Orbital Aging: A Computed Tomography-Based Study of 240 Orbits.

BACKGROUND: Previous studies have attempted to explain age-related changes to the orbit in isolation, often producing conflicting results. The authors used highly accurate imaging software to analyze computed tomographic scans to characterize changes related to age objectively. METHODS: In this case-control study, patients seen in an ear, nose, and throat clinic were screened for study entry. Male and female participants were divided into two age groups (20 to 30 years and 60 to 75 years). Primary outcomes included measurement of bony orbital dimensions, volume of soft tissues (muscle and fat volume), and anterior globe position. Three-dimensional reconstructions were created of each orbit allowing these measurements. The generalized estimating equation was used so that both orbits from each patient could be included without any bias. RESULTS: The final sample included 240 orbits from 120 patients. There were 30 patients in each age group. Among female participants, the bony orbital volume ( p < 0.05), fat volume ( p < 0.01), and central width ( p < 0.001) of the bony orbit increased with age. The anterior globe position was significantly greater in older female participants ( p < 0.01). For male participants, the fat volume ( p < 0.0001) and central height ( p < 0.03) increased with age; the lateral rim moved posteriorly with age ( p < 0.007). The anterior globe position was not different between the age groups in male participants ( p = 0.56). CONCLUSION: The female bony orbit expands with age and is associated with a more anterior position of the globe; the male bony orbital volume remains the same and the lateral rim moves posteriorly.

Angioleiomyoma of the nasolacrimal duct: case report and literature review.

Angioleiomyomas are benign tumors composed of smooth muscle and vascular endothelium. While infrequent in overall prevalence, they are exceptionally rare in the head and neck. Herein, we describe the case of a 65-year-old female who was found to have an angioleiomyoma of the right nasolacrimal duct. Endoscopic excision of the lesion along with medial maxillectomy and dacryocystorhinostomy was performed without complication. The current report is one of the few reported cases of angioleiomyoma of the lacrimal drainage system.

Contralateral Pectoralis Flap for Repair of Spinal Hardware-Associated Fistula.

We report a case of a recurrent hypopharyngeal fistula following spinal hardware placement that required multiple procedures. The course was complicated by a medication error and ultimately the fistula resolved after contralateral pectoralis muscle flap.

Pott's Puffy Tumor.

Pott's puffy tumor is a potential complication of acute frontal sinusitis, characterized by subperiosteal abscess and osteomyelitis of the frontal bone. It can be managed with a combination of open and endoscopic sinus surgery and intravenous antibiotic therapy. In the current report, a 15-year-old male presented with a classic case of Pott's puffy tumor which was managed with bilateral ethmoidectomies, frontal sinusotomies, and frontal sinus trephination, resulting in discharge on intravenous antibiotic therapy and subsequent complete resolution of symptoms.

Intraparotid Facial Nerve Schwannoma Mimicking Primary Parotid Neoplasm.

The following report is of a 36-year-old male who presented with a growing mass in the region of the parotid gland. Initial fine needle aspiration biopsy suggested a primary neoplasm of the parotid gland, but subsequent frozen section analysis intraoperatively demonstrated a schwannoma of the facial nerve. An intracapsular enucleation of the schwannoma was performed in order to preserve the fibers of the motor nerve.

A Case of Melkersson-Rosenthal Syndrome Treated With 5-FU.

The rarity of Melkersson-Rosenthal syndrome, or orofacial granulomatosis, can present with persistent midface bogginess. The management for previous reported cases has included corticosteroid injections, antihistamines, and antibiotics. In the current reported case, the patient was treated with 5-fluorouracil and has been responding positively. Additionally, the patient has not shown signs of steroid atrophy.

Schwannoma of the Supraglottis.

Hoarseness lasting greater than 2 weeks should be thoroughly evaluated. Here, a case is presented of a 38-year-old female with a 10-year history of dysphonia. Endoscopic examination confirmed the presence of a supraglottic mass, for which operative biopsy and imaging were performed. Pathology confirmed the diagnosis of supraglottic schwannoma. This was excised endoscopically with close management postoperatively to monitor for rapid recurrence and airway compromise. At one month postoperatively, the patient is still mildly dysphonic but vocally improved and the operative site continues to heal well.

Wound healing with topical BRAF inhibitor therapy in a diabetic model suggests tissue regenerative effects.

Wound healing is a multi-step process to rapidly restore the barrier function. This process is often impaired in diabetic patients resulting in chronic wounds and amputation. We previously found that paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway via topical administration of the BRAF inhibitor vemurafenib accelerates wound healing by activating keratinocyte proliferation and reepithelialization pathways in healthy mice. Herein, we investigated whether this wound healing acceleration also occurs in impaired diabetic wounds and found that topical vemurafenib not only improves wound healing in a murine diabetic wound model but unexpectedly promotes hair follicle regeneration. Hair follicles expressing Sox-9 and K15 surrounded by CD34+ stroma were found in wounds of diabetic and non-diabetic mice, and their formation can be prevented by blocking downstream MEK signaling. Thus, topically applied BRAF inhibitors may accelerate wound healing, and promote the restoration of improved skin architecture in both normal and impaired wounds.

Unilateral mydriasis following septoplasty with inferior turbinate reduction.

Nasal septoplasty and inferior turbinate reduction are common procedures performed in the treatment of nasal obstruction. These procedures are generally considered to be safe with minimal reported complications. Herein, we describe a case of a 43-year-old female who developed transient unilateral mydriasis following septoplasty with inferior turbinate reduction, likely due to the sympathomimetic agents used for vasoconstriction and mucosal decongestion.

Lower eyelid blepharoplasty: An overview.

Of the two common techniques of lower blepharoplasty, the transconjunctival approach is limited to young patients with prominent herniation of lower fat pad without skin excess and the transcutaneous approach to patients requiring skin excision. However, the current trends not only highlight the traditional sculpting of the three orbital fat pads in lower lid blepharoplasty but also additional relocation of the intraorbital fats for correcting the inferior orbital hollowing. The purpose of this review is to analyze the published literature on common types, techniques, indications, and outcomes of the multiple surgical variants of lower lid blepharoplasty often aimed at treating the redundant skin, steatoblepharon, tear trough deformity, lid laxity, and dermatochalasis, thereby to correct the negative vector and inferior orbital hollowing along with effacement of the lid cheek junction. An extensive survey of peer-reviewed literature published in English in electronic databases, as well as bibliographies from cited articles, was conducted. Databases such as MEDLINE PubMed, the Cochrane Library, and Embase were scanned using relevant medical subject heading (MeSH) terms. Clinical studies with a minimum of five study cases were included. Level III evidence, case reports, letters, editorials, and case series with fewer than five eyes were excluded. This article provides a concise overview of available literature and as such no meta-analysis was done due to the narrowed scope of the involved studies and the variety in surgical approaches and techniques of lower lid blepharoplasty.

In Vivo Measurement of the Human Vitreous Chamber Volume Using Computed Tomography Imaging of 100 Eyes.

Purpose: To accurately measure the vitreous chamber volume (VCV) in humans using high-resolution computed tomography (CT) scanning techniques combined with three-dimensional analysis software. Potential relationships between age, axial length, and VCVs were also explored. Methods: In this retrospective study, the eyes of 100 healthy individuals were studied. Scans were acquired during clinical care and did not show any signs of orbital pathology. Exclusion criteria included any ocular history. CT scans were acquired with a slice thickness of 0.7 mm, and volumetric analysis was carried out using the MIMICS image analysis software version 19.0 (Materialise, Leuven, Belgium). Results: The final sample included 100 eyes from 50 patients (30 women, 20 men). The mean age was 48.67 ± 20.72 years, and the age range was 18 to 91 years. The mean VCV was 4.649.99 ± 0.426.54 mm3 for women and 4.969.0 ± 0.465.20 mm3 for men. We found a significant correlation between age and VCV (P < 0.001), axial length and VCV (P < 0.001), and age and axial length (P < 0.005). Conclusions: The VCV appears to be greater than the current consensus suggests. This work also suggests that the VCV is associated with age and axial length, indicating that it is dynamic and may change throughout adulthood. Translational Relevance: This information regarding the volume of the vitreous chamber is useful for our understanding of proper dosage and behavior of agents we commonly insert into the vitreous chamber.

Development and Evaluation of an Objective Tympanic Membrane Visualization Assessment Technique.

OBJECTIVES: To introduce an inexpensive method for objectively evaluating otoscopic visualization of the tympanic membrane wherein learners match what they visualize in standardized patients to tympanic membrane photographs. METHODS: Two standardized patients had photographs taken of their tympanic membranes using a commercially-available digital otoscope. First- and third-year medical students were asked to perform an otoscopic examination on each patient using a conventional handheld otoscope and to match what they saw with the correct tympanic membrane image among distractor photographs belonging to other patients. The ability of students to match the standardized patients' tympanic membrane to the correct photographs was assessed before and after a didactic training session. These measurements were compared between the two cohort groups for construct validity. RESULTS: Fifty-one first-year medical students (with no previous otoscopy experience) and 44 third-year medical students (with otoscopy experience from completing pediatric and family medicine clinical clerkships) were recruited to voluntarily participate in this study. At baseline, a larger percentage of third-year students correctly matched both tympanic membranes compared to first-year students (27% vs 8%, P < .01). After otoscopy training, correct matching of both tympanic membranes significantly improved among both first-year students (8-31%, P < .01) and third-year students (27-54%, P < .01). CONCLUSION: The use of tympanic membrane photographs from standardized patients provides a novel technique for objectively assessing proficiency in otoscopic visualization of the middle ear. The concept is low cost, uses live patients, and can be easily implemented in pre-clinical instruction and beyond.

A Qualitative Appraisal of Neurotology Fellowship Websites.

OBJECTIVE: To assess the accessibility and breadth of online information regarding neurotology fellowship programs by appraising individual fellowship websites as well as two popular online databases. METHODS: The American Neurotology Society Program Information Page (ANSPIP), the American Medical Association's Fellowship and Residency Electronic Interactive Database (FREIDA), and three online search engines (Google, Yahoo, Bing) were assessed for accessibility to individual fellowship websites. Each program's ANSPIP data sheet and fellowship-specific website were then evaluated for the presence of 18 characteristics of interest to the neurotology fellowship applicant. RESULTS: All three search engines yielded 23 (96%) Accreditation Council for Graduate Medical Education (ACGME)-accredited neurotology fellowship websites. Searching "Neurotology fellowships" in Google, Yahoo, and Bing required exploring up to nine pages of search results to identify all of the ACGME-accredited program-specific websites. Direct links to program websites were found on 12 (55%) and 3 (13%) of the ANSPIP and FREIDA fellowship pages, respectively. Of the 18 characteristics of interest, the ANSPIP data sheet and individual program websites on average delineated 8.0 and 7.8 characteristics, respectively. Ninety-one percent of fellowship websites included program coordinator information, general program description, and breadth of surgical exposure. In contrast, work/life balance, postfellowship placement, and current fellow(s) were least commonly displayed (4%, 9%, 13% respectively). One-hundred percent of ANSPIP data sheets included program coordinator information, number of fellows, and affiliated hospital(s), whereas none of the pages included selection criteria, application requirements, description of location, or work/life balance. CONCLUSION: Although most neurotology fellowship programs have websites or ANSPIP data sheets, many of them lack information that has been previously demonstrated to be valued by applicants. Furthermore, incongruence of information between these sources may lead to confusion, applicant stress, and reflect poorly on fellowship programs. Perhaps a standardized list of ACGME-required data points to be posted on websites would facilitate the application process.

Utility of a smartphone-enabled otoscope in the instruction of otoscopy and middle ear anatomy.

PURPOSE: To present the utility of a smartphone-enabled otoscope as a teaching adjunct in pre-clinical otoscopy training. METHODS: 60 pre-clinical medical students were randomized into either a control group using a conventional otoscope or an experimental group using a smartphone-enabled otoscope. Participants in each group were trained to use their assigned device and were given time to practice on a colleague's ear. Participants then completed a questionnaire indicating their ability to visualize anatomical landmarks of the middle ear as well as their confidence in performing a middle ear examination using their device. RESULTS: Compared to participants using the conventional otoscope, significantly more students using the smartphone-enabled otoscope identified the umbo (93% versus 63%, P = 0.005), the short process of the malleus (67% versus 33%, P = 0.008), the cone of light (100% versus 70%, P = 0.001), and the pars flaccida (60% versus 33%, P = 0.03). Furthermore, participants who used the smartphone-enabled otoscope reported significantly increased confidence in performing otoscopy compared to those who used a conventional otoscope (4.1 ± 0.7 versus 2.8 ± 0.9, P < 0.001). Finally, participants rated the smartphone-enabled otoscope as an excellent teaching aid for otoscopy training. CONCLUSION: The smartphone-enabled otoscope serves as a valuable teaching tool for pre-clinical otoscopy education. After using the device, pre-clinical students were more confident in performing a middle ear examination and in identifying important anatomical landmarks of the middle ear.

Primary Resistance to PD-1 Blockade Mediated by JAK1/2 Mutations.

Loss-of-function mutations in JAK1/2 can lead to acquired resistance to anti-programmed death protein 1 (PD-1) therapy. We reasoned that they may also be involved in primary resistance to anti-PD-1 therapy. JAK1/2-inactivating mutations were noted in tumor biopsies of 1 of 23 patients with melanoma and in 1 of 16 patients with mismatch repair-deficient colon cancer treated with PD-1 blockade. Both cases had a high mutational load but did not respond to anti-PD-1 therapy. Two out of 48 human melanoma cell lines had JAK1/2 mutations, which led to a lack of PD-L1 expression upon interferon gamma exposure mediated by an inability to signal through the interferon gamma receptor pathway. JAK1/2 loss-of-function alterations in The Cancer Genome Atlas confer adverse outcomes in patients. We propose that JAK1/2 loss-of-function mutations are a genetic mechanism of lack of reactive PD-L1 expression and response to interferon gamma, leading to primary resistance to PD-1 blockade therapy. SIGNIFICANCE: A key functional result from somatic JAK1/2 mutations in a cancer cell is the inability to respond to interferon gamma by expressing PD-L1 and many other interferon-stimulated genes. These mutations result in a genetic mechanism for the absence of reactive PD-L1 expression, and patients harboring such tumors would be unlikely to respond to PD-1 blockade therapy. Cancer Discov; 7(2); 188-201. ©2016 AACR.See related commentary by Marabelle et al., p. 128This article is highlighted in the In This Issue feature, p. 115.

Cutaneous wound healing through paradoxical MAPK activation by BRAF inhibitors.

BRAF inhibitors are highly effective therapies for the treatment of BRAF(V600)-mutated melanoma, with the main toxicity being a variety of hyperproliferative skin conditions due to paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway in BRAF wild-type cells. Most of these hyperproliferative skin changes improve when a MEK inhibitor is co-administered, as it blocks paradoxical MAPK activation. Here we show how the BRAF inhibitor vemurafenib accelerates skin wound healing by inducing the proliferation and migration of human keratinocytes through extracellular signal-regulated kinase (ERK) phosphorylation and cell cycle progression. Topical treatment with vemurafenib in two wound-healing mice models accelerates cutaneous wound healing through paradoxical MAPK activation; addition of a mitogen-activated protein kinase kinase (MEK) inhibitor reverses the benefit of vemurafenib-accelerated wound healing. The same dosing regimen of topical BRAF inhibitor does not increase the incidence of cutaneous squamous cell carcinomas in mice. Therefore, topical BRAF inhibitors may have clinical applications in accelerating the healing of skin wounds.