Associations of pre-diagnosis physical activity with treatment tolerance and treatment efficacy in breast cancer patients with neoadjuvant chemotherapy.

PURPOSE: Higher pre-diagnosis physical activity (PA) is associated with lower all-cause mortality in breast cancer (BCa) patients. However, the association with pathological complete response (pCR) is unclear. We investigated the association between pre-diagnosis PA level and chemotherapy completion, dose delay, and pCR in BCa patients receiving neoadjuvant chemotherapy (NACT). METHODS: 180 stage I-III BCa patients receiving NACT (mean [SD] age of diagnosis: 60.8 [8.8] years) in the Sister Study were included. Self-reported recreational and total PA levels were converted to metabolic equivalent of task-hours per week (MET-hrs/wk). The pCR was defined as no invasive or in situ residual in breast or lymph node (ypT0 ypN0). Multivariable logistic regression analyses estimated odds ratios (ORs) and 95% confidence intervals (CIs) for treatment outcomes. RESULTS: In this sample, 45 (25.0%) BCa patients achieved pCR. Higher pre-diagnosis recreational PA was not associated with lower likelihood of chemotherapy completion (highest vs. lowest tertile: OR = 0.87, 95% CI = 0.30-2.56; Ptrend = 0.84), greater dose delay (OR = 1.45, 95% CI = 0.54-3.92; Ptrend = 0.46), or greater odds of pCR (OR = 1.28, 95% CI = 0.49-3.34; Ptrend = 0.44). Associations were similar for pre-diagnosis total PA. Meeting the recommended level of recreational PA was not associated with pCR overall (≥ 7.5 vs. < 7.5 MET-hrs/wk: OR = 1.33, 95% CI = 0.59-3.01). CONCLUSIONS: Although small sample size and limited information on exercise closer to time of diagnosis limit interpretation, pre-diagnosis PA was not convincingly associated with treatment tolerance or treatment efficacy in BCa patients receiving NACT. Future investigations are needed to better understand the impact of pre-diagnosis PA on BCa treatment.

Association between pre-diagnosis recreational physical activity and risk of breast cancer recurrence: the California Teachers Study.

PURPOSE: Studies have reported inverse associations of pre-diagnosis recreational physical activity (RPA) level with all-cause and breast cancer (BCa)-specific mortality among BCa patients. However, the association between pre-diagnosis RPA level and BCa recurrence is unclear. We investigated the association between pre-diagnosis RPA level and risk of BCa recurrence in the California Teachers Study (CTS). METHODS: Stage I-IIIb BCa survivors (n = 6,479) were followed with median of 7.4 years, and 474 BCa recurrence cases were identified. Long-term (from high school to age at baseline questionnaire, or, age 55 years, whichever was younger) and baseline (past 3 years reported at baseline questionnaire) pre-diagnosis RPA levels were converted to metabolic equivalent of task-hours per week (MET-hrs/wk). Multivariable Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of BCa recurrence overall and by estrogen receptor (ER)/progesterone receptor (PR) status. RESULTS: Long-term RPA was not associated with BCa recurrence risk (ptrend = 0.99). The inverse association between baseline pre-diagnosis RPA level and BCa recurrence risk was marginally significant (≥26.0 vs. <3.4 MET-hrs/wk: HR = 0.79, 95% CI = 0.60-1.03; ptrend = 0.07). However, the association became non-significant after adjusting for post-diagnosis RPA (ptrend = 0.65). An inverse association between baseline pre-diagnosis RPA level and BCa recurrence risk was observed in ER-PR- cases (≥26.0 vs. <3.4 MET-hrs/wk: HR = 0.31, 95% CI = 0.13-0.72; ptrend = 0.04), but not in ER+ or PR+ cases (ptrend = 0.97). CONCLUSIONS: Our data indicates that the benefit of baseline RPA on BCa recurrence may differ by tumor characteristics. This information may be particularly important for populations at higher risk of ER-PR- BCa.

The promise and challenges of multi-cancer early detection assays for reducing cancer disparities.

Since improvements in cancer screening, diagnosis, and therapeutics, cancer disparities have existed. Marginalized populations (e.g., racial and ethnic minorities, sexual and gender minorities, lower-income individuals, those living in rural areas, and persons living with disabilities) have worse cancer-related outcomes. Early detection of cancer substantially improves outcomes, yet uptake of recommended cancer screenings varies widely. Multi-cancer early detection (MCED) tests use biomarkers in the blood to detect two or more cancers in a single assay. These assays show potential for population screening for some cancers-including those disproportionally affecting marginalized communities. MCEDs may also reduce access barriers to early detection, a primary factor in cancer-related outcome disparities. However, for the promise of MCEDs to be realized, during their development and testing, we are obligated to be cautious to design them in a way that reduces the myriad of structural, systematic, and personal barriers contributing to disparities. Further, they must not create new barriers. Population studies and clinical trials should include diverse populations, and tests must work equally well in all populations. The tests must be affordable. It is critical that we establish trust within marginalized communities, the healthcare system, and the MCED tests themselves. Tests should be expected to have high specificity, as a positive MCED finding will trigger additional, oftentimes invasive and expensive, imaging or other diagnosis tests and/or biopsies. Finally, there should be a way to help all individuals with a positive test to navigate the system for follow-up diagnostics and treatment, if warranted, that is accessible to all.

Associations Between Leisure-Time Physical Activity Level and Peripheral Immune Cell Populations in the US General Population, Analysis of the National Health and Nutrition Examination Survey Data, 1999-2018.

BACKGROUND: Chronic levels of inflammation are associated with higher risk of many chronic diseases. Physical activity (PA) lowers the risk of cancer, cardiovascular disease (CVD), diabetes and others. One mechanism for PA-induced protection may be through the immune system. We investigated the association between leisure-time PA and peripheral immune cell populations in a large nationally representative sample of the US general population. METHODS: A total of 17,093 participants [mean (SE) age of 41.6 (0.3) years] of the National Health and Nutrition Examination Survey 1999-2018 were included. Self-reported leisure-time PA was converted to metabolic equivalent of task hours per week (MET-hrs/wk). White blood cell (WBC) count, WBC ratios, and platelet count were derived. Multivariable linear regression analyses were used to estimate associations between leisure-time PA level and peripheral immune cell populations. Multivariable logistic regression analyses were used to estimate associations between leisure-time PA and metrics of WBC count and neutrophil-to-lymphocyte ratio (NLR) which may predict mortality. RESULTS: A higher leisure-time PA level was associated with a lower WBC count (> 14.0 vs. < 1.2 MET-hrs/wk adjusted mean (95% confidence interval [CI]): 7.12 (6.86, 7.38) vs. 7.38 (7.12, 7.64) 1000 cells/µL, Ptrend < 0.001) and a lower NLR (> 14.0 vs. < 1.2 MET-hrs/wk adjusted mean (95% CI) 2.04 (1.90, 2.18) vs. 2.13 (1.99, 2.28), Ptrend = 0.007). Leisure-time PA level was not associated with lymphocyte-to-monocyte ratio (LMR; Ptrend = 0.25) or platelet-to-lymphocyte ratio (PLR; Ptrend = 0.69). Compared to the lowest leisure-time PA level (< 1.2 MET-hrs/wk), the highest leisure-time PA level (≥ 14.0 MET-hrs/wk) was associated with a lower probability of a high WBC count (> 8.1 × 109 cells/L; odds ratio [OR] = 0.76, 95% CI = 0.66-0.88) and high NLR (> 2.68; OR = 0.84, 95% CI = 0.72-0.99), which may predict CVD and all-cause mortality. The highest leisure-time PA level also linked to a lower probability of a high WBC count (≥ 8.3 × 109 cells/L; OR = 0.76, 95% CI = 0.66-0.88), which may predict cancer mortality. CONCLUSIONS: We observed an inverse association between leisure-time PA level, WBC count, and NLR, particularly for neutrophil levels. These results suggest that participants at higher levels of leisure-time PA may have lower levels of inflammation, which may be important for future chronic disease outcomes.

Clinicopathological characteristics and treatment outcomes of oesophageal cancer patients in Uganda.

Background: Oesophageal cancer is the seventh most common cancer and the sixth leading cause of cancer death worldwide, and its incidence varies globally. In Uganda, the incidence and trend are on the increase. However, there is a paucity of published data regarding this population's oesophageal cancer clinicopathologic characterisation and treatment outcomes. Objectives: To study the patients' clinicopathologic characteristics and treatment outcomes of oesophageal cancer over 10 years at the Uganda Cancer Institute. Methods: Patients' charts with histologically confirmed diagnoses of oesophageal cancer for 2009-2019 were identified. Case information, which included patient demographics, history of alcohol use or smoking, tumour location, histological type, tumour grade, clinical TNM (Tumour, Node, Metastasis) staging treatment exposure and treatment outcomes, was evaluated retrospectively. The median survival time was estimated with the Kaplan-Meier method and the median follow-up period was estimated using the reverse Kaplan-Meier. Results: 1,965 oesophageal cancer patients were identified; 1,380(70.23%) were males and 585(29.77 %) females, their mean age was 60.20 years (±12.66). Most males had a history of both alcohol consumption and smoking 640(46.38%). The lower third of the oesophagus was the most common anatomical location 771(39.24%). The majority had squamous cell carcinoma histological type 1,783(90.74%) followed by adenocarcinomas 182(9.26%) in the distal oesophagus. Poorly differentiated tumour grade 743(37.81%) was predominant. The majority of the patients were in stage IVB, 733(37.30%), and most patients were planned for the best supportive care, 731(37.20%). Radiation alone was offered to 621(31.60%) and feeding gastrostomy to 249(12.70%). Treatment outcomes: at the time of the current analysis, 58.68% had died, 1.48% were alive and 39.84% were lost to follow-up. The median follow-up period was 65 months (IQR:35.83-83.30) with a median survival time of 4.47 months (95% CI: 4.17-4.80). Conclusion: Treatment outcomes of Ugandan oesophageal cancer patients seeking care are poor as most patients present with advanced disease. There is a significant loss of follow-up after treatment initiation. Therefore, reduction in exposure to known modifiable risk factors, early detection and timely referral for treatment strategies are needed to improve outcomes of these patients in our population. Designing interventions to improve treatment adherence is necessary.

InterMEL: An international biorepository and clinical database to uncover predictors of survival in early-stage melanoma.

INTRODUCTION: We are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. We also evaluated tissue-derived predictors of extracted nucleic acids' quality and success in downstream testing. This ongoing study will target 1,000 melanomas within the international InterMEL consortium. METHODS: Following a pre-established protocol, participating centers ship formalin-fixed paraffin embedded (FFPE) tissue sections to Memorial Sloan Kettering Cancer Center for the centralized handling, dermatopathology review and histology-guided coextraction of RNA and DNA. Samples are distributed for evaluation of somatic mutations using next gen sequencing (NGS) with the MSK-IMPACTTM assay, methylation-profiling (Infinium MethylationEPIC arrays), and miRNA expression (Nanostring nCounter Human v3 miRNA Expression Assay). RESULTS: Sufficient material was obtained for screening of miRNA expression in 683/685 (99%) eligible melanomas, methylation in 467 (68%), and somatic mutations in 560 (82%). In 446/685 (65%) cases, aliquots of RNA/DNA were sufficient for testing with all three platforms. Among samples evaluated by the time of this analysis, the mean NGS coverage was 249x, 59 (18.6%) samples had coverage below 100x, and 41/414 (10%) failed methylation QC due to low intensity probes or insufficient Meta-Mixed Interquartile (BMIQ)- and single sample (ss)- Noob normalizations. Six of 683 RNAs (1%) failed Nanostring QC due to the low proportion of probes above the minimum threshold. Age of the FFPE tissue blocks (p<0.001) and time elapsed from sectioning to co-extraction (p = 0.002) were associated with methylation screening failures. Melanin reduced the ability to amplify fragments of 200bp or greater (absent/lightly pigmented vs heavily pigmented, p<0.003). Conversely, heavily pigmented tumors rendered greater amounts of RNA (p<0.001), and of RNA above 200 nucleotides (p<0.001). CONCLUSION: Our experience with many archival tissues demonstrates that with careful management of tissue processing and quality control it is possible to conduct multi-omic studies in a complex multi-institutional setting for investigations involving minute quantities of FFPE tumors, as in studies of early-stage melanoma. The study describes, for the first time, the optimal strategy for obtaining archival and limited tumor tissue, the characteristics of the nucleic acids co-extracted from a unique cell lysate, and success rate in downstream applications. In addition, our findings provide an estimate of the anticipated attrition that will guide other large multicenter research and consortia.

TLE3 Sustains Luminal Breast Cancer Lineage Fidelity to Suppress Metastasis.

Breast cancer subtypes and their phenotypes parallel different stages of the mammary epithelial cell developmental hierarchy. Discovering mechanisms that control lineage identity could provide novel avenues for mitigating disease progression. Here we report that the transcriptional corepressor TLE3 is a guardian of luminal cell fate in breast cancer and operates independently of the estrogen receptor. In luminal breast cancer, TLE3 actively repressed the gene-expression signature associated with highly aggressive basal-like breast cancers (BLBC). Moreover, maintenance of the luminal lineage depended on the appropriate localization of TLE3 to its transcriptional targets, a process mediated by interactions with FOXA1. By repressing genes that drive BLBC phenotypes, including SOX9 and TGFß2, TLE3 prevented the acquisition of a hybrid epithelial-mesenchymal state and reduced metastatic capacity and aggressive cellular behaviors. These results establish TLE3 as an essential transcriptional repressor that sustains the more differentiated and less metastatic nature of luminal breast cancers. Approaches to induce TLE3 expression could promote the acquisition of less aggressive, more treatable disease states to extend patient survival. SIGNIFICANCE: Transcriptional corepressor TLE3 actively suppresses SOX9 and TGFß transcriptional programs to sustain the luminal lineage identity of breast cancer cells and to inhibit metastatic progression.

Integrating primary care, shared decision making, and community engagement to facilitate equitable access to multi-cancer early detection clinical trials.

Effective implementation of cancer screening programs can reduce disease-specific incidence and mortality. Screening is currently recommended for breast, cervical, colorectal and lung cancer. However, initial and repeat adherence to screening tests in accordance with current guidelines is sub-optimal, with the lowest rates observed in historically underserved groups. If used in concert with recommended cancer screening tests, new biospecimen-based multi-cancer early detection (MCED) tests could help to identify more cancers that may be amendable to effective treatment. Clinical trials designed to assess the safety and efficacy of MCED tests to assess their potential for reducing cancer mortality are needed and many are underway. In the conduct of MCED test trials, it is crucial that participant recruitment efforts successfully engage participants from diverse populations experiencing cancer disparities. Strategic partnerships involving health systems, clinical practices, and communities can increase the reach of MCED trial recruitment efforts among populations experiencing disparities. This goal can be achieved by developing health system-based learning communities that build understanding of and trust in biomedical research; and by applying innovative methods for identifying eligible trial patients, educating potential participants about research trials, and engaging eligible individuals in shared decision making (SDM) about trial participation. This article describes how a developing consortium of health systems has used this approach to encourage the uptake of cancer screening in a wide range of populations and how such a strategy can facilitate the enrollment of persons from diverse patient and community populations in MCED trials.

Abdominopelvic MR to CT registration using a synthetic CT intermediate.

Accurate coregistration of computed tomography (CT) and magnetic resonance (MR) imaging can provide clinically relevant and complementary information and can serve to facilitate multiple clinical tasks including surgical and radiation treatment planning, and generating a virtual Positron Emission Tomography (PET)/MR for the sites that do not have a PET/MR system available. Despite the long-standing interest in multimodality co-registration, a robust, routine clinical solution remains an unmet need. Part of the challenge may be the use of mutual information (MI) maximization and local phase difference (LPD) as similarity metrics, which have limited robustness, efficiency, and are difficult to optimize. Accordingly, we propose registering MR to CT by mapping the MR to a synthetic CT intermediate (sCT) and further using it in a sCT-CT deformable image registration (DIR) that minimizes the sum of squared differences. The resultant deformation field of a sCT-CT DIR is applied to the MRI to register it with the CT. Twenty-five sets of abdominopelvic imaging data are used for evaluation. The proposed method is compared to standard MI- and LPD-based methods, and the multimodality DIR provided by a state of the art, commercially available FDA-cleared clinical software package. The results are compared using global similarity metrics, Modified Hausdorff Distance, and Dice Similarity Index on six structures. Further, four physicians visually assessed and scored registered images for their registration accuracy. As evident from both quantitative and qualitative evaluation, the proposed method achieved registration accuracy superior to LPD- and MI-based methods and can refine the results of the commercial package DIR when using its results as a starting point. Supported by these, this manuscript concludes the proposed registration method is more robust, accurate, and efficient than the MI- and LPD-based methods.

Landscape of mutations in early stage primary cutaneous melanoma: An InterMEL study.

It is unclear why some melanomas aggressively metastasize while others remain indolent. Available studies employing multi-omic profiling of melanomas are based on large primary or metastatic tumors. We examine the genomic landscape of early-stage melanomas diagnosed prior to the modern era of immunological treatments. Untreated cases with Stage II/III cutaneous melanoma were identified from institutions throughout the United States, Australia and Spain. FFPE tumor sections were profiled for mutation, methylation and microRNAs. Preliminary results from mutation profiling and clinical pathologic correlates show the distribution of four driver mutation sub-types: 31% BRAF; 18% NRAS; 21% NF1; 26% Triple Wild Type. BRAF mutant tumors had younger age at diagnosis, more associated nevi, more tumor infiltrating lymphocytes, and fewer thick tumors although at generally more advanced stage. NF1 mutant tumors were frequent on the head/neck in older patients with severe solar elastosis, thicker tumors but in earlier stages. Triple Wild Type tumors were predominantly male, frequently on the leg, with more perineural invasion. Mutations in TERT, TP53, CDKN2A and ARID2 were observed often, with TP53 mutations occurring particularly frequently in the NF1 sub-type. The InterMEL study will provide the most extensive multi-omic profiling of early-stage melanoma to date. Initial results demonstrate a nuanced understanding of the mutational and clinicopathological landscape of these early-stage tumors.

Training the next generation of translational scientists: The Case Western Reserve University Translational Fellows Program.

Background: An important part of biomedical research is the translation of discoveries into clinical or community applications that impact patient health. For a vast majority of clinical applications and sustainable community interventions, a time-tested way to get innovations to patients is through licensing of the technology and commercial development, often through startups. While biomedical scientists and trainees are schooled in discovery research, the processes of commercialization are foreign or intimidating. Further, many trainees will not aspire to a faculty position, and other avenues of advancement are desirable. Methods: At Case Western Reserve University, we developed and launched a Translational Fellows Program to provide such training for the community, focusing specifically on graduate students and postdoctoral fellows. The goals of this program include familiarizing our trainees with the principles of entrepreneurship, product development, and startups. This is accomplished through study of their laboratory's technology to identify points of translational focus and to increase awareness to potentially move ideas and products toward societal impact. This program leverages much of our existing infrastructure and provides a mechanism for the prioritization of the translation of the technology as well as "release-time" to promote effort. Results: Launched in summer 2020, our first cohort had 3 of the 12 fellows launching startups based on their technology and submitting an National Institutes of Health Small Business Innovation Research (SBIR) proposal. At least 80% reported increased knowledge and confidence in five of six key translational competencies. Conclusion: We are now continuing and improving the program and searching for sustainable support to stabilize the program for a long-term productive future.

Obesity accelerates acute promyelocytic leukemia in mice and reduces sex differences in latency and penetrance.

OBJECTIVE: Obesity has emerged as a prominent risk factor for multiple serious disease states, including a variety of cancers, and is increasingly recognized as a primary contributor to preventable cancer risk. However, few studies of leukemia have been conducted in animal models of obesity. This study sought to characterize the impact of obesity, diet, and sex in a murine model of acute promyelocytic leukemia (APL). METHODS: Male and female C57BL/6J.mCG+/PR mice, genetically predisposed to sporadic APL development, and C57BL/6J (wild type) mice were placed on either a high-fat diet (HFD) or a low-fat diet (LFD) for up to 500 days. RESULTS: Relative to LFD-fed mice, HFD-fed animals displayed increased disease penetrance and shortened disease latency as indicated by accelerated disease onset. In addition, a diet-responsive sex difference in APL penetrance and incidence was identified, with LFD-fed male animals displaying increased penetrance and shortened latency relative to female counterparts. In contrast, both HFD-fed male and female mice displayed 100% disease penetrance and insignificant differences in disease latency, indicating that the sexual dimorphism was reduced through HFD feeding. CONCLUSIONS: Obesity and obesogenic diet promote the development of APL in vivo, reducing sexual dimorphisms in disease latency and penetrance.

Descriptive Epidemiology of Women in the Emergency Department With Gonorrhea and Chlamydial Infection in the United States.

Demographic characteristics, risk factors, and clinical variables associated with gonorrhea and chlamydial infection in women being treated in emergency departments (EDs) in the United States are incompletely characterized. We used univariable and multivariable regression analyses on 17,411 encounters from women 18 years and older who presented to EDs in northeast Ohio and were tested for gonorrhea or chlamydial infection. There were 1,360 women (7.8%) who had Chlamydia trachomatis infection and 510 (2.9%) who had Neisseria gonorrhoeae infection. Those infected with C. trachomatis or N. gonorrhoeae were younger (23.8 vs. 29.2 years), unmarried (97.7% vs. 90.1%), Black (93.3% vs. 88.0%), infected with Trichomonas vaginalis (39.9% vs. 27.2%), diagnosed with urinary tract infection (15.7% vs. 10.6%), and treated for gonorrhea and chlamydial infection during the ED visit (31.6% vs. 17.4%) (all ps < .001). Women infected with C. trachomatis or N. gonorrhoeae had more urine white blood cells (WBCs) (23.9 vs. 16.4 cells per high-power field [HPF]) and leukocyte esterase (1.2+ vs. 0.8+) on urinalysis. They had more WBCs (18.5 vs. 12.4 cells/HPF) and odds of having T. vaginalis infection (12.8% vs. 8.2%) on vaginal wet preparation (all ps < .001). Women infected with C. trachomatis were more likely to be younger and not Black; they were less likely to be treated for gonorrhea and chlamydial infection in the ED and to have lower levels of urine WBCs, leukocyte esterase, and blood than those infected with N gonorrhoeae (all ps ≤ .05).

Disparities in smoking prevalence and associations with mental health and substance use disorders in underserved communities across the United States.

BACKGROUND: Smoking contributes to the top 3 deadliest cancers, cancers of the lung, colon, and pancreas, which account for nearly 40% of all cancer-related deaths in the United States. Despite historicly low smoking rates, substantial disparities remain among people with mental health conditions and substance use disorders (SUDs). METHODS: The study examined the prevalence of smoking among adults from underserved communities who are served at federally qualified health centers through an analysis of the 2014 Health Center Patient Survey. Furthermore, the study assessed associations of smoking with co-occurring mental health conditions and SUDs among adult smokers (n = 1735). RESULTS: The prevalence of smoking among health center patients was 28.1%. Among current smokers, 59.1% had depression and 45.4% had generalized anxiety. Non-Hispanic Black smokers had more than 2 times the odds of reporting SUDs (adjusted odds ratio [aOR], 2.13; 95% confidence interval [CI], 1.06-4.30). Individuals at or below 100% of the federal poverty level had more than 2 times the odds of having mental health conditions (aOR, 2.55; 95% CI, 1.58-4.11), and those who were unemployed had more than 3 times the odds for SUDs (aOR, 3.21; 95% CI, 1.27-8.10). CONCLUSIONS: The prevalence of smoking in underserved communities is nearly double the national prevalence. In addition, the study underscores important socioeconomic determinants of health in smoking cessation behavior and the marked disparities among individuals with mental health conditions and SUDs. Finally, the findings illuminate the unique need for tailored treatments supporting cancer prevention care to address challenges confronted by vulnerable populations.

Prediction model for gonorrhea, chlamydia, and trichomoniasis in the emergency department.

OBJECTIVE: History and physical examination findings can be unreliable for prediction of genitourinary tract infections and differentiation of urinary tract infections from sexually transmitted infections (STIs). The study objective was to develop a prediction tool to more accurately identify patients with STIs. METHODS: A retrospective review of 64,490 emergency department (ED) encounters between April 18, 2014, and March 7, 2017, where patients age 18 years or older had urinalysis and urine culture or testing for gonorrhea, chlamydia, or trichomonas, was used to develop a prediction model for men and women with Neisseria gonorrhoeae or Chlamydia trachomatis, or both, and for women with Trichomonas vaginalis. The data set was randomly divided into two-thirds discovery and one-third validation. Groups were assigned through a random number generator. Backward step regression modeling was used to identify the best model for each outcome. RESULTS: With use of age, race, marital status, and findings from vaginal wet preparation (white blood cells [WBCs], clue cells, and yeast) and urinalysis (squamous epithelial cells, protein, leukocyte esterase, and WBCs), the models had areas under the receiver operating characteristic curve of 0.80 for men with N gonorrhoeae or C trachomatis, or both; 0.75 for women with N gonorrhoeae or C trachomatis, or both; and 0.73 for women with T vaginalis. CONCLUSIONS: The model estimated likelihood of ED patients having STIs was reasonably accurate with a limited number of demographic and laboratory variables. In the absence of point-of-care STI testing, use of a prediction tool for STIs may improve antimicrobial stewardship.

Characteristics and outcomes of patients with multiple myeloma at the Uganda Cancer Institute.

PURPOSE: Data on multiple myeloma (MM) in sub-Sahara Africa is scarce. In Uganda, there is a progressively increasing incidence of MM over the years. METHODS: We performed a retrospective study on 217 patients with MM at the UCI using purposive sampling method. The objectives of the study were to determine the clinical characteristics, treatment outcomes, 5 year overall survival and predictors of survival of patients with MM at the UCI from 01 January 2008 to 31 December 2012. RESULTS: There were 119 (54.8%) males; the mean(SD) age of the study population at presentation was 59(12.8) years; 183(84.3%) patients presented with bone pain, and 135 (61.9%) had skeletal pathology; 186(85.3%) were HIV negative, and 152(70%) had Durie-Salmon stage III. The median overall survival was 2.5 years, (95% CI, 0.393-0.595); factors significantly associated with worse survival were Durie-Salmon stage III disease, HR=5.9, 95% CI (1.61 - 21.74; P=0.007) and LDH >225 U/L HR=3.3, 95% CI (0.57 - 5.92; P=0.029). CONCLUSION: Most patients with multiple myeloma at the UCI were diagnosed at a relatively young age, presented with late stage disease and bone pain, and had a shorter survival time. Factors associated with worse survival were Durie-Salmon stage III and LDH >225 U/L.

Pleiotropy-guided transcriptome imputation from normal and tumor tissues identifies candidate susceptibility genes for breast and ovarian cancer.

Familial, sequencing, and genome-wide association studies (GWASs) and genetic correlation analyses have progressively unraveled the shared or pleiotropic germline genetics of breast and ovarian cancer. In this study, we aimed to leverage this shared germline genetics to improve the power of transcriptome-wide association studies (TWASs) to identify candidate breast cancer and ovarian cancer susceptibility genes. We built gene expression prediction models using the PrediXcan method in 681 breast and 295 ovarian tumors from The Cancer Genome Atlas and 211 breast and 99 ovarian normal tissue samples from the Genotype-Tissue Expression project and integrated these with GWAS meta-analysis data from the Breast Cancer Association Consortium (122,977 cases/105,974 controls) and the Ovarian Cancer Association Consortium (22,406 cases/40,941 controls). The integration was achieved through application of a pleiotropy-guided conditional/conjunction false discovery rate (FDR) approach in the setting of a TWASs. This identified 14 candidate breast cancer susceptibility genes spanning 11 genomic regions and 8 candidate ovarian cancer susceptibility genes spanning 5 genomic regions at conjunction FDR < 0.05 that were >1 Mb away from known breast and/or ovarian cancer susceptibility loci. We also identified 38 candidate breast cancer susceptibility genes and 17 candidate ovarian cancer susceptibility genes at conjunction FDR < 0.05 at known breast and/or ovarian susceptibility loci. The 22 genes identified by our cross-cancer analysis represent promising candidates that further elucidate the role of the transcriptome in mediating germline breast and ovarian cancer risk.

Early antenatal counseling in the outpatient setting for high-risk pregnancies: a randomized control trial.

OBJECTIVES: Determine if antenatal counseling delivered in the outpatient setting improves parental knowledge and satisfaction without contributing to anxiety. STUDY DESIGN: Randomized control trial at a large academic institution. Mothers at risk for preterm delivery were enrolled following routine maternal-fetal medicine (MFM) visits and randomized to early antenatal counseling of prematurity or standard counseling by MFM providers. The primary outcome was parental knowledge of prematurity. Secondary outcomes included parental satisfaction, anxiety scores, and compliance with recommended follow-up. RESULTS: Seventy-six women were enrolled, 38 in each group. Early counseling group had higher knowledge scores (86.3 vs 64.3, p = <0.001) and parental satisfaction (p = 0.003). Anxiety scores were similar between the two groups (38.2 vs 40.4, p = 0.53). No difference was noted in compliance with follow-up. CONCLUSIONS: Antenatal counseling in the high-risk outpatient setting improved parental knowledge and satisfaction without leading to increased anxiety.

Nursing Student Perceptions of Home Visit Simulation Scenarios.

ABSTRACT: Ensuring quality clinical placement in community health nursing courses is challenging as faculty cannot observe all nursing students and little consistency is found in student experiences. Simulation can supplement traditional clinical experiences. Two home visit scenarios with learning objectives were developed. Students conducted the scenarios in the role of nurse or nursing student and completed evaluations of the experience. The findings suggest students perceived they were able to meet the learning objectives in each scenario regardless of which role was played. Home visit simulations were beneficial to student learning in the community health nursing course.

Hospital System Adoption of Magnetic Seeds for Wireless Breast and Lymph Node Localization.

BACKGROUND: As an alternative to traditional wire localization, an inducible magnetic seed system can be used to identify and remove nonpalpable breast lesions and axillary lymph nodes intraoperatively. We report the largest single-institution experience of magnetic seed placement for operative localization to date, including feasibility and short-term outcomes. METHODS: Patients who underwent placement of a magnetic seed in the breast or lymph node were identified from July 2017 to March 2019. Imaging findings, core needle biopsy, surgical pathology results, and type of surgery were collected. Outcomes included procedural complications, magnetic seed and biopsy clip retrieval rates, and need for additional surgery. RESULTS: A total of 842 magnetic seeds were placed by nine radiologists in 673 patients and retrieved by six surgeons at six operative locations. The majority of breast lesions were malignant (395/659, 59.9%); 136 seeds were placed for lymph node localization. The overall magnetic seed retrieval rate was 98.6%, whereas the biopsy clip retrieval rate was 90.9%. Only six patients (0.7%) experienced a complication from magnetic seed placement. Reexcision was performed in 15.2% of patients with breast cancer; 9.6% of benign/high risk lesions were upgraded to malignancy at surgical excision. CONCLUSIONS: The magnetic seed technique is safe, effective, and accurate for localization of breast lesions and lymph nodes, and importantly uncouples surgery from the localization procedure. The high magnetic seed retrieval rate and low reexcision rate may reflect the accuracy of magnetic marker placement as a "second chance" localization procedure, especially in cases with biopsy clip migration.