Co-transcriptional genome surveillance by HUSH is coupled to termination machinery.

The HUSH complex recognizes and silences foreign DNA such as viruses, transposons, and transgenes without prior exposure to its targets. Here, we show that endogenous targets of the HUSH complex fall into two distinct classes based on the presence or absence of H3K9me3. These classes are further distinguished by their transposon content and differential response to the loss of HUSH. A de novo genomic rearrangement at the Sox2 locus induces a switch from H3K9me3-independent to H3K9me3-associated HUSH targeting, resulting in silencing. We further demonstrate that HUSH interacts with the termination factor WDR82 and-via its component MPP8-with nascent RNA. HUSH accumulates at sites of high RNAPII occupancy including long exons and transcription termination sites in a manner dependent on WDR82 and CPSF. Together, our results uncover the functional diversity of HUSH targets and show that this vertebrate-specific complex exploits evolutionarily ancient transcription termination machinery for co-transcriptional chromatin targeting and genome surveillance.

Female but Not Male Mice Deficient in Soluble IgM Are Susceptible to Chemically Induced Glomerular Injury.

B cell-targeted therapies are effective for treating multiple different kidney diseases in humans and also protect mice from Adriamycin nephropathy. Because glomerular IgM is frequently seen in both humans and mice with "nonimmune" forms of glomerular disease, we hypothesized that natural IgM binds to epitopes displayed in the injured glomerulus, exacerbating injury. To test this hypothesis, we induced Adriamycin nephropathy in BALB/C mice that cannot secrete soluble IgM (sIgM-/- mice) and compared them with BALB/C controls. Contrary to our prediction, we found that female sIgM-/- mice developed higher mortality and more severe kidney injury after injection of Adriamycin. The absence of soluble IgM did not reduce glomerular complement activation, and IgG was seen deposited within the injured glomeruli. Furthermore, we discovered that female sIgM-/- mice have higher levels of anti-cardiolipin IgG, and that IgG from these mice binds to epitopes in the injured kidney. These findings indicate that natural IgM may prevent generation of autoreactive IgG. Circulating levels of anti-cardiolipin IgG decreased after induction of kidney injury in female mice, consistent with deposition of the Abs in injured tissues. Better understanding of the mechanisms by which the immune system modulates and amplifies kidney injury may enable the development of targeted therapies to slow kidney disease progression.

Selective silencing of euchromatic L1s revealed by genome-wide screens for L1 regulators.

Transposable elements, also known as transposons, are now recognized not only as parasitic DNA, the spread of which in the genome must be controlled by the host, but also as major players in genome evolution and regulation. Long interspersed element-1 (LINE-1, also known as L1), the only currently autonomous mobile transposon in humans, occupies 17% of the genome and generates inter- and intra-individual genetic variation, in some cases resulting in disease. However, how L1 activity is controlled and the function of L1s in host gene regulation are not completely understood. Here we use CRISPR-Cas9 screening strategies in two distinct human cell lines to provide a genome-wide survey of genes involved in the control of L1 retrotransposition. We identify functionally diverse genes that either promote or restrict L1 retrotransposition. These genes, which are often associated with human diseases, control the L1 life cycle at the transcriptional or the post-transcriptional level in a manner that can depend on the endogenous L1 nucleotide sequence, underscoring the complexity of L1 regulation. We further investigate the restriction of L1 by the protein MORC2 and by the human silencing hub (HUSH) complex subunits MPP8 and TASOR. HUSH and MORC2 can selectively bind evolutionarily young, full-length L1s located within transcriptionally permissive euchromatic environments, and promote deposition of histone H3 Lys9 trimethylation (H3K9me3) for transcriptional silencing. Notably, these silencing events often occur within introns of transcriptionally active genes, and lead to the downregulation of host gene expression in a HUSH-, MORC2-, and L1-dependent manner. Together, these results provide a rich resource for studies of L1 retrotransposition, elucidate a novel L1 restriction pathway and illustrate how epigenetic silencing of transposable elements rewires host gene expression programs.

Risk Factors for Infection Recurrence After Surgical Resection of Advanced Stage Osteonecrosis of the Mandible.

BACKGROUND: Advanced stage osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ) are challenging disease entities requiring multimodal therapy including surgical resection. However, risk factors associated with infection recurrence are poorly understood. PURPOSE: The purpose of this study was to identify risk factors associated with infection recurrence following resection of advanced stage ORN or MRONJ of the mandible. STUDY DESIGN, SETTING, SAMPLE: This was a retrospective cohort study including patients who underwent segmental mandibulectomy for management of ORN or MRONJ between 2016 and 2021 at the authors' institution. Subjects who did not have margin viability data were excluded. PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: The primary predictor variable was viability of resection margins on histopathologic analysis (viable or nonviable). Secondarily, other risk factors categorized as demographic (age, sex, race), medical (comorbidities), and perioperative (reconstructive modality, antibiotic duration, microbiological growth) were evaluated. MAIN OUTCOME VARIABLE: The primary outcome variable was time to infection recurrence defined as time from surgical resection to clinical diagnosis of a fistula tract, abscess, or persistent inflammatory symptoms necessitating surgical intervention. COVARIATES: Not applicable. ANALYSES: Descriptive and bivariate statistics were used to identify associations between risk factors and time to infection recurrence. A significance level of P ≤ .05 was considered significant. RESULTS: The cohort consisted of 57 subjects with a mean age of 63.3 ± 10.0 years (71.9% Male, 75.4% White) treated for ORN (47.4%) or MRONJ (52.6%). A total of 19/57 (33%) subjects developed a recurrence of infection with 1 and 2 year survival of 75.8 and 66.2%, respectively. Nonviable resection margins were associated with earlier time to infection recurrence (P ≤ .001, hazard ratio (HR) = 11.9, 95% confidence interval (CI) = 3.84 to 36.7) as was younger age (P = .005, HR = 0.921, 95% CI = 0.869 to 0.976) and atypical pathogen growth on culture (P = .002, HR = 8.58, 95% CI = 2.24 to 32.8). CONCLUSIONS AND RELEVANCE: Histopathologic margin viability was associated with earlier time to infection recurrence following resection of advanced stage ORN or MRONJ of the mandible. Additional studies are needed to identify interventions that may improve outcomes in this demographic.

Is Insurance Payer Associated With Hospital Admission of Emergency Department Patients With Mandible Fractures?

BACKGROUND: There is a lack of consensus on the optimal triage pathway for emergency department (ED) patients with mandibular fractures. It remains unclear if patient insurance payers predict hospital admission given potentially competing logistical and health system incentives. PURPOSE: To generate nationally representative estimates of the frequency of hospital admission and its association with primary insurance payers for ED patients with mandible fractures. METHODS: This retrospective cohort study used the 2018 Nationwide Emergency Department Sample, the largest all-payer database in the United States, to identify patients with mandible fractures. The database includes a stratified sample with discharge weights to generate nationally representative estimates. Patients with other facial fractures and/or concomitant injuries that independently warranted admission were excluded. PREDICTOR: The primary predictor variable was primary payer (public, private, self-pay, and other/no charge). OUTCOME VARIABLE: The primary outcome variable was hospital admission (yes/no). COVARIATES: Covariates included patient-, medical/injury-, and hospital-related variables. ANALYSES: Descriptive statistics, along with bivariate and multivariate logistic regression with Bonferroni correction, were used to produce national estimates and identify predictors of admission. P < .01 was considered significant. RESULTS: The cohort included 27,238 weighted encounters involving isolated mandible fractures, of which 5,345(20%) were admitted. The payers for admitted patients were 46% public, 25% private, 22% self-pay, and 7% no charge/other. In bivariate analyses, public insurance was associated with a higher likelihood of admission than private insurance (RR 1.24, 95% CI 1.06 to 1.45), though there was no association in the multivariate model (OR 1.03, 95% CI 0.83 to 1.28). In multivariate analysis, higher Charlson Comorbidity Index (OR 1.32, 95% CI 1.18 to 1.48), alcohol-related disorder (OR 3.47, 95% CI 2.74 to 4.39), substance-related disorder (OR 1.43, 95% CI 1.20 to 1.71), and more mandible fractures (OR 3.08, 95% CI 2.65 to 3.59) were associated with admission. Compared to body fractures, subcondylar (OR 3.83, 95% CI 2.39 to 6.14), angle (OR 3.53, 95% CI 2.84 to 6.09), and symphysis (OR 4.14, 95% CI 2.84 to 6.09) fractures had higher odds of admission. Finally, level I (OR 4.11, 95% CI 2.41 to 6.98) and level II (OR 3.16, 95% CI 1.85 to 5.39) trauma centers had higher odds of admission. CONCLUSIONS: In 2018, 20% of ED patients with isolated mandible fractures were admitted. Several patient and hospital characteristics were predictors of admission. Insurance status was not associated with admission.

Interfacility Emergency Department Transfer for Midface Fractures in the United States.

PURPOSE: Interfacility hospital transfer for isolated midfacial fractures is common but rarely clinically necessary. The purpose of this study was to generate nationally representative estimates regarding the incidence, risk factors, and cost of transfer for isolated midface fractures. METHODS: This was a retrospective cohort study using the Nationwide Emergency Department Sample 2018 to identify patients with isolated midface fractures. The primary predictor variable was hospital trauma center designation (Level I, Level II, Level III, and nontrauma center). The primary outcome variable was hospital transfer. Total emergency department (ED) charges were also assessed. Covariates were demographic, medical, injury-related, and hospital characteristics. Descriptive, bivariate, and multiple logistic regression statistics were used to evaluate the incidence and predictors of interfacility transfer. RESULTS: During the study period, there were 161,022 ED encounters with a midface fracture as primary diagnosis, of which 5,680 were transferred (3.53%). In an unadjusted analysis, evaluation at a nontrauma center, level III trauma center, nonteaching hospital, and numerous demographic, medical, and injury-related variables were associated with transfer (P ≤ .001). In the adjusted model, the strongest independent predictors for hospital transfer were evaluation at a nontrauma center (odds ratio [OR] = 16.2, 95% confidence interval [CI] = 13.6-19.4), level III trauma center (OR = 13.4, 95% CI = 11.1-16.1) or level II trauma center (OR = 3.25, 95% CI = 2.66-3.98), any Le Fort fracture (OR = 12.0, 95% CI = 10.4-14.0), orbital floor fracture (OR = 3.73, 95% CI = 3.48-4.00), history of cerebrovascular event (OR = 2.74, 95% CI = 2.18-3.45), and cervical spine injury (OR = 5.87, 95% CI = 4.79-7.20) (P ≤ .001). The average ED charge per encounter was $7,206 ± 9,294 for a total nationwide charge of approximately 1.16 billion dollars. Transferred subjects had total ED charges of $97 million, not including additional charges at the recipient hospital. CONCLUSION: Isolated midface fractures are transferred infrequently, but given the high incidence have substantial healthcare costs. Predictors of transfer were mixed rather than clustered within one variable type, although it is likely that transfers are driven in part by lack of access to maxillofacial specialists given the predominance of hospital covariates. Programs evaluating necessity of transfer and facilitating specialist evaluation in the outpatient setting may reduce healthcare expenditures for these injuries.

Is Preoperative Serum Albumin Predictive of Adverse Outcomes in Head and Neck Cancer Surgery?

BACKGROUND: Patients with head and neck cancer are at increased risk of malnutrition due to tumor burden and surgical morbidity. PURPOSE: The purpose of this study was to evaluate the association between preoperative serum albumin and 30-day adverse outcomes in patients undergoing head and neck cancer surgery. STUDY DESIGN, SETTING, SAMPLE: This was a retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program database. Patients undergoing an ablative head and neck cancer procedure were included. Patients who had an unclear tumor location based on coding or missing outcome data were excluded. PREDICTOR VARIABLE: The primary predictor variable was preoperative albumin categorized as low (<3.4 g/dL), intermediate (3.4 to 3.9 g/dL), or high (>3.9 g/dL). OUTCOME VARIABLE: The primary outcome variable was intensive care unit (ICU)-level complications scored using the Clavien-Dindo classification system. This is a tool used to grade surgical complications, with grade IV and V complications defined as requiring ICU-level care. COVARIATES: Covariates were demographic (age, sex, body mass index), medical (smoking, functional status, weight loss), and perioperative (concurrent procedures, tumor location, reconstructive modality). ANALYSES: Descriptive, bivariate, and multiple logistic regression with bootstrap resampling statistics were used to evaluate the association between albumin and adverse outcomes. A significance level of P ≤ .05 was significant. RESULTS: A total of 4,491 subjects met inclusion criteria and had a documented albumin. There were 435 subjects with low albumin levels, 1,305 with intermediate levels, and 2,751 with high levels. In bivariate analysis, low albumin levels were associated with an increased risk of ICU-level complications, any complication, extended length of stay, and adverse discharge disposition (all P ≤ .001), while high levels were protective (all P ≤ .001). In bootstrapped multivariate analysis using intermediate albumin as the reference group and adjusting for demographics, tumor location, and reconstructive modality among others, low albumin levels were an independent predictor of ICU-level complications (P = .008, odds ratio, 1.64; 95% confidence interval, 1.14 to 2.40), while high levels were protective (P = .014, odds ratio, 0.689; 95% confidence interval, 0.521 to 0.923). CONCLUSIONS: Preoperative serum albumin was an independent predictor of adverse outcomes following ablative head and neck cancer procedures.

Are There Differences in Opioid Prescriptions to Urban and Rural Patients by Oral and Maxillofacial Surgeons in Massachusetts From 2011 to 2021?

PURPOSE: Oral-maxillofacial surgeons (OMSs) are frequent prescribers of opioid analgesics. It remains unclear if prescription patterns differ for urban versus rural patients, given potential differences in access to and delivery of care. This study aimed to characterize urban-rural differences in opioid analgesic prescriptions to patients in Massachusetts by OMSs from 2011 to 2021. METHODS: This retrospective cohort study used the Massachusetts Prescription Monitoring Program database to identify Schedule II and III opioid prescriptions by providers with specialty of oral and maxillofacial surgery from 2011 to 2021. The primary predictor variable was patient geography (urban/rural) and secondary predictor was year (2011-2021). The primary outcome variable was milligram morphine equivalent (MME) per prescription. Secondary outcome variables were days' supply per prescription and number of prescriptions received per patient. Descriptive and linear regression statistics were performed to analyze differences in prescriptions to urban and rural patients each year and throughout the study period. RESULTS: The study data, which includes OMS opioid prescriptions (n = 1,057,412) in Massachusetts from 2011 to 2021, ranged annually between 63,678 and 116,000 prescriptions to between 58,000 and 100,000 unique patients. The cohorts each year ranged between 48 and 56% female with mean ages between 37 and 44 years. There were no differences in the mean number of patients per provider in urban and rural populations in any year. The study sample had a large majority of urban patients (>98%). MME per prescription, days' supply per prescription, and prescriptions received per patient were all generally similar between urban and rural patients each year, with the largest MME per prescription difference in 2019 (87.3 for rural to 73.9 for urban patients, P < .01). From 2011 to 2021, all patients had a steady decrease in MME per prescription (ß = -6.64, 95% confidence interval: -6.81, -6.48; R2 = 0.39) and day's supply per prescription (ß = -0.1, 95% confidence interval: -0.1, -0.09; R2 = 0.37). CONCLUSION: In Massachusetts, there were similar opioid prescribing patterns by oral and maxillofacial surgeons to urban and rural patients from 2011 to 2021. There has also been a steady decrease in the duration and total dosage of opioid prescriptions to all patients. These results are consistent with multiple statewide policies over the last several years aimed at curbing opioid overprescribing.

Advancing the Actionability of Mental Health Information: Identifying Online, Evidence-Based Mental Health Resources.

To improve the dissemination and actionability of mental health research, many mental health professionals have developed online informational resources to increase the general public's awareness of mental health difficulties and available treatments. Yet, limited information exists on the quality and scope of these resources. This study aimed to explore the scope and quantity of online, free, evidence-based mental health resources. Fifty-two mental health professionals nominated 178 resources, which predominantly consisted of homepages and links to more information. When reviewing the original nominations, our team identified an additional 290 resources (e.g., fact sheets linked from a nominated homepage). Of the 468 total nominated resources, 72 were screened out due to not meeting the inclusion criteria of being free (inter-screener reliability = 95%), evidence-based (inter-screener reliability = 94%), and online (inter-screener reliability = 96%). Nominated resources most commonly covered anxiety and obsessive-compulsive disorder (n = 67) and suicide (n = 60). Resources providing information about the mental health problem were most common (n = 210) and resources providing information about immediate help (e.g., hotline) were least common (n = 57). Our findings indicate many free, online, evidence-based resources are available and raise questions of whether efforts to disseminate mental health research are recreating the issue of information overload. Other considerations and future directions for improving the utilization and synthesizing of available resources are discussed.

Translation readthrough mitigation.

A fraction of ribosomes engaged in translation will fail to terminate when reaching a stop codon, yielding nascent proteins inappropriately extended on their C termini. Although such extended proteins can interfere with normal cellular processes, known mechanisms of translational surveillance are insufficient to protect cells from potential dominant consequences. Here, through a combination of transgenics and CRISPR­Cas9 gene editing in Caenorhabditis elegans, we demonstrate a consistent ability of cells to block accumulation of C-terminal-extended proteins that result from failure to terminate at stop codons. Sequences encoded by the 3' untranslated region (UTR) were sufficient to lower protein levels. Measurements of mRNA levels and translation suggested a co- or post-translational mechanism of action for these sequences in C. elegans. Similar mechanisms evidently operate in human cells, in which we observed a comparable tendency for translated human 3' UTR sequences to reduce mature protein expression in tissue culture assays, including 3' UTR sequences from the hypomorphic 'Constant Spring' haemoglobin stop codon variant. We suggest that 3' UTRs may encode peptide sequences that destabilize the attached protein, providing mitigation of unwelcome and varied translation errors.

Is Cleft Lip or Palate a Risk Factor for Perioperative Complications in Orthognathic Surgery?

PURPOSE: Perioperative outcomes following cleft orthognathic surgery are not well established. The purpose of this study was to compare the incidence of orthognathic specific complications (OSCs) in patients with and without cleft lip and/or palate. METHODS: The American College of Surgeons National Surgical Quality Improvement Program adult and pediatric databases were used to enroll patients undergoing orthognathic surgery. The primary predictor variable was a prior diagnosis of cleft lip and/or palate: cleft versus noncleft. The primary outcome variable was OSCs (yes/no) within 30 days of the index operation. Descriptive, bivariate, and multiple logistic regression statistics were computed to measure the association between cleft status and OSCs. RESULTS: The study sample was composed of 1,149 subjects: 98 in the cleft group and 1,051 in the noncleft group. The incidence of OSCs was 6.1 and 4.7% for the cleft and noncleft groups, respectively (P = .461). After adjusting for age, cleft status, bone grafting, segmentation of the maxilla, and history of bleeding disorder, classification as American Society of Anesthesiologists (ASA) III (P = .002, odds ratio [OR] = 3.92, 95% confidence interval [CI] 1.63-9.40), ASA IV (P = .039, OR = 9.47, 95% CI 1.12-80.4), and isolated mandibular osteotomies (P = .006, OR = 3.23, 95% CI 1.40-7.48) were independent predictors of OSCs. Length of stay was 1.66 ± 1.14 days compared to 1.37 ± 3.74 days for the cleft and noncleft groups, respectively (P = .443). CONCLUSIONS: There was no significant difference in the incidence of perioperative OSCs and length of hospital stay between cleft and noncleft patients. Cleft status was not an independent predictor of OSCs; instead, greater ASA classification and isolated mandibular osteotomies were the only predisposing factors. Patients with clefts undergoing orthognathic surgery do not have an increased risk of short-term OSCs within the limitations of this study.

Evaluation of Accessibility and Content of Oral and Maxillofacial Surgery Fellowship Program Websites.

PURPOSE: Opportunities for graduating oral and maxillofacial surgery residents to pursue fellowship training are expanding. However, there is a paucity of information in the literature for prospective applicants in our specialty. The purpose of this study was to evaluate the accessibility and content of oral and maxillofacial surgery fellowship program websites (FPWs). METHODS: The authors designed a cross-sectional study including oral and maxillofacial surgery fellowship programs in North America listed on 4 major websites: 1) The American Association of Oral and Maxillofacial Surgeons, 2) The American Academy of Craniomaxillofacial Surgeons Match, 3) The American Dental Association, and 4) The American Academy of Cosmetic Surgery. The existence and accessibility of stand-alone FPWs from these listings were assessed. Content scores were generated based on the presence or absence of 23 content variables related to program characteristics, fellow recruitment, and fellow education on listings and available webpages. Descriptive and bivariate statistics were used to evaluate the relationship between predictor variables and content scores. RESULTS: A total of 44 fellowship programs were included. Of these fellowships, 26 (59.1%) had a stand-alone FPW. The mean content score was 10.8 ± 4.82 out of a maximum of 23. Content scores were significantly greater for head and neck oncology fellowships (P ≤ .001), programs with a stand-alone FPW (P ≤ .001), and Commission on Dental Accreditation-accredited programs (P = .046). Programs with a stand-alone FPW had content scores 1.87 times greater than those without and was the predictor variable with the greatest mean difference between groups. There was no significant difference in content scores with respect to geographic region. CONCLUSIONS: Oral and maxillofacial surgery FPWs demonstrate deficiencies in content areas relevant to prospective applicants. Optimizing the content of FPWs may represent an opportunity to better inform and recruit graduating residents into fellowship programs.

Is Preoperative Serum Albumin Predictive of Adverse Surgical Outcomes in Maxillofacial Fracture Repair?

PURPOSE: Malnutrition has been recognized as a predictor of postoperative adverse outcomes across many surgical subspecialties. The purpose of this study was to evaluate the relationship between serum albumin and adverse outcomes in patients undergoing operative repair of maxillofacial fractures. METHODS: The authors utilized the 2011 to 2018 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) databases to identify patients with facial fractures undergoing operative repair. The primary predictor variable was preoperative serum albumin level. Outcome variables included complications and other adverse outcomes occurring within 30 days of the index operation. Descriptive, bivariate, and multiple logistic regression statistics were utilized to evaluate the relationship between serum albumin and adverse outcomes. RESULTS: During the study period 1211 subjects underwent operative repair of a facial fracture and had a documented serum albumin level. Of these subjects, 1037 (85.6%) had normal albumin levels and 174 (14.4%) had hypoalbuminemia. A total of 90 subjects experienced a complication (7.43%), although albumin level was not associated with surgical complications or any complication. In bivariate analysis, subjects with hypoalbuminemia were significantly more likely to have an extended length of stay (P ≤ .001), adverse discharge disposition (P ≤ .001), and be readmitted (P = .002). In multivariate analysis, hypoalbuminemia was an independent predictor of an extended length of stay (P ≤ .001, 95% CI 2.50 to 7.62), adverse discharge disposition (P = .048, 95% CI 1.01 to 3.75), and readmission (P = .041, 95% CI 1.03 to 3.47). CONCLUSIONS: Serum albumin was not an independent predictor of complications after maxillofacial trauma repair. However, it was an independent predictor of other adverse outcomes including extended length of stay, adverse discharge disposition, and readmission. Targeted nutritional optimization may represent an opportunity to improve outcomes in this demographic.

Is Intensive Care Unit Monitoring Necessary After Maxillomandibular Advancement for Management of Obstructive Sleep Apnea?

PURPOSE: Maxillomandibular advancement (MMA) is an accepted treatment modality for obstructive sleep apnea. The purpose of this study was to evaluate the incidence of complications requiring an intensive care unit (ICU) level of care and the necessity of routine overnight ICU airway monitoring after MMA. PATIENTS AND METHODS: This was a retrospective cohort study of patients undergoing MMA at Massachusetts General Hospital from 2003 to 2020. The primary predictor variable was postoperative admission to the ICU versus post anesthesia care unit (PACU) or ward. The primary outcome variable was grade IV or V complications as scored using the Clavien-Dindo classification system. The secondary outcome variables included postoperative SpO2 nadir and length of hospital stay. Descriptive and bivariate statistics were computed to measure the association between complications and predictor variables. RESULTS: The study sample consisted of 104 patients (74.0% male, mean age 37.6 ± 12.1 years), 61 of whom were admitted to the ICU (58.7%). During the initial 24 hours of airway monitoring, the mean SpO2 nadir was 93.7 ± 2.59% for patients admitted to the ICU compared with 94.0 ± 6.56% for patients admitted to the PACU or ward (P = .862). Patients experienced 2 grade IV complications (1.92%) and no grade V complications, with no statistical association between complications and postoperative admission location (P = 1.000). Age (P = .002) and operative time (P = .046) were the only variables statistically associated with grade IV or V complications. There was no difference in length of hospital stay between patients admitted to the ICU (2.64 ± 1.37 days) versus PACU or ward (2.58 ± 1.62 days). CONCLUSIONS: The incidence of complications requiring ICU-level care after MMA for obstructive sleep apnea is low. Additional studies are warranted to guide development of feasible, cost-effective perioperative protocols for patients undergoing MMA.

Does the Modified Frailty Index (mFI-5) Predict Adverse Outcomes in Maxillofacial Fracture Repair?

PURPOSE: Frailty has been recognized as a predictor of postoperative adverse outcomes in many surgical subspecialties. The purpose of this study was to evaluate the relationship between frailty and complications in patients undergoing operative repair of facial fractures. METHODS: The authors utilized the 2011 to 2018 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) databases to identify patients with facial fractures undergoing operative repair. The primary predictor variable was frailty as measured by the 5-Factor Modified Frailty Index (mFI-5). The primary outcome variable was the postoperative complication rate. Descriptive, bivariate, and multiple logistic regression statistics were utilized to evaluate the relationship between frailty and complications. RESULTS: During the study period, 4,290 subjects underwent operative repair of a facial fracture. Of these subjects, 4,086 (83.0%) were classified as nonfrail, 626 (12.7%) as moderately frail, and 208 (4.20%) as severely frail. A total of 237 subjects experienced a complication (4.82%), and the incidence of complications increased in a stepwise manner with increasing frailty (P ≤ .001). In multivariate regression, age (P = .050, 95% CI = 1.00 to 1.02), Native Hawaiian/Pacific Islander race (P = .018, 95% CI = 1.23 to 8.63), classification as moderately frail (P = .010, 95% CI = 1.15 to 2.66), classification as severely frail (P = .032, 95% CI = 1.06 to 3.70), mandibular fractures (P = .004, 95% CI = 1.24 to 2.98), and wound classification as contaminated (P ≤ .001, 95% CI = 1.53 to 4.57) or dirty/infected (P = .020, 95% CI = 1.16 to 5.55) were independent predictors of complications. Severely frail subjects also had greater length of hospital admission (P ≤ .001) and higher 30-day readmission rates (P ≤ .001). CONCLUSIONS: Frailty is an independent predictor of complications following facial fracture repair and is associated with greater length of hospital admission and 30-day readmission rates.

Females Have Worse Overall and Disease-Specific Survival in Human Papillomavirus-Negative Oropharyngeal Squamous Cell Carcinoma.

PURPOSE: Although sex (male vs female) has been identified as an independent prognostic factor in human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), the role of sex in HPV-negative OPSCC is less understood. The purpose of this study is to measure the association between sex and HPV-negative OPSCC disease-specific survival (DSS) and overall survival (OS). METHODS: This longitudinal, retrospective study examined cases of HPV-negative OPSCC diagnosed in the United States between 2013 and 2016 from the Surveillance, Epidemiology, and End Results database. Patients with primary OPSCC and known HPV-negative status were included. Those with HPV-positive or unknown status and primary lesions located outside the oropharynx were excluded. The primary predictor variable was patient sex (male vs female). Primary outcome variables of interest included DSS and OS. The following patient-level covariates were also assessed: age, race, insurance status, primary anatomical site and histological type of lesion, histologic grade and stage, and disease outcome. A survival analysis was conducted using univariate and multivariate analyses via a cox proportional hazard regression model. An α value less than 0.05 was considered statistically significant. RESULTS: The study sample consisted of 2,565 cases (25.1% female) of HPV-negative OPSCC. Females presented with lower histologic grade (P = .015) and earlier stage (P = .003). Females demonstrated worse DSS (P < .001) and OS (P < .001). After multivariate adjustment, female sex (hazard ratio [HR] = 1.38; 95% confidence interval [CI], 1.13 to 1.67; P = .002), advanced age (HR = 1.672; 95% CI, 1.07 to 2.60; P = .023), advanced overall stage (HR = 4.69; 95% CI, 1.54 to 14.267; P = .006), TNM stage (T4: HR = 5.74; 95% CI, 3.86 to 8.55, P < .001, N3: HR = 3.48; 95% CI, 2.17 to 5.58; P < .001, and M1: HR = 2.80; 95% CI, 2.09 to 3.74; P < .001), subjects residing in counties with the highest rates of smoking (HR = 1.29; 95% CI, 1.01 to 1.65; P = .044), and the lack of surgical treatment in patients treated with radiation and/or chemotherapy (HR = 1.44; 95% CI, 1.08 to 1.91; P = .012) were correlated with poorer DSS and OS. CONCLUSION: Females with HPV-negative OPSCC demonstrated worse DSS and OS despite better typical prognostic signs such as histologic grade and clinical stage.

Orthognathic Surgery in Older Patients: Is Age Associated With Perioperative Complications?

PURPOSE: The incidence of older patients undergoing orthognathic surgery is increasing. The purpose of this study is to evaluate the association between age and perioperative adverse outcomes in patients undergoing orthognathic surgery. METHODS: This is a retrospective cohort study of patients undergoing orthognathic surgery in the 2011 to 2019 American College of Surgeons National Surgical Quality Improvement Program databases. The primary predictor variable was age group (≥40 or <40 years). The primary outcome variable was adverse outcomes occurring within 30 days of the index operation. Descriptive, bivariate, and Firth logistic regression statistics were utilized to evaluate association between age and adverse outcomes. RESULTS: During the study period, 1,226 patients underwent an orthognathic procedure and 835 subjects were included. Of these subjects, 145 were 40 years or older (17.4%) and 690 were less than 40 years (82.6%). Subjects 40 years or older were more likely to be American Society of Anesthesiologists (ASA) classification II (P ≤ .001), ASA III (P ≤ .001), or diagnosed with obstructive sleep apnea (P ≤ .001). A total of 34 subjects experienced an adverse outcome (4.07%), though there was no significant difference in the incidence of adverse outcomes between age groups (P = .152). In bivariate analysis, hypertension on medication (P = .037), procedure type (P = .001), and segmented Le Fort I osteotomies (P = .039) were associated with adverse outcomes. After controlling for age, hypertension on medication, segmented Le Fort I osteotomies, and diagnosis of obstructive sleep apnea, isolated mandibular osteotomies were the only independent predictors of adverse outcomes (odds ratio 2.64; 95% confidence interval, 1.06 to 7.24; P = .038). Length of stay was 1.38 ± 1.43 days for the 40 years or older group compared to 1.06 ± 1.18 in the <40 group (P = .012). CONCLUSIONS: Despite higher ASA classifications, older patients did not have a significantly greater incidence of perioperative adverse outcomes including airway complications, nor was increased age associated with adverse outcomes in bivariate or multivariate analysis.

Mandibular Fracture Repair in Older Adults: Is Age Associated With Adverse Outcomes?

PURPOSE: The purpose of this study was to measure the association between age and adverse outcomes in patients undergoing open reduction internal fixation (ORIF) of mandibular fractures. METHODS: This was a retrospective cohort study utilizing the American College of Surgeons National Surgical Quality Improvement Program databases (2011 to 2019) to identify patients with mandibular fractures treated with ORIF. The primary predictor variable was age (<45 years, 45 to 54 years, 55 to 64 years, 65 to 74 years, and ≥75 years). The primary outcome variable was surgical complications. Secondary outcome variables included any complication, extended length of stay (LOS ≥95th percentile), and adverse discharge destination. Covariates included demographic, medical, and perioperative covariates. Descriptive, bivariate, and multiple logistic regression statistics were utilized to evaluate the association between age and adverse outcomes. RESULTS: During the study period, 2,843 patients underwent ORIF of a mandibular fracture, and 2,168 subjects were included. There were 1,673 subjects aged <45 years (77.2%), 240 subjects aged 45 to 54 years (11.1%), 155 subjects aged 55 to 64 years (7.10%), 53 subjects aged 65 to 74 years (2.40%), and 47 subjects aged ≥75 years (2.20%). A total of 148 subjects (6.83%) experienced a surgical complication; the incidence of surgical complications increased in a step-wise fashion with each decade of life (P ≤ .001). In bivariate analysis, subjects aged 65 to 74 years were more likely to experience extended LOS (P = .004), whereas subjects aged ≥75 years were more likely to have an extended LOS (P ≤ .001) and an adverse discharge destination (P ≤ .001). In multivariate analysis, age 65 to 74 years was an independent predictor of any complication (P = .032, 95% confidence interval [CI] = 1.08 to 5.37), extended LOS (P = .001, 95% CI = 1.72 to 8.79), and adverse discharge destination (P = .050, 95% CI = 1.00 to 14.4), whereas age ≥75 years was an independent predictor of surgical complications (P = .043, 95% CI = 1.03 to 6.68), any complication (P = .018, 95% CI = 1.20 to 6.75), extended LOS (P = .001, 95% CI = 2.35 to 12.3), and an adverse discharge destination (P ≤ .001, 95% CI = 3.01 to 33.2). CONCLUSIONS: The elderly are at increased risk of adverse outcomes with step-wise increases in the odds of select outcomes with increasing age.

Do Patterns of Opioid Prescriptions to Medicare Beneficiaries Differ Between Oral and Maxillofacial Surgeons Practicing in Urban and Rural Settings?

PURPOSE: This study compared opioid prescription patterns among oral and maxillofacial surgeons (OMSs) treating Medicare beneficiaries in urban and rural settings, in an effort to identify avenues to further promote responsible opioid prescribing in a patient demographic vulnerable to opioid diversion. MATERIALS AND METHODS: This study used Medicare Provider Utilization and Payment Data from 2014 to 2018, focusing on providers labeled as an OMS. Rural-urban commuting area codes were used to categorize each OMS as urban or rural. The demographic variables included total number of OMSs, provider gender, beneficiaries per provider, beneficiaries' age, and beneficiary hierarchal condition category (proxy for clinical complexity). The outcome variables included opioid prescribing rate, opioid claims per provider, opioid claims per beneficiary, and number of days' supply of opioids per claim. Descriptive statistics, χ2 tests, 2-tailed t tests, and Wilcoxon rank-sum tests were used as appropriate. RESULTS: Across all years, the data consisted of mostly urban and male OMSs. The mean number of Medicare beneficiaries prescribed opioids per OMS varied widely, and the mean age of beneficiaries was 70.4 ± 4.4 and 69.9 ± 4.1 years for urban and rural OMSs, respectively. Mean opioid claims per provider were higher among rural OMSs, with large standard deviations among both rural and urban OMSs. However, there were no significant differences in the opioid prescribing rate or in the mean opioid claims per beneficiary in all 5 years included in the study. There were also no clinically significant differences between urban and rural OMSs in the number of days' supply per claim (between 3 and 4 days in all periods). However, in each year, there was a significantly higher proportion of urban OMSs who prescribed more than 7 days' supply per claim. CONCLUSIONS: Opioid prescription practices were generally similar between rural and urban OMSs treating Medicare beneficiaries. The small subset of longer-term opioid prescribers, which were more prevalent in urban areas, warrants further investigation.

Interfacility Emergency Department Transfer for Mandibular Fractures in the United States.

PURPOSE: Interfacility hospital transfer for isolated mandibular fractures is common but rarely clinically necessary. The purpose of this study was to generate nationally representative estimates regarding the incidence, risk factors, and cost of transfer for isolated mandibular fractures. METHODS: This was a retrospective cohort study using the Nationwide Emergency Department Sample 2018 to identify patients with isolated mandibular fractures. The primary predictor variable was hospital trauma center designation (Level I, Level II, Level III, and nontrauma center). The primary outcome variable was hospital transfer. Total emergency department (ED) charges were also assessed. Covariates were demographic, medical, injury-related, and hospital characteristics. Descriptive, bivariate, and multiple logistic regression statistics were used to evaluate the incidence and predictors of interfacility transfer. RESULTS: A total of 28,357 encounters with mandibular fracture as the primary diagnosis were included. Within this cohort there were 2,893 hospital transfers (10.2%). In unadjusted analysis, evaluation at a nontrauma center, level III trauma center, metropolitan nonteaching hospital, nonmetropolitan nonteaching hospital, micropolitan region, and history of cerebrovascular event was associated with hospital transfer (P ≤ .001). In the adjusted model, independent predictors (risk factors) for hospital transfer were evaluation at a nontrauma center (P ≤ .001, odds ratio [OR] = 12.8, 95% confidence interval [CI] = 6.43 to 25.4), level III trauma center (P ≤ .001, OR = 10.7, 95% CI = 5.25 to 21.7), nonmetropolitan nonteaching hospital (P ≤ .001, OR = 2.45, 95% CI = 1.73 to 3.46), metropolitan nonteaching hospital (P ≤ .001, OR = 1.57, 95% CI = 1.20 to 2.06), cervical spine injury (P = .002, OR = 3.53, 95% CI = 1.61 to 7.75), fractures of the mandibular body (P = .007, OR = 1.33, 95% CI = 1.08 to 1.64), and unspecified mandibular fractures (P = .006, OR = 1.49, 95% CI = 1.12 to 1.99). The average ED charge per encounter was $7,482 ± 565 for a total nationwide charge of $212,172,264. Transferred subjects had total ED charges of $25,632,974, not including additional charges incurred at the recipient hospital. CONCLUSION: Isolated mandibular fractures are common injuries that are frequently transferred and cost the healthcare system millions of dollars annually. Hospital characteristics rather than medical or injury-related variables were the strongest predictors of transfer, suggesting that transfers are primarily driven by need to access maxillofacial surgical services. Programs evaluating necessity of transfer and facilitating specialist evaluation in the outpatient setting may reduce healthcare expenditures for this injury.