tbuckley/cabot-search huggingface dataset:
NOVEL DIRECT AND INDIRECT EFFECTS OF RISK FACTORS FOR EXERCISE ASSOCIATED MUSCLE CRAMPING (EAMC) IN A COHORT OF 41 698 DISTANCE RUNNERS
Authors: Esmè Jordaan, Martin Schwellnus
Journal: British Journal of Sports Medicine (2017)

Background We recently identified novel risk factors for EAMC in distance runners, including age, gender, racing distance, a history of chronic diseases, medication, training and competition load, and running injuries. The relationships between these risk factors for EAMC are over-simplified, and complex path relationships between these risk factors and EAMC have not been investigated. Objective The objective of the analysis was to explore the complex relationships among the risk factors associated with EAMC by means of path analysis, in order to estimate direct as well as indirect path relationships between the risk factors and EAMC. In addition, we sought to explore total effects by aggregating the direct and indirect effects. Design and Settings 41 698 runners (21 km and 56 km), who were part of a 2-year prospective cohort study. Type of Study Path analysis of prospective data. Main Outcome Measurements Indirect, direct and total path estimates of the predictors of EAMC in distance runners. Results Body Mass Index (BMI) and age were significant indirect predictors of EAMC (p&lt;0.0001), while training and competition load, a history of chronic disease, medication use for chronic disease, and a history of running injuries were significant direct predictors for EAMC (p&lt;0.0001). Gender was a significant direct as well as indirect predictor of EAMC (P&lt;0.0001) and thus the total effect gives the overall impact of gender as a predictor of EAMC. Conclusions Using a path analysis approach, novel risk factors for EAMC (indirect and direct relationships) were identified, indicating that the risk factors associated with EAMC are complex. Indirect risk factors do not impact directly on EAMC, but rather through their effects on direct risk factors. These data enable clinicians to better understand these complex relationships of risk factors and can apply this to knowledge in the prevention, diagnosis and management of EAMC in athletes.
Margaret McCartney: Health inequality has to be political
Authors: Margaret McCartney
Journal: BMJ (2017)

The horrific fire at Grenfell Tower may prove to be a landmark in the national consciousness. Many of our problems are in plain sight. We’re so used to them that they seem unwieldy, just “the way things are.” The tower block that is now a tomb housed many immigrants on whom London depends—working in jobs that mean antisocial hours, hard graft, and low wages.

The social housing was owned by the local council. The residents’ association repeatedly raised concerns about safety in the block. Whatever an inquiry finds, it’s clear that the residents did not feel listened to, and dozens have died.

We know that poor people …
A phase 1 dose-escalation study of IPH2102 (lirilumab, BMS-986015, LIRI), a fully human anti KIR monoclonal antibody (mAb) in patients (pts) with various hematologic (HEM) or solid malignancies (SOL).
Authors: Norbert Vey, Anthony Goncalves, Lionel Karlin, Sophie Lebouvier-Sadot, Florence Broussais, Delphine Marie, Dominique Berton-Rigaud, Pascale Andre, Robert Albert Zerbib, Renaud Buffet, Thomas Prébet, Aude Charbonnier, Jerome Rey, Arnaud Pigneux, Jaafar Bennouna, Nicolas Boissel, Gilles A. Salles
Journal: Journal of Clinical Oncology (2015)

3065 Background: Inhibitory Killer Immunoglobulin-like receptors (KIRs) negatively regulate the killing, by NK cells, of tumors expressing their HLA class I ligands. We showed safety of 1st generation mAb targeting the major inhibitory KIRs (Vey et al Blood 2012).LIRI is a 2nd generation anti KIR mAb. The objectives of this study were to evaluate the safety and PK/PD of LIRI in pretreated pts with HEM or SOL with no or slowly progressive disease. Methods: In the dose escalation 3+3 phase 1 part, six dose levels of LIRI were evaluated: 0.015, 0.3, 1, 3, 6, and 10 mg/kg administered q4w x 4; the time between the first 2 infusions was adjusted to KIR desaturation (KIR occupancy < 30%). In a cohort expansion, pts were treated at 0.015 and 3 mg/kg q4w x 4 Results: Twenty and 17 patients were treated in the dose escalation and cohort expansion parts, respectively Overall median age was 62 years (33-73); 22 had HEM (5 AML, 6 CLL and 11 NHL) and 15, SOL (7 ovarian [OC], 6 breast [BC], and 2 others cancers). LIRI was generally well tolerated with no DLT in the dose-escalation; MTD was not reached. Related AEs observed in > 10% of the pts included fatigue/asthenia (30% of pts), pruritus (20%), infusion related reaction (14%), headache (11%). Only one SAE (G3 urticaria, at 0.015 mg/kg) was reported as treatment-related. Release of cytokines in serum was rare and mild to moderate. Eighteen patients (49%) discontinued the study prematurely including 13 because of disease progression, 3 for AE's and 2 for other reasons. Full KIR occupancy ( > 95%) was sustained during > 4 weeks for dose-levels ≥ 0.3 mg/kg. Conclusions: LIRI was generally well tolerated up to the highest tested dose of 10 mg/kg which was associated with prolonged KIR occupancy. Based on these results, LIRI is currently investigated in a randomized phase 2 trial as maintenance therapy for elderly pts with AML in CR1 and in several phase 1 studies in combination with other immune checkpoints inhibitors or a cytotoxic mAb.
PALOMA-2: Primary results from a phase III trial of palbociclib (P) with letrozole (L) compared with letrozole alone in postmenopausal women with ER+/HER2– advanced breast cancer (ABC).
Authors: Richard S. Finn, Miguel Martin, Hope S. Rugo, Stephen E. Jones, Seock-Ah Im, Karen A. Gelmon, Nadia Harbeck, Oleg N. Lipatov, Janice Maria Walshe, Stacy L. Moulder, Eric Roland Gauthier, Dongrui (Ray) Lu, Sophia Randolph, Véronique Diéras, Dennis J. Slamon
Journal: Journal of Clinical Oncology (2016)

507 Background: Hormonal therapy (HT) is the mainstay for patients (pts) with ER+ BC. P, a cyclin-dependent kinase 4/6 inhibitor, blocks growth of ER+/HER2– BC preclinical models. In PALOMA-1, an open-label Ph 2 trial, addition of P to L improved median PFS vs L alone (20.2 months [mo] vs 10.2 mo) in pts with first-line ER+/HER2– ABC with acceptable safety, leading to accelerated FDA approval. PALOMA-2 is a randomized double-blind Ph 3 trial designed to confirm these results. Methods: 666 postmenopausal pts with no prior systemic therapy for ABC were randomized 2:1 to receive P (oral 125 mg/d; 3 wks on/1 wk off) + L (2.5 mg/d continuously) or PLB + L every 28 days until disease progression, consent withdrawal or death. Pts were stratified by disease site, disease-free interval from end of (neo)adjuvant therapy, and prior HT (yes/no). Primary endpoint: investigator-assessed PFS; key secondary endpoints: overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR=CR + PR + SD ≥24 wks), patient-reported outcomes and safety. Tumor assessments were every 12 wks. 347 events were needed with 90% power to detect a hazard ratio (HR) ≤0.69 in favor of P+L (1-sided α=0.025). Results: By 26 Feb 2016, 331 PFS events occurred. Baseline characteristics were well balanced. Median PFS was 24.8 mo (P+L) vs 14.5 mo (PLB+L) (HR=0.58 [0.46–0.72], P<0.000001). ORR was improved with P+L (42.1% vs 34.7%, P=0.031; 55.3% vs 44.4% in pts with measurable disease [P=0.013]). CBR was 84.9% vs 70.3% (P<.0001). Common adverse events (AEs; all grades) with P+L vs PLB+L were neutropenia (79.5% vs 6.3%), fatigue (37.4% vs 27.5%), nausea (35.1% vs 26.1%), arthralgia (33.3% vs 33.8%) and alopecia (32.9% vs 15.8%). Most common severity seen was G3 for neutropenia (56.1%) and G1 for the other AEs. Febrile neutropenia was seen only with P+L (2.5%). Permanent discontinuation due to AEs was 9.7% (P+L) vs 5.9% (PLB+L). OS data are immature; final OS analysis is pending. Conclusion: PALOMA-2 expands and confirms the significant clinical benefit and safety of P+L in ER+/HER2– ABC pts who had not received prior systemic therapy for their advanced disease. Clinical trial information: NCT01740427.
EUROASPIRE III: lifestyle, risk factor and therapeutic management in people at high risk of developing cardiovascular disease: cross-sectional survey in 12 European countries
Authors: Kornelia Kotseva, Catriona Jennings, Gui De Backer, Dirk De Bacquer, Philippe Amouyel, Dan Gaita, Ulrich Keil, Andre Pajak, Zeljko Reiner, David Wood
Journal: Circulation (2010)
Screening for Obesity in Children and Adolescents
Authors: David C. Grossman, Kirsten Bibbins-Domingo, Susan J. Curry, Michael J. Barry, Karina W. Davidson, Chyke A. Doubeni, John W. Epling, Alex R. Kemper, Alex H. Krist, Ann E. Kurth, C. Seth Landefeld, Carol M. Mangione, Maureen G. Phipps, Michael Silverstein, Melissa A. Simon, Chien-Wen Tseng
Journal: JAMA (2017)

<h3>Importance</h3> Based on year 2000 Centers for Disease Control and Prevention growth charts, approximately 17% of children and adolescents aged 2 to 19 years in the United States have obesity, and almost 32% of children and adolescents are overweight or have obesity. Obesity in children and adolescents is associated with morbidity such as mental health and psychological issues, asthma, obstructive sleep apnea, orthopedic problems, and adverse cardiovascular and metabolic outcomes (eg, high blood pressure, abnormal lipid levels, and insulin resistance). Children and adolescents may also experience teasing and bullying behaviors based on their weight. Obesity in childhood and adolescence may continue into adulthood and lead to adverse cardiovascular outcomes or other obesity-related morbidity, such as type 2 diabetes. <h3>Subpopulation Considerations</h3> Although the overall rate of child and adolescent obesity has stabilized over the last decade after increasing steadily for 3 decades, obesity rates continue to increase in certain populations, such as African American girls and Hispanic boys. These racial/ethnic differences in obesity prevalence are likely a result of both genetic and nongenetic factors (eg, socioeconomic status, intake of sugar-sweetened beverages and fast food, and having a television in the bedroom). <h3>Objective</h3> To update the 2010 US Preventive Services Task Force (USPSTF) recommendation on screening for obesity in children 6 years and older. <h3>Evidence Review</h3> The USPSTF reviewed the evidence on screening for obesity in children and adolescents and the benefits and harms of weight management interventions. <h3>Findings</h3> Comprehensive, intensive behavioral interventions (≥26 contact hours) in children and adolescents 6 years and older who have obesity can result in improvements in weight status for up to 12 months; there is inadequate evidence regarding the effectiveness of less intensive interventions. The harms of behavioral interventions can be bounded as small to none, and the harms of screening are minimal. Therefore, the USPSTF concluded with moderate certainty that screening for obesity in children and adolescents 6 years and older is of moderate net benefit. <h3>Conclusions and Recommendation</h3> The USPSTF recommends that clinicians screen for obesity in children and adolescents 6 years and older and offer or refer them to comprehensive, intensive behavioral interventions to promote improvements in weight status. (B recommendation)
Soking, helicobacter pylori infection and epithelial cadherin expression in gastric mucosa
Authors: J Garvin, M Joyce, I Tobbia, L O'Grady, R Waldron
Journal: Endoscopy (2005)

Introduction: E-cadherin, the predominant cell-adhesion molecule expressed in epithelial tissue, and its associated catenin proteins are reduced in early diffuse gastric cancer and preinvasive lesions. Tobacco smoking and helicobacter pylori infection are linked to the development of gastric cancer. We aimed to determine if smoking and H. pylori infection were associated with reduced expression of e-cadherin and the catenins.
A network analysis to compare biomarker profiles in patients with and without diabetes mellitus in acute heart failure
Authors: Abhinav Sharma, Biniyam G. Demissei, Jasper Tromp, Hans L. Hillege, John G. Cleland, Christopher M. O'Connor, Marco Metra, Piotr Ponikowski, John R. Teerlink, Beth A. Davison, Michael M. Givertz, Daniel M. Bloomfield, Howard Dittrich, Dirk J. van Veldhuisen, Gad Cotter, Justin A. Ezekowitz, Mohsin A.F. Khan, Adriaan A. Voors
Journal: European Journal of Heart Failure (2017)
Progression free survival and toxicity with dose variations of everolimus in metastatic hormone receptor positive breast cancer.
Authors: Melanie Anne Sheen, Susmitha Apuri, Roohi Ismail-Khan
Journal: Journal of Clinical Oncology (2016)

e12058 Background: Everolimus is a sirolimus derivative that inhibits the mTOR (mammalian target of rapamycin) pathway. The BOLERO-2 trial showed improved progression free survival (PFS) with combined everolimus and exemestane versus exemestane alone in metastatic hormone receptor positive post-menopausal breast cancer patients. The initial dose of everolimus was 10mg and allowed for two dose reductions, 5mg daily and 5mg every other day. No data is available on PFS or toxicity for patients who were started, or dose reduced and maintained, on lower doses. We undertook a retrospective evaluation of PFS in patients with dose variations to determine if dose reductions adversely affect survival. Methods: Patients who were treated with the combination of everolimus and exemestane at Moffitt Cancer Center from April 26, 2012 - May 31, 2015 were obtained from our pharmacy database. A total of 138 patients met criteria consistent with BOLERO-2 patients. Chart review was performed to obtain data points. Results: PFS for the cohort as a total was 7.2 months. 77 patients were started on 10mg daily, 29 patients were started on 7.5mg daily, and 31 patients were started on 5mg daily. Dose reduction occurred in 47% of patients started on 10mg and 41% of patients started on 7.5mg. 22.5% of all patients discontinued treatment for toxicity, 75% of whom started on doses > 5mg. PFS comparison of starting 10mg to the average alternate dose (6.23 mg) was Hazard Ratio (HR) 1.15 (95% CI: 0.77-1.72) p = 0.49. PFS comparison of starting 10mg vs 7.5mg was HR 1.08 (95% CI: 0.65-1.80),p = 0.76 and starting 10mg vs. 5mg was HR 1.21 (95% CI: 0.76-1.95) p = 0.43. Conclusions: There was no significant difference in PFS between starting the recommended dose or a lower dose. Patients initiated on lower doses were less likely to require dose reductions or discontinue due to toxicity even with later dose increases. This data suggests that progression may not be limited by initiating lower, less toxic doses of everolimus. Therefore, if oncologists are more comfortable starting a lower dose, survival may not be adversely affected and patients may be more compliant, deriving a prolonged benefit from the combination.
Prognostic awareness, prognostic communication, and cognitive function in patients with malignant glioma
Authors: Eli L Diamond, Holly G Prigerson, Denise C Correa, Anne Reiner, Katherine Panageas, Maria Kryza-Lacombe, Justin Buthorn, Elizabeth C Neil, Alex M Miller, Lisa M DeAngelis, Allison J Applebaum
Journal: Neuro-Oncology (2017)

Malignant glioma (MG) is a devastating neuro-oncologic disease with almost invariably poor prognosis. Prognostic awareness (PA) is the awareness of incurable disease and shortened life expectancy (LE). Accurate PA is associated with favorable psychological outcomes at the end of life (EoL) for patients with cancer; however, little is known about PA or prognostic communication in MG. Moreover, research has yet to evaluate the impact of cognitive impairment on PA and preferred forms of communication.Fifty MG patients and 32 paired caregivers were evaluated in this exploratory study with a semi-structured PA assessment aimed to measure their awareness of MG incurability and LE. Full PA was defined as awareness of MG incurability and accurate estimate of LE. The assessment included a survey about preferences for prognostic communication (items from the Prognosis and Treatment Perceptions Questionnaire), neurocognitive assessment (Hopkins Verbal Learning Test-Revised, Trail Making Test Parts A and B, and the Controlled Oral Word Association Test), and measurements of mood (Hospital Anxiety and Depression Scale) and quality of life (Functional Assessment of Cancer Therapy-Brain [FACT-Br]).Twenty (40%) patients and 22 (69%) caregivers had full PA. Thirty (60%) patients and 23 (72%) caregivers reported that prognostic information was extremely or very important, and 21 (42%) patients and 16 (50%) caregivers desired more prognostic information. Patients with memory impairment more frequently believed that prognostic information was important (P = 0.04, P = 0.03) and desired more information (P = 0.05, P = 0.003) as compared with those without impairment.Most MG patients were unaware of their LE. Memory impairment may influence preferences for prognostic information.
Aggressive Imaging Features in a Malignant Pheochromocytoma With a Novel Mutation of the SDHB Gene
Authors: Soon-Ah Park, Dae Ho Lee, Hun Soo Kim
Journal: Clinical Nuclear Medicine (2017)

We describe a 15-year-old boy with a huge bilateral adrenal pheochromocytoma that had a de novo germline mutation in the succinate dehydrogenase subunit B (SDHB) gene. F-FDG PET/CT revealed bilateral metabolically active large masses in the adrenal glands and the activated brown adipose tissues. The I-MIBG scintigraphic findings revealed only a mild accumulation of MIBG in the right adrenal mass, but a high uptake in the left adrenal mass. Thus, F-FDG PET/CT imaging may be more effective than I-MIBG scintigraphy for the evaluation of pheochromocytomas that are associated with highly malignant characteristics resulting from mutations of the SDHB gene.
The incidence of cardiomyopathy in <i>BRCA1</i> and <i>BRCA2</i> mutation carriers after anthracycline-based adjuvant chemotherapy.
Authors: Edward Pearson, Anju Nair, Yahya Daoud, Joanne Lorraine Blum
Journal: Journal of Clinical Oncology (2016)

e13033 Background: Anthracyclines, commonly used drugs for the treatment of breast cancer, are associated with a risk of cardiotoxicity, manifesting in varying severity from an asymptomatic decline in left ventricular ejection fraction (LVEF) to overt congestive heart failure (CHF). Recent murine model studies demonstrated that BRCA2 deficiency increases the risk of anthracycline induced cardiac failure andBRCA1 deficiency may lead to increased rates of heart failure and cardiac death following an ischemic cardiac event. Methods: We conducted a retrospective case-control study to compare the incidence of anthracycline-induced cardiotoxicity in germline BRCA1 or BRCA2 mutation carriers, with a BRCA1 and BRCA2 wild-type, age matched population with similar baseline characteristics. The primary endpoint was the development of cardiomyopathy defined as either CHF or decline in LVEF. Results: We identified 102 BRCA mutation carriers with breast cancerfrom the Hereditary Breast Cancer Risk Program at Baylor University Medical Center (55 with BRCA1; 45 with BRCA2; 2 with both BRCA1 and BRCA2 mutation) who received anthracycline-based adjuvant or neo-adjuvant chemotherapy and compared them to a matched cohort with wild type BRCA gene status. We found a 4.9% incidence of cardiomyopathy in the BRCA mutation carriers and 5.2% incidence in the matched controls (p = 0.99). Cox Proportional Hazard analysis showed only trastuzumab (p-value = 0.0001; HR = 12.0, 95% CI (3.8-39.4)) exposure and hypertension (p-value = .0015; HR = 5.9, 95% CI (2.0-18.4)) to be significantly associated with the development of cardiomyopathy in both groups. Conclusions: These results fail to support the hypothesis that BRCA mutation carriers are at increased risk for anthracycline-induced cardiomyopathy. These findings have implications for the management of early stage breast cancer among BRCA mutation carriers.
Interleukin-8 secretion by human intestinal epithelial cells at physiological oxygen concentrations
Authors: I Leegte, AM O'Hara, L O'Mahony, F Shanahan
Journal: Endoscopy (2006)

Aims: The human gastrointestinal tract is relatively anaerobic (physiologic oxygen levels of 4.5%), but despite this the vast majority of cell-culture studies have been performed at atmospheric oxygen levels (21% oxygen). In this study, we aimed to determine whether culturing intestinal epithelial cells at atmospheric oxygen skews responses to pro-inflammatory stimuli compared to culturing at gut physiologic oxygen levels.
Perioperative epidural analgesia and recurrence-free survival for ovarian cancer surgery: A retrospective analysis.
Authors: Dominique Koensgen, Alexander Mustea, Barbara Rosanowski, Bianca Leutzow, Thomas Hesse, Maciej Patrzyk, Claus Dieter Heidecke, Marek Zygmunt, Michael Wendt, Taras Usichenko
Journal: Journal of Clinical Oncology (2013)

e16534 Background: Current experimental and clinical data suggest that perioperative factors may influence the long-term outcome after cancer surgery. Recent retrospective analyses have shown the reduction of cancer recurrence and metastatic spread in patients after tumor surgery receiving perioperative regional and neuraxial analgesia. The aim was to investigate whether perioperative epidural anesthesia is associated with the decreased disease recurrence and increased survival after primary tumor debulking in patients with ovarian cancer. Methods: Retrospective analysis of consecutive patients with primary ovarian cancer who underwent radical multivisceral surgery between 01/2003 and 12/2010 under either general anesthesia plus opioid analgesia (group A) or general anesthesia plus epidural anesthesia (group B), was performed. Cancer recurrence-free survival and total survival times after surgery were compared between the groups using Mann-Whitney test. The analysis was strengthened by Kaplan-Meier survival estimates for each group with comparison using the log-rank test. Results: Data of 105 (88%) of patients (group A: 33; group B: 72) were available for analysis. The median (interquartile range-IQR) follow-up time 27 (17-58) months. The groups were comparable regarding age, body-mass index, ASA physiological status, FIGO staging, tumor residual and use of adjuvant platinum-based chemotherapy. The median (IQR) time to recurrence of cancer was 31 (15-63) months in group A vs. 18 (10-35) months in group B (p = 0.017). Longer recurrence-free survival was associated with general anesthesia and opioid analgesia (hazard ratio 1.52; 95% confidence interval 1.4-1.56; p = 0.008). Conclusions: In contrast to previous investigations, perioperative epidural anesthesia was associated with decreased survival in patients after ovarian cancer surgery.