tbuckley/cabot-search huggingface dataset:
Late toxicity and quality of life from GETUG-AFU 22 study.
Authors: Igor Latorzeff, Stephane Guerif, Sandra Pelissier, Emmanuel Meyer, Julien Fraisse, Stephane Supiot, Gilles Crehange, Edouard Lagneau, Philippe Ronchin, Ahmed Benyoucef, Ali Hasbini, Pascal Pommier, Guy De Laroche, Laurent Salomon, Paul Sargos
Journal: Journal of Clinical Oncology (2020)

331 Background: Radical prostatectomy (RP) is recommended as a standard treatment for localized prostate cancer. However no recommendations exist for pts with immediate detectable PSA after RP. Methods: Pts with localized prostate cancer, treated by RP (R0 or R1), with a PSA level post-RP ≥0.2 ng/mL and ≤2 ng/mL at randomization and N0 M0 on imaging were included. Pts were randomized (1:1) to radiotherapy (RT) alone (RT arm) or 6 months degarelix hormone therapy (HT) with RT (RT+HT arm). RT consisted of pelvic irradiation (46 Gy in 23 Fr) with a boost on the prostate bed (66 Gy in 33 Fr). The primary endpoint was event-free survival (EFS). Acute and late toxicities were evaluated as secondary endpoints and scored using CTCAE V4.0 scale. Quality of life (QOL) was assessed with QLQ-C30 and QLQ-PR25 questionnaires at 12 and 24 months. Late toxicity was reported at 24 months. Results: From Jan-2013 to Sept-2015, 125 pts were included (RT arm: 64 pts; RT+HT arm: 61). Median follow up is 38 months (31.4; 44). The baseline characteristics are well-balanced between two arms: median age was 66 yrs (50-77), all men having an ECOG ≤1 (ECOG 0 in 92%), a median Gleason score of 7 (3-9), a median PSA of 0.3 ng/mL (0.09-1.82) post-RP and 0.6 ng/mL (0.12-3.65) at randomization. All pts received 33 Fr of RT. In the RT+HT arm 98.4% of pts received the 6 months of HT planned. All pts were eligible for safety analysis. At 24 months, no difference in late genitourinary (GU) or gastrointestinal (GI)toxicity was observed between the two arms (p=0.145) Grade 3 late toxicities were reported for 15/125 pts (12%): 8/64 pts (6.5%) in the RT arm and 7/61 pts (5.5%) in RT+HT arm (NS) and no toxicity grade &gt;3 was observed. Evaluation of QOL was assessable at 12 and 24 months of FU for 80%/89% pts and 59%/77% pts in RT/RT-HT arms respectively. At 12 months QLQ-PR25 HT related symptoms was significantly more important in the RT-HT arm (p=0.04). At 24 months no significant difference in QLQC-30 or QLQ-PR25 analysis was reported. Conclusions:, At 24 months in this phase II trial no significant difference in GI/GU toxicity and.QOL was observed between the two arms. GETUG-AFU 22 efficacy analysis is still pending. Clinical trial information: NCT01994239.
67P Analysis of Local-Regional Recurrence in Young Women (≤ 35Y) Receiving Mastectomy for Operable Breast Cancer
Authors: L.C. Tang, C.Y. Zhu, G.H. Di, J.L. Ma, Z.Z. Yang, X.L. Yu, Z.M. Shao, J.Y. Chen
Journal: Annals of Oncology (2012)
Change in blood eosinophils following treatment with inhaled corticosteroids may predict long-term clinical response in COPD
Authors: Alexander G. Mathioudakis, Andras Bikov, Philip Foden, Lies Lahousse, Guy Brusselle, Dave Singh, Jørgen Vestbo
Journal: European Respiratory Journal (2020)

There is an emerging role for blood eosinophil count (EOS) as a biomarker to guide inhaled corticosteroid (ICS) therapy in COPD. Since ICS administration could influence EOS, we hypothesised that change in EOS following treatment with ICS may predict outcomes of long-term therapy. In a post hoc analysis of ISOLDE, a 3-year, double-blind trial comparing 500 µg fluticasone propionate twice daily with placebo in 751 patients with moderate-to-severe COPD, we evaluated whether the initial changes in EOS during ICS treatment were predictive of ICS treatment response. EOS change within 1 year after the introduction of ICS was strongly predictive of treatment response. A suppressed EOS was associated with treatment effect. Characteristically, in patients with EOS suppression of ≥200 cells·μL −1 , ICS use was associated with a decelerated rate of decline of forced expiratory volume in 1 s (FEV 1 ), by 32 mL·year −1 , and a 30% reduction in the exacerbation rate. In contrast, in patients experiencing an increase in EOS of ≥200 cells·μL −1 , ICS use was associated with an accelerated rate of decline of FEV 1 , by 37 mL·year −1 and an 80% increase in the exacerbation rate (p&lt;0.0001). EOS change was not predictive of clinical response with regards to health status evaluated using the St George's Respiratory Questionnaire. These findings suggest that EOS change after ICS administration may predict clinical response to ICS therapy in patients with moderate-to-severe COPD at risk of exacerbations. ICS administration may be associated with more frequent exacerbations and an accelerated lung function decline in the 20% of patients in whom EOS increases after the administration of ICS. These hypothesis-generating observations will need validation in prospectively designed studies. The ISOLDE trial was conducted before the ICJME recommended a prospective registration of RCT protocols.
Abstract 15195: Improvement of Heart Failure Self-Care and Patient Readmission With Caregiver Education
Authors: Linda Clements, Debra K Moser, Terry A Lennie, Susan K Frazier, Misook L Chung
Journal: Circulation (2018)

Introduction: Caregivers play an important role in supporting patients’ management of heart failure (HF), but they are commonly excluded in HF self-care education. The purpose of this study was to ...
Lithocholic acid increases intestinal phosphate and calcium absorption in a vitamin D receptor dependent but transcellular pathway independent manner
Authors: Nobuhiro Hashimoto, Isao Matsui, Satoshi Ishizuka, Kazunori Inoue, Ayumi Matsumoto, Karin Shimada, Shota Hori, Dong Geun Lee, Seiichi Yasuda, Yusuke Katsuma, Sachio Kajimoto, Yohei Doi, Satoshi Yamaguchi, Keiichi Kubota, Tatsufumi Oka, Yusuke Sakaguchi, Yoshitsugu Takabatake, Takayuki Hamano, Yoshitaka Isaka
Journal: Kidney International (2020)
Optimal Antithrombotic Regimens for Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention
Authors: Renato D. Lopes, Hwanhee Hong, Ralf E. Harskamp, Deepak L. Bhatt, Roxana Mehran, Christopher P. Cannon, Christopher B. Granger, Freek W. A. Verheugt, Jianghao Li, Jurriën M. ten Berg, Nikolaus Sarafoff, Pascal Vranckx, Andreas Goette, C. Michael Gibson, John H. Alexander
Journal: JAMA Cardiology (2020)

Antithrombotic treatment in patients with atrial fibrillation (AF) and percutaneous coronary intervention (PCI) presents a balancing act with regard to bleeding and ischemic risks.To evaluate the safety and efficacy of 4 antithrombotic regimens by conducting an up-to-date network meta-analysis and to identify the optimal treatment for patients with AF undergoing PCI.Online computerized database (MEDLINE).Five randomized studies were included (N = 11 542; WOEST, PIONEER AF-PCI, RE-DUAL PCI, AUGUSTUS, ENTRUST-AF PCI).The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used in this network meta-analysis, in which bayesian random-effects models were applied. The data were analyzed from September 9 to 29, 2019.The primary safety outcome was thrombolysis in myocardial infarction (TIMI) major bleeding and the primary efficacy outcome was trial-defined major adverse cardiovascular events (MACE).The total number of participants included in the study was 11 532. The mean age of the participants ranged from 70 to 72 years, 69% to 83% were male, 20% to 26% were female, and the participants were predominantly white (>90%). Compared with vitamin K antagonists (VKA) plus dual antiplatelet therapy (DAPT) (reference), the odds ratios (ORs) (95% credible intervals) for TIMI major bleeding were 0.57 (0.31-1.00) for VKA plus P2Y12 inhibitor, 0.69 (0.40-1.16) for non-VKA oral anticoagulant (NOAC) plus DAPT, and 0.52 (0.35-0.79) for NOAC plus P2Y12 inhibitor. For MACE, using VKA plus DAPT as reference, the ORs (95% credible intervals) were 0.97 (0.64-1.42) for VKA plus P2Y12 inhibitor, 0.95 (0.64-1.39) for NOAC plus DAPT, and 1.03 (0.77-1.38) for NOAC plus P2Y12 inhibitor.The findings of this study suggest that an antithrombotic regimen of VKA plus DAPT should generally be avoided, because regimens in which aspirin is discontinued may lead to lower bleeding risk and no difference in antithrombotic effectiveness. The use of a NOAC plus a P2Y12 inhibitor without aspirin may be the most favorable treatment option and the preferred antithrombotic regimen for most patients with AF undergoing PCI.
The Advanced Renal Cell Carcinoma Sorafenib (ARCCS) expanded access trial: Safety and efficacy in patients (pts) with prior bevacizumab (BEV) treatment
Authors: H. A. Drabkin, R. A. Figlin, W. M. Stadler, T. E. Hutson, J. Hajdenberg, L. Chu, D. Trent, L. T. Campos, F. Kelly, R. M. Bukowski
Journal: Journal of Clinical Oncology (2007)

5041 Background: Sorafenib (SOR) is an oral multi-kinase inhibitor of tumor-cell angiogenesis and proliferation. Phase III (TARGETs) data have demonstrated prolonged progression-free survival in pts with advanced clear cell renal cell carcinoma (RCC) in whom prior therapy failed. Activity of SOR following treatment with BEV, an anti-vascular endothelial growth factor and antiangiogenic monoclonal antibody, has not been evaluated. Methods: A subset analysis was conducted to describe safety and efficacy in the SOR expanded access program in North America for pts receiving prior BEV. Inclusion criteria for this open-label, nonrandomized trial included advanced RCC; ineligibility for, or lack of access to, other SOR clinical trials; age =15 years; ECOG PS of 0–2; recovery from prior treatment; adequate prior treatment of brain metastases. Major exclusion criteria included life expectancy &lt;2 months; active coronary artery disease, ischemia or hypertension; severe renal impairment requiring dialysis. Pts previously treated with BEV required =28 days from last dose, no =Grade 3 hemorrhagic episode during therapy, and no history of =Grade 2 hemorrhagic event 6 mos prior to BEV treatment. Results: Of the 2,488 pts in ARCCS valid for safety analysis, 289 pts had received prior BEV: 65% male with median age 61 yrs. Grade 3 and 4 toxicities occurring in &gt;2% of prior BEV pts included hand-foot skin reaction 9.0%; fatigue 6.9%; hypertension 4.8%; dehydration, dyspnea, anorexia, and abdominal pain 3.1%; back pain, rash/desquamation, and mucositis 2.8%; pleural effusion and diarrhea 2.1%. Of the 195 BEV-pretreated pts evaluable for response, 152 (77.5%) had stable disease and 5 (2.5%) had confirmed partial responses (PR). There were 26 (13.3%) unconfirmed PRs reported according to RECIST, 4 of which missed a second scan due to US ARCCS enrollment ceasing upon FDA approval of SOR in 12/05. Conclusions: We observed activity of SOR following BEV therapy for advanced RCC. AEs in this subset were generally well tolerated and similar to those in the overall ARCCS population. Further investigation is warranted to elucidate mechanisms for response to SOR following prior antiangiogenic treatment. [Table: see text]
冠動脈疾患患者においてシロリムス溶出ステント(SES)内の新規動脈硬化病変はアテローム硬化の進行程度を反映しているかもしれない
Authors: Kuroda Masaru, Shinke Toshiro, Ohtake Hiromasa, Nakagawa Masayuki, Inoue Takumi, Hariki Hirotoshi, Ohsue Tsuyoshi, Taniguchi Yu, Iwasaki Masamichi, Nishio Ryo, Hiranuma Noritoshi, Kinutani Hiroto, Konishi Akihide, Hirata Ken-ichi
Journal: Circulation (2013)
Considerations and methods for placebo controls in surgical trials (ASPIRE guidelines)
Authors: David J Beard, Marion K Campbell, Jane M Blazeby, Andrew J Carr, Charles Weijer, Brian H Cuthbertson, Rachelle Buchbinder, Thomas Pinkney, Felicity L Bishop, Jonathan Pugh, Sian Cousins, Ian A Harris, L Stefan Lohmander, Natalie Blencowe, Katie Gillies, Pascal Probst, Carol Brennan, Andrew Cook, Dair Farrar-Hockley, Julian Savulescu, Richard Huxtable, Amar Rangan, Irene Tracey, Peter Brocklehurst, Manuela L Ferreira, Jon Nicholl, Barnaby C Reeves, Freddie Hamdy, Samuel CS Rowley, Jonathan A Cook
Journal: The Lancet (2020)
People with severe mental health conditions are let down by lack of local rehabilitation services
Authors: Jacqui Thornton
Journal: BMJ (2020)

A lack of national standards for the rehabilitation of people with severe mental health conditions and no agreed definition of appropriate out-of-area treatment is hindering efforts to deliver services, a report has found.1

Some people with severe mental health conditions, such as psychosis, need long term care for both their physical and mental health, says the report by Rethink Mental Illness and the Royal College of Psychiatrists.

It is especially important for these patients to have local services because a major focus of their rehabilitative care is on social inclusion and maintaining and building links with family support networks and with services in the community, said Rajesh Mohan, from the Royal College of Psychiatrists, and Mark Winstanley, chief executive of Rethink Mental Illness, …
PET scanning and patient reported dysphagia before and after chemotherapy (CT) for prediction of pathological response after CT and chemoradiotherapy (CRT) in patients with locally advanced esophageal cancer (EC): A multicenter phase ll trial of the Swiss
Authors: K. Ribi, E. Nitzsche, J. Schuller, B. Klaeser, T. Hany, A. Roth, V. Hess, M. Zuend, N. Lombriser, T. Ruhstaller
Journal: Journal of Clinical Oncology (2007)

4587 Background: Only responding patients (pts) ultimately benefit from preoperative therapy for locally advanced EC. To predict response quality after CRT and detect non-responders earlier, we evaluated changes from baseline in FDG uptake by PET scans and patient reported dysphagia after two cycles of CT. Methods: Pts with resectable, locally advanced squamous cell carcinoma or adenocarcinoma of the esophagus were treated with 2 cycles of CT with docetaxel/cisplatin (DC) q3w followed by CRT (DC weekly x5 with concomitant 45 Gy RT) and surgery. PET imaging using [F]-deoxyglucose (FDG) uptake and subjective dysphagia assessment using a quality of life module specific to EC (EORTC QLQ-OES24) were performed at baseline and after the 2nd cycle of CT. 40% decrease of FDG uptake was prospectively hypothesized to be an early predictor for a pathological complete remission (tumor regression grade 1, TRG) and subtotal regression (TRG 2) after the CRT. The predictive value of improvement in dysphagia was tested by analysis of covariance with baseline dysphagia as covariate. Results: Out of included 66 pts, 56 completed preoperative therapy and surgery. Dysphagia scores (range 0–100) were available in 51 pts, mean changes were 14 (n=13), 12 (n=16) and 12 (n=22) for pts with TRG 1, 2 or &gt;2, respectively, lacking any significance. 44 pts had two PET scans (5: centers not participating, 3: no FDG-uptake at baseline, 4: second scan too late or not done). Mean FDG-decrease was 49% (n=7), 44% (n=17), 15% (n=20) for pts with TRG 1, 2 or &gt;2, respectively. Less than 40% reduction in FDG uptake predicted non-response (TRG&gt;2) with sensitivity 70%, specificity 50%, negative predictive value 70% and positive predictive value 50%. FDG- uptake reduction indicated reduced risk of TRG&gt;2 in a logistic regression model (p&lt;0.01, 95%-CI 2–273). Conclusions: Decreased FDG uptake in sequential PET scans strongly correlates with tumor response, but is not accurate enough to early identify non- responders. Early improvement of dysphagia after 2 cycles CT did not predict TRG after CRT. No significant financial relationships to disclose.
Clustered CTCF binding is an evolutionary mechanism to maintain topologically associating domains
Authors: Elissavet Kentepozidou, Sarah J. Aitken, Christine Feig, Klara Stefflova, Ximena Ibarra-Soria, Duncan T. Odom, Maša Roller, Paul Flicek
Journal: Genome biology (2020)

Abstract Background CTCF binding contributes to the establishment of a higher-order genome structure by demarcating the boundaries of large-scale topologically associating domains (TADs). However, despite the importance and conservation of TADs, the role of CTCF binding in their evolution and stability remains elusive. Results We carry out an experimental and computational study that exploits the natural genetic variation across five closely related species to assess how CTCF binding patterns stably fixed by evolution in each species contribute to the establishment and evolutionary dynamics of TAD boundaries. We perform CTCF ChIP-seq in multiple mouse species to create genome-wide binding profiles and associate them with TAD boundaries. Our analyses reveal that CTCF binding is maintained at TAD boundaries by a balance of selective constraints and dynamic evolutionary processes. Regardless of their conservation across species, CTCF binding sites at TAD boundaries are subject to stronger sequence and functional constraints compared to other CTCF sites. TAD boundaries frequently harbor dynamically evolving clusters containing both evolutionarily old and young CTCF sites as a result of the repeated acquisition of new species-specific sites close to conserved ones. The overwhelming majority of clustered CTCF sites colocalize with cohesin and are significantly closer to gene transcription start sites than nonclustered CTCF sites, suggesting that CTCF clusters particularly contribute to cohesin stabilization and transcriptional regulation. Conclusions Dynamic conservation of CTCF site clusters is an apparently important feature of CTCF binding evolution that is critical to the functional stability of a higher-order chromatin structure.
Obesity: medical leaders call for end to “stigmatising” language
Authors: Gareth Iacobucci
Journal: BMJ (2020)

The Royal College of Physicians (RCP) and more than 100 medical and scientific organisations around the world have called for an end to “unscientific, stigmatising language” around obesity.

In a consensus statement published in the journal Nature Medicine on 4 March to coincide with the first World Obesity Day, the organisations argued for strong policies and legislation to prevent weight based discrimination.1

The …
Global Disability Burdens of Diabetes-Related Lower-Extremity Complications in 1990 and 2016
Authors: Yuqi Zhang, Peter A. Lazzarini, Steven M. McPhail, Jaap J. van Netten, David G. Armstrong, Rosana E. Pacella
Journal: Diabetes Care (2020)

No study has reported global disability burden estimates for individual diabetes-related lower-extremity complications (DRLECs). The Global Burden of Disease (GBD) study presents a robust opportunity to address this gap.GBD 2016 data, including prevalence and years lived with disability (YLDs), for the DRLECs of diabetic neuropathy, foot ulcer, and amputation with and without prosthesis were used. The GBD estimated prevalence using data from systematic reviews and DisMod-MR 2.1, a Bayesian meta-regression tool. YLDs were estimated as the product of prevalence estimates and disability weights for each DRLEC. We reported global and sex-, age-, region-, and country-specific estimates for each DRLEC for 1990 and 2016.In 2016, an estimated 131 million people (1.8% of the global population) had DRLECs. An estimated 16.8 million YLDs (2.1% global YLDs) were caused by DRLECs, including 12.9 million (95% uncertainty interval 8.30-18.8) from neuropathy only, 2.5 million (1.7-3.6) from foot ulcers, 1.1 million (0.7-1.4) from amputation without prosthesis, and 0.4 million (0.3-0.5) from amputation with prosthesis. Age-standardized YLD rates of all DRLECs increased by between 14.6% and 31.0% from 1990 estimates. Male-to-female YLD ratios ranged from 0.96 for neuropathy only to 1.93 for foot ulcers. The 50- to 69-year-old age-group accounted for 47.8% of all YLDs from DRLECs.These first-ever global estimates suggest that DRLECs are a large and growing contributor to the disability burden worldwide and disproportionately affect males and middle- to older-aged populations. These findings should facilitate policy makers worldwide to target strategies at populations disproportionately affected by DRLECs.
Abstract P499: <i>24-month Follow-up Of The ‘Stand And Move At Work’</i> Sedentary Behavior Intervention: Effects On Workplace Sitting Time
Authors: Miranda Larouche, Meynard J Toledo, Sarah L Mullane, Sarah A Rydell, Brenna J Vuong, Linda H Feltes, Nathan R Mitchell, Junia N de Brito, Kristina Hasanaj, Neil Carlson, Glenn A Gaesser, Noe C Crespo, J. M Oakes, Mark A Pereira, Matthew P Buman
Journal: Circulation (2020)

Multicomponent interventions that use sit-stand workstations (SSW) to reduce workplace sitting time have been largely successful. However, the long-term maintenance (i.e., &gt;12 months) of this behavior change is relatively unknown. We aimed to evaluate the 24-month maintenance of reductions in workplace sitting time, along with the effects of introducing the SSW after 12 months of multicomponent intervention only. We used data from Stand and Move at Work, a two-arm multi-site group randomized trial of 24 worksites (12 worksites per arm; N=630, 74% female, 45±11 years of age). Worksites in the STAND+ arm received 12 months of a multilevel (i.e., worksite policy, environmental, and individual-level strategies) intervention to increase light-intensity physical activity, along with a SSW, to increase standing time. Worksites in the MOVE+ arm (i.e., comparator) received the same multilevel intervention but were not provided with the SSW until after the intervention ended at 12 months. Sitting time was assessed for 7 consecutive days using the activPAL3c micro accelerometer at baseline, 12, and 24 months. Results are presented below in table form. In STAND+ , sitting time at 24 months, relative to baseline, was significantly reduced and similar in magnitude of change to what was observed at 12 months. In MOVE+ , sitting time at 24 months (a year after the SSW was introduced), relative to baseline, was significantly reduced but markedly smaller in magnitude of change than observed during the STAND+ active intervention period (i.e., 0 to 12 months). These results support the use of SSW coupled with a multicomponent intervention for optimal and long-term maintenance of reductions in workplace sitting time. Hierarchical regression models were adjusted for worksite clustering, age, sex, and baseline BMI.
TCT-739 TAVI Karlsruhe (TAVIK) - a comparison of minimal invasive and surgical aortic valve replacement in patients with severe symptomatic aortic stenosis and intermediate risk for conventional surgery
Authors: Gerhard Schymik, M. Heimeshoff, Peter Bramlage, A. Wuerth, Lothar Pilz, J.-S. Schymik, Rainer Wondraschek, Bernd-Dieter Gonska, Herbert Posival, C. Schmitt, Holger Schroefel
Journal: Journal of the American College of Cardiology (2013)