Faculty Bibliography

OBJECTIVES/OBJECTIVE:To determine whether a validated trauma triage tool can identify which middle-aged and geriatric trauma patients with tibial shaft and plateau fractures are at risk for costly admissions and poorer hospital quality measures. DESIGN/METHODS:Prospective cohort study. SETTING/METHODS:Level 1 trauma center. PATIENTS/PARTICIPANTS/METHODS:64 patients over the age of 55 hospitalized with isolated tibial shaft or plateau fractures. INTERVENTION/METHODS:Patients with either isolated tibial plateau fractures or tibial shaft fractures over a three year period were prospectively enrolled in an orthopedic trauma registry. Demographic information, injury severity, and comorbidities were assessed and incorporated into the STTGMA score, a validated trauma triage score that calculates inpatient mortality risk upon admission. Patients were then grouped into tertiles based on their STTGMA score. MAIN OUTCOME MEASUREMENTS/METHODS:Length of stay, complications, discharge location, and direct variable costs. RESULTS:64 patients met inclusion criteria. 33 (51.6%) patients presented with tibial plateau fractures and 31 (48.4%) with tibial shaft fractures. The mean age was 66.7 ± 10.2 years. Mean length of stay was significantly different between risk groups with a mean of 6.8 ± 4 days (p<0.001). While 19 (90.5%) of minimal risk patients were discharged home, only 7 (33.3%) and 5 (22.7%) of moderate and high-risk patients were discharged home, respectively (p<0.001). Higher risk patients experienced a significantly greater number of complications during hospitalization but had no differences in the need for ICU level care (p=0.027 and p=0.344, respectively). The total cost difference between the lowest and highest risk group was nearly 50% ($14070 ± 8056 vs $25147 ± 14471, mean difference $11077; p=0.022). CONCLUSION/CONCLUSIONS:Application of the STTGMA triage tool allows for prediction of key hospital quality measures and cost of hospitalization that can improve clinical decision-making. LEVEL OF EVIDENCE/METHODS:Prognostic Level III.

OBJECTIVES:(1) To demonstrate how a risk assessment tool modified to account for the COVID-19 virus during the current global pandemic is able to provide risk assessment for low-energy geriatric hip fracture patients. (2) To provide a treatment algorithm for care of COVID-19 positive/suspected hip fractures patients that accounts for their increased risk of morbidity and mortality. SETTING:One academic medical center including 4 Level 1 trauma centers, 1 university-based tertiary care referral hospital, and 1 orthopaedic specialty hospital. PATIENTS/PARTICIPANTS:One thousand two hundred seventy-eight patients treated for hip fractures between October 2014 and April 2020, including 136 patients treated during the COVID-19 pandemic between February 1, 2020 and April 15, 2020. INTERVENTION:The Score for Trauma Triage in the Geriatric and Middle-Aged ORIGINAL (STTGMAORIGINAL) score was modified by adding COVID-19 virus as a risk factor for mortality to create the STTGMACOVID score. Patients were stratified into quartiles to demonstrate differences in risk distribution between the scores. MAIN OUTCOME MEASUREMENTS:Inpatient and 30-day mortality, major, and minor complications. RESULTS:Both STTGMA score and COVID-19 positive/suspected status are independent predictors of inpatient mortality, confirming their use in risk assessment models for geriatric hip fracture patients. Compared with STTGMAORIGINAL, where COVID-19 patients are haphazardly distributed among the risk groups and COVID-19 inpatient and 30 days mortalities comprise 50% deaths in the minimal-risk and low-risk cohorts, the STTGMACOVID tool is able to triage 100% of COVID-19 patients and 100% of COVID-19 inpatient and 30 days mortalities into the highest risk quartile, where it was demonstrated that these patients have a 55% rate of pneumonia, a 35% rate of acute respiratory distress syndrome, a 22% rate of inpatient mortality, and a 35% rate of 30 days mortality. COVID-19 patients who are symptomatic on presentation to the emergency department and undergo surgical fixation have a 30% inpatient mortality rate compared with 12.5% for patients who are initially asymptomatic but later develop symptoms. CONCLUSION:The STTGMA tool can be modified for specific disease processes, in this case to account for the COVID-19 virus and provide a robust risk stratification tool that accounts for a heretofore unknown risk factor. COVID-19 positive/suspected status portends a poor outcome in this susceptible trauma population and should be included in risk assessment models. These patients should be considered a high risk for perioperative morbidity and mortality. Patients with COVID-19 symptoms on presentation should have surgery deferred until symptoms improve or resolve and should be reassessed for surgical treatment versus definitive nonoperative treatment with palliative care and/or hospice care. LEVEL OF EVIDENCE:Prognostic Level III. See Instructions for Authors for a complete description of Levels of Evidence.

The SARS-COV-2 (COVID-19) pandemic has placed unprecedented challenges on the health care system in the United States with New York City at its epicenter. By the end of the 8 week (4/23/2020) since the virus's emergence in New York City, there have been 142,432 confirmed COVID-19 cases and 10,977 deaths attributed to complications from COVID-19-related illnesses. Secondary to policies enacted by the New York State government to limit spread of the virus, Orthopedic Surgery departments at hospitals around the area have witnessed an abrupt change in clinical demands. At a local level one trauma hospital in Queens, New York, Orthopedic Surgery elective cases have been cancelled, trauma consult volume has experienced a sharp decline, and both residents and attendings have been repurposed to meet the new clinical demands of this medical crisis. Our own orthopedic surgery service has adopted care for patients normally admitted to an internal medicine service in a novel Ortho-Medical COVID-19 management team. We prepared this primer to make our experience with caring for COVID-19 patents available as a reference for other surgical subspecialty services preparing to adjust the clinical focus of their hospital teams during this or future pandemics. LEVEL OF EVIDENCE:: Level V.

OBJECTIVES/OBJECTIVE:To examine one health system's response to the essential care of its hip fracture population during the COVID-19 pandemic and report on its effect on patient outcomes. DESIGN/METHODS:Prospective cohort study SETTING:: Seven musculoskeletal care centers with New York City and Long Island. PATIENTS/PARTICIPANTS/METHODS:138 recent and 115 historical hip fracture patients. INTERVENTION/METHODS:Patients with hip fractures occurring between February 1, 2020 and April 15, 2020 or between February 1, 2019 and April 15, 2019 were prospectively enrolled in an orthopedic trauma registry and chart reviewed for demographic and hospital quality measures. Patients with recent hip fractures were identified as COVID positive (C+), COVID suspected (Cs) or COVID negative (C-). MAIN OUTCOME MEASUREMENTS/METHODS:Hospital quality measures, inpatient complications and mortality rates. RESULTS:Seventeen (12.2%) patients were confirmed C+ by testing and another 14 (10.1%) were suspected (Cs) of having had the virus but were never tested. The C+ cohort, when compared to Cs and C- cohorts, had: an increased mortality rate (35.3% vs 7.1% vs 0.9%), increased length of hospital stay, a greater major complication rate and a greater incidence of ventilator need postoperatively. CONCLUSIONS:COVID-19 had a devastating effect on the care of hip fracture patients during the pandemic. Although practice patterns generally remained unchanged, treating physicians need to understand the increased morbidity and mortality in hip fracture patients complicated by COVID-19. LEVEL OF EVIDENCE/METHODS:Prognostic Level III. See Instructions for Authors for a complete description of Levels of Evidence.

Lateral compression type 1 pelvic fractures comprise a spectrum of injuries of varying stability. The clinician should be cognizant of signs and symptoms of instability including complete sacral fractures, bilateral ramus fractures, displacement greater than 1 cm, high-energy mechanism, and inability to bear weight. Management of these injuries is controversial, but the clinician should consider examination under anesthesia and potentially surgical stabilization.

Purpose/UNASSIGNED:The purpose of this study was 2-fold: 1) to investigate the age-related frequency, demographics and distribution of the middle-aged and geriatric orthopedic trauma population and 2) to describe the age-related frequency and distribution of hospital quality measure outcomes and inpatient cost. Methods/UNASSIGNED:All patients > 55 years of age who required orthopedic, trauma, or neurosurgery consults at 3 hospitals within an academic medical center from 2014 to 2017 were prospectively followed. On initial evaluation, each patient's demographics, injury severity, and functional status were collected. Patients were grouped into low and high-energy mechanism cohorts and divided into 5 groups based on age. Hospital quality measures including length of stay, complications, discharge location, and cost of care was compared between age groups. Data were analyzed using ANOVA and Chi-square tests. Results/UNASSIGNED:A total of 3965 patients were included in this study of which 3268 (82%) sustained low-energy trauma and 697 (18%) sustained high-energy trauma. With increasing age, more patients had more comorbidities, were less likely to be community ambulators, and more likely to use assistive devices (p < 0.05). Patients in older age groups had longer lengths of stay, more complications, were more likely to need ICU level care, and were less likely to be discharged home (p < 0.05). Rates of mortality were also greater in patients of more advanced age in both low and high-energy cohorts, and the calculated risk triage tool (STTGMA) score increased with each age bracket (p < 0.05). Total cost of care differed between age groups in the low-energy cohort (p = 0.003). Conclusion/UNASSIGNED:This epidemiological study provides a clear picture of the frequency and distribution of demographic, physiologic characteristics, outcomes, and cost of care in a middle-aged and geriatric orthopedic trauma population as evaluated by the STTGMA risk tool. Risk profiling of geriatric trauma patients allows for the establishment of baseline norms.

Purpose/UNASSIGNED:To characterize the volume and variation in orthopedic consults and surgeries that took place during a period of social distancing and pandemic. Methods/UNASSIGNED:All orthopedic consults and surgeries at an urban level 1 trauma center from 3/22/20-4/30/2020 were retrospectively reviewed (the social distancing period). Data from the same dates in 2019 were reviewed for comparison. Age, gender, Score for Trauma Triage in the Geriatric and Middle Aged (STTGMA) score and injury type were queried. Operating room data collected included: type of surgery performed, inpatient or outpatient status, and if the cases were categorized as elective, trauma or infectious cases. Results/UNASSIGNED:Compared to 2019, there was a 48.3% decrease in consult volume in 2020. The 2020 population was significantly older (44.0 vs 52.6 years-old, p = 0.001) and more male (65% vs 35%, p = 0.021). There were 23 COVID positive patients, 10 of which died within the collection period. Consult distribution dramatically changed, with decreases in ankle fractures, distal radius fractures and proximal humerus fractures of 76.5%, 77.4% and 55.0%, respectively. However, there was no significant difference in volume of hip, tibial shaft and femoral shaft fractures (p > 0.05). In 2020, there was a 41.4% decrease in operating room volume, no elective cases were performed, and cases were primarily trauma related. Conclusions/UNASSIGNED:During a period of pandemic and social distancing, the overall volume of orthopedic consults and surgeries significantly declined. However, hip fracture volume remained unchanged. Patients presenting with orthopedic injuries were older, and at higher risk for inpatient mortality.

BACKGROUND:Chemotherapy and targeted therapies have made important strides in cancer treatment yet they often fail and new therapies are still needed. Here, we employed a phenotypic screen to identify and analyze the mechanism of action of novel small molecules that interfere with critical pathways involved in tumor cell growth, using chemoresistant A375 melanoma cells as a model. METHODS:Cell culture studies were performed in ATCC-recommended media. Compounds, and compound libraries were obtained from Boston University or purchased commercially. Effects on A375 cell viability, proliferation and morphology were determined by Celigo Image Cytometer and viability staining. Anticancer activity of the lead compound was tested in a xenograft nude mouse model. Signaling and cell death pathways were analyzed by SDS-PAGE and immunoblotting, and/or fluorescence microscopy. RESULTS:After evaluating 4477 compounds, one hit compound CB533 was identified that caused significant reduction of A375 cell growth. CB533 is an unexplored 1,4-naphthoquinone (NQ) derivative which unlike 1,4-NQ, induced rapid cell death without generating reactive oxygen species (ROS). Structure-activity relationship analysis showed that a pyrrolidine in the 1,4-NQ nucleus in lead compound Pyr-1 yielded optimal activity. CB533 and Pyr-1 had growth-suppressing effects on a large variety of chemotherapy-resistant cancer cell lines in the nano to picomolar range. Pyr-1 also significantly reduced growth of MDA-MB-231 breast cancer cells in nude mice. Pyr-1 rapidly induced activation of major stress pathways and autophagy, which was efficiently blocked by ERK, and somewhat by PI3K inhibitors. CONCLUSION/CONCLUSIONS:CB533 and lead Pyr-1 represent novel broad-spectrum, anticancer compounds that are up to 1000-fold more potent than plumbagin, a natural 1,4-NQ with known anticancer activity. Since the growth suppression activities of CB533 and Pyr-1 are unaffected by the chemotherapy resistance of cancer cells, these compounds have promising therapeutic potential. The pyrrolidine in the 3 position of the 1,4-NQ nucleus of Pyr-1 is a critical component of the pharmacophore. Pyr-1-induced cellular stress was mediated by an ERK, and to a lesser extent by an AKT-dependent pathway without involving apoptosis. Our data suggest that Pyr-1 derives its greatly enhanced antitumor activity via mimicking ROS-induced stress signaling without generating ROS, and likely committing cells to autophagy.