DNA Mutational and Copy Number Variation Profiling of Primary Craniofacial Osteosarcomas by Next-Generation Sequencing.

BACKGROUND: Craniofacial osteosarcomas (CFOS) are uncommon malignant neoplasms of the head and neck with different clinical presentation, biological behavior and prognosis from conventional osteosarcomas of long bones. Very limited genetic data have been published on CFOS. METHODS: In the current study, we performed comprehensive genomic studies in 15 cases of high-grade CFOS by SNP array and targeted next generation sequencing. RESULT: Our study shows high-grade CFOS demonstrate highly complex and heterogenous genomic alterations and harbor frequently mutated tumor suppressor genes TP53, CDKN2A/B, and PTEN, similar to conventional osteosarcomas. Potentially actionable gene amplifications involving CCNE1, AKT2, MET, NTRK1, PDGFRA, KDR, KIT, MAP3K14, FGFR1, and AURKA were seen in 43% of cases. GNAS hotspot activating mutations were also identified in a subset of CFOS cases, with one case representing malignant transformation from fibrous dysplasia, suggesting a role for GNAS mutation in the development of CFOS. CONCLUSION: High-grade CFOS demonstrate highly complex and heterogenous genomic alterations, with amplification involving receptor tyrosine kinase genes, and frequent mutations involving tumor suppressor genes.

Osteoblastoma of the thumb with a novel PRSS44::ALK fusion and literature review of osteoblastoma of hands and feet bones.

Osteoblastomas (OBs) are benign neoplasms constituting approximately 1% of primary bone tumors with a predilection for the spine and sacrum. We describe an OB of the proximal phalanx of the left thumb in a 38-year-old female. MRI of left hand demonstrated a 29-mm mildly expansile enhancing lesion involving the entire proximal phalanx of the first digit. Histology displayed a bone-forming tumor consisting of trabeculae of remodeled woven bone framed by plump osteoblasts in a vascularized background. Next-generation sequencing analysis identified a PRSS44::ALK fusion gene.

Non-neoplastic bone, joint, and soft tissue pathology: What every pathologist should know.

The diagnosis of bone and soft tissue tumors is a skill which requires experience across multiple disciplines while their incidence is small. By contrast, the numbers of patients with non-tumorous diseases of bones, soft tissues, and joints dwarfs primary tumors by several orders of magnitude. The ability to successfully diagnose non-neoplastic diseases requires a knowledge of bone development, structure, remodeling, imaging, and tissue processing. This review summarizes the alterations of bones, joints, and to a lesser extent soft tissues that are encountered in the practice of everyday surgical pathology.

Sclerosing epithelioid fibrosarcoma of bone with hybrid features: clinicopathologic, radiologic, and molecular analysis of three cases.

Sclerosing epithelioid fibrosarcoma (SEF) occurring as a primary bone tumor is exceptionally uncommon. Even more rare are cases of SEF that show morphologic overlap with low-grade fibromyxoid sarcoma (LGFMS). Such hybrid lesions arising within the bone have only rarely been reported in the literature. Due to their variegated histomorphology and non-specific radiologic features, these tumors may pose diagnostic difficulties. Herein we describe three molecularly confirmed primary bone cases of sclerosing epithelioid fibrosarcoma that demonstrated prominent areas showing the features of LGFMS and with areas resembling so-called hyalinizing spindle cell tumor with giant rosettes (HSCTGR). Two patients were female and one was male aged 26, 47, and 16, respectively. The tumors occurred in the femoral head, clavicle, and temporal bone. Imaging studies demonstrated relatively well-circumscribed radiolucent bone lesions with enhancement on MRI. Cortical breakthrough and soft tissue extension were present in one case. Histologically the tumors all demonstrated hyalinized areas with SEF-like morphology as well as spindled and myxoid areas with LGFMS-like morphology. Two cases demonstrated focal areas with rosette-like architecture as seen in HSCTGR. The tumors were all positive for MUC4 by immunohistochemistry and cytogenetics, fluorescence in-situ hybridization, and next-generation sequencing studies identified EWSR1 gene rearrangements confirming the diagnosis in all three cases.Hybrid SEF is exceedingly rare as a primary bone tumor and can be difficult to distinguish from other low-grade spindled and epithelioid lesions of bone. MUC4 positivity and identification of underlying EWSR1 gene rearrangements help support this diagnosis and exclude other tumor types.

A Call to Action to Train Underrepresented Minorities in Surgical Subspecialties and Fellowships.

BACKGROUND: With each succession along the surgical career pathway, from medical school to faculty, the percentage of those who identify as underrepresented in medicine (URiM) decreases. We sought to evaluate the demographic trend of surgical fellowship applicants, matriculants, and graduates over time. STUDY DESIGN: The Electronic Residency Application Service and the Graduate Medical Education Survey for general surgery fellowships in colorectal surgery, surgical oncology, pediatric surgery, thoracic surgery, and vascular surgery were retrospectively analyzed (2005 to 2020). The data were stratified by race and gender, descriptive statistics were performed, and time series were evaluated. Race/ethnicity groups included White, Asian, other, and URiM, which is defined as Black/African American, Hispanic/Latino(a), Alaskan or Hawaiian Native, and Native American. RESULTS: From 2005 to 2020, there were 5,357 Electronic Residency Application Service applicants, 4,559 matriculants, and 4,178 graduates to surgery fellowships. Whites, followed by Asians, represented the highest percentage of applicants (62.7% and 22.3%, respectively), matriculants (65.4% and 23.8% respectively), and graduates (65.4% and 24.0%, respectively). For URiMs, the applicants (13.4%), matriculants (9.1%), and graduates (9.1%) remained significantly low (p < 0.001). When stratified by both race and gender, only 4.6% of the applicants, 2.7% of matriculants, and 2.4% of graduates identified as both URiM and female compared to White female applicants (20.0%), matriculants (17.9%), and graduates (16.5%, p < 0.001). CONCLUSIONS: Significant disparities exist for URiMs in general surgery subspecialty fellowships. These results serve as a call to action to re-examine and improve the existing processes to increase the number of URiMs in the surgery subspecialty fellowship training pathway.

Hyper-Realistic Advanced Surgical Skills Package with Cut Suit Simulator Improves Trainee Surgeon Confidence in Operative Trauma.

BACKGROUND: Adequate exposure to operative trauma is not uniform across surgical residencies, and therefore it can be challenging to achieve competency during residency alone. This study introduced the Cut Suit surgical simulator with an Advanced Surgical Skills Package, which replicates traumatic bleeding and organ injury, into surgery resident training across multiple New York City trauma centers. METHODS: Trainees from 6 ACS-verified trauma centers participated in this prospective, observational trial. Groups of 3-5 trainees (post-graduate year 1-6) from 6 trauma centers within the largest public healthcare network in the U.S. participated. Residents were asked to perform various operative tasks including rescucitative thoracotomy, exploratory laprotomy, splenectomy, hepatorrhaphy, retroperitoneal exploration, and small bowel resection on a severely injured simulated patient. Pre- and post-course surveys were used to evaluate trainees' confidence performing these procedures and quizzes were used to evaluate participants' knowledge acquisition after the simulation. RESULTS: One hundred twenty-three surgery residents participated in the evaluation. 68% of participants agreed that the simulation was similar to actual surgery. After the simulation, the percentage of residents reporting being "more confident" or "most confident" in independently managing operative trauma patients increased by 42% (P < .01). There was a significant increase in the proportion of residents reporting being "more confident" or "most confident" managing all procedures performed. Post-activity quiz scores improved by an average of 20.4 points. DISCUSSION: The Cut Suit surgical simulator with ASSP is a realistic and useful adjunct in training surgeons to manage complex operative trauma.

Disparity in Transport of Critically Injured Patients to Trauma Centers: Analysis of the National Emergency Medical Services Information System (NEMSIS).

BACKGROUND: Patient morbidity and mortality decrease when injured patients meeting CDC Field Triage Criteria (FTC) are transported by emergency medical services (EMS) directly to designated trauma centers (TCs). This study aimed to identify potential disparities in the transport of critically injured patients to TCs by EMS. STUDY DESIGN: We identified all patients in the National EMS Information System (NEMSIS) database in the National Association of EMS State Officials East region from January 1, 2018, to December 31, 2019, with a final prehospital acuity of critical or emergent by EMS. The cohort was stratified into patients transported to TCs or non-TCs. Analyses consisted of descriptive epidemiology, comparisons, and multivariable logistic regression analysis to measure the association of demographic features, vital signs, and CDC FTC designation by EMS with transport to a TC. RESULTS: A total of 670,264 patients were identified as sustaining an injury, of which 94,250 (14%) were critically injured. Of those 94,250 critically injured, 56.0% (52,747) were transported to TCs. Among all critically injured women (n = 41,522), 50.4% were transported to TCs compared with 60.4% of critically injured men (n = 52,728, p < 0.001). In a multivariable logistic regression model, critically injured women were 19% less likely to be taken to a TC compared with critically injured men (OR 0.81, 95% CI 0.71-0.93, p = 0.003). CONCLUSIONS: Critically injured female patients are less likely to be transported to TCs when compared with their male counterparts. Performance improvement processes that assess EMS compliance with field triage guidelines should explicitly evaluate for sex-based disparities. Further studies are warranted.

Epithelioid osteoblastoma. Clinicopathologic and immunohistochemical study of 17 cases.

Seventeen cases of epithelioid osteoblastoma were reviewed. The tumors most commonly arose from the vertebrae (7 cases), followed by the mandible (3), sacrum (2), bones of the foot (2), and femur, rib, and scapula (1 each). Patients' ages ranged from 5 to 33 years. The tumors measured from 2.0 to 6.5 cm in the greatest diameter (mean = 4.1 cm) and most patients presented with low-grade pain at the affected site. Imaging studies showed expansile lytic lesions with cortical thickening and a mild rim of sclerosis. Histologically all tumors were characterized by active production of bone with a fibrovascular stroma containing microtrabecular aggregates of bone matrix. The osteoblastic proliferation was atypical and showed enlarged cells with prominent nucleoli and abundant cytoplasm imparting them with a striking epithelioid appearance. Immunohistochemical studies showed variable results that caused difficulties for interpretation; 4 of 12 cases showed strong nuclear positivity for FOS, 2 of 12 cases showed strong diffuse nuclear positivity for FOSB; the remaining cases showed variable, sometimes overlapping patterns, considered to be indeterminate. Ki-67 proliferation marker showed low nuclear positivity (∼2%) in 10 cases and a slight increase (<10%) in two cases. Clinical follow-up was available in 14 patients; one patient experienced a recurrence at six months that was treated with additional curetting; the remainder of the patients were all alive and well without evidence of recurrence from 1 to 22 years (median follow up = 3 years). Epithelioid osteoblastoma is an unusual variant of osteoblastoma that has the potential for simulating a malignancy and does not appear to be associated with a more aggressive behavior.

Examination of Intersectionality and the Pipeline for Black Academic Surgeons.

IMPORTANCE: The lack of underrepresented in medicine physicians within US academic surgery continues, with Black surgeons representing a disproportionately low number. OBJECTIVE: To evaluate the trend of general surgery residency application, matriculation, and graduation rates for Black trainees compared with their racial and ethnic counterparts over time. DESIGN, SETTING, AND PARTICIPANTS: In this nationwide multicenter study, data from the Electronic Residency Application Service (ERAS) for the general surgery residency match and Graduate Medical Education (GME) surveys of graduating general surgery residents were retrospectively reviewed and stratified by race, ethnicity, and sex. Analyses consisted of descriptive statistics, time series plots, and simple linear regression for the rate of change over time. Medical students and general surgery residency trainees of Asian, Black, Hispanic or Latino of Spanish origin, White, and other races were included. Data for non-US citizens or nonpermanent residents were excluded. Data were collected from 2005 to 2018, and data were analyzed in March 2021. MAIN OUTCOMES AND MEASURES: Primary outcomes included the rates of application, matriculation, and graduation from general surgery residency programs. RESULTS: Over the study period, there were 71 687 applicants, 26 237 first-year matriculants, and 24 893 graduates. Of 71 687 applicants, 24 618 (34.3%) were women, 16 602 (23.2%) were Asian, 5968 (8.3%) were Black, 2455 (3.4%) were Latino, and 31 197 (43.5%) were White. Women applicants and graduates increased from 29.4% (1178 of 4003) to 37.1% (2293 of 6181) and 23.5% (463 of 1967) to 33.5% (719 of 2147), respectively. When stratified by race and ethnicity, applications from Black women increased from 2.2% (87 of 4003) to 3.5% (215 of 6181) (P < .001) while applications from Black men remained unchanged (3.7% [150 of 4003] to 4.6% [284 of 6181]). While the matriculation rate for Black women remained unchanged (2.4% [46 of 1919] to 2.3% [52 of 2264]), the matriculation rate for Black men significantly decreased (3.0% [57 of 1919] to 2.4% [54 of 2264]; P = .04). Among Black graduates, there was a significant decline in graduation for men (4.3% [85 of 1967] to 2.7% [57 of 2147]; P = .03) with the rate among women remaining unchanged (1.7% [33 of 1967] to 2.2% [47 of 2147]). CONCLUSIONS AND RELEVANCE: Findings of this study show that the underrepresentation of Black physicians at every stage in surgical training pipeline persists. Black men are especially affected. Identifying factors that address intersectionality and contribute to the successful recruitment and retention of Black trainees in general surgery residency is critical for achieving racial and ethnic as well as gender equity.

Ossifying Fibroma of Non-odontogenic Origin: A Fibro-osseous Lesion in the Craniofacial Skeleton to be (Re-)considered.

In the cranio-facial skeleton, a heterogeneous group of well characterized fibro-osseous lesions can be distinguished. Whereas fibrous dysplasia can affect any skeletal bone, ossifying fibroma and cemento-osseous dysplasia exclusively develop in the cranio-facial region, with most subtypes restricted to the tooth bearing areas of the jaws. Herein we present a series of 20 fibro-osseous lesions that developed mostly in the frontal bone and in the mandible, presenting as expansile intramedullary tumors with a unique histologic appearance and an indolent clinical course. We provide evidence that these tumors are distinct from the categories included in the WHO classification and are therefore currently unclassifiable. The definition of cemento-ossifying fibroma as an odontogenic neoplasm developing only in close proximity to teeth should be re-considered and incorporate also extragnathic lesions as shown here.

Underrepresented Minorities in Surgical Residencies: Where are They? A Call to Action to Increase the Pipeline.

OBJECTIVE: To describe and evaluate trends of general surgery residency applicants, matriculants, and graduates over the last 13 years. SUMMARY OF BACKGROUND DATA: The application and matriculation rates of URMs to medical school has remained unchanged over the last three decades with Blacks and Hispanics representing 7.1% and 6.3% of matriculants, respectively. With each succession along the surgical career pathway, from medical school to residency to a faculty position, the percentage of URMs decreases. METHODS: The Electronic Residency Application Service to General Surgery Residency and the Graduate Medical Education Survey of residents completing general surgery residency were retrospectively analyzed (2005-2018). Data were stratified by race, descriptive statistics were performed, and time series were charted. RESULTS: From 2005 to 2018, there were 71,687 Electronic Residency Application Service applicants to general surgery residencies, 26,237 first year matriculants, and 24,893 general surgery residency graduates. Whites followed by Asians represented the highest percentage of applicants (n = 31,197, 43.5% and n = 16,602, 23%), matriculants (n = 16,395, 62.5% and n = 4768, 18.2%), and graduates (n = 15,239, 61% and n = 4804, 19%). For URMs, the applicants (n = 8603, 12%, P < 0.00001), matriculants (n = 2420, 9.2%, P = 0.0158), and graduates (n = 2508, 10%, P = 0.906) remained significantly low and unchanged, respectively, whereas the attrition was significantly higher (3.6%, P = 0.049) when compared to Whites (2.6%) and Asians (2.9%). CONCLUSION: Significant disparities in the application, matriculation, graduation, and attrition rates for general surgery residency exists for URMs. A call to action is needed to re-examine and improve existing recommendations/paradigms to increase the number of URMs in the surgery training pipeline.

A multiple casualty incident clinical tracking form for civilian hospitals.

BACKGROUND: While mass-casualty incidents (MCIs) may have competing absolute definitions, a universally accepted criterion is one that strains locally available resources. In the fall of 2017, a MCI occurred in New York and Bellevue Hospi-tal received multiple injured patients within minutes; lessons learned included the need for a formalized, efficient patient and injury tracking system. Our objective was to create an organized MCI clinical tracking form for civilian trauma centers. METHODS: After the MCI, the notes of the surgeon responsible for directing patient triage were analyzed. A suc-cinct, organized template was created that allows MCI directors to track demographics, injuries, interventions, and other important information for hmultiple patients in a real-time fashion. This tool was piloted during a subsequent MCI. RESULTS: In late 2018, the hospital received six patients following another MCI. They arrived within a 4-minute window, with 5 patients being critically injured. Two emergent surgeries and angioembolizations were performed. The tool was used by the MCI director to prioritize and expedite care. All physicians agreed that the tool assisted in organizing diagnostic and therapeutic triage. CONCLUSIONS: During MCIs, a streamlined patient tracking template assists with information recall and communica-tion between providers and may allow for expedited care.

Novel FEMASK-score, a histopathologic assessment for destructive Charcot neuropathic arthropathy, reveals intraneural vasculopathy and correlates with progression and best treatment.

BACKGROUND: Charcot neuropathic arthropathy is a debilitating, rapidly destructive degenerative joint disease that occurs in diabetic, neuropathic midfoot. Clinicoradiologic assessment for Charcot neuropathic arthropathy previously relied on Eichenholtz stage. There is limited histopathologic data on this entity. We wanted to independently develop a histopathologic scoring system for Charcot neuropathic arthropathy. DESIGN: Retrieval of surgical pathology midfoot specimens from Charcot patients (2012-2019) were analyzed to evaluate joint soft tissue and bone. Considering progression from large (≥half 40× hpf) to small (

A multiple casualty incident clinical tracking form for civilian hospitals.

BACKGROUND: While mass-casualty incidents (MCIs) may have competing absolute definitions, a universally ac-cepted criterion is one that strains locally available resources. In the fall of 2017, a MCI occurred in New York and Bellevue Hospital received multiple injured patients within minutes; lessons learned included the need for a formal-ized, efficient patient and injury tracking system. Our objective was to create an organized MCI clinical tracking form for civilian trauma centers. METHODS: After the MCI, the notes of the surgeon responsible for directing patient triage were analyzed. A suc-cinct, organized template was created that allows MCI directors to track demographics, injuries, interventions, and other important information for multiple patients in a real-time fashion. This tool was piloted during a subsequent MCI. RESULTS: In late 2018, the hospital received six patients following another MCI. They arrived within a 4-minute window, with 5 patients being critically injured. Two emergent surgeries and angioembolizations were performed. The tool was used by the MCI director to prioritize and expedite care. All physicians agreed that the tool assisted in orga-nizing diagnostic and therapeutic triage. CONCLUSIONS: During MCIs, a streamlined patient tracking template assists with information recall and communica-tion between providers and may allow for expedited care.

Early Anti-Xa Assay-Guided Low Molecular Weight Heparin Chemoprophylaxis Is Safe in Adult Patients with Acute Traumatic Brain Injury.

This study evaluated the safety of early anti-factor Xa assay-guided enoxaparin dosing for chemoprophylaxis in patients with TBI. We hypothesized that assay-guided chemoprophylaxis would be comparable in the risk of intracranial hemorrhage (ICH) progression to fixed dosing. An observational analysis of adult patients with blunt traumatic brain injury (TBI) was performed at a Level I trauma center from August 2016 to September 2017. Patients in the assay-guided group were treated with an initial enoxaparin dose of 0.5 mg/kg, with peak anti-factor Xa activity measured four hours after the third dose. Prophylactic range was defined as 0.2 to 0.5 IU/mL with a dose adjustment of ± 10 mg based on the assay result. The assay-guided group was compared with historical fixed-dose controls and to a TBI cohort from the most recent Trauma Quality Improvement Project dataset. Of 179 patients included in the study, 85 were in the assay-guided group and 94 were in the fixed-dose group. Compared with the fixed-dose group, the assay-guided group had a lower Glasgow Coma Score and higher Injury Severity Score. The proportion of severe (Abbreviated Injury Score, head ≥3) TBI, ICH progression, and venous thromboembolism rates were similar between all groups. The assay-guided and fixed-dose groups had chemoprophylaxis initiated earlier than the Trauma Quality Improvement Project group. The assay-guided group had the highest percentage of low molecular weight heparin use. Early initiation of enoxaparin anti-factor Xa assay-guided venous thromboembolism chemoprophylaxis has a comparable risk of ICH progression to fixed dosing in patients with TBI. These findings should be validated prospectively in a multicenter study.

Osteoblastoma-like osteosarcoma: high-grade or low-grade osteosarcoma?

AIMS: Osteoblastoma-like osteosarcoma is a rare variant of osteosarcoma (1% of all osteosarcomas), histologically similar to osteoblastoma. In the current World Health Organisation (WHO) classification, osteoblastoma-like osteosarcoma is classified within the group of conventional (high-grade) osteosarcomas. However, several published cases have been actually regarded as low-grade malignant tumours. As strict morphological criteria to distinguish between low- and high-grade lesions are not available, we reviewed our series of osteoblastoma-like osteosarcomas in the attempt to identify clinical and morphological features predictive of aggressiveness. METHODS AND RESULTS: We retrieved 15 cases of osteoblastoma-like osteosarcoma from the files of the Istituto Ortopedico Rizzoli. Patients received various treatments. Five patients developed metastasis and five patients developed local recurrences (all after incomplete surgery). Eleven patients were alive without disease, while four patients died of their disease. Statistical analysis revealed a statistically significant (P = 0.048) lower disease-free survival in patients with areas of conventional (high-grade) osteosarcoma. CONCLUSIONS: With the important limitation of a small cohort of patients, the presence of areas of conventional (high-grade) osteosarcoma is the only parameter to predict the aggressiveness of osteoblastoma-like osteosarcoma.

Chemistry of Sputter-Deposited Lithium Sulfide Films.

Lithium sulfide (Li2S) is under intense study because it is the insulating discharge product of ultrahigh energy density lithium-sulfur (Li-S) batteries and a candidate cathode material for lithium-metal-free Li-S cells. In this work, we report the fabrication of an apparatus for sputter deposition of Li2S films ranging in thickness from a few nanometers to several micrometers at rates over 2 nm min-1. High-temperature annealing of the films is shown to produce crystalline films of high chemical purity Li2S for the first time. We provide evidence via complementary X-ray photoelectron and Raman spectroscopy that sputter deposition produces a unique sulfide structure composed of polymer-like chains of Li2S units. The electrochemistry of these films is markedly different from annealed crystalline Li2S, which is shown to be electrochemically inactive. The full theoretical capacity of the as-deposited sulfide structure could be realized during galvanostatic charge, suggesting a facile, solid-state charge process. Finally, we explore trends in the plasma chemistry that lead to nonstoichiometry and depth inhomogeneity during Li2S sputter deposition.