tbuckley/cabot-search huggingface dataset:
Yield and Efficiency of Novel Intensified Tuberculosis Case-Finding Algorithms for People Living with HIV
Authors: Christina Yoon, Fred C. Semitala, Lucy Asege, Jane Katende, Sandra Mwebe, Alfred O. Andama, Elly Atuhumuza, Martha Nakaye, Derek T. Armstrong, David W. Dowdy, Charles E. McCulloch, Moses Kamya, Adithya Cattamanchi
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

The recommended tuberculosis (TB) intensified case finding (ICF) algorithm for people living with HIV (symptom-based screening followed by Xpert MTB/RIF [Xpert] testing) is insufficiently sensitive and results in unnecessary Xpert testing.To evaluate whether novel ICF algorithms combining C-reactive protein (CRP)-based screening with urine Determine TB-LAM (TB-LAM), sputum Xpert, and/or sputum culture could improve ICF yield and efficiency.We compared the yield and efficiency of novel ICF algorithms inclusive of point-of-care CRP-based TB screening and confirmatory testing with urine TB-LAM (if CD4 count ≤100 cells/μl), sputum Xpert, and/or a single sputum culture among consecutive people living with HIV with CD4 counts less than or equal to 350 cells/μl initiating antiretroviral therapy in Uganda.Of 1,245 people living with HIV, 203 (16%) had culture-confirmed TB including 101 (49%) patients with CD4 counts less than or equal to 100 cells/μl. Compared with the current ICF algorithm, point-of-care CRP-based TB screening followed by Xpert testing had similar yield (56% [95% confidence interval, 49-63] vs. 59% [95% confidence interval, 51-65]) but consumed less than half as many Xpert assays per TB case detected (9 vs. 4). Addition of TB-LAM did not significantly increase diagnostic yield relative to the current ICF algorithm but provided same-day diagnosis for 26% of TB patients with advanced HIV. Addition of a single culture to TB-LAM and Xpert substantially improved ICF yield, identifying 78% of all TB cases.Point-of-care CRP-based screening can improve ICF efficiency among people living with HIV. Addition of TB-LAM and a single culture to Xpert confirmatory testing could enable HIV programs to increase the speed of TB diagnosis and ICF yield.
A phase 1b study of napabucasin (NAPA) + weekly paclitaxel (PTX) in patients (pts) with advanced thymoma and thymic carcinoma.
Authors: Maitri Kalra, Gregory Michael Cote, Rebecca Suk Heist, Aaron John Spittler, Song Yu, Matthew Hitron, Patrick J. Loehrer
Journal: Journal of Clinical Oncology (2018)

e20578 Background: NAPA is an oral investigational agent, hypothesized to inhibit cancer stemness pathways, including the STAT3 pathway implicated in cancer stem-cell viability. A clinical trial evaluated NAPA + PTX and a cohort for patients (pts) with advanced, previously treated thymoma and thymic carcinoma was opened. Methods: This is an open-label, multicenter study (NCT01325441) of NAPA + PTX for advanced, previously treated thymoma and thymic carcinoma. Objectives were safety and evaluation of antitumor activity. Pts received NAPA 240 or 480 mg BID + PTX 80 mg/m2IV weekly for 3 of every 4 wks. Tumor assessments were every 8 wks per RECIST 1.1. Data cut-off was Jan 2018. Results: From Aug 2015 to Dec 2017, 16 pts (6 thymic carcinoma, 10 thymoma) enrolled. All pts received prior therapy (avg 2.5 regimens; range 1 – 6) and 3 had prior taxane. Median treatment duration was 26 wks (range 2 to 62), excluding 4 pts still on therapy. Grade 3 AEs included: diarrhea 13%; vomiting 6%; and abdominal pain 7%. There were 2 deaths on study not thought to be treatment related (perforated bowel, autoimmune myocarditis; both in thymoma patients). In 6 pts with thymic carcinoma, 4 had partial response (PR) and 1 had stable disease (SD). The objective response rate (ORR) was 67%; the disease control rate (DCR, % with CR, PR, or SD) was 83%. One pt. remained on treatment without progression (PD) at 10 wks and 5 pts (83%) have discontinued (PD [3], investigator decision [1], pt request [1]). The proportion alive without PD at 24 wks was 60% (3 of 5) excluding 1 pt on active treatment < 24 wks without PD. In 10 pts with thymoma, 2 had PR and 3 had SD out of 8 with imaging (2 had not yet reached 1st imaging timepoint). The ORR was 25% and DCR was 63%. Three pts (30%) remained on treatment without PD at 6 wks, 6 wks, and 18 wks, respectively. The proportion alive without PD at 24 weeks was 43% (3 of 7), excluding the pts who were on treatment < 24 wks without PD. Conclusions: In a heavily pretreated population of pts with advanced thymic carcinoma and thymoma, NAPA + PTX demonstrated clinical activity and reasonable clinical safety. Further clinical evaluation of the combination regimen is warranted in this population, particularly in thymic carcinoma. Clinical trial information: NCT01325441.
Improved clinical responses with the concomitant use of an anti-GD2 monoclonal antibody and chemotherapy in newly diagnosed children with high-risk (HR) neuroblastoma (NB): Preliminary results of a phase II study.
Authors: Wayne Lee Furman, Sara Michele Federico, Mary B McCarville, Andrew M. Davidoff, Matthew J. Krasin, Jianrong Wu, Rachel Christine Brennan, Michael William Bishop, Victor M. Santana, Armita Bahrami, Gwendolyn Anthony, Stephen D Gillies, Paul M. Sondel, Wing H. Leung, Alberto S. Pappo
Journal: Journal of Clinical Oncology (2016)

10501 Background: The chimeric anti-GD2 mAb dinutuximab improves EFS in HR NB when administered in the setting of minimal residual disease following intensive chemotherapy (CT) (Yu et al. NEJM 2010). We evaluated the feasibility and activity of a humanized anti-GD2 mAb with a single point mutation (K322A) that reduces complement-dependent lysis, hu14.18K322A, given concomitantly with CT in newly diagnosed children with HR NB. Methods: Patients (pts) received induction CT (6 cycles) as described by Park (JCO 29:4351, 2011; induction CT used in most recent COG HR NB trial) with hu14.18K332A (on d 2-5 40mg/m2/d x 4d), GM-CSF and low dose IL-2. The primary objective was to compare the response rate (RR) after the initial two courses of CT with cyclophosphamide (CTX)/topotecan (TPT) and hu14.18K322A to the RR reported by Park et al., using identical CT with granulocyte colony-stimulating factor and without hu14.18K322A, GM-CSF and IL-2, in a two-stage group sequential design. Results: At the interim analysis of 20 evaluable pts, (10 male; median age 34 m (range 6 – 180 m), 16 INSS stage 4, 12 MYCN amplified), all pts had significant benefit. The RR after the first two courses of therapy was 80% (95% CI 56%-94%) with 15 PRs, 1 VGPR and 4 with SD (primary tumor volume decreased by 47, 75, 81 and 96%); Pain from the anti-GD2 mAb was well controlled by continuous infusion narcotics initiated prior to the start of hu14.18K322A and adjusted as needed. Eleven of 21 pts had hu14.18K322A infusions extended because of the development of cough, hypoxia and/or hypotension. All pts received all planned doses of hu14.18K322A. Conclusions: The addition of hu14.18K322A to two courses of CTX / TPT is well tolerated and has significant activity (16/20 (80%) ≥ PR) compared to 12/30 (40%) ≥ PR reported by Park et al. in a similar group of pts who received two courses of CTX/TPT alone (p = 0.0057). Accrual is ongoing. Anti-GD2 mAbs given concomitantly with CT warrant further evaluation. Clinical trial information: NCT01857934.
Effect of echocardiogram prior to induction therapy for acute myeloid leukemia on detection of cardiac dysfunction and treatment modifications.
Authors: Jennifer C. Yui, Mythri Mudireddy, Mrinal Patnaik, Naseema Gangat, Aref Al-Kali, Michelle A. Elliott, William J. Hogan, Carl C. Hook, Alexandra P. Wolanskyj, Animesh Dev Pardanani, Hector R. Villarraga, Mark Robert Litzow, Ayalew Tefferi, Kebede Begna
Journal: Journal of Clinical Oncology (2017)

e18514 Background: Standard induction therapy for acute myeloid leukemia (AML) includes “cytarabine and anthracycline”. Anthracyclines are known to cause acute, subacute and chronic cardiac complications ( Lefrak , EA et al, Cancer 1973:32(2):302-314; Singal, PK et al, NEJM 1998;339(13):900-905). It is recommended to do base line cardiac function assessment with echocardiogram prior to induction therapy containing anthracycline. This study was done to find the frequency of changes made in avoiding anthracycline usage following this evaluation. Methods: The Mayo clinic data base was interrogated to identify patients with newly diagnosed AML who underwent echocardiogram prior to anthracycline containing induction chemotherapy. Echocardiogram results, including left ventricular ejection fraction (LVEF), diastolic dysfunction, valvular disease, and any resultant treatment alterations were reviewed. Results: Three hundred twenty six patients were identified. The median (range) age was 61 (17-82) years and 62% were male. The median (range) LVEF was 65% (30-87), and 3 (0.9%) patients had LVEF &lt; 50% (range 30-47%). Of these 3 patients, 1 had 4 vessel CABG a decade ago, his EF was 46% and treated with full dose idarubicin; 2 of them presented with blastic crisis, 1 had EF 46% and improved to 51% after 5 days and then given daunorubicin, the other one had an EF of 30% and treated with 50% dose reduced cytarabine alone. Sixty five (23%) patients had previous chemotherapy or radiation exposure, including 24 (7.4 %) with previous anthracycline, 14 (4.3%) had prior radiation to the chest wall. No patient with previous chemotherapy or radiation exposure had a reduced LVEF. Conclusions: Echocardiography prior to anthracycline therapy rarely detects abnormal LVEF. Screening echo may be helpful in those presented with leukemic blastic crisis or had previous exposure to chemo-radiation.
Expression of kynurenine aminotransferase I as a prognostic factor in the context of the occurrence of neurological symptoms during chemotherapy.
Authors: Rodryg Ramlau, Joanna Gazdulska, Joanna Rybacka-Mossakowska, Slawomir Michalak
Journal: Journal of Clinical Oncology (2018)

e22081 Background: Neurological symptoms in the course as well as after completed chemotherapy are one of the most frequently reported complications affecting the quality of life of patients. Methods: The study involved 221 patients with lung cancer treated with chemotherapy between November 2013 and February 2014. The blood was collected from each participant before treatment and 6 months after the end of treatment. In addition, each patient underwent a neurological testing at the beginning of therapy and 6 months after the end of treatment. The activity of kynurenine aminotransferase I was evaluated based on the amount of kynurenic acid (KYNA) produced, measured in buffer containing 50 mM NaOAc and 350 mM ZnOAc at pH = 5.47 added to the reaction mixture. Fluorescence measurements were performed using a Flx800 fluorometer (BioTek, USA) with excitation at 344 nm and emission at 398 nm. KAT activity was expressed as μmol of kynurenic acid formed in one hour per milliliter. Results: Small cell carcinoma occurred in 25 patients, squamous cell carcinoma in 62 patients, adenocarcinoma in 85 patients, large cell carcinoma in 6 patients and NOS carcinoma in 43 patients. Patients received chemotherapy regimens consisting of cisplatin or carboplatin in combination with etoposide or vinorelbine or gemcitabine or premetrexed. In the studied 6 months after the treatment, 39% patients developed symptoms of sensory-motor neuropathy, 36% symptoms of motor neuropathy and 16% symptoms of cerebellar syndrome. In laboratory tests, the occurrence of new neurological symptoms was associated with an increase in the expression of kynurenine aminotransferase (673.47: 0-134.94 pg / mg of protein, median and interquartile range, P < 0.05). Analysis of ROC curves showed a significant prognostic significance of kynurenine aminotransferase in the context of appearance of neurological complications in the course of chemotherapy sensitivity of 100%, specificity 66% Conclusions: The activity of kynurenine aminotransferase I is a prognostic factor in the context of the occurrence of new neuropathy symptoms during chemotherapy.
A retrospective study of shrinking field radiation therapy during chemoradiotherapy in stage III non-small cell lung cancer.
Authors: Shuiyun Han, Gang Lin, Chenxue Jiang, Xiaojiang Sun, Guodong Shi, Zhun Wang, Yuezhen Wang, Yaping Xu, Weimin Mao
Journal: Journal of Clinical Oncology (2016)

8545 Background: This study aimed to investigate the feasibility of shrinking field radiotherapy after complete or partial response during chemoradiotherapy in stage III non-small cell lung cancer (NSCLC). Methods: Retrospective study of 97 patients with stage III NSCLC with a good response to chemoradiotherapy (without surgery; September 2009 to November 2014). Computed tomography was performed after 40-50 Gy to evaluate the effect. Fifty patients underwent resimulation CT scans; radiation volume was redelineated and shrunk (boost of 6-20 Gy to shrunken PTV). Gross tumor volume (GTV), PTV, acute symptomatic irradiation-induced pneumonia (ASIP), progression patterns and overall survival (OS) were assessed. Results: Of 97 patients who achieved complete or partial response after a median total dose of 60.0 Gy (range, 50.0-70.0 Gy), 50 patients received shrinking field radiation therapy (median reduction in PTV between plans, 184.2 cm3; range, 28.1-449.7 cm3). Mean Primary GTV (116.8 vs. 102.9 cm3) and PrimaryPTV (493.0 vs. 458.0 cm3) were higher in shrinking field than non-shrinking field group. The dose to the Second PTV (P = 0.168, Mann-Whitney test) and ≥60.0 Gy dose rate (70% vs. 61.7%, P = 0.389) in the shrinking field group tended to be higher. The incidence of ASIP was 20.6% (20/97) overall, 18% for shrinking field group and 23.4% for another group (P = 0.511). The incidence of disease progression was significantly lower in the shrinking field group (60% vs. 87.2%, P = 0.002). Compared to non-shrinking field group, the shrinking field group had similar OS (median, 29 vs. 30 months, P = 0.546) and better median PFS (median, 19 vs. 14 months, P =0.945); however, these trends were non-significant. Conclusions: Shrinking field radiotherapy in NSCLC good responders during chemoradiotherapy seems safe with lesser toxicity tendency and lower incidence of disease progression, and potentially spares normal tissues and enables dose escalation, especially for patients with large tumors. Relapse Non-shrinking Field group (n=47) Shrinking Field group (n=50) P value Local relapse (LR) 22 (46.8%) 15 (30%) Distant metastasis (DM) 16 (34.0%) 12 (24%) LR+DM 3 (6.4.0%) 3 (6%) Total 41 (87.2%) 30 (60%) 0.002
The Croonian Lectures on Adaptation and Disease: Delivered at the Royal College of Physicians, June 21st, 1917
Authors: J. G. Adami
Journal: BMJ (1917)

JUNE 30, -Ig- d 2XDICAL JOUNA I J0 97 enteritis bacilli oc-cur frequently in flies in the natural state, and tllat the utmost care is necessary in dis- criminating between these and the true enteritis-producing organisms.
TCT-800 Immediate and long-term predictor score of success after percutaneous mitral balloon valvoplasty
Authors: Luiz Eugênio Prota Filho, Caio Viana Queiroz, Fabricio Wohnrath, Felipe Carboni, Gisele Cunha da Silva, Joselyn Castro, Wandemberg da Silva, Rafael Alexandre Meneguz-Moreno, Jose Costa, Mercedes Maldonado, Nisia Gomes, Sergio Braga, Auristela Ramos, Zilda Meneghelo, Dimytri Siqueira, Cesar Augusto Esteves, Amanda Sousa, J. Eduardo Sousa, Alexandre Abizaid
Journal: Journal of the American College of Cardiology (2018)
Abstract A031: Androgen deprivation therapy-induced TGFBI signaling promotes EMT and bone metastasis of prostate cancer
Authors: Yen-Nien Liu, Wei-Yu Chen, Yuan-Chin Tsai, Hsiu-Lien Yeh, Florent Suau, Jiaoti Huang
Journal: Cancer Research (2018)

Abstract Metastatic progression in patients with prostate cancer is common despite pharmacologic inhibition of androgen receptor signaling. This drug resistance is associated with increased signaling through the transforming growth factor-β (TGF-β) signaling pathway. We found the type I/II/IV collagen-binding protein transforming growth factor-β (TGF-β)-induced (TGFBI) is an important factor in the epithelial-to-mesenchymal transition (EMT) and malignant progression of prostate cancer. We identified that an androgen-responsive gene, SPDEF, navigates between AR and TGFβ signaling during prostate cancer progression to metastasis though a physical interaction with the promoter region of the TGFBI gene. We show that loss of AR-regulated SPDEF induces TGFBI expression in prostate cancer cells, leading to drastic and aggressive physiologic changes. Furthermore, we confirmed the negative correlation between SPDEF and TGFβ singling in prostate cancer patients and demonstrated that ADT can reduce SPDEF and increase TGFβ signaling. Our results support an inhibitory role of the AR on TGFβ signaling through SPDEF-mediated suppression of TGFBI, and that disruption of this pathway promotes metastatic progression in prostate cancer. Citation Format: Yen-Nien Liu, Wei-Yu Chen, Yuan-Chin Tsai, Hsiu-Lien Yeh, Florent Suau, Jiaoti Huang. Androgen deprivation therapy-induced TGFBI signaling promotes EMT and bone metastasis of prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr A031.
Aspirin-Exacerbated Respiratory Disease
Authors: Andrew A. White, Donald D. Stevenson
Journal: New England Journal of Medicine (2018)

About 7% of patients with asthma have mucosal swelling, nasal polyps, and worsening of asthma in response to aspirin and other COX-1 inhibitors. Symptoms may be managed with glucocorticoids, antihistamines, and aspirin desensitization.
Transcriptomic and immunophenotypic profiles of melanoma tissue from patients (pts) treated with anti-PD-1 +/- ipilimumab to define mechanisms of response and resistance.
Authors: Tuba Nur Gide, Camelia Quek, Alexander M. Menzies, Jason Madore, Rebecca Velickovic, Matthew Wongchenko, Yibing Yan, Matteo S. Carlino, Alexander David Guminski, Robyn Saw, Ines Silva, Umaimainthan Palendira, John F. Thompson, Richard A. Scolyer, Georgina V. Long, James S. Wilmott
Journal: Journal of Clinical Oncology (2018)

9518 Background: Immune checkpoint blockade improves the survival of patients with metastatic melanoma, but many patients fail to respond to immunotherapy and the lack of accurate predictors of response or progression remains a major clinical problem. We investigated potential mechanisms of response and resistance to anti-PD1 +/- ipilimumab. Methods: 141 melanoma biopsies from advanced melanoma pts treated with anti-PD-1 monotherapy (n= 54), or anti-PD1 + ipilimumab (n= 51) were classified as responders (CR/PR/SD > 6 mo) or non-responders (SD≤6 mo/PD) based on RECIST. The transcriptomic and immunophenotypic profiles of 105 baseline (PRE) and 36 early-during treatment (EDT) tumor biopsies from pts treated with monotherapy (n= 33 responders, n= 21 non-responders) or anti-PD-1 + ipilimumab (n= 38 responders, n= 13 non-responders) were characterized via RNA sequencing and multiplex immunofluorescence. Results: Responders to monotherapy displayed increased expression of genes associated with a Type 1 interferon response, tissue-resident T-cells and drug targets (TIGIT, ADAR, ADORA2A, CD137, IDO1 and LAG3) (diff. p < 0.05). Genes unique to anti-PD-1 + ipilimumab responders included T-cell and NK-cell genes EOMES, CD48, CD96, and FASLG. Non-responders displayed significantly higher expression of genes associated with WNT signaling along with novel hypoxic and metabolic pathways, including CA9 and NABP1 (p < 0.05). Non-responders with high CD8/PD-L1 densities expressed novel immune drug targets (IDO1 expressed by 37% of monotherapy non-responders, ICOS (37%), TNFRSF9 (26%), LAG3 (16%), TIGIT (16%) and ADORA2A (16%)). In contrast, TIL-low tumors displayed a lack of expression of the aforementioned targets (42% of monotherapy and 86% of anti-PD-1 + ipilimumab non-responders). Conclusions: These findings demonstrate that combinations of novel drug targets may provide clinical benefits in non-responding and non-CR responding patients with high TILs. TIL-low non-responders may require modulation of WNT, hypoxic and metabolic pathways to overcome resistance, facilitating the development of novel synergistic drug targets.
Patient-clinician communication and oral chemotherapy adherence.
Authors: Jennifer Elston Lafata, Daniel Gratie, Bobbie K Nguyen
Journal: Journal of Clinical Oncology (2018)

e18849 Background: Cancer care increasingly includes oral chemotherapy. We summarize the literature on patient-clinician communication and patient adherence to curative oral chemotherapy, and explore if effective communication is occurring in oncology practices. Methods: Using adherence, non-adherence, communication, treatment satisfaction, discordance, barriers, discontinuation and oral chemotherapy agent names, we searched for studies of patient-clinician communication and oral chemotherapy use. Literature available before December 28, 2017 was searched via PubMed. Two authors independently reviewed abstracts to identify studies for full review. We excluded studies of metastatic disease only, hormone/endocrine therapy, and those not measuring medication adherence. We additionally identified patient-oncologist conversations by searching audio-recorded office visits from a national physician panel. We searched oncology visit transcripts electronically for keywords relevant to oral chemotherapy discussions among patients with cancer. Two authors independently reviewed audio-recordings / transcripts, coding for presence of key communication behaviors as identified from the systematic review. Results: The initial search identified 279 articles, of which 121 were retained after title review. After reading abstracts, we retrieved the full text for 32 articles. Studies focused on a diversity of communication behaviors, including discussions of medication side effects and treatment goals. Studies also used a variety of means by which to measure medication adherence, including patient-self report and pharmacy refills. Most audio-recorded office visit conversations were void of key communication behaviors found to be supportive of patients’ medication adherence. Conclusions: We found few studies that assessed the relationship between clinician-patient communication and medication adherence. Furthermore, among a national sample of oncology office visits, we found that office visit conversations often fall short of what could be considered optimal. As the use of oral chemotherapy continues to expand, it is important to learn how office visit and other communication can support patients’ oral chemotherapy use.