Brain-wide neural activity underlying memory-guided movement.

Behavior relies on activity in structured neural circuits that are distributed across the brain, but most experiments probe neurons in a single area at a time. Using multiple Neuropixels probes, we recorded from multi-regional loops connected to the anterior lateral motor cortex (ALM), a circuit node mediating memory-guided directional licking. Neurons encoding sensory stimuli, choices, and actions were distributed across the brain. However, choice coding was concentrated in the ALM and subcortical areas receiving input from the ALM in an ALM-dependent manner. Diverse orofacial movements were encoded in the hindbrain; midbrain; and, to a lesser extent, forebrain. Choice signals were first detected in the ALM and the midbrain, followed by the thalamus and other brain areas. At movement initiation, choice-selective activity collapsed across the brain, followed by new activity patterns driving specific actions. Our experiments provide the foundation for neural circuit models of decision-making and movement initiation.

EASI-FISH for thick tissue defines lateral hypothalamus spatio-molecular organization.

Determining the spatial organization and morphological characteristics of molecularly defined cell types is a major bottleneck for characterizing the architecture underpinning brain function. We developed Expansion-Assisted Iterative Fluorescence In Situ Hybridization (EASI-FISH) to survey gene expression in brain tissue, as well as a turnkey computational pipeline to rapidly process large EASI-FISH image datasets. EASI-FISH was optimized for thick brain sections (300 µm) to facilitate reconstruction of spatio-molecular domains that generalize across brains. Using the EASI-FISH pipeline, we investigated the spatial distribution of dozens of molecularly defined cell types in the lateral hypothalamic area (LHA), a brain region with poorly defined anatomical organization. Mapping cell types in the LHA revealed nine spatially and molecularly defined subregions. EASI-FISH also facilitates iterative reanalysis of scRNA-seq datasets to determine marker-genes that further dissociated spatial and morphological heterogeneity. The EASI-FISH pipeline democratizes mapping molecularly defined cell types, enabling discoveries about brain organization.

Gene Essentiality Profiling Reveals Gene Networks and Synthetic Lethal Interactions with Oncogenic Ras.

The genetic dependencies of human cancers widely vary. Here, we catalog this heterogeneity and use it to identify functional gene interactions and genotype-dependent liabilities in cancer. By using genome-wide CRISPR-based screens, we generate a gene essentiality dataset across 14 human acute myeloid leukemia (AML) cell lines. Sets of genes with correlated patterns of essentiality across the lines reveal new gene relationships, the essential substrates of enzymes, and the molecular functions of uncharacterized proteins. Comparisons of differentially essential genes between Ras-dependent and -independent lines uncover synthetic lethal partners of oncogenic Ras. Screens in both human AML and engineered mouse pro-B cells converge on a surprisingly small number of genes in the Ras processing and MAPK pathways and pinpoint PREX1 as an AML-specific activator of MAPK signaling. Our findings suggest general strategies for defining mammalian gene networks and synthetic lethal interactions by exploiting the natural genetic and epigenetic diversity of human cancer cells.

Absolute Quantification of Matrix Metabolites Reveals the Dynamics of Mitochondrial Metabolism.

Mitochondria house metabolic pathways that impact most aspects of cellular physiology. While metabolite profiling by mass spectrometry is widely applied at the whole-cell level, it is not routinely possible to measure the concentrations of small molecules in mammalian organelles. We describe a method for the rapid and specific isolation of mitochondria and use it in tandem with a database of predicted mitochondrial metabolites ("MITObolome") to measure the matrix concentrations of more than 100 metabolites across various states of respiratory chain (RC) function. Disruption of the RC reveals extensive compartmentalization of mitochondrial metabolism and signatures unique to the inhibition of each RC complex. Pyruvate enables the proliferation of RC-deficient cells but has surprisingly limited effects on matrix contents. Interestingly, despite failing to restore matrix NADH/NAD balance, pyruvate does increase aspartate, likely through the exchange of matrix glutamate for cytosolic aspartate. We demonstrate the value of mitochondrial metabolite profiling and describe a strategy applicable to other organelles.

A Genome-wide CRISPR Screen in Toxoplasma Identifies Essential Apicomplexan Genes.

Apicomplexan parasites are leading causes of human and livestock diseases such as malaria and toxoplasmosis, yet most of their genes remain uncharacterized. Here, we present the first genome-wide genetic screen of an apicomplexan. We adapted CRISPR/Cas9 to assess the contribution of each gene from the parasite Toxoplasma gondii during infection of human fibroblasts. Our analysis defines ∼200 previously uncharacterized, fitness-conferring genes unique to the phylum, from which 16 were investigated, revealing essential functions during infection of human cells. Secondary screens identify as an invasion factor the claudin-like apicomplexan microneme protein (CLAMP), which resembles mammalian tight-junction proteins and localizes to secretory organelles, making it critical to the initiation of infection. CLAMP is present throughout sequenced apicomplexan genomes and is essential during the asexual stages of the malaria parasite Plasmodium falciparum. These results provide broad-based functional information on T. gondii genes and will facilitate future approaches to expand the horizon of antiparasitic interventions.

The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway.

Amino acids signal to the mTOR complex I (mTORC1) growth pathway through the Rag GTPases. Multiple distinct complexes regulate the Rags, including GATOR1, a GTPase activating protein (GAP), and GATOR2, a positive regulator of unknown molecular function. Arginine stimulation of cells activates mTORC1, but how it is sensed is not well understood. Recently, SLC38A9 was identified as a putative lysosomal arginine sensor required for arginine to activate mTORC1 but how arginine deprivation represses mTORC1 is unknown. Here, we show that CASTOR1, a previously uncharacterized protein, interacts with GATOR2 and is required for arginine deprivation to inhibit mTORC1. CASTOR1 homodimerizes and can also heterodimerize with the related protein, CASTOR2. Arginine disrupts the CASTOR1-GATOR2 complex by binding to CASTOR1 with a dissociation constant of ~30 µM, and its arginine-binding capacity is required for arginine to activate mTORC1 in cells. Collectively, these results establish CASTOR1 as an arginine sensor for the mTORC1 pathway.

An Essential Role of the Mitochondrial Electron Transport Chain in Cell Proliferation Is to Enable Aspartate Synthesis.

The mitochondrial electron transport chain (ETC) enables many metabolic processes, but why its inhibition suppresses cell proliferation is unclear. It is also not well understood why pyruvate supplementation allows cells lacking ETC function to proliferate. We used a CRISPR-based genetic screen to identify genes whose loss sensitizes human cells to phenformin, a complex I inhibitor. The screen yielded GOT1, the cytosolic aspartate aminotransferase, loss of which kills cells upon ETC inhibition. GOT1 normally consumes aspartate to transfer electrons into mitochondria, but, upon ETC inhibition, it reverses to generate aspartate in the cytosol, which partially compensates for the loss of mitochondrial aspartate synthesis. Pyruvate stimulates aspartate synthesis in a GOT1-dependent fashion, which is required for pyruvate to rescue proliferation of cells with ETC dysfunction. Aspartate supplementation or overexpression of an aspartate transporter allows cells without ETC activity to proliferate. Thus, enabling aspartate synthesis is an essential role of the ETC in cell proliferation.

CHP1 Regulates Compartmentalized Glycerolipid Synthesis by Activating GPAT4.

Cells require a constant supply of fatty acids to survive and proliferate. Fatty acids incorporate into membrane and storage glycerolipids through a series of endoplasmic reticulum (ER) enzymes, but how these enzymes are regulated is not well understood. Here, using a combination of CRISPR-based genetic screens and unbiased lipidomics, we identified calcineurin B homologous protein 1 (CHP1) as a major regulator of ER glycerolipid synthesis. Loss of CHP1 severely reduces fatty acid incorporation and storage in mammalian cells and invertebrates. Mechanistically, CHP1 binds and activates GPAT4, which catalyzes the initial rate-limiting step in glycerolipid synthesis. GPAT4 activity requires CHP1 to be N-myristoylated, forming a key molecular interface between the two proteins. Interestingly, upon CHP1 loss, the peroxisomal enzyme, GNPAT, partially compensates for the loss of ER lipid synthesis, enabling cell proliferation. Thus, our work identifies a conserved regulator of glycerolipid metabolism and reveals plasticity in lipid synthesis of proliferating cells.

Cellpose: a generalist algorithm for cellular segmentation.

Many biological applications require the segmentation of cell bodies, membranes and nuclei from microscopy images. Deep learning has enabled great progress on this problem, but current methods are specialized for images that have large training datasets. Here we introduce a generalist, deep learning-based segmentation method called Cellpose, which can precisely segment cells from a wide range of image types and does not require model retraining or parameter adjustments. Cellpose was trained on a new dataset of highly varied images of cells, containing over 70,000 segmented objects. We also demonstrate a three-dimensional (3D) extension of Cellpose that reuses the two-dimensional (2D) model and does not require 3D-labeled data. To support community contributions to the training data, we developed software for manual labeling and for curation of the automated results. Periodically retraining the model on the community-contributed data will ensure that Cellpose improves constantly.

Symptomatic brain metastases in melanoma.

Although clinical outcomes in metastatic melanoma have improved in recent years, the morbidity and mortality of symptomatic brain metastases remain challenging. Response rates and survival outcomes of patients with symptomatic melanoma brain metastases (MBM) are significantly inferior to patients with asymptomatic disease. This review focusses upon the specific challenges associated with the management of symptomatic MBM, discussing current treatment paradigms, obstacles to improving clinical outcomes and directions for future research.

A randomised controlled trial of Standard Of Care versus RadioAblaTion in Early Stage HepatoCellular Carcinoma (SOCRATES HCC).

BACKGROUND: Therapeutic options for early-stage hepatocellular carcinoma (HCC) in individual patients can be limited by tumor and location, liver dysfunction and comorbidities. Many patients with early-stage HCC do not receive curative-intent therapies. Stereotactic ablative body radiotherapy (SABR) has emerged as an effective, non-invasive HCC treatment option, however, randomized evidence for SABR in the first line setting is lacking. METHODS: Trans-Tasman Radiation Oncology Group (TROG) 21.07 SOCRATES-HCC is a phase II, prospective, randomised trial comparing SABR to other current standard of care therapies for patients with a solitary HCC ≤ 8 cm, ineligible for surgical resection or transplantation. The study is divided into 2 cohorts. Cohort 1 will compromise 118 patients with tumors ≤ 3 cm eligible for thermal ablation randomly assigned (1:1 ratio) to thermal ablation or SABR. Cohort 2 will comprise 100 patients with tumors > 3 cm up to 8 cm in size, or tumors ≤ 3 cm ineligible for thermal ablation, randomly assigned (1:1 ratio) to SABR or best other standard of care therapy including transarterial therapies. The primary objective is to determine whether SABR results in superior freedom from local progression (FFLP) at 2 years compared to thermal ablation in cohort 1 and compared to best standard of care therapy in cohort 2. Secondary endpoints include progression free survival, overall survival, adverse events, patient reported outcomes and health economic analyses. DISCUSSION: The SOCRATES-HCC study will provide the first randomized, multicentre evaluation of the efficacy, safety and cost effectiveness of SABR versus other standard of care therapies in the first line treatment of unresectable, early-stage HCC. It is a broad, multicentre collaboration between hepatology, interventional radiology and radiation oncology groups around Australia, coordinated by TROG Cancer Research. TRIAL REGISTRATION: anzctr.org.au, ACTRN12621001444875, registered 21 October 2021.

Is Insurance Payor Associated With Hospital Admission of Emergency Department Adult Patients With Odontogenic Infections?

BACKGROUND: Patients who present to the emergency department (ED) with severe odontogenic infections are often hospitalized for surgical drainage and medical management. However, inpatient management of these patients can be financially burdensome. While medical indications for hospital admission are well established, it remains unclear if patient insurance status is associated with admission. PURPOSE: The purpose of this study was to determine the nationally representative estimates of the incidence of hospital admission for patients with odontogenic infections and the association with insurance payor. STUDY DESIGN, SETTING, SAMPLE: This retrospective cohort study used the 2018 Nationwide Emergency Department Sample. Patients with odontogenic infections (based on International Classification of Diseases, 10th Revision codes) were included. Patients aged <18 years or who had missing data were excluded. PREDICTOR VARIABLE: The primary predictor variable was primary payor (private insurance, Medicare, Medicaid, self-pay, and other). MAIN OUTCOME VARIABLE: The primary outcome variable was hospital admission (yes/no). COVARIATES: Covariates included sociodemographic, medical, infection, and hospital variables. ANALYSES: Descriptive, bivariate, and multivariable logistic regression analyses were used to determine national estimates and predictors of admission. Odds ratios and 99% confidence intervals were computed. Discharge weights were accounted for in all analyses to provide nationally representative estimates. RESULTS: This study included 31,221 weighted ED encounters, of which 10,451 (33.5%) were admitted. In the study cohort, 7,687 (24.6%) had private insurance, 5,046 (16.2%) had Medicare, 10,070 (32.3%) had Medicaid, 7,436 (23.8%) were self-pay, and 982 (3.1%) had other. Bivariate analysis suggested that payor status was significantly associated with hospital admission (P < .01). The multivariable analysis showed that self-pay patients had significantly lower odds of hospital admission compared to those with private insurance (odds ratio, 0.54; 99% confidence interval, 0.42-0.70). Other independent predictors of hospital admission included infection in more than 1 location based on International Classification of Diseases, 10th Revision code, higher Charlson comorbidity index, and alcohol/substance use disorders. CONCLUSION AND RELEVANCE: Approximately one-third of patients presenting to the ED with odontogenic infections were admitted. Patients with no insurance were less likely to be admitted compared to those with private insurance. This finding may reflect multiple possibilities, including hospital financial incentives.

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.

Delayed Gastric Emptying and Gastric Remnant Function After Pancreaticoduodenectomy: A Systematic Review of Objective Assessment Modalities.

BACKGROUND: Delayed gastric emptying (DGE) is a frequent complication after pancreaticoduodenectomy (PD). The diagnosis of DGE is based on International Study Group for Pancreatic Surgery (ISGPS) clinical criteria and objective assessments of DGE are infrequently used. The present literature review aimed to identify objective measures of DGE following PD and determine whether these measures correlate with the clinical definition of DGE. METHODS: A systematic search was performed using the MEDLINE Ovid, EMBASE, Google Scholar and CINAHL databases for studies including pancreatic surgery, delayed gastric emptying and gastric motility until June 2022. The primary outcome was modalities undertaken for the objective measurement of DGE following PD and correlation between objective measurements and clinical diagnosis of DGE. Relevant risk of bias analysis was performed. RESULTS: The search revealed 4881 records, of which 46 studies were included in the final analysis. There were four objective modalities of DGE assessment including gastric scintigraphy (n = 28), acetaminophen/paracetamol absorption test (n = 10), fluoroscopy (n = 6) and the 13C-acetate breath test (n = 3). Protocols were inconsistent, and reported correlations between clinical and objective measures of DGE were variable; however, amongst these measures, at least one study directly or indirectly inferred a correlation, with the greatest evidence accumulated for gastric scintigraphy. CONCLUSION: Several objective modalities to assess DGE following PD have been identified and evaluated, however are infrequently used. Substantial variability exists in the literature regarding indications and interpretation of these tests, and there is a need for a real-time objective modality which correlates with ISGPS DGE definition after PD.

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.

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.

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.

Impact of the EndoPredict genomic assay on treatment decisions for oestrogen receptor-positive early breast cancer patients: benefits of physician selective testing.

PURPOSE: Genomic tests improve accuracy of risk prediction for early breast cancers but these are expensive. This study evaluated the clinical utility of EndoPredict®, in terms of impact on adjuvant therapy recommendations and identification of parameters to guide selective application. METHODS: Patients with ER-positive, HER2-negative, and early-stage invasive breast cancer were tested with EndoPredict®. Two cohorts were recruited: one consecutively and another at clinical team discretion. Systemic treatment recommendations were recorded before and after EndoPredict® results were revealed to the multidisciplinary team. RESULTS: 233 patients were recruited across five sites: 123 consecutive and 110 at clinical team discretion. In the consecutive cohort 50.6% (62/123) cases were classified high risk of recurrence by EndoPredict®, compared with 62.7% (69/110) in the selective cohort. A change in treatment recommendation was significantly more likely (p < 0.0001) in the selective cohort (43/110, 39.1%) compared to the consecutive group (11/123, 8.9%). The strongest driver of selective recruitment was intermediate grade histology, whilst logistic regression modelling demonstrated that nodal status (p < 0.001), proliferative rate (p = 0.001), and progesterone receptor positivity (p < 0.001) were the strongest discriminators of risk. CONCLUSION: Whilst molecular risk can be predicted by traditional variables in a high proportion of cases, EndoPredict® had a greater impact on treatment decisions in those cases selected for testing at team discretion. This is indicative of the robust ability of the clinical team to identify cases most likely to benefit from testing, underscoring the value of genomic tests in the oncologists' tool kit.

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.