Virtual Surgical Planning and Three-Dimensional Models for Precision Sinonasal and Skull Base Surgery.

Sinonasal and skull base malignancies represent a rare, heterogenous group of pathologies with an incidence of 0.556 per 100,000 persons in the population. Given the numerous critical anatomic structures located adjacent to the sinonasal cavity and skull base, surgery for tumors in this region requires careful pre-operative planning with the assistance of radiological imaging and intraoperative image guidance technologies to reduce the risk of complications. Virtual surgical planning (VSP) and three-dimensional models (3DMs) are adjunctive technologies which assist clinicians to better visualize patient anatomy using enhanced digital radiological images and physical stereolithographic models based on patients' personal imaging. This review summarizes our institutional experience with VSP and 3DMs in sinonasal and skull base surgical oncology. A clinical case series is used to thematically illustrate the application of VSP and 3DMs in surgical ablation, reconstruction, patient communication, medical education, and interdisciplinary teamwork in sinonasal and skull base surgery.

Understanding frozen section histopathology in Sinonasal and anterior skull base malignancy and proposed reporting guidelines.

BACKGROUND: Intraoperative frozen section histopathology (IFSH) in sinonasal and skull base surgery although widely used is not well studied. METHODS: We reviewed a database of sinonasal and anterior skull base tumors, between 1973 and 2019, and identified 312 suitable operative cases. Clinicopathologic data was collected and analyzed, in addition to descriptive data for histopathological reports classified as "ambiguous," or "limited/insufficient-quality/quantity." RESULTS: Overall, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for IFSH were 90.2%, 97.5%, 94.2%, 95.6%, and 95.2%, respectively. IFSH for adenocarcinoma, salivary carcinoma, and SCC all demonstrated a better clinical utility with a sensitivity of 90% or greater, while it was less than 90% for esthesioneuroblastoma, melanoma, and sarcoma. Other factors such as unclear reporting, poor quality specimens, or limited quality specimens were shown to lower diagnostic performance. Based on limitations identified, we proposed a novel IFSH reporting algorithm to improve IFSH in sinonasal and skull base surgery. CONCLUSIONS: IFSH is an accurate and clinically useful technique in sinonasal and skull base surgery patients; however, limitations exist.

Factors predicting pharyngocutaneous fistula in patients after salvage laryngectomy for laryngeal malignancy - A multicenter collaborative cohort study.

OBJECTIVES: Pharyngocutaneous fistula (PCF) is a major morbidity of salvage total laryngectomy (TL). Understanding the factors predicting PCF is fundamental to managing laryngeal cancer. We aim to assess factors associated with PCF following salvage TL in a multicenter, international retrospective cohort study of academic centers in the US and Canada. RESULTS: In total, 550 patients post-salvage TL were identified (mean [SD; range] age, 64 [10.4; 32-90] years; 465 [85 %] male and 84 [15 %] female) between 2000 and 2014. Rate of PCF was 23 % (n = 127) with median time to PCF of 2.9 weeks. Surgical management of PCF was required in 43 % (n = 54) while 57 % (n = 73) required wound care alone. Rates of PCF differed by primary treatment modality [radiation, 20 % (n = 76); chemoradiation, 27 % (n = 40); not available (n = 6)] and use of vascularized tissue in pharyngeal closure [free/regional flap, 18 % (n = 25); no vascularized tissue/primary closure, 24 % (n = 98); not available (n = 4)]. There was no statistically significant association between PCF and treatment with chemoradiation (HR, 1.32; 95 % CI, 0.91-1.93, p = 0.14) or lack of vascularized tissue reconstruction (HR, 1.41, 95 % CI 0.91-2.18, p = 0.12). Significant association between PCF and advanced stage (T3 or T4), positive margin, close margin (<5mm), lymphovascular invasion and pre-operative tracheostomy were identified on univariable analysis. Positive surgical margin (HR, 1.91; 95 % CI, 1.11 to 3.29) was the only significant association on multivariable analysis. CONCLUSION: We highlight positive surgical margin as the only variable significantly associated with increased risk of PCF following salvage TL on multivariable analysis in a large cohort across several major head and neck oncology centers.

Stimulated Raman Histology for Rapid Intra-Operative Diagnosis of Sinonasal and Skull Base Tumors.

OBJECTIVE: Intra-operative stimulated Raman histology (SRH) is a novel technology that uses laser spectroscopy and color-matching algorithms to create images similar to the formalin-fixed paraffin-embedded (FFPE) section. We aim to assess the accuracy of SRH in a novel range of sinonasal and skull base tumors. METHODS: Select patients undergoing sinonasal and skull base surgery using the Invenio Imaging™ Nio™ Laser Imaging SRH system between June 2020 and September 2021 were assessed. The SRH images were reviewed for pathologic features similar to frozen section (FS) and FFPE. Time taken for results and diagnostic concordance was assessed. RESULTS: Sixty-seven SRH images from 7 tumor types in 12 patients were assessed. Pathologies included squamous cell carcinoma, rhabdomyosarcoma, inverted papilloma, adenoid cystic carcinoma, SMARCB1-deficient sinonasal carcinoma, mucosal melanoma, metastatic colonic adenocarcinoma, and meningioma. Tumor was identified in 100% of lesional specimens, with characteristic diagnostic features readily appreciable on SRH. Median time for diagnosis was significantly faster for SRH (4.3 min) versus FS (44.5 min; p = <.0001). Where SRH sample site matched precisely to FS (n = 32/67, 47.8%), the same diagnosis was confirmed in 93.8%. Sensitivity, specificity, precision, and overall accuracy of SRH were 93.3%, 94.1%, 93.8%, and 93.3%, respectively. Near-perfect concordance was seen between SRH and FS (Cohen's kappa [κ] = 0.89). CONCLUSION: Stimulated Raman histology can rapidly produce images similar to FFPE H&E in sinonasal and skull base tumors. This technology has the potential to act as an adjunct or alternative to standard FS. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:2142-2147, 2022.

Diagnostic approach to patients at risk of otogenic skull base osteomyelitis.

BACKGROUND: Otogenic skull base osteomyelitis (OSBO) is rare and potentially fatal sequelae of otitis externa. Accurate and timely diagnosis is important due to rising incidence, morbidity and costs associated with treatment. Consensus on the diagnostic approach for OSBO has yet to be reached, in particular the utility of imaging modalities. AIMS/OBJECTIVES: This study reviews a single institution's high-volume experience of OSBO, with the aim of analysing clinicopathologic features and imaging studies to develop a diagnostic algorithm. MATERIAL AND METHODS: A retrospective review of patients admitted with OSBO from 2009 to 2019, was performed. After applying inclusion and exclusion criteria, 103 patients with 106 unique episodes of suspected OSBO were selected. De-identified information including patient demographics, clinicopathologic features and imaging outcomes was recorded and analysed. RESULTS: HbA1c ≥ 7% significantly predicted for OSBO in univariate (OR 7.83, 95% CI 1.85-33.16, p = 0.01) and multivariate analyses (OR 5.21, 95% CI 1.05-25.81, p = 0.04). The CT/technetium-99m/gallium-67 combination produced better diagnostic accuracy for OSBO (AUROC 0.96, 95% CI 0.92-1), when compared to a CT/MRI combination (AUROC 0.86, 95% CI 0.79-0.93). CONCLUSIONS AND SIGNIFICANCE: Once there is a clinical suspicion for OSBO, diagnosis is established by synthesising results from clinical assessment, pathologic investigations and imaging modalities. The imaging utilised to diagnose OSBO should vary according to the clinical situation and limitations of each modality.

Massive vagal schwannoma in an 11-year-old girl.

We describe an unusual case of a young girl presenting with a large vagal schwannoma necessitating a transcervical-mandibulotomy approach for total tumor resection. The presentation is unique due to the size of the lesion, the patient's age, the operative approach, and molecular pathology.

Systemic methylprednisolone for hearing preservation during cochlear implant surgery: A double blinded placebo-controlled trial.

AIM: To assess whether a single, peri-operative, high dose of methylprednisolone can improve the preservation of residual acoustic hearing following cochlear implantation (CI). METHODS: This was a double blinded placebo-controlled trial, performed in a tertiary academic centre. The hypothesis was that methylprednisolone would improve the preservation of hearing, and lower electrode impedances. Adult patients (18-85 years) with hearing at 85 dB or better at 500 Hz in the ear to be implanted were randomly allocated to either treatment (methylprednisolone, 1g administered intravenously upon induction of anaesthesia) or control (normal saline infusion). As per standard clinical practice, all patients received a routine dose of dexamethasone (8 mg intravenously) on induction of anaesthesia. Implantation was undertaken with a slim and flexible lateral wall electrode via the round window. Surgical technique was routine, with adherence to soft surgical principles. The primary outcome was hearing preservation within 20 dB at 500 Hz, 12 months following cochlear implantation. Secondary outcomes included hearing preservation at 6 weeks and 3 months, monopolar electrode impedance, and Consonant-Vowel-Consonant (CVC) Phoneme scores at 3 and 12 months after surgery. RESULTS: Forty-five patients were enrolled into the control group and 48 patients received the steroid. The number of patients achieving hearing preservation at 12 months did not differ significantly between those receiving methylprednisolone treatment and the controls. There were no differences in hearing preservation at any frequency at either 6 weeks or 3 months after implantation. Neither CVC phoneme scores nor electrode impedances differed between the groups. CONCLUSIONS: This paper demonstrates that high-dose local steroid injection at surgery was not effective in preventing a loss of residual hearing, improving speech perception, or lowering electrode impedances. The findings were contrary to the experimental literature, and emerging clinical evidence that steroid elution from implant electrodes influences cochlear biology in humans. We found no evidence to support the widely-held practice of administering intravenous steroids in the perioperative period, in an attempt to preserve residual hearing.

Bupropion for the treatment of apathy in Huntington's disease: A multicenter, randomised, double-blind, placebo-controlled, prospective crossover trial.

OBJECTIVE: To evaluate the efficacy and safety of bupropion in the treatment of apathy in Huntington's disease (HD). METHODS: In this phase 2b multicentre, double-blind, placebo-controlled crossover trial, individuals with HD and clinical signs of apathy according to the Structured Clinical Interview for Apathy-Dementia (SCIA-D), but not depression (n = 40) were randomized to receive either bupropion 150/300mg or placebo daily for 10 weeks. The primary outcome parameter was a significant change of the Apathy Evaluation Scale (AES) score after ten weeks of treatment as judged by an informant (AES-I) living in close proximity with the study participant. The secondary outcome parameters included changes of 1. AES scores determined by the patient (AES-S) or the clinical investigator (AES-C), 2. psychiatric symptoms (NPI, HADS-SIS, UHDRS-Behavior), 3. cognitive performance (SDMT, Stroop, VFT, MMSE), 4. motor symptoms (UHDRS-Motor), 5. activities of daily function (TFC, UHDRS-Function), and 6. caregiver distress (NPI-D). In addition, we investigated the effect of bupropion on brain structure as well as brain responses and functional connectivity during reward processing in a gambling task using magnetic resonance imaging (MRI). RESULTS: At baseline, there were no significant treatment group differences in the clinical primary and secondary outcome parameters. At endpoint, there was no statistically significant difference between treatment groups for all clinical primary and secondary outcome variables. Study participation, irrespective of the intervention, lessened symptoms of apathy according to the informant and the clinical investigator. CONCLUSION: Bupropion does not alleviate apathy in HD. However, study participation/placebo effects were observed, which document the need for carefully controlled trials when investigating therapeutic interventions for the neuropsychiatric symptoms of HD. TRIAL REGISTRATION: ClinicalTrials.gov 01914965.

Dental clinical teaching: perceptions of students and teachers.

The objective of this study was to explore perceptions of dental student clinicians and clinical teachers about dental clinical teaching to provide primary data for dental researchers and educators. Student focus group data provided background for development of a questionnaire that explored three themes related to clinical teaching. Twenty-one teachers and forty-five student respondents completed the twenty-five-item questionnaire in 2003. In the theme of the teacher/student relationship, no statistically significant differences were seen between teacher and student group perceptions. In the theme of educational theory applied in dental clinical teaching, a statistically significant difference was seen between teacher and student groups in the value of preclinical instruction in senior clinical years and in the value of a clinical log book. In the theme of skills required for clinical dental practice, a statistically significant difference was seen between teacher and student groups in the value of a critical appreciation of evidence-based practice as one of the skills. The study overall indicates that the dental clinical learning environment supports close perceptual conformity between students and clinical teachers in regard to what each group considers to be "good practice" in clinical teaching. The findings of this study indicate that some techniques that have been advocated to enhance clinical learning, such as evidence-based teaching methods, require further investigation.

Herpes simplex virus ICP27 activation of stress kinases JNK and p38.

We previously reported that herpes simplex virus type 1 (HSV-1) can activate the stress-activated protein kinases (SAPKs) p38 and JNK. In the present study, we undertook a comprehensive and comparative analysis of the requirements for viral protein synthesis in the activation of JNK and p38. Infection with the UL36 mutant tsB7 or with UV-irradiated virus indicated that both JNK and p38 activation required viral gene expression. Cycloheximide reversal or phosphonoacetic acid treatment of wild-type virus-infected cells as well as infection with the ICP4 mutant vi13 indicated that only the immediate-early class of viral proteins were required for SAPK activation. Infection with ICP4, ICP27, or ICP0 mutant viruses indicated that only ICP27 was necessary. Additionally, we determined that in the context of virus infection ICP27 was sufficient for SAPK activation and activation of the p38 targets Mnk1 and MK2 by infecting with mutants deleted for various combinations of immediate-early proteins. Specifically, the d100 (0-/4-) and d103 (4-/22-/47-) mutants activated p38 and JNK, while the d106 (4-/22-/27-/47-) and d107 (4-/27-) mutants did not. Finally, infections with a series of ICP27 mutants demonstrated that the functional domain of ICP27 required for activation was located in the region encompassing amino acids 20 to 65 near the N terminus of the protein and that the C-terminal transactivation activity of ICP27 was not necessary.

Inhibition of the stress-activated kinase, p38, does not affect the virus transcriptional program of herpes simplex virus type 1.

To investigate the impact of stress kinase p38 activation on HSV-1 transcription, we performed a global transcript profile analysis of viral mRNA using an oligonucleotide-based DNA microarray. RNA was isolated from Vero cells infected with the KOS strain of HSV-1 in the presence or absence of SB203580, a pyridinyl imidazole inhibitor of p38. Under conditions that eliminated ATF2 activation but had no effect on c-Jun, and reduced virus yield by 85-90%, no effect on accumulation of viral IE, DE, or L transcripts was observed by array analysis or selected Northern blot analysis at 2, 4, and 6 h post infection. Results of array data from cells infected with the ICP27 mutant d27-1 in the presence or absence of SB203580 only reflected the known restricted transcription phenotype of the ICP27 mutant. This result is consistent with a role for p38 activation on virus replication lying downstream of the essential role of ICP27 in DE and perhaps late transcription regulation. No effect of SB203580 on transcription was detected after infection with the ICP0 mutant 7134, at 0.5 or 5.0 PFU/cell, though decreases in the rate of accumulation of all kinetic classes of mRNA could be detected, relative to wt virus. These results indicate that inhibiting p38 activity in Vero cells, while significantly reducing wt virus yield, demonstrated no obvious impact on the program of viral transcription.

Development and application of a monoclonal-antibody technique for counting Aureococcus anophagefferens, an alga causing recurrent brown tides in the Mid-Atlantic United States.

A method was developed for the rapid detection and enumeration of Aureococcus anophagefferens, the cause of harmful algal blooms called "brown tides" in estuaries of the Mid-Atlantic United States. The method employs a monoclonal antibody (MAb) and a colorimetric, enzyme-linked immunosorbent assay format. The MAb obtained exhibits high reactivity with A. anophagefferens and very low cross-reactivities with a phylogenetically diverse array of other protists and bacteria. Standard curves are constructed for each 96-well microtiter plate by using known amounts of a preserved culture of A. anophagefferens. This approach allows estimation of the abundance of the alga in natural samples. The MAb method was compared to an existing method that employs polyclonal antibodies and epifluorescence microscopy and to direct microscopic counts of A. anophagefferens in samples with high abundances of the alga. The MAb method provided increased quantitative accuracy and greatly reduced sample processing time. A spatial survey of several Long Island estuaries in May 2000 using this new approach documented a range of abundances of A. anophagefferens in these bays spanning nearly 3 orders of magnitude.