tbuckley/cabot-search huggingface dataset:
Association of Light Physical Activity Measured by Accelerometry and Incidence of Coronary Heart Disease and Cardiovascular Disease in Older Women
Authors: Andrea Z. LaCroix, John Bellettiere, Eileen Rillamas-Sun, Chongzhi Di, Kelly R. Evenson, Cora E. Lewis, David M. Buchner, Marcia L. Stefanick, I-Min Lee, Dori E. Rosenberg, Michael J. LaMonte
Journal: JAMA Network Open (2019)

<h3>Importance</h3> To our knowledge, no studies have examined light physical activity (PA) measured by accelerometry and heart disease in older women. <h3>Objective</h3> To investigate whether higher levels of light PA were associated with reduced risks of coronary heart disease (CHD) or cardiovascular disease (CVD) in older women. <h3>Design, Setting, and Participants</h3> Prospective cohort study of older women from baseline (March 2012 to April 2014) through February 28, 2017, for up to 4.91 years. The setting was community-dwelling participants from the Women's Health Initiative. Participants were ambulatory women with no history of myocardial infarction or stroke. <h3>Exposures</h3> Data from accelerometers worn for a requested 7 days were used to measure light PA. <h3>Main Outcomes and Measures</h3> Cox proportional hazards regression models estimated hazard ratios (HRs) and 95% CIs for physician-adjudicated CHD and CVD events across light PA quartiles adjusting for possible confounders. Light PA was also analyzed as a continuous variable with and without adjustment for moderate to vigorous PA (MVPA). <h3>Results</h3> Among 5861 women (mean [SD] age, 78.5 [6.7] years), 143 CHD events and 570 CVD events were observed. The HRs for CHD in the highest vs lowest quartiles of light PA were 0.42 (95% CI, 0.25-0.70;<i>P</i>for trend &lt;.001) adjusted for age and race/ethnicity and 0.58 (95% CI, 0.34-0.99;<i>P</i>for trend = .004) after additional adjustment for education, current smoking, alcohol consumption, physical functioning, comorbidity, and self-rated health. Corresponding HRs for CVD in the highest vs lowest quartiles of light PA were 0.63 (95% CI, 0.49-0.81;<i>P</i>for trend &lt;.001) and 0.78 (95% CI, 0.60-1.00;<i>P</i>for trend = .004). The HRs for a 1-hour/day increment in light PA after additional adjustment for MVPA were 0.86 (95% CI, 0.73-1.00;<i>P</i>for trend = .05) for CHD and 0.92 (95% CI, 0.85-0.99;<i>P</i>for trend = .03) for CVD. <h3>Conclusions and Relevance</h3> The present findings support the conclusion that all movement counts for the prevention of CHD and CVD in older women. Large, pragmatic randomized trials are needed to test whether increasing light PA among older women reduces cardiovascular risk.
An Australian single institution experience in treating primary glioblastoma multiforme from 2010-2012.
Authors: Lucy Gately, Anna Collins, Michael Murphy, Anthony J. Dowling
Journal: Journal of Clinical Oncology (2015)

e13043 Background: Over half of all glioblastoma multiforme (GBM) cases are diagnosed in patients older than 65 years. Several series demonstrate a median overall survival of 4-5 months in this age group (Iwamoto et al 2008), compared with 12-14 months in patients up to 70 years of age (Stupp et al 2005). Single institution studies have also found that patients aged over 65 are less likely to receive comprehensive treatment. This retrospective audit aims to identify patterns of care and survival at a single institution in Melbourne, Australia. Methods: Consecutive histological diagnoses of primary GBM from January 2010 to December 2012 were retrospectively identified from pathological and medical records. Demographic, treatment and survival characteristics were recorded until death or the censor date of 1st January 2015. Survival was estimated by the Kaplan-Meier method. Significant factors in univariate analyses (p < .05) were included in a multivariate Cox proportional hazards model to predict overall survival. Planned sub-group analyses (chi square, independent samples ttest, or Fishers exact test) were conducted to identify differences between elderly (defined as ≥ 70 years) and younger cohorts. Results: The cohort included 166 patients, of which 36% were elderly. Compared with those aged less than 70 years: the elderly cohort had a poorer performance status (ECOG 3-4: 32% vs 12%, p = .005); a poorer median overall survival (2.6 months vs 11.5 months, p < .001); and was less likely to receive adjuvant treatments (no treatment: 55% vs 21%, p < .001). Yet, age was not a significant predictor of poorer overall survival (HR 1.0; 0.99 -1.03; p > .05), after adjusting for other clinical factors. Significant predictors of poorer overall survival were poor performance status (p = .04), bilateral tumours (p = .03), surgical biopsy only (p = .001), and not receiving adjuvant radiation and temozolomide (p < .001). Conclusions: In patients diagnosed with GBM, those older than 70 years often present with poor performance status, are less likely to receive adjuvant treatments and have inferior overall survival compared with younger patients. Treatment recommendations should be based on performance status and fitness, not age alone.
RENAVIV: A randomized phase III, double-blind, placebo-controlled study of pazopanib with or without abexinostat in patients with locally advanced or metastatic renal cell carcinoma.
Authors: Rahul Raj Aggarwal, Scott Thomas, Ralph J. Hauke, Luke T. Nordquist, Pamela N. Munster
Journal: Journal of Clinical Oncology (2019)

TPS681 Background: Abexinostat is a pan-histone deacetylase (HDAC) inhibitor that has shown promising activity in prior pre-clinical studies and early phase clinical trials. A phase 1b study of pazopanib plus abexinostat (Aggarwal et al. J Clin Oncol 2017) demonstrated strikingly durable responses in patients (pts) with clear cell renal cell carcinoma (RCC), including one patient with previously refractory disease with ongoing response for &gt; 5 years’ duration. Induction of histone acetylation in peripheral blood mononuclear cells (PBMCs) was associated with durable treatment response. We hypothesize that the addition of abexinostat to pazopanib will significantly improve outcomes in patients with clear cell RCC. Methods: RENAVIV is a global, randomized, double-blind, placebo-controlled, two arm phase 3 study of pazopanib plus abexinostat versus pazopanib plus placebo, in pts with locally advanced or metastatic RCC with clear cell component. Up to one prior line of immunotherapy is allowed. Prior VEGF-targeting tyrosine kinase inhibitor treatment is prohibited. Stratification factors include: 1) Prior immunotherapy (yes/no) and 2) prognostic group (good, intermediate, poor). Pts randomized to pazopanib + placebo have the option of crossing over to receive pazopanib plus abexinostat at the time of disease progression. The primary endpoint is PFS by independent review committee. Secondary endpoints include PFS by investigator assessment, overall survival, safety, objective response rate (ORR), duration of response, patient-reported quality of life, and outcomes in cross-over population. Planned correlative studies include association between histone acetylation and HDAC expression in PBMCs with clinical outcomes. The total planned accrual is 413 pts, estimated to provide 90% power to detect a hazard ratio of 0.67 in the comparison of PFS between experimental versus control arms, with an overall two-sided type I error rate of 0.025. A pre-specified minimum of 50% of patients are required to have received prior immunotherapy. The first patient was enrolled in October 2018. Clinical trial information: NCT03592472.
Response and Outcomes of Third-Line Tyrosine Kinase Inhibitor Therapy on Patients with Chronic Phase Chronic Myeloid Leukemia
Authors: Maliha Khan, Hagop M. Kantarjian, Jing Ning, Mary Akosile, Wen Li, Gautam Borthakur, Nitin Jain, Courtney D. DiNardo, William G Wierda, Farhad Ravandi, Guillermo Garcia-Manero, Marina Konopleva, Tapan Kadia, Naveen Pemmaraju, Philip A Thompson, Naval Daver, Elias J. Jabbour, Jorge E. Cortes
Journal: Blood (2017)
FGFR3 mutation as a prognostic indicator in patients with urothelial carcinoma: A systematic review and meta-analysis.
Authors: Sidra Khalid, Bassam Mohammed Basulaiman, Jeff Emack, Christopher M. Booth, David Hernandez-Barajas, Ignacio Duran, Martin Smoragiewicz, Eitan Amir, Francisco Vera-Badillo
Journal: Journal of Clinical Oncology (2019)

411 Background: Mutations in the fibroblast growth factor receptor-3 (FGFR3) have been implicated in urothelial tumorigenesis. The role of FGFR3 inhibitors in urothelial carcinoma is being explored in clinical trials. Here we explore the association between FGFR3 mutations and survival in urothelial carcinoma. Methods: We conducted a systemic review of electronic databases to identify studies published 1985-2018. Studies were included if they described the associated between FGFR3 mutations and outcomes of non-muscle invasive (NMI) and muscle invasive (MI) urothelial carcinomas. We used a composite endpoint of progression-free and recurrence-free survival (PRFS). Analysis was performed in Revman software. Hazard ratios (HR) and the 95% confidence intervals (CI) were obtained and entered; and then weighted and pooled in a meta-analysis with random effect modelling. The statistical tests were two sided. Results: Twelve retrospective and prospective studies comprising a total of 2162 patients were included. Analysis was done for two groups. The first group, included 1651 patients with NMI urothelial carcinomas; 886 (53.6%) of these had FGFR3 mutation. Compared to FGFR3 wild type, FGFR3 mutation did not influence PRFS (HR = 1.01, CI = 0.79-1.29, p = 0.95); I 2 42%. In the second analysis, 511 patients with NMI and MI urothelial carcinomas were evaluated; 30% (n = 151) of which had FGFR3 mutation. In this group, FGFR3 mutation was not associated with PRFS (HR = 1.46, CI = 0.45-4.71, p = 0.53); I 2 90%. Conclusions: Our meta-analysis does not show an association between FGFR3 mutation status and PRFS in urothelial carcinoma. [Table: see text]
Predictors of need for urgent enteral feeding access in esophageal cancer patients during neoadjuvant or definitive chemoradiation.
Authors: Tolutope Oyasiji, Aniqa Kohen, Wei Tan, David Mattson, Steven N. Hochwald, Usha Malhotra
Journal: Journal of Clinical Oncology (2015)

e15054 Background: Adverse effects of neoadjuvant or definitive CRT can cause or worsen malnutrition and dehydration/electrolyte imbalances in esophageal cancer patients. Disruption of treatment can occur, and may compromise outcome. Routine placement of enteral feeding access prior to treatment is controversial. In order to select those patients best suited for enteral feeding access, we sought to identify predictors of urgent enteral feeding access and hospitalization for dehydration/ malnutrition in esophageal cancer patients during treatment. Methods: All esophageal cancer patients without enteral feeding access prior to starting neoadjuvant or definitive CRT at our institution, from 2004 through 2014, were retrospectively reviewed. Primary endpoint was urgent placement of enteral feeding access and/ or hospitalization for IV hydration/ TPN during treatment. Results: 211 patients (77% neoadjuvant CRT & 23% definitive CRT) were identified- 86% were male; 48% were ≥ 65 years old; 63% presented with dysphagia; and adenocarcinoma (89%) was the predominant histology. 63% of patients developed esophagitis (grade 1 = 33%, grade 2 = 20% & grade 3 = 10%). Radiation modality was well documented for 205 patients (97%) - IMRT (19%), VMAT (50%) and 3D conformal (28%). Primary endpoint event was observed in 28 patients (13%) - urgent enteral feeding access (14 patients) and hospitalization for IV hydration/ TPN for malnutrition (14 patients). Univariate analysis showed that dysphagia, 3D conformal radiation and esophagitis were significantly associated with the primary endpoint (all p values < 0.05). Esophagitis ( grade 1 -OR 14.5, 95% CI 3.5-61.2; grade 2- OR 21.5 , 95% CI 12.0-3749.3; grade 3- OR 3097.1, 95% CI 41.8-229577.1 ; p = 0.0003) was the only independent predictor of need for urgent enteral feeding access and/ or hospitalization for IV hydration/ TPN during neoadjuvant or definitive CRT. Conclusions: Our data suggests that pre-treatment enteral feeding access should be considered in esophageal cancer patients that have dysphagia at presentation; will be treated with 3D conformal radiation modality or at the earliest sign of esophagitis during treatment.
Role of HE4, CA125, and ultrasound in risk assessment in pelvic mass patients: Results from a prospective, multicentric study.
Authors: Elena Ioana Braicu, Uwe Torsten, Herbert Mecke, Rolf Richter, Kerstin Ames, Lars Hellmeyer, Kati Hasenbein, Gerhard Nohe, Frank Chen, Carmen Rosa Beteta, Ricarda Isermann, Radoslav Chekerov, Marcelo Bustamante, Anna-Maria Dueckelmann, Miriam Christophi, Mueller Bodo, N. Monetaer, Mathias Zimmermann, Janine Bonness-Zaloum, Jalid Sehouli
Journal: Journal of Clinical Oncology (2015)

5535 Background: Ovarian cancer (OC) lacks of specific symptoms and biomarkers for early diagnosis. Advanced stages are associated with poor survival. CA125 and HE4 are overexpressed in OC. Their role in early diagnosis is controversial discussed. Ultrasound criteria (e.g. IOTA algorithms) seem to improve the sensitivity and specificity for risk assessment. Methods: In a prospective, multicentric study performed in 676 pelvic mass patients, transvaginal ultrasound together with blood sampling and biomarker analysis were performed. All patients had an ovarian (including para-ovarian and tubal) mass and underwent a standardized ultrasound examination, according to IOTA criteria, prior to surgery. ROMA algorithm combining CA125, HE4 and menopausal status, was used to distinguish between benign and malignant disease. An online data base was provided for the prospective documentation of clinical parameters, ultrasound, surgical methods and histology. Patients were included at 7 clinics in Berlin. All samples were analyzed centralized at Labor Berlin. These results represent the analysis of the training cohort. Results: From the 676 patients, 57% were premenopausal, 13.3% were diagnosed with OC, 4.3% with borderline tumors, 0.2% Krukenberg tumors and 0.8% rare malignancies of the ovary. The area under the receiver operating characteristic curve (AUC) for the discrimination between benign and malignant tumors was for CA125 0.840 and 0.899, for HE4 0.860 and 0.885 and for ROMA 0.863 and 0.930 in pre-and postmenopausal patients, respectively. The IOTA LR2 model includes one clinical and five ultrasound predictors: age, presence of ascites, presence of papillations with detectable blood flow, maximum diameter of largest solid component, irregular cyst walls and presence of acoustic shadows. IOTA LR2 reached an AUC of 0.971 in premenopausal and of 0.748 in postmenopausal patients. Conclusions: HE4 performed slightly better than CA125 in risk assessment in premenopausal patients, nevertheless ultrasound criteria could best discriminate between benign and malignant disease in premenopausal patients. In postmenopausal patients, ROMA reached the best sensitivity and specificity.
Cetuximab plus chemotherapy as second line treatment of patient with metastatic colorectal cancer after failure of cetuximab containing regiment in first line: Single cancer center experience.
Authors: Michal Vocka, Libor Stanek, Lubos B. Petruzelka
Journal: Journal of Clinical Oncology (2015)

e14678 Background: Combination of targeted and standard cytotoxic therapy (CT) has been shown to significantly increase both overall (OS) and progression free (PFS) in patients with metastatic colorectal cancer (mCRC). There are no data about treatment results with cetuximab (cet) and chemotherapy after failure of first line treatment containing cet. Methods: A retrospective analysis of pts with mCRC treated with cet-containing regimen beyond first line progression was conducted for all pts treated from January 2012 to December 2014. The primary objective was to evaluate the efficacy of cet beyond first line progression. Results: A total of 16 pts were identified. The median age was 61,3 (range 42,7-73,2) and at baseline all pts had an ECOG performance status (PS( of 0 or 1 (46% and 54% resp). Metastases were localized in the liver in 75% of pts and in lungs in 19%. All pts were KRAS exon2 wild type. In the first line 15 pts were treated with FOLFOX4 and one with FOLFIRI. In the second line 12 pts were treated with FOLFIRI, 3 with irinotecan monotherapy and 1 with FOLFOX 4. The median PFS for first line was 12,5 month and median PFS for second line was 7,3 months. The median overall survival was 40,15 months. Tissue samples of 13 pts were available for reanalysis of RAS and BRAF. Two mutation of NRAS were found. No BRAF mutation was found. The median PFS1 for RAS wt pts (N = 10) was 14,5 month and PFS2 was 13,4 months (8 pts are still on treatment). The median overall survival was not reached. Conclusions: The small retrospective analysis shows results of cet plus CT beyond progression after failure of cet-containing regimens in first line. RAS and BRAF wild type status together with good PS play key role in selection of pts who may profit from continuing treatment with cet plus CT.
Comparison of a picosecond alexandrite laser versus a Q-switched alexandrite laser for the treatment of nevus of Ota: A randomized, split-lesion, controlled trial
Authors: Yiping Ge, Ying Yang, Lifang Guo, Mengli Zhang, Qiuju Wu, Rong Zeng, Huizhen Rong, Gaorong Jia, Hualing Shi, Jing Fang, Tong Lin
Journal: Journal of the American Academy of Dermatology (2019)
Protecting women and children in conflict settings
Authors: Zulfiqar A Bhutta, Michelle F Gaffey, Karl Blanchet, Ron Waldman, Kamran Abbasi
Journal: BMJ (2019)

A recent Save the Children report highlighted that some 357 million children, one in every six children in the world, currently live in a conflict zone. 1 Almost half of them live in severe conflict settings.Wagner et al 2 estimate that a child born within 50 km of an armed conflict event in Africa has a 7.7% excess risk of dying in infancy.This equates to 5.2 more deaths per 1000 births than during periods without conflict in the same region (95% confidence interval 3.7 to 6.7).Predictably, this effect increases with severity of conflict.
THU0744-HPR Effectiveness of profibro mobile app on quality of life, symptoms and self-care agency in patients with fibromyalgia: a randomised, single-blind trial
Authors: S.L.K. Yuan, A.P. Marques
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> ProFibro is the first free mobile Android application in Brazilian Portuguese for fibromyalgia (FM). It was developed as a complementary Mobile Health resource in FM management for the promotion of self-care. Its main functions are educational animation, self-monitoring, sleep strategies, scheduling, exercise, hints through notifications, practice of gratitude with a diary and family adjustments. <h3>Objectives</h3> to assess the effectiveness of ProFibro in the improvement of health-related quality of life, symptoms and self-care agency of patients with FM. <h3>Methods</h3> Forty subjects with FM, aged 19–59 years, were randomised into ProFibro and a control group. ProFibro group received a smartphone with the mobile app and subjects were instructed to use it for 6 weeks, while control group received a paper booklet of similar content. Subjects were assessed at baseline and after 6 weeks with the Revised Fibromyalgia Impact Questionnaire (FIQR), Widespread Pain Index (WPI), Pain Visual Analogue Scale (VAS), Symptom Severity (SS) Scale and Revised Appraisal of Self-Care Agency Scale. <h3>Results</h3> Control group showed significant improvement only in SS compared to baseline. ProFibro group showed significant improvements in SS and FIQR overall impact domain. In intergroup comparison, no differences in change scores were found. <h3>Conclusions</h3> Findings suggest that both ProFibro app and the booklet are effective for reducing symptom severity. ProFibro may also reduce the overall impact of FM in the quality of life. More studies with larger sample sizes and longer periods of intervention are needed to confirm the findings of the present study. <h3>References</h3> [1] Yuan SLK, Marques AP. Development of a Mobile Application to Promote Self-Care in Brazilian Patients with Fibromyalgia [abstract]. In: WCPT Congress Proceedings 2017 Jul 2–4; Cape Town. London: WCPT 2017. Abstract Nr. SI-PL-1081. [2] Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Katz RS, Mease P, et al. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res (Hoboken)2010;62:600–10. [3] Paiva ES, Heymann RE, Rezende MC, Helfenstein M, Jr, Martinez JE, Provenza JR, et al. A Brazilian Portuguese version of the Revised Fibromyalgia Impact Questionnaire (FIQR): a validation study. Clin Rheumatol2013;32:1199–206. [4] Marques AP, Assumpcao A, Matsutani LA, Pereira CAB, Lage L. Pain in Fibromyalgia and Discriminative Power of the Instruments: Visual Analog Scale, Dolorimetry and the Mcgill Pain Questionnaire. Acta Reumatol Port2008;33:345–51. [5] Damasio BF, Koller SH. The Appraisal of Self-Care Agency Scale - Revised (ASAS-R): adaptation and construct validity in the Brazilian context. Cad Saude Publica2013;29:2071–82. <h3>Disclosure of Interest</h3> None declared
Biochemichal recurrence in prostate cancer after salvage surgery in correlation to the site of reccurrent disease.
Authors: David Pfister, Jasmin Pullankavumkal, Friederike Haidl, Axel Heidenreich
Journal: Journal of Clinical Oncology (2019)

306 Background: Due to improved diagnostic tools salvage surgery is getting more popular after failure of primary local treatment as radical prostatectomy or radiotherapy. We analyzed PSA progression free survival (PFS) after radical prostatectomy and or radiotherapy in accordance to the location of the recurrence and the performed salvage surgery. Methods: We retrospectively analyzed 274 patients with salvage surgeries. 142, 18, and 114 patients underwent salvage radical prostatectomy (SPRE, Group1), locoregional recurrences mainly in seminal vesical remnants (SVR, Group2) or salvage lymph node dissection (SLND, Group3). All patients were diagnosed either by Choline- or more lately PSMA-PET CT. All surgeries had been done open. In Group1 radical prostatectomy and lymph node dissection, in Group 2 the seminal vesicals and in Group3 an ipsilateral pelvic lymph node dissection had been performed due to imaging results. Results: Median age at time of surgery was 67(62-72)years. Median PSA was 3.1(1.45-5.45)ng/ml. Radiotherapy or hormone therapy before salvage surgery in Group 1,2,3 was done in 100%, 61,1%, 54,39% and 12,6%, 27,8%, 18,42% of the patients. Median progression free survival in Group 1, 2, 3 is 41(11.104), 29 (8-47) and 8 (2-21) months (p &lt; 0.001). PSA PFS in Group1/2 and Group 1/3 differed significantly with an HR of 1.85 (95%CI;1,0-3.44) and HR of 2.72 (95%CI; 1,84-4,04). Only age at time of surgery and interval from primary treatment to salvage procedure in months were significant predictors in an univariate Cox regression analysis. Conclusions: We demonstrate that the best biochemical control in salvage surgeries is achieved in patients with isolated recurrence in the prostate after radiotherapy. The effect of salvage surgery decreases with increasing distance of the site of recurrence to the prostate.
Negative pressure dressings are no better than standard dressings for open fractures
Authors: Rob Cook, Vaughan Thomas, Rosie Martin
Journal: BMJ (2019)

The study Effect of negative pressure wound therapy vs standard wound management on 12-month disability among adults with severe open fracture of the lower limb: the WOLLF randomised clinical trial. Costa ML, Achten J, Bruce J, et al; UK WOLLF Collaboration Published on 9 October 2018 JAMA 2018;319:2280-8. This project was funded by the National Institute for Health Research Health Technology Assessment Programme (project number 10/57/20). To read the full NIHR Signal, go to: https://discover.dc.nihr.ac.uk/content/signal-000655/negative-pressure-dressings-are-no-better-than-standard-dressings-for-open-fractures