tbuckley/cabot-search huggingface dataset:
Trastuzumab versus observation for HER2 nonamplified early breast cancer with circulating tumor cells (EORTC 90091-10093, BIG 1-12, Treat CTC): a randomized phase II trial
Authors: M. Ignatiadis, S. Litière, F. Rothe, S. Riethdorf, C. Proudhon, T. Fehm, K. Aalders, H. Forstbauer, P.A. Fasching, E. Brain, P. Vuylsteke, E. Guardiola, R. Lorenz, K. Pantel, K. Tryfonidis, W. Janni, M. Piccart, C. Sotiriou, B. Rack, J.-Y. Pierga
Journal: Annals of Oncology (2018)

Trastuzumab improves the outcome of women with HER2 positive breast cancer. We aimed to assess whether trastuzumab decreases the detection rate of circulating tumor cells (CTCs) in women with high risk, HER2 nonamplified, early breast cancer.The EORTC 90091-10093 BIG 1-12 Treat CTC is a phase II trial, conducted in 70 hospitals and 6 CTC laboratories across 5 European countries. Patients with centrally confirmed HER2 nonamplified breast cancer and ≥1 centrally confirmed CTC per 15 ml of blood by CellSearch® following surgery and (neo)adjuvant chemotherapy were randomized (1 : 1) to 6 cycles of trastuzumab intravenously versus 18 weeks of observation. Randomization was stratified for center, locally confirmed estrogen receptor status and adjuvant versus neoadjuvant chemotherapy. The primary end point was rate of detection of ≥1 CTC per 15 ml of blood at week 18. Secondary end points were invasive disease-free survival (iDFS) and cardiac safety.Between 30 April 2013 and 17 October 2016, 1317 patients were screened; 95 (7.2%) had detectable CTC(s), and 63 (4.8%) were randomized to trastuzumab (n = 31) or observation (n = 32). Fifty-eight patients were assessable for the primary end point, 29 in each arm. In 9 of the 58 patients, CTC(s) were still detected at week 18 : 5 in the trastuzumab and 4 in the observation arm (one-sided Fisher's exact test, P = 0.765). An Independent Data Monitoring Committee recommended stopping further accrual for futility for the primary end point. Median follow-up at database lock was 13 months (IQR 4-16.5). The 1-year iDFS was 93.8% (95% CI 77.3-98.4) in the observation versus 84.8% (95% CI 63.4-94.2) in the trastuzumab arm. No grade 2-4 cardiac events were observed in the trastuzumab arm.Trastuzumab does not decrease the detection rate of CTCs in HER2 nonamplified, nonmetastatic breast cancer.
AB0320 Impact of rheumatoid arthritis on life quality: before and after treatment
Authors: X. Grapton, P. Lemesle, L. Arabian, V. Strotz
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Life quality issues in rheumatoid arthritis (RA) are often spontanously mentioned by patients or identified by rheumatologists. Besides classic follow up parameters like DAS28, we have to consider those issues to improve our patients life quality. <h3>Objectives</h3> Explore and quantify the impact of RA on life quality via everyday’s life and psychological items and the effect of treatment on them. <h3>Methods</h3> RA cases were collected by a group of 20 private practice rheumatologists in the Paris area. Basic informations about the patient and his disease were provided by his rheumatologist. Questionnaire including 12 themes and 41 items was filled in by the patient. <h3>Results</h3> 167 cases collected: 82% women, mean age 57 years, 56% moderate and 14% severe disease, 76% ACPA positive, 73% structural damage. Initial DAS28 4,7. Post treatment DAS28 2.7. Drugs: classic DMARDs 95%, corticosteroids 73%, biological DMARDs 22%, combination therapy 76%. Life quality issues are spontaneously mentioned by 55% of the patients. Before treatment, psychological well-being and housework ability are altered in more than 50% of the patients. Impact on economy, food and social life occurs in less than 25% of the cases. Life quality is mostly altered by pain (85%), then fatigue (75%) and handicap (58%). We find a correlation between the severity of RA and the importance of the impact on psychological well-being, sexual life and hobbies. After treatment, psychological well-being improves in 53% of the patients, and social life, work, getting about and sexual life in 45%–32%. Items improved around 50% of the patients are in order: sleep, relation to other people, feeling excluded, social life, depression, sick leave, concentration problems, anxiety and shopping. We find and improvement in a third of cases in house-keeping, going out, sports and libido. 72% of the patients feel a lack of listening by their families, even under treatment. <h3>Conclusions</h3> Treatment of RA, including drugs and associated measures, reduces the frequency of negative impact on life quality. We observe that, when DAS28 drops by 43%, the frequency of RA related repercussions diminishes by 31% (14%–50%) on the chosen items. All the items are impacted by RA before treatment and stay impacted after treatment, but less frequently, except family relations. More than one patient of 2 gains correct sleep and almost half of them aren’t depressed or anxious anymore. Impact on social activity and house-keeping activity are less frequently improved. Regarding these facts, the rheumatologist has to accomplish a tight follow-up and suggest, besides drug treatment, associated measures like physiotherapy, professionnel activity and environment adaptation and rest among others. A qualitative evaluation of the improvement will be the subject of a further study. <h3>Disclosure of Interest</h3> None declared
Nonopioids and opioids gave similar relief for back pain or osteoarthritis but nonopioids had fewer adverse effects
Authors: Brian Budenholzer
Journal: Annals of Internal Medicine (2018)

Source Citation Krebs EE, Gravely A, Nugent S, et al. Effect of opioid vs nonopioid medications on pain-related function in patients with chronic back pain or hip or knee osteoarthritis pain: the SPACE randomized clinical trial. JAMA. 2018;319:872-82. 29509867
SP0149 The patient’s perspective of living with complex regional pain syndrome
Authors: R. Connett
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> There is wide acknowledgement in medical literature that CRPS is a very painful condition that can be severely debilitating and adversely affect quality of life. In an attempt to assist the many highly caring, gifted and dedicated clinicians who want to understand what this actually means from the perspective of those who live with the condition relentlessly day by day, I shall attempt to bring such a statement to life. I shall speak mainly from my own journey of learning to live with CRPS since 2001, but shall also draw on the experiences fellow sufferers have shared with me, and humbly contribute some key messages for the clinicians who come into contact with patients pre or post diagnosis. <h3>Disclosure of Interest</h3> None declared
Margaret McCartney: Summer holidays create a special “low value” activity visa
Authors: Margaret McCartney
Journal: BMJ (2018)

A summer campaign is in full tropical swing. “Contact your GP or travel health professional at least four to six weeks before your trip to check whether you need any vaccinations and if any of your prescribed medication contains what are known as ‘controlled drugs.’” That’s advice from the Foreign and Commonwealth Office, issued through its advertising agency.1

I’m not sure what work the Foreign Office would like GPs to stop doing to fit this in. I’m not even sure what it means by a “travel health professional.” But, even though I’ve done no cost effectiveness analysis, I’m confident that it isn’t doable.

The …
NLRC5 deficiency protects against acute kidney injury in mice by mediating carcinoembryonic antigen–related cell adhesion molecule 1 signaling
Authors: Quanxin Li, Ziying Wang, Yan Zhang, Jiaqing Zhu, Liang Li, Xiaojie Wang, Xiaoyang Cui, Yu Sun, Wei Tang, Chengjiang Gao, Chunhong Ma, Fan Yi
Journal: Kidney International (2018)
Effect of itraconazole or rifampicin on the pharmacokinetics (PK) of osimertinib (AZD9291).
Authors: Karthick Vishwanathan, James Chih-Hsin Yang, Jong-Seok Lee, Matthew Krebs, Paul A. Dickinson, Khanh Bui, Doris Weilert, Karen So, Karen Thomas, R Donald Harvey
Journal: Journal of Clinical Oncology (2016)

e14100 Background: Osimertinib is a potent, oral, irreversible EGFR-TKI with efficacy in pts with EGFR-TKI sensitizing (EGFRm) and T790M mutation positive advanced NSCLC. Metabolism of osimertinib and its metabolites (AZ5104 and AZ7550) is mediated by cytochrome P450 (CYP)3A4 and CYP3A5. We report drug-drug interaction results (Part A) from 2 Phase I open-label, 2-part clinical studies that investigated the effects of strong CYP3A4 inhibition (itraconazole) or induction (rifampicin) on osimertinib PK in pts with EGFRm NSCLC that had progressed after prior treatment with EGFR-TKI. Part B (ongoing) further evaluates pt safety on osimertinib. Methods: Study 12 (NCT02157883) Part A evaluated the effect of multiple doses of itraconazole on the single-dose PK of osimertinib. Pts received a single dose of osimertinib 80 mg on Days 1 and 10 and itraconazole capsules (200 mg twice daily) on Days 6–18. Study 13 (NCT02197247) Part A evaluated the effect of multiple-dose rifampicin on steady-state (ss) PK of osimertinib on Days 28/29, 49/50 and 77/78. Pts received osimertinib 80 mg once daily (qd) on Days 1–77, co-administered with rifampicin (600 mg qd) on Days 29–49. Results: Thirty-six of 39 and 40 of 41 treated pts had evaluable osimertinib data for Study 12 and Study 13, respectively. The geometric least squares mean (GLSM) ratios (90% CIs) of osimertinib + itraconazole / osimertinib alone for Cmax and AUC were 80% (73–87) and 124% (115–135), respectively; below the predefined no effect 90% CI limit of 200%. The GLSM ratios of osimertinib + rifampicin / osimertinib alone for Css,max and AUCss were 27% (24–30) and 22% (19–24), respectively. The induction effect of rifampicin was seen within 7 days of rifampicin initiation and continued for the duration of treatment, reaching ss by 3 weeks. Induction abated 3 weeks after rifampicin discontinuation, with osimertinib Css,max and AUCss values similar to baseline within 4 weeks of rifampicin discontinuation. Osimertinib was well tolerated with reported adverse events consistent with its known safety profile. Conclusions: These studies show that osimertinib concentration and exposure is not affected by strong CYP3A4 inhibitors and is significantly decreased with strong CYP3A inducers. Clinical trial information: NCT02157883 and NCT02197247.
Biomarker assessment of the CBCSG006 trial: a randomized phase III trial of cisplatin plus gemcitabine compared with paclitaxel plus gemcitabine as first-line therapy for patients with metastatic triple-negative breast cancer
Authors: J. Zhang, Y. Lin, X.J. Sun, B.Y. Wang, Z.H. Wang, J.F. Luo, L.P. Wang, S. Zhang, J. Cao, Z.H. Tao, J. Wu, Z.M. Shao, W.T. Yang, X.C. Hu
Journal: Annals of Oncology (2018)

BackgroundCBCSG006 trial reported the superior efficacy of cisplatin plus gemcitabine (GP) regimen than paclitaxel plus gemcitabine (GT) regimen as first-line treatment of metastatic triple-negative breast cancer (mTNBC). This study focused on the updated survival data and the explorations of potential biomarkers for efficacy.Patients and methodsGerm-line mutations of homologous recombination (HR) panel, BRCA1/2 included, were evaluated in 55.9% (132/236) patients. PD-L1 expression was evaluated in 48.3% (114/236) patients. A nonparametric sliding-window subpopulation treatment effect pattern plot (STEPP) methodology was used to analyze the absolute survival benefits. All statistical tests were two-sided.ResultsMedian progression-free survival (PFS) was 7.73 [95% confidence interval (CI) 6.46–9.00] months for GP arm and 6.07 (95% CI 5.32–6.83) months for GT arm (P= 0.005). No significant difference in overall survival (OS) was observed. There was significant interaction between HR status and treatment for PFS and status of HR deficient significantly correlated with higher objective response rate (ORR) and longer PFS in GP arm than in GT arm (71.9% versus 38.7%, P= 0.008; 10.37 versus 4.30 months, P= 0.011). There was no significant interaction between germ-line BRCA1/2 (gBRCA1/2) status and treatment for PFS. Patients with gBRCA1/2 mutation had numerically higher ORR and prolonged PFS in GP arm than in GT arm (83.3% versus 37.5%, P= 0.086; 8.90 versus 3.20 months, P= 0.459). There was no significant interaction between PD-L1 status and treatment for PFS, and no significant differences in ORR, PFS or OS between two arms regardless of PD-L1 status. In STEPP analysis, patients with lower composite risks had more absolute benefits in PFS than those with higher composite risks.ConclusionsGP regimen has superior efficacy than GT regimen as first-line chemotherapy for mTNBC patients. Germ-line mutations of BRCA1/2 and HR panel are possible biomarkers for better performance of cisplatin-based regimens. A composite risk model was developed to guide patient selection for GP treatment in TNBC patients.Trial registrationClinicalTrials.gov, NCT01287624.
OP0182 Gout and dementia in the elderly: a medicare claims study
Authors: J.A. Singh, J.D. Cleveland
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The pursuit of a link between gout/hyperuricemia and dementia has led to contradictory results. Most observational studies, including population-based studies, showed that hyperuricemia was associated with a higher risk of dementia and less cognitive dysfunction, while a few studies found hyperuricemia to be associated with a lower risk of dementia. Recently, a large French population-based study in the elderly (65 years or older) showed that hyperuricemia was associated with a higher risk of dementia and with MRI changes of ageing in the brain. <h3>Objectives</h3> To assess whether gout in the elderly is associated with a risk of incident dementia. <h3>Methods</h3> We used the 5% Medicare claims data for this observational cohort study. We used multivariable-adjusted Cox proportional hazard models to assess the association of gout with incident dementia, adjusting for potential confounders/covariates including demographics (age, race, gender), comorbidities (Charlson-Romano comorbidity index), and medications commonly used for cardiac diseases (statins, beta-blockers, diuretics, and angiotensin converting enzyme (ACE)-inhibitors) and gout (allopurinol and febuxostat). <h3>Results</h3> In our cohort of 1.23 million Medicare beneficiaries, 65 324 had incident dementia. The crude incidence rates in people without and with gout were 7.36 and 13.58 per 1000 person-years, respectively. In multivariable-adjusted analyses, gout was independently associated with a significantly higher hazard ratio of incident dementia, with a hazard ratio [HR] of 1.17 (95% CI, 1.13, 1.21); sensitivity analyses confirmed the main findings. Compared to age 65 to &lt;75 years, older age groups were associated with 3.3 and 6.3-fold higher hazards of dementia; hazards were also higher for females, Black race or people with higher medical comorbidity. Subgroup analyses indicated that gout was significantly associated with dementia in patients without key comorbidities (CAD, hyperlipidemia, CVD, diabetes, hypertension) with HR ranging 1.20–1.57, but not in patients with each of these comorbidities, except CAD, with HR 0.97–1.07 (table 1). <h3>Conclusions</h3> Gout was independently associated with 17%–20% higher risk of incident dementia in the elderly. Future studies need to understand the pathogenic pathways involved in this increased risk. <h3>Acknowledgements</h3> This material is the result of work supported by research funds from the Division of Rheumatology at the University of Alabama at Birmingham and the resources and use of facilities at the Birmingham VA Medical Centre, Birmingham, Alabama, USA. <h3>Disclosure of Interest</h3> J. Singh Grant/research support from: Takeda, Savient, Consultant for: Savient, Takeda, Regeneron, Merz, Iroko, Bioiberica, Crealta/Horizon and Allergan pharmaceuticals, WebMD, UBM LLC and the American College of Rheumatology, J. Cleveland: None declared
FRI0521 Combining fractal- and entropy-based bone texture analysis for the prediction of osteoarthritis: data from the multicenter osteoarthritis study (MOST)
Authors: R. Ljuhar, Z. Bertalan, S. Nehrer, B. Norman, H.-P. Dimai, A. Fahrleitner-Pammer, D. Ljuhar
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Osteoarthritis (OA) is one of the leading causes of long-term pain and disabilities associated with musculoskeletal disorders. Effective treatment and disease-progression slowdown depend on early detection and quantification of risk. However, current disease parameters, like joint space width (JSW), have proven to be insufficient for the prediction of OA. <h3>Objectives</h3> The purpose of the present study was to investigate if combining fractal- and entropy-based bone texture analyses with joint space width (JSW) and joint space area (JSA) may improve prediction of OA. Conventional posterior-anterior (PA) knee radiographs of men and women were obtained from the Multicenter Osteoarthritis Study (MOST) database, which provides valuable information to identify and define modifiable biomechanical, bone and structural, nutritional, and other risk factors for new disease and progression of existing disease.<sup>1</sup> <h3>Methods</h3> Oriented fractal- and entropy based texture algorithms were developed, using state-of-the-art computer hardware and software as well as specific machine-learning algorithms. The selected subchondral area used for textural analyses included 4 regions of interest (ROI) in the proximal tibia and one on each condyle of the distal femur (figure 1). Furthermore, JSW and JSA were assessed using newly developed and fully automated software. <h3>Results</h3> 1092 conventional knee radiographs obtained from one study centre were screened for eligibility. Of these, a total of 574 radiographs (230 women, 344 men) met the inclusion criteria, i.e. a Kellgren &amp; Lawrence (KL) score of 0 at baseline. At month 84, 41 female and 79 male patients had developed KL≥1, and 189 female and 265 male patients remained at KL0. Area-Under-the-Curve (AUC) for incident OA using JSW/JSA and clinical features was 0.67±0.08 for women, and 0.61±0.1 for men. In contrast, combining fractal/entropy-based texture, JSW/A and clinical features resulted in significantly improved AUC for women and men (0.80±0.07 for women and 0.69±0.1 for men, respectively). To test whether these differences in predicting incident-OA were significant, we performed classifier comparison: t=3.84; p&lt;10–3 for women, and t=3.38; p&lt;10–3 for men. <h3>Conclusions</h3> This study provides strong evidence, that a combination of fractal- and entropy-based textural analyses of plain subchondral bone radiographs together with JSW/A and clinical features is superior to JSW/A and clinical features alone in predicting incident OA in men and women. <h3>Reference</h3> [1] http://most.ucsf.edu/studyoverview.asp <h3>Disclosure of Interest</h3> R. Ljuhar Shareholder of: ImageBiopsy Lab, Z. Bertalan : None declared, S. Nehrer: None declared, B. Norman : None declared, H.-P. Dimai : None declared, A. Fahrleitner-Pammer: None declared, D. Ljuhar: None declared
Ventilation inhomogeneity in infants with recurrent wheezing
Authors: Zihang Lu, Rachel E Foong, Krzysztof Kowalik, Theo J Moraes, Ayanna Boyce, Aimee Dubeau, Susan Balkovec, Per Magnus Gustafsson, Allan B Becker, Piush J Mandhane, Stuart E Turvey, Wendy Lou, Felix Ratjen, Malcolm Sears, Padmaja Subbarao
Journal: Thorax (2018)

Background The care of infants with recurrent wheezing relies largely on clinical assessment. The lung clearance index (LCI), a measure of ventilation inhomogeneity, is a sensitive marker of early airway disease in children with cystic fibrosis, but its utility has not been explored in infants with recurrent wheezing. Objective To assess ventilation inhomogeneity using LCI among infants with a history of recurrent wheezing compared with healthy controls. Methods This is a case–control study, including 37 infants with recurrent wheezing recruited from outpatient clinics, and 113 healthy infants from a longitudinal birth cohort, the Canadian Healthy Infant Longitudinal Development study. All infants, at a time of clinical stability, underwent functional assessment including multiple breath washout, forced expiratory flows and body plethysmography. Results LCI z-score values among infants with recurrent wheeze were 0.84 units (95% CI 0.41 to 1.26) higher than healthy infants (mean (95% CI): 0.26 (−0.11 to 0.63) vs −0.58 (−0.79 to 0.36), p&lt;0.001)). Nineteen percent of recurrently wheezing infants had LCI values that were above the upper limit of normal (&gt;1.64 z-scores). Elevated exhaled nitric oxide, but not symptoms, was associated with abnormal LCI values in infants with recurrent wheeze (p=0.05). Conclusions Ventilation inhomogeneity is present in clinically stable infants with recurrent wheezing.
Long-term Outcomes of Lifestyle Intervention to Prevent Diabetes in American Indian and Alaska Native Communities: The Special Diabetes Program for Indians Diabetes Prevention Program
Authors: Luohua Jiang, Ann Johnson, Katherine Pratte, Janette Beals, Ann Bullock, Spero M. Manson
Journal: Diabetes Care (2018)

Evidence for long-term translational effectiveness of lifestyle interventions in minority populations is scarce. This article reports long-term outcomes, for up to 10 years, of such an intervention to prevent diabetes in American Indian and Alaska Native (AI/AN) communities.
Short-Term Fasting Reveals Amino Acid Metabolism as a Major Sex-Discriminating Factor in the Liver
Authors: Sara Della Torre, Nico Mitro, Clara Meda, Federica Lolli, Silvia Pedretti, Matteo Barcella, Luisa Ottobrini, Daniel Metzger, Donatella Caruso, Adriana Maggi
Journal: Cell Metabolism (2018)

Sex impacts on liver physiology with severe consequences for energy metabolism and response to xenobiotic, hepatic, and extra-hepatic diseases. The comprehension of the biology subtending sex-related hepatic differences is therefore very relevant in the medical, pharmacological, and dietary perspective. The extensive application of metabolomics paired to transcriptomics here shows that, in the case of short-term fasting, the decision to maintain lipid synthesis using amino acids (aa) as a source of fuel is the key discriminant for the hepatic metabolism of male and female mice. Pharmacological and genetic interventions indicate that the hepatic estrogen receptor (ERα) has a key role in this sex-related strategy that is primed around birth by the aromatase-dependent conversion of testosterone into estradiol. This energy partition strategy, possibly the result of an evolutionary pressure enabling mammals to tailor their reproductive capacities to nutritional status, is most important to direct future sex-specific dietary and medical interventions.