Maackia Amurensis Seed Lectin (MASL) and soluble human podoplanin (shPDPN) Sequence Analysis and Effects on Human Oral Squamous Cell Carcinoma (OSCC) Cell Migration and Viability

Maackia amurensis lectins serve as research and botanical agents that bind to sialic residues on proteins. For example, M. amurensis seed lectin (MASL) targets the sialic acid modified podoplanin (PDPN) receptor to suppress arthritic chondrocyte inflammation, and inhibit tumor cell growth and motility. However, M. amurensis lectin nomenclature and composition are not clearly defined. Here, we sought to definitively characterize MASL and its effects on tumor cell behavior. We utilized SDS-PAGE and LC-MS/MS to find that M. amurensis lectins can be divided into two groups. MASL is a member of one group which is composed of subunits that form dimers, evidently mediated by a cysteine residue in the carboxy region of the protein. In contrast to MASL, members of the other group do not dimerize under nonreducing conditions. These data also indicate that MASL is composed of 4 isoforms with an identical amino acid sequence, but unique glycosylation sites. We also produced a novel recombinant soluble human PDPN receptor (shPDPN) with 17 threonine residues glycosylated with sialic acid moieties with potential to act as a ligand trap that inhibits OSCC cell growth and motility. In addition, we report here that MASL targets PDPN with very strong binding kinetics in the nanomolar range. Moreover, we confirm that MASL can inhibit the growth and motility of human oral squamous cell carcinoma (OSCC) cells that express the PDPN receptor. Taken together, these data characterize M. amurensis lectins into two major groups based on their intrinsic properties, clarify the composition of MASL and its subunit isoform sequence and glycosylation sites, define sialic acid modifications on the PDPN receptor and its ability to act as a ligand trap, quantitate MASL binding to PDPN with KD in the nanomolar range, and verify the ability of MASL to serve as a potential anticancer agent

Legal Liability in Iatrogenic Orbital Injury

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99620/1/lary24000.pd

Adjuvant therapies utilization pattern and survival outcomes in high-grade head and neck soft tissue sarcoma; a population based study

•Head and neck soft tissue sarcoma is a unique disease with poor survival outcome.•Radiotherapy improves the survival in high-grade disease.•Radiotherapy dose and technique don’t accentuate the survival benefit.•Chemotherapy was not associated with significant survival benefit. Head and neck soft tissue sarcoma (HNSTS) is a distinct entity within the soft tissue sarcoma group and the evidence supporting treatment options for this disease is poorly defined. Using the National Cancer Database, this study aims to reveal adjuvant therapy utilization patterns and their outcomes. HNSTS patients constituted 6.5% of all sarcoma patients and the analysis was limited to non-metastatic patients who underwent resection between 2004 and 2012. Chi-square test assessed the distribution of demographic, tumor and treatment variables in the treatment subgroups. Kaplan-Meier method estimated overall survival and proportional hazards model estimated survival hazard ratios for prognostic factors including age, comorbidity, gender, race, size, grade, margin status, histology, chemotherapy administration and radiotherapy technique/dose. The cohort included 2493 patients with a median age of 62years. Adjuvant therapies were more frequently delivered in high-grade, large tumors and with positive surgical margins. Limiting the analysis to 788 high-grade HNSTS patients, adjunctive radiotherapy improved 5-year survival from 44% (95% confidence interval (CI): 38–50) to 49% (CI: 43–55); reducing mortality hazards ratio by 24% (p<0.001). On multivariate analysis, older age, positive surgical margins and large tumor size were significant predictors of poor survival. These findings were consistent after propensity score analysis. Our analysis suggests that adjuvant radiotherapy is associated with improved survival in high-grade HNSTS. Higher dose and precise technique did not accentuate this benefit; however, further studies are needed to refine the treatment strategies, including the role of chemotherapy in the management of this rare disease

Academic Benchmarks for Otolaryngology Leaders

This study aimed to characterize current benchmarks for academic otolaryngologists serving in positions of leadership and identify factors potentially associated with promotion to these positions. Information regarding chairs (or division chiefs), vice chairs, and residency program directors was obtained from faculty listings and organized by degree(s) obtained, academic rank, fellowship training status, sex, and experience. Research productivity was characterized by (a) successful procurement of active grants from the National Institutes of Health and prior grants from the American Academy of Otolaryngology-Head and Neck Surgery Foundation Centralized Otolaryngology Research Efforts program and (b) scholarly impact, as measured by the h-index. Chairs had the greatest amount of experience (32.4 years) and were the least likely to have multiple degrees, with 75.8% having an MD degree only. Program directors were the most likely to be fellowship trained (84.8%). Women represented 16% of program directors, 3% of chairs, and no vice chairs. Chairs had the highest scholarly impact (as measured by the h-index) and the greatest external grant funding. This analysis characterizes the current picture of leadership in academic otolaryngology. Chairs, when compared to their vice chair and program director counterparts, had more experience and greater research impact. Women were poorly represented among all academic leadership positions

Image-guidance in endoscopic sinus surgery: is it associated with decreased medicolegal liability?

BackgroundThe use of image-guidance (IG) in endoscopic sinus surgery (ESS) has escalated over the last decade despite a lack of consensus that its use improves outcomes or decreases complications. One theoretical reason for using IG in ESS is its potential to minimize legal liability should an adverse outcome occur. In this study, we aimed to characterize the role of IG in ESS litigation, and further detail other factors in pertinent cases. A secondary objective was to characterize recent malpractice litigation for other relevant factors. MethodsRelevant cases from Westlaw were examined to determine whether the use of IG played a role in initiating litigation in ESS malpractice suits. Factors such as patient demographics and alleged cause(s) of malpractice litigation were examined. ResultsOut of 30 malpractice cases from 2004 to April 2013, 4 (13.3%) mentioned the use of IG during ESS, although this did not appear to be a factor affecting the plaintiff's decision to initiate litigation, nor the case outcomes. In the 26 cases (86.7%) in which IG was not used, its non-use was not specified as an alleged cause of negligence. Eleven (36.7%) cases were resolved in the defendant's favor. Frequently-cited factors included iatrogenic injury (83.3%), permanent deficits (66.7%), needing additional surgery (63.3%), orbital and intracranial injury, and perceived deficits in informed consent (40.0%). ConclusionThe use of IG was not found to be a factor in ESS litigation. This suggests that not using IG does not necessarily make one more vulnerable to malpractice litigation

Head and Neck Microvascular Reconstruction in the Elderly

Objective: Analyze the effects of advanced age on outcomes in microvascular reconstruction of the head and neck. Presentation: 6:3