Mutation signature analysis identifies increased mutation caused by tobacco smoke associated DNA adducts in larynx squamous cell carcinoma compared with oral cavity and oropharynx.

Squamous cell carcinomas of the head and neck (HNSCC) arise from mucosal keratinocytes of the upper aero-digestive tract. Despite a common cell of origin and similar driver-gene mutations which divert cell fate from differentiation to proliferation, HNSCC are considered a heterogeneous group of tumors categorized by site of origin within the aero-digestive mucosa, and the presence or absence of HPV infection. Tobacco use is a major driver of carcinogenesis in HNSCC and is a poor prognosticator that has previously been associated with poor immune cell infiltration and higher mutation numbers. Here, we study patterns of mutations in HNSCC that are derived from the specific nucleotide changes and their surrounding nucleotide context (also known as mutation signatures). We identify that mutations linked to DNA adducts associated with tobacco smoke exposure are predominantly found in the larynx. Presence of this class of mutation, termed COSMIC signature 4, is responsible for the increased burden of mutation in this anatomical sub-site. In addition, we show that another mutation pattern, COSMIC signature 5, is positively associated with age in HNSCC from non-smokers and that larynx SCC from non-smokers have a greater number of signature 5 mutations compared with other HNSCC sub-sites. Immunohistochemistry demonstrates a significantly lower Ki-67 proliferation index in size matched larynx SCC compared with oral cavity SCC and oropharynx SCC. Collectively, these observations support a model where larynx SCC are characterized by slower growth and increased susceptibility to mutations from tobacco carcinogen DNA adducts

Design and Printing of a Low-Cost 3D-Printed Nasal Osteotomy Training Model: Development and Feasibility Study.

BACKGROUND: Nasal osteotomy is a commonly performed procedure during rhinoplasty for both functional and cosmetic reasons. Teaching and learning this procedure proves difficult due to the reliance on nuanced tactile feedback. For surgical simulation, trainees are traditionally limited to cadaveric bones, which can be costly and difficult to obtain. OBJECTIVE: This study aimed to design and print a low-cost midface model for nasal osteotomy simulation. METHODS: A 3D reconstruction of the midface was modified using the free open-source design software Meshmixer (Autodesk Inc). The pyriform aperture was smoothed, and support rods were added to hold the fragments generated from the simulation in place. Several models with various infill densities were printed using a desktop 3D printer to determine which model best mimicked human facial bone. RESULTS: A midface simulation set was designed using a desktop 3D printer, polylactic acid filament, and easily accessible tools. A nasal osteotomy procedure was successfully simulated using the model. CONCLUSIONS: 3D printing is a low-cost, accessible technology that can be used to create simulation models. With growing restrictions on trainee duty hours, the simulation set can be used by programs to augment surgical training

Postoperative Opioid-Prescribing Practices in Nasal Surgery: A Prospective Study

Introduction: Within facial plastic and reconstructive surgery (FPRS), prescription practices have trended toward prescribing larger amounts of perioperative opioids. However, there is limited literature regarding the postoperative pain experience and opioid consumption for FPRS. The purpose of our study was to investigate opioid prescription and consumption following procedures of the nose, with the aim of developing evidence-based guidelines for postoperative pain management. Methods: In this prospective single center study, morphine milligram equivalents (MME) consumption and pain scores were collected in 72 patients who underwent nasal surgery. Patient demographics, MME use, and pain scores were examined. MME use was compared to patient demographics, surgical procedure type, and postoperative pain scores. Results: In total, 3427 MME were prescribed: 2082 MME (60.8%) were used, leaving 1345 MME (39.2%). Patients were prescribed a total average of 47.6 ± 23.6 MME. Four (5.6%) patients required a second prescription. Average pain peaked on postoperative day 0 (POD0) and trended downwards. Visual analog scale (VAS) score dropped from 5.5 ± 2.8 on POD0 to 1.7 ± 1.9 at POD office visit. Mean POD follow-up visit was 7.0. Obesity, smoking (current and former), and history of opioid use were negative predictors of opioid consumption in postoperative patients (P\u3c0.05). Discussion: A significant portion of opioid prescriptions are not consumed by patients after nasal surgery, and several factors may explain why some patients use fewer opioids. Assessing opioid consumption for nasal procedures will guide prescribing practices. Our results indicate that prescription practices can likely be down titrated in select patients

Should all Status 1A patients be prioritized over high MELD patients? Concept of Risk Stratification in Extremely Ill Liver Transplant Recipients

BACKGROUND: Status 1A patients are prioritized over liver disease patients regardless of model for end-stage liver disease (MELD) score. We aimed to identify groups with high waitlist mortality in Status 1A and MELD\u3e/=40 patients to determine who would most benefit from transplantation. METHODS: Data on patients listed as Status 1A (n=4447) and MELD\u3e/=40 (n=3663) over 15 years (2002 to 2017) obtained from UNOS/OPTN registry. They were divided into two; derivation and validation groups. Risk factors associated with 28-day waitlist mortality were identified in derivation group and provided risk scores to divide patients into risk groups. Score system was applied to validation group to check its applicability. RESULTS: Risk factors for waitlist mortality in Status 1A included life support, performance status, severe coagulopathy, severe hypo or hypernatremia, and grade 3-4 encephalopathy. Risk factors in MELD\u3e/=40 included higher MELD scores (\u3e/=45), age, sex, race, life support, and encephalopathy. On comparing 7-day and 28-day mortality, both were higher in Status 1A and MELD\u3e/=40 high-risk groups compared to low-risk groups in the derivation group (p\u3c0.001). Probability of transplantation was lowest for high-risk MELD\u3e/=40 patients compared to all other groups (p\u3c0.001). These findings were reproduced in the validation set. Our proposed risk stratification system also showed acceptable 1 year graft and patient survival in high-risk groups. CONCLUSIONS: Our risk scoring system for extremely ill liver transplant candidates successfully stratified risk of waitlist mortality. Waitlist outcomes might be improved by modifications involving categorization of patients based on presence/absence of risk factors

Liver transplant patients with MELD\u3e50 at listing have poor waitlist outcomes and similar post transplant survival to status 1a patients

Background: Allocation of liver allografts is prioritized to Status 1A patients over end-stage liver disease patients. We aimed to analyze waitlist and transplant outcomes of Status 1A and extremely ill patients with MELD\u3e40 patients. Methods: Using United Network for Organ Sharing registry data, we retrospectively evaluated LT waitlist mortality, probability of LT and survival after LT between adults in the United States with Status 1A or ESLD with MELD \u3e40 listed for LT from July 1st 2013 to March 31st 2017. Competing waitlist outcomes such as death, transplant and removal from list were evaluated using Gray test. Transplant outcomes were analyzed using Kaplan-Meier method and log rank test. Results: During this time period, 611 patients were listed as Status 1A, 1140 were listed with a MELD between 40 to 50 and 62 with MELD\u3e50. Probability of transplant within 7 days was highest in Status 1A compared to MELD 40-50 and MELD\u3e50 (71.0% Vs 55.1% & 54.1%, p\u3c0.001). Death on waitlist within 7 days was highest in MELD\u3e50 compared to MELD 40-50 and Status 1A (22.9% Vs 13.8% & 16.4%, p=0.035). Probability of removal from waitlist within 7 days due to recovery was highest in Status 1A compared to MELD 40-50 and MELD\u3e50 (6.9% Vs 0.1% & 0%, p\u3c0.001). After transplant, no instantaneous 1 year risk of graft loss was observed between MELD\u3e50 and Status 1A (HR 1.8, CI 0.82-4.00, p=0.14) as well as MELD 40-50 and Status 1A (HR 1.07, CI 0.75-1.52, p=0.71). Instantaneous 1 year mortality showed a similar finding (HR 1.82, CI 0.77-4.3, p=0.16 & HR 1.13, CI 0.77-1.65, p=0.53). Conclusion: MELD\u3e50 have higher probability of death within 7 days on waitlist and similar graft and patient survival compared to MELD 40-50 and Status 1A patients. Hence MELD\u3e50 may be considered ahead of Status 1A in the allocation of liver grafts