tbuckley/cabot-search huggingface dataset:
Compartmental Analysis of T-cell Clonal Dynamics as a Function of Pathologic Response to Neoadjuvant PD-1 Blockade in Resectable Non–Small Cell Lung Cancer
Authors: Jiajia Zhang, Zhicheng Ji, Justina X. Caushi, Margueritta El Asmar, Valsamo Anagnostou, Tricia R. Cottrell, Hok Yee Chan, Prerna Suri, Haidan Guo, Taha Merghoub, Jamie E. Chaft, Joshua E. Reuss, Ada J. Tam, Richard L. Blosser, Mohsen Abu-Akeel, John-William Sidhom, Ni Zhao, Jinny S. Ha, David R. Jones, Kristen A. Marrone, Jarushka Naidoo, Edward Gabrielson, Janis M. Taube, Victor E. Velculescu, Julie R. Brahmer, Franck Housseau, Matthew D. Hellmann, Patrick M. Forde, Drew M. Pardoll, Hongkai Ji, Kellie N. Smith
Journal: Clinical Cancer Research (2019)

Neoadjuvant PD-1 blockade is a promising treatment for resectable non-small cell lung cancer (NSCLC), yet immunologic mechanisms contributing to tumor regression and biomarkers of response are unknown. Using paired tumor/blood samples from a phase II clinical trial (NCT02259621), we explored whether the peripheral T-cell clonotypic dynamics can serve as a biomarker for response to neoadjuvant PD-1 blockade.T-cell receptor (TCR) sequencing was performed on serial peripheral blood, tumor, and normal lung samples from resectable NSCLC patients treated with neoadjuvant PD-1 blockade. We explored the temporal dynamics of the T-cell repertoire in the peripheral and tumoral compartments in response to neoadjuvant PD-1 blockade by using the TCR as a molecular barcode.Higher intratumoral TCR clonality was associated with reduced percent residual tumor at the time of surgery, and the TCR repertoire of tumors with major pathologic response (MPR; <10% residual tumor after neoadjuvant therapy) had a higher clonality and greater sharing of tumor-infiltrating clonotypes with the peripheral blood relative to tumors without MPR. Additionally, the posttreatment tumor bed of patients with MPR was enriched with T-cell clones that had peripherally expanded between weeks 2 and 4 after anti-PD-1 initiation and the intratumoral space occupied by these clonotypes was inversely correlated with percent residual tumor.Our study suggests that exchange of T-cell clones between tumor and blood represents a key correlate of pathologic response to neoadjuvant immunotherapy and shows that the periphery may be a previously underappreciated originating compartment for effective antitumor immunity.See related commentary by Henick, p. 1205.
Sequential CD19- and Bcma-Specific Chimeric Antigen Receptor T Cell Treatment for RRMM: Report from a Single Center Study
Authors: Lingzhi Yan, Zhi Yan, Jingjing Shang, Xiaolan Shi, Song Jin, Liqing Kang, Su Qu, Jin Zhou, Huizhu Kang, Ruju Wang, Ying Yao, Jing Wang, Weiqin Yao, Guanghua Chen, Lei Yu, Depei Wu, Fu Cheng Cheng
Journal: Blood (2019)
PD-L1 profile of nasopharyngeal cancer patients in Indonesia
Authors: H. Handoko, S.A. Gondhowiardjo, M. Adham, L. Lisnawati, D.L. Tobing, H. Kodrat, I.M. Haryoga, A.G. Dwiyono, Y.A. Kristian, T.B. Mayang Permata
Journal: Annals of Oncology (2019)
Updated overall survival (OS) from extended follow up in ARCHER 1050: A randomized phase III study comparing dacomitinib with gefitinib as first-line therapy for patients (pts) with EGFR mutations
Authors: T.S.K. Mok, Y. Cheng, X. Zhou, K.H. Lee, K. Nakagawa, S. Niho, R. Linke, R. Rosell, J. Corral, M.R. Migliorino, A. Pluzanski, K. Noonan, Y. Tang, K.D. Wilner, Y.-L. Wu
Journal: Annals of Oncology (2019)
Exercise treatment effect modifiers in persistent low back pain: an individual participant data meta-analysis of 3514 participants from 27 randomised controlled trials
Authors: Jill A Hayden, Maria N Wilson, Samuel Stewart, Jennifer L Cartwright, Andrea O Smith, Richard D Riley, Maurits van Tulder, Tom Bendix, Francesca Cecchi, Leonardo O P Costa, Ninna Dufour, Manuela L Ferreira, Nadine E Foster, Maruti R Gudavalli, Jan Hartvigsen, Pieter Helmhout, Jan Kool, George A Koumantakis, Francisco M Kovacs, Tiina Kuukkanen, Audrey Long, Luciana G Macedo, Luciana A C Machado, Chris G Maher, Wolf Mehling, Giovanni Morone, Tom Peterson, Eva Rasmussen-Barr, Cormac G Ryan, Tuulikki Sjögren, Rob Smeets, J Bart Staal, Monica Unsgaard-Tøndel, Henry Wajswelner, Ella W Yeung
Journal: British Journal of Sports Medicine (2019)

Background Low back pain is one of the leading causes of disability worldwide. Exercise therapy is widely recommended to treat persistent non-specific low back pain. While evidence suggests exercise is, on average, moderately effective, there remains uncertainty about which individuals might benefit the most from exercise. Methods In parallel with a Cochrane review update, we requested individual participant data (IPD) from high-quality randomised clinical trials of adults with our two primary outcomes of interest, pain and functional limitations, and calculated global recovery. We compiled a master data set including baseline participant characteristics, exercise and comparison characteristics, and outcomes at short-term, moderate-term and long-term follow-up. We conducted descriptive analyses and one-stage IPD meta-analysis using multilevel mixed-effects regression of the overall treatment effect and prespecified potential treatment effect modifiers. Results We received IPD for 27 trials (3514 participants). For studies included in this analysis, compared with no treatment/usual care, exercise therapy on average reduced pain (mean effect/100 (95% CI) −10.7 (−14.1 to –7.4)), a result compatible with a clinically important 20% smallest worthwhile effect. Exercise therapy reduced functional limitations with a clinically important 23% improvement (mean effect/100 (95% CI) −10.2 (−13.2 to –7.3)) at short-term follow-up. Not having heavy physical demands at work and medication use for low back pain were potential treatment effect modifiers—these were associated with superior exercise outcomes relative to non-exercise comparisons. Lower body mass index was also associated with better outcomes in exercise compared with no treatment/usual care. This study was limited by inconsistent availability and measurement of participant characteristics. Conclusions This study provides potentially useful information to help treat patients and design future studies of exercise interventions that are better matched to specific subgroups. Protocol publication https://doi.org/10.1186/2046-4053-1-64
Frailty Among Older Decompensated Heart Failure Patients
Authors: Ambarish Pandey, Dalane Kitzman, David J. Whellan, Pamela W. Duncan, Robert J. Mentz, Amy M. Pastva, M. Benjamin Nelson, Bharathi Upadhya, Haiying Chen, Gordon R. Reeves
Journal: JACC Heart Failure (2019)
Tisagenlecleucel Chimeric Antigen Receptor (CAR) T-Cell Therapy for Adults with Diffuse Large B-Cell Lymphoma (DLBCL): Real World Experience from the Center for International Blood &amp; Marrow Transplant Research (CIBMTR) Cellular Therapy (CT) Registry
Authors: Samantha Jaglowski, Zhen-Huan Hu, Yiyun Zhang, Manali Kamdar, Monalisa Ghosh, Premal Lulla, Joshua Sasine, Miguel-Angel Perales, Peiman Hematti, Sarah Nikiforow, Patricia Steinert, Margit Jeschke, Lan Yi, Raghav Chawla, Lida Pacaud, Mary M. Horowitz, Eric Bleickardt, Marcelo C. Pasquini
Journal: Blood (2019)
Antigen presentation through MHC class I and class II pathways induced by various DC-tumor fusion cells
Authors: Shigeo Koido, Yasuhiro Tanaka, Masaya Ohana, Chunlei Liu, Jianlin Gong
Journal: Cancer Research (2004)

4709  We have demonstrated that CD4+ and CD8+ T cells are involved in the antitumor immunity induced by DC-tumor fusion cells. To further dissect the role of antigen presentation through MHC class I and/or class II pathways, in the present study, we created various types of DC-tumor fusion cells by alternating the DC and/or tumor fusion partners. Fusions of MC38/MUC1 carcinoma cells (MHC class I and MUC1-positive and MHC class II-negative) with dendritic cells (DC) from wild-type (WT-DC), MHC class I knockout (IKO-DC), or class II knockout (IIKO-DC) mice created FC/WT-DC (MUC1, MHC class I and class II positive), FC/IKO-DC (MUC1, MHC class I and class II positive) and FC/IIKO-DC (MUC1 and MHC class I positive), respectively. MHC class II- and MUC1-positive fusion cells were constructed by fusion of B16/MUC1 melanoma cells (MUC1-positive, MHC class I and class II-negative) with IKO-DC (FC/B16/IKO-DC). Immunization of MUC1 transgenic (MUC1.Tg) mice with 5 x 105 FC/WT-DC (N=13), FC/IKO-DC (N=12) and FC/IIKO-DC (N=13) provided 100, 91.7 and 61.5% protection against tumor challenge with MC38/MUC1 cells, respectively. By contrast, all the mice immunized with irradiated MC38/MUC1 tumor cells or DC alone developed tumors. One group of MUC1.Tg mice (N=14) were immunized with 5 x 105 FC/B16/IKO-DC and then challenged with B16/Ia+/MUC1 on one side of the flank and MC38/MUC1 on another side. Immunization with FC/B16/IKO-DC resulted in 100 and 78.6% protection against tumor challenge by B16/Ia+/MUC1 and MC38/MUC1, respectively. These results are of interest since the antitumor immunity induced by immunization with FC/B16/IKO-DC is able to inhibit the growth of MHC class II-negative tumor. In addition, the in vivo results were correlated well with the induction of antigen-specific cytotoxic T lymphocytes (CTL). Collectively, these results indicate that while both CD4+ and CD8+ T cells are involved in the immune responses induced by the DC/tumor fusion cells, CD4+ T cells activated through MHC class II pathway play a more important role in the antitumor tumor immunity.
Resolution of Sickle Cell Disease Manifestations in Patients Treated with Lentiglobin Gene Therapy: Updated Results from the Phase 1/2 Hgb-206 Group C Study
Authors: Julie Kanter, John F. Tisdale, Markus Y. Mapara, Janet L. Kwiatkowski, Lakshmanan Krishnamurti, Manfred Schmidt, Alexandra L. Miller, Francis J. Pierciey, Wenmei Huang, Jean-Antoine Ribeil, Alexis A. Thompson, Mark C. Walters
Journal: Blood (2019)
Abstract 11552: Breast Arterial Calcification and Risk of Heart Failure
Authors: Quan M Bui, Avinash Toomu, Paula Anzenberg, Taelor Getz, Mohammad Eghtedari, Lori Daniels
Journal: Circulation (2019)

Introduction: Breast arterial calcification (BAC), detectable on mammography, has emerged as a potential risk stratification tool and surrogate marker of cardiovascular disease that comes with no a...
Treatment of neoplastic fever and sweats in two cancer patients with oxybutynin.
Authors: Thomas J. Smith, Mark Yarchoan, Roberto Antonio Leon-Ferre, Wendy Tucker, Charles L. Loprinzi
Journal: Journal of Clinical Oncology (2019)

128 Background: Treatment for neoplastic fevers and sweating (NFS) is usually accomplished successfully with non-steroidal drugs (NSAIDs) such as naproxen, but such therapies may be contraindicated in some patients due to drug interactions, bleeding diathesis, renal disease, or cirrhosis. Options for treating NFS in such patients are limited. Methods: We report the first use of oxybutynin (OxyB), commonly used for hyperhidrosis and increasingly used for hormonally mediated hot flashes (Smith TJ, NEJM 2018; Leon-Ferre R, SABCS 2018, under review in JNCI Cancer Spectrum, for NFS in NSAID-ineligible or refractory patients. Results: Two patients with NFS were treated. The first was a 70 year old (yo) woman with cholangiocarcinoma with 3 months of NFS for whom naproxen was ineffective and who was starting chemotherapy. Within 2 hours after 2.5 mg OxyB q12h her sweating was gone, and her fever, which had been up to 100.4F, never resumed. The second was a 52 yo male with cirrhosis and hepatocellular carcinoma who was prescribed 2.5 mg q12h OxyB with lysis of his fever within hours and cessation of his sweating. To date, over one month has passed with no reduction in efficacy. Conclusions: OxyB may be a successful treatment modality for patients with NFS who cannot be treated with or are refractory to NSAIDs. Further research is warranted to ensure stability of results over time and to monitor for side effects.
Polatuzumab Vedotin: Honing in on Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Authors: Jennifer R. Shingleton, Sandeep S. Dave
Journal: Journal of Clinical Oncology (2019)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. November 06, 2019 ARTICLE CITATION DOI: 10.1200/JCO.19.02587 Journal of Clinical Oncology - published online before print November 26, 2019 PMID: 31770050 Polatuzumab Vedotin: Honing in on Relapsed or Refractory Diffuse Large B-Cell Lymphoma Jennifer R. Shingleton, PhD1xJennifer R. ShingletonSearch for articles by this author; and Sandeep S. Dave, MD1xSandeep S. DaveSearch for articles by this author Show More 1Duke University, Durham, NC https://doi.org/10.1200/JCO.19.02587 First Page Full Text PDF Figures and Tables © 2019 by American Society of Clinical Oncology Companion Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma
The maternal six week postnatal check
Authors: Adam D Jakes, Pippa Oakeshott, Debra Bick
Journal: BMJ (2019)

### What you need to know

A 29 year old woman is seeing her general practitioner for a six week postnatal check after having her first baby. Her labour was induced at 41+0 weeks’ gestation for post-dates and she had a vaginal birth with a second degree tear. Her baby is well, exclusively breastfed, and gaining weight. Her partner has returned to work after parental leave and she has no family who live in the area. 

The maternal six week postnatal check is a long established part of routine postnatal care. It typically includes a review of the woman’s physical and mental health, the events of her pregnancy and birth, and discussion of future health considerations.1 It is also an opportunity to identify the 10-15% of women who may develop postnatal depression,234 provide ongoing management of medical complications of pregnancy such as gestational hypertension or gestational diabetes,56 and discuss postpartum contraception. This article offers an approach to the maternal six week (or 6-8 week) postnatal check.

If possible, check the woman’s maternity care discharge summary before the consultation so that you are aware of her medical and previous pregnancy history, the circumstances surrounding the birth, and the health of her baby.

A 10 or 15 minute consultation is a short time to cover everything, …
Xenotransplanted Human Cortical Neurons Reveal Species-Specific Development and Functional Integration into Mouse Visual Circuits
Authors: Daniele Linaro, Ben Vermaercke, Ryohei Iwata, Arjun Ramaswamy, Baptiste Libé-Philippot, Leila Boubakar, Brittany A. Davis, Keimpe Wierda, Kristofer Davie, Suresh Poovathingal, Pier-Andrée Penttila, Angéline Bilheu, Lore De Bruyne, David Gall, Karl-Klaus Conzelmann, Vincent Bonin, Pierre Vanderhaeghen
Journal: Neuron (2019)

How neural circuits develop in the human brain has remained almost impossible to study at the neuronal level. Here, we investigate human cortical neuron development, plasticity, and function using a mouse/human chimera model in which xenotransplanted human cortical pyramidal neurons integrate as single cells into the mouse cortex. Combined neuronal tracing, electrophysiology, and in vivo structural and functional imaging of the transplanted cells reveal a coordinated developmental roadmap recapitulating key milestones of human cortical neuron development. The human neurons display a prolonged developmental timeline, indicating the neuron-intrinsic retention of juvenile properties as an important component of human brain neoteny. Following maturation, human neurons in the visual cortex display tuned, decorrelated responses to visual stimuli, like mouse neurons, demonstrating their capacity for physiological synaptic integration in host cortical circuits. These findings provide new insights into human neuronal development and open novel avenues for the study of human neuronal function and disease.Video AbstracteyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiI4MjY1MTEyMzljMjcxN2RkYmQyNzhmNTk2Nzg1YzA2OSIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjU5NTExNzE3fQ.UAhhrbUCifeaiUvLhp5pOtY8DNsMFQeL-cSGiO_fksWLU1PhQ0wApDGgvn-gi4dAdb8IfnvClU-2yAcIAFag1NMdUN4vZ3JcvTngv4h58c_GtPzS2VSs3yTRzn0S4wU6jJxM2I4tLMg5KC8XaeUDrz383dI206zAAmHrEmSCMGzlEdkrz6XYSNAey9LBwEBVYh4umz5yAA7iRr8l7bxnJ1zDatezejzEvu_G66L5jZ2ozKyA0p0iD_4yBh0hkZTnNg9UQOxJCmX_2D4kTLRymPpBjAR_NEZ93d_Yo9SWw4lJudwKF1Q9XsIRTwB5n-IUYagcLKFb0ktJcs4ToUatcA(mp4, (13.09 MB) Download video
Effect of corounding versus consult service for cancer inpatients on staff outcomes of teamwork and job satisfaction.
Authors: Seow Lin Goh, Xuan Rui Koh Audrey, Patricia Soek Hui Neo, Grace Meijuan Yang
Journal: Journal of Clinical Oncology (2019)

85 Background: Traditionally, palliative care in most hospitals is delivered through consult-based services i.e relying on the primary physician to initiate a referral to a palliative care specialist. Supportive and Palliative Care Review Kit (SPARK) is a newly developed integrated model of care that involves a Palliative Consultant and an Advanced Practice Nurse (APN) co-rounding with the oncologist to provide bedside palliative care advice alongside the oncology team. Methods: To evaluate the effect of this new model on staff outcomes of teamwork and job satisfaction, a survey was conducted in March 2018 before the new SPARK model was started and 1 year later in March 2019. The survey was adapted from the Primary Care Team Dynamics Survey and Physician Worklife Survey, with higher scores indicating better outcomes. Categorical variables were analysed using chi-square test and continuous variables were analysed using student’s t-test. Results: Before the new SPARK model was started in March 2018, email invitations were sent to 89 oncology and palliative care physicians. Fifty five complete responses was received (61.8% response rate). A year after the new SPARK model was started, email invitations were sent to 23 oncology and palliative care physicians who had experienced the new model of care, of which 8 complete responses were returned (34% response rate). There was no significant differences in demographics between the two time points and in the total and domain scores between before and after SPARK. In the ‘personal time’ domain of the physician worklife survey, scores were better after SPARK (73.8± 6.68) compared to before SPARK (68.4 ± 8.70). This may be due to increased independence experienced by the APN co-rounding with the oncology team. The flexibility in team-rounding creates more personal time allowing the APN to be involved in other non-clinical tasks. Conclusions: While there were no statistically significant differences in the overall work experience, team dynamics and job satisfaction one year after the SPARK model, this may be due to small sample size.
Reply to Turnbull <i>et al.</i> and to Hulme <i>et al.</i>
Authors: Oded Breuer, Andre Schultz, Lidija Turkovic, Nicholas de Klerk, Anthony D. Keil, Siobhain Brennan, Joanne Harrison, Colin Robertson, Philip J. Robinson, Peter D. Sly, Sarath Ranganathan, Stephen M. Stick, Daan Caudri
Journal: American Journal of Respiratory and Critical Care Medicine (2019)
Single Cell Transcriptome Analysis Reveals Disease-Defining T Cell Subsets in the Tumor Microenvironment of Classic Hodgkin Lymphoma
Authors: Tomohiro Aoki, Lauren C. Chong, Katsuyoshi Takata, Katy Milne, Monirath Hav, Anthony Colombo, Elizabeth Chavez, Tomoko Miyata-Takata, Vivian Lam, Chanel Ghesquiere, Daniel Kos, Talia Goodyear, Allen W. Zhang, Xuehai Wang, Saeed Saberi, Jiarui W. Ding, Pedro Farinha, Andrew P. Weng, Kerry J Savage, David W. Scott, Gerald Krystal, Brad H. Nelson, Anja Mottok, Akil Merchant, Sohrab P Shah, Christian Steidl
Journal: Blood (2019)
Postexposure Prophylaxis for HIV After Sexual Assault
Authors: J. E. Myles
Journal: JAMA (2000)

This paper presents the findings of a retrospective review of charts of sexual assault survivors who were offered postexposure prophylaxis (PEP) between April 1998 and November 1999 at San Francisco General Hospital. The total cost of PEP medications was also computed. Overall, it is noted that one-third of the 367 sexual assault survivors chose to initiate PEP. Men who were anally raped are at the highest risk for HIV transmission and were most likely to initiate PEP. Among women, on the other hand, those who were non-White and homeless were less likely to accept PEP. In the context of cost, the total per-person cost of medication dispensed during the study period (US$65 per person offered PEP) is comparable to other medications offered routinely following sexual assault, such as azithromycin for chlamydia prophylaxis (US$43 per treatment). However, there is no definitive evidence that PEP is effective in preventing HIV seroconversion after sexual assault. It is suggested that in developing rational policy recommendation offering HIV PEP after sexual assault, further studies are needed to better delineate the rates of HIV seroprevalence among sexual assailants, the efficacy of PEP after sexual exposure, and the psychological benefits or harm incurred by the sexually assaulted patients.
Prevalence, Characteristics, and Prognosis of Early Chronic Obstructive Pulmonary Disease. The Copenhagen General Population Study
Authors: Yunus Çolak, Shoaib Afzal, Børge G. Nordestgaard, Jørgen Vestbo, Peter Lange
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Identification of younger adults at high risk of developing chronic obstructive pulmonary disease (COPD) could lead to implementation of preventive measures before disease onset and halt progression.Objectives: To investigate the prevalence, characteristics, and prognosis of individuals with early COPD in the general population.Methods: We investigated 105,630 randomly chosen adults from a Danish contemporary population-based cohort. Early COPD was defined as FEV1/FVC less than the lower limit of normal in individuals under 50 years of age with 10 pack-years or greater of tobacco consumption.Measurements and Main Results: Among 8,064 individuals under 50 years of age with 10 pack-years or greater of tobacco consumption, 1,175 (15%) had early COPD, of whom 58% were current smokers. Individuals with early COPD more often had chronic respiratory symptoms, severe lung function impairment, asthma, and a history with bronchitis/pneumonia. During the 14.4-year follow-up, we observed 117 acute hospitalizations with obstructive lung disease, 227 acute hospitalizations with pneumonia, and 185 deaths among the 8,064 younger adults. Compared with individuals without COPD, those with early COPD had multivariable adjusted hazard ratios of 6.42 (95% confidence interval, 3.39-12.2) for acute obstructive lung disease hospitalizations, 2.03 (1.43-2.88) for acute pneumonia hospitalizations, and 1.79 (1.28-2.52) for all-cause mortality.Conclusions: Among individuals under 50 years of age and 10 pack-years or greater of tobacco consumption from the general population, 15% fulfill criteria of early COPD. Individuals with early COPD more often have chronic respiratory symptoms and severe lung function impairment, and an increased risk of acute respiratory hospitalizations and early death.
Azacitidine for Post-Remission Therapy in Elderly Patients with Acute Myeloid Leukemia : Final Results of the Qoless AZA-Amle Randomized Trial
Authors: Esther Natalie Oliva, Anna Candoni, Prassede Salutari, Francesco Di Raimondo, Gianluigi Reda, Debora Capelli, Pasquale Niscola, Carmine Selleri, Pellegrino Musto, Ernesto Vigna, Antonio Volpe, Nicola Cascavilla, Donato Mannina, Paola Carluccio, Maria Elena Zannier, Elisa Mauro, Alessandra Freyrie, Carla Mazzone, Bruno Martino, Caterina Alati
Journal: Blood (2019)