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Purpose: This retrospective cohort study evaluated whether linked electronic health record (EHR) pharmacy data were adequately complete and timely to detect primary nonadherence to breast cancer adjuvant endocrine therapy (AET)., Materials and Methods: Linked EHR pharmacy data were extracted from the EHR for patients with stage 0 to III breast cancer who had their first prescription order for AET between 2016 and 2021. Patients with the first dispense event within 90 days of the prescription were classified as having sufficient or insufficient data available for early detection of primary adherence., Results: A total of 1,446 eligible patients had a first AET prescription order between 2016 and 2021; these orders were routed to 871 unique pharmacies, of which 856 (98.2%) were contracted with the linked EHR pharmacy database and 15 (1.8%) were not contracted. Among the 1,428 patients with a first prescription sent to a contract pharmacy, 164 (13%) had incomplete linked EHR pharmacy data refresh events to assess primary adherence. Among the 1,244 patients with at least 1 refresh event after their first prescription, 82% occurred within 90 days and were sufficiently timely for early detection of primary adherence. Overall, 32% of patients would benefit from an intervention to verify or improve primary adherence to AET., Conclusion: Although linked EHR pharmacy data have adequate completeness of contract pharmacy data, local configurations of data refresh events tailored to medication reconciliation workflows are incomplete (13%) and insufficiently timely (32%) to fully support clinical decision support (CDS) for early detection of primary medication nonadherence. Prospective CDS interventions using linked EHR pharmacy data are possible with enhancements to the frequency and timeliness of refresh events.

Objective: Changes in a patient's reported breast density status (dense vs nondense) trigger modifications in their cancer risk profile and supplemental screening recommendations. This study tracked the frequency and longitudinal sequence of breast density status changes among patients who received serial mammograms., Methods: This IRB-approved, HIPAA-compliant retrospective cohort study tracked breast density changes among patients who received at least 2 mammograms over an 8-year study period. BI-RADS density assessment categories A through D, visually determined at the time of screening, were abstracted from electronic medical records and dichotomized into either nondense (categories A or B) or dense (categories C or D) status. A sequence analysis of longitudinal changes in density status was performed using Microsoft SQL., Results: A total of 58 895 patients underwent 231 997 screening mammograms. Most patients maintained the same BI-RADS density category A through D (87.35% [51 444/58 895]) and density status (93.35% [54 978/58 859]) throughout the study period. Among patients whose density status changed, the majority (97% [3800/3917]) had either scattered or heterogeneously dense tissue, and over half (57% [2235/3917]) alternated between dense and nondense status multiple times., Conclusion: Our results suggest that many cases of density status change may be attributable to intra- and interradiologist variability rather than to true underlying changes in density. These results lend support to consideration of automated density assessment because breast density status changes can significantly impact cancer risk assessment and supplemental screening recommendations., (© Society of Breast Imaging 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Importance: Outcomes for patients with unresectable stage III non-small cell lung cancer (NSCLC) treated with chemoradiation therapy (CRT) have improved with adjuvant immune checkpoint inhibitors, with a reported 5-year overall survival benefit of approximately 10% for adjuvant durvalumab vs placebo after completion of CRT without progression and with preserved performance status. Starting atezolizumab prior to CRT may allow more patients to benefit from immunotherapy., Objective: To evaluate clinical outcomes of patients treated with atezolizumab before and after CRT for unresectable stage III NSCLC., Design, Setting, and Participants: This single-cohort, phase II, nonrandomized controlled trial was conducted at 11 US sites. Patients with pathologically confirmed, unresectable stage III NSCLC who were treatment naive and had good performance status were enrolled between January 3, 2018, and July 24, 2019. Data were locked on March 21, 2023., Interventions: Patients received four 21-day cycles of atezolizumab, 1200 mg intravenously, with therapy administered on day 1 of each cycle. Patients not experiencing tumor progression continued to CRT (60 Gy to involved fields) concurrent with weekly carboplatin area under the curve of 2 and paclitaxel, 50 mg/m2, followed by planned consolidation carboplatin area under the curve of 6 and paclitaxel, 200 mg/m2, for two 21-day cycles. Patients not experiencing progression continued atezolizumab, 1200 mg, every 21 days to complete 1 year of therapy., Main Outcomes and Measures: The primary end point was the disease control rate at 12 weeks. Secondary end points were progression-free survival, overall survival, overall response rate, safety, and translational science end points., Results: A total of 62 patients (median [range] age, 63.9 [38.1-86.5] years; 32 female [51.6%]) were enrolled and received at least 1 dose of atezolizumab. The disease control rate at 12 weeks was 74.2% (80% CI, 65.7%-81.4%). Median progression-free survival was 30.0 months (95% CI, 15.8 to not evaluable), and the median overall survival was not reached. The overall survival rate at 24 months was 73.7% (95% CI, 63.4%-85.7%), and the overall response rate was 66.2%. Seventeen patients (27.4%) experienced grade 3 or higher immune-related adverse events, including 1 with grade 5 pneumonitis and 1 with grade 4 Guillain-Barré syndrome. Thirty patients (48.4%) experienced grade 3 or higher treatment-related adverse events., Conclusions and Relevance: These findings suggest that neoadjuvant atezolizumab merits further study based on safety and encouraging outcomes., Trial Registration: ClinicalTrials.gov Identifier: NCT03102242.

Background: This study introduced Zentangle®, which involves drawing simple, repetitive lines and shapes to create patterns, as a tool to promote wellness for oncology nurses in a clinical practice setting., Objectives: The purpose of this study was to determine whether Zentangle used as a meditative activity in an acute time frame decreased stress, fatigue, and burnout while increasing professional quality of life and well-being in oncology nurses., Methods: Twenty-six oncology nurses participated in a two-hour Zentangle class and received materials to complete art over four weeks. The Perceived Stress Scale, the Warwick-Edinburgh Mental Wellbeing Scale, the Patient-Reported Outcomes Measurement Information System-29, and the Professional Quality of Life measure were administered at selected periods. Twenty-four participants completed the study., Findings: Nurses' well-being, socialization, anxiety, fatigue, secondary traumatic stress levels, and stress levels improved significantly. Most participants noted they would continue using Zentangle after the study. Zentangle is another tool to advance nurses' wellness by encouraging self-care.

Importance: Disparities in patient access and use of health care portals have been documented. Limited research has evaluated disparities in portal use during and after the COVID-19 pandemic., Objective: To assess prevalence of health care portal use before, during, and after the most restrictive phase of the pandemic (2019-2022) among the COVID-19 & Chronic Conditions (C3) cohort and to investigate any disparities in use by sociodemographic factors., Design, Setting, and Participants: This cohort study uses data from the C3 study, an ongoing, longitudinal, telephone-based survey of participants with multiple chronic conditions. Participants were middle aged and older-adult primary care patients who had an active portal account, recruited from a single academic medical center in Chicago, Illinois, between 2019 and 2022. Data were analyzed between March and June 2022., Main Outcomes and Measures: Outcomes of portal use (ie, number of days of portal login by year) were recorded for all study participants by the electronic data warehouse. All parent studies had uniform sociodemographic data and measures of social support, self-efficacy, health literacy, and health activation., Results: Of 536 participants (mean [SD] age, 66.7 [12.0] years; 336 [62.7%] female), 44 (8.2%) were Hispanic or Latinx, 142 (26.5%) were non-Hispanic Black, 322 (60.1%) were non-Hispanic White, and 20 individuals (3.7%) identified as other race, including Asian, Native American or Alaskan Native, and self-reported other race. In multivariable analyses, portal login activity was higher during the 3 years of the COVID-19 pandemic compared with the 2019 baseline. Higher portal login activity was associated with adequate health literacy (incidence rate ratio [IRR], 1.51; 95% CI, 1.18-1.94) and multimorbidity (IRR, 1.38; 95% CI, 1.17-1.64). Lower portal activity was associated with older age (≥70 years: IRR, 0.69; 95% CI, 0.55-0.85) and female sex (IRR, 0.77; 95% CI, 0.66-0.91). Compared with non-Hispanic White patients, lower portal activity was observed among Hispanic or Latinx patients (IRR, 0.66; 95% CI, 0.49-0.89), non-Hispanic Black patients (IRR, 0.68; 95% CI, 0.56-0.83), and patients who identified as other race (IRR, 0.42; 95% CI, 0.28-0.64)., Conclusions and Relevance: This cohort study using data from the C3 study identified changes in portal use over time and highlighted populations that had lower access to health information. The COVID-19 pandemic was associated with an increase in portal use. Sociodemographic disparities by sex and age were reduced, although disparities by health literacy widened. A brief validated health literacy measure may serve as a useful digital literacy screening tool to identify patients who need further support.

Background: CAPRA (NCT02565992) evaluated Coxsackievirus A21 (V937) + pembrolizumab for metastatic/unresectable stage IIIB-IV melanoma., Methods: Patients received intratumoral V937 on days 1, 3, 5, and 8 (then every 3 weeks [Q3W]) and intravenous pembrolizumab 2 mg/kg Q3W from day 8. Primary endpoint was safety., Results: Median time from first dose to data cutoff was 32.0 months. No dose-limiting toxicities occurred; 14% (5/36) of patients experienced grade 3‒5 treatment-related adverse events. Objective response rate was 47% (complete response, 22%). Among 17 responders, 14 (82%) had responses ≥ 6 months. Among 8 patients previously treated with immunotherapy, 3 responded (1 complete, 2 partial). Responses were associated with increased serum CXCL10 and CCL22, suggesting viral replication contributes to antitumor immunity. For responders versus nonresponders, there was no difference in baseline tumor PD-L1 expression, ICAM1 expression, or CD3 + infiltrates. Surprisingly, the baseline cell density of CD3 + CD8 - T cells in the tumor microenvironment was significantly lower in responders compared with nonresponders (P = 0.0179)., Conclusions: These findings suggest responses to this combination may be seen even in patients without a typical "immune-active" microenvironment., Trial Registration Number: NCT02565992., (© 2022. The Author(s).)

Purpose: Patient-reported outcomes are considered the gold standard for documenting treatment-related toxicities and cancer-related symptoms in the management of oncology patients. Poor concordance between patients and health care professionals (HCPs) on patients' symptoms has been documented. The purpose of this study is to examine the association between social desirability, a response style, and symptom reporting in a colorectal cancer clinic., Methods: Patients being treated for colorectal cancer completed a social desirability measure and a symptom measure before their appointment in the oncology clinic. The HCP who saw the patient completed a symptom measure for the patient after the clinic visit., Results: One hundred sixty-nine patients consented to participate in the study. The majority of the patients had stage 4 disease. There was a statistically significant positive correlation between social desirability and overall reported symptom burden. There was a statistically significant negative correlation between social desirability and concordance between the patient and the HCP on the patient's symptoms. Social desirability scores were stable over the course of 1 year., Conclusion: Sensitivity to social desirability effects seems to play an important role in patient self-report of symptoms. As social desirability is a stable quality, patients sensitive to it may be persistently at risk for undertreatment of symptoms due to limited symptom reporting., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The adoption of docetaxel for systemic treatment of metastatic prostate cancer (PCa), in both castration-sensitive (mCSPC) and castration-resistant (mCRPC) settings, is poorly understood. This study examined the real-world utilization of docetaxel in these patients and their outcomes., Methods: A retrospective population-based study used administrative data from Ontario, Canada, to identify men aged ≥66 years who were diagnosed with de novo mCSPC or mCRPC between 2014 and 2019 and received docetaxel. The study assessed treatment tolerability and toxicity, and survival in both cohorts. Descriptive and comparative statistical analysis were conducted., Results: The study identified 11.2% (399/3556) and 13.2% (203/1534) patients diagnosed with de novo mCSPC and with mCRPC who received docetaxel respectively. The median age in both cohorts was 72 years (IQR: 68-76). Overall, 43.9% (n = 175) patients with de novo mCSPC and 52.1% (n = 85) with mCRPC completed ≥6 cycles of docetaxel. Over two-fifth also needed dose adjustments in both cohorts. Hospitalization or emergency department visit for febrile neutropenia were noted in 15.8% (n = 63) of de novo mCSPC patients and similarly in 19% (n = 31) of mCRPC cohort. The median survival of PCa patients who completed ≥6 cycles of docetaxel was significantly longer relative to those who completed <4 cycles: 32.7 vs. 23.5 months (p < 0.001) for mCSPC and 20.5 vs. 10.7 (p = 0.012) for mCRPC respectively., Conclusions: In this population-based study of elderly patients with metastatic PCa, treatment with docetaxel was associated with poor tolerability and higher toxicity compared with clinical trials. Receipt of limited cycles and reduced overall dose of docetaxel were associated with inferior overall survival., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: The 2018 ACR recommendations for breast cancer screening in women at higher than average risk include new recommendations for supplemental breast MRI for patients with personal histories of breast cancer (PHBCs) who carry hereditary cancer gene mutations, have dense breast tissue, or were diagnosed before 50 years of age. In comparison, prior guidelines recommended supplemental MRI only for women with PHBCs who carried hereditary cancer gene mutations. The aim of this study was to quantify the increase in the number of patients with breast cancer for whom supplemental breast MRI would now be recommended., Methods: Data were extracted from the electronic health records of patients presenting for screening or diagnostic mammography at an urban academic medical center between July 20, 2020, and July 19, 2021. Data extracted included patient-reported PHBC, age at time of breast cancer diagnosis, and hereditary cancer gene mutation carrier status. Descriptive statistics are reported, evaluating the rate of eligibility for supplemental breast MRI in a retrospective population given the new ACR guidelines., Results: Of the 2,950 patients with self-reported PHBCs who presented for breast cancer screening in the year between July 2020 and July 2021, 1,805 (61%) met the criteria for supplemental breast MRI according to the 2018 guidelines compared with only 3.6% using pre-2018 guidelines., Conclusions: Measuring the impact of the 2018 ACR supplemental MRI recommendations using real-world data at a single urban academic medical center demonstrated a 15-fold increase in potential eligibility for supplemental breast MRI in patients with PHBCs., (Published by Elsevier Inc.)

Background: Breast cancer risk assessment is a powerful tool that guides recommendations for supplemental breast cancer screening and genetic counseling. The Tyrer-Cuzick 8 (TC8) model is widely used for calculating breast cancer risk and thus helps determine if women qualify for supplemental screening or genetic counseling. However, the TC8 model may underestimate breast cancer risk in Black women. This study sought to assess this disparity., Methods: Data on race, breast density, body mass index (BMI), and TC8 scores were retrospectively extracted from the electronic medical record (EMR). Logistic regressions were run to evaluate racial differences in TC8 scores. Summary and correlation statistics determined relationships between BMI, breast density, and race. Rank biserial correlations were employed to explore the impact of breast density and BMI on TC8 scores., Results: Of 15,356 patients, 5796 were White and 5813 were Black. Black patients had higher rates of BMI ≥ 27 compared with White women (79.2% vs. 45.7%), lower rates of breast density (35.1% vs. 56.2%), and lower rates of high-risk TC8 scores (10.7% vs. 17.5%, OR = 1.6646). There was an inverse relationship between TC8 score and BMI (r rb  = - 0.04) and a direct relationship between TC8 score and breast density (r rb  = 0.37)., Discussion: Black women are less likely to have high-risk TC8 scores despite having only marginally lower breast cancer incidence rates and higher breast cancer mortality rates than White women. This suggests that the TC8 model underestimates breast cancer risk in Black women, possibly due to lower rates of breast density and higher BMIs among Black women., (© 2022. Society of Surgical Oncology.)

Background: Compassion fatigue (CF) and burnout are well described phenomena among oncology nurses. Physical activity (PA) has been shown to reduce CF and burnout., Objectives: The purpose of this pilot study was to determine the feasibility of promoting PA and assessing its impact on CF and burnout among RNs across three ambulatory care cancer clinics., Methods: A convenience sample of nurses with varying roles were invited to participate. Feasibility was assessed by participant accrual and retention rates. CF and burnout were assessed at weeks 0, 6, and 12. The Yale Physical Activity Survey was used to obtain self-reported PA, and daily steps were tracked using participants' personal devices., Findings: Stress scores decreased. Burnout scores demonstrated levels of low emotional exhaustion, moderate depersonalization, and moderate to high personal achievement. Leisurely walking increased significantly, and average daily step counts increased by 37% for weekdays, 10% for weekend days, and 29% for the total week.

Importance: Given that mycosis fungoides-cutaneous T-cell lymphoma (MF/CTCL) is chronic, there is a need for additional therapies with minimal short- and long-term adverse effects. Topical synthetic hypericin ointment, 0.25%, activated with visible light is a novel, nonmutagenic photodynamic therapy (PDT)., Objectives: To determine the efficacy and safety of topical synthetic hypericin ointment, 0.25%, activated with visible light as a nonmutagenic PDT in early-stage MF/CTCL., Design, Settings, and Participants: This was a multicenter, placebo-controlled, double-blinded, phase 3 randomized clinical trial (FLASH study) conducted from December 2015 to November 2020 at 39 academic and community-based US medical centers. Participants were adults (≥18 years) with early-stage (IA-IIA) MF/CTCL., Interventions: In cycle 1, patients were randomized 2:1 to receive hypericin or placebo to 3 index lesions twice weekly for 6 weeks. In cycle 2, all patients received the active drug for 6 weeks to index lesions. In cycle 3 (optional), both index and additional lesions received active drug for 6 weeks., Main Outcomes and Measures: The primary end point was index lesion response rate (ILRR), defined as 50% or greater improvement in modified Composite Assessment of Index Lesion Severity (mCAILS) score from baseline after 6 weeks of therapy for cycle 1. For cycles 2 and 3, open label response rates were secondary end points. Adverse events (AEs) were assessed at each treatment visit, after each cycle, and then monthly for 6 months. Data analyses were performed on December 21, 2020., Results: The study population comprised 169 patients (mean [SD] age, 58.4 [16.0] years; 96 [57.8%] men; 120 [72.3%] White individuals) with early-stage MF/CTCL. After 6 weeks of treatment, hypericin PDT was more effective than placebo (cycle 1 ILRR, 16% vs 4%; P = .04). The ILRR increased to 40% in patients who received 2 cycles of hypericin PDT (P < .001 vs cycle 1 hypericin) and to 49% after 3 cycles (P < .001 vs cycle 1 hypericin). Significant clinical responses were observed in both patch and plaque type lesions and were similar regardless of age, sex, race, stage IA vs IB, time since diagnosis, and number of prior therapies. The most common treatment-related AEs were mild local skin (13.5%-17.3% across cycles 1-3 vs 10.5% for placebo in cycle 1) and application-site reactions (3.2%-6.9% across cycles 1-3 vs 4% for placebo in cycle 1). No drug-related serious AEs occurred., Conclusion and Relevance: The findings of this randomized clinical trial indicate that synthetic hypericin PDT is effective in early-stage patch and plaque MF/CTCL and has a favorable safety profile., Trial Registration: ClinicalTrials.gov Identifier: NCT02448381.

Small non-coding RNAs are potential diagnostic biomarkers for lung cancer. Mitochondria-derived small RNA (mtRNA) is a novel regulatory small non-coding RNA that only recently has been identified and cataloged. Currently, there are no reports of studies of mtRNA in human lung cancer. Currently, normalization methods are unstable, and they often fail to identify differentially expressed small non-coding RNAs (sncRNAs). In order to identify reliable biomarkers for lung cancer screening, we used a ratio-based method using mtRNAs newly discovered in human peripheral blood mononuclear cells. In the discovery cohort (AUC = 0.981) and independent validation cohort (AUC = 0.916) the prediction model of eight mtRNA ratios distinguished lung cancer patients from controls. The prediction model will provide reliable biomarkers that will allow blood-based screening to become more feasible and will help make lung cancer diagnosis more accurate in clinical practice., (© 2022 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Genetic counselors (GCs) and healthcare interpreters (HIs) are key members of the healthcare team when providing genetic counseling services to patients with Limited English Proficiency (LEP); however, the working relationship between GCs and HIs and the role each member plays within a genetic counseling session is unclear. Previous studies assessing this relationship have been qualitative and limited in sample size (Agather et al., 2018, Journal of Genetic Counseling, 26, 1388; Krieger et al., 2018, Journal of Genetic Counseling, 26, 1388; Lara-Otero et al., 2019, Health Communication, 34, 1608; Rosenbaum et al., 2020, Journal of Genetic Counseling, 29, 352). This study utilized a quantitative approach to allow for sampling of larger populations and to simultaneously understand current perspectives of GCs and HIs regarding each other's and their own roles within a genetic counseling session. GC and HI participants from the United States were recruited via email to complete an online survey with questions regarding interactions prior to a session, roles during a session, and opportunities for collaboration and constraints in the working relationship. Descriptive and inferential statistics were utilized to analyze responses of GCs and HIs. 130 GC and 40 HI participants were included in this study. There were statistically significant differences (p < .001) in responses between GC and HI participants on the expected distribution of roles during a session in advocacy, psychosocial and cultural domains. Additionally, this study identified that HI desired resources and training regarding genetics and genetic counseling are currently not being met. To our knowledge, this is the largest study to simultaneously survey GC and HI perspectives on these topics. Our findings suggest the need for greater communication and collaboration between GCs and HIs to ensure high-quality care for patients with LEP. Integrating a pre-session meeting between the GC and HI for sessions with patients with LEP and increasing education for GCs and HIs on the roles each group brings into a session is warranted to optimize this collaborative relationship and patient care., (© 2022 The Authors. Journal of Genetic Counseling published by Wiley Periodicals LLC on behalf of National Society of Genetic Counselors.)

Purpose: We examined emotional distress in cancer survivors diagnosed as adolescents or young adults (AYAs) versus cancer survivors diagnosed as middle/older adults and versus the general population without a history of cancer., Methods: Using the 2014-2017 National Health Interview Surveys, 2500 AYA survivors (initial cancer diagnosed between aged 15-39 years) were matched with 2500 middle/older adult survivors (initial cancer diagnosed at aged ≥40 years) as well as with 1609 from the general population without a history of cancer. Multinomial logistic regression models estimated the risk of emotional distress (measured using the validated Kessler distress (K6) scale) in the study population (AYA vs. middle/older adult cancer survivors and vs. general population without cancer), adjusting for known covariates., Results: Emotional distress was more prevalent among AYAs (average age 52.8 ± 19.1 years) than middle/older adult (average age 67.4 ± 14.0 years) cancer survivors (moderate: 25.5% vs. 19.4%; and severe: 6.4% vs. 4.4% [P < .0001]); however, there was no difference in emotional distress between AYA cancer survivors (moderate: 26.8% and severe: 7.5%) versus general population without cancer (moderate: 23.7% and severe: 6.2%). In the multivariable multinomial analyses, AYA cancer survivors had higher risk of reporting emotional distress (adjusted relative risk = 1.45; 95% confidence interval = 1.13-1.86) than middle/older adult cancer survivors., Conclusion: Psychosocial support may be especially needed for cancer survivors diagnosed as adolescents or young adults to mitigate adverse psychosocial outcomes., (Copyright © 2022. Published by Elsevier Inc.)

Many patients with metastatic breast cancer develop liver metastases. A rare complication of this is hepatopulmonary syndrome (HPS), which is associated with exertional dyspnea and intrapulmonary shunting. We present a patient who presented with HPS as a consequence of liver metastases and subsequently treated with chemotherapy leading to resolution of her symptoms., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 by S. Karger AG, Basel.)

Purpose: Clinical notes function as the de facto handoff between providers and assume great importance during unplanned medical encounters. An organized and thorough oncology history is essential in care coordination. We sought to understand reader preferences for oncology history organization by comparing between chronologic and narrative formats., Methods: A convenience sample of 562 clinicians from 19 National Comprehensive Cancer Network Member Institutions responded to a survey comparing two formats of oncology histories, narrative and chronologic, for the same patient. Both histories were consensus-derived real-world examples. Each history was evaluated using semantic differential attributes ( thorough , useful , organized , comprehensible , and succinct ). Respondents choose a preference between the two styles for history gathering and as the basis of a new note. Open-ended responses were also solicited., Results: Respondents preferred the chronologic over the narrative history to prepare for a visit with an unknown patient (66% preference) and as a basis for their own note preparation (77% preference) ( P < .01). The chronologic summary was preferred in four of the five measured attributes ( useful , organized , comprehensible , and succinct ); the narrative summary was favored for thoroughness ( P < .01). Open-ended responses reflected the attribute scoring and noted the utility of content describing social determinants of health in the narrative history., Conclusion: Respondents of this convenience sample preferred a chronologic oncology history to a concise narrative history. Further studies are needed to determine the optimal structure and content of chronologic documentation for oncology patients and the provider effort to use this format., Competing Interests: Jessica M. SugalskiEmployment: ArchimedicLeadership: ArchimedicStock and Other Ownership Interests: ArchimedicPatents, Royalties, Other Intellectual Property: My spouse holds several patents related to his role as President of Archimedic. Companies include Cooper Surgical, ZSX Medical, and Becton Dickinson Mia LevyEmployment: SeqTech DiagnosticsLeadership: PersonalisStock and Other Ownership Interests: Personalis, GenomOncologyHonoraria: RocheConsulting or Advisory Role: Personalis, GenomOncology Inc, RocheResearch Funding: GenomOncologyPatents, Royalties, Other Intellectual Property: Royalties from GenomOncology for licensing of MyCancerGenome contentTravel, Accommodations, Expenses: RocheNo other potential conflicts of interest were reported.

Treatment of metastatic melanoma has changed dramatically in the past 5 years with the approval of six new agents (vemurafenib, dabrafenib, trametinib, ipilimumab, pembrolizumab, and nivolumab) by the US Food and Drug Administration (FDA). This review will compare the immunotherapies recently approved by the FDA (ipilimumab, nivolumab and pembrolizumab) with the long-approved immunotherapy, interleukin-2. Additional consideration will be given to the evolving landscape, including the opportunities for combination regimens. Immunotherapies have distinct mechanisms of action and unique response kinetics that differ from conventional cytotoxic and targeted therapies, and have a range of adverse events that can be safely managed by experienced health-care providers. Data suggest immunotherapies can result in long-term survival in a proportion of patients. This dynamic and evolving field of immunotherapy for melanoma will continue to offer challenges in terms of optimal patient management for the foreseeable future.

Background/aim: Head and neck cancers are often treated with extended courses of radiotherapy (RT), which may prove excessively toxic for frail patients. Split course RT (SCRT) delivers two courses of RT separated by 4-6 weeks, personalizing treatment intensity based on response. In this study, we present our updated experience using this technique., Patients and Methods: From a single institution database, we identified patients considered for SCRT. For patients undergoing a second course of RT, cumulative incidence of locoregional recurrence (LRR) and overall survival (OS) are reported., Results: A total of 98 patients were included, of whom seventy-five percent underwent a second course of RT. The most common fractionation was 30 Gy in 10 fractions for each course, with a median cumulative dose of 60 Gy. In those undergoing a second course of RT, median OS was 9.7 months and cumulative incidence of LRR at 6, 12, and 24 months was 17.0%, 23.1%, and 29.4%, respectively., Conclusion: SCRT offers an attractive treatment paradigm to personalize radiation intensity based on patient tolerance, while maintaining reasonable safety and efficacy in those unfit for standard full course RT., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Competing Interests: Conflicts of Interest The authors do not report any disclosures or conflicts of interest related to this manuscript.

De novo cases of metastatic prostate cancer (mCSPC) are associated with poorer prognosis. To assist in clinical decision-making, we aimed to determine the prognostic utility of commonly available laboratory-based markers with overall survival (OS). In a retrospective population-based study, a cohort of 3556 men aged ≥66 years diagnosed with de novo mCSPC between 2014 and 2019 was identified in Ontario (Canada) administrative database. OS was assessed by using the Kaplan-Meier method. Multivariate Cox regression analysis was performed to evaluate the association between laboratory markers and OS adjusting for patient and disease characteristics. Laboratory markers that were assessed include neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), albumin, hemoglobin, serum testosterone and PSA kinetics. Among the 3556 older men with de novo mCSPC, their median age was 77 years (IQR: 71-83). The median survival was 18 months (IQR: 10-31). In multivariate analysis, a statistically significant association with OS was observed with all the markers (NLR, PLR, albumin, hemoglobin, PSA decrease, reaching PSA nadir and a 50% PSA decline), except for testosterone levels. Our findings support the use of markers of systemic inflammation (NLR, PLR and albumin), hemoglobin and PSA metrics as prognostic indicators for OS in de novo mCSPC.

Purpose: Tumor next-generation sequencing reports typically generate trial recommendations for patients based on their diagnosis and genomic profile. However, these require additional refinement and prescreening, which can add to physician burden. We wanted to use human prescreening efforts to efficiently refine these trial options and also elucidate the high-value parameters that have a major impact on efficient trial matching., Methods: Clinical trial recommendations were generated based on diagnosis and biomarker criteria using an informatics platform and were further refined by manual prescreening. The refined results were then compared with the initial trial recommendations and the reasons for false-positive matches were evaluated., Results: Manual prescreening significantly reduced the number of false positives from the informatics generated trial recommendations, as expected. We found that trial-specific criteria, especially recruiting status for individual trial arms, were a high value parameter and led to the largest number of automated false-positive matches., Conclusion: Reflex clinical trial matching approaches that refine trial recommendations based on the clinical details as well as trial-specific criteria have the potential to help alleviate physician burden for selecting the most appropriate trial for their patient. Investing in publicly available resources that capture the recruiting status of a trial at the cohort or arm level would, therefore, allow us to make meaningful contributions to increase the clinical trial enrollments by eliminating false positives.

Objective: While screening for psychosocial distress is now the standard of care in oncology, little guidance is available on how best to deliver services in response to identified needs. The American Psychosocial Oncology Society (APOS) convened a task force with the goal of creating a framework that could aid in planning services and justifying requests for resources., Methods: Ten experts from multiple disciplines within psychosocial oncology served on the task force, first meeting together as a larger group over 2 days to set an agenda and then subsequently working in smaller teams to execute the goals. The task force used consensus methods for developing recommendations., Results: Three principles were identified for the framework. First, psychosocial oncology is a key component of population health, and population-based approaches to care delivery are required. Second, several key parameters shape psychosocial oncology services: resources, aims, and scope. To guide resource allocation, example priorities were identified for the aims and scope of services. Finally, cancer care centers should strive to ensure the delivery of high-quality psychosocial oncology care across all components of care. A range of practices was ranked by their potential contributions to achieving that goal., Conclusions: This framework may aid in planning, evaluating, and refining the delivery of responsive psychosocial oncology services., (© 2020 John Wiley & Sons, Ltd.)

This phase 1 study sought to characterize the safety, tolerability, and pharmacokinetic behavior of VLX1570, a small molecule inhibitor of the deubiquitinases (DUBs) that remove sterically bulky ubiquitin chains from proteins during processing in the19S regulatory subunit of the proteasome, in patients with relapsed and refractory multiple myeloma (MM). Fourteen patients were treated with escalating doses of VLX1570 ranging from 0.05 to 1.2 mg/kg as a brief intravenous (IV) infusion on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. Due to its poor aqueous solubility, VLX1570 was formulated in polyethylene glycol, polyoxyethylated castor oil, and polysorbate 80 and administered as a brief intravenous (IV) infusion via a central venous catheter. Anti-myeloma effects were noted at doses at or above 0.6 mg/kg, however, two patients treated at the 1.2 mg/kg dose level experienced severe, abrupt, and progressive respiratory insufficiency, which was associated with diffuse pulmonary infiltrates on imaging studies, similar to those rarely noted with bortezomib and other inhibitors of the 20S proteasome, culminating in death. Although the contribution of VLX1570's formulation to the pulmonary toxicity could not be ruled out, the severity and precipitous nature of the toxicity and the steep relationship between dose and toxicity, the study was discontinued. Despite the severe pulmonary toxicity noted with VLX1570, efforts directed at identifying DUB inhibitors with greater therapeutic indices appear warranted based on the unique mechanism of action, robustness of preclinical antitumor activity, and activity of the DUB inhibitors in MM resistant to PIs targeting the 20S proteasome subunit.

Culture bump theory provides a practical and goal-oriented framework for addressing cultural differences that can impact communication and patient care. Differences in language and culture, coupled with a lack of knowledge or competency regarding these differences, often contribute to 'culture bumps' between healthcare providers and patients. Interpreters serve the unique role of 'cultural brokers', going beyond bridging the linguistic divide to close cultural gaps. Research from the perspective of interpreters focused on culture bumps and cultural competency within genetic counseling sessions is lacking. We aimed to assess interpreters' experiences with significant 'culture bumps' in genetic counseling sessions, obtain interpreters' perspectives regarding genetic counselors' gaps in cultural competency, and explore interpreters' perceptions of the impact of cultural competency on the genetic counseling sessions. Spanish and Polish interpreters experienced in working in person with genetic counselors were recruited through interpreter supervisors at medical centers, hospitals, and interpreter training and service agencies in the Chicagoland area. Using a semi-structured interview guide, phone interviews were conducted with eligible participants and transcribed verbatim. A codebook was developed between two coders, and inter-rater reliability was assessed (κ = 0.82). Grounded theory was used as a guiding principle to code data. The results of this study revealed significant culture bumps identified by interpreters in genetic counseling sessions in the areas of exchange of information, gender and family dynamics, and incorporation of religious and faith beliefs. Interpreters identified the impact on rapport, both negative and positive, due to gaps and strengths in cultural competency, respectively. These responses offer useful insight for training and providing practicing genetic counselors with tools to promote cultural competency, in order to provide optimal care for patients with limited English proficiency (LEP). Further research is necessary to explore these concepts within other languages and cultures, as well as to determine the most appropriate methods for implementing these suggestions for improvement., (© 2020 National Society of Genetic Counselors.)

Background: Strong evidence supports the benefits of the Mediterranean diet, but little is reported among patients and nurses regarding knowledge about the diet and its health benefits., Objectives: A pre-/post-test practice initiative was implemented to identify level of knowledge about the Mediterranean diet in patients with cancer and nursing staff and to provide education about the diet's health benefits., Methods: A 17-item survey was developed to assess knowledge and willingness to try or recommend the Mediterranean diet, current practices, and general nutrition knowledge. A 10-minute education session was provided to patients and nursing staff. Descriptive statistics were used., Findings: The majority of patients reported eating from one to four servings of fruits and vegetables daily. For patients and nursing staff, post-education session scores demonstrated increased knowledge, willingness to try the diet, and perceived effectiveness of the diet.

Purpose: We report treatments and outcomes in a contemporary patient population with HER2-positive metastatic breast cancer (MBC) by hormone receptor (HR) status from the Systemic Therapies for HER2-positive Metastatic Breast Cancer Study (SystHERs)., Experimental Design: SystHERs (NCT01615068) was an observational, prospective registry study of U.S.-based patients with newly diagnosed HER2-positive MBC. Endpoints included treatment patterns and clinical outcomes., Results: Of 977 eligible patients (enrolled from 2012 to 2016), 70.1% ( n = 685) had HR-positive and 29.9% ( n = 292) had HR-negative disease. Overall, 59.1% (405/685) of patients with HR-positive disease received any first-line endocrine therapy (with or without HER2-targeted therapy or chemotherapy); 34.9% (239/685) received HER2-targeted therapy + chemotherapy + sequential endocrine therapy. Patients with HR-positive versus HR-negative disease had longer median overall survival (OS; 53.0 vs 43.4 months; hazard ratio, 0.70; 95% confidence interval, 0.56-0.87). Compared with patients with high HR-positive staining (10%-100%, n = 550), those with low HR-positive staining (1%-9%, n = 60) received endocrine therapy less commonly (64.2% vs 33.3%) and had shorter median OS (53.8 vs 40.1 months). Similar median OS (43.4 vs 40.1 months) was observed in patients with HR-negative versus low HR-positive tumors (1%-9%)., Conclusions: Despite evidence that first-line HER2-targeted therapy, chemotherapy, and sequential endocrine therapy improves survival in patients with HR-positive, HER2-positive disease, only 34.9% of patients in this real-world setting received such treatment. Patients with low tumor HR positivity (1%-9%) had lower endocrine therapy use and worse survival than those with high tumor HR positivity (10%-100%)., (©2020 American Association for Cancer Research.)

Given the high prevalence (30-35%) of psychosocial and psychiatric morbidity amongst cancer patients in any phase of the disease trajectory, screening for emotional problems and disorders has become mandatory in oncology. As a process, screening begins at the entry to the cancer care system and continues at clinically meaningful times, periodically during active cancer care, or when clinically indicated. The goal is to facilitate proper referral to psychosocial oncology specialists for more specific assessment and care, as well as treatment and evaluation of the response, according to the implementation of distress management guidelines. In this editorial, we will provide a non-exhaustive overview of relevant protocols, with particular reference to the National Comprehensive Cancer Network (NCCN) Distress Management in Oncology Guidelines, and review the challenges and the problems in implementing screening, and the assessment and management of psychosocial and psychiatric problems in cancer centres and community care.

Background: High stress levels over time can contribute to compassion fatigue and burnout and negatively affect individual health and well-being., Objectives: A pre-/post-test initiative was implemented to determine the effects of massage chair sessions on ambulatory cancer center nurses (RNs and advanced practice providers) based on their perceived stress, blood pressure (BP), and heart rate (HR)., Methods: A mechanical massage chair was available for 20-minute sessions in a secure room, and nurses self-recorded perceived stress using a visual analog scale, as well as BP and HR using a wrist cuff device. Descriptive statistics and paired t tests were used to assess nurse characteristics and differences before and after massage chair sessions., Findings: Nurses participated in 200 massage chair sessions during a six-month period. Significant reductions were noted in perceived stress, systolic and diastolic BP, and HR. These data indicate that providing a relaxing room with chair massage has favorable effects on nurses' perceived stress, BP, and HR.

Background: Concern over high false-positive rates and the potential for unintended harm to patients is a critical component of the lack of widespread adoption of lung cancer screening., Methods: An institutional database was used to identify patients who underwent lung cancer screening between 2/2015 and 2/2018 at Rush University Medical Center and Rush Oak Park Hospital. Reads were executed by dedicated thoracic radiologists and communicated using the Lung Imaging Reporting and Data System (Lung-RADS V.1)., Results: Six hundred and four patients were screened over the study period. We identified 21 primary lung cancers and 8 incidental cancers. We identified a false-positive rate of 17.5%. Only 9 patients underwent further investigative workup for benign disease (5.3%); however, only 4 (2.9%) of those patients were found to have inflammatory or infectious lesions, which are common mimickers of lung cancer. Excluding Lung-RADS category 3 for the purpose of quantifying risk of unintended harm from unnecessary procedures, we found a 6.9% false-positive rate, while diagnosing 25% of all Lung-RADS category 4 patients with primary lung cancer., Conclusion: False-positive rates in lung cancer screening programs continue to decline with improved radiologic expertise. Additionally, false-positive reporting overestimates the risk of unintended harm from further investigative procedures as only a percentage of positive findings are generally considered for tissue diagnosis (i.e., Lung-RADS category 4).

Aims: Acute myeloid leukemia (AML) treatment typically involves remission induction chemotherapy followed by consolidation chemotherapy. New treatments for AML have recently been introduced, including a chemotherapy formulation called CPX-351, which is administered via less time-intensive IV infusion than the standard "7 + 3" continuous infusion regimen of cytarabine plus an anthracycline. The purpose of this study was to estimate utilities that could be used in economic modeling of AML treatment. Materials and methods: In time trade-off interviews, participants from the UK general population valued 12 health states drafted based on literature and clinician interviews. To identify disutility associated with chemotherapy, two types of induction and four types of consolidation were added to an otherwise identical health state describing AML. The decrease in utility when adding these chemotherapy regimens represents the disutility of each regimen. Five additional health states were valued to estimate utilities associated with other AML treatments. Results: Two hundred participants completed interviews. Mean (SD) utilities were 0.55 (0.31) for pre-treatment AML and 0.66 (0.29) for AML in temporary remission. Adding any chemotherapy significantly decreased utility ( p  < 0.0001). Induction had a mean disutility of -0.11 with CPX-351 and -0.15 with 7 + 3. Mean disutility for consolidation ranged from -0.03 with outpatient CPX-351 to -0.11 with inpatient 5 + 2. Utilities are also reported for other AML treatments (e.g. transplant, low-intensity chemotherapy). Limitations: One limitation is that the differences in adverse event profiles between the treatment regimens were based on clinician opinion. Future use of CPX-351 in clinical trials or clinical settings will provide additional information on its adverse event profile. Conclusions: While all chemotherapy regimens were associated with disutility, regimens with shorter hospitalization and less time-intensive infusion were generally perceived as preferable. These utilities may be useful in cost-utility models comparing the value of AML treatments.

Two patients diagnosed with advanced head and neck cancer were treated with cetuximab 400 mg/m 2 intravenously for one loading dose followed by 250 mg/m 2 IV on days 1, 8, and 15 along with paclitaxel 80 mg/m 2 and cisplatin 30 mg/m 2 intravenously on days 1 and 8 repeated every 21 days for three cycles (CPP). Maintenance cetuximab 250 mg/m 2 intravenously weekly was continued following the aforementioned regimen for one year or until disease progression. Patient A was diagnosed with squamous cell carcinoma of the parotid gland treated initially with parotidectomy and radiation therapy. After the detection of multiple lung metastases, he received three cycles of CPP and maintained a stable disease after one year. Patient B was diagnosed with metastatic laryngeal cancer and was initially treated with three cycles of docetaxel, cisplatin, and continuous infusion fluorouracil (TPF) followed by chemoradiation with cisplatin. After one year, recurrence was observed, and she was treated with laryngopharyngectomy. After another year, recurrence was observed , and CPP was initiated. Further progression was noted shortly after completion of cycle 3. There are limited data supporting the use of regimens similar to CPP in advanced head and neck cancer. Further study is needed to determine the relative efficacy and safety of CPP compared with other regimens containing monoclonal antibodies targeting the epidermal growth factor receptor, taxanes, platinum agents, and/or fluorouracil.

Objective: The aims of the project are to increase knowledge related to opioids and improve adherence to evidence-based interventions for sedation monitoring and assessment in adult inpatients receiving opioids for pain through delivery of an interprofessional online program., Background: Preventable opioid-induced respiratory depression is a patient safety risk in hospitals. Sedation and respiratory assessment and monitoring guidelines and tools are available to improve practice., Methods: An interprofessional team identified organization-specific drivers of opioid-induced sedation and respiratory depression using process improvement methodology, developed interventions, and evaluated clinician opioid knowledge and documentation practice., Results: Opioid knowledge survey responses improved after the interventions. Audits showing improved appropriate documentation by RNs of the correct sedation scale were performed over 2 separate 3-month periods., Conclusions: Clinicians demonstrated increased knowledge about newly adopted sedation and monitoring practices targeted to prevent opioid-induced respiratory depression.

Purpose The approval history, pharmacology, pharmacokinetics, clinical trials, efficacy, dosing recommendations, drug interactions, safety, place in therapy, and economic considerations of gefitinib are reviewed. Summary Lung cancer is one of the most commonly diagnosed cancers and is the leading cause of cancer death. Platinum-based chemotherapy and tyrosine kinase inhibitors, such as erlotinib and afatinib, are recommended therapies for nonsmall cell lung cancer. The European Medicines Association based their approval of gefitinib on the randomized, multicenter Iressa Pan-Asia Study (IPASS, NCT00322452) and a single-arm study showing effectiveness in Caucasians (IFUM, NCT01203917). Both studies were recently referenced by the United States Food & Drug Administration to reapprove gefitinib for the first-line treatment of advanced nonsmall cell lung cancer with epidermal growth factor receptor exon 19 deletions or exon 21 substitution. Diarrhea, acneiform rash, and interstitial lung disease are known side effects of gefitinib. Conclusion Use of gefitinib for the first-line therapy of metastatic nonsmall cell lung cancer with epidermal growth factor receptor exon 19 deletions (residues 747-750) or exon 21 substitution mutation (L858R) is well-documented and supported.

Patients with primary central nervous system lymphoma (PCNSL) treated in the 'real-world' setting do not represent those treated on clinical trials and might not be treated similarly. We studied characteristics and variability in care for 113 newly diagnosed PCNSL patients treated at 5 institutions in the Chicago area between 2000 and 2012. In 111 patients, single modality therapy with a high dose methotrexate (HD-MTX) regimen +/- rituximab, was most commonly employed (n = 65), and 34 underwent radiotherapy (+/- systemic therapy). Fifty-eight of 108 patients received rituximab. Twenty-nine of 110 patients (26%) received intrathecal chemotherapy (ITC). Overall response rate was 80% (47% complete responses). With a median follow-up of 18·7 months, median overall survival (OS) was 65·2 months. In univariate analysis, HD-MTX (median OS 72·7 vs. 2·7 months, P < 0·001) and rituximab (median not reached versus 28·4 months, P = 0·005) impacted OS favourably. This significance was sustained regardless of immune status and in multivariate analysis. Whole brain radiotherapy (WBRT) resulted in a trend for improved OS as compared with systemic therapy alone (P = 0·09), while ITC did not impact survival. Clinical practice has evolved to exclude WBRT and ITC while incorporating rituximab with clinical outcomes comparable in immuno-competent/compromised patients and similar to those achieved in recent clinical trials., (© 2017 John Wiley & Sons Ltd.)

Interleukin-17 (IL-17), a proinflammatory cytokine, mainly produced by Th17 cells, participates in both innate and adaptive immune responses and is involved in various diseases, including infectious diseases, autoimmune disorders and cancer. Emerging evidence indicates that IL-17 not only has an oncogenic role in tumorigenesis by regulating tumor angiogenesis and enhancing tumor immune evasion but also exerts anti-tumor functions by enhancing natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) activation and through the recruitment of neutrophils, NK cells and CD4 + and CD8 + T cells to tumor tissue. In this review, we provide an overview on the basic biology of IL-17 and recent findings regarding its enigmatic double-edged features in tumorigenesis, with special attention to the roles of IL-17 produced by tumor cells interacting with other factors in the tumor microenvironment., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Rearrangement of MYC is associated with a poor prognosis in patients with diffuse large B cell lymphoma (DLBCL) and B cell lymphoma unclassifiable (BCLU), particularly in the setting of double hit lymphoma (DHL). However, little is known about outcomes of patients who demonstrate MYC rearrangement without evidence of BCL2 or BCL6 rearrangement (single hit) or amplification (>4 copies) of MYC. We identified 87 patients with single hit lymphoma (SHL), 22 patients with MYC-amplified lymphoma (MYC amp) as well as 127 DLBCL patients without MYC rearrangement or amplification (MYC normal) and 45 patients with DHL, all treated with either R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or intensive induction therapy. For SHL and MYC amp patients, the 2-year progression-free survival rate (PFS) was 49% and 48% and 2-year overall survival rate (OS) was 59% and 71%, respectively. SHL patients receiving intensive induction experienced higher 2-year PFS (59% vs. 23%, P = 0·006) but similar 2-year OS as compared with SHL patients receiving R-CHOP. SHL DLBCL patients treated with R-CHOP, but not intensive induction, experienced significantly lower 2-year PFS and OS (P < 0·001 for both) when compared with MYC normal patients. SHL patients appear to have a poor prognosis, which may be improved with receipt of intensive induction., Competing Interests: The authors have declared no conflicts of interest., (© 2016 John Wiley & Sons Ltd.)

Surgical site infection (SSI) remains one of the most important causes of healthcare-associated infections, accounting for ~17 % of all hospital-acquired infections. Although short-term perioperative treatment with high fraction of inspired oxygen (FiO2) has shown clinical benefits in reducing SSI in colorectal resection surgeries, the true clinical benefits of FiO2 therapy in reducing SSI remain unclear because randomized controlled trials on this topic have yielded disparate results and inconsistent conclusions. To date, no animal study has been conducted to determine the efficacy of short-term perioperative treatments with high (FiO2>60 %) versus low (FiO2<40 %) oxygen in reducing SSI. In this report, we designed a rat model for muscle surgery to compare the effectiveness of short-term perioperative treatments with high (FiO2=80 %) versus a standard low (FiO2=30 %) oxygen in reducing SSI with Pseudomonas aeruginosa - one of the most prevalent Gram-negative pathogens, responsible for nosocomial SSIs. Our data demonstrate that 5 h perioperative treatment with 80 % FiO2 is significantly more effective in reducing SSI with P. aeruginosa compared to 30 % FiO2 treatment. We further show that whilst 80 % FiO2 treatment does not affect neutrophil infiltration into P. aeruginosa-infected muscles, neutrophils in the 80 % FiO2-treated and infected animal group are significantly more activated than neutrophils in the 30 % FiO2-treated and infected animal group, suggesting that high oxygen perioperative treatment reduces SSI with P. aeruginosa by enhancing neutrophil activation in infected wounds.

Background: Snail is a typical transcription factor that could induce epithelial-mesenchymal transition (EMT) and cancer progression. There are some related reports about the clinical significance of snail protein expression in gastric cancer. However, the published results were not completely consistent. This study was aimed to investigate snail expression and clinical significance in gastric cancer., Results: A systematic review of PubMed, CNKI, Weipu, and Wanfang database before March 2015 was conducted. We established an inclusion criterion according to subjects, method of detection, and results evaluation of snail protein. Meta-analysis was conducted using RevMan4.2 software. And merged odds ratio (OR) and 95 % CI (95 % confidence interval) were calculated. Also, forest plots and funnel plot were used to assess the potential of publication bias. A total of 10 studies were recruited. The meta-analysis was conducted to evaluate the positive rate of snail protein expression. OR and 95 % CI for different groups were listed below: (1) gastric cancer and para-carcinoma tissue [OR = 6.15, 95 % CI (4.70, 8.05)]; (2) gastric cancer and normal gastric tissue [OR = 17.00, 95 % CI (10.08, 28.67)]; (3) non-lymph node metastasis and lymph node metastasis [OR = 0.40, 95 % CI (0.18, 0.93)]; (4) poor differentiated cancer, highly differentiated cancer, and moderate cancer [OR = 3.34, 95 % CI (2.22, 5.03)]; (5) clinical stage TI + TII and stage TIII + TIV [OR = 0.38, 95 % CI (0.23, 0.60)]; (6) superficial muscularis and deep muscularis [OR = 0.18, 95 % CI (0.11, 0.31)]., Conclusions: Our results indicated that the increase of snail protein expression may play an important role in the carcinogenesis, progression, and metastasis of gastric cancer. And this result might provide instruction for the diagnosis, therapy, and prognosis of gastric cancer.

Stable blood based miRNA species have allowed for the differentiation of patients with various types of cancer. Therefore, specific blood-based miRNA might be considered as a methodology which could be informative of the presence of cancer potentially from multiple distinct organ sites. Recently, miR-21 has been identified as an "oncomir" in various tumors while miR-152 as a tumor suppressor. In this study, we investigated whether circulating miR-21 and miR-152 can be used for early detection of lung cancer (LuCa), colorectal carcinoma (CRC), breast cancer (BrCa) and prostate cancer (PCa), with distinguishing cancer from various benign lesions on these organ sites. We measured the two miRNA levels by using real-time RT-PCR in plasma samples from a total of 204 cancer patients, 159 various benign lesions, and 228 normal subjects. We observed significantly elevated expression of miR-21 and miR-152 in LuCa, CRC, and BrCa when compared with normal controls. We also found upregulation of plasma miR-21 and miR-152 levels in patients with benign lesions of lung and breast, as compared to normal controls, respectively. No significant expression variation of the two miRNAs was observed in PCa or prostatic benign lesions as compared to healthy controls. Receiver operating characteristic (ROC) analyses revealed that miR-21 and/or miR-152 can discriminate LuCa, CRC and BrCa from normal controls. Our results suggest that plasma miR-21 and miR-152 may serve as non-specific noninvasive biomarkers for early screening of LuCa, CRC, and BrCa, but not PCa.

Growing demand for and limited geographic access to genetic counseling services is increasing the need for alternative service delivery models (SDM) like telephone genetic counseling (TGC). Little research has been done on genetic counselors' perspectives of the practice of TGC. We created an anonymous online survey to assess whether telephone genetic counselors believed the tasks identified in the ABGC (American Board of Genetic Counseling) Practice Analysis were performed similarly or differently in TGC compared to in person genetic counseling (IPGC). If there were differences noted, we sought to determine the nature of the differences and if additional training might be needed to address them. Eighty eight genetic counselors with experience in TGC completed some or all of the survey. Respondents identified differences in 13 (14.8%) of the 88 tasks studied. The tasks identified as most different in TGC were: "establishing rapport through verbal and nonverbal interactions" (60.2%; 50/83 respondents identified the task as different), "recognizing factors affecting the counseling interaction" (47.8%; 32/67), "assessing client/family emotions, support, etc." (40.1%; 27/66) and "educating clients about basic genetic concepts" (35.6%; 26/73). A slight majority (53.8%; 35/65) felt additional training was needed to communicate information without visual aids and more effectively perform psychosocial assessments. In summary, although a majority of genetic counseling tasks are performed similarly between TGC and IPGC, TGC counselors recognize that specific training in the TGC model may be needed to address the key differences.

Background: Gene expression profiling is being widely applied in cancer research to identify biomarkers for clinical endpoint prediction. Since RNA-seq provides a powerful tool for transcriptome-based applications beyond the limitations of microarrays, we sought to systematically evaluate the performance of RNA-seq-based and microarray-based classifiers in this MAQC-III/SEQC study for clinical endpoint prediction using neuroblastoma as a model., Results: We generate gene expression profiles from 498 primary neuroblastomas using both RNA-seq and 44 k microarrays. Characterization of the neuroblastoma transcriptome by RNA-seq reveals that more than 48,000 genes and 200,000 transcripts are being expressed in this malignancy. We also find that RNA-seq provides much more detailed information on specific transcript expression patterns in clinico-genetic neuroblastoma subgroups than microarrays. To systematically compare the power of RNA-seq and microarray-based models in predicting clinical endpoints, we divide the cohort randomly into training and validation sets and develop 360 predictive models on six clinical endpoints of varying predictability. Evaluation of factors potentially affecting model performances reveals that prediction accuracies are most strongly influenced by the nature of the clinical endpoint, whereas technological platforms (RNA-seq vs. microarrays), RNA-seq data analysis pipelines, and feature levels (gene vs. transcript vs. exon-junction level) do not significantly affect performances of the models., Conclusions: We demonstrate that RNA-seq outperforms microarrays in determining the transcriptomic characteristics of cancer, while RNA-seq and microarray-based models perform similarly in clinical endpoint prediction. Our findings may be valuable to guide future studies on the development of gene expression-based predictive models and their implementation in clinical practice.

The IKZF2 rs12619285 polymorphism is associated with the eosinophil count, which has multidimensional functions in the pathogenesis of coronary heart disease (CHD). The aim of the present study was to investigate the contribution of the IKZF2 rs12619285 polymorphism to the risk of CHD in a Han Chinese population. In total, 721 CHD cases and 631 non-CHD controls were recruited for an association study of the IKZF2 rs12619285 polymorphism. Genotyping was performed using the melting temperature-shift polymerase chain reaction method. No statistically significant association was observed between the IKZF2 rs12619285 polymorphism and CHD (odds ratio, 1.139, 95% confidence interval, 0.927-1.334; P=0.17). In addition, subgroup analyses by gender or age were unable to identify any association between IKZF2 rs12619285 and CHD (P>0.05), and there was no significant correlation between IKZF2 rs12619285 and the severity of CHD (P>0.05). The power of the case-control study was determined to be 63.3%. In addition, the G allele frequency was calculated as 63.6% in the Han Chinese population, which was similar to the 59.3% recorded for the HapMap Chinese population of Han Chinese individuals living in Beijing, compared with 24.3% in European descendents (HapMap-CEU). Therefore, the results indicated that the IKZF2 rs12619285 polymorphism was not associated with CHD in a Han Chinese population. The discrepancy in the association between rs12619285 and CHD may be due to the ethnic differences between Han Chinese and European populations.

In patients with malignancy, the major barrier to achieving complete response is emergence of resistance to current chemotherapeutic agents. One of the major mechanisms by which tumour cells become resistant to therapies is by altering cellular drug targets through mutations and/or deletions. Resistance by this mechanism is achieved more easily if the drug has limited cellular targets and/or processes. We hypothesized that as Pseudomonas aeruginosa exotoxin T (ExoT) targets six proteins that are required for cancer cell survival and proliferation, it is highly unlikely for cancer cells to develop resistance to this toxin. We assessed ExoT's cytotoxicity against multiple invasive and highly resistant tumour cell lines in order to evaluate its potential as a chemotherapeutic agent. Our data demonstrated that ExoT induced potent cytotoxicity in all tumour cell lines that we examined. Collectively, our data highlighted the potential of ExoT as a possible chemotherapeutic candidate for the treatment of cancer., (© 2015 The Authors.)

Our objective was to explore associations of circulating factors implicated in insulin-like growth factor- 1 receptor (IGF-1R) signaling with clinical outcomes of patients with acute myeloid leukemia (AML). Pretreatment blood samples from patients with non-M3 AML (n = 30) were collected prospectively and levels of IGF binding proteins (IGFBPs) 1-7 and IGF-1 (free and total) were established at diagnosis and statistically evaluated. Baseline levels of IGFBP-1 and -6 below respective thresholds of 8.8 ng/mL and 237 ng/mL were associated (p = 0.0347 and 0.0099, respectively) with superior progression-free survival, whereas baseline levels of IGFBP -1, -2, -6 and -7 below the respective thresholds of 8.8, 28.8, 237 and 119 ng/mL were strongly associated (p = 0.0004, 0.0085, 0.0031, 2.46 × 10(- 7), respectively) with improved overall survival. These findings provide promising evidence that IGFBP signatures could be used as predictive tools in AML, with applications in remission surveillance and the development of IGFBP-directed biologic therapy.

Decline in CD4 T cell immune responses is associated with aging. Although a number of immunological defects have been identified in elderly mice (>18 months old), a key early-onset immune defect at middle age could be a driver or contributor to defective CD4 T cell responses. Our studies demonstrate that age-related alterations in DC subsets within the priming environment of middle-aged mice (12 months old) correlate with and can directly contribute to decreases in antigen-specific CD4 T cell Th1 differentiation, which measured by T-bet and IFN-γ expression, was decreased significantly in T cells following VSV infection or s.c. immunization with a protein antigen in the context of immune stimulation via OX40. The deficient Th1 phenotype, observed following protein antigen challenge, was found to be the result of an age-related decrease in an inflammatory DC subset (CD11b+ Gr-1/Ly6C+) in the dLN that corresponded with T cell dysfunction. In the virus model, we observed significant changes in two DC subsets: mDCs and pDCs. Thus, different, early age-related changes in the DC profile in the priming environment can significantly contribute to impaired Th1 differentiation, depending on the type of immunological challenge., (© 2014 Society for Leukocyte Biology.)