Racial Differences and Injury Pattern Variation: Impact of COVID-19 on a Bronx Trauma Center.

BACKGROUND: New York City (NYC) became the epicenter of the COVID-19 pandemic in 2020. The Bronx, with the highest rates of poverty and violent crime of all NYC boroughs and a large Black and Hispanic population, was at increased risk of COVID-19 and its sequelae. We aimed to identify temporal associations among COVID-19 and trauma admission volume, demographics, and mechanism of injury (MOI). METHODS: A retrospective review of prospectively collected data was conducted from a Level II trauma center in the Bronx. January 1st-September 30th for both 2019 (Pre-COVID) and 2020 (COVID) were compared. Pre-COVID and COVID cohorts were subdivided into EARLY (March-May) and LATE (June-September) subgroups. Demographics and trauma outcomes were compared. RESULTS: Trauma admissions were similar between Pre-COVID and COVID. During COVID, there was an increased percentage of Black patients (Black Hispanic 20.1% vs 15.2% and Black Non-Hispanic 39.4% vs 34.1%, P < .05), younger patients (26-35 years old: 22.6% vs 17.6%, P < .05), and out-of-pocket payors (6.0% vs 1.6%, P < .05). Trauma severity outcomes were mixed-some measures supported increased severity; others showed no difference or decreased severity. During COVID, there was a rise in total penetrating injuries (27.4% vs 20.8%, P < .05), MVC (13.2% vs 7.1, P < .05), and firearm injuries (11.6% vs 6.0%, P < .05). Additionally, during LATE COVID, there was a resurgence of total penetrating, total blunt, MVC, falls, cyclists/pedestrians struck, and firearm injuries. DISCUSSION: Our results emphasize MOI variations and racial differences of trauma admissions to a Level II trauma center in the Bronx during COVID-19. These findings may help trauma centers plan during pandemics and encourage outreach between trauma centers and community level organizations following future healthcare disasters.

Implementation of a multidisciplinary perinatal emergency response team improves time to definitive obstetrical evaluation and fetal assessment.

BACKGROUND: Trauma is the leading cause of nonobstetric death during pregnancy and is associated with an increased risk of maternal and fetal mortality. In an effort to improve the delivery of care to pregnant trauma patients, we developed an institutional multidisciplinary quality initiative designed to improve response times of nontrauma specialists and ensure immediate availability of resources. We hypothesized that implementation of a perinatal emergency response team (PERT) would improve time to patient and fetal evaluation and monitoring by the obstetrics (OB) team and improve both maternal and fetal outcomes. METHODS: We performed a 6-year (2012-2018) retrospective cohort analysis of consecutive pregnant trauma patients presenting to our university-affiliated, level I trauma center. Patients in the pre-PERT cohort (before April 2015) were compared with a post-PERT cohort. Variables analyzed included patient demographics, mechanism of injury, Injury Severity Score, and level of trauma activation. The main outcome measure was time to OB evaluation. Secondary outcomes included time to cardiotocometry, and mortality. RESULTS: Of 92 pregnant trauma patients, there were 50 patients (54.3%) in the pre-PERT cohort and 42 (45.7%) in the post-PERT group. Blunt injuries predominated (98.9%), with the most common mechanism being motor vehicle collisions (76.1%), followed by assaults (13%) and falls (6.5%). The mean time to obstetrical evaluation was 44 minutes in the pre-PERT cohort compared with 14 minutes in the post-PERT cohort (p = 0.001). There was a significant decrease in level I (highest acuity) trauma activations pre-PERT and post-PERT (46% vs. 21%, p = 0.01), and the time to cardiotocography was significantly decreased post-PERT implementation (72 vs. .37 min, p = 0.01) CONCLUSION: Implementation of a multidisciplinary PERT improves time to evaluation by the OB team and time to cardiotocometry in the pregnant trauma patient. LEVEL OF EVIDENCE: Retrospective review, level IV.

AMH/MIS as a contraceptive that protects the ovarian reserve during chemotherapy.

The ovarian reserve represents the stock of quiescent primordial follicles in the ovary which is gradually depleted during a woman's reproductive lifespan, resulting in menopause. Müllerian inhibiting substance (MIS) (or anti-Müllerian hormone/AMH), which is produced by granulosa cells of growing follicles, has been proposed as a negative regulator of primordial follicle activation. Here we show that long-term parenteral administration of superphysiological doses of MIS, using either an adeno-associated virus serotype 9 (AAV9) gene therapy vector or recombinant protein, resulted in a complete arrest of folliculogenesis in mice. The ovaries of MIS-treated mice were smaller than those in controls and did not contain growing follicles but retained a normal ovarian reserve. When mice treated with AAV9/MIS were paired with male breeders, they exhibited complete and permanent contraception for their entire reproductive lifespan, disrupted vaginal cycling, and hypergonadotropic hypogonadism. However, when ovaries from AAV9-MIS-treated mice were transplanted orthotopically into normal recipient mice, or when treatment with the protein was discontinued, folliculogenesis resumed, suggesting reversibility. One of the important causes of primary ovarian insufficiency is chemotherapy-induced primordial follicle depletion, which has been proposed to be mediated in part by increased activation. To test the hypothesis that MIS could prevent chemotherapy-induced overactivation, mice were given carboplatin, doxorubicin, or cyclophosphamide and were cotreated with AAV9-MIS, recombinant MIS protein, or vehicle controls. We found significantly more primordial follicles in MIS-treated animals than in controls. Thus treatment with MIS may provide a method of contraception with the unique characteristic of blocking primordial follicle activation that could be exploited to prevent the primary ovarian insufficiency often associated with chemotherapy.

CD44 Splice Variant v8-10 as a Marker of Serous Ovarian Cancer Prognosis.

CD44 is a transmembrane hyaluronic acid receptor gene that encodes over 100 different tissue-specific protein isoforms. The most ubiquitous, CD44 standard, has been used as a cancer stem cell marker in ovarian and other cancers. Expression of the epithelial CD44 variant containing exons v8-10 (CD44v8-10) has been associated with more chemoresistant and metastatic tumors in gastrointestinal and breast cancers, but its role in ovarian cancer is unknown; we therefore investigated its use as a prognostic marker in this disease. The gene expression profiles of 254 tumor samples from The Cancer Genome Atlas RNAseqV2 were analyzed for the presence of CD44 isoforms. A trend for longer survival was observed in patients with high expression of CD44 isoforms that include exons v8-10. Immunohistochemical (IHC) analysis of tumors for presence of CD44v8-10 was performed on an independent cohort of 210 patients with high-grade serous ovarian cancer using a tumor tissue microarray. Patient stratification based on software analysis of staining revealed a statistically significant increase in survival in patients with the highest levels of transmembrane protein expression (top 10 or 20%) compared to those with the lowest expression (bottom 10 and 20%) (p = 0.0181, p = 0.0262 respectively). Expression of CD44v8-10 in primary ovarian cancer cell lines was correlated with a predominantly epithelial phenotype characterized by high expression of epithelial markers and low expression of mesenchymal markers by qPCR, Western blot, and IHC. Conversely, detection of proteolytically cleaved and soluble extracellular domain of CD44v8-10 in patient ascites samples was correlated with significantly worse prognosis (p<0.05). Therefore, presence of transmembrane CD44v8-10 on the surface of primary tumor cells may be a marker of a highly epithelial tumor with better prognosis while enzymatic cleavage of CD44v8-10, as detected by presence of the soluble extracellular domain in ascites fluid, may be indicative of a more metastatic disease and worse prognosis.

AAV9 delivering a modified human Mullerian inhibiting substance as a gene therapy in patient-derived xenografts of ovarian cancer.

To improve ovarian cancer patient survival, effective treatments addressing chemoresistant recurrences are particularly needed. Mullerian inhibiting substance (MIS) has been shown to inhibit the growth of a stem-like population of ovarian cancer cells. We have recently engineered peptide modifications to human MIS [albumin leader Q425R MIS (LRMIS)] that increase production and potency in vitro and in vivo. To test this novel therapeutic peptide, serous malignant ascites from highly resistant recurrent ovarian cancer patients were isolated and amplified to create low-passage primary cell lines. Purified recombinant LRMIS protein successfully inhibited the growth of cancer spheroids in vitro in a panel of primary cell lines in four of six patients tested. Adeno-associated virus (AAV) -delivered gene therapy has undergone a clinical resurgence with a good safety profile and sustained gene expression. Therefore, AAV9 was used as a single i.p. injection to deliver LRMIS to test its efficacy in inhibiting growth of palpable tumors in patient-derived ovarian cancer xenografts from ascites (PDXa). AAV9-LRMIS monotherapy resulted in elevated and sustained blood concentrations of MIS, which significantly inhibited the growth of three of five lethal chemoresistant serous adenocarcinoma PDXa models without signs of measurable or overt toxicity. Finally, we tested the frequency of MIS type II receptor expression in a tissue microarray of serous ovarian tumors by immunohistochemistry and found that 88% of patients bear tumors that express the receptor. Taken together, these preclinical data suggest that AAV9-LRMIS provides a potentially well-tolerated and effective treatment strategy poised for testing in patients with chemoresistant serous ovarian cancer.

Cicatricial external auditory canal stenosis caused by ectodermal dysplasia: Rapp-Hodgkin syndrome.

We present a case of recurrent cicatricial stenosis of the external ear canals caused by ectodermal dysplasia, specifically Rapp-Hodgkin syndrome, in a 45-year-old woman. No form of medical or surgical management has produced durable patency of the patient's ear canals, and her hearing loss is being managed with hearing aids. Topical management of the recurring external otitis slows the process but has been unsuccessful in preventing restenosis of both external auditory canals.