Improving Operating Room Efficiency in Otolaryngology-Head and Neck Surgery: A Scoping Review.

OBJECTIVE: One minute of operating room (OR) time costs $36 to 37. However, ORs are notoriously inefficient. There is growing literature on improving OR efficiency, but no formal review of this topic within otolaryngology has been performed. This study reviews and synthesizes the current literature on improving OR efficiency within otolaryngology. DATA SOURCES: MEDLINE, EMBASE, Web of Science, CINAHL, Cochrane Library, preprints.org, and medRxiv were searched on November 4, 2022. REVIEW METHODS: Published English studies were included if they reported on metrics for improving OR efficiency within otolaryngology. There were no publication date restrictions. Articles were screened by 2 reviewers. Preferred Reporting Items for Systematic Reviews and Meta-analysis reporting for scoping reviews was followed. RESULTS: The search yielded 9316 no-duplicate articles; 129 articles were included. Most of the studies reported on head and neck procedures (n = 52/129). The main tactics included surgical considerations: hemostatic devices, techniques, and team/simultaneous approaches; anesthetic considerations: local anesthetic and laryngeal mask airways; procedure location considerations: procedures outside of the OR and remote technologies; standardization: equipment, checklists, and personnel; scheduling considerations: use of machine learning for booking, considering patient/surgeon factors, and utilizing dedicated OR time/multidisciplinary teams for on-call cases. CONCLUSION: The current literature brings to attention numerous strategies for improving OR efficiency within otolaryngology. Applying these strategies and implementing novel techniques to manage surgical cases may assist in offloading overloaded health care systems and improving access to care while facilitating patient safety and outcomes. Anticipated barriers to implementation include resistance to change, funding, and the current strain on health care systems and providers.

The genomic and evolutionary landscapes of anaplastic thyroid carcinoma.

Anaplastic thyroid carcinoma is arguably the most lethal human malignancy. It often co-occurs with differentiated thyroid cancers, yet the molecular origins of its aggressivity are unknown. We sequenced tumor DNA from 329 regions of thyroid cancer, including 213 from patients with primary anaplastic thyroid carcinomas. We also whole genome sequenced 9 patients using multi-region sequencing of both differentiated and anaplastic thyroid cancer components. Using these data, we demonstrate thatanaplastic thyroid carcinomas have a higher burden of mutations than other thyroid cancers, with distinct mutational signatures and molecular subtypes. Further, different cancer driver genes are mutated in anaplastic and differentiated thyroid carcinomas, even those arising in a single patient. Finally, we unambiguously demonstrate that anaplastic thyroid carcinomas share a genomic origin with co-occurring differentiated carcinomas and emerge from a common malignant field through acquisition of characteristic clonal driver mutations.

One-year Outcomes after Discharge from Noncardiac Surgery and Association between Predischarge Complications and Death after Discharge: Analysis of the VISION Prospective Cohort Study.

BACKGROUND: In previous analyses, myocardial injury after noncardiac surgery, major bleeding, and sepsis were independently associated with most deaths in the 30 days after noncardiac surgery, but most of these deaths occurred during the index hospitalization for surgery. The authors set out to describe outcomes after discharge from hospital up to 1 yr after inpatient noncardiac surgery and associations between predischarge complications and postdischarge death up to 1 yr after surgery. METHODS: This study was an analysis of patients discharged after inpatient noncardiac surgery in a large international prospective cohort study across 28 centers from 2007 to 2013 of patients aged 45 yr or older followed to 1 yr after surgery. The study estimated (1) the cumulative postdischarge incidence of death and other outcomes up to a year after surgery and (2) the adjusted time-varying associations between postdischarge death and predischarge complications including myocardial injury after noncardiac surgery, major bleeding, sepsis, infection without sepsis, stroke, congestive heart failure, clinically important atrial fibrillation or flutter, amputation, venous thromboembolism, and acute kidney injury managed with dialysis. RESULTS: Among 38,898 patients discharged after surgery, the cumulative 1-yr incidence was 5.8% (95% CI, 5.5 to 6.0%) for all-cause death and 24.7% (95% CI, 24.2 to 25.1%) for all-cause hospital readmission. Predischarge complications were associated with 33.7% (95% CI, 27.2 to 40.2%) of deaths up to 30 days after discharge and 15.0% (95% CI, 12.0 to 17.9%) up to 1 yr. Most of the association with death was due to myocardial injury after noncardiac surgery (15.6% [95% CI, 9.3 to 21.9%] of deaths within 30 days, 6.4% [95% CI, 4.1 to 8.7%] within 1 yr), major bleeding (15.0% [95% CI, 8.3 to 21.7%] within 30 days, 4.7% [95% CI, 2.2 to 7.2%] within 1 yr), and sepsis (5.4% [95% CI, 2.2 to 8.6%] within 30 days, 2.1% [95% CI, 1.0 to 3.1%] within 1 yr). CONCLUSIONS: One in 18 patients 45 yr old or older discharged after inpatient noncardiac surgery died within 1 yr, and one quarter were readmitted to the hospital. The risk of death associated with predischarge perioperative complications persists for weeks to months after discharge.

A sinonasal NUT midline carcinoma in an 84-year-old man undergoing radiation and proton therapy.

NUT midline carcinomas are rare, aggressive, and poorly differentiated tumors that must be considered in the differential diagnosis of midline head and neck tumors. Despite the scarce data, proton therapy could be an option for some patients.

Ultrasound-guided wire localisation: a GPS for hidden head and neck tumours? A case series.

Objectives: Ultrasound-guided wire (USGW) localisation for small non-palpable tumours before a revision head and neck surgery is an attractive pre-operative option to facilitate tumour identification and decrease potential complications. We describe five cases of pre-operative USGW localisation of non-palpable head and neck lesions to facilitate surgical localisation and resection. Methods: All patients undergoing pre-operative USGW localisation for non-palpable tumours of the head and neck region at London Health and Sciences Center, London, Ontario, Canada, were included. All the USGW localisations were performed by the same interventional radiologist, and the surgeries were performed by fellowship trained head and neck surgeons. Results: Five patients were included. All patients were undergoing revision surgery for recurrent or persistent disease. All successfully underwent a pre-operative USGW localisation of the non-palpable lesion before revision surgery. All lesions were localised intra-operatively with no peri-operative complications. Conclusions: USGW localisation is a safe and effective pre-operative technique for the identification of small non-palpable head and neck tumours.

Canadian women in otolaryngology: head and neck surgery part 2-challenges in family planning, fertility, and lactation.

BACKGROUND: Previous literature demonstrates that female surgeons face difficulties in family planning, meeting breastfeeding goals, leadership and advancement opportunities. These issues have received limited attention in Canadian surgeons despite different maternity leave patterns compared to the general Canadian population. We sought to describe the experience of otolaryngologist-head and neck surgeons in family planning, fertility, and lactation and to identify the role of gender and career stage in these experiences. METHODS: A RedCAP® survey was disseminated to Canadian otolaryngology-head and neck surgeons and residents from March to May of 2021 through social media and the national listserv. This survey examined fertility, pregnancy losses, and infant feeding. Major independent variables include gender and career stage (faculty and resident). Dependent variables include respondent experiences with fertility, number of children, and length of parental leave. Responses were tabulated and presented descriptively to communicate the experience of Canadian otolaryngologists. Further, statistical comparisons such as chi-square and t-tests were employed to identify relationships between these variables. Thematic analysis was conducted for narrative comments. RESULTS: We received 183 completed surveys (22% response rate). 54% of females versus 13% of males agreed that career influenced their ability to have children (p = 0.002). 74% of female respondents without children have concerns about future fertility compared to 4% of men (p < 0.001). Furthermore, 80% of women versus 20% of men have concerns about future family planning (p < 0.001). The average maternity leave was 11.5 weeks for residents, and 22.2 weeks for staff. Additionally, significantly more women than men stated that maternity leave impacted advancement opportunities (32% vs. 7%) and salary/remuneration (71% vs. 24%) (p < 0.001). Over 60% of those choosing to pump breastmilk at work reported having inadequate time, space, and breastmilk storage. In total, 62% of breastfed infants were receiving breastmilk at 1 year. CONCLUSION: Canadian female otolaryngologists-head and neck surgeons face challenges in family planning, ability to conceive, and breastfeeding. Focused effort is required to provide an inclusive environment that helps all otolaryngologists-head and neck surgeons achieve both their career and family goals, regardless of gender or career stage.

Canadian Women in Otolaryngology-Head and Neck Surgery part 1: the relationship of gender identity to career trajectory and experiences of harassment.

INTRODUCTION: Women in surgical specialties face different challenges than their male peers. However, there is a paucity of literature exploring these challenges and their effects on a Canadian surgeon's career. METHODS: A REDCap® survey was distributed to Canadian Otolaryngology-Head and Neck Surgery (OHNS) staff and residents in March 2021 using the national society listserv and social media. Questions examined practice patterns, leadership positions, advancement, and experiences of harassment. Gender differences in survey responses were explored. RESULTS: 183 completed surveys were obtained, representing 21.8% of the Canadian society membership [838 members with 205 (24.4%) women]. 83 respondents self-identified as female (40% response rate) and 100 as male (16% response rate). Female respondents reported significantly fewer residency peers and colleagues identifying as their gender (p < .001). Female respondents were significantly less likely to agree with the statement "My department had the same expectations of residents regardless of gender" (p < .001). Similar results were observed in questions about fair evaluation, equal treatment, and leadership opportunities (all p < .001). Male respondents held the majority of department chair (p = .028), site chief (p = .011), and division chief positions (p = .005). Women reported experiencing significantly more verbal sexual harassment during residency (p < .001), and more verbal non-sexual harassment as staff (p = .03) than their male colleagues. In both female residents and staff, this was more likely to originate from patients or family members (p < .03). DISCUSSION: There is a gender difference in the experience and treatment of OHNS residents and staff. By shedding light on this topic, as a specialty we can and must move towards greater diversity and equality.

Risk Factors for Poor Survival Outcomes in Parotid Metastatic Cutaneous Squamous Cell Carcinoma.

OBJECTIVE: We aimed to analyze risk factors associated with poor survival outcomes for metastatic cutaneous head-and-neck SCC to the parotid. METHODS: All patients undergoing surgery for metastatic cutaneous SCC to the parotid with curative intent between 2011 and 2018, were reviewed. Demographic and clinical characteristics were evaluated. Histopathological data including tumor size and histology, tumor grade, TNM stage, resection margins, lymphovascular invasion, and perineural invasion, were analyzed. Overall survival (OS), disease-specific survival (DSS), and freedom from locoregional recurrence (LRR) were assessed. RESULTS: Ninety patients were included (mean age, 77 years; 75 men [83.3%]). A total parotidectomy was performed in 48 patients (53.3%), and 42 (46.7%) underwent a superficial parotidectomy. Seventy patients (77.8%) underwent adjuvant RT. The median follow-up was 31 months (20-39 months). Tumor volume ≥ 50 cm3 and a shorter RT duration (<20 days) were associated with reduced OS (p = 0.002 and p = 0.01, p = 0.02 and p = 0.009, respectively), and DSS (p = 0.004 and p = 0.02, p = 0.04 and p = 0.02, respectively) on univariable and multivariable analysis, respectively. Only a shorter RT duration was associated with worse freedom from LRR on univariable and multivariable analysis, (p = 0.04 and p < 0.001, respectively). However, with death as a competing risk, a shorter duration of RT was not significantly associated with freedom from LRR. CONCLUSION: A shorter duration of adjuvant RT, and excised tumor volume ≥50 cm3 were predictive factors of reduced OS and DSS, and a shorter duration of RT was also associated with reduced freedom from LRR in patients with metastatic SCC to the parotid gland. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:1163-1168, 2023.

Bell's palsy misdiagnosis: characteristics of occult tumors causing facial paralysis.

OBJECTIVE: The aim of this study was to report the incidence and clinical course of a series of patients who were misdiagnosed with Bell's palsy and were eventually proven to have occult neoplasms. METHODS: Two hundred forty patients with unilateral facial paralysis who were assessed at the facial nerve reanimation clinic, Victoria Hospital, London Health Science Centre, from 2008 through 2017 were reviewed. Persistent paralysis without recovery was the presenting complaint. RESULTS: Nine patients (3.8%) who were proven to have occult neoplasms initially presented with a diagnosis of Bell's palsy. The mean diagnostic delay was 43.5 months. Four patients were proven to have skin cancers, 3 patients had parotid cancers, and 2 patients had facial nerve schwannomas as a final diagnosis. Initial magnetic resonance imaging (MRI) was performed in all 9 patients and 8 underwent a follow-up MRI. An occult tumor was identified upon review of the original MRI in one patient and at follow-up MRI in 8 patients. The mean time interval between the initial and follow-up imaging was 30.8 months. The disease status at most recent follow-up were no evidence of disease in 2 patients (22%) and alive with disease in 7 patients (78%). An irreversible, progressive pattern of facial paralysis combined with pain, multiple cranial neuropathies or history of skin cancer were predictable risk factors for occult tumors. Seven out of the 9 patients (77.8%) underwent at least one type of facial reanimation surgery, and the final subjective results by the surgeon were available for 5 patients. Three out of the 5 (60%) patients who were available for final subjective analysis were reported as Grade III according to the modified House-Brackmann scale. CONCLUSION: Occult facial nerve neoplasm should be suspected in patients with progressive and irreversible facial paralysis but the diagnosis may only become evident with follow-up imaging. Facial reanimation surgery is a satisfactory option for these patients.

Demographic and pathologic factor regression to a growth rate model of p16-negative oral cavity squamous cell carcinoma.

Objectives: The current study aims to quantify the growth rate of p16-negative oral cavity squamous cell carcinoma, characterize causative relationships between demographic risk factors and tumor growth, and examine pathologic findings associated with the tumor growth rate at a tertiary care institution. It is hypothesized that causative relationships will be drawn between the individual sociodemographic and pathologic factors and oral cavity p16-negative squamous cell carcinoma growth rate. Methods: Prospectively recruited participants, receiving surgical intervention only, were followed from initial staging CT scan to surgical resection. Interval growth was calculated in cm3/week. Demographic information including age, sex, smoking history, alcohol consumption history, previous all-type malignancy, previous chemotherapy treatment, previous head or neck radiation exposure, and time interval elapsed between diagnosis and surgery was collected from each participant, and regression analysis was applied to determine causality. Results: Summary statistics revealed a mean growth rate for the study sample of 1.385cm3/week. Statistically significant regression correlations were detected between tumor growth and alcohol consumption, origination at the retromolar trigone, and clinical nodal stage. Conclusions: Through a small prospective cohort sample, the current study suggests clinical associations between alcohol consumption, origination at the retromolar trigone, and clinical nodal stage with rate of tumor growth. Future work will validate these relationships in a larger patient cohort, and against stronger modeling techniques. Level of Evidence: Prospective non-random cohort design.

Assessment of Toxic Effects and Survival in Treatment Deescalation With Radiotherapy vs Transoral Surgery for HPV-Associated Oropharyngeal Squamous Cell Carcinoma: The ORATOR2 Phase 2 Randomized Clinical Trial.

Importance: The optimal approach for treatment deescalation in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is unknown. Objective: To assess a primary radiotherapy (RT) approach vs a primary transoral surgical (TOS) approach in treatment deescalation for HPV-related OPSCC. Design, Setting, and Participants: This international, multicenter, open-label parallel-group phase 2 randomized clinical trial was conducted at 9 tertiary academic cancer centers in Canada and Australia and enrolled patients with T1-T2N0-2 p16-positive OPSCC between February 13, 2018, and November 17, 2020. Patients had up to 3 years of follow-up. Interventions: Primary RT (consisting of 60 Gy of RT with concurrent weekly cisplatin in node-positive patients) vs TOS and neck dissection (ND) (with adjuvant reduced-dose RT depending on pathologic findings). Main Outcomes and Measures: The primary end point was overall survival (OS) compared with a historical control. Secondary end points included progression-free survival (PFS), quality of life, and toxic effects. Results: Overall, 61 patients were randomized (30 [49.2%] in the RT arm and 31 [50.8%] in the TOS and ND arm; median [IQR] age, 61.9 [57.2-67.9] years; 8 women [13.6%] and 51 men [86.4%]; 31 [50.8%] never smoked). The trial began in February 2018, and accrual was halted in November 2020 because of excessive toxic effects in the TOS and ND arm. Median follow-up was 17 months (IQR, 15-20 months). For the OS end point, there were 3 death events, all in the TOS and ND arm, including the 2 treatment-related deaths (0.7 and 4.3 months after randomization, respectively) and 1 of myocardial infarction at 8.5 months. There were 4 events for the PFS end point, also all in the TOS and ND arm, which included the 3 mortality events and 1 local recurrence. Thus, the OS and PFS data remained immature. Grade 2 to 5 toxic effects occurred in 20 patients (67%) in the RT arm and 22 (71%) in the TOS and ND arm. Mean (SD) MD Anderson Dysphagia Inventory scores at 1 year were similar between arms (85.7 [15.6] and 84.7 [14.5], respectively). Conclusions and Relevance: In this randomized clinical trial, TOS was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year. Long-term follow-up is required to assess OS and PFS outcomes. Trial Registration: Clinicaltrials.gov Identifier: NCT03210103.

Transoral robotic surgery for the identification of unknown primary head and neck squamous cell carcinomas: Its effect on the wait and the weight.

BACKGROUND: Neck carcinoma of unknown primary (CUP) is a frequent scenario. Transoral robotic mucosectomies (TORM) of pharynx have increased rate of primary identification, but come with cost of treatment delay. METHODS: We reviewed patients who underwent CUP protocol from 2014 to 2020. Patients with cervical nodes carcinoma and failure to localize a primary source were classified as CUP. We determined primary identification rate and postoperative complications. RESULTS: We included 65 patients underwent TORM. Surgical approach consisted of lingual and/or palatine tonsillectomies. The primary detection rate was 49.2%. Average weight reduction was 2.5 ± 4.3 kg. The average number of days from consultation to definitive treatment was 52.2 ± 18.3. CONCLUSION: A systematic approach to patients with CUP showed a promising primary identification rate compared to panendoscopy alone. TORM carries a small risk of complications. The benefits of primary identification must be weighed with the morbidity and delay to definitive treatment.

Introduction and expression of PIK3CAE545K in a papillary thyroid cancer BRAFV600E cell line leads to a dedifferentiated aggressive phenotype.

Anaplastic thyroid cancer (ATC) is a rare, aggressive form of undifferentiated thyroid cancer, which exhibits rapid progression and is almost universally fatal. At least a subset of ATC is thought to arise from pre-existing well-differentiated thyroid cancer, most frequently papillary thyroid cancer (PTC). While PIK3CA mutations are rare in PTC, they are common in ATC and tend to co-occur with BRAF mutations. This provided the rationale for our study to identify the potential role of PIK3CA mutations in the progression from well-differentiated to undifferentiated thyroid cancer. We introduced PIK3CAE545K into the LAM1 PTC cell line, which carries a BRAFV600E mutation. In culture, the engineered cell line (LAM1:PIK3CAE545K) proliferated faster and demonstrated increased clonogenic potential relative to the parental line carrying an empty vector (LAM1EV). Both the LAM1EV and LAM1:PIK3CAE545K edited lines were implanted into hind flanks of athymic nude mice for in vivo determination of disease progression. While tumour weights and volumes were not significantly higher in LAM1:PIK3CAE545K mice, there was a decrease in expression of thyroid differentiation markers TTF-1, thyroglobulin, PAX8 and B-catenin, suggesting that introduction of PIK3CAE545K led to dedifferentiation in vivo. Collectively, this study provides evidence of a role for PIK3CAE545K in driving disease progression from a well-differentiated to an undifferentiated thyroid cancer; however, over-expression was not a determinant of an accelerated growth phenotype in ATC.

Glutamate and N-Acetylaspartate Alterations Observed in Early Phase Psychosis: A Systematic Review of Proton Magnetic Resonance Spectroscopy Studies.

Glutamate and N-acetylaspartate have been investigated in the neuropathology of chronic schizophrenia, with fewer studies focusing on early phase psychosis. Additionally, there has been little review and synthesis of the literature focused on multiple brain regions. This systematic review aims to provide a clear report of the current state of research on glutamate and n-acetylaspartate concentrations in early phase psychosis (defined as the first five years following psychosis onset) in multiple brain regions. Existing literature was searched systematically to compile reports of glutamate/glutamate+glutamine (Glx) and n-acetylaspartate absolute levels and ratios in both male and female individuals with early phase psychosis. Reports on glutamate/Glx concentrations in the medial prefrontal region and thalamus were varied, but the majority of reports suggested no alterations in EPP. No studies reported glutamate alterations in the hippocampus or cerebellum. There was no evidence for n-acetylaspartate alterations in the caudate, basal ganglia, and medial prefrontal cortex, and minimal evidence for NAA reductions in the thalamus, anterior cingulate cortex, and hippocampus. Future research should focus on the regions that are less commonly reported, and should aim to explore possible confounds, such as medication status and substance use.

Randomized Trial of Radiotherapy Versus Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma: Long-Term Results of the ORATOR Trial.

PURPOSE: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has risen rapidly, because of an epidemic of human papillomavirus infection. The optimal management of early-stage OPSCC with surgery or radiation continues to be a clinical controversy. Long-term randomized data comparing these paradigms are lacking. METHODS: We randomly assigned patients with T1-T2, N0-2 (≤ 4 cm) OPSCC to radiotherapy (RT) (with chemotherapy if N1-2) versus transoral robotic surgery plus neck dissection (TORS + ND) (with or without adjuvant therapy). The primary end point was swallowing quality of life (QOL) at 1-year using the MD Anderson Dysphagia Inventory. Secondary end points included adverse events, other QOL outcomes, overall survival, and progression-free survival. All analyses were intention-to-treat. Herein, we present long-term outcomes from the trial. RESULTS: Sixty-eight patients were randomly assigned (n = 34 per arm) between August 10, 2012, and June 9, 2017. Median follow-up was 45 months. Longitudinal MD Anderson Dysphagia Inventory analyses demonstrated statistical superiority of RT arm over time (P = .049), although the differences beyond 1 year were of smaller magnitude than at the 1-year timepoint (year 2: 86.0 ± 13.5 in the RT arm v 84.8 ± 12.5 in the TORS + ND arm, P = .74; year 3: 88.9 ± 11.3 v 83.3 ± 13.9, P = .12). These differences did not meet the threshold to qualify as a clinically meaningful change at any timepoint. Certain differences in QOL concerns including more pain and dental concerns in the TORS + ND arm seen at 1 year resolved at 2 and 3 years; however, TORS patients started to use more nutritional supplements at 3 years (P = .015). Dry mouth scores were higher in RT patients over time (P = .041). CONCLUSION: On longitudinal analysis, the swallowing QOL difference between primary RT and TORS + ND approaches persists but decreases over time. Patients with OPSCC should be informed about the pros and cons of both treatment options (ClinicalTrials.gov identifier: NCT01590355).

Validity of functional patient-reported outcomes in head and neck oncology: A systematic review.

Malignancy and treatment effects in head and neck oncology can be devastating to functional aspects of patient life such as swallowing, blinking, speech, salivation, and facial expression. Historically, the subjective nature of patient experience has resulted in difficulty with quantification and measurement of functional outcomes. Patient-Reported Outcomes (PROs) are questionnaires developed with patient input, forming the new gold standard for clinician assessment of subjective functional outcomes. The current review aims to identify and characterize the validation of PROs pertaining to four critical functional outcomes in head and neck oncology: swallowing, speech, dry mouth, and chewing. A literature search was conducted using MEDLINE, EMBASE, and the Cochrane databases for published, English language, peer-reviewed abstracts involving patients ≥ 18 years of age. Of 708 results, 705 were excluded at abstract or full text screening for not meeting inclusion criteria, exclusion of head and neck SCC patients in development, or absence of a functional domain measurement. The three reviewed studies-Xerostomia Questionnaire, Swallowing Outcomes After Laryngectomy, and Edmonton 33-exhibited strong reliability and construct and content validity, though two applied only to individual functional outcomes within specific patient populations receiving radiation or laryngectomy. While many PROs have been developed in head and neck oncology, very few properly employed extensive patient input in the development process. Further work must be committed to increasing head and neck cancer patient input in PRO development, particularly in the functional domains of speech and chewing.

Development of a novel micro-bead force spectroscopy approach to measure the ability of a thermo-active polymer to remove bacteria from a corneal model.

Microbial keratitis occurs from the infection of the cornea by fungi and or bacteria. It remains one of the most common global causes of irreversible blindness accounting for 3.5% (36 million) of blind people as of 2015. This paper looks at the use of a bacteria binding polymer designed to bind Staphylococcus aureus and remove it from the corneal surface. Mechanical unbinding measurements were used to probe the interactions of a thermo-active bacteria-binding polymer, highly-branched poly(N-isopropyl acrylamide), functionalised with modified vancomycin end groups (HB-PNIPAM-Van) to bacteria placed on rabbit corneal surfaces studied ex-vivo. This was conducted during sequential temperature phase transitions of HB-PNIPAM-Van-S. aureus below, above and below the lower critical solution temperature (LCST) in 3 stages, in-vitro, using a novel micro-bead force spectroscopy (MBFS) approach via atomic force microscopy (AFM). The effect of temperature on the functionality of HB-PNIPAM-Van-S. aureus showed that the polymer-bacteria complex reduced the work done in removing bacterial aggregates at T > LCST (p < 0.05), exhibiting reversibility at T < LCST (p < 0.05). At T < LCST, the breaking force, number of unbinding events, percentage fitted segments in the short and long range, and the percentage of unbinding events occurring in the long range (> 2.5 µm) increased (p < 0.05). Furthermore, the LCST phase transition temperature showed 100 × more unbinding events in the long-range z-length (> 2.5 µm) compared to S. aureus aggregates only. Here, we present the first study using AFM to assess the reversible mechanical impact of a thermo-active polymer-binding bacteria on a natural corneal surface.

Does HPV Subtype Predict Outcomes in Head and Neck Cancers?

BACKGROUND: Recently, reanalysis of The Cancer Genome Atlas study demonstrated that human papillomavirus (HPV) genotypes in head and neck cancers other than HPV-16 have inferior survival to HPV-16-positive tumors. We aimed to examine the association of HPV subtypes and survival in a large cohort of patient samples from our institution. METHODS: Fresh frozen primary site biopsy samples were collected either in clinic or at the time of surgery. Patient demographic, staging, and survival data were also collected. Tumors were tested for HPV subtypes by quantitative polymerase chain reaction (qPCR). Univariable and multivariable analyses were performed using Cox proportional hazards regression. RESULTS: 280 patient biopsy samples were collected between 2011 and 2017. Mean ± standard deviation (SD) age was 61.9 ± 11.1 years and most patients (78%) were male. The majority of cancers were of the oral cavity (60%) or oropharynx (25%) and 30% had HPV-positive disease. Median follow-up was 3.76 years and 96/280 patients (34%) developed recurrences. Patients with p16-positive versus negative disease had significantly improved 5-year overall survival (OS, 77.6% vs. 53.3%; p=0.009) and progression-free survival (PFS, 67.3% vs. 41.0%, p=0.006). Similarly improved 5-year OS and PFS were observed for patients with HPV-positive versus negative disease (65.0% vs. 55.0%, p=0.084; 53.3% vs. 43.2%, p=0.072, resp.). Patients with HPV-16 compared to other HPV diseases had worse 5-year OS and PFS (62.1% vs. 88.9%, p=0.273; 49.0% vs. 88.9%, p=0.081, resp.). CONCLUSIONS: In contrast to the data derived from The Cancer Genome Atlas, patients with HPV-16 tumors trended towards decreased PFS and OS compared with tumors driven by other HPV genotypes. Further larger multi-institutional studies are necessary to understand the relationship between other HPV genotypes and survival in head and neck squamous cell carcinomas.

Survival outcomes of patients with subglottic squamous cell carcinoma : a study of the National Cancer Database.

BACKGROUND: Subglottic squamous cell carcinoma (SCC) represents less than 5% of all laryngeal cancers. Our objective was to better characterize survival using the National Cancer Database (NCDB) registry from 2004 to 2015. RESULTS: 403 patients met inclusion criteria. 63.8% presented with advanced-stage disease. Treatment regimens were as follows: 15.9% underwent surgery alone, 16.9% underwent surgery followed by adjuvant therapy, and 67.2% underwent primary chemo/radiation (C/RT). Five-year overall survival (OS) was 58.6% for Stage I and II patients, 49.1% for Stage III, and 36.3% for stage IV. Adjusted OS for all-stage patients was worse with C/RT compared to upfront surgery (40.6% vs. 58.4%; HR 1.83 [95%CI 1.29-2.61] p < 0.001) and adjusted OS for stage 4 disease was significantly worse with C/RT compared to surgery (26.0% vs. 45.2%, HR 1.79 [95%CI 1.17-2.73] p = 0.007). CONCLUSION: Majority of patients were treated with primary C/RT. Adjusted survival favors upfront surgery versus C/RT, especially in patients with Stage IV disease.