Development of normalized quantitative measures of lumbar disc degeneration.

Background: Lumbar disc degeneration (DD) is widely regarded as a likely contributor to low back pain (LBP), but the association between DD and LBP is relatively weak. No known studies have normalized quantitative measures of DD severity relative to multiple variables such as age, height, and disc level. This study developed normalized quantitative measures (z-scores) of disc signal intensity (DSI) and disc height (DH) to rate relative severity of DD. Methods: Raw (unnormalized) quantitative measures of DSI and DH alongside potential normalization variables were acquired from MRI scans and clinical data of 76 patients. The associations between the raw quantitative measures and potential normalization variables were investigated to develop the normalized quantitative measures (z-scores) of DSI and DH. Construct validity was assessed by comparing the normalized measures to an experienced radiologist's subjective measures of relative severity of DSI and DH loss. Results: CSF signal intensity, age, and disc level were significantly associated with raw DSI (R 2 = 0.06, 0.25, and 0.09, respectively). Lumbar height and disc level were significantly associated with raw DH (R 2 = 0.13 and 0.31). Normalizing DSI and DH by these variables resulted in stronger relationships (R 2 = 0.39 and 0.37) than raw DSI and DH (R 2 = 0.24 and 0.31) with the radiologist's subjective measures. Normalized DSI and DH were both normally distributed (p = 0.32 and 0.12). Conclusions: Construct validity and the distributions suggested that normalized quantitative measures of DSI and DH are better than existing measures of DSI and DH at rating relative DD severity. Determining whether normalized quantitative measures are more predictive of clinical outcomes is important future research.

Supercharged deep inferior epigastric perforator flap for reconstruction of soft tissue defect after excision of giant invasive squamous cell carcinoma of the thigh in a refractory diabetic with Pseudomonas aeruginosa infection.

Patients with large defects after oncologic surgery often require enhanced surgical planning to optimize reconstructive outcomes. As such, medically complex patients require innovative solutions when utilizing abdominal flaps due to concern for ischemia of the distal tissue. Vascular augmentations, such as supercharging or turbocharging, serve to increase perfusion in these medical complex patients to ensure flap survival. In this report, we highlight the use of a supercharged bilateral pedicled deep inferior epigastric perforator (DIEP) flap in a patient with a 231 cm2 thigh defect in the setting of uncontrolled diabetes. A 57-year-old male with poorly-controlled diabetes (blood sugar prior to surgery 510 mg/dL) and iron deficiency anemia presented with a two-year history of a large nonmetastatic squamous cell carcinoma (SCC) measuring 19 × 9 cm2 on the right thigh. Positron emission tomography/computed tomography and biopsies of the right retroperitoneal and inguinal lymph nodes diagnosed the mass as Stage 3 localized SCC. After excision, we performed immediate reconstruction of the resultant defect with a supercharged bilateral pedicled DIEP flap. The flap was pedicled on the ipsilateral DIEP and the contralateral perforator was anastomosed to the descending branch of the lateral circumflex femoral artery (DLCFA) at the inferior aspect of the defect. A venous coupler was used for the veins and the arteries were hand-sewn in end-to-end fashion. The supercharged bilateral pedicled DIEP flap was utilized for enhanced augmented perfusion to the distal edge of the pedicled flap in a high-risk patient. The patient's clinical course was complicated by a Pseudomonas infection of a small hematoma requiring operative washout and debridement of necrotic fat. However, the flap survived and covered the defect completely. The patient required outpatient antibiotics for the Pseudomonas infection which resolved completely without further need for operative intervention. At 6-month follow up, the reconstruction was stable with no tumor recurrence on clinical exam. Our results suggest that a supercharged pedicled DIEP flap may be a viable option for large defects of the thigh and can may be utilized in medically complex patients with poor capacity for wound healing.

Tracheoesophageal Fistula as a Complication of Prolonged Ventilation in COVID-19: Description of Reconstruction and Review of the Literature.

Infection with COVID-19 pneumonia may necessitate intubation and mechanical ventilation. Viral inflammation and pressure necrosis may lead to scarring, stenosis, and in severe cases, fistula formation. Nonmalignant tracheoesophageal fistulas (TEF) represent a surgical challenge and may necessitate locoregional tissue transfer and tracheal resection to prevent recurrence and maintain airway patency. We present a case of TEF in a 63-year-old female secondary to prolonged mechanical ventilation in the setting of COVID pneumonia, detailing the clinical findings and surgical repair. Primary closure of the esophageal defect with pectoralis major muscle flap onlay and tracheal resection, with median sternotomy for access, provided successful intervention, allowing for subsequent tracheostomy decannulation and return to a complete oral diet. This case offers further evidence of the increased risk of airway complications in COVID-19 infection and provides otolaryngologists with an example of a rare surgical approach useful in management.

Video-Based Tracheostomy Care Education for Medical Students.

Objective: Tracheostomy is a common procedure that requires management by a multidisciplinary team of health care providers across a range of surgical and nonsurgical specialties. Nonsurgical health care providers have demonstrated a lack of knowledge and confidence in tracheostomy care, which improve with tracheostomy education programs. However, tracheostomy care is rarely included in preresidency medical education. The purpose of this study is to evaluate the effectiveness of a tracheostomy care video on third-year medical students' knowledge of and confidence in performing tracheostomy care. Methods: Prior to beginning clinical rotations, third-year medical students completed a 10-question tracheostomy care knowledge test (100 points total) and 11-question confidence survey (110 points total). After watching an 18-minute teaching video on tracheostomy care, students repeated the knowledge test and confidence survey. Results: An overall 147 medical students completed the educational module. After they watched the tracheostomy education video, their average score on the knowledge test improved from 57.8 to 88.9 out of 100 (P < .0001), and their average rating in confidence improved from 12.7 to 49.1 out of 110 (P < .0001). Students rated the helpfulness of the video a 7.4 out of 10. Discussion: Medical students' knowledge of tracheostomy care and confidence in caring for patients with tracheostomies improved after watching the video. Tracheostomy education should be included in early medical education so that future physicians of various specialties can better care for this patient population. Implications for Practice: Internet-published videos are an accessible educational resource with great potential application to various topics within otolaryngology, including tracheostomy care.

Association of Neoadjuvant Pembrolizumab for Oral Cavity Squamous Cell Carcinoma With Adverse Events After Surgery in Treatment-Naive Patients.

Importance: Pembrolizumab, a monoclonal antibody targeting programmed cell death 1, is currently approved by the US Food and Drug Administration for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). The potential neoadjuvant role of programmed cell death 1 inhibitors in primary surgical management of HNSCC and effects on surgical outcomes are poorly understood. Objective: To evaluate the incidence of postoperative adverse events in treatment-naive patients with advanced oral cavity cancer receiving neoadjuvant pembrolizumab when compared with matched controls, as part of a window-of-opportunity multi-institutional clinical trial assessing neoadjuvant pembrolizumab for locally advanced HNSCC. Design, Setting, and Participants: This retrospective cohort study at a single tertiary academic institution included treatment-naive patients with local regionally advanced oral cavity squamous cell carcinoma (OCSCC) who were undergoing surgical resection. Exposures: Patients with local regionally advanced resectable OCSCC who received neoadjuvant pembrolizumab were retrospectively reviewed for postoperative adverse events. Controls were matched by age, race, smoking status, and overall cancer stage based on historical data at the same institution. Matched-cohort analysis was performed using a McNemar test to assess differences between the groups. Main Outcomes and Measures: Incidence of adverse events following surgical resection of advanced OCSCC within 30 days of surgery and on continued follow-up. Results: A total of 64 patients (32 as part of the prospective clinical trial and 32 as controls; mean [SD] age, 59.6 [10.3] years; 28 [44%] women) were included in the analysis. Postoperative adverse events in the 32 patients receiving pembrolizumab included lymphedema (n = 20 [63%]), trismus (n = 7 [22%]), return to operating room (n = 7 [22%]), wound infection (n = 7 [22%]), fistula (n = 6 [19%]), wound dehiscence (n = 4 [13%]), flap failure (n = 3 [9%]), and hematoma (n = 2 [6%]). The matched control group demonstrated similar complication rates without considerable differences, except for trismus (n = 16 [50%]), which was greater by a difference of 28.1% (95% CI, 5.6%-50.6%) in the control group. Conclusions and Relevance: This cohort study examined surgical complications among patients with local regionally advanced OCSCC treated with neoadjuvant pembrolizumab and found that serious adverse events were similar to those in patients who underwent standard-of-care treatment. This suggests that there is no increased perioperative morbidity in the use of preoperative treatment with immunotherapy. Further prospective studies are needed to validate these findings for oral cavity cancer and other subsites of the head and neck.

Phase II Clinical Trial of Neoadjuvant and Adjuvant Pembrolizumab in Resectable Local-Regionally Advanced Head and Neck Squamous Cell Carcinoma.

PURPOSE: Patients with resected, local-regionally advanced, head and neck squamous cell carcinoma (HNSCC) have a one-year disease-free survival (DFS) rate of 65%-69% despite adjuvant (chemo)radiotherapy. Neoadjuvant PD-1 immune-checkpoint blockade (ICB) has demonstrated clinical activity, but biomarkers of response and effect on survival remain unclear. PATIENTS AND METHODS: Eligible patients had resectable squamous cell carcinoma of the oral cavity, larynx, hypopharynx, or oropharynx (p16-negative) and clinical stage T3-T4 and/or two or more nodal metastases or clinical extracapsular nodal extension (ENE). Patients received neoadjuvant pembrolizumab 200 mg 1-3 weeks prior to surgery, were stratified by absence (intermediate-risk) or presence (high-risk) of positive margins and/or ENE, and received adjuvant radiotherapy (60-66 Gy) and concurrent pembrolizumab (every 3 weeks × 6 doses). Patients with high-risk HNSCC also received weekly, concurrent cisplatin (40 mg/m2). Primary outcome was one-year DFS. Secondary endpoints were one-year overall survival (OS) and pathologic response (PR). Safety was evaluated with CTCAE v5.0. RESULTS: From February 2016 to October 2020, 92 patients enrolled. The median age was 59 years (range, 27-80), 30% were female, 86% had stage T3-T4, and 69% had ≥N2. At a median follow-up of 28 months, one-year DFS was 97% (95% CI, 71%-90%) in the intermediate-risk group and 66% (95% CI, 55%-84%) in the high-risk group. Patients with a PR had significantly improved one-year DFS relative to patients without response (93% vs. 72%, hazard ratio 0.29; 95% CI, 11%-77%). No new safety signals were identified. CONCLUSIONS: Neoadjuvant and adjuvant pembrolizumab increased one-year DFS rate in intermediate-risk, but not high-risk, HNSCC relative to historical control. PR to neoadjuvant ICB is a promising surrogate for DFS.

Primary cervical ganglioneuroblastoma, nodular subtype.

Primary cervical ganglioneuroblastoma is rare and reports of its subtypes are limited. This case series describes two pediatric patients with the nodular subtype of primary cervical ganglioneuroblastoma with lymphatic spread. Clinical course, diagnosis, and management of this rare tumor are discussed with emphasis on the importance of including neuroblastic tumors in the differential diagnosis of pediatric neck masses. We also report the use of nerve monitoring of the recurrent laryngeal nerve as a surrogate for the vagus nerve during a pediatric neck dissection.

Predicting pain recovery in patients with acute low back pain: a study protocol for a broad validation of a prognosis prediction model.

BACKGROUND: The clinical course of acute low back pain (LBP) is generally favourable; however, there is significant variability in the prognosis of these patients. A clinical prediction model to predict the likelihood of pain recovery at three time points for patients with acute LBP has recently been developed. The aim of this study is to conduct a broad validation test of this clinical prediction model, by testing its performance in a new sample of patients and a different setting. METHODS: The validation study with a prospective cohort design will recruit 420 patients with recent onset non-specific acute LBP, with moderate pain intensity, seeking care in the emergency departments of hospitals in São Paulo, Brazil. The primary outcome measure will be days to recovery from pain. The predicted probability of pain recovery for each individual will be computed based on predictions of the development model and this will be used to test the performance (calibration and discrimination) in the validation dataset. DISCUSSION: The findings of this study will better inform about the performance of the clinical prediction model, helping both clinicians and patients. If the model's performance is acceptable, then future research should evaluate the impact of the prediction model, assessing whether it produces a change in clinicians' behaviour and/or an improvement in patient outcomes. ETHICS AND DISSEMINATION: Ethics were granted by the Research Ethics Committee of the Universidade Cidade de São Paulo, #20310419.4.0000.0064. Study findings will be disseminated widely through peer-reviewed publications and conference presentations.

Determining the molecular landscape and impact on prognosis in HPV-associated head and neck cancer.

BACKGROUND: Human papillomavirus (HPV) associated head and neck squamous cell carcinoma (HNSCC) has a better prognosis than HNSCC due to other risk factors. However, there is significant heterogeneity within HPV-associated HNSCC and 25% of these patients still do poorly despite receiving aggressive therapy. We currently have no good molecular tools to differentiate and exclude this "high-risk" sub-population and focus on "low-risk" patients for clinical trials. This has been a potential barrier to identifying successful de-escalation treatment strategies in HPV-associated HNSCC. We conducted an analysis of molecular markers with a well-known role in the pathogenesis of HPV-associated HNSCC and hypothesized that these markers could help independently predict recurrence and prognosis in these patients and therefore help identify at the molecular level "low-risk" patients suitable for de-escalation trials. METHODS: We analyzed 24 tumor specimens of patients with p16+ HNSCC who underwent definitive resection as primary treatment. Tissue microarray (TMA) was generated from the 24 pathology blocks and immunohistochemistry (IHC) was performed using highly specific antibodies for our chosen biomarkers (PI3K-PTEN, AKT pathway, mTOR, 4EBP1, S6, and pAMPK, ERCC-1). Transcriptome data was also obtained for 7 p16+ HNSCC patients from The Cancer Genome Atlas (TCGA). Data from the TMA and TCGA were analyzed for association of relapse-free survival (RFS) and overall survival (OS) with protein and gene expression of the chosen biomarkers. RESULTS: Increased pAMPK protein activity by IHC and AMPK gene expression by TCGA gene expression data was correlated with improved RFS with a trend towards statistical significance. CONCLUSIONS: This data suggests that increased pAMPK activity and expression may portend a better prognosis in HPV-associated HNSCC undergoing primary definitive resection. However, these findings require validation in larger studies.

Examination of a Subgroup of Patients With Chronic Low Back Pain Likely to Benefit More From Pilates-Based Exercises Compared to an Educational Booklet.

OBJECTIVE: To investigate whether 2 previously published classification approaches, the updated treatment-based classification system and a Pilates subgroup defined by a preliminary clinical prediction rule, could identify patients with chronic low back pain who would benefit more from Pilates exercises compared to an educational booklet. DESIGN: Secondary analysis of a randomized controlled trial. METHODS: Two hundred twenty-two patients received advice and were randomly allocated to a group that received an educational booklet with no additional treatment (n = 74) or a group that received Pilates-based exercise treatment (n = 148) 2 or 3 times a week. At baseline, using a treatment-based classification system, patients were classified as having a good prognosis (positive movement control) or a poor prognosis. Similarly, using the Pilates clinical prediction rule, patients were classified as having a good prognosis (positive) or a poor prognosis (negative). The analysis was conducted using linear regression models to analyze the interaction between subgroup characteristics and treatment effect size, with changes in pain and disability from baseline to 6 weeks after randomization as dependent variables. RESULTS: None of the interaction terms for pain and disability were statistically significant. The treatment effect of Pilates versus an educational booklet was similar in all subgroups. CONCLUSION: The treatment-based classification system and the Pilates clinical prediction rule did not differentiate subgroups of patients with chronic low back pain who were more or less likely to benefit more from Pilates compared to an educational booklet. J Orthop Sports Phys Ther 2020;50(4):189-197. Epub 23 Aug 2019. doi:10.2519/jospt.2019.8839.

Maternity and paternity leave in otolaryngology residency training in the United States.

OBJECTIVES/HYPOTHESIS: This study evaluates the existence and nature of maternity and paternity leave policies for residents during otolaryngology training. The study sought to survey program directors (PDs) on the impact of parental leave. STUDY DESIGN: Cross-sectional survey. METHODS: An electronic survey was sent to 103 otolaryngology residency PDs. A link to a 10-page, 30-question survey was provided. Descriptive statistics and comments were collected. RESULTS: Forty-one respondents (39.8%) completed the survey, all of whom were from university-based programs. Programs from the Midwest (n = 11, 26.8%), Northeast (n = 12, 29.3%), South (n = 12, 29.3%) and West (n = 6, 14.6%) were represented. Sixteen (42%) programs reported having a written formal maternity leave policy for trainees, and 13 (32%) programs had a paternity-specific policy. Four programs reported using short-term disability, whereas 11 programs reported using the Family Medical Leave Act to accommodate parental leave. Policies primarily followed the Accreditation Council for Graduate Medical Education and American Board of Otolaryngology guidelines, with factors such as clinical duties and call schedules left to the programs' discretion. Although the majority of PDs (56%) reported support of residents who planned to become pregnant during training, many expressed concerns regarding the burden on co-residents and the difficulty of fulfilling training obligations for the resident taking leave. CONCLUSIONS: Many institutions do not have parental leave policies and logistics regarding leave are left to the discretion of individual programs. Surveyed PDs addressed the challenges of becoming a parent during training and the potential burden placed on the program when trainees take leave. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:1093-1099, 2019.

Can Predictive Modeling Identify Head and Neck Oncology Patients at Risk for Readmission?

Objective Unplanned readmission within 30 days is a contributor to health care costs in the United States. The use of predictive modeling during hospitalization to identify patients at risk for readmission offers a novel approach to quality improvement and cost reduction. Study Design Two-phase study including retrospective analysis of prospectively collected data followed by prospective longitudinal study. Setting Tertiary academic medical center. Subjects and Methods Prospectively collected data for patients undergoing surgical treatment for head and neck cancer from January 2013 to January 2015 were used to build predictive models for readmission within 30 days of discharge using logistic regression, classification and regression tree (CART) analysis, and random forests. One model (logistic regression) was then placed prospectively into the discharge workflow from March 2016 to May 2016 to determine the model's ability to predict which patients would be readmitted within 30 days. Results In total, 174 admissions had descriptive data. Thirty-two were excluded due to incomplete data. Logistic regression, CART, and random forest predictive models were constructed using the remaining 142 admissions. When applied to 106 consecutive prospective head and neck oncology patients at the time of discharge, the logistic regression model predicted readmissions with a specificity of 94%, a sensitivity of 47%, a negative predictive value of 90%, and a positive predictive value of 62% (odds ratio, 14.9; 95% confidence interval, 4.02-55.45). Conclusion Prospectively collected head and neck cancer databases can be used to develop predictive models that can accurately predict which patients will be readmitted. This offers valuable support for quality improvement initiatives and readmission-related cost reduction in head and neck cancer care.

Acute sialadenitis associated with 2017-2018 influenza A infection: A case series.

The influenza A virus has accounted for the majority of influenza infections in the 2017 to 2018 flu season, with the typical clinical presentation including fever, myalgias, malaise, and nonproductive cough. Notably this season, we have recognized a cluster of influenza A cases presenting as severe neck and facial swelling, with the subsequent diagnosis of sialadenitis. Whereas previous authors have demonstrated isolated case reports of sialadenitis associated with influenza A infection, herein we describe the clinical history, laboratory values, and radiographic findings of four patients presenting to our institution in January 2018 with acute sialadenitis and influenza A infection. Laryngoscope, 2500-2502, 2018.

Decreased plasma DEK Oncogene Levels Correlate with p16-Negative Disease and Advanced Tumor Stage in a Case-Control Study of Patients with Head and Neck Squamous Cell Carcinoma.

Head and neck cancer (HNC) remains the sixth most common malignancy worldwide and survival upon recurrence and/or metastasis remains poor. HNSCC has traditionally been associated with alcohol and nicotine use, but more recently the Human Papilloma Virus (HPV) has emerged as a favorable prognostic risk factor for oropharyngeal HNSCC. However, further stratification with additional biomarkers to predict patient outcome continues to be essential. One candidate biomarker is the DEK oncogenic protein, which was previously detected in the urine of patients with bladder cancer and is known to be secreted by immune cells such as macrophages. Here, we investigated if DEK could be detected in human plasma and if DEK levels correlated with clinical and pathological variables of HNSCC. Plasma was separated from the peripheral blood of newly diagnosed, untreated HNSCC patients or age-matched normal healthy controls and analyzed for DEK protein using ELISA. Plasma concentrations of DEK protein were lower in p16-negative tumors compared to both normal controls and patients with p16-positive tumors. Patients with lower plasma concentrations of DEK were also more likely to have late stage tumors and a lower white blood cell count. Contrary to previously published work demonstrating a poor prognosis with high intratumoral DEK levels, we show for the first time that decreased concentrations of DEK in patient plasma correlates with poor prognostic factors, including HPV-negative status as determined by negative p16 expression and advanced tumor stage.

Validation of American Thyroid Association Ultrasound Risk Assessment of Thyroid Nodules Selected for Ultrasound Fine-Needle Aspiration.

OBJECTIVE: The aim of this study was to validate the American Thyroid Association (ATA) sonographic risk assessment of thyroid nodules. METHODS: The ATA sonographic risk assessment was prospectively applied to 206 thyroid nodules selected for ultrasound-guided fine-needle aspiration (US-FNA), and analyzed with The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), as well as surgical pathology for the subset undergoing surgical excision. RESULTS: The analysis included 206 thyroid nodules averaging 2.4 cm (range 1-7 cm; standard error of the mean 0.07). Using the ATA US pattern risk assessment, nodules were classified as high (4%), intermediate (31%), low (38%), and very low (26%) risk of malignancy. Nodule size was inversely correlated with sonographic risk assessment, as lower risk nodules were larger on average (p < 0.0001). Malignancy rates determined by cytology/surgical pathology were high 100%, intermediate 11%, low 8%, and very low 2%, which were closely aligned with ATA malignancy risk estimates (high 70-90%, intermediate 10-20%, low 5-10%, and very low 3%). ATA US pattern risk assessment also appropriately predicted the proportion of nodules classified as malignant or suspicious for malignancy through TBSRTC classification-high (77%), intermediate (6%), low (1%), and very low 0%-as well as benign TBSRTC classification-high (0%), intermediate (47%), low (61%), and very low (70%) (p < 0.0001). Malignancy rates of surgically excised, cytologically indeterminate nodules followed ATA sonographic risk stratification (high 100%, intermediate 21%, low 17%, and very low 12%; p = 0.003). CONCLUSION: This prospective study supports the new ATA sonographic pattern risk assessment for selection of thyroid nodules for US-FNA based upon TBSRTC and surgical pathology results. In the setting of indeterminate cytopathology, nodules categorized as atypia of undetermined significance/follicular lesion of undetermined significance with ATA high-risk sonographic patterns have a high likelihood of being malignant.