Non-Binary Trauma Patients: Delineating a Vulnerable, At-Risk Population.

INTRODUCTION: An increasing proportion of the population identifies as non-binary. This marginalized group may be at differential risk for trauma compared to those who identify as male or female, but physical trauma among non-binary patients has not yet been examined at a national level. METHODS: All patients aged ≥ 16 years in the National Trauma Data Bank were included (2021-2022). Demographics, injury characteristics, and outcomes after trauma among non-binary patients were compared to males and females. The goal was to delineate differences between groups to inform the care and future study of non-binary trauma patients. RESULTS: In total, 1,012,348 patients were included: 283 (<1%) non-binary, 610,904 (60%) male, and 403,161 (40%) female patients. Non-binary patients were younger than males or females (median age 44 vs 49 vs 67 years, P < .001) and less likely to be White race/ethnicity (58% vs 60% vs 74%, P < .001). Despite non-binary patients having a lower median Injury Severity Score (5 vs 9 vs 9, P < .001), mortality was highest among non-binary and male patients than females (5% vs 5% vs 3%, P < .001). DISCUSSION: In this study, non-binary trauma patients were younger and more likely minority races/ethnicities than males or females. Despite having a lower injury severity, non-binary patient mortality rates were comparable to those of males and greater than for females. These disparities identify non-binary trauma patients as doubly marginalized, by gender and race/ethnicity, who experience worse outcomes after trauma than expected based on injury severity. This vulnerable patient population deserves further study to identify areas for improved trauma delivery care.

A Novel COVID-19 Severity Score is Associated With Survival in Patients Undergoing Percutaneous Dilational Tracheostomy.

INTRODUCTION: Tracheostomy in patients with COVID-19 is a controversial and difficult clinical decision. We hypothesized that a recently validated COVID-19 Severity Score (CSS) would be associated with survival in patients considered for tracheostomy. METHODS: We reviewed 77 mechanically ventilated COVID-19 patients evaluated for decision for percutaneous dilational tracheostomy (PDT) from March to June 2020 at a public tertiary care center. Decision for PDT was based on clinical judgment of the screening surgeons. The CSS was retrospectively calculated using mean biomarker values from admission to time of PDT consult. Our primary outcome was survival to discharge, and all patient charts were reviewed through August 31, 2021. ROC curve and Youden index were used to estimate an optimal cut-point for survival. RESULTS: The mean CSS for 42 survivors significantly differed from that of 35 nonsurvivors (CSS 52 versus 66, P = 0.003). The Youden index returned an optimal CSS of 55 (95% confidence interval 43-72), which was associated with a sensitivity of 0.8 and a specificity of 0.6. The median CSS was 40 (interquartile range 27, 49) in the lower CSS (<55) group and 72 (interquartile range 66, 93) in the high CSS (≥55 group). Eighty-seven percent of lower CSS patients underwent PDT, with 74% survival, whereas 61% of high CSS patients underwent PDT, with only 41% surviving. Patients with high CSS had 77% lower odds of survival (odds ratio = 0.2, 95% confidence interval 0.1-0.7). CONCLUSIONS: Higher CSS was associated with decreased survival in patients evaluated for PDT, with a score ≥55 predictive of mortality. The novel CSS may be a useful adjunct in determining which COVID-19 patients will benefit from tracheostomy. Further prospective validation of this tool is warranted.

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.

A disturbing trend: An analysis of the decline in surgical critical care fellowship training of Black and Hispanic surgeons.

BACKGROUND: Underrepresented minorities in medicine (URiMs) are disproportionally represented in surgery training programs. Rates of URiMs applying to and completing General Surgery residency remain low. We hypothesized that the patterns of URiMs disparities would persist into surgical critical care (SCC) fellowship applicants, matriculants, and graduates. METHODS: We performed a retrospective analysis of SCC applicants, matriculants, and graduates from 2005 to 2020 using the graduate medical education resident survey and analyzed applicant characteristics using the Surgical Critical Care and Acute Care Surgery Fellowship Application Service from 2018 to 2020. The data were stratified by race/ethnicity and sex. Indicator variables were created for Asian, Hispanic, White, and Black trainees. Yearly proportions for each race/ethnicity and sex categories completing or enrolling in a program were calculated and plotted over time with Loess smoothing lines and overlying 95% confidence bands. The yearly rate and statistical significance of change over time were tested with linear regression models with race/ethnicity and sex proportion as the dependent variables and year as the explanatory variable. RESULTS: From 2005 to 2020, there were a total of 2,481 graduates. Black men accounted for 4.7% of male graduates with a significant decline of 0.3% per year for the study period of those completing the fellowship (p = 0.02). Black women comprised 6.4% of female graduates and had a 0.6% decline each year (p < 0.01). A similar trend was seen with Hispanic men, who comprised 3.2% of male graduates and had a 0.3% annual decline (p = 0.02). White men had a significant increase in both matriculation to and graduation from SCC fellowships during the same interval. Similarly, Black and Hispanic applicants declined from 2019 to 2020, while the percentage of White applicants increased. CONCLUSION: Disparities in URiMs representation remain omnipresent in surgery and extend from residency training to SCC fellowship. Efforts to enhance the recruitment and retention of URiMs in SCC training are warranted. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; level IV.

Robotic ileocolic resection with intracorporeal anastomosis for Crohn's disease.

The robotic platform can overcome limitations of the laparoscopic approach, particularly in the facilitation of intracorporeal anastomosis creation. We aim to share our institutional experience with robotic ileocolic resection for Crohn's disease (CD) and compare it to a laparoscopic cohort. We identified patients who underwent ileocolic resection for CD with a purely robotic (R) or laparoscopic (L) approach between February 2015 and 2018. Chart review was performed and preoperative, intraoperative, and postoperative data was collected. A total of 47 patients with a mean age of 35.2 years old were identified and 61% were female. Seventy percent [n = 33, (23 females, 69.6%)] of the cases were performed robotically and 30% of the cases [n = 14, (6 females, 42.8%)] were performed laparoscopically. The groups were well matched for age, gender, BMI as well as disease related factors (CD duration; clinical classification and location), perioperative immunosuppression, and surgical history. Time to bowel function was shorter by about 1 day in the robotic group (R: 1.9 ± 0.88 days vs. L: 2.7 ± 0.8 days, p = 0.003). Mean operative time was longer in the robotic group by 51 min and this difference was significant (p = 0.03), however 30.3% of patients underwent ureteral stent placement, which can account for added time in robotic cases. There were less conversions in the robotic group [R: 1(4.3%) vs. L: 1(7%)], but this was not significant. There were no intraoperative complications in either group. Complication (L: 21.4% vs. R: 15.1%, p = 0.605) and reoperation rates (L: 0% vs. R: 3.03%, p = 0.429) were similar. Robotic ileocolic resection for Crohn's disease is as safe and feasible as the laparoscopic approach. This was accomplished with no leaks, major morbidity or mortality and comparable length of stay, with 1 day shorter return of bowel function, and with a lower overall complication rate. The robotic approach offers advantages in Crohn's disease which should be studied further in prospective studies.

Human breast cancer metastases to the brain display GABAergic properties in the neural niche.

Dispersion of tumors throughout the body is a neoplastic process responsible for the vast majority of deaths from cancer. Despite disseminating to distant organs as malignant scouts, most tumor cells fail to remain viable after their arrival. The physiologic microenvironment of the brain must become a tumor-favorable microenvironment for successful metastatic colonization by circulating breast cancer cells. Bidirectional interplay of breast cancer cells and native brain cells in metastasis is poorly understood and rarely studied. We had the rare opportunity to investigate uncommonly available specimens of matched fresh breast-to-brain metastases tissue and derived cells from patients undergoing neurosurgical resection. We hypothesized that, to metastasize, breast cancers may escape their normative genetic constraints by accommodating and coinhabiting the neural niche. This acquisition or expression of brain-like properties by breast cancer cells could be a malignant adaptation required for brain colonization. Indeed, we found breast-to-brain metastatic tissue and cells displayed a GABAergic phenotype similar to that of neuronal cells. The GABAA receptor, GABA transporter, GABA transaminase, parvalbumin, and reelin were all highly expressed in breast cancer metastases to the brain. Proliferative advantage was conferred by the ability of breast-to-brain metastases to take up and catabolize GABA into succinate with the resultant formation of NADH as a biosynthetic source through the GABA shunt. The results suggest that breast cancers exhibit neural characteristics when occupying the brain microenvironment and co-opt GABA as an oncometabolite.

Strategic design for pediatric neurosurgery missions across the Western Hemisphere.

BACKGROUND: With growing interest in global health, surgeons have created outreach missions to improve health care disparities in less developed countries. These efforts are mainly episodic with visiting surgeons performing the operations and minimal investment in local surgeon education. To create real and durable advancement in surgical services in disciplines that require urgent patient care, such as pediatric neurosurgery, improving the surgical armamentarium of the local surgeons must be the priority. METHODS: We propose a strategic design for extending surgical education missions throughout the Western Hemisphere in order to transfer modern surgical skills to local neurosurgeons. A selection criteria and structure for targeted missions is a derivative of logistical and pedagogical lessons ascertained from previous missions by our teams in Peru and Ukraine. RESULTS: Outreach programs should be applied to hospitals in capital cities to serve as a central referral center for maximal impact with fiscal efficiency. The host country should fulfill several criteria, including demonstration of geopolitical stability in combination with lack of modern neurosurgical care and equipment. The mission strategy is outlined as three to four 1-week visits with an initial site evaluation to establish a relationship with the hospital administration and host surgeons. Each visit should be characterized by collaboration between visiting and host surgeons on increasingly complex cases, with progressive transfer of skills over time. CONCLUSION: A strategic approach for surgical outreach missions should be built on collaboration and camaraderie between visiting and local neurosurgeons, with the mutual objective of cost-effective targeted renovation of their surgical equipment and skill repertoire.

Lineage mapping and characterization of the native progenitor population in cellular allograft.

BACKGROUND CONTEXT: The gold standard for bone grafting remains the autograft. However, the attractiveness of autograft is counterbalanced by donor site morbidity. To mimic autograft-and its fundamental properties of osteoconductivity, osteoinductivity, and osteogenicity-novel bone grafting materials such as cellular allograft (Osteocel Plus) are composed of allograft in which the progenitor cells are preserved. However, the true identity of these cells remains obscure largely due to the lack of specific bona fide antigenic markers for stem versus progenitor cells. PURPOSE: To characterize the stem and progenitor population in cellular allograft, Osteocel Plus. STUDY DESIGN: To determine whether cells endogenous to a cellular allograft undergo extensive self-renewal (a functional hallmark of stem cells), we employed a novel use of lineage mapping using a modern and refined replication incompetent lentiviral library with high complexity to uniquely label single cells with indelible genetic tags faithfully passed on to all progeny, allowing identification of highly proliferative clones. We used genetic and proteomic profiling as well as functional assays to show that these cells are capable of multipotential differentiation (the second functional hallmark of stem cells). Use of these two functional hallmarks enabled us to establish the existence of a stem and progenitor cell population in cellular allografts. METHODS: Specifically, we employed (1) cellular dissociation and (2) in vitro expansion and differentiation capacity of cells released from cellular allograft. We determined differential gene expression profiling of a bona fide human mesenchymal stem cell line and cells from cellular allograft using focused PCR arrays mesenchymal stem cell (MSC) and osteogenesis associated. Proteomic profiling of cells from cellular allograft was performed using (1) immunofluorescence for BMP-2, Runx2 SMADs, CD44, Stro-1, Collagen, RANKL, Osterix Osteocalcin, and Ki67; (2) flow cytometry for Ki67, CD44, Stro-1, Thy1, CD146, and Osteocalcin; and (3) enzyme-linked immunosorbent assays (ELISA) for BMP-2, Osteocalcin, RANKL, Osteoprotegrin, and Osteocalcin. Clonal analysis of cells from cellular allograft was performed utilizing advance lentivirus lineage mapping techniques and massive parallel sequencing. Alizarin Red, Alcian Blue, and Oil red O staining assessed tripotential differentiation capacity. RESULTS: Serial trypsinization of allograft cellular bone matrix yielded approximately 1×105 cells per mL with viability greater than 90%. Cells expressed a panel of 84 MSC-associated genes in a pattern similar to but not identical to pure MSCs; specifically, 59 of 84 genes showed less than a 2.5-fold change in both cell types. Protein analysis showed that cellular allograft -derived cells maintained in nondifferentiation media expressed the early osteo-progenitor markers BMP-2, SMADs, and Runx2. Corresponding flow cytometry data for MSC markers revealed the presence of Stro-1 (49%), CD44 (99%), CD90 (42%), and CD146 (97%). Lineage mapping indicated that 62% of clones persisted and generated progeny through 10 passages, strongly suggesting the presence of bona fide stem cells. Passage 10 clones also exhibited tri-lineage differentiation capacity into osteogenic (Alizarin Red with H&E counterstain), chondrogenic (Alcian Blue), and adipogenic (Oil red O). Cells that did not proliferate through 10 passages presumably differentiated along an osteo-progenitor lineage. CONCLUSION: These data indicate that cellular allograft (Osteocel Plus) contains a heterogeneous population of cells with most cells demonstrating the capacity for extensive self-renewal and multipotential differentiation, which are hallmarks of stem cells. Whether stem cell-enriched allografts function comparably to autograft will require further studies, and their efficacy in facilitating arthrodesis will depend on randomized clinical studies.

Pediatric neurosurgery outreach: sustainability appraisal of a targeted teaching model in Kiev, Ukraine.

PURPOSE: This study evaluates the efficacy of operative skill transfer in the context of targeted pediatric outreach missions completed in Kiev, Ukraine. In addition the ability to create sustainable surgical care improvement is investigated as an efficient method to improve global surgical care. METHODS: Three 1-week targeted neurosurgical missions were performed (2005-2007) to teach neuroendoscopy, which included donation of the necessary surgical equipment, so the host team can deliver newly acquired surgical skills to their citizens after the visiting mission team departs. The neuroendoscopy data for the 4 years after the final mission in 2007 was obtained. RESULTS: After performing pediatric neurosurgery missions in 2005-2007, with a focus on teaching neuroendoscopy, the host team demonstrated the sustainability of our educational efforts in the subsequent 4 years by performing cases independently for their citizens. Since the last targeted mission of 2007, neuroendoscopic procedures have continued to be performed by the trained host surgeons. In 2008, 33 cases were performed. In 2009 and 2010, 29 and 22 cases were completed, respectively. In 2011, local neurosurgeons accomplished 27 cases. To date, a total of 111 operations have been performed over the past 4 years independent of any visiting team, illustrating the sustainability of educational efforts of the missions in 2005-2007. CONCLUSIONS: Effective operative skill transfer to host neurosurgeons can be accomplished with limited international team visits using a targeted approach that minimizes expenditures on personnel and capital. With the priority being teaching of an operative technique, as opposed to perennially performing operations by a visiting mission team, sustainable surgical care was achieved and perpetuated after missions officially concluded.

Stem cell-mediated osteogenesis: therapeutic potential for bone tissue engineering.

Intervertebral disc degeneration often requires bony spinal fusion for long-term relief. Current arthrodesis procedures use bone grafts from autogenous bone, allogenic backed bone, or synthetic materials. Autogenous bone grafts can result in donor site morbidity and pain at the donor site, while allogenic backed bone and synthetic materials have variable effectiveness. Given these limitations, researchers have focused on new treatments that will allow for safe and successful bone repair and regeneration. Mesenchymal stem cells have received attention for their ability to differentiate into osteoblasts, cells that synthesize new bone. With the recent advances in scaffold and biomaterial technology as well as stem cell manipulation and transplantation, stem cells and their scaffolds are uniquely positioned to bring about significant improvements in the treatment and outcomes of spinal fusion and other injuries.

Clinical efficacy of stem cell mediated osteogenesis and bioceramics for bone tissue engineering.

Lower back pain is a common disorder that often requires bony spinal fusion for long-term relief. Current arthrodesis procedures use bone grafts from autogenous bone, allogenic backed bone or synthetic materials. Autogenous bone grafts can result in donor site morbidity and pain at the donor site, while allogenic backed bone and synthetic materials have variable effectiveness. Given these limitations, researchers have focused on new treatments that will allow for safe and successful bone repair and regeneration. Mesenchymal stem cells (MSCs) have received attention for their ability to differentiate into osteoblasts, cells that synthesize the extracellular matrix and regulate matrix mineralization. Successful bone regeneration requires three elements: MSCs that serve as osteoblastic progenitors, osteoinductive growth factors and their pathways that promote development and differentiation of the cells as well as an osteoconductive scaffold that allows for the formation of a vascular network. Future treatments should strive to combine mesenchymal stem cells, cell-seeded scaffolds and gene therapy to optimize the efficiency and safety of tissue repair and bone regeneration.

Emerging role of brain metastases in the prognosis of breast cancer patients.

Cancer starts with one rogue cell. Through mutations and genomic alterations, the cell acquires specific and stem cell-like characteristics necessary for invasion of a distant organ and ultimately metastasis. Metastatic brain cancer is a particularly formidable disease because of its poor prognosis and the highly resistant nature of the tumor to chemotherapy. Although several types of primary tumors have a tendency to metastasize to the brain, the incidence of brain metastases has increased dramatically in some subsets of breast cancer patients. Several conventional treatments are available, but success is limited and often short-lived. Given that no standard treatment options exist, there is a significant need to investigate the biology of these clinically recalcitrant tumors.