tbuckley/cabot-search huggingface dataset:
Cardiovascular risk profile in Olympic athletes: an unexpected and underestimated risk scenario
Authors: Flavio D’Ascenzi, Stefano Caselli, Federico Alvino, Barbara Digiacinto, Erika Lemme, Massimo Piepoli, Antonio Pelliccia
Journal: British Journal of Sports Medicine (2018)

Background Prevalence of cardiovascular (CV) risk factors has been poorly explored in subjects regularly engaged in high-intensity exercise programmes. Our aim was, therefore, to assess the prevalence and distribution of CV risk factors in a large population of competitive athletes, to derive the characteristics of athlete’s lifestyle associated with the best CV profile. Methods 1058 Olympic athletes (656 males, 402 females), consecutively evaluated in the period 2014–2016, represent the study population. Prevalence and distribution of CV risk factors was assessed, in relation to age, body size and sport. Findings Dyslipidemia was the most common risk (32%), followed by increased waist circumference (25%), positive family history (18%), smoking habit (8%), hypertension (3.8%) and hyperglycaemia (0.3%). Large subset of athletes (418, 40%) had none or 1 (414, 39%) risk factor, while only a few (39, 3.7%) had 3/4 CV risk factors. The group without risks largely comprised endurance athletes (34%). Ageing was associated with higher total and low-density lipoprotein cholesterol, triglycerides (p&lt;0.001) and glycaemia (p=0.002) and lower high-density lipoprotein cholesterol. On multivariate logistic regression analysis, age, BMI and body fat were identified as independent predictors of increased CV risk. Interpretation Dyslipidemia and increased waist circumference are common in elite athletes (32% and 25%, respectively). A large proportion (40%) of athletes, mostly endurance, are totally free from risk factors. Only a minority (3%) presents a high CV risk, largely expression of lifestyle and related to modifiable CV risk factors.
A phase 1 study of ALX148, a CD47 blocker, alone and in combination with established anticancer antibodies in patients with advanced malignancy and non-Hodgkin lymphoma.
Authors: Nehal J. Lakhani, Patricia LoRusso, Navid Hafez, Anuradha Krishnamurthy, Timothy J. O'Rourke, Manali K. Kamdar, Philip Fanning, Yonggang Zhao, Feng Jin, Hong Wan, Jaume Pons, Sophia Randolph, Wells A. Messersmith
Journal: Journal of Clinical Oncology (2018)

3068 Background: CD47, a marker of self, is a myeloid checkpoint that is upregulated by tumor cells to evade the host's immune response. ALX148 is a fusion protein comprised of an engineered high affinity CD47 binding domain of SIRPα genetically linked to an inactive Fc region of human immunoglobulin. We have previously shown ALX148 blocks CD47 and safely enhances the activity of targeted anticancer antibodies and checkpoint inhibitors through Fc dependent and independent mechanisms in nonclinical models (ASH 2017 #112). Methods: As of Feb 07, 2018, 30 patients (pts) were enrolled to escalating dose cohorts of ALX148 (0.3 mg/kg [mpk] IV every week [QW] - 30 mpk every other week [QoW]) as a single agent (Part 1) or in combination with standard regimens of pembrolizumab (P), trastuzumab (T), or rituximab (R) (Part2). The primary endpoint for each Part is first cycle dose limiting toxicity (DLT). Tumor response, pharmacokinetics (PK), and CD47 target occupancy (TO) are also characterized. Results: Part 1 results are summarized. 25 pts received single agent ALX148. 22 pts experienced any AE. Maximum CTCAE treatment related AEs that occurred in > 1 pt were Dizziness 2G1; Fatigue 3G1; Headache 4G1; Rash 1G1,1G2; and Thrombocytopenia 2G3. Two pts experienced a DLT (Neutropenia with infection, 3mpk; Thrombocytopenia with significant bleed, 30 mpk). There were 4 pts who reported ≥G3 AE (Infection 1G3, 3mpk; Pancreatitis 1G3, 30 mpk; Thrombocytopenia 1G3, 3 mpk and 1G3, 30 mpk; Neutropenia 1G4, 3mpk) and 1G5 Death (30mpk; etiology being investigated). No single agent MTD was identified, and the maximum administered dose (MAD) was 30 mpk QoW. Four pts achieved stable disease including 1 pt with NSCLC who had a 15% tumor reduction. ALX148 demonstrated linear PK at doses ≥ 10 mpk QW and full TO at doses ≥ 3 mpk QW. To date, 5 Part 2 pts received ALX148 (10 mpk QW) in combination (3 with P; 1 with T; 1 with R). Conclusions: ALX148 is generally well tolerated in pts with advanced tumors with favorable PK/TO characteristics at doses evaluated. The MAD of single agent ALX148 is 30 mpk QoW. Accrual to the Part 2 combination cohorts is ongoing. Clinical trial information: NCT03013218.
Abstract MP052: Neither Insulin Secretion nor Genotype Pattern Modify 12-Month Weight Loss Effects of Healthy Low-Fat vs. Healthy Low-Carbohydrate Diets Among Adults with Obesity
Authors: Christopher D Gardner, Michelle Hauser, Liana Del Gobbo, John Trepanowski, Joseph Rigdon, John Ioannidis, Abby King, Manisha Desai
Journal: Circulation (2017)

Background: Dietary modification remains an essential component of successful weight loss strategies. No one dietary strategy has been determined to be superior to others for the general population. Studies that contrast reducing dietary fat vs. carbohydrate report consistently high within-group variability in dietary adherence and weight loss. Previous research by our group and others suggest that insulin-glucose dynamics or genotype patterns may modify diet effects. Objective: To determine if within-group weight loss variability on a Healthy Low-Fat (HLF) vs. a Healthy Low Carbohydrate (HLC) diet can be attributed to underlying factors such as insulin-glucose dynamics (i.e., insulin resistance and secretion) or genotype pattern. We hypothesized the above factors would be effect modifiers of HLF and HLC diets on 12-month weight loss. Methods: Generally healthy, non-diabetic adults, 18-50 years, BMI 28-40 kg/m 2 , were randomized to HLF or HLC with no specific prescribed energy restriction for 12 months (n=609). Health educators delivered the intervention in 22 1-hr group classes. Data were collected at 0, 3, 6, &amp; 12 months. Dietary intake was assessed by three 24-hour recalls/time point. Clinical data includes: 75-g glucose oral glucose tolerance tests (insulin concentration at 30 minutes [Ins-30], a measure of insulin secretion), genotyping (3-SNP multilocus genotype: Low-Fat Genotype vs. Low-Carb Genotype, UK Biobank Axiom® array), body composition (DXA), resting energy expenditure (indirect calorimetry), epigenetics, proteomics, subcutaneous adipose tissue, microbiota, and standard CVD risk indicators. Results: At 12 months participants collectively lost 6,559 lbs. Retention was 79%, with equal dropout between arms. Range of weight change in both diet arms was ~80 lbs (-60 to +20 lbs). Macronutrient distribution at 12 months was 48% vs. 30% carbohydrate, 29% vs. 45% fat, and 21% vs. 23% protein for HLF and HLC, respectively. Both groups reported achieving and maintaining an average ~500 kcal deficit relative to baseline. Weight loss was similar for HLF vs. HLC: -12.1 ± 1.1 lbs vs. -13.8 ± 1.0 lbs, mean ± SEM. Neither Ins-30 (p for interaction = 0.84) nor genotype pattern (p for interaction = 0.20) modified the effect of diet on 12-month weight loss. Conclusions: Despite substantial weight loss, high within-group variability, and strong dietary differentiation between groups, neither baseline Ins-30 nor genotype pattern modified the effect of diet on 12-month weight loss. Focus on a healthy diet in both diet arms is novel in the context of many previous Low-Fat vs. Low-Carb studies and may have diminished expected effect modification. The extensive data set collected will be used to explore this and other potential explanatory factors.
Using a multi-disciplinary process-mapping approach for care plan program design.
Authors: Meredith Jones
Journal: Journal of Clinical Oncology (2017)

e18203 Background: The Center for Medicare and Medicaid Innovation has challenged oncology practices to engage in practice transformation activities through participation in the Oncology Care Model (OCM). One difficult requirement of OCM is the creation of care plans inclusive of the 13 IOM components. Though OCM does not require that care plans be given to patients, true practice transformation exists not only with care plan creation, but with delivery and education to patients and caregivers. Many challenges to care plan implementation exist, starting with the lack of staff dedicated to the care planning process. Methods: Two multi-disciplinary teams representing the Medical Oncology Clinic were formed to simulate and process-map current workflow, incorporating care plan generation and delivery. First, teams process-mapped current workflows utilizing existing staff to establish a baseline. Second, teams added care planning to the baseline and determined whether existing or new staff would be needed to accomplish the OCM care plan requirements. Both teams received the same 6 care planning steps: 1. Enter patient demographics into software, 2. Give patient survey, 3. Enter clinical information in software, 4. Generate plan, 5. Print/deliver plan, and 6. Scan into EMR. Results: Both teams completed process mapping with minimal variation at baseline. However, the teams disagreed on responsible staff for each care planning step. Both teams agreed, though, that 4 out of 6 steps must be completed by RNs, NPs or Physicians. Both teams also indicated that current RN staffing levels would not accommodate capacity to add care planning responsibilities to existing positions, due to the time-consuming nature of the care planning process. Conclusions: Multi-Disciplinary teams recommended addition of RN Care Coordinator positions to oversee the care planning process. Successful implementation requires hiring adequate numbers of RN Care Coordinators that, with a reasonable caseload each, will manage the process, track patients and evaluate outcomes. Future opportunities exist to research the impact that the addition of both care plan delivery and RN Care Coordinators have on patient satisfaction and outcomes.
The Application of Biomaterials to Tissue Engineering Neural Retina and Retinal Pigment Epithelium
Authors: Nicola C. Hunt, Dean Hallam, Valeria Chichagova, David H. Steel, Majlinda Lako
Journal: Advanced Healthcare Materials (2018)

Abstract The prevalence of degenerative retinal disease is ever increasing as life expectancy rises globally. The human retina fails to regenerate and the use of human embryonic stem cells (hESCs) and human‐induced pluripotent stem cells (hiPSCs) to engineer retinal tissue is of particular interest due to the limited availability of suitable allogeneic or autologous tissue. Retinal tissue and its development are well characterized, which have resulted in robust assays to assess the development of tissue‐engineered retina. Retinal tissue can be generated in vitro from hESCs and hiPSCs without biomaterial scaffolds, but despite advancements, protocols remain slow, expensive, and fail to result in mature functional tissue. Several recent studies have demonstrated the potential of biomaterial scaffolds to enhance generation of hESC/hiPSC‐derived retinal tissue, including synthetic polymers, silk, alginate, hyaluronic acid, and extracellular matrix molecules. This review outlines the advances that have been made toward tissue‐engineered neural retina and retinal pigment epithelium (RPE) for clinical application in recent years, including the success of clinical trials involving transplantation of cells and tissue to promote retinal repair; and the evidence from in vitro and animal studies that biomaterials can enhance development and integration of retinal tissue.
The role of adiposity in the association between type 2 diabetes and the risk of breast cancer.
Authors: Maria Bota, Philippe Autier, Peter Boyle
Journal: Journal of Clinical Oncology (2018)

1573 Background: Studies have shown an increased risk of breast cancer (BC) among women with type 2 diabetes (T2D). This association could be causal, related to hyperglycaemia or hyperinsulinaemia, or could be triggered by other factors such as obesity and physical inactivity which are known risk factors for T2D and for BC in post-menopausal women. Methods: A meta-analysis was performed to assess the risk of BC in T2D patients compared to non-diabetic women, with special attention to changes in the risk of BC when the body mass index (BMI) was included in multivariate analyses. Studies were selected if they had a prospective design. Studies that compared BC incidence in T2D women to the incidence in the general population were excluded. Summary relative risks (SRR) and 95% confidence intervals (CI) were computed using random-effects models. Results: Eighteen studies were included in the meta-analysis, based on 28,230,143 person-years of follow-up and 320,111 BC cases. Compared to non-diabetic women, the SRR of BC among T2D women was 1.13 (95% CI: 1.04, 1.24). There was a large amount of unexplained heterogeneity of results across studies (I² = 95%), but no indication of publication bias. Three studies reported the risk of BC by BMI category, with a consistently higher risk of BC associated with increasing BMI. In the 9 studies that adjusted for adiposity, the SRR decreased to 1.05 (95% CI: 0.97, 1.14) while the heterogeneity of results across studies reduced to I² = 21%. Only two studies reported data by menopausal status. In contrast, in the 9 studies that did not adjust for adiposity, the SRR increased to SRR = 1.19 (95% CI: 1.01, 1.39), while the heterogeneity remained high (I² = 98%). Five studies reported data for post-menopausal women only, with a SRR of 1.13 (95% CI: 0.89; 1.44) and high heterogeneity (I² = 94%) with one study representing 82% of the weight in the meta-analysis. Conclusions: This analysis provides evidence for a moderately increased risk of BC in T2D women. The effect of the adjustment for BMI on the SRR and on the heterogeneity suggests that the higher risk of BC among women with T2D may not be due to the diabetes itself but to adiposity. New studies should examine the relationship between BC, T2D and adiposity in premenopausal women.
A retrospective cohort study of PD-L1 expression in recurrent and/or metastatic squamous cell carcinoma of the head and neck (SUPREME-HN).
Authors: Sara I. Pai, Ezra Cohen, Derrick Lin, George Fountzilas, Edward S. Kim, Holger Mehlhorn, Neus Baste, Daniel Clayburgh, Loren Lipworth, Carlo Resteghini, Nawar Shara, Takashi Fujii, Jun Zhang, Michael Stokes, David Lawrence, Asud Khaliq, Giovanni Melillo, Norah Shire
Journal: Journal of Clinical Oncology (2017)

6040 Background: Patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) have a poor prognosis. Targeting the PD-1/PD-L1 axis has resulted in clinically meaningful antitumor activity and improved overall survival (OS) in R/M HNSCC patients. Tumoral PD-L1 expression correlates with response to blocking PD-1/PD-L1 antibodies. We investigated the prognostic value of PD-L1 expression in R/M HNSCC patients. Methods: Archival tumor samples from R/M HNSCC patients diagnosed between March 2011 and June 2015 at 12 institutions in 6 countries were stained for PD-L1 and clinic-demographic data were abstracted from medical records. Tumoral PD-L1 protein expression was assessed with the validated Ventana SP263 assay and scored as high (≥25% of tumor cells [TC]) or low/negative ( &lt; 25% of TC). Extracted data included demographic and tumor characteristics, treatment patterns, and clinical outcomes. Descriptive analyses were conducted and survival estimated by the Kaplan-Meier method. OS was defined from the diagnosis index date of R/M disease to time of death. Results: As ofSeptember 26, 2016 (interim analysis), data were available for 143 patients of whom 138 were eligible for analysis. Median age was 62.0 years (range, 28.0−88.0), 76.8% were male, and 84.0% were white. PD-L1 protein expression was high in 43 patients (31.2%), low/negative in 91 (65.9%), and unknown in 4 (2.9%). Median OS (8.2 vs. 8.8 months; P = 0.94) and progression-free survival (PFS) from the start of first-line (6.0 vs. 5.6 months; P = 0.29) or second-line therapy (7.1 vs. 1.8 months; P = 0.11) did not significantly differ between PD-L1 high and low/negative patients, respectively. There were no significant differences in OS based on PD-L1 status within subgroups defined by age, race, tobacco or alcohol use, primary tumor site, performance status, metastatic disease at diagnosis, or treatment with platinum-based chemotherapy. Conclusions: Interim analyses indicate that PD-L1 status is not associated with OS or PFS in R/M HNSCC patients.
Aphthous ulcer drug inhibits prostate tumor metastasis by targeting IKKɛ/TBK1/NF-κB signaling
Authors: Chaping Cheng, Zhongzhong Ji, Yaru Sheng, Jinming Wang, Yujiao Sun, Huifang Zhao, Xiaoxia Li, Xue Wang, Yuman He, Jufang Yao, Li Wang, Chenlu Zhang, Yanjing Guo, Jianming Zhang, Wei-Qiang Gao, Helen He Zhu
Journal: Theranostics (2018)

Tumor metastasis is the major cause of death for prostate cancer (PCa) patients. However, the treatment options for metastatic PCa are very limited. Epithelial-mesenchymal transition (EMT) has been reported to be an indispensable step for tumor metastasis and is suggested to associate with acquisition of cancer stem cell (CSC) attributes. We propose that small-molecule compounds that can reverse EMT or induce mesenchymal-epithelial transition (MET) of PCa cells may serve as drug candidates for anti-metastasis therapy. Methods: The promoters of CDH1 and VIM genes were sub-cloned to drive the expression of firefly and renilla luciferase reporter in a lentiviral vector. Mesenchymal-like PCa cells were infected with the luciferase reporter lentivirus and subjected to drug screening from a 1274 approved small-molecule drug library for the identification of agents to reverse EMT. The dosage-dependent effect of candidate compounds was confirmed by luciferase reporter assay and immunoblotting. Wound-healing assay, sphere formation, transwell migration assay, and in vivo intracardiac and orthotopic tumor xenograft experiments were used to evaluate the mobility, metastasis and tumor initiating capacity of PCa cells upon treatment. Possible downstream signaling pathways affected by the candidate compound treatment were analyzed by RNA sequencing and immunoblotting. Results: Drug screening identified Amlexanox, a drug used for recurrent aphthous ulcers, as a strong agent to reverse EMT. Amlexanox induced significant suppression of cell mobility, invasion, serial sphere formation and in vivo metastasis and tumor initiating capacity of PCa cells. Amlexanox treatment led to downregulation of the IKK-ɛ/ TBK1/ NF-κB signaling pathway. The effect of Amlexanox on EMT reversion and cell mobility inhibition can be mimicked by other IKK-ɛ/TBK1 inhibitors and rescued by reconstitution of dominant active NF-κB. Conclusions: Amlexanox can sufficiently suppress PCa metastasis by reversing EMT through downregulating the IKK-ɛ/TBK1/NF-κB signaling axis.
Reviewing the pattern of care and treatment effectiveness for glioblastomas, a university affiliated community hospital experience.
Authors: Steven Jubelirer, Adrian Renaldi, Amy Wells, Christine A. Welch, Muhammad Yasin
Journal: Journal of Clinical Oncology (2018)

e18866 Background: Glioblastoma multiforme (GBM) is the most common and deadliest form of brain tumors in adults; hence, its treatment has been challenging for clinicians and long-term survival rate has been unsatisfactory. This study sought to determine the additive benefit of Temozolomide in survival of GBM patients at a community based teaching hospital. Methods: Data were obtained from the hospital cancer registry and additional information was collected from patient charts between the years 1994 and 2015. Patients over the age of 18, with documented pathologic diagnosis of GBM, and had tumor resection surgery were included in the study population. Results: The mean age was 62.6 year (range 22-88) for the 329 subjects. Males represented 55.6% of the study population, and 97.3 were Caucasian. Univariate, analysis revealed that those given Temozolomide had a median survival of 19.4 ± 1.9 months, while those who did not received Temozolomide had a median survival of 10.2 ± 1 months (p < .0001). Multivariate analysis showed that those that did not receive Temozolomide were 1.4 times (CI: 1.1-1.9; p < .02), those ≥ 60 years of age were 2.0 times (CI: 1.4-2.6: p < .0001), and those having diabetes were 1.6 times (CI: 1.6- 2.3; p < .01), more likely to be deceased in three years. Conclusions: In this investigation, Temozolomide, age, and diabetes were contributing factors in the survival of GBM patients. This study demonstrates the impact of Temozolomide on the improvement in survival of glioblastoma patients at a large community based teaching hospital.
SP0140 Psychological support and education as the main aspects of systemic lupus erythematosus “my life” programme for patients
Authors: K Nowicka-Sauer, M Koseda-Dragan, M Hebanowski
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The objective of our previous research was to investigate the main problems, needs and emotional state of patients with SLE. We found that the sensation of limited knowledge of the disease, mood disturbances, depression, anxiety, pain and fatigue are the most common problems of our patients. As we know, the psychological wellbeing and the attitude towards the disease are important factors influence individuals’ lives. In connexion with it we tried to create the programme which would help our patients to understand their illness, to improve their “living with lupus” and to find the more effective and satisfying way of coping with SLE (if needed). In this work we are presenting the main goals of the SLE “MY LIFE” PROGRAMME including medical and possible psychological consequences of lupus and methods which we are going to use in our programme. <h3>Objectives of the SLE “My Life” programme</h3> The most important aims are: to increase knowledge about the disease to reduce anxiety to improve self-care and self-management to “wake up” an activity and independence to increase psychological self-awareness to give support to activate family members and/or friends <h3>Methods</h3> “What is lupus?” – “Education meetings” for patients and patients’ family members and/or friends with physician and psychologist “What does lupus mean to me?” – oral sessions: learning self-observation skills referring to: pain fatigue symptoms of the disease and flare symptoms emotions/feelings/thoughts – what do the patients think of e.g. their fears/anger, relatives/relationship, life/future etc. “What can I do?” – “active session”: practising self-observation and self-care results – “My experiences, my success”. “Am I satisfied?” – the evaluation of the programme.The patients’ satisfaction and the effectivity of the programme are going to be evaluated.