Integrating simulation and interpretive description to explore operating room leadership: critical event continuing education.

In Obstetrics and Gynecologic operating room emergencies, the surgeon cannot both operate and lead a suddenly expanded and redirected team response. However, one of the most often used approaches to interprofessional continuing education designed to improve teams' ability to respond to unanticipated critical events still emphasizes surgeon leadership. We developed Explicit Anesthesia and Nurse Distributed (EXPAND) Leadership to imagine a workflow that might better distribute emergency leadership task responsibilities and practices. The purpose of this exploratory study was to investigate teams' responses to distributing leadership during an interprofessional continuing education simulated obstetrical emergency. We used interpretive descriptive design in a secondary analysis of teams' post-simulation reflective debriefings. One-hundred sixty providers participated, including OB-Gyn surgeons, anesthesiologists, CRNAs, scrub technicians, and nurses. Using reflective thematic analysis, we identified three core themes: 1) The surgeon is focused on the surgical field, 2) Explicit leadership initiates a nurse transition from follower to leader in a hierarchical environment, and 3) Explicit distributed leadership enhances teamwork and taskwork. Continuing education which uses distributed leadership to improve teams' ability to respond to an obstetric emergency is perceived to enhance team members' response to the critical event . The potential for nurses' career growth and professional transformation was an unexpected finding associated with this continuing education which used distributed leadership. Our findings suggest that healthcare educators should consider ways in which distributed leadership may improve teams' response to critical events in the operating room.

Geographic differences in community oncology provider and practice location characteristics in the central United States.

PURPOSE: How care delivery influences urban-rural disparities in cancer outcomes is unclear. We sought to understand community oncologists' practice settings to inform cancer care delivery interventions. METHODS: We conducted secondary analysis of a national dataset of providers billing Medicare from June 1, 2019 to May 31, 2020 in 13 states in the central United States. We used Kruskal-Wallis rank and Fisher's exact tests to compare physician characteristics and practice settings among rural and urban community oncologists. FINDINGS: We identified 1,963 oncologists practicing in 1,492 community locations; 67.5% practiced in exclusively urban locations, 11.3% in exclusively rural locations, and 21.1% in both rural and urban locations. Rural-only, urban-only, and urban-rural spanning oncologists practice in an average of 1.6, 2.4, and 5.1 different locations, respectively. A higher proportion of rural community sites were solo practices (11.7% vs 4.0%, P<.001) or single specialty practices (16.4% vs 9.4%, P<.001); and had less diversity in training environments (86.5% vs 67.8% with <2 medical schools represented, P<.001) than urban community sites. Rural multispecialty group sites were less likely to include other cancer specialists. CONCLUSIONS: We identified 2 potentially distinct styles of care delivery in rural communities, which may require distinct interventions: (1) innovation-isolated rural oncologists, who are more likely to be solo providers, provide care at few locations, and practice with doctors with similar training experiences; and (2) urban-rural spanning oncologists who provide care at a high number of locations and have potential to spread innovation, but may face high complexity and limited opportunity for care standardization.

Entinostat, a selective HDAC1/2 inhibitor, potentiates the effects of olaparib in homologous recombination proficient ovarian cancer.

OBJECTIVE: Poly ADP ribose polymerase inhibitors (PARPi) are most effective in BRCA1/2 mutated ovarian tumors. Better treatments are needed for homologous recombination HR-proficient cancer, including CCNE1 amplified subtypes. We have shown that histone deacetylase inhibitors (HDACi) sensitize HR-proficient ovarian cancer to PARPi. In this study, we provide complementary preclinical data for an investigator-initiated phase 1/2 clinical trial of the combination of olaparib and entinostat in recurrent, HR-proficient ovarian cancer. METHODS: We assessed the in vitro effects of the combination of olaparib and entinostat in SKOV-3, OVCAR-3 and primary cells derived from CCNE1 amplified high grade serous ovarian cancer (HGSOC) patients. We then tested the combination in a SKOV-3 xenograft model and in a patient-derived xenograft (PDX) model. RESULTS: Entinostat potentiates the effect of olaparib in reducing cell viability and clonogenicity of HR-proficient ovarian cancer cells. The combination reduces peritoneal metastases in a SKOV-3 xenograft model and prolongs survival in a CCNE1 amplified HR-proficient PDX model. Entinostat also enhances olaparib-induced DNA damage. Further, entinostat decreases BRCA1, a key HR repair protein, associated with decreased Ki-67, a proliferation marker, and increased cleaved PARP, a marker of apoptosis. Finally, entinostat perturbs replication fork progression, which increases genome instability. CONCLUSION: Entinostat inhibits HR repair by reducing BRCA1 expression and stalling replication fork progression, leading to irreparable DNA damage and ultimate cell death. This work provides preclinical support for the clinical trial of the combination of olaparib and entinostat in HR-proficient ovarian cancer and suggests potential benefit even for CCNE1 amplified subtypes.

Disparities in ovarian cancer survival at the only NCI-designated cancer center in Kansas.

BACKGROUND: This study examined the impact of geographic distance on survival outcomes for patients receiving treatment for ovarian cancer at the only NCI-designated cancer center (NCI-CC) in Kansas. METHODS: We identified ovarian cancer patients treated at the University of Kansas Cancer Center between 2010 and 2015. Demographic factors and clinical characteristics were abstracted. The main outcome measure was overall survival according to geographic distance from the institution. Kaplan Meier survival curves and Cox proportional hazard models were generated using SAS v9.4. RESULTS: 220 patients were identified. Survival analysis based on distance from the institution demonstrated that patients who lived ≤10 miles from the institution had worse overall survival (p = 0.0207) and were more likely to have suboptimal cytoreductive surgery (p = 0.0276). Lower estimated median income was also associated with a 1.54 increased risk of death, 95% CI (1.031-2.292), p = 0.0347. CONCLUSIONS: We determined that ovarian cancer survival disparities exist in our patient population. Lower rates of optimal cytoreductive surgery has been identified as a possible driver of poor prognosis for patients who lived in proximity to our institution.

Does a Multidisciplinary Approach to Invasive Breast Cancer Care Improve Time to Treatment and Patient Compliance?

PURPOSE: This study aimed to evaluate whether comprehensive multidisciplinary care (cMDC) for breast cancer patients affected time from diagnosis to treatment, compliance with appointments and to assess for racial disparities. METHODS: This institutional review board approved retrospective study included adult patients diagnosed with invasive breast cancer between February 2015 and February 2017 and treated at an academic health system where the cMDC program was implemented in February 2016. The cMDC and non-cMDC groups as well as black and white patients were compared to assess time from diagnosis (date of pathology result indicating invasive breast cancer) to treatment (date of surgery or chemotherapy). Compliance was measured by appointments characterized as "no shows" or "canceled due to personal reasons" in the electronic medical record. RESULTS: Of 541 patients (419 cMDC and 122 non-cMDC), mean time from diagnosis to treatment was significantly longer for blacks than whites in the non-cMDC group (46.9 ± 64.6 days vs 28.2 ± 14.8 days, p = 0.024) and the cMDC group (39.9 ± 34.1 days vs 31.4 ± 16.3 days, p = 0.001). Of 38 (7.2%) patients who started treatment > 60 days after diagnosis, 25 (65.8%) were black. Implementation of cMDC significantly improved patient compliance (missed appointments 4.9 ± 7.6 non-cMDC vs 3.2 ± 4.6 cMDC, p = 0.029). CONCLUSION: Use of cMDC for invasive breast cancer at our institution highlighted an area for improvement for care administered to blacks and improved patient compliance with appointments.

CCNE1 and BRD4 co-amplification in high-grade serous ovarian cancer is associated with poor clinical outcomes.

OBJECTIVE: High-grade serous ovarian cancer (HGSOC) is the most common and lethal histological subtype of epithelial ovarian cancer. HGSOC with cyclin E1 gene (CCNE1) amplification and bromodomain and extraterminal 4 (BRD4) amplification have been associated with poor outcomes. Our objective was to evaluate clinical outcomes of HGSOC with co-amplification of CCNE1 and BRD4 and high protein expression of cyclin E and BRD4. METHODS: Copy number amplification data were extracted from The Cancer Genome Atlas (TCGA) for 579 HGSOC. Reverse phase protein array (RPPA) TCGA data were used to determine cyclin E and BRD4 protein expression in 482 HGSOC. Cyclin E and BRD4 protein expression by immunohistochemistry (IHC) was evaluated in a tissue microarray (TMA) of 110 HGSOC. Measured clinical outcomes were survival and platinum sensitivity. RESULTS: Of 30% of HGSOC with amplifications in CCNE1 or BRD4, 8% have both CCNE1 and BRD4 amplification. Protein expression of cyclin E and BRD4 are positively correlated, both by RPPA (r = 0.23; p < 0.001) and by IHC (r = 0.21; p = 0.025). Patients with CCNE1 and BRD4 co-amplified HGSOC have worse overall survival than patients without amplifications, 39.94 vs 48.06 months (p = 0.029). High protein expression of cyclin E, but not BRD4, was associated with poor overall survival (HR 1.62, 1.04-2.53, p = 0.033) and platinum resistance (p = 0.016). CONCLUSION: HGSOC with CCNE1 and BRD4 co-amplification are associated with poor overall survival. Further studies are warranted to determine the use of protein expression by IHC as a surrogate marker for CCNE1 and BRD4 co-amplified HGSOC.

Utilization of genetic testing in breast cancer treatment after implementation of comprehensive multi-disciplinary care.

To evaluate the utilization of genetic testing after implementing a comprehensive multi-disciplinary care (cMDC) program for breast cancer and to assess for racial disparities. This retrospective study included patients newly diagnosed with invasive breast cancer 1 year before and 1 year after implementing a cMDC program to assess the rate of genetic referrals. Appropriate genetic referrals were defined by age, family history, triple-negative status, and personal history based on National Comprehensive Cancer Network guidelines. Secondary outcomes included rates of recommended testing, actual testing, compliance, and equity in genetic referrals across demographics (race, insurance type, and hospital site). Statistical analyses used the Fisher exact test or chi-square test. The 431 patients identified included 116 non-cMDC and 315 cMDC patients. Following implementation of cMDC, a significant increase occurred not only in appropriate genetic referrals (35.3%-55.5%) but also in inappropriate referrals (1.7%-15.5%) (P = .001). Overall attendance increased among both cohorts, Caucasians were more compliant with attending their genetic appointment compared to their African American counterparts (non-cMDC P = .025, cMDC P = .004). In the cMDC group, African Americans demonstrated a 6% increase in attendance compared to a 2% decrease among Caucasians. More appropriate genetic referrals were made to those with private insurance following implementation of cMDC. Utilizing a cMDC approach to breast cancer care may help increase appropriate utilization of genetics.

Definitive radiation therapy for cervical cancer: Non-white race and public insurance are risk factors for delayed completion, a pilot study.

This is a pilot study to assess whether racial disparities exist in time to initiation and completion of external beam pelvic radiation therapy and brachytherapy in cervical cancers treated with definitive chemoradiation. A retrospective analysis was conducted on all cervical cancer patients treated with definitive radiotherapy between 2006 and 2016 at a single institution. Patient demographics including age, race, insurance status and stage at diagnosis were obtained. Analyses were performed according to the following definitions of wait times: interval from pathologic diagnosis of cervical cancer to (Siegel et al., 2016) initiation of radiation therapy, (Yoo et al., 2017) completion of external beam radiation therapy and (DeSantis et al., 2016) completion of external beam radiation therapy plus brachytherapy if indicated. Of 50 women, 21 self-identified as white, 25 as black and 4 as Hispanic. Due to small numbers, Hispanic women were included with black women as a non-white group. The average age was 52 years for women in this cohort. Mean days to initiation of radiation therapy were 41.8 days: 33.7 days among white patients versus 47.8 days for non-white patients (p-value 0.101). Mean days from diagnosis to completion of external beam pelvic radiation therapy were 81.3 days: 70.9 days among white patients versus 88.9 days among non-white patients (p-value 0.006). Non-white patients were more likely to have public insurance, which was also associated with a longer time to completion of radiation treatment. We conclude that non-white patients experienced delays to completing external beam radiation therapy, which was no longer present after adjusting for insurance status.

Time to Clinical Follow-up after Abnormal Mammogram among African American and Hispanic Women.

BACKGROUND: Time to clinical follow-up after an abnormal mammogram may be a significant factor contributing to breast cancer health disparities. OBJECTIVE: Evaluate time to follow-up in a cross-sectional cohort of African American and Hispanic women who obtained mammogram screening at a county facility. METHODS: Time to follow-up was assessed in days after an abnormal mammogram to subsequent clinical care in a cross-sectional study of 74 women. RESULTS: The median number of days until clinical follow-up after an abnormal mammogram for women in the study was 30 days (Range: 0-357 days). There was a statistically significant difference in the time-to-biopsy among women who had incomplete mammograms and women who had comorbid conditions. CONCLUSIONS: This data indicates that county services provide clinical follow-up in compliance with recommended guidelines of 30 days. However, women with incomplete mammograms and comorbid conditions may be at a higher risk of experiencing delays in diagnosis and treatment.

Rate of Urologic Injury with Robotic Hysterectomy.

STUDY OBJECTIVE: To evaluate rates of urologic injury in patients who underwent robotic hysterectomy compared with laparoscopic, vaginal, and open hysterectomy. DESIGN: A retrospective analysis (Canadian Task Force classification II-2). SETTING: Henry Ford Health System, 2013 to 2016. PATIENTS: Women who underwent robotic, vaginal, laparoscopic, and open abdominal hysterectomy. INTERVENTIONS: Robotic hysterectomy, laparoscopic-assisted vaginal hysterectomy, total laparoscopic hysterectomy, laparoscopic supracervical hysterectomy, vaginal hysterectomy, and abdominal hysterectomy. MEASUREMENTS AND MAIN RESULTS: To identify patients with urologic injury, a departmental database for quality improvement was searched for reported urologic injuries. In addition, patients who had urology consultation within 90 days of hysterectomy were screened for injury. A total of 3114 hysterectomies were identified by retrospective chart review. One thousand eighty-eight robotic, 782 laparoscopic, 304 vaginal, and 940 abdominal hysterectomies were analyzed for urologic complications. A total of 27 injuries were confirmed (7 during laparoscopic hysterectomy, 10 during robotic hysterectomy, 1 during vaginal hysterectomy, and 9 during abdominal hysterectomy). The overall rate of urologic injury was 0.87% with a 0.55% risk of bladder injury and a 0.32% risk of injury to the ureter. When the route of hysterectomy was taken into account, the risk of urologic injury was 0.92% for robotic hysterectomy, 0.90% for laparoscopic hysterectomy, 0.33% for vaginal hysterectomy, and 0.96% for open hysterectomy. The mean body mass index (BMI) for all patients was 32.7 kg/m2; injured patients had a mean BMI of 34.6 kg/m2, and noninjured patients had a mean BMI of 32.0 kg/m2 (p = .10). CONCLUSION: Rates of urologic injury with robotic hysterectomy are similar to those of laparoscopic hysterectomy in our population. BMI was not significantly different in patients who had urologic injuries. Surgeon volume was not associated with risk for urologic injury.

Placental Chorangiosis: Increased Risk for Cesarean Section.

We describe a patient with Class C diabetes who presented for nonstress testing at 36 weeks and 4 days of gestation with nonreassuring fetal heart tones (NRFHT) and oligohydramnios. Upon delivery, thrombosis of the umbilical cord was grossly noted. Pathological analysis of the placenta revealed chorangiosis, vascular congestion, and 40% occlusion of the umbilical vein. Chorangiosis is a vascular change of the placenta that involves the terminal chorionic villi. It has been proposed to result from longstanding, low-grade hypoxia in the placental tissue and has been associated with such conditions such as diabetes, intrauterine growth restriction (IUGR), and hypertensive conditions in pregnancy. To characterize chorangiosis and its associated obstetric outcomes we identified 61 cases of "chorangiosis" on placental pathology at Henry Ford Hospital from 2010 to 2015. Five of these cases were omitted due to lack of complete records. Among the 56 cases, the cesarean section rate was 51%, indicated in most cases for nonreassuring fetal status. Thus, we suggest that chorangiosis, a marker of chronic hypoxia, is associated with increased rates of cesarean sections for nonreassuring fetal status because of long standing hypoxia coupled with the stress of labor.

MARCH ubiquitin ligases alter the itinerary of clathrin-independent cargo from recycling to degradation.

Following endocytosis, internalized plasma membrane proteins can be recycled back to the cell surface or trafficked to late endosomes/lysosomes for degradation. Here we report on the trafficking of multiple proteins that enter cells by clathrin-independent endocytosis (CIE) and determine that a set of proteins (CD44, CD98, and CD147) found primarily in recycling tubules largely failed to reach late endosomes in HeLa cells, whereas other CIE cargo proteins, including major histocompatibility complex class I protein (MHCI), trafficked to both early endosome antigen 1 (EEA1) and late endosomal compartments in addition to recycling tubules. Expression of the membrane-associated RING-CH 8 (MARCH8) E3 ubiquitin ligase completely shifted the trafficking of CD44 and CD98 proteins away from recycling tubules to EEA1 compartments and late endosomes, resulting in reduced surface levels. Cargo affected by MARCH expression, including CD44, CD98, and MHCI, still entered cells by CIE, suggesting that the routing of ubiquitinated cargo occurs after endocytosis. MARCH8 expression led to direct ubiquitination of CD98 and routing of CD98 to late endosomes/lysosomes.