Purpose: Mitochondria are highly susceptible to oxidative damage. Although mitochondrial function decreases with oxidative damage, overall mitochondrial DNA (mtDNA) content increases to compensate for general mitochondrial dysfunction. We performed quantitative polymerase chain reaction for genes specific to mitochondrial and nuclear genomes to investigate relative mitochondrial abundance in a spectrum of dysplastic head and neck lesions.Experimental Design: DNA from mild, moderate, and severe dysplasias, as well as invasive tumors and normal mucosal cells, was extracted. Using quantitative polymerase chain reaction, mitochondrial to nuclear DNA ratios were determined by quantification of cytochrome c oxidase subunit 1 (CoxI) and -actin genes.Results: Mean CoxI/-actin DNA ratios for mild, moderate, and severe premalignant lesions were 0.0529, 0.0607, and 0.1021, respectively. The mean ratio for the normal mucosal cells contained in saliva was 0.0537, whereas the mean ratio for tumors was 0.1667. As a whole, our experimental model demonstrated significance (P ؍ 0.0358). Comparisons between individual categories showed borderline significance when compared with the normal group, with P values of 0.0673, 0.0747, and 0.0824 for moderate and severe dysplasia and invasive tumor, respectively. Conclusions:Head and neck squamous cell carcinomas arise through premalignant intermediates and may be merely morphologic manifestations of accumulated genetic alterations. In keeping with this molecular tumor progression model, our study shows that mtDNA increases according to histopathologic grade, a phenomenon that may be a feedback mechanism that compensates for a generalized decline in respiratory chain function. Therefore, high mtDNA content may be another marker of genetic alteration, a measure of relative DNA injury, and a surrogate measure of histopathologic grade.
Significant advances in the functional outcomes achieved with cochlear implantation will likely require tissue-engineering approaches to improve the neural prosthesis interface. One strategy is to direct spiral ganglion neuron (SGN) axon growth in a highly organized fashion to approximate or contact stimulating electrodes. Here we assessed the ability of micropatterns induced by photopolymerization in methacrylate (MA) polymer systems to direct cultured neonatal rat SGN neurite growth and alignment of SG Schwann cells (SGSCs). SGN survival and neurite length were comparable among various polymer compositions. Remarkably, there was no significant difference in SGN survival or neurite length between laminin and non-laminin coated MA polymer substrates, suggesting high biocompatibility with SG tissue. Micropatterning with photopolymerization generated microchannels with a ridge periodicity of 50 µm and channel depths of 0.6–1.0 µm. SGN neurites grew within the grooves of the microchannels. These topographies strongly induced alignment of dissociated SGN neurites and SGSCs to parallel the pattern. By contrast, fibroblasts failed to align with the micropattern suggesting cell specific responses to topographical cues. SGN neurites extending from explants turned to parallel the pattern as they encountered the microchannels. The extent of turning was significantly correlated with angle at which the neurite initially encountered the pattern. These results indicate that SGN neurites respond to microtopographical features and that these features can be used to direct neurite growth in a highly organized fashion.
The endoscopic approach to pituitary surgery offers tumor outcomes comparable to those of open surgery, with no greater incidence of complications and an improved rhinology-specific quality of life.
Objectives Acute invasive fungal sinusitis (AIFS) remains a significant cause of morbidity and mortality in the immunocompromised patient population. Early diagnosis is key to improving patient outcomes. Frozen section biopsies have been shown to decrease time to diagnosis when compared with permanent pathology. However, its accuracy has not been adequately described in the literature, specifically in regard to AIFS. The aim of this study is to evaluate the statistical diagnostic accuracy of frozen sections and to review the etiology, clinical presentation, and current diagnostic protocols in management of AIFS. Study Design Case series with chart review. Setting Tertiary referral center. Subjects and Methods Retrospective review included 67 pathologic records in Co-Path, with search criteria including invasive fungal, clinical history, frozen section, and final diagnosis between the dates of 2006 and 2015. Results Sixty-seven cases were reviewed per the search criteria in Co-Path. Of these, 31 met further criteria of having had frozen section analysis. Variables such as sensitivity, specificity, positive predictive value, and negative predictive value were assessed. All 21 positive frozen sections correlated with positive permanent pathology, giving a positive predictive value of 100%. Frozen section biopsies were 87.5% sensitive and 100% specific. Conclusion Early diagnosis of AIFS has been shown to decrease morbidity and mortality. Frozen section biopsies remain key in obtaining an early diagnosis among patients with a high clinical suspicion for invasive fungal sinusitis. Frozen section biopsies positive for invasive fungal pathology were universally consistent with definitive diagnosis.
Significant heterogeneity exists with regard to performance of specific tasks aimed at minimizing error during ESS. Utilization of the ESS Checklist standardized practice across four institutions and significantly increased the likelihood that individual safety tasks were performed during the course of sinus surgery.
Background Although overall success rates of endoscopic sinus surgery (ESS) range from 76.0–97.5%, ongoing or recurrent symptoms may require revision surgery. Previous studies have shown that revision status is not a predictor of outcomes following ESS, but no distinction has been made between patients undergoing a single or multiple revision procedure. The purpose of this study was to compare quality-of-life (QOL) outcomes and associated risk factors of patients undergoing primary ESS, first revision, second, third, fourth, fifth or more revision ESS. Methods Demographic and risk factor data were collected from a multi-institutional prospective cohort of 552 patients undergoing primary (n=221) and revision (n=331) ESS for chronic rhinosinusitis. Mean preoperative Lund-Mackay CT scan scores, pre-/post-operative Lund-Kennedy endoscopy scores, Rhinosinusitis Disability Index (RSDI), and Chronic Sinusitis Survey (CSS) outcomes were analyzed using chi-squared testing and one-way ANOVA. Results Mean preoperative RSDI and CSS measurements were similar between primary ESS and all revision groups. Significantly more primary ESS patients met rigorous criteria for a minimally important difference in QOL improvement than revision ESS patients (73.8% vs.61.6%; p=0.003). There was no significant difference in mean QOL improvement between revision groups (all p≥0.174) even when comparing patients with and without nasal polyposis (all p≥0.312). Conclusions Generally patients undergoing primary, first revision, and multiple revision ESS showed post-operative improvement in QOL scores. More primary ESS patients had significant QOL improvement compared to revision ESS patients. There were no significant differences in mean QOL improvement between first, second, third, fourth, or fifth or more revision ESS.
BackgroundPathologic diagnosis remains the gold standard for final diagnosis of acute invasive fungal sinusitis (AIFS); however, other less invasive tests could suggest the presence of AIFS in at‐risk populations where early diagnosis is crucial. Serum galactomannan Aspergillus antigen has been shown to correlate with a diagnosis of invasive pulmonary aspergillosis; however, it has not adequately been evaluated in regard to AIFS. The objective of this study is to evaluate the statistical relevance of galactomannan in predicting diagnosis of AIFS.MethodsThis study was a retrospective review of pathologic records using Co‐Path from 2006 to 2017, incorporating 2 separate searches with designated criteria identifying patients who received pathologic evaluation for invasive fungal sinusitis. Electronic medical records were subsequently reviewed. After exclusions isolating at‐risk populations and removing duplications, 78 cases were reviewed using the indicated search criteria. Of these, 38 met further criteria of having had both pathologic evaluation and galactomannan analysis. Statistical variables were assessed, as well as all‐cause mortality. Peak and closest galactomannan levels were evaluated.ResultsOverall, galactomannan had a sensitivity of 44.8% (95% confidence interval [CI], 26.5% to 64.3%), specificity of 100% (95% CI, 66.4% to 100%), positive predictive value of 100% (95% CI, 74.3% to 100%), and negative predictive value of 36% (95% CI, 18.0% to 57.5%). No significant association was observed in galactomannan status and mortality in this patient population.ConclusionPositive serum galactomannan can be an indication of AIFS in patients with a high clinical suspicion. In our study, a positive galactomannan always correlated with a positive pathologic diagnosis. However, given its low sensitivity, one must use caution in relying on galactomannan as a screening tool in diagnosis of AIFS.
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