bluuebunny/crossref_metadata_2025 huggingface dataset:
CLO19-045: Safety of Immune Checkpoint Inhibitors in Cancer Patients With Microsatellite Instability-High (MSI-H) Status: An Experience From Qatar
Authors: El-Hadi Omar Nabil , Nasser Sahar , Gasim Mahmoud , Khanna Maneesh , Nashwan Abdulqadir J. , Feilchenfeldt Jonas W. , Rasul Kakil , Hamad Anas
Published: March 2019

Background: Microsatellite instability-high (MSI-H) is shown to predict response to the immune checkpoint inhibitors (ICPi). Recently, the FDA granted an accelerated approval for the use of pembrolizumab in any solid tumor and nivolumab in metastatic colorectal cancer in patients with MSI-H. However, the immune-related adverse events (irAEs) exhibit a unique heterogeneous spectrum than conventional chemotherapy adverse drug reactions (ADRs). Underestimating the irAEs could be potentially lethal. Objectives: To evaluate the irAEs; their management, and outcome in MSI-H patients treated with ICPi at the National Center for Cancer Care and Research (NCCCR) in Qatar. Methods: All patients with MSI-H and treated with ICPi at the NCCCR between January 2015 and June 2018 were reviewed retrospectively. Radiologic assessment of irAEs and Naranjo score were used to estimate and confirm the probability of ADRs. Patient demographics, immunotherapy treatment, reported irAEs, and their management were collected. Results: Of the total cohort of patients receiving ICPIs; 9 patients with MSI-H were identified; all received pembrolizumab. 45% (n=4) of the patients were still actively on treatment; 22% (n=2) received only 1 dose then passed away; 22 % (n=2) discontinued because of disease progression; and 11% (n=1) of the patients received 2 cycles as neoadjuvant treatment. To the best of our knowledge, this is the biggest cohort of cancer patients with MSI-H in the Middle East. Calculated Naranjo score was 7 in 45% of the patients (n=4) and 5 in 22 % of patient (n=2), which indicates a probable ADR. 34% of the patients (n=3) did not experience ADRs till the date of data cutoff. 8 irAEs were seen in 67% (n=6) of the patients (Table 1). Based on laboratory or radiologic confirmation, 87.5% (n=7) were irAEs and 12.5% (n=1) was not related to pembrolizumab. Laboratory findings confirmed 25% of the ADRs and radiologic findings confirmed 75% of the ADRs. Of those who developed irARs, 3 patients required a hold of treatment, 1 needed monitoring, and 2 required pharmacologic interventions. There was one patient who received empirical pharmacologic intervention at which evaluation showed no relation to immunotherapy. Conclusion: irAEs can sometimes be unpredictable, rare, and often missed. Frequent monitoring and early management of these suspected or confirmed adverse effects is life saving and should be done in a multidisciplinary approach.
EPR19-73: Risk of Gastrointestinal and Hepatic Toxicities in Patients With Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer Treated With CDK4/6 Inhibitors
Authors: Sultan Anita , Swarup Sriman , Ball Somedeb , Quirch Miguel , Arevalo Meily , Myat Yin M. , Aung Ye , Zaw Myo H. , Thein Kyaw Z.
Published: March 2019

Background: CDK4 and CDK6 are cyclin-dependent kinases that control transition between G1 and S phases of the cell cycle, hence controlling cell cycle progression by reversible combination with cyclin D1. In cancer cell, CDK4/6 activity is overexpressed, which can lead to amplification or overexpression of the genes encoding for CDK 4/6 or the cyclin D. Additionally, loss of endogenous INK4 inhibitors can also lead to over activity of CDK4 and CDK6. We undertook a meta-analysis of randomized controlled trials (RCT) to determine the risk of gastrointestinal (GI) and hepatic toxicities associated with CDK 4/6 inhibitors. Methods: We conducted a comprehensive literature search using MEDLINE, EMBASE databases, and meeting abstracts from inception through September 2018. In our analysis, we incorporated RCTs that mention GI toxicities and elevation of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) as adverse effects. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% CI. Random effects model was applied. Results: A total of 4,557 patients with advanced breast cancer from 7 phase III and 1 phase II RCTs were eligible. The study arms used were palbociclib/ribociclib/abemaciclib or placebo in combination with letrozole or anastrozole or fulvestrant or other hormonal agents. The RR of all-grade side effects were as follows: diarrhea, 1.691 (95% CI: 1.220–2.345; P=.002); nausea, 1.632 (95% CI: 1.447–1.840; P<.001); vomiting, 1.684 (95% CI: 1.256–2.259, P=.001); stomatitis, 2.160 (95% CI: 1.332–3.503; P=.002); elevated AST, 1.832 (95% CI: 1.312–2.558; P<.001); and elevated ALT, 2.150 (95% CI: 1.649–2.803; P<.001). The RR of high-grade side effects were as follows: diarrhea, 2.592 (95% CI: 0.853–7.877; P=.093); nausea, 1.326 (95% CI: 0.589–2.988; P=.496); vomiting, 1.089 (95% CI: 0.479–2.476; P=.839); stomatitis, 2.097 (95% CI: 0.502–0.753; P=.310); elevated AST, 2.274 (95% CI: 1.173–4.410; P=.015); and elevated ALT, 3.988 (95% CI: 2.387–6.663; P<.001). Conclusions: Our study demonstrated that the risk of developing all grade GI toxicities and all grades of hepatic side effects including grade 3 and 4, was high in CDK 4/6 inhibitors group, compared to control arm, and prompt intervention with good supportive care is required.
CLO19-024: Risk of Atrial Fibrillation and Pulmonary Toxicities in Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Treated With Ibrutinib
Authors: Adhikari Nimesh , Zaw Myo H. , Swarup Sriman , Sultan Anita , Sharma Upama , Thi Wai P. , Yee Nay N. , Htwe Khaing K. , Naing Tun W. , Thein Kyaw Z.
Published: March 2019

Background: Bruton’s tyrosine kinase (BTK), a kinase downstream of the B-cell receptor, involves in the B cell survival and proliferation and has become an attractive therapeutic target. Ibrutinib is an oral potent, covalent inhibitor of BTK and hence employed in many hematologic malignancies. We performed a systematic review and pooled analysis of randomized controlled trials (RCTs) to determine the risk of atrial fibrillation (AF) and pulmonary toxicities among patients treated with ibrutinib. Methods: We performed a comprehensive literature search using MEDLINE, EMBASE databases, and meeting abstracts through September 2018. Phase 3 RCTs that mention AF and pulmonary toxicities as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio with 95% CI. Random effects model was applied. Results: 4 phase III RCTs with a total of 1,383 patients with chronic lymphocytic leukemia or small lymphocytic lymphoma were eligible. Studies comparing Ibrutinib (I) vs ofatumumab, I vs chlorambucil, I+ bendamustine (B)+ rituximab (R) vs placebo + B+ R, and I vs R were included in the analysis. The AF incidence was 41 (5.686%) in the ibrutinib group vs 8 (1.208%) in the control arm. The relative risk (RR) for AF was statistically significant at 3.825 (95% CI: 1.848–7.917; P<.0001) and RD was 0.041 (95% CI: 0.023–0.059; P<.0001). The RR of all-grade side effects was as follows: cough, 1.133 (95% CI: 0.724–1.773; P=.584); edema, 1.375 (95% CI: 0.943–2.006; P=.098); pneumonia, 1.227 (95% CI: 0.884–1.703; P=.221); and upper respiratory infections (URI), 1.075 (95% CI: 0.809–1.429; P=.616). The RR of high-grade side effects was as follows: cough, 0.373 (95% CI: 0.063–2.209; P=.277); edema, 1.232 (95% CI: 0.199–7.649; P=.822); pneumonia, 1.277 (95% CI: 0.847–1.926; P=.243); and URI, 1.555 (95% CI: 0.239–10.127; P=.644). Conclusion: Our meta-analysis demonstrated that patients on ibrutinib noted a significant increase in the risk of atrial fibrillation with a relative risk of 3.825. However, the risk of pulmonary toxicities was not statistically increased in the ibrutinib group.
CLO19-055: Implementing Scalp Cooling: Considerations and Best Practice
Authors: Unthank Brittany , Brophy Lynne Laurence , Radcliff Lindsey , Basinger Heidi , Bourque Sabrenna
Published: March 2019

Background: Scalp cooling is a useful technique for decreasing hair loss and reducing the stigma patients feel when they experience alopecia. It was used for a period of time in the U.S. more than 20 years ago and then was removed from the market while use continued in Europe. Recently, better equipment has been developed and approved by the FDA for use with patients who have solid tumors. Current evidence supports this technology and will be summarized in this presentation. Discussion: Setting up scalp cooling as an offered service at any setting presents many challenges and changes in workflow affecting physicians and nursing staff. The purpose of this presentation is to prepare oncology providers who wish to implement scalp cooling using a machine based system at their setting. Our implementation process will be used as a teaching case study. Product support, logistics, patient satisfaction, equipment, and education needs will be discussed. This project description will highlight the steps taken to implement scalp cooling at a comprehensive cancer center for breast and gynecology oncology patients. Initial efforts to review the literature, investigate equipment choices, and compare use with other centers will be reviewed. The management aspects of setting up a new service, eg, business plan, physical plan considerations, informed consent, costs, staffing, workflow, clinic schedules, safety, and staff education will be shared. Important tips for keeping patients safe and comfortable while achieving maximum therapeutic benefit will be discussed. Evaluation will be presented in the form of lessons learned during implementation resulting in more efficient work flow and greater patient comfort during scalp cooling. Patient satisfaction data will be disseminated. Conclusion: The oncology community is eager to provide patients with scalp cooling, but no literature to date has described the management aspects of implementation. This presentation will offer comprehensive information to assist in addressing anticipated needs when initiating scalp cooling.
CLO19-042: Quality Assurance for Cancer Radiotherapy: An Update on the Ottawa Hospital Peer Review Experience
Authors: Malone Shawn , Gaviolli Eduardo , Malone Julia , Renaud Julie
Published: March 2019

Background: Peer review is an important quality assurance (QA) tool in cancer care. For radiotherapy (XRT), peer review is challenging because of the complexity of XRT targets and treatment planning and significant patient numbers. During review target and contour, volumes of adjacent normal tissues are evaluated. The XRT dose to targets/normal tissues are assessed for coverage and safety. Timing of review is important, ideally occurring prior to start of XRT or before 25% of XRT dose is delivered to allow for change (CPQR, 2015). Cancer Care Ontario (CCO) has yearly targets for review of curative/adjuvant courses: 2015, 50%; 2016, 60%; 2017, 75%; and 2018, 80%. In the past 2 years, CCO has focused on introducing peer review for complex cases of palliative XRT. The Ottawa Hospital (TOH) is one of 14 Ontario Regional Ca Centers. TOH services 1.3 million people, and 4,500 patients receive XRT per year. Methods: We reviewed peer review rates for curative and palliative XRT at TOH to assess improvements in QA over the last 4 years. We evaluated if TOH met CCO targets. Timing for peer review was assessed. We evaluated if peer review rates varied by tumour site. Rates of plan modification were recorded by year and tumor site. Reasons for plan modification were evaluated. Results: 3,694 curative/adjuvant courses were completed in 2018. Peer review increased over 4 years: 2015, 62%; 2016, 64%; 2017, 80%, 2018, 84 %. Optimal timing of peer review improved over 4 years (% completed prior to 1st XRT): 2015, 43%; 2016, 44%; 2017, 58%; 2018, 64%. For palliative QA, 21 % were peer reviewed (improvement of 14% over 2017). In 2018, peer review varied by tumor site (range: 61% to 97%); however, for most sites, rates improved over 4 years. Following peer review, a change was recommended in 8% (2% major, 6% minor). The rate did not differ over 4 years (8.2% 2015 vs 8.0% 2018). Recommended changes varied by tumor site (range, 0%–18%). Conclusions: Peer review is an important tool ensuring safe quality XRT. At TOH there has been a significant improvement in peer review over the last 4 years. TOH exceeds provincial targets for curative courses completed, and more peer review activities are being completed prior to the start of the treatment. Rates of peer review and recommended changes vary dramatically amongst tumor sites. Reasons for these variations will be explored in future research. Extension of peer review to palliative XRT has recently been implemented to further improve quality cancer care.
CLO19-032: Skin Cancer of the Nose: Outcome in 405 Cases Treated With Accelerated High Dose Rate Radiation Therapy
Authors: Flores Nicholas E. , Mian T. A. , Liu D.
Published: March 2019

Overview: Between 2013 and 2016, we treated 1,500 cases of nonmelanoma skin cancer using high-dose radiation therapy. In this series, 405 cases involved the nose. Patient selection was limited to age >35 years, tumor size <40 mm in diameter and <5 mm thick. Demographics included 86.7% basal, 12.8% squamous, 1 lymphoma, 1 melanoma. Size by treatment field: 66.9% 10mm, 28.1% 20mm, 4.7% 35mm, and <1% 50mm. Age: 76.8 years median (37.3–99.7 years) Methods: Radiation therapy was administered following guidelines suggested by ASTRO and AAPM using either a 6MeV LINAC electron beam or 50kV x-ray source. The majority of patients received 4,000 cGy in 500 cGy fractions given twice weekly. Prescribed treatment depth was zero (0) mm for non-bulky disease. Bolus was used for all electron treatments. Wax-coated nasal shields were used for lateralized or large midline lesions. Devitalized tumor was debrided and/or treatment depth modified during treatment as needed. Treatment interruptions were rare, usually due to infection, and limited to less than 2 weeks. Results: 99% of patients maintained a complete response at 2 years (0.2–3.7 years) median follow-up, with 1 edge-of-field progression and 1 in-field recurrence. Side effects seen included transient nasal mucositis (10%) limited to lateralized or large midline lesions, superficial infection (<1%) limited to patients with a history of moderate to severe acne and/or patients applying cosmetic concealers during treatment. No chronic nasal dryness, cartilage necrosis, ophthalmic injury, nasolacrimal disruption, or dental complications occurred. Patient satisfaction/cosmesis: patient-scored functional and cosmetic outcomes ranged from very good to excellent in 100% of patients. Conclusion: Accelerated high dose rate radiation therapy using either LINAC electron beam or electronic brachytherapy is an effective and well-tolerated treatment option for carefully selected patients with basal and squamous cell skin cancer of the nose. Response rates for electron beam or low-energy x-rays with this dose schedule were similar. When compared to surgery, radiation therapy results in high patient satisfaction and excellent cosmesis without the need for lengthy postoperative care or reconstruction. When compared to conventional radiation therapy, the high response rates, smaller field sizes, shorter treatment times, and reduced radiation dose to adjacent critical tissues makes electronic brachytherapy a useful addition to standard techniques.
HSR19-113: Valued Outcomes in the Cancer Experience (VOICE™): Scale Development and Initial Validation
Authors: Zaleta Alexandra K. , McManus Shauna , Buzaglo Joanne S. , Yuen Eva Y. N. , Olson Julie S. , Miller Melissa F. , Hurley Karen , Shockney Lillie D. , Goldberger Sara , Golant Mitch , Stein Kevin
Published: March 2019

Background: Despite growing recognition that patient preferences and values should inform cancer care, patients’ views continue to be under-represented. We developed a quantitative tool, Valued Outcomes in the Cancer Experience (VOICE), to measure patient priorities and to understand discrepancies between what matters most to patients and what patients believe they can control. This study presents VOICE development and initial validation. Methods: 459 cancer patients completed an online survey and rated level of importance and perceived control for 54 value items (0=not at all; 4=very much). Items were derived from patient and caregiver focus groups and included themes such as independence, functional abilities, planning for the future, symptom management, health knowledge, and social support. Participants also completed validated measures of hope, optimism, quality of life, financial toxicity, spiritual well-being, illness perceptions, social support, self-efficacy, intolerance of uncertainty, and cancer-related distress. Iterative exploratory factor analysis (EFA) with direct oblique rotation, magnitude of importance and control ratings, and Pearson correlations between items and validation measures were used to inform scale refinement. Results: Participants were 86% non-Hispanic white; mean age=60 years, SD=10; 38% breast cancer, 18% blood, 9% lung, 9% prostate; mean time since diagnosis=6.5 years, SD=6; 22% metastatic. Items that did not load in the EFA, or were not associated with conceptually relevant validation measures, were removed or reworded. The final EFA explained over half of the variance in the data and demonstrated good fit, with absolute and relative fit indices in established acceptable ranges (P<.001). The refined VOICE measure addresses diverse themes including access to care, maintaining independence, longevity, shared decision making, illness understanding, symptom management, emotional support, connection to illness community, spirituality, and end of life preparation. Conclusions: The study results demonstrate a framework for developing a quantitative, multidimensional measure of patient values. By understanding what matters most to patients, VOICE is positioned to bring patient preferences to the foreground of cancer care, contribute to shared decision making, and enhance care. Next steps include further validation of this tool in diverse settings, including oncology practices and community-based organizations.
HSR19-078: Human Papillomavirus Status and Survival Among Patients With Oropharyngeal Cancer: Analyses of a United States Health System
Authors: Aggarwal Himani , Li Li , Carter Gebra Cuyun , Fraeman Kathy , Berger Ariel
Published: March 2019

Background: The incidence of oropharyngeal cancer (OPC) due to tobacco and alcohol, respectively, has been declining, while that linked to human papilloma virus (HPV) has been rising. Epidemiologic, biologic, and prognostic characteristics of OPC differ by HPV-status. This study compared overall survival (OS) among HPV-positive and -negative patients with OPC in a real-world setting. Methods: This retrospective observational study used electronic medical records data from the Geisinger Health System to select patients diagnosed with OPC between January 1, 2010 and September 30, 2015. Patients were designated as HPV-positive if the HPV or P16 test closest to the diagnosis date was positive. All other patients were deemed HPV-negative. Descriptive statistics and relevant statistical tests were used to compare baseline characteristics by HPV status; survival by HPV status was examined using Kaplan–Meier methods and multivariable Cox models. Results: In this study, 152 patients met all selection criteria; 110 (72.4%) were HPV-positive. HPV-positive patients were more likely to be men (89.1% vs 73.8%; P=.019) and to have lymph node involvement (88.2% vs 59.5%; P=.0008); they were less likely to have cerebrovascular disease (6.9% vs. 23.5%; P=.01), or distant metastases (1.8% vs 9.5%; P=.029) vs HPV-negative patients. Among HPV-positive patients, 75.5%, 12.7%, and 10.9% had squamous cell carcinoma NOS, basaloid squamous cell carcinoma, and squamous cell carcinoma large cell non-keratinizing, respectively; corresponding values for HPV-negative patients were 85.7%, 0.0%, and 2.4%, respectively (P=.0013). HPV-positive patients were nominally younger than HPV-negative patients (median: 58 vs 61 years; P=.085). Log-rank test showed OS of HPV-positive patients (median OS from treatment initiation: not reached) is higher than of HPV-negative patients (median OS: 3.7 years; P=.002). In multivariable analyses, HPV-negative status was associated with increased mortality risk (P=.0035); other significant risk factors included alcohol use, diabetes, and distant metastases. Conclusions: HPV-positive status was associated with a decreased risk of mortality among OPC patients in this study. Despite the small sample size and potential violation of assumption of proportional hazard rate, this study underscores the prognostic implication of HPV status in OPC, which may have important ramifications in optimizing treatment decisions among this patient population.
CLO19-029: Dosing Patterns of Nilotinib Use in SIMPLICITY, an Observational Study in Chronic Phase Chronic Myeloid Leukemia (CP-CML) Patients (Pts) in Routine Clinical Practice
Authors: Cortes Jorge , Chen Clara , Mauro Michael , Kumar Neela , Davis Catherine , Goldberg Stuart L.
Published: March 2019

Introduction: Dosing patterns of nilotinib (NIL) in chronic phase chronic myelogenous leukemia (CP-CML) patients (Pts) have not been well documented outside of clinical trials. SIMPLICITY (NCT01244750) is an ongoing observational study exploring tyrosine kinase inhibitor (TKI) use in routine clinical practice among CP-CML pts receiving TKIs in the US and Europe since 2010. This analysis reports NIL dosing patterns and explores predictors of dose reductions. A subset analysis focusing on the first-line (1L) approved dose of 300 mg twice daily (BID) will also be presented. Methods: Only SIMPLICITY pts receiving 1L NIL BID (n=349/408) were included. Baseline demographics and dosing patterns (starting dose, dose changes, time to dose reduction, and duration of therapy [DoT]) were analyzed descriptively. Statistical comparisons were made using t-tests, the Mann-Whitney U test for continuous variables, and chi-square for categorical variables. Logistic regression models were used to identify factors associated with dose reductions. Results: Of the 349 pts treated with 1L NIL, 281 (80.5%) started at the standard dose of 300 mg (BID) or the 400 mg (BID) dose for imatinib-resistance/intolerance, and 37 (10.6%) and 31 pts (8.9%) started on 150‒200 mg BID and 450‒800 mg BID. European pts were more likely to start on a dose >400 mg BID than US pts (P<.0001). Pts at academic centers were more likely to start on >400 mg BID than those treated at community practices (P<.0029). Among the pts starting NIL at 300 or 400 mg (BID) in 1L, 70.9% remained on these doses; 26.6% received a dose reduction (median time to dose reduction: 80.5 days); and 2.5% received a dose increase. Median DoT with NIL was 30.4 vs 43.9 months for pts with vs without a dose reduction (P=NS). The main reason for dose reduction was intolerance (n=51; 68.9%); in 51% of pts, a specific side effect was cited. Dose reductions were more likely in patients at academic centers (odds ratio=1.996; P=.021), but not in pts experiencing baseline fatigue (OR=1.799; P=0.072). Conclusions: Most pts treated with 1L NIL were started on 300 or 400 mg (BID); however, 1 in 4 pts required a dose reduction, most often due to intolerance. Physicians at academic centers were more likely to reduce the NIL dose than those in community practices. DoT with NIL for pts who received a dose reduction was shorter than that for those who did not. These findings will aid clinical decisions on dose optimization and maintaining response, whilst improving the patient quality of life.
QIM19-137: Effect of Socioeconomic Factors on Survival in Veterans With Acute Myeloid Leukemia
Authors: Modhia Falgun Mahendrakumar , Johnston Sarah E. , Zhao Daniel , Mody Ankur , Khalil Mohammad O.
Published: March 2019

Background: There is limited information about socioeconomic factors effect on survival in veterans with acute myeloid leukemia (AML). Few studies published between the 1960s and 1980s suggested higher risks for leukemia mortality among veterans who were smokers. Few studies investigated socioeconomic factors like insurance status, care at private or academic center, marital status, and median household income effect on outcomes. Alcohol use and AML outcomes co-relation is not well studied in literature. Methods: Medical records of AML patients at the Oklahoma City VAHCS between 2010 and 2017 were reviewed. Information collected included home distance from treatment center (≤40 miles vs >40 miles), marital status at diagnosis, tobacco use in the 3 months preceding diagnosis, history of alcohol abuse, level of college education (college education vs less than college education). Fisher-exact test was used for differences in survival rates. Kaplan-Meier analysis was used to estimate the survival and log-rank test to determine differences among groups. Results: Total number of veterans were 28. 15 patients (56%) had poor risk disease, 8 (30%) had intermediate risk disease, and 4 (15%) had good risk disease. Median survival for the whole group was 9.3 months. Patients with poor and intermediate risk cytogenetic/molecular status had median survival of 5.5 and 37.7 months, respectively (P=.0066). There was an insufficient number of deaths in the good risk group at the time of this analysis. Median survival for veterans with history of alcohol use was 66 vs 7 months (P=.15). Median survival for veterans who had some college education vs less than college education was 26.1 vs 6.9 (P=.14). Median survival for veterans with history of tobacco use within 3 months of diagnosis vs others was 6.9 vs 26.1 (P=.11). Median survival for veterans who were married at diagnosis vs non-married was 14 vs 7.89 (P=.29). Median survival for veterans who lived >40 miles from treatment center vs ≤40 miles was 7.43 vs 37.7 months (P=.5). Conclusions: In our retrospective single institute study, poor risk cytogenetic/molecular risk group was associated with inferior survival. While there appeared to be a trend towards worse survival in association with lower education, smoking, non-married status, and longer distance from treatment center, none of these factors had a statistically significant effect. Larger studies are needed to confirm such observations.
HSR19-108: A Meta-Analysis of Randomized Controlled Trials (RCTs) for Efficacy and Safety of Vascular Endothelial Growth Factor Tyrosine Kinase Inhibitors (VEGF-TKIs) Adjuvant Therapy in High-Risk Renal Cell Cancer (RCC)
Authors: Riaz Irbaz Bin , Malik Saad Ullah , Husnain Muhammad , Ain Riaz Sipra Qurat Ul , Faridi Warda , Gondal Farva R. , Ho Thanh , Yadav Siddhartha , Wang Zhen , Kohli Manish
Published: March 2019

Background: Four large RCTs (ASSURE, S-TARC, PROTECT, ATLAS) tested adjuvant VEGF-TKI therapy in high risk RCC. The results were variable for efficacy and there were concerns for increased toxicity and decline in quality of life (QoL). We performed an updated meta-analysis including results of ATLAS trial to asses a risk-benefit for adjuvant post-operative treatments in high risk RCC patients by assessing reported disease-free survival (DFS), overall survival (OS), and toxicity endpoints. Methods: Literature search was done using Medline, CENTRAL, and Embase. The DerSimonian and Laird random effects model was used to pool estimates for DFS, OS, and common side effects across the 4 trials. A subgroup analysis was performed for sunitinib alone because of its FDA approval. Heterogeneity was assessed with Cochrane Q statistic and was quantified with I2 test. Risk for bias was assessed using the Cochrane Collaboration’s tool. Results: The 4 RCTs included 4,820 patients. Adjuvant therapy with TKIs yielded no significant improvement in DFS or OS as compared to placebo (DFS HR=0.916; 95% CI, 0.832–1.009 and OS HR=1.09; 95% CI, 0.886–1.150). Separate analysis of DFS in sunitinib vs placebo did not show any benefit (2 studies, N=1,909; HR=0.90; 95% CI, 0.67–1.19). Use of TKIs was associated with significantly increased risk of drug toxicity. Increased risk of grade 3 or 4 adverse events (RR=5.110; 95% CI, 3.765–6.935), diarrhea (RR=10.725; 95% CI, 4.672–24.622), fatigue (RR=3.310; 95% CI, 1.879–5.829), hypertension (RR=4.274; 95% CI, 3.452–5.292) and palmar/plantar dysesthesia (RR=20.53; 95% CI, 9.006–46.801) was observed. There was no statistically significant heterogeneity amongst included trials. QoL endpoints were inconsistently reported. Risk of bias was low. Conclusions: This pooled analysis provides further evidence that there is no OS or DFS benefit associated with adjuvant TKI treatment. There was a significantly increased risk of grade 3 or 4 toxicity in greater than half of the patient population leading to decline in QoL during TKI therapy. Carefully selected very high-risk patients who can tolerate these agents without dose modifications may benefit from adjuvant TKI approach.
A vida sexual sob prova: impactos da vida profissional na construção da experiência sexual
Authors: Policarpo Verónica
Published: March 2019

De que forma a vida sexual dos portugueses é afetada pela vida profissional? Este artigo tenta responder a esta questão a partir de 35 biografias sexuais, recolhidas numa pesquisa mais alargada sobre sexualidade na sociedade portuguesa. Partindo dos conceitos de experiência sexual e prova social, tenta-se compreender como os indivíduos articulam o que lhes acontece nestas duas esferas da vida (profissional e sexual), construindo a sua experiência a partir de três lógicas de ação: integração, estratégia e subjetivação. Os resultados apontam para a diversidade de modalidades de construção da experiência, visível em três plataformas: as relações entre a agenda profissional e a agenda sexual; a gestão da informação, em ambiente profissional, a respeito de experiências fora da heteronorma; e os impactos na vida sexual da mobilidade geográfica decorrente da vida profissional. O sujeito sexual constrói-se assim na tensão entre a adesão a papéis familiares, profissionais e sexuais; na gestão de recursos, oportunidades e estratégias nestes campos da vida; e no maior ou menor distanciamento reflexivo em relação aos mesmos, conquistando para si um espaço emancipatório de identidade.
The relationship between serum uric acid within the normal range and β-cell function in Chinese patients with type 2 diabetes: differences by body mass index and gender
Authors: Zhong Xing , Zhang Deyuan , Yang Lina , Du Yijun , Pan Tianrong
Published: March 2019

Background

Elevated serum uric acid (SUA) has a positive correlation with insulin secretion and insulin resistance indexes. However, whether weight- and gender-specific differences regarding the relationship between SUA within the normal range and β-cell function and insulin resistance exist is unknown in type 2 diabetes mellitus (T2DM) patients.

Methods

A total of 380 patients with type 2 diabetes were divided into two groups as overweight/obesity (n = 268) and normal weight (n = 112). Each group were again divided into low (LSUA) and high normal SUA (HSUA). The HbA1c, C-peptide, SUA, creatinine, and lipids profiles were measured. HOMA2IR and HOMA%2B were estimated using fasting glucose and C-peptide by homeostasis model assessment (HOMA). Pearson’s correlations and multiple linear regression analyses were conducted to assess the associations between SUA levels and islet function indexes.

Results

In overweight/obesity subgroup, the levels of body mass index, fasting C-peptide (FCP), P2hCP, fasting CPI (FCPI), postprandial CPI (PPCPI), ΔC-peptide, HOMA2%B, and HOMA2IR were higher in HSUA group than in LSUA group. In contrast, the HbA1c, FBS, and P2hBS were lower in HSUA than in LSUA. In normal weight subgroup, there were no differences between the HSUA than LSUA group in terms of clinical characteristics. Pearson’s correlations indicated that there were no significant correlations between SUA and insulin secretory capacity in normal weight group, but in overweight/obesity group, SUA had positive significant correlations with P2hCP, FCPI, PPCPI, ΔC-peptide, and HOMA2%B. In the female group, there were no significant correlations between SUA and insulin secretory capacity. However, in the male group, SUA had positive significant correlations with insulin secretory capacity include P2hCP, FCPI, PPCPI, ΔC-peptide, and HOMA2%B. Multiple linear regression showed that SUA was significantly associated with HOMA2%B, but not with HOMA2IR in overweight/obesity and male group.

Conclusions

Our study shows that SUA levels within normal range were associated with β-cell function in T2DM patients with overweight/obesity or male. This finding supports that the association between SUA within normal range and insulin secretion ability differs by weight and sex.
A dimensão política da economia solidária no ambiente rural: uma análise comparativa das categorias sociais de agricultores familiares e assentados da reforma agrária
Authors: Nascimento Diego , Oliveira Eziel , Benini Elcio Gustavo , Mello Gabriel Sgrignoli , Figueiredo Neto Leonardo , Teixeira Wladimir
Published: March 2019

Este trabalho teve como objeto de estudo a dimensão política da economia solidária, na singularidade do ambiente rural brasileiro. Seu objetivo principal foi a análise comparativa da participação política dos empreendimentos solidários rurais classificados em agricultores familiares e assentados da reforma agrária. Especificamente, investigou as formas de organização econômica e a participação política daqueles empreendimentos, pari passu com suas motivações e conquistas em organizações solidárias. A pesquisa foi realizada com base nos microdados do Sistema de Informação em Economia Solidária (SIES), consolidados pela Secretaria Nacional de Economia Solidária (SENAES) do Ministério do Trabalho (MTE), o que compreendeu uma população de 19.708 organizações mapeadas. Para exploração, organização e análise dos dados, foram utilizadas as probabilidades condicionais dos grupos selecionados, tendo como condicionalidade principal a participação em movimentos sociais, políticos ou sindicais. De acordo com os resultados obtidos, não obstante os grupos comparados tenham características organizativas similares, a participação política dos assentados da reforma agrária demonstrou-se mais significativa em relação às organizações de agricultores familiares, apresentando-se, ainda, como uma variável condicional explicativa no que se refere às principais conquistas dos empreendimentos solidários.
Dry Matter Yield and Quality of Two Temperate and Two Tropical Forage Legume Hays Harvested at Early-Flowering in Jos, Nigeria
Authors: Akpensuen T. T. , Amodu J. T. , Tanko R. J. , Luka J. S. , Namo O. A. T. , Hassan M. R.
Published: March 2019

The study was designed to evaluate the dry matter yield and quality of two temperate (T. Pratense and T. repens) and two tropical forage legumes (S. guianensis and C.molle) harvested at early-flowering stage for hay in a cool tropical environment of Vom, Jos, Plateau State, Nigeria. The legumes were planted in the month of June, 2015 and 2016 in a 4 x 4 Latin Square Design with four replicates in plots measuring 5 m x 3 m. The forages were harvested at early-flowering stage for yield components, dry matter yield and nutrient quality evaluation.

The result showed that C. molle was significantly (P<0.01) higher in height in the two seasons compared to the other legumes. Number of leaves per plant was higher (P<0.01) significantly in S. guianensis (125.00) in 2015 whereas, T. repens had higher (P<0.01) value (187.25) in 2016 cropping season.  Stylosanthes guianensis produced significantly (P<0.01) higher dry matter with 10.42 t ha-1 in 2015, while the dry matter yield obtained from C. molle (2.90 t ha-1) was the highest in 2016. Trifolium pratense and T. repens were scored excellent grade, while Stylosanthes guianensis and Centrosema molle were scored good in quality. Crude protein content was significantly (P<0.01) higher in T. repens (18.38%) compared to T. pratense (16.50 %), whereas S. guianensis produced the least value of 13.83%. The crude fibre content of the of the forage materials on the other hand was significantly higher (P<0.0I) in S. guianensis (37.29 %) compared to the other forage legumes.

The temperate forage legumes in this trial were higher in nutrient content, but lower in dry matter yield. Therefore, the forage crops may serve as better supplementary feeds for livestock feeding especially during the dry season.
An in vivo protease activity assay for investigating the functions of the Escherichia coli membrane protease HtpX
Authors: Yoshitani Kohei , Hizukuri Yohei , Akiyama Yoshinori
Published: March 2019

Escherichia coli HtpX is an M48 family zinc metalloproteinase located in the cytoplasmic membrane. Previous studies suggested that it is involved in the quality control of membrane proteins. However, its in vivo proteolytic function has not been characterized in detail, mainly because the physiological substrates have not been identified and no model substrate that allows sensitive detection of the protease activity is available. We constructed a new model substrate of HtpX and established an in vivo semiquantitative and convenient protease activity assay system for HtpX. This system enables detection of differential protease activities of HtpX mutants carrying mutations in conserved regions. This system would also be useful for investigating the functions of HtpX and its homologs in other bacteria.
PADDAS syndrome associated with hair dysplasia caused by a de novo missense variant of PUM1
Authors: Bonnemason‐Carrere Paul , Morice‐Picard Fanny , Pennamen Perrine , Arveiler Benoit , Fergelot Patricia , Goizet Cyril , Hellegouarch Mélanie , Lacombe Didier , Plaisant Claudio , Raclet Virginie , Rooryck Caroline , Lasseaux Eulalie , Trimouille Aurélien
Published: March 2019

PUM1 has been very recently reported as responsible for a new form of developmental disorder named PADDAS syndrome. We describe here an additional patient with early onset developmental delay, epilepsy, microcephaly, and hair dysplasia, with a de novo heterozygous missense variant of PUM1: c.3439C > T, p.(Arg1147Trp). This variant was absent from databases and predicted deleterious by multiple softwares. The same missense variant has been reported by Gennarino et al., in a girl with much more severe epilepsy. Our report is in favor of a variable expressivity of PADDAS syndrome, and broadens the phenotypic spectrum with the description of hair dysplasia.
Experience of chromosomal microarray applied in prenatal and postnatal settings in Hong Kong
Authors: Cheng Shirley S. W. , Chan Kelvin Y. K. , Leung Kelphen K. P. , Au Patrick K. C. , Tam Wai‐Keung , Li Samuel K. M. , Luk Ho‐Ming , Kan Anita S. Y. , Chung Brian H. Y. , Lo Ivan F. M. , Tang Mary H. Y.
Published: March 2019

Chromosomal microarray (CMA) is recommended as a first tier investigation for patients with developmental delay (DD), intellectual disability (ID), autistic spectrum disorder (ASD), and multiple congenital anomalies (MCA). It is widely used in the prenatal and postnatal settings for detection of chromosomal aberrations. This is a retrospective review of all array comparative genomic hybridization (aCGH/ array CGH) findings ascertained in two major prenatal and postnatal genetic diagnostic centers in Hong Kong from June 2012 to December 2017. Medical records were reviewed for cases with pathogenic and variants of uncertain clinical significance (VUS). Classification of copy number variants (CNVs) was based on current knowledge and experience by August 2018. The aims of this review are to study the diagnostic yield of array CGH application in prenatal and postnatal settings in Hong Kong and to describe the spectrum of abnormalities found. Prenatal indications included abnormal ultrasound findings, positive Down syndrome screening, abnormal noninvasive prenatal test results, advanced maternal age and family history of chromosomal or genetic abnormalities. Postnatal indications included unexplained DD, ID, ASD, and MCA.

A total of 1,261 prenatal subjects and 3,096 postnatal patients were reviewed. The prenatal diagnostic yield of pathogenic CNV and VUS (excluding those detectable by karyotype) was 3.5%. The postnatal diagnostic yield of pathogenic CNV was 15.2%. The detection rates for well‐defined microdeletion and microduplication syndromes were 4.6% in prenatal and 6.1% (1 in 16 index patients) in postnatal cases, respectively. Chromosomes 15, 16, and 22 accounted for over 21 and 25% of pathogenic CNVs detected in prenatal and postnatal cohorts, respectively. This review provides the first large scale overview of genomic imbalance of mostly Chinese patients in prenatal and postnatal settings.
Broadband Reflection in Polymer‐Stabilized Cholesteric Liquid Crystals via Thiol–Acrylate Chemistry
Authors: Hu Wei , Chen Mei , Wang Qian , Zhang Lanying , Yuan Xiaotao , Chen Feiwu , Yang Huai
Published: March 2019

Thiols are prone to react with a multitude of various functional groups in high yields, which has been widely used for surface‐ and particle‐patterning, bioorganic synthesis, polymer modification, imprint nanolithography, the fabrication of optical components, hydrogel synthesis, and the curing of hard protective coatings. In this work, a chiral thiol with a high helical twisting power was synthesized through a novel synthetic route with high selectivity, yield, and cost‐effectiveness. It was then used to fabricate a liquid‐crystal composite film with ultra‐wide broadband reflection via thiol click chemistry. Cholesteric liquid‐crystal materials with broadband reflection have many potential applications for broadband polarizers, polarizer‐free displays, organic optical data storage media, smart switchable reflective windows, and continuous waveband laser protection.
Ultra‐Tough Inverse Artificial Nacre Based on Epoxy‐Graphene by Freeze‐Casting
Authors: Huang Chuanjin , Peng Jingsong , Wan Sijie , Du Yi , Dou Shixue , Wagner Hanoch Daniel , Tomsia Antoni P. , Jiang Lei , Cheng Qunfeng
Published: March 2019

Epoxy nanocomposites combining high toughness with advantageous functional properties are needed in many fields. However, fabricating high‐performance homogeneous epoxy nanocomposites with traditional methods remains a great challenge. Nacre with outstanding fracture toughness presents an ideal blueprint for the development of future epoxy nanocomposites. Now, high‐performance epoxy‐graphene layered nanocomposites were demonstrated with ultrahigh toughness and temperature‐sensing properties. These nanocomposites are composed of ca. 99 wt % organic epoxy, which is in contrast to the composition of natural nacre (ca. 96 wt % inorganic aragonite). These nanocomposites are named an inverse artificial nacre. The fracture toughness reaches about 4.2 times higher than that of pure epoxy. The electrical resistance is temperature‐sensitive and stable under various humidity conditions. This strategy opens an avenue for fabricating high‐performance epoxy nanocomposites with functional properties.
Synthesis, characterization, and electrical properties of polypyrrole–bimetallic oxide composites
Authors: Khan Hamayun , Malook Khan , Shah Mutabar
Published: March 2019

In this study, polypyrrole (PPy) and its bimetallic oxide composites (PPy–V2O5–MnO2) were synthesized via a modified chemical oxidation polymerization method in the aqueous medium with FeCl3·6H2O as an oxidant. The synthesized materials were characterized with various analytical techniques to investigate their structural, crystallographic, thermal, morphological, optical, and electrical properties. The Fourier transform infrared study confirmed the successful synthesis of the materials, whereas the X‐ray diffraction analyses showed the amorphous and crystalline natures of the PPy and PPy–V2O5–MnO2composites, respectively. The bimetallic oxide content improved the thermal stability of the composites, as ratified by thermal analysis. The synthesized PPy had a globular and spongy nature, whereas the composites were mixtures of short and long rod‐shaped particles. The bimetallic oxide blend enhanced the doping, surface area and semiconducting nature of composites, and lower electrical resistance compared with those of the PPy. The resistance of the synthesized materials depended on the V2O5–MnO2blend content in the composites and the temperature. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2020,137, 47680.
Polyvinylpyrrolidone electrospun nanofibers doped with Eu3+: Fabrication, characterization, and application in gas sensors
Authors: Terra Idelma A. A. , Sanfelice Rafaela C. , Scagion Vanessa P. , Tomazio Nathalia B. , Mendonça Cleber R. , Nunes Luiz A. O. , Correa Daniel S.
Published: March 2019

Polymer nanofibers (NFs)‐based optical sensors hold great potential to fabricate low‐cost devices capable to monitor different volatile organic compounds (VOCs) related to healthcare and environmental conditions. For instance, ammonia detection is a subject of paramount importance, owing to the serious health problems associated to the exposition to this volatile. In this context, here, we report on the development of optical electrospun NFs composed of polyvinylpyrrolidone (PVP) doped with Europium (Eu3+) aiming at the detection of ammonia. The fabricated NFs were characterized by scanning electron microscopy, transmission electron microscopy, energy‐dispersive X‐ray spectroscopy, fluorescence microscopy, photoluminescence, and excited state lifetime spectroscopies. The luminescence properties changes were evaluated by exposing the PVP_Eu3+ NFs to ammonia and other distinct interfering VOCs including toluene, tetrahydrofuran, acetone, triethylamine, acetic acid, and chloroform. The sensor exhibited a linear response to ammonia exposition in the concentration range from 0 to 50 ppm, yielding a detection limit of 4.7 ppm. Our results indicate the potential application of PVP_Eu3+ electrospun NFs in optical sensors for ammonia detection at room temperature based on luminescence quenching. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47775.
How does Donor Dissection Influence Medical Students' Perceptions of Ethics? A Cross‐Sectional and Longitudinal Qualitative Study
Authors: Stephens Georgina C. , Rees Charlotte E. , Lazarus Michelle D.
Published: March 2019

The contribution of donor dissection to modern anatomy pedagogy remains debated. While short‐term anatomy knowledge gains from dissection are questionable, studies suggest that donor dissection may have other impacts on students including influencing medical students' professional development, though evidence for such is limited. To improve the understanding of how anatomy education influences medical student professional development, the cross‐sectional and longitudinal impacts of donor dissection on medical students' perceptions of ethics were explored. A cross‐sectional and longitudinal qualitative study was undertaken at an Australian university where student responses to online discussion forums and in‐person interviews were analyzed. Data were collected across the 1.5 years that undergraduate medical students received anatomy instruction (three semesters during first and second years). A total of 207 students participated in the online discussion forums, yielding 51,024 words; 24 students participated in at least 1 of 11 interviews, yielding over 11 hours of interview data. Framework analysis identified five themes related to ethics in an anatomical education context: (1) Dignity, (2) Beneficence, (3) Consent, (4) Justification for versus the necessity of dissection, and (5) Dichotomy of objectification and personification. The dominant themes of students' ethical perceptions changed with time, with a shift from focusing on donors as people, toward the utility of donors in anatomy education. Additionally, themes varied by student demographics including gender, ancestry, and religiosity. Together this study suggests a strong impact of donor dissection on priming students' focus on medical ethics and provides further advocacy for formal and purposeful integration of medical ethics with anatomy education.