tbuckley/cabot-search huggingface dataset:
Nintedanib in patients with progressive fibrosing interstitial lung diseases—subgroup analyses by interstitial lung disease diagnosis in the INBUILD trial: a randomised, double-blind, placebo-controlled, parallel-group trial
Authors: Athol U Wells, Kevin R Flaherty, Kevin K Brown, Yoshikazu Inoue, Anand Devaraj, Luca Richeldi, Teng Moua, Bruno Crestani, Wim A Wuyts, Susanne Stowasser, Manuel Quaresma, Rainer-Georg Goeldner, Rozsa Schlenker-Herceg, Martin Kolb, S. Abe, M. Aburto, O. Acosta, C. Andrews, D. Antin-Ozerkis, G. Arce, M. Arias, S. Avdeev, A. Barczyk, R. Bascom, E. Bazdyrev, P. Beirne, E. Belloli, M.A. Bergna, E. Bergot, N. Bhatt, S. Blaas, B. Bondue, F. Bonella, E. Britt, K. Buch, J. Burk, H. Cai, A. Cantin, D.M. Castillo Villegas, A. Cazaux, S. Cerri, S. Chaaban, N. Chaudhuri, V. Cottin, B. Crestani, G. Criner, C. Dahlqvist, S. Danoff, J. Dematte D'Amico, D. Dilling, P. Elias, N. Ettinger, J. Falk, E.R. Fernández Pérez, A. Gamez-Dubuis, G. Giessel, A. Gifford, M. Glassberg, C. Glazer, J. Golden, L. Gómez Carrera, J. Guiot, R. Hallowell, H. Hayashi, J. Hetzel, N. Hirani, L. Homik, B. Hope-Gill, D. Hotchkin, K. Ichikado, M. Ilkovich, Y. Inoue, S. Izumi, E. Jassem, L. Jones, S. Jouneau, R. Kaner, J. Kang, T. Kawamura, R. Kessler, Y. Kim, K. Kishi, H. Kitamura, M. Kolb, Y. Kondoh, C. Kono, D. Koschel, M. Kreuter, T. Kulkarni, J. Kus, F. Lebargy, A. León Jiménez, Q. Luo, Y. Mageto, T.M. Maher, S. Makino, S. Marchand-Adam, C. Marquette, R. Martinez, M. Martínez, R. Maturana Rozas, Y. Miyazaki, S. Moiseev, M. Molina-Molina, L. Morrison, L. Morrow, T. Moua, A. Nambiar, Y. Nishioka, H. Nunes, M. Okamoto, J. Oldham, M. Otaola, M. Padilla, J.S. Park, N. Patel, A. Pesci, W. Piotrowski, L. Pitts, H. Poonyagariyagorn, A. Prasse, S. Quadrelli, W. Randerath, R. Refini, M. Reynaud-Gaubert, F. Riviere, J.A. Rodríguez Portal, I. Rosas, M. Rossman, Z. Safdar, T. Saito, N. Sakamoto, M. Salinas Fénero, J. Sauleda, S. Schmidt, M.B. Scholand, M. Schwartz, S. Shapera, O. Shlobin, B. Sigal, A. Silva Orellana, D. Skowasch, J.W. Song, S. Stieglitz, H. Stone, M. Strek, T. Suda, H. Sugiura, H. Takahashi, H. Takaya, T. Takeuchi, K. Thavarajah, L. Tolle, S. Tomassetti, K. Tomii, C. Valenzuela, C. Vancheri, F. Varone, S. Veeraraghavan, A. Villar, S. Weigt, L. Wemeau, W. Wuyts, Z. Xu, V. Yakusevich, Y. Yamada, H. Yamauchi, D. Ziora
Journal: The Lancet Respiratory Medicine (2020)
A phase II study of irinotecan and docetaxel in patients with platinum-resistant relapsed epithelial ovarian cancer
Authors: T. Matsumoto, M. Hiura, T. Oshita, E. Hirata, Y. Shiroyama, J. Wroblewski, T. Yokoyama, T. Nogawa
Journal: Journal of Clinical Oncology (2007)

16062 Background: Patients with epithelial ovarian cancer are often diagnosed with advanced-stage disease. Although clinical complete remissions are obtained in the majority of patients through a combination of cytoreductive surgery and chemotherapy, relapse is common. Relapsed patients with a short treatment-free interval (TFI) after prior chemotherapy have a poor prognosis. We conducted a pilot study of irinotecan (CPT-11) and docetaxel (DTX) in patients with platinum-resistant relapsed epithelial ovarian cancer. Methods: Eligible patients must have at least one platinum and paclitaxel-containing regimen, and recur with a TFI of less than 6 months. CPT-11 60 mg/m 2 and DTX 30 mg/m 2 were administrated on days 1, 8, 15 of a 28-day cycle. Eligibility included preserved organ function, aged 20–75, and ECOG performance status 0 or 1. The primary endpoint was response rate, and secondary objectives were duration of response, time to progression (TTP) and safety. Toxicity was assessed using NCI-CTCAE ver.2.0. Results: Between 12/2000 and 4/2005, 26 patients were enrolled, 24 of whom were eligible. The median age was 57.5 years (range 35–75). A total of 99 cycles were analyzed, median number of cycles was 3 (range 1–12). Grade 3/4 hematologic toxicities occurred in 33.3% for anemia, 4.2% for thrombocytopenia, 50.0% for leucopenia, and 62.5% for neutropenia. Non-hematologic grade 3/4 toxicities were not observed. Efficacy based on RECIST criteria was available for 20 patients, and the overall response rate was 10% (2 PR) with SD in 40%. In addition, of 4 patients with no measurable diseases, 2 patients had a confirmed PR by CA125 criteria (GCIG). Over all, clinical benefit (PR, SD) was seen in 63.6% of patients. The median duration of response was 17 weeks (range 2–49). The median TTP was 31 weeks (range 7–86). Conclusions: These results suggest that weekly treatment with CPT-11 and DTX is feasible and effective chemotherapy regimen for platinum-resistant relapsed ovarian cancer. No significant financial relationships to disclose.
Induction of VEGF secretion in ovarian cancer by PDGF BB
Authors: D. Matei, S. Kelich, L. Cao, N. Menning, R. Emerson, R. Emerson, J. Rao, G. Sledge
Journal: Journal of Clinical Oncology (2007)

5557 Background: We identified the PDGFR as a potential target in epithelial ovarian carcinoma (EOC). This led us to test whether inhibition of the receptor affects ovarian cancer cell proliferation and survival and regulates other processes critical to tumor growth and metastasis. We postulated that the PDGF-PDGFR axis regulates VEGF secretion in EOC. Methods: VEGF secretion in ovarian tumors, cancer cells, serum and ascites was measured by IHC, Western Blot and ELISA. The HOG Gyn03–62 protocol was a phase II protocol for patients with recurrent platinum resistant EOC. Patients were treated with imatinib and docetaxel. Serum and tumor samples from patients enrolled on this protocol were analyzed for VEGF. Results: VEGF expression was quantified by IHC in ovarian tumors. Of 21 PDGFR expressing ovarian tumors, seven specimens immunostained strongly for VEGF and six tumors demonstrated 2+ VEGF reactive extracellular (secreted) material. PDGF and VEGF secretion was measured in 17 specimens of malignant EOC ascites. The levels of PDGF BB and VEGF were strongly correlated (Pearson coefficient =0.728, p-value=0.001), suggesting that the two pathways interconnect. There was no correlation between PDGF AA and VEGF levels. VEGF levels were measured in 13 paired serum samples from patients enrolled in the clinical protocol HOG: Gyn03–62, before and after treatment. VEGF serum levels were stabilized or decreased in 9 of 13 EOC patients treated with imatinib. In conditioned media from primary cells, VEGF secretion was four fold higher for tumor derived cells than for cells derived from the normal ovarian epithelium. PDGF increased ten-fold VEGF secretion in PDGFR expressing immortalized ovarian cells (C272/hTert/E7 and C889/hTert), while imatinib reduced VEGF production to basal state. The effects of imatinib were mediated via inhibition of Akt and MAPK pathways, by stabilization of HIF1 alpha. In ovarian cancer cells overexpressing consitutively active Akt, imatinib inhibited only partially the secretion of VEGF compared to control cells, suggesting that the PI3K/Akt pathway is significantly implicated in PDGF-stimulated VEGF secretion. Conclusions: These results suggest that by blocking the PDGFR, imatinib inhibits VEGF production. This affects the tumor microenvironment favoring ovarian tumor growth and metastasis. No significant financial relationships to disclose.
Successful treatment of childhood astrocytomas with cisplatin and irinotecan
Authors: J. Mora, O. Cruz, A. Parareda, C. de Torres, A. Guillen, R. Navarro, G. Garcia, J. Costa
Journal: Journal of Clinical Oncology (2007)

9508 Background: Childhood astrocytomas are a heterogeneous group of neoplasms for which non-surgical management is controversial. After a pilot study suggesting that irinotecan/cisplatin (I/C) may be effective for spinal cord astrocytomas in children (Mora et al, Neuro-Oncol 2007), we initiated a phase II trial for progressing astrocytomas with the aim of avoiding radiation therapy for low grade's and improve outcome for high grade's. Methods: The indication for adjuvant therapy was based upon histology, the extent of surgical resection, and the presence of clinical or neuroradiological signs of progression. Weekly Irinotecan (50 mg/m 2 and 65 mg/m 2 the last 2 cycles) and Cisplatin (30 mg/m 2 ) for four consecutive weeks (1 cycle), and a total of 4 cycles was used. Results: Since 2004, 17 children aged 7m-17y were treated including 5 WHO grade I, 6 grade II, 3 grade III, and 3 non biopsied tumors: 2 intrinsic brain-stem tumors (BST) and 1 optic-pathway (OP) tumor. No patient had clinical signs of neurofibromatosis. Primary sites included 4 supratentorial, 3 BST, 3 OP, 1 cerebellar, and 6 spinal tumors. Gross total resection was performed in 1 case, subtotal in 4 and only biopsy in 9. Six patients received chemotherapy and one radiotherapy prior to the I/C regimen. Vomiting was easily controlled except for patients with BST. All but 2 patients, because of C allergy, completed the protocol with no documented ototoxic, renal, or GI side effects. Eleven (65%) pts had a complete clinical response, including 1 BST and all the spinal cord cases. Remarkably all the clinical responses were rapid, within the first 1–2 weeks of treatment. Twelve (70%) pts had a &lt;25 [O1] % reduction of the tumor size at the end of therapy including 2 spinal cord cases that achieved complete radiological responses 10 months after the end of therapy. One BST patient progressed on therapy. Thus far, none of the low grade cases have received radiotherapy, although median f/u is only 1 year. All pts are alive and well. Conclusions: Remarkable clinicoradiological responses and avoidance of radiotherapy was obtained using the I/C regimen for childhood astrocytoma. No significant financial relationships to disclose.
Abstract P534: Is a Positive Family History of Cardiovascular Diseases Associated With Ideal Cardiovascular Health in the Community? The Polish Norwegian Study
Authors: Georgeta Vaidean, Marta Manczuk, Sandeep Vansal
Journal: Circulation (2020)

Introduction: Self-reported family history of cardiovascular diseases (FHxCVD) is associated with an increased cardiovascular risk. In contrast to genetic profiling, FHxCVD has the advantage that it reflects not only genetic susceptibility, but also factors related to a shared environment and behaviors. Ideal cardiovascular health (ICVH) is a summary indicator of behavioral and major subsequent biological factors. FHxCVD is presumed to motivate the adoption of a healthy lifestyle, yet little evidence exists to support this hypothesis in a community setting. Hypothesis: We assessed the hypothesis that self-reported family history of cardiovascular diseases is associated with ICVH in a community based study. Methods: We used cross-sectional, baseline data of 10934 participants, age 45 to 64 years free of cardiovascular diseases in an ongoing cohort study (PONS). Data were collected through structured questionnaires and fasting blood samples. Ideal cardiovascular health was defined according to the American Heart Association criteria (7 metrics assessed at 3 levels: ideal, intermediate, and poor). FHxCVD was self-reported, based on three questions inquiring about coronary heart disease, stroke, hypertension in parents and siblings. We considered a positive FHxCVD if an affirmative answer to any of these three questions was reported. We used multivariable logistic models and adjusted for age, sex, education, place of residence, health care services. Results: The prevalence of poor CVH (0-2 ideal metrics) was 63% and of ideal CVH (6, 7 ideal metrics) was 0.07%. The prevalence of a positive FHxCVD was 77%. Mean (SD) for ICVH score was 2.20 (1.06), with no difference between those with positive and negative FHxCVD. A positive FHxCVD was associated with increased odds of a poor cardiovascular health (0-2 health components), OR (95%CI) 1.12 (1.01-1.23), after adjusting for age, sex, education, rural residence and health care services. Among participants with known history of hypertension, having a positive family history of HTN (but not of CHD or stroke) was associated with lower odds of having their blood pressure controlled (OR 0.83 , 95%CI 0.71-0.96), after multivariable adjustment. Conclusion: In this community-based study we found that self-reported FHxCVD is not accompanied by healthy behaviors. In spite of its personal value, simple knowledge of one’s FHxCVD may not suffice as motivator for lifestyle changes.
In Reply
Authors: Hanna Sanoff, Harry Bleiberg, Richard Goldberg
Journal: Journal of Clinical Oncology (2007)

In case of colorectal cancer, 26% of all deaths due to colorectal cancer occurred in people from birth to 64 years, while they consumed 41% to 43% of treatment cost.People older than 65 account for 74% of deaths due to colorectal cancer and received only 57% to 59% of all of the treatment cost (Fig 1).Taking into consideration even the natural course of these diseases, there is a shift between the distribution of treatment cost of and deaths due to breast and colorectal cancer in favor of younger age groups.Max et al reported a similar finding in cervical cancer, where almost two thirds (64%) of the deaths due to cervical cancer occurred among women younger than 65, while they represent 84.2% of hospital costs.Most of these differences are derived from the different preferences in treatment, and the undertreatment of senior patients older than 65 years resulted in a higher breast cancer mortality. 6 Our study also confirmed that older colorectal cancer patients are less likely to receive treatment. 7lthough the undertreatment of elderly population can be explained partly by the general health status of senior people, it is a major challenge for oncologists to balance the risks and benefits of treatment in elderly patients on an individual level.Health care financing agencies face the same challenge in providing equal access to treatment for elderly patients on a population level.
Abstract P024: Associations Between Carotid-femoral And Estimated Pulse Wave Velocity In Older Adults: The Atherosclerosis Risk In Communities (ARIC) Study
Authors: Patricia Pagan Lassalle, Michelle L Meyer, Kevin S Heffernan, Adam W Kiefer, Lauren C Bates, Erik D Hanson, Masahiro Horiuchi, Erin Michos, Anna Kucharska-newton, Kunihiro Matsushita, Timothy Hughes, Hirofumi Tanaka, Lee Stoner
Journal: Circulation (2021)

Background: Carotid to femoral pulse wave velocity (cfPWV), the gold-standard measure of aortic stiffness, is associated with the incidence of cardiovascular disease (CVD) events. Most cfPWV measurements depend on technical proficiency, which limit broader implementation in clinical settings. Recently, an estimated pulse wave velocity (ePWV) measure derived from age and mean arterial pressure (MAP) has been shown to be associated with the risk of CVD events and all-cause mortality and may be a simple alternative to cfPWV. However, ePWV is poorly predictive in non-White individuals, possibly because it was originally developed from European Cohorts. Consequently, our purpose was to: estimate the strength of association between cfPWV and ePWV, and determine whether agreement is consistent across race. Hypothesis: cfPWV and ePWV are in good agreement and association would be consistent across race. Methods: We included Black and White older adults (n= 4,478; 75.2 [5.0] years) from visit 5 (2011-13) of the community-based Atherosclerosis Risk in Communities Study (ARIC). cfPWV was measured using an automated cardiovascular screening device. ePWV was calculated as presented in Fig 1. Association between cfPWV and ePWV was determined using Pearson’s correlation coefficient (r) and Bland-Altman plots. Results: As reported in Fig 1, there was a weak (r=0.35) correlation between cfPWV and ePWV for the total population, with similar correlations when stratified by Blacks (r=0.31) and Whites (r=0.36). Bland-Altman plots indicated significant systematic differences between cfPWV and ePWV (-0.17 m/s, 95% confidence interval: -0.25 to -0.09 m/s, P &lt;.001), which was consistent by race. Conclusion: In older adults, there was weak correlation between cfPWV and ePWV and systematic differences in agreement. Our results do not support ePWV as a surrogate measure of cfPWV in a sample of older White and Black adults.
A prospective study of oxaliplatin and capecitabine (CapOx) in metastatic colorectal cancer (MCRC) with baseline stratification according to resectability status
Authors: D. J. Watkins, C. Jackson, Y. Chua, G. Chong, A. R. Norman, G. Brown, S. Mudan, N. Karanjia, D. Cunningham
Journal: Journal of Clinical Oncology (2007)

4024 Background: Consideration of metastasectomy is now standard practice in the management of selected patients (pts) with stage IV MCRC. As a result, modification to the current staging system has been suggested to more clearly define subgroups of stage IV pts. As yet, there are no prospective data comparing the outcomes of pts according to resectability status. This phase II study evaluates the outcomes of pts according to baseline resectability status, and examines the utility of CapOx chemotherapy as a neoadjuvant treatment strategy. Methods: Eligible pts had received no prior chemotherapy for MCRC. At study entry imaging review was undertaken and pts stratified into 3 groups according to resectability status; non-resectable (group 1), potentially resectable liver disease (group 2), resectable liver disease (group 3). All pts received identical chemotherapy; capecitabine 2,000mg/m 2 d1–14 and oxaliplatin 130mg/m 2 d 1 repeated every 3 weeks. Repeat imaging was undertaken every 4 cycles. For pts in groups 2 &amp; 3, all imaging was reviewed by a specialist hepatic MDT, where feasible metastasectomy was undertaken following 4 or 8 cycles of chemotherapy. Planned enrolment was 130 pts, with study endpoints including; response rate, PFS &amp; OS. Results: 129 pts are enrolled. Median age 62 (range 29–78). Median number of cycles delivered 8 (range 1–12). Grade III/IV toxicities; diarrhoea 14%, neutropenia 7.8%, peripheral neuropathy 2%. 60 day all cause mortality 3.1%. There have been no post operative deaths following liver resection. Median follow up is 19.3 months. Outcome data for each group is summarised below. Conclusion: CapOx chemotherapy is safe and well tolerated when used as a neoadjuvant treatment strategy. This prospective study clearly demonstrates the wide variation in outcomes according to baseline resectability status, and highlights the need for modification to the staging system to account for these patient subgroups in future studies. [Table: see text] [Table: see text]
Abstract P257: Obesity and Diabetes are Jointly Associated With Low Fruit and Vegetable Consumption and Low Physical Activity in Adults With Stroke
Authors: Ryan Bailey, Monica Serra
Journal: Circulation (2020)

Introduction: Engaging in unhealthy behaviors (poor diet, insufficient physical activity) increases risk for recurrent stroke, and can be compounded by obesity and diabetes. Although engaging in healthy behaviors is recommended for managing chronic conditions, the joint association of obesity and diabetes with diet and physical activity in stroke survivors is unknown. Purpose: To compare prevalences of low fruit and vegetable consumption (Low_FV, &lt;1 fruit and &lt;1 vegetable daily), low physical activity (Low_PA, &lt;150 minutes of weekly moderate-intensity physical activity), and both Low_FV and Low_PA (Low_FV&amp;PA) in stroke survivors, stratified by obesity-diabetes status (neither condition, obesity only, diabetes only, obesity &amp; diabetes). Methods: Cross-sectional data from 32,876 noninstitutionalized, U.S. stroke survivors aged ≥45 years from the 2015 and 2017 Behavioral Risk Factor Surveillance System were examined. Weighted, age-adjusted prevalence estimates and adjusted odds ratios (AOR, adjusted for age, sex, race, income, education, and marital status) and 95% CIs were calculated. Results: Prevalences and AORs are displayed in the Table. Prevalences of Low_FV and Low_PA exceeded 50% across obesity-diabetes groups. Prevalences were highest in respondents with obesity &amp; diabetes and lowest in respondents with neither condition across outcome variables. Compared to respondents with neither condition, odds for Low_PA were increased for respondents with obesity &amp; diabetes and obesity only; odds for Low_FV&amp;PA were increased only for respondents with obesity &amp; diabetes. Conclusions: Our results indicated a joint effect of obesity and diabetes with Low_PA and Low_FV&amp;PA, placing stroke survivors with both chronic conditions at greatest risk for not engaging in protective health behaviors. Regardless of obesity-diabetes status, Low_FV and Low_PA exceeded 50%. Targeted interventions that modify these unhealthy behaviors should be explored for decreasing recurrent stroke risk among stroke survivors.
Restoring Cellular Energetics Promotes Axonal Regeneration and Functional Recovery after Spinal Cord Injury
Authors: Qi Han, Yuxiang Xie, Josue D. Ordaz, Andrew J. Huh, Ning Huang, Wei Wu, Naikui Liu, Kelly A. Chamberlain, Zu-Hang Sheng, Xiao-Ming Xu
Journal: Cell Metabolism (2020)

Axonal regeneration in the central nervous system (CNS) is a highly energy-demanding process. Extrinsic insults and intrinsic restrictions lead to an energy crisis in injured axons, raising the question of whether recovering energy deficits facilitates regeneration. Here, we reveal that enhancing axonal mitochondrial transport by deleting syntaphilin (Snph) recovers injury-induced mitochondrial depolarization. Using three CNS injury mouse models, we demonstrate that Snph−/− mice display enhanced corticospinal tract (CST) regeneration passing through a spinal cord lesion, accelerated regrowth of monoaminergic axons across a transection gap, and increased compensatory sprouting of uninjured CST. Notably, regenerated CST axons form functional synapses and promote motor functional recovery. Administration of the bioenergetic compound creatine boosts CST regenerative capacity in Snph−/− mice. Our study provides mechanistic insights into intrinsic regeneration failure in CNS and suggests that enhancing mitochondrial transport and cellular energetics are promising strategies to promote regeneration and functional restoration after CNS injuries.
Demonstration of distinct pathways of mast cell‐dependent inhibition of Treg generation using murine bone marrow‐derived mast cells
Authors: Sara Benede, Leticia Tordesillas, Cecilia Berin
Journal: Allergy (2020)

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WHO 2019 guidelines on drug-resistant tuberculosis treatment: based on evidence or expert opinion?
Authors: Lorenzo Guglielmetti, Helena Huerga, Uzma Khan, Francis Varaine
Journal: European Respiratory Journal (2020)

<b>World Health Organization guidelines on drug-resistant tuberculosis should make a clear distinction between evidence, expert opinion and assumptions to allow appreciation of the uncertainty around the recommendations</b>http://bit.ly/2FHxmyW