Goal-Concordance in Children with Complex Chronic Conditions.

OBJECTIVES: To characterize delivery of goal-concordant end-of-life (EOL) care among children with complex chronic conditions and to determine factors associated with goal-concordance. STUDY DESIGN: This was a retrospective review of goals of care discussions for 272 children with at least 1 complex chronic condition who died at a tertiary care hospital between January 1, 2014, and December 31, 2017. Goals of care and code status were assessed before and within the last 72 hours of life. Goals of care discussions were coded as full interventions; considering withdrawal of interventions (palliation); planned transition to palliation; or actively transitioning/transitioned to palliation. RESULTS: In total, 158 children had documented goals of care discussions before and within the last 72 hours of life, 18 had goals of care discussions only >72 hours before death, 54 only in the last 72 hours of life, and 42 had no documented goals of care. For children with goals of care, EOL care was goal-concordant for 82.2%, discordant in 7%, and unclear in 10.8%. Black children had a greater than 8-fold greater odds of discordant care compared with White children (OR 8.34, P = .007). Comparison of goals of care and code status before and within the last 72 hours of life revealed trends toward nonescalation of care. Specifically, rates of active palliation increased from 11.7% to 63.0%, and code status shifted from 32.6% do not resuscitate to 65.2% (P < .001). CONCLUSIONS: In this cohort, a majority of children had documented goals of care discussions and received goal-concordant EOL care. However, Black children had greater odds of receiving goal-discordant care. Goals of care and code status shifted toward palliation during the last 72 hours of life.

Lifestyle Factors and Other Influences on Medical Students Choosing a Career in Emergency Medicine.

OBJECTIVE: The purpose of this study was to determine which lifestyle factors influence medical students who choose a career in emergency medicine (EM). METHODS: Final-year medical students from 10 medical schools were surveyed after the National Residency Match Program match but prior to graduation regarding preferred medical specialty and lifestyle preferences. Responses from students pursuing EM regarding importance of lifestyle factors were compared to students interested in other specialties. RESULTS: A total of 453 of 1,575 invited medical students completed an electronic survey. EM was the third most preferred specialty. Students selecting EM were less likely to endorse "having control of work schedule" as being important (p < 0.005), but more likely to endorse "having time off work" as important (p < 0.05). When students were asked what specific factors were important in choosing a specialty, EM students differed from other students in the importance of flexible work schedule, time outside of work, and balance between work and personal life (p < 0.001). Fewer EM students endorsed that having a "low-stress work day" was an important consideration in their specialty choice (p < 0.001). CONCLUSIONS: In this study representing 10 medical schools, graduating medical students who prefer EM as opposed to other specialties exhibit differences in lifestyle factors deemed important when choosing a specialty as a physician. Further investigation regarding any potential link to these factors and career longevity is warranted.

Examination and prognostic implications of the unique microenvironment of breast cancer brain metastases.

PURPOSE: Brain metastases (BM) are a complication of advanced breast cancer (BC). Histology of melanoma BM offers prognostic value; however, understanding the microenvironment of breast cancer brain metastases (BCBM) is less characterized. This study reports on four histological biomarkers, gliosis, immune infiltrate, hemorrhage, necrosis, and their prognostic significance in BCBM. METHODS: A biobank of 203 human tissues from patients who underwent craniotomy for BCBM was created across four academic institutions. Degree of gliosis, immune infiltrate, hemorrhage, and necrosis were identified and scored via representative H&E stain (0-3+). Overall survival (OS) was estimated using the Kaplan-Meier method. Cox proportional hazards regression evaluated prognostic value of the biomarkers in the context of standard clinical characteristics. RESULTS: BCBM subtype (available for n = 158) was 36% Her2+, 26% hormone receptor (HR)+/Her2- 38% HR-/Her2- (triple negative, TN). Gliosis was observed in 82% (116/141) of BCBM, with immune infiltrate 44% (90/201), hemorrhage 82% (166/141), and necrosis 87% (176/201). Necrosis was significantly higher in TNBC (p < 0.01). Presence of gliosis, immune infiltrate, and hemorrhage correlated with improved OS (p = 0.03, p = 0.03, p = 0.1), while necrosis correlated with inferior OS (p = 0.01). Improved OS was associated with gliosis in TN (p = 0.02), and immune infiltrate (p = 0.001) and hemorrhage (p = 0.07) in HER2+. In a multivariable model for OS, incorporating these biomarkers with traditional clinical variables improved the model fit (p < 0.001). CONCLUSION: Gliosis confers superior prognosis in TNBC BM; immune infiltrate and hemorrhage correlate with superior prognosis in HER2+ BCBM. Understanding the metastatic microenvironment of BCBM refines prognostic considerations and may unveil novel therapeutic strategies.

Perceived Value of a Skills Laboratory With Virtual Reality Simulator Training in Arthroscopy: A Survey of Orthopedic Surgery Residents.

BACKGROUND: Arthroscopy is one of the most common procedures performed by orthopedic surgeons. Virtual reality (VR) simulation in general surgery residency training has been increasing over the past decade, but it has seen little use in the field of orthopedic surgery. OBJECTIVE: To determine osteopathic orthopedic surgery residents' perceived value of having access to a VR simulator before performing an arthroscopic procedure on a live patient. METHODS: A survey was developed and sent to all US osteopathic orthopedic surgery residency programs to be disseminated to all of their current residents. The survey consisted of 12 questions, which included Likert-type scale responses and yes or no responses. RESULTS: Fifty-eight residents out of approximately 507 responded. Forty-one of 57 respondents (72%) were in year 1 of residency when they performed their first arthroscopy, and 53 of 57 (93%) were not very comfortable when they performed their first arthroscopy. With respect to VR simulator exposure, approximately 31of 51 (61%) reported no exposure to a VR simulator, and 40 of 50 (80%) reported that their program did not provide a skills laboratory where they could practice arthroscopy. Of 50 respondents, 37 (74%) believed that a skills laboratory was important, 28 (56%) believed that a resident should perform 1 to 10 arthroscopies in a skills laboratory before performing one in the operating room, 34 (60%) believed that skills acquired in a skills laboratory would transfer to the operating room, and 33 (66%) agreed that every residency program should provide a skills laboratory. However, 29 (58%) believed that a skills laboratory would not improve patient safety. CONCLUSION: Osteopathic orthopedic surgery residents indicated that they would benefit from the addition of an arthroscopic skills laboratory with a VR simulator. Furthermore, they believed that the skills learned in the skills laboratory would transfer to the operating room and would increase their comfort level with the procedure.

Changing Natural History of HER2-Positive Breast Cancer Metastatic to the Brain in the Era of New Targeted Therapies.

BACKGROUND: Given the wide adoption of human epidermal growth factor receptor 2 (HER2)-targeted therapies for advanced HER2-positive breast cancer, we studied the natural history of patients with HER2-positive breast cancer brain metastases (BCBM) over time. PATIENTS AND METHODS: Patients with HER2-positive BCBM identified from a prospectively maintained database at the University of North Carolina were divided into 3 cohorts by year of BCBM diagnosis. Cohorts were selected by year of HER2-targeted therapy US Food and Drug Administration approval. Overall survival (OS), time to first metastasis, time to BCBM, and BCBM survival were estimated by the Kaplan-Meier method. Associations between OS after BCBM and clinical variables were assessed by Cox proportional hazards regression models. RESULTS: One hundred twenty-three patients were identified. Median age was 51 years, and 58% were white and 31% African American. OS from initial breast cancer diagnosis improved over time: 3.6 years (95% confidence interval [CI], 2.8-6.1) in the 1998-2007 cohort, 6.6 years (95% CI, 4.5-8.6) in the 2008-2012 cohort, and 7.6 years (95% CI, 4.4-9.6) in the 2013-2015 cohort (P = .05). While time from initial diagnosis to first metastasis did not differ (P = .12), time to BCBM increased over time (2.6 years [95% CI, 1.3-3.5] for 1998-2007; 2.6 years [95% CI, 2.1-4.3] for 2008-2012, and 3.3 years [95% CI, 2.2-6] for 2013-2015; P = .05). Although OS from BCBM did not significantly differ by cohort, patients who received HER2-targeted therapy after BCBM had a prolonged OS (2.1 years [95% CI, 1.6-2.6] vs. 0.65 years [95% CI, 0.4-1.3]; P = .001). CONCLUSION: OS from initial breast cancer diagnosis significantly improved over time for patients with HER2-positive breast cancer who develop BCBM, now exceeding 7 years; survival from BCBM diagnosis may now exceed 2 years.

ACTIVITY OF TRASTUZUMAB-EMTANSINE (TDM1) IN HER2-POSITIVE BREAST CANCER BRAIN METASTASES: A CASE SERIES.

The incidence of breast cancer brain metastasis (BCBM) is increasing due in part to improved management of systemic disease and prolonged survival. Despite this growing population of patients, there exists little consensus for the treatment of HER2-positive BCBM. Lapatinib, the only brain permeable targeted agent for HER2-positive cancer, has demonstrated limited intracranial response rates and little improvement in progression free survival (PFS) for HER-2 positive patients. Size constraints are believed to prevent larger monoclonal antibodies, such as pertuzumab and trastuzumab, from crossing the blood brain barrier (BBB). However, emerging evidence reveals that the BBB is perturbed in the setting of metastases, allowing for improved penetrance of these larger targeted agents. The disrupted BBB may allow for passage of ado-trastuzumab emtansine (TDM1), though little clinical information about its activity in BCBM patients is currently known.

A Multidisciplinary Breast Cancer Brain Metastases Clinic: The University of North Carolina Experience.

BACKGROUND: Breast cancer brain metastasis (BCBM) confers a poor prognosis and is unusual in requiring multidisciplinary care in the metastatic setting. The University of North Carolina at Chapel Hill (UNC-CH) has created a BCBM clinic to provide medical and radiation oncology, neurosurgical, and supportive services to this complex patient population. We describe organization and design of the clinic as well as characteristics, treatments, and outcomes of the patients seen in its first 3 years. METHODS: Clinical and demographic data were collected from patients in a prospectively maintained database. Descriptive statistics are reported as percentages and means. The Kaplan-Meier method was used to estimate time-to-event outcomes. RESULTS: Sixty-five patients were seen between January 2012 and January 2015. At the time of presentation to the BCBM clinic, most patients (74%) had multiple (≥2) brain metastases and had received prior systemic (77%) and whole-brain radiation therapy and/or central nervous system stereotactic radiosurgery (65%) in the metastatic setting. Seventy-eight percent returned for a follow-up visit; 32% were enrolled in a clinical trial. Median time from diagnosis of brain metastasis to death was 2.11 years (95% confidence interval [CI] 1.31-2.47) for all patients, 1.15 years (95% CI 0.4-2.43) for triple-negative breast cancer, 1.31 years (95% CI 0.51-2.52) for hormone receptor-positive/HER2- breast cancer, and 3.03 years (95% CI lower limit 1.94, upper limit not estimable) for HER2+ breast cancer (p = .0037). CONCLUSION: Patients with BCBM have unique and complex needs that require input from several oncologic disciplines. The development of the UNC-CH multidisciplinary BCBM clinic is a model that can be adapted at other centers to provide coordinated care for patients with a challenging and complex disease. IMPLICATIONS FOR PRACTICE: Patients with breast cancer brain metastases often require unique multidisciplinary care to meet the numerous and uncommon challenges associated with their conditions. Here, the development and characteristics of a clinic designed specifically to provide for the multidisciplinary needs of patients with breast cancer brain metastases are described. This clinic may serve as a model for other institutions interested in creating specialty clinics with similar objectives.

Comparison of conventional polyethylene wear and signs of cup failure in two similar total hip designs.

Multiple factors have been identified as contributing to polyethylene wear and debris generation of the acetabular lining. Polyethylene wear is the primary limiting factor in the functional behavior and consequent longevity of a total hip arthroplasty (THA). This retrospective study reviewed the clinical and radiographic data of 77 consecutive THAs comparing in vivo polyethylene wear of two similar acetabular cup liners. Minimum follow-up was 7 years (range 7-15). The incidence of measurable wear in a group of machined liners sterilized with ethylene oxide and composed of GUR 1050 stock resin was significantly higher (61%) than the compression-molded, GUR 1020, O2-free gamma irradiation sterilized group (24%) (P = 0.0004). Clinically, at a 9-year average followup, both groups had comparable HHS scores and incidence of thigh or groin pain, though the machined group had an increased incidence of osteolysis and annual linear wear rate.

The rapidly evolving field of plant centromeres.

Meiotic and mitotic chromosome segregation are highly conserved in eukaryotic organisms, yet centromeres--the chromosomal sites that mediate segregation--evolve extremely rapidly. Plant centromeres have DNA elements that are shared across species, yet they diverge rapidly through large- and small-scale changes. Over evolutionary time-scales, centromeres migrate to non-centromeric regions and, in plants, heterochromatic knobs can acquire centromere activity. Discerning the functional significance of these changes will require comparative analyses of closely related species. Combined with functional assays, continued efforts in plant genomics will uncover key DNA elements that allow centromeres to retain their role in chromosome segregation while allowing rapid evolution.