Faculty Bibliography

OBJECTIVES/HYPOTHESIS: Assessment of scholarly productivity as measured by research output is a key component of decisions regarding appointment and advancement in academic otolaryngology. An increasing number of graduating residents are pursuing postresidency fellowships, and evaluation of research productivity among these subspecialists is important in determining their role in academic otolaryngology departments. The h-index is a reliable indicator of research productivity, as it takes into account both quantity and relevance of research contributions. Our objective was to evaluate and compare trends in research productivity among the various otolaryngology subspecialties. STUDY DESIGN: Analysis of research productivity trends among otolaryngology subspecialties using the h-index. METHODS: Faculty members from 92 academic otolaryngology departments were organized by subspecialty and academic rank, and their research productivity, as measured by the h-index, was calculated using the Scopus database. RESULTS: Fellowship-trained otolaryngologists in academic programs had higher h-indices than non-fellowship-trained otolaryngologists. Head and neck surgeons and otologists had significantly higher research productivity than their peers in other otolaryngology subspecialties. Analysis of the subspecialties of chairpersons indicated that 62% were either head and neck surgeons or otologists. CONCLUSIONS: Fellowship-trained otolaryngologists had higher h-indices, and faculty members trained in the subspecialties with the highest research productivity were disproportionately represented in positions of leadership within academic otolaryngology, probably reflecting the importance of research contributions in the academic advancement process, although other factors, such as educational contributions and clinical performance, may also be important factors. Laryngoscope, 2012.

Sinonasal mucosal melanomas (SNMM) of the head and neck regions are rare and aggressive malignancies. Although they can affect patients of any ethnicity, they are more numerous in Chinese patients. The diagnosis and treatment of these tumors can be challenging. Recent studies have reported that Sox10 is a sensitive melanocytic marker for cutaneous melanoma (Nonaka et al. in Am J Surg Pathol 32:1291-1298, 2008). In addition, a CD117 (c-kit) gene mutation has been identified in cutaneous melanomas, indicating that there may be potential therapeutic benefits of tyrosine kinase inhibitors, such as Imatinib. The purpose of this study was to detect and test the immunohistochemical expression of Sox10 and c-kit in mucosal melanomas (MM) arising in the nasal cavities of Chinese patients. Twenty eight patients with mucosal melanomas of the nasal cavity were treated in two major hospitals in China. All cases had been locally diagnosed as primary SNMM. We confirmed all diagnoses with positive immunohistochemical stains for S100 and HMB-45. Additionally, automated immunohistochemistry was performed using a goat polyclonal Sox10 antibody and a monoclonal c-kit antibody counterstained using a standard avidin-biotin complex method. Immunohistochemical positive expression of Sox10 was defined by nuclear stain; and positivity for c-kit resulted in a distinct membranous staining. The extent of nuclear positivity for Sox10 and membranous stain for c-kit was graded by 4 board certified pathologists as follows: 1+, 1-25 % of positive tumor cells; 2+, 25-50 %; 3+, 50-75 %; and 4+, >/=75 %. Sox10 nuclear expression was found in all cases (100 %), with 4+ staining in 26 out of 28 cases (92.8 %) and 3+ staining in two cases with (7.1 %). The overall positivity for S100 staining was 23 out of 28 (82.1 %), with 1+ staining in 10 cases, 2+ staining in 6 cases, 3+ staining in 7 cases, and no staining in 5 cases. The sensitivity and intensity of Sox10 immunohistochemistry were both higher than with S100 immunohistochemistry. Immunopositivity of membranous stain for c-kit (CD117) was seen in 24 out of 28 cases (85.7 %), including 6 tumors that were 4+, eight that were 3+, six that were 2+, and four that showed 1+ staining. Our results demonstrate that Sox10 is a sensitive marker for SNMM and it may possess diagnostic value in addition to that of S100 protein. The expression of c-kit in the majority of MMs suggests that it may be useful in the assessment of these tumors for potential treatment with tyrosine kinase inhibitors.

The epidermal growth factor receptor (EGFR) signaling pathway is frequently dysregulated in a variety of human malignancies. As a result, agents have been developed to selectively inhibit the tyrosine kinase function of EGFR (EGFR-TKI) for cancer therapy. However, the clinical efficacy of these drugs to date has been limited by both acquired and intrinsic resistance. Macroautophagy, a process of intracellular proteolysis, has been shown to be activated in response to EGFR targeted therapy. However, the specific role of the induction of autophagy remains controversial. Here we show that autophagy is induced in a dose-dependent manner by in vitro treatment of multiple cancer cell lines with EGFR-TKI. Additionally, we find that in cells highly resistant to EGFR-TKI, autophagy is not robustly activated and that co-treatment of these cells with rapamycin, a known inducer of autophagy, can partially restore sensitivity to EGFR-TKI. Finally, we demonstrate that, in resistant cell lines, EGFR-TKI sensitivity can be further inhibited by siRNA-mediated depletion of the critical autophagy protein ATG7. Thus, our data suggests that defective autophagy may be an EGFR-TKI resistance mechanism and that activation of autophagy may be a viable strategy to augment the cytotoxic effect of EGFR-TKIs.

Cortical inhibitory circuits are formed by gamma-aminobutyric acid (GABA)-secreting interneurons, a cell population that originates far from the cerebral cortex in the embryonic ventral forebrain. Given their distant developmental origins, it is intriguing how the number of cortical interneurons is ultimately determined. One possibility, suggested by the neurotrophic hypothesis, is that cortical interneurons are overproduced, and then after their migration into cortex the excess interneurons are eliminated through a competition for extrinsically derived trophic signals. Here we characterize the developmental cell death of mouse cortical interneurons in vivo, in vitro and after transplantation. We found that 40% of developing cortical interneurons were eliminated through Bax (Bcl-2-associated X)-dependent apoptosis during postnatal life. When cultured in vitro or transplanted into the cortex, interneuron precursors died at a cellular age similar to that at which endogenous interneurons died during normal development. Over transplant sizes that varied 200-fold, a constant fraction of the transplanted population underwent cell death. The death of transplanted neurons was not affected by the cell-autonomous disruption of TrkB (tropomyosin kinase receptor B), the main neurotrophin receptor expressed by neurons of the central nervous system. Transplantation expanded the cortical interneuron population by up to 35%, but the frequency of inhibitory synaptic events did not scale with the number of transplanted interneurons. Taken together, our findings indicate that interneuron cell death is determined intrinsically, either cell-autonomously or through a population-autonomous competition for survival signals derived from other interneurons.

OBJECTIVE To investigate whether training otorhinolaryngology residents to criterion performance levels (proficiency) on the Endoscopic Sinus Surgery Simulator produces individuals whose performance in the operating room is at least equal to those who are trained by performing a fixed number of surgical procedures. DESIGN Prospective cohort. SETTING Two academic medical centers in New York City. PARTICIPANTS Otorhinolaryngology junior residents composed of 8 experimental subjects and 6 control subjects and 6 attending surgeons. INTERVENTION Experimental subjects achieved benchmark proficiency criteria on the Endoscopic Sinus Surgery Simulator; control subjects repeated the surgical procedure twice. MAIN OUTCOME MEASURES Residents completed validated objective tests to assess baseline abilities. All subjects were videotaped performing an initial standardized surgical procedure. Residents were videotaped performing a final surgery. Videotapes were assessed for metrics by an expert panel. RESULTS Attendings outperformed the residents in most parameters on the initial procedure. Experimental and attending groups outperformed controls in some parameters on the final procedure. There was no difference between resident groups in initial performance, but the experimental subjects outperformed the control subjects in navigation in the final procedure. Most important, there was no difference in final performance between subgroups of the experimental group on the basis of the number of trials needed to attain proficiency. CONCLUSIONS Simulator training can improve resident technical skills so that each individual attains a proficiency level, despite the existence of an intrinsic range of abilities. This proficiency level translates to at least equal, if not superior, operative performance compared with that of current conventional training with finite repetition of live surgical procedures.