photography capture in only two dimensions. The use of three-dimensional imaging may be applicable to numerous clinical settings.

Chylothorax results from injury to the thoracic duct or one of its branches. It is an uncommon but possibly serious complication of thoracic or head and neck surgery. We report a case of thoracic duct transection complicating a total laryngectomy with bilateral selective neck dissection for subglottic squamous cell carcinoma. High-output Jackson Pratt drainage was noted, resulting in patient hypovolemia that was unresponsive to volume resuscitation. Treatment consisted of percutaneous embolization of the thoracic duct proximal to the transection that subsequently normalized chylous output.