Faculty Bibliography

PURPOSE:To compare differences in the contour of the anterior and posterior glenoid in 3-dimensional computed tomography reconstructions as a reason for variability in estimating glenoid bone loss. METHODS:Three reviewers digitally placed 11 points (1 at 6 o'clock, 5 from 3 to 6 o'clock, and 5 from 6 to 9 o'clock) along the inferior half of glenoid 3-dimensional computed tomography reconstructions of 32 cadaveric specimens. A best-fit circle for the whole glenoid was determined from all 11 points. The anterior 6 points determined an anterior-based circle, as for estimation of posterior bone loss. The posterior 6 points determined a posterior-based circle, as for estimation of anterior bone loss. The area and radii were determined for all circles. Individual intraclass correlations were used to evaluate reliability. Paired t-tests and Wilcoxon signed rank tests were used to compare areas and radii of the anterior and posterior circles relative to the best-fit glenoid circle. Significance was defined as P < .05. RESULTS:There was good-to-excellent inter-rater reliability for the overall best-fit circle (intraclass correlation coefficient [ICC] = 0.97 [95% confidence interval (CI), 0.95-0.99]), anterior circle (ICC = 0.82 [95% CI, 0.71-0.90]), and posterior circle (ICC = 0.78 [95% CI, 0.65-0.88]). The average area of the posterior-based circle was significantly greater than the area of the best-fit circle for the intact glenoid (111% [95% CI, 104.3%-117.7%]; P = .0016). The average radius of the posterior-based circle was significantly larger than the radius of the intact glenoid (105% [95% CI, 101.7%-108.3%]; P = .0042). There were no significant differences between the average area (96% [95% CI, 89.0%-103.0%]; P = .16) and average radius (97% [95% CI, 93.5%-100.5%]; P = .19) for the anterior-based circle relative to the actual whole glenoid. CONCLUSIONS:Estimation of anterior glenoid bone loss based on the normal posterior glenoid rim may overestimate glenoid bone loss because of differences in the contour of the anterior and posterior glenoid, whereas estimations of posterior glenoid bone loss based on the anterior rim did not differ significantly from the intact glenoid. CLINICAL RELEVANCE:A circle based on the remaining intact portion of the injured glenoid may lead to an inaccurate estimate of glenoid bone loss.

OBJECTIVE:Given rising scrutiny of healthcare expenditures, understanding intervention costs is increasingly important. This study aimed to compare and characterize costs for vestibular schwannoma (VS) management with microsurgery and radiosurgery to inform practice decisions and appraise cost reduction strategies. METHODS:In conjunction with medical records, internal hospital financial data were used to evaluate costs. Total cost was divided into index costs (costs from arrival through discharge for initial intervention) and follow-up costs (through 36 months) for 317 patients with unilateral VSs undergoing initial management between June 2011 and December 2015. A retrospective matched cohort based on tumor size with 176 patients (88 undergoing each intervention) was created to objectively compare costs between microsurgery and radiosurgery. The full sample of 203 patients treated with resection and 114 patients who underwent radiosurgery was used to evaluate a broad range of outcomes and identify cost contributors within each intervention group. RESULTS:Within the matched cohort, average index costs were significantly higher for microsurgery (100% by definition, because costs are presented as a percentage of the average index cost for the matched microsurgery group; 95% CI 93-107) compared to radiosurgery (38%, 95% CI 38-39). Microsurgery had higher average follow-up costs (1.6% per month, 95% CI 0.8%-2.4%) compared to radiosurgery (0.5% per month, 95% CI 0.4%-0.7%), largely due to costs incurred in the initial months after resection. A major contributor to total cost and cost variability for both resection and radiosurgery was the need for additional interventions in the follow-up period, which were necessary due to complications or persistent functional deficits. Although tumor size was not associated with increased total costs for radiosurgery, linear regression analysis demonstrated that, for patients who underwent microsurgery, each centimeter increase in tumor maximum diameter resulted in an estimated increase in total cost of 50.2% of the average index cost of microsurgery (95% CI 34.6%-65.7%) (p < 0.001, R2 = 0.17). There were no cost differences associated with the proportion of inpatient days in the ICU or with specific surgical approach for patients who underwent resection. CONCLUSIONS:This study is the largest assessment to date based on internal cost data comparing VS management with microsurgery and radiosurgery. Both index and follow-up costs are significantly higher when tumors were managed with resection compared to radiosurgery. Larger tumors were associated with increased resection costs, highlighting the incremental costs associated with observation as the initial management.

OBJECTIVECerebral venous sinus thrombosis (CVST) is a known complication of surgeries near the major dural venous sinuses. While the majority of CVSTs are asymptomatic, severe sinus thromboses can have devastating consequences. The objective of this study was to prospectively evaluate the true incidence and risk factors associated with postoperative CVST and comment on management strategies.METHODSA prospective study of 74 patients who underwent a retrosigmoid, translabyrinthine, or suboccipital approach for posterior fossa tumors, or a supratentorial craniotomy for parasagittal/falcine tumors, was performed. All patients underwent pre- and postoperative imaging to evaluate sinus patency. Demographic, clinical, and operative data were collected. Statistical analysis was performed to identify incidence and risk factors.RESULTSTwenty-four (32.4%) of 74 patients had postoperative MR venograms confirming CVST, and all were asymptomatic. No risk factors, including age (p = 0.352), BMI (p = 0.454), sex (p = 0.955), surgical approach (p = 0.909), length of surgery (p = 0.785), fluid balance (p = 0.943), mannitol use (p = 0.136), tumor type (p = 0.46, p = 0.321), or extent of resection (p = 0.253), were statistically correlated with thrombosis. All patients were treated conservatively, with only 1 patient receiving intravenous fluids. There were no instances of venous infarctions, hemorrhages, or neurological deficits. The rate of CSF leakage was significantly higher in the thrombosis group than in the nonthrombosis group (p = 0.01).CONCLUSIONSThis prospective study shows that the radiographic incidence of postoperative CVST is higher than that previously reported in retrospective studies. In the absence of symptoms, these thromboses can be treated conservatively. While no risk factors were identified, there may be an association between postoperative CVST and CSF leak.

BACKGROUND:Nasal device-related pressure ulcers are scarcely addressed in the literature. OBJECTIVES/OBJECTIVE:To assess the prevalence and severity of cutaneous and mucosal nasogastric tube (NGT)-associated pressure ulcers (PU) in critically ill patients and to define predictors for their formation. METHODS:A single center observational study of intensive care unit patients with a NGT for more than 48 hours was conducted. Nasal skin was evaluated for PU. Ulcers were graded according to their depth. Consenting patients underwent a nasoendoscopic examination to evaluate intranasal mucosal injury. RESULTS:The study comprised 50 patients, 17 of whom underwent nasoendoscopic examination. Mean time of NGT presence in the nose was 11.3 ± 6.17 days. All patients had some degree of extranasal PU, 46% were low grade and 54% were high grade. Predictors for high grade extranasal PU compared to low grade PU were higher peak Sepsis-related Organ Failure Assessment (SOFA) scores (11.52 vs. 8.87, P = 0.009), higher peak C-reactive protein (CRP) levels (265.3 mg/L vs. 207.58, P = 0.008), and bacteremia (33.3% vs. 8.7%, P = 0.037). The columella was the anatomical site most commonly involved and the most severely affected. The number of intranasal findings and their severity were significantly higher in the nasal cavity containing the NGT compared to its contralateral counterpart (P = 0.039 for both). CONCLUSIONS:NGTs cause injury to nasal skin and mucosa in critically ill patients. Patients with bacteremia, high CRP, and high SOFA scores are at risk for severe ulcers, warranting special monitoring and preventive measures.

OBJECTIVE:To assess the anatomical and functional features of the vocal folds during different phases of the female menstrual cycle. METHODS:An observational study of 17 healthy fertile female volunteers not using hormonal contraception was carried out. Each volunteer underwent two examinations: first, during the early days of the menstrual cycle when progesterone levels are low (p-depletion), and second, during premenstruation when progesterone levels are high (p-peak). The workup included blood hormone levels, Voice Handicap Index, acoustic analysis, rigid telescopy, stroboscopy, and narrow band imaging. The videos were evaluated by blinded observers. RESULTS:The participants' mean age was 31.7 ± 5.6 (range 23-43). Progesterone levels were 13- to 45-fold higher in p-peak relative to p-depletion. No significant differences were detected in Voice Handicap Index scores, stroboscopic reports, or acoustic analysis between p-peak and p-depletion examinations. Analyzing the rigid telescopy and narrow band imaging videos, the observers tended to estimate the different laryngeal subsites more vascularized during the p-peak examination. Moreover, this tendency was significantly correlated with blood progesterone levels during the p-depletion examinations; the lower the blood progesterone levels were during p-depletion, the higher the probability for the observers to estimate the p-peak examinations more vascularized (P value = 0.024). CONCLUSIONS:Alterations in laryngeal vascular characteristics are evident throughout the menstrual cycle and may suggest increased congestion during premenstrual days. Variations in progesterone levels during the menstrual cycle correlate with laryngeal vascular changes. Hormone-related alterations in vocal folds' vascularity may have a role in the variability of vocal performance in certain women.

PURPOSE:To assess the safety of medical-ward bedside percutaneous dilatational tracheostomy (GWB-PDT). MATERIALS AND METHODS:A retrospective study of all patients who underwent elective GWB-PDT between 2009 and 2015. A joint otolaryngology-ICU team performed all GWB-PDTs. The patients were followed until decannulation, discharge or death. Complications were divided into early (within 24 h) and late, and into minor and major. RESULTS:Two hundred and fifty six patients were included in the study. The mean age was 77.7 ± 11.8 Medical history included cardiac comorbidities (42.6%) and cerebrovascular accidents (34.4%). Overall, 48 patients (18.9%) had 60 complications, of which 70% (42/60) were minor (13 early; 29 late complications). Fifteen patients (5.9%) had major complications. Eight patients had early major complications (loss of airway - two patients [0.8%], pneumothorax - two patients [0.8%], resuscitation - one patient [0.4%], and a single patient (0.4%) died within 24 h following PDT). Two additional patients (0.8%) underwent conversion to an open tracheostomy. Seven patients had late complications (airway complications in six patients [2.3%] and major bleeding in a single patient [0.4%]). Of the seven patients with late major complications, three had two major complications. Half of the complications occurred by POD 3. CONCLUSION:GWB-PDT is a feasible and safe solution for tracheostomies in general-ward ventilated patients.

BACKGROUND: Tumor heterogeneity presents a major challenge to cancer diagnosis and treatment. In addition to interpatient tumor variability, intratumoral heterogeneity characterized by distinct molecular and phenotypic profiles is increasingly recognized as a major cause of therapy resistance and cancer recurrence. Because DNA methylation patterns are largely responsible for determining cell-type-specific functioning, we hypothesized that distinct DNA methylation and proteomic alterations could be identified in histologically-defined invasive and proliferative tumor cell populations in human isocitrate dehydrogenase 1 (IDH1)- mutated and wild-type glioblastoma (GBM).
METHOD(S): Formalin-fixed paraffin-embedded tissue sections of human adult IDH1-mutated and wild-type GBM were laser-microdissected (LM) into perinecrotic pseudopalisading tumor cells (PPCs), non-pseudopalisading tumor core cells (NPPCs), invasive subpial spread (SPS) and perivascular satellitosis tumor cells and brain adjacent to tumor cells prior to analysis and compared to non-microdissected tumor (NMT) and/or germline DNA. Genomewide DNA methylation and chromosomal copy numbers were determined with Infinium MethylationEPIC 850K BeadChip and intratumoral DNA methylation patterns compared by unsupervised hierarchical clustering. Label-free quantitative liquid chromatography-mass spectrometry of proteins was performed and proteins differentially expressed across LM areas subjected to pathway enrichment analysis.
RESULT(S): Unsupervised hierarchical classification of DNA methylation patterns for each LM area and NMT demonstrated remarkable clustering for all patients, based on methylation probe and methylated gene patterns. Proteomics analysis showed upregulation of hypoxia-inducible factor-1 inducible proteins in hypoxic PPCs. Out of 1819 proteins quantified, 5 were overexpressed and 9 underexpressed more than 10-fold in SPS compared with NPPCs and associated with alterations in metabolism, transport, extracellular matrix and apoptosis. Correlation of protein expression and DNA methylation patterns was noted.
CONCLUSION(S): Compared to NPPCs, SPS cells migrating toward the invasive edge share a relatively consistent epigenetic and proteomic signature, suggesting potentially targetable common mechanism(s) of invasion shared among GBM

BACKGROUND: Up to 20% of meningiomas are aggressive tumors with high recurrence rates and poor prognosis. Biomarkers predicting the risk of an unfavorable clinical course are lacking although aberrations in NF2, increased copy number variations and a hypomethylated phenotype have been associated with more aggressive behavior. Mutational signatures (MS) are characteristic patterns of somatic mutations seen in cancer genomes associated with aging, exposure to certain mutagens, or defective DNA repair. We aimed to identify MS patterns in clinically aggressive meningiomas.
METHOD(S): We performed whole exome sequencing of 18 de novo meningiomas (locally invasive and recurrent WHO I, n=6; atypical WHO II, n=4; anaplastic WHO III, n=8). Median PFS was 18.9 months. Copy numbers and DNA methylation phenotype were assessed by DNA methylation array analysis. Mutational signatures were identified using published signature algorithms (COSMIC).
RESULT(S): MS1 and MS5 (aging) were found in 18 (100%) cases. MS associated with defective DNA MMR were highly prevalent: MS20 and MS26 were detected in 18 (100%) and MS6 in 2 (12%) cases. MS12 (unknown etiology) was present in 14 (82%) cases. Despite the association with defective DNA MMR, none (0%) of the MS6 cases harbored somatic mutations associated with DNA MMR while MS12 tumors were enriched for mutations in DNA MMR (43%), chromatin remodeling (36%) and other cancer-associated genes (7%). MS6 tumors had significantly lower indels compared to non-MS6 tumors (p=0.01). Tumors with mutations in chromatin remodeling genes had a significantly higher rate of single nucleotide variants (SNVs) compared to cases without such mutations (p=0.02).
CONCLUSION(S): MS associated with defective DNA MMR were highly prevalent in this set of aggressive meningiomas. However, despite the association with DNA MMR, MS6 meningiomas harbored no somatic mutations associated with DNA MMR while MS12 tumors were enriched for mutations in DNA MMR, chromatin remodeling and cancerassociated genes