Washington University School Of Medicine Research Articles

Abstract 14548: Coronary and Aortic Calcification Are Common in Men With Recurrent Prostate Cancer Undergoing PET/CT Imaging

Background: Men who receive androgen deprivation therapy for prostate cancer may be at increased risk for cardiovascular events. Vascular calcification is predictive of coronary events in the general population. The prevalence of vascular calcification in men with prostate cancer is not known. Methods: 211 consecutive patients who underwent 18F-fluciclovine positron emission tomography (PET) /computed tomography (CT) at Washington University School of Medicine for recurrent prostate cancer were retrospectively identified. Clinical, demographic, and cardiac biomarker data were obtained from the medical record. Coronary and aortic calcification were qualitatively assessed on non-gated CT scans using standardized scoring systems. Results: Among 211 men with recurrent prostate cancer, median age was 69 (IQR 64, 75) years. Cardiovascular comorbidities were common (70% hypertension, 65% hyperlipidemia, 20% diabetes mellitus, 47% current or former smoking). 21% carried a clinical diagnosis of coronary artery disease while 6% had peripheral vascular disease. On CT imaging, 147 patients (70%) had coronary artery calcification of whom 29 (20%) had severe calcification. Additionally, 189 patients (90%) had aortic calcification on CT imaging of whom 48 (25%) had severe thoracic aortic calcification and 109 (58%) had severe calcification at the aortoiliac bifurcation. Conclusions: Coronary and peripheral vascular calcification are common on PET/CT imaging in men with prostate cancer. Vascular calcification on CT imaging may have utility for cardiovascular risk stratification and guiding implementation of cardiovascular therapies in men receiving androgen deprivation therapy.

The relationship between cancer fatalism and education.

Fatalism is defined by feelings of pessimism, hopelessness, and powerlessness regarding cancer outcomes. Early researchers reported associations between race and cancer fatalism. Yet current evidence suggests that social determinants of health are better predictors of cancer fatalism than race. Therefore, the aim of this study was to examine the association between age, race, education, and cancer fatalism. Three hundred ninety (n = 390) women who attended a screening mammogram at the Joanne Knight Breast Health Center at Siteman Cancer Center at Washington University School of Medicine (St. Louis, MO) completed the Powe Fatalism Inventory (PFI), a 15-item self-report instrument used to operationalize cancer fatalism. We used Pearson's correlation, independent samples t-tests, one-way ANOVA with post hoc tests, and linear regression to analyze the relationships between PFI total scores and age, race, and education. There were no differences between the mean PFI scores for Non-Hispanic Whites (1.89, SD 0.55) and African Americans (2.02, SD 0.76, p = 0.092, 95% CI 0.27 to 0.02). We found significant differences between the mean PFI scores across levels of education. Women who attained a high school degree or less (n = 72) reported higher PFI scores (2.24, SD 0.77) than women who attended some college or post-high school vocational training (n = 111; 1.95, SD 0.61) and women with a college or postgraduate degree (n = 206; 1.83, SD 0.57). When PFI score was regressed onto age, race, and education, only education significantly explained fatalism (B = -0.19, p < 0.001). In this study, cancer fatalism did not differ between Non-Hispanic White and African American women attending a screening mammogram. However, lower educational levels were associated with higher cancer fatalism. The previously observed associations between race and cancer fatalism may be explained by racial disparities in social determinants of health, such as education. Importantly, study findings indicate that the people with the greatest need for cancer fatalism interventions are those with lower educational levels.

Discussion: Doxycycline-Coated Silicone Breast Implants Reduce Acute Surgical-Site Infection and Inflammation.

Houston, Texas; and St. Louis, Mo. From the Division of Infectious Diseases, Department of Internal Medicine, and the Department of Microbiology and Molecular Genetics, McGovern Medical School; Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, University of Texas Health Sciences Center; and the Division of Plastic and Reconstructive Surgery, Washington University School of Medicine in St. Louis. Received for publication February 29, 2020; accepted April 30, 2020. Disclosure:Dr. Myckatyn receives advisory board fees from Allergan and RTI and investigator-initiated grant funds, royalties, and advisory board fees from RTI. Dr. Walker has no financial interests to disclose. Terence M. Myckatyn, M.D., Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, 1020 North Mason, Suite 110, Saint Louis, Mo. 63141, [email protected], Instagram: terrymyckatyn, Twitter: @DrMyckatyn

Asthma is associated with increased risk of intubation but not hospitalization or death in coronavirus disease 2019

Asthma is associated with increased risk of intubation but not hospitalization or death in coronavirus disease 2019

Aerobic Capacity (V̇O2peak) In Congenital Heart Disease Versus Heart Failure: Prognostic Implications

Introduction VO2peak (peak oxygen consumption) during cardiopulmonary exercise testing is a key prognostic test in patients with non-congenital heart failure (HF). It helps physicians decide which HF patients would derive the greatest survival benefit from cardiac transplant. The predictive value of VO2peak in patients with congenital heart disease on outcomes is not as clear. Hypotheses 1) VO2peak will predict event-free survival in patients with congenital cardiac disease; 2) Patients with congenital heart disease will have longer event-free survival for the primary outcome of death, heart transplant, or LVAD placement compared to patients with heart failure with reduced ejection fraction (HFrEF) even after adjustment for VO2peak. Methods Patients were from a registry of cardiac patients who completed an exercise test in the VO2 Laboratory at Washington University School of Medicine between May 1993 and October 2012. Patients with HFrEF (left ventricular ejection fraction Results A total of 276 patients (138 congenital, 138 HFrEF) were included. Mean (±SD) age was 33.9 ± 11.7y in the congenital group and 40.3 ± 9.7 in the HFrEF group (p=0.00001). Women made up 44.9% of each sample. VO2peak was 21.56 ± 7.15 ml•kg−1•min−1 in the congenital group and 15.99 ± 5.95 ml•kg−1•min−1 in the HFrEF group (p Conclusions A congenital cardiac diagnosis portends longer event-free survival compared to patients with non-congenital HFrEF. Further studies are warranted to investigate if peak VO2 can be used to guide timing for cardiac transplant in the congenital cardiac population.

Local complement activation is associated with primary graft dysfunction after lung transplantation.

BACKGROUNDThe complement system plays a key role in host defense but is activated by ischemia/reperfusion injury (IRI). Primary graft dysfunction (PGD) is a form of acute lung injury occurring predominantly due to IRI, which worsens survival after lung transplantation (LTx). Local complement activation is associated with acute lung injury, but whether it is more reflective of allograft injury compared with systemic activation remains unclear. We proposed that local complement activation would help identify those who develop PGD after LTx. We also aimed to identify which complement activation pathways are associated with PGD.METHODSWe performed a multicenter cohort study at the University of Pennsylvania and Washington University School of Medicine. Bronchoalveolar lavage (BAL) and plasma specimens were obtained from recipients within 24 hours after LTx. PGD was scored based on the consensus definition. Complement activation products and components of each arm of the complement cascade were measured using ELISA.RESULTSIn both cohorts, sC4d and sC5b-9 levels were increased in BAL of subjects with PGD compared with those without PGD. Subjects with PGD also had higher C1q, C2, C4, and C4b, compared with subjects without PGD, suggesting classical and lectin pathway involvement. Ba levels were higher in subjects with PGD, suggesting alternative pathway activation. Among lectin pathway–specific components, MBL and FCN-3 had a moderate-to-strong correlation with the terminal complement complex in the BAL but not in the plasma.CONCLUSIONComplement activation fragments are detected in the BAL within 24 hours after LTx. Components of all 3 pathways are locally increased in subjects with PGD. Our findings create a precedent for investigating complement-targeted therapeutics to mitigate PGD.FUNDINGThis research was supported by the NIH, American Lung Association, Children’s Discovery Institute, Robert Wood Johnson Foundation, Cystic Fibrosis Foundation, Barnes-Jewish Hospital Foundation, Danish Heart Foundation, Danish Research Foundation of Independent Research, Svend Andersen Research Foundation, and Novo Nordisk Research Foundation.

Editorial introductions

Editorial introductions

Washington University School of Medicine.

Washington University School of Medicine.

The George Washington University School of Medicine and Health Sciences.

The George Washington University School of Medicine and Health Sciences.

Composer and Broadway Pianist Invites Listeners ‘Inside His Head’

Composer and Broadway Pianist Invites Listeners ‘Inside His Head’

Bibliometric Analysis of Top 100 Most Cited Articles on Intraventricular Hemorrhage

Intraventricular hemorrhage (IVH) is a rare cause of intracranial bleeding across all age groups, with dismal sequelae in most of the affected population. The reported data on IVH are numerous, with multiple levels of evidence. We performed a citation-based analysis to identify the most-cited reports on IVH. A thorough search of the Scopus database was conducted using "intraventricular hemorrhage" as the search keyword. The 100 most cited studies were stratified in descending order. The reports were reviewed in-depth and categorized accordingly. Bibliometric parameters of interest were obtained for analysis. The most-cited studies had been published between 1927 and 2017. Most (n= 60) had been published between 1980 and 2000. The most-cited studies had received a total of 16,512 citations, with an average of 174 citations per report. Studies on pathogenesis were the most prolific, with 23 articles included. A total of 13 randomized controlled trials were identified. The top contributing country was the United States, with 67 reports. The leading institution was the Washington University School of Medicine in St. Louis, Missouri, with 11 studies. Pediatrics was the most active journal, with 20 studies. The present collection of highly cited studies can aid in the understanding of chronological trends and could serve as an efficient guide to delineate the reports involved in the evidence-based practice of the management of IVH.

Abstract 1158: Hormone gene expression and mammographic breast density in postmenopausal women

Abstract Introduction: Mammographic breast density (MBD), which reflects the amount of epithelial and stromal tissues relative to adipose tissue in the breast, is a strong risk factor for breast cancer. MBD declines with menopause, highlighting the role of endogenous hormones. Nevertheless, studies evaluating the associations of circulating hormone levels with MBD report conflicting results. Only a limited number of studies have addressed the genomic signatures of MBD, which may better capture the broader transcriptional changes associated with MBD and more accurately quantify hormonal exposure than circulating hormone levels. We therefore investigated the associations of hormonal gene expression with MBD in postmenopausal women. Methods: We recruited 368 mid-life postmenopausal women (ages 50-64 years) who had annual screening mammogram at Washington University School of Medicine, St. Louis, MO between October 2017 and September 2018. Each participant completed a blood draw and a questionnaire on breast cancer risk factors. We used Volpara software to measure volumetric percent density (VPD, %), dense volume (VD, cm3) and non-dense volume (NDV, cm3). Prolactin (PRL), progesterone (PGR), estrogen receptor 1 (ESR1), signal transducer and activator of transcription (STAT1), and STAT5 gene expression were measured in total RNA isolated from plasma using NanoString nCounter system. Statistical analyses were performed with the NanoString nSolver Analysis Software. Fold changes in gene expression and p-values were calculated using nCounter default settings. Analyses were adjusted for body mass index (BMI), age, age at menarche, parity/age at first birth, race, and menopausal hormone use. VPD, DV, and NDV were log10 transformed to ensure the normality of the residuals. Results: The mean age of study participants was 57.9 years. The mean BMI was 31.3kg/m2. The average VPD, DV, and NDV were 6.2%, 121.2 cm3, and 2134.4 cm3, respectively. There were strong correlations between STAT1 and STAT5 gene expression (r=0.59, p-value&amp;lt;0.0001), and moderate correlations between ESR1 and PGR gene expression (r=0.43, p-value&amp;lt;0.0001). ESR1 gene expression was associated with VPD, while PGR and STAT5 were marginally associated with NDV. One unit increase in ESR1 gene expression was associated with a 29% (95% CI 2-64%) increase in VPD (p-value=0.03). One unit increase in STAT5 gene expression was associated with an 8% (p-value=0.05) increase in NDV, while one unit increase in PGR gene expression was associated with a 20% (p-value=0.06) decrease in NDV. Hormone gene expression was not associated with DV. Conclusions: We provide novel data on the associations of endogenous hormone gene expression with MBD in postmenopausal women. Future studies characterizing transcriptomic changes in hormone signaling and MBD are needed, as targeting these pathways could be used to reduce MBD for breast cancer prevention. Citation Format: Rachel L. Mintz, Mei Wang, Shuai Xu, Chris Markovic, Adetunji T. Toriola. Hormone gene expression and mammographic breast density in postmenopausal women [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1158.

Factors that Influence Underrepresented in Medicine (UIM) Medical Students to Pursue a Career in Academic Pediatrics

PurposeThe purpose of this study was to explore the experiences of medical students who are underrepresented in medicine (UIM) from two urban medical centers with an interest in pursuing academic pediatrics. MethodsFocus groups were conducted at Children's National Hospital (CN) at three different times with UIM medical students from two urban medical centers. The investigator team was comprised of both junior and senior UIM and non-UIM pediatric academic faculty with experience in qualitative research. Twenty medical students UIM from Howard University College of Medicine (HUCM) and George Washington University School of Medicine and Health Sciences (GWSMHS) participated in the focus groups. The medical students targeted were first, second and fourth years to review experiences pre-and post-third year clerkships. ResultsEighteen of the 20 students completed the demographic data of which 16 identified as Black/African-American. Fifteen of the participants were female and 3 were male. Findings indicated that mentorship, serving as role models, working with children and seeing UIM academic pediatricians positively influenced the students to pursue academic pediatrics. Family had a major influence on students’ interest to pursue medicine. A barrier to pursuing academic pediatrics for UIM medical students included educational debt and lack of knowledge about the field. The students felt that there were fewer expectations of them during secondary school years which affected them throughout their journey to medical school. ConclusionsEarly mentorship for UIM medical students is important to increase exposure to academic pediatrics. Future study on the experience of UIM medical students and their pursuit of academic roles could help produce a more diverse workforce. Also, pipeline programs for students to be exposed to academic pediatrics early in their education career would be beneficial.

Selective Dorsal Rhizotomy for the Treatment of Spastic Triplegic Cerebral Palsy.

BackgroundSpastic triplegia is a recognized subtype of cerebral palsy (CP). In the course of treating spastic triplegic children with selective dorsal rhizotomy (SDR), we found that some children who had “minimal or mild involvement” in the stronger arm improved strikingly after undergoing SDR. Some of them became independent ambulators, which was an outcome that is not usually achieved in spastic quadriplegic children. However, the literature currently contains no data on the natural clinical course and the effects of CP interventions on spastic triplegia.ObjectivesOur aim was to elucidate the clinical characteristics of spastic triplegia and the effects of SDR on functional outcomes and the quality of life after childhood SDR.MethodsThe Institutional Review Board of the Washington University School of Medicine approved this quality of life survey (number: 201908177). The subjects of this study were children and adults (ages: 3.9-23.8 years at the time of the survey completion; mean: 12.1 ± 5.1 years) with spastic triplegic CP who had undergone SDR (ages: 2.2-15.9 years; mean: 6.1 ± 3.2 years) between 2003 and 2018 at the St. Louis Children’s Hospital. The follow-up period ranged from 1-16 years (mean: 6.0 ± 4.3 years). The study included a 76-patient cohort selected from a total of 253 spastic triplegic CP patients who had undergone SDR. All 253 patients were contacted via email or postal mail soliciting their participation in the study including the survey. The cohort included all patients who responded. The survey included questions on demographic information, quality of life, perceptions of health and the SDR procedure, motor and ambulatory functions, braces and orthotics, pain issues, side effects of SDR, and post-SDR treatment.ResultsThirteen patients had presented with scissored gait, and these patients had undergone partial ventral rhizotomy (PVR) of L1-3 ventral roots immediately after the completion of SDR. Of note, 91% of 76 patients reported that SDR improved their quality of life, and 93% would recommend the procedure to other patients. After SDR, 21 more patients were able to run, 14 more played recreational sports, and 18 more could walk without using walking aids. Sixteen fewer patients used a wheelchair for long-distance walking and in crowds; 37 and 32 patients reported an improvement in the more affected arm and hand, respectively. Sixty-eight patients were able to regularly strengthened their muscles at least once a week, and 60 patients regularly stretched their legs. However, 53 patients required assistance with bathing or showering, 50 with getting dressed, and 56 with grooming or hygiene. Forty-eight patients had orthopedic surgery after SDR. Percutaneous hamstring-lengthening was the most common type of orthopedic surgery performed. Three of 13 patients who received PVR and SDR required adductor release. Six patients used medications for spasticity or dystonia. No late side effects of SDR were observed.ConclusionsOur report elucidates the clinical features of spastic triplegia before and after SDR. A distinct clinical feature was the wide variation in ambulatory functions, ranging from total independent walking to wheelchair mobility. The vast majority of patients felt that SDR improved their motor functions and quality of life. PVR also resulted in favorable outcomes, with only three of 13 patients requiring additional adductor release surgery. There were no late complications related to SDR surgery.

Editorial introductions

Editorial introductions

Low Prenatal Choline, Maternal Infection Linked to Attention Problems

Low Prenatal Choline, Maternal Infection Linked to Attention Problems

James W. Fleshman, MD, FACS, FASCRS.

It is always a wonderful experience to have the opportunity to work with and introduce one of your mentors on any project. Dr. James W. Fleshman is the Helen Buchman and Stanley Joseph Seeger endowed professor of surgery at Baylor University Medical Center in Dallas, TX. He completed medical school and surgery residency at Washington University School of Medicine in St. Louis, MO, and Colon and Rectal Surgery Fellowship at the University of Toronto. He served as the chief of colorectal surgery at Washington University in St. Louis for several years prior to his current position as the chief of surgery at Baylor University Medical Center at Dallas.

Closure.

Department of Obstetrics and Gynecology, Washington University School of Medicine in St. Louis, St. Louis, Missouri. Corresponding author: D. Michael Nelson, MD, PhD, Department of Obstetrics and Gynecology, Washington University School of Medicine in St. Louis, St. Louis, MO; email: [email protected]. Financial Disclosure The author did not report any potential conflicts of interest. The author has confirmed compliance with the journal's requirements for authorship. Peer reviews and author correspondence are available at https://links.lww.com/AOG/B825.

In Memoriam: Daniel (Danny) Santa Cruz, MD

In Memoriam: Daniel (Danny) Santa Cruz, MD

Predicting Hearing Loss for Cancer Patients Before Treatment

Most of us will have a loved one hear the devastating words, “You have cancer.” As he or she processes this news, quick treatment decisions must be made. Cancer treatment side effects, such as hearing loss, often come with uncertainties. Our team sought to provide clarity to patients with head and neck cancer on their expected hearing loss before treatment.shutterstock/Iurii Motov, Health care, hearing loss, cancer.Figure 1: The standard model (post-treatment data) is as accurate as the predictive model (pretreatment data). Health care, hearing loss, cancer.Figure 2: Screenshot of the web-based app. Health care, hearing loss, cancer.Each year, more than half a million people develop head and neck cancer, and more than a quarter million die from it.1 Treatment options include surgery, radiation therapy, and chemotherapy (cisplatin). These therapies can cause permanent hearing loss and other side effects, including kidney damage (nephropathy), extreme dry mouth (xerostomia), and loss of healthy tissue (radiation necrosis).2-8 Despite the negative impact of hearing loss on patients’ quality of life, it can be overlooked.9 In 2014, our division of adult audiology at Washington University School of Medicine in St. Louis began providing care for head and neck cancer patients in collaboration with otolaryngology physicians. One of our team members attended a weekly multidisciplinary tumor board to better understand a patient's treatment journey and their challenges in streamlining the process for our patients. We were able to provide audiological care within existing structures to avoid disruptions by reaching out to our multidisciplinary partners. Working with the radiation oncology department, we built standard referral patterns to increase patient follow-up while reducing patient burden through same-day appointments. Baseline audiological testing was incorporated into our department's Head & Neck Cancer Multi-Disciplinary Clinic launched in 2016. The clinic allowed patients to see multiple medical professionals—a radiation oncologist, a medical oncologist, a head and neck cancer surgeon, a speech therapist, and an audiologist—all on the same day. This was appreciated by patients since they could complete their pre-treatment cancer appointments in one morning instead of a month. At these appointments, many patients often asked about what to expect of their hearing after treatment, which made us realize a gap: We could only provide general information about the effects of ototoxic medications, but couldn't address our patients’ needs. As a result, our team decided to explore options for how we could predict post-treatment hearing loss before treatment to provide better counseling. PREDICTING HEARING LOSS A literature review only revealed options that could predict hearing loss after treatment because they relied on final treatment doses. After identifying this gap in information, our team decided to create a new resource for patients. We studied 242 patients using an internal database and data from Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis, the Washington University Oncology Data Services Cancer Registry, Varian (a radiation oncology treatment planning software), and AudBase (a clinical audiometric database). We collected demographic information, tobacco and alcohol use, tumor characteristics (stage, histology, and proximity to the cochlea), and treatment methods (surgery, surgery with clean margins, cisplatin treatment regimen, total cumulative cisplatin dose, and mean cochlear radiotherapy dose) for each patient. Next, we analyzed the data to determine if they could be used to predict post-treatment hearing (pure-tone average [PTA] of 1, 2, 4 kHz) and help counsel patients on their hearing before treatment. We built two key models: one that used proxy measures available before treatment (location of the tumor and planned chemotherapy treatment regimen) and another that relied on final treatment doses. The results were identical: Using pre-treatment measures was as accurate as using post-treatment measures (Fig. 1). The pretreatment factors that we found predicted hearing loss were age, pre-treatment hearing, location of the tumor, and planned treatment chemotherapy dose. Using these factors, our model explained 80 percent of a patient's post-treatment hearing (1, 2, 4 kHz PTA), had a sensitivity of 80 percent and a specificity of 75 percent for predicting post-treatment hearing loss greater or less than 35 dB HL. To our knowledge, we created the first model capable of accurately predicting post-treatment hearing loss before treatment. Our team converted the model into a user-friendly internet-based tool. To use the tool, an audiologist inputs the predictive factors into a web-based application at the baseline hearing test (Fig. 2). The audiologist can then use this information to counsel his or her patient on realistic expectations regarding the patient's post-treatment hearing; however, the model is not yet ready for widespread implementation. We are working to validate it in a new cohort of patients with head and neck cancer.10 Once completed, we plan to publish the data and share our findings to support patients across the country. Each patient we see is someone's loved one. We hope our tool makes their journey a little easier.