Landmarks for the preservation of the middle temporal artery during mastoid surgery: Cadaveric dissection study.

IMPORTANCE: The middle temporal artery flap is a vascularized periosteal flap that is highly useful for otologic reconstruction including the middle cranial fossa, mastoidectomy defect, and external auditory canal. The course of the artery is close to the external auditory canal and is easily injured during preliminary exposure and elevation of flaps. OBJECTIVES: To describe the course of the middle temporal artery in relation to the external auditory canal and the superficial temporal artery in order to enhance preservation and use in otologic reconstruction. DESIGN: Dissection of preserved, injected cadaveric temporal bones. SETTING: Anatomical laboratory. PARTICIPANTS: Seven cadaveric temporal bones. INTERVENTION: Temporal bones were dissected in a planar manner to identify the middle temporal artery along the squamous temporal bone to its origin. The superior border of the external auditory canal was divided, horizontally, into thirds to create three measurement points. Distances between the middle temporal artery and the bony portion of the external auditory canal were then determined. MAIN OUTCOMES AND MEASURES: Horizontal diameter of the external auditory canal, distance from the superior-most border of the external auditory canal to the middle temporal artery, various patterns of the middle temporal artery. RESULTS: The middle temporal artery branched from the superficial temporal artery in all specimens. Mean horizontal diameter of the external auditory canal was 9.97mm. Mean distances between the bony portion of the external auditory canal and middle temporal artery for the first, second, and third points along the horizontal diameter of the external auditory canal were 1.57, 2.96, and 4.02mm, respectively. In at least one specimen, the artery dipped into the external auditory canal. CONCLUSIONS AND RELEVANCE: The middle temporal artery runs closest to the external auditory canal at the anterosuperior border. To preserve the middle temporal artery for use in reconstruction after otologic surgery, the surgeon should avoid dissection superior to the external auditory canal until the artery is positively identified.

Excavating meningoencephaloceles: A newly recognized entity.

BACKGROUND: Spontaneous cerebrospinal fluid (CSF) leaks are largely attributed to idiopathic intracranial hypertension and typically present as skull base defects with or without prolapse of intracranial contents. However, in our practice, we have encountered a distinct type of spontaneous CSF leak that presents in a different manner. OBJECTIVE: To discuss a newly-classified, difficult to treat, subset of spontaneous CSF leaks that present as excavation of the bone of the skull base in a tunnel- or canal-like fashion by a meningocele or meningoencephalocele instead of as a localized area of bony dehiscence. METHODS: A retrospective review was performed at a tertiary care rhinology practice to identify a subset of CSF leak patients with an excavating/canal-like skull base defect visualized radiographically on computed tomography (CT) scan or magnetic resonance imaging and/or endoscopically in the operating room. RESULTS: The cohort of patients consisted of 7 females and 1 male with an average age of 53.6 years and a self-reported race of 4:3:1 African-American:Caucasian:Indian. All patients presented with CSF rhinorrhea. The most common leak site was the cribriform and upper septum. Six of the 8 patients had multiple defects and/or progression of their skull base defects, and 5 patients required multiple and/or repeat repairs in the operating room. Seven of the 8 patients underwent a cisternogram because the excavating nature of the leaks made it difficult to identify the specific leak site on high-resolution CT scan alone. CONCLUSION: In spontaneous CSF leaks that are difficult to identify or recur soon after a proper repair, an excavating pattern should be considered. Failure to recognize this type of leak and all of its tributaries, to fully unroof the excavated bone to completely resect the meningocele, and to visualize and close the site of origin will likely result in failure and recurrence of CSF leak.

Skeletal muscle action of estrogen receptor α is critical for the maintenance of mitochondrial function and metabolic homeostasis in females.

Impaired estrogen receptor α (ERα) action promotes obesity and metabolic dysfunction in humans and mice; however, the mechanisms underlying these phenotypes remain unknown. Considering that skeletal muscle is a primary tissue responsible for glucose disposal and oxidative metabolism, we established that reduced ERα expression in muscle is associated with glucose intolerance and adiposity in women and female mice. To test this relationship, we generated muscle-specific ERα knockout (MERKO) mice. Impaired glucose homeostasis and increased adiposity were paralleled by diminished muscle oxidative metabolism and bioactive lipid accumulation in MERKO mice. Aberrant mitochondrial morphology, overproduction of reactive oxygen species, and impairment in basal and stress-induced mitochondrial fission dynamics, driven by imbalanced protein kinase A-regulator of calcineurin 1-calcineurin signaling through dynamin-related protein 1, tracked with reduced oxidative metabolism in MERKO muscle. Although muscle mitochondrial DNA (mtDNA) abundance was similar between the genotypes, ERα deficiency diminished mtDNA turnover by a balanced reduction in mtDNA replication and degradation. Our findings indicate the retention of dysfunctional mitochondria in MERKO muscle and implicate ERα in the preservation of mitochondrial health and insulin sensitivity as a defense against metabolic disease in women.

Estrogen receptor (ER)α-regulated lipocalin 2 expression in adipose tissue links obesity with breast cancer progression.

Obesity is associated with increased breast cancer (BrCA) incidence. Considering that inactivation of estrogen receptor (ER)α promotes obesity and metabolic dysfunction in women and female mice, understanding the mechanisms and tissue-specific sites of ERα action to combat metabolic-related disease, including BrCA, is of clinical importance. To study the role of ERα in adipose tissue we generated fat-specific ERα knock-out (FERKO) mice. Herein we show that ERα deletion increased adipocyte size, fat pad weight, and tissue expression and circulating levels of the secreted glycoprotein, lipocalin 2 (Lcn2), an adipokine previously associated with BrCA development. Chromatin immunoprecipitation and luciferase reporter studies showed that ERα binds the Lcn2 promoter to repress its expression. Because adipocytes constitute an important cell type of the breast microenvironment, we examined the impact of adipocyte ERα deletion on cancer cell behavior. Conditioned medium from ERα-null adipocytes and medium containing pure Lcn2 increased proliferation and migration of a subset of BrCA cells in culture. The proliferative and promigratory effects of ERα-deficient adipocyte-conditioned medium on BrCA cells was reversed by Lcn2 deletion. BrCA cell responsiveness to exogenous Lcn2 was heightened in cell types where endogenous Lcn2 expression was minimal, but components of the Lcn2 signaling pathway were enriched, i.e. SLC22A17 and 3-hydroxybutyrate dehydrogenase (BDH2). In breast tumor biopsies from women diagnosed with BrCA we found that BDH2 expression was positively associated with adiposity and circulating Lcn2 levels. Collectively these data suggest that reduction of ERα expression in adipose tissue promotes adiposity and is linked with the progression and severity of BrCA via increased adipocyte-specific Lcn2 production and enhanced tumor cell Lcn2 sensitivity.

Racial Disparity Among the Head and Neck Cancer Population.

Head and neck cancer is the ninth most common cancer in the USA, accounting for 3.3 % of all cancers. The incidence of head and neck cancer has plateaued recently; however, morbidity and mortality continue to remain high. Moreover, racial disparity between African-American and White patients has been studied in the head and neck community, and a vast difference still remains in mortality rate and late stage at presentation. A review of the English literature was performed using PubMed/MEDLINE for demographics, epidemiology, and studies that focused on the disparity in head and neck cancer between African-American and White patients. Age-adjusted incidence of head and neck cancer is increased in African-Americans, while the 5-year survival is decreased compared to Whites. African-American patients present with more advanced disease. When receiving similar multidisciplinary care, the overall survival was not significantly different, but racial disparity often persists in treatment regimens. Socioeconomic determinants such as insurance status play a critical role in racial disparity, along with low levels of public awareness, a lack of knowledge of specific risk factors, and a sense of mistrust that is seen in the African-American population. Disparity in the head and neck cancer community is worrisome, and although efforts have been taken to decrease the disparity, a significant difference exists. Fortunately, the disparity is reversible and can be eliminated. To do so, it is critical to extend to underserved community programs that provide appropriate screening and diagnosis, with subsequent follow-up and treatment following the standards of care.

The nasal floor pedicled flap: a novel technique for use in skull base reconstruction.

BACKGROUND: Skull base reconstruction can be accomplished using various donor sites. Vascularized tissue, commonly the nasoseptal flap, is the most effective option for large defects or high flow leaks. In cases where the septum cannot be used, a mucoperiosteal flap from the nasal floor, pedicled from the sphenopalatine artery, is a viable option without reported outcomes. The aim of this work was to describe this flap and to report successful outcomes in a cohort of patients. METHODS: Retrospective chart review of patients seen by the senior author from 2011 to 2013 requiring skull base reconstruction for defects with cerebrospinal fluid leak. RESULTS: A total of 108 patients underwent endoscopic skull base reconstruction. Ten patients had reconstruction with use of a pedicled nasal floor flap. Mean age was 53.3 years. Defects involved the ethmoid roof in 5 patients, sellar floor in 2, clivus in 2, and planum sphenoidale in 1. Reasons why the septal flap could not be used were intentional sacrifice due to disease involvement, sacrifice for proper exposure, or previous septal perforation. Mean length of follow-up was 10.2 (range, 4 to 25) months. No patient developed cerebrospinal fluid leaks postoperatively. CONCLUSION: Nasal floor pedicled flaps are an effective alternative to nasoseptal flaps for reconstruction of the skull base, and have not been previously described in the literature. Outcomes are promising in our small cohort of patients. If the septum must be sacrificed, attention should be paid to the nasal floor, which provides a large mucoperiosteal flap that can be consistently exposed and elevated by the experienced surgeon.

Inferior meatus surgery for distal nasolacrimal duct obstructions: long-term outcomes and treatment paradigm.

IMPORTANCE: Epiphora is a symptom resulting from obstruction of the nasolacrimal system. Classically, dacryocystorhinostomy has been performed to relieve epiphora. However, this does not address distal obstruction. Inferior meatus (IM) surgery at or near Hasner's valve has been shown to have a 92.8% short-term success rate in treating distal nasolacrimal duct (NLD) obstruction. In addition, IM surgery for proximal obstruction has shown poor success rates. Differentiation between distal and proximal obstruction would allow for more appropriate treatment and improved patient outcomes. To date, no study has addressed long-term outcomes or the workup for distal and proximal NLD obstructions. OBJECTIVE: To report long-term outcomes in a subset of patients with epiphora due to distal NLD obstruction who underwent IM surgery and to present a treatment paradigm to differentiate distal from proximal NLD obstruction. DESIGN, SETTING, AND PARTICIPANTS: This retrospective medical record review with follow-up telephone survey was conducted at a tertiary referral center. Participants were patients surgically treated for epiphora from July 2006 to March 2010. INTERVENTION: Inferior meatus surgery was performed to relieve epiphora in patients with distal NLD obstruction. MAIN OUTCOMES AND MEASURES: Improvement or resolution of epiphora. RESULTS: Seventeen patients were contacted for follow-up; 13 patients responded, representing 18 nasolacrimal systems. One patient (2 sides) was excluded owing to the surgical specimen showing leukemic infiltrates. Mean time of follow-up was 6.2 years. Ten sides had distal NLD obstruction. Of the nasolacrimal systems with distal obstruction, 9 had long-term subjective improvement of symptoms (90%). No patient had nasal complications. CONCLUSIONS AND RELEVANCE: Directed IM endoscopic surgery resulted in long-term improvement of epiphora in 90% of nasolacrimal systems when performed for distal NLD obstruction. A treatment paradigm was developed and is detailed herein.

Morphologic variations of clinically normal mallei and incudes.

OBJECTIVES: Various features and shapes of malleus and incus are reported. Partially or unaddressed are their bilateral symmetry, correlation with otitis media, and concordance of features and shapes. Such information may contribute to the understanding of malleus and incus ontogeny and the installation and function of implantable middle ear devices. We sought to address the following hypotheses: (1) a cranium's malleus and incus have bilateral symmetry, with respect to their features and shapes; (2) features and shapes of malleus and incus are unrelated to the mastoid size indicator of childhood otitis media; and (3) an ear's malleus and incus have concordant features and shapes (ie, the presence or absence of a feature or shape of a malleus or incus is associated with the presence or absence of another feature or shape in that ear's malleus or incus). METHODS: Postmortem material-analysis prevalence study of 41 adult crania without clinical otitis media. Mastoid sizes were assessed radiographically. RESULTS: Most mallei had lateral processes and inflected manubrium tips. Most incudes had concave superior borders of their short processes, non-notched inferior borders of their short processes, and anteriorly curved anterior edges of their long processes. Only I feature, absence of the lateral process of the malleus, was suggested to have a relationship to small mastoid size. Concordance was not found for any shape or feature of the malleus or incus. CONCLUSION: Clinically normal mallei and incudes have feature and shape variations that are mostly bilaterally symmetric.

The role of laryngoscopy in the diagnosis of spasmodic dysphonia.

IMPORTANCE: Spasmodic dysphonia (SD) can be difficult to diagnose, and patients often see multiple physicians for many years before diagnosis. Improving the speed of diagnosis for individuals with SD may decrease the time to treatment and improve patient quality of life more quickly. OBJECTIVE: To assess whether the diagnosis of SD can be accurately predicted through auditory cues alone without the assistance of visual cues offered by laryngoscopic examination. DESIGN, SETTING, AND PARTICIPANTS: Single-masked, case-control study at a specialized referral center that included patients who underwent laryngoscopic examination as part of a multidisciplinary workup for dysphonia. Twenty-two patients were selected in total: 10 with SD, 5 with vocal tremor, and 7 controls without SD or vocal tremor. INTERVENTIONS: The laryngoscopic examination was recorded, deidentified, and edited to make 3 media clips for each patient: video alone, audio alone, and combined video and audio. These clips were randomized and presented to 3 fellowship-trained laryngologist raters (A.D.R., A.T.H., and A.M.K.), who established the most probable diagnosis for each clip. Intrarater and interrater reliability were evaluated using repeat clips incorporated in the presentations. MAIN OUTCOMES AND MEASURES: We measured diagnostic accuracy for video-only, audio-only, and combined multimedia clips. These measures were established before data collection. Data analysis was accomplished with analysis of variance and Tukey honestly significant differences. RESULTS: Of patients with SD, diagnostic accuracy was 10%, 73%, and 73% for video-only, audio-only, and combined, respectively (P < .001, df = 2). Of patients with vocal tremor, diagnostic accuracy was 93%, 73%, and 100% for video-only, audio-only, and combined, respectively (P = .05, df = 2). Of the controls, diagnostic accuracy was 81%, 19%, and 62% for video-only, audio-only, and combined, respectively (P < .001, df = 2). CONCLUSIONS AND RELEVANCE: The diagnosis of SD during examination is based primarily on auditory cues. Viewing combined audio and video clips afforded no change in diagnostic accuracy compared with audio alone. Laryngoscopy serves an important role in the diagnosis of SD by excluding other pathologic causes and identifying vocal tremor.

HSP72 is a mitochondrial stress sensor critical for Parkin action, oxidative metabolism, and insulin sensitivity in skeletal muscle.

Increased heat shock protein (HSP) 72 expression in skeletal muscle prevents obesity and glucose intolerance in mice, although the underlying mechanisms of this observation are largely unresolved. Herein we show that HSP72 is a critical regulator of stress-induced mitochondrial triage signaling since Parkin, an E3 ubiquitin ligase known to regulate mitophagy, was unable to ubiquitinate and control its own protein expression or that of its central target mitofusin (Mfn) in the absence of HSP72. In wild-type cells, we show that HSP72 rapidly translocates to depolarized mitochondria prior to Parkin recruitment and immunoprecipitates with both Parkin and Mfn2 only after specific mitochondrial insult. In HSP72 knockout mice, impaired Parkin action was associated with retention of enlarged, dysmorphic mitochondria and paralleled by reduced muscle respiratory capacity, lipid accumulation, and muscle insulin resistance. Reduced oxygen consumption and impaired insulin action were recapitulated in Parkin-null myotubes, confirming a role for the HSP72-Parkin axis in the regulation of muscle insulin sensitivity. These data suggest that strategies to maintain HSP72 may provide therapeutic benefit to enhance mitochondrial quality and insulin action to ameliorate complications associated with metabolic diseases, including type 2 diabetes.

Reconstruction of upper lip avulsion after dog bite: case report and review of literature.

IMPORTANCE: Upper lip avulsion after traumatic dog bite is a serious cause of facial disfigurement for which there is no consensus on management in the acute setting. OBJECTIVE: This review was prompted by a case at our institution and is intended to display the available evidence in the management of the patient after dog bite injury to the upper lip. Our main goals are to create a management algorithm using current evidence and to stimulate further clinical investigation to improve outcomes in patients with facial dog bite injuries. EVIDENCE REVIEW: A review of English literature was performed using Pubmed/MEDLINE for case reports and case series of lip replantation using microvascular anastomosis. Additional review of hyperbaric oxygen therapy, medicinal leech therapy, lip reconstruction methods, and reapproximation was performed. Reference searches were performed for all retrieved articles. FINDINGS: Microvascular replantation is a successful method of acute management in dog bite injuries of the lip. Hyperbaric oxygen therapy and medicinal leech therapy improve outcomes. Immediate cross-lip flaps and immediate reapproximation are alternative techniques that can be performed in the acute setting, but further investigation is required. CONCLUSIONS: The repair of the upper lip after a dog bite is a priority due to the functional and psychiatric sequelae associated with facial disfigurement. Microvascular replantation should be considered first-line. Immediate reapproximation without microvascular reanastomosis and immediate reconstruction may also be performed. A stepwise clinical algorithm may aid the surgeon in the acute management of dog bite trauma to the lip.

Myeloid-specific estrogen receptor alpha deficiency impairs metabolic homeostasis and accelerates atherosclerotic lesion development.

ERα is expressed in macrophages and other immune cells known to exert dramatic effects on glucose homeostasis. We investigated the impact of ERα expression on macrophage function to determine whether hematopoietic or myeloid-specific ERα deletion manifests obesity-induced insulin resistance in mice. Indeed, altered plasma adipokine and cytokine levels, glucose intolerance, insulin resistance, and increased adipose tissue mass were observed in animals harboring a hematopoietic or myeloid-specific deletion of ERα. A similar obese phenotype and increased atherosclerotic lesion area was displayed in LDL receptor-KO mice transplanted with ERα(-/-) bone marrow. In isolated macrophages, ERα was necessary for repression of inflammation, maintenance of oxidative metabolism, IL-4-mediated induction of alternative activation, full phagocytic capacity in response to LPS, and oxidized LDL-induced expression of ApoE and Abca1. Furthermore, we identified ERα as a direct regulator of macrophage transglutaminase 2 expression, a multifunctional atheroprotective enzyme. Our findings suggest that diminished ERα expression in hematopoietic/myeloid cells promotes aspects of the metabolic syndrome and accelerates atherosclerosis in female mice.