tbuckley/cabot-search huggingface dataset:
Hepatic sinusoidal obstruction syndrome and short-term application of 6-thioguanine in pediatric acute lymphoblastic leukemia
Authors: Martin Stanulla, Elke Schaeffeler, Anja Möricke, Swantje Buchmann, Martin Zimmermann, Svitlana Igel, Kjeld Schmiegelow, Christian Flotho, Hans Hartmann, Sabine Illsinger, Axel Sauerbrey, Stefanie V. Junk, Peter Schütte, Laura Hinze, Melchior Lauten, Simon Modlich, Reinhard Kolb, Claudia Rossig, Georg Schwabe, Astrid K. Gnekow, Gudrun Fleischhack, Paul Gerhard Schlegel, Holger J. Schünemann, Christian P. Kratz, Gunnar Cario, Martin Schrappe, Matthias Schwab
Journal: Leukemia (2021)

Long-term treatment with 6-thioguanine (6-TG) for pediatric acute lymphoblastic leukemia (ALL) is associated with high rates of hepatic sinusoidal obstruction syndrome (SOS). Nevertheless, current treatment continues to use short-term applications of 6-TG with only sparse information on toxicity. 6-TG is metabolized by thiopurine methyltransferase (TPMT) which underlies clinically relevant genetic polymorphism. We analyzed the association between hepatic SOS reported as a serious adverse event (SAE) and short-term 6-TG application in 3983 pediatric ALL patients treated on trial AIEOP-BFM ALL 2000 (derivation cohort) and defined the role of TPMT genotype in this relationship. We identified 17 patients (0.43%) with hepatic SOS, 13 of which with short-term exposure to 6-TG (P < 0.0001). Eight of the 13 patients were heterozygous for low-activity TPMT variants, resulting in a 22.4-fold (95% confidence interval 7.1-70.7; P ≤ 0.0001) increased risk of hepatic SOS for heterozygotes in comparison to TPMT wild-type patients. Results were supported by independent replication analysis. All patients with hepatic SOS after short-term 6-TG recovered and did not demonstrate residual symptoms. Thus, hepatic SOS is associated with short-term exposure to 6-TG during treatment of pediatric ALL and SOS risk is increased for patients with low-activity TPMT genotypes.
Virus-specific NK cell memory
Authors: Sam Sheppard, Joseph C. Sun
Journal: The Journal of Experimental Medicine (2021)

NK cells express a limited number of germline-encoded receptors that identify infected or transformed cells, eliciting cytotoxicity, effector cytokine production, and in some circumstances clonal proliferation and memory. To maximize the functional diversity of NK cells, the array and expression level of surface receptors vary between individual NK cell “clones” in mice and humans. Cytomegalovirus infection in both species can expand a population of NK cells expressing receptors critical to the clearance of infected cells and generate a long-lived memory pool capable of targeting future infection with greater efficacy. Here, we discuss the pathways and factors that regulate the generation and maintenance of effector and memory NK cells and propose how this understanding may be harnessed therapeutically.
T cell infiltration on local CpG-B delivery in early-stage melanoma is predominantly related to CLEC9A<sup>+</sup>CD141<sup>+</sup> cDC1 and CD14<sup>+</sup> antigen-presenting cell recruitment
Authors: Bas D Koster, Marta López González, Mari FCM van den Hout, Annelies W Turksma, Berbel JR Sluijter, Barbara G Molenkamp, Paul AM van Leeuwen, Saskia Vosslamber, Rik J Scheper, Alfons JM van den Eertwegh, M Petrousjka van den Tol, Ekaterina J Jordanova, Tanja D de Gruijl
Journal: Journal for ImmunoTherapy of Cancer (2021)

We previously reported CpG-B injection at the primary tumor excision site prior to re-excision and sentinel node biopsy to result in immune activation of the sentinel lymph node (SLN), increased melanoma-specific CD8+ T cell rates in peripheral blood, and prolonged recurrence-free survival. Here, we assessed recruitment and activation of antigen-presenting cell (APC) subsets in the SLN and at the injection site in relation to T cell infiltration.Re-excision skin specimens from patients with clinical stage I-II melanoma, collected 7 days after intradermal injection of either saline (n=10) or 8 mg CpG-B (CPG7909, n=12), were examined by immunohistochemistry, quantifying immune subsets in the epidermis, papillary, and reticular dermis. Counts were related to flow cytometric data from matched SLN samples. Additional in vitro cultures and transcriptional analyses on peripheral blood mononuclear cells (PBMCs) were performed to ascertain CpG-induced APC activation and chemokine profiles.Significant increases in CD83+, CD14+, CD68+, and CD123+ APC were observed in the reticular dermis of CpG-B-injected skin samples. Fluorescent double/triple staining revealed recruitment of both CD123+BDCA2+ plasmacytoid dendritic cells (DCs) and BDCA3/CD141+CLEC9A+ type-1 conventional DC (cDC1), of which only the cDC1 showed considerable levels of CD83 expression. Simultaneous CpG-B-induced increases in T cell infiltration were strongly correlated with both cDC1 and CD14 counts. Moreover, cDC1 and CD14+ APC rates in the reticular dermis and matched SLN suspensions were positively correlated. Flow cytometric, transcriptional, and chemokine release analyses of PBMC, on in vitro or in vivo exposure to CpG-B, indicate a role for the activation and recruitment of both cDC1 and CD14+ monocyte-derived APCs in the release of CXCL10 and subsequent T cell infiltration.The CpG-B-induced concerted recruitment of cDC1 and CD14+ APC to the injection site and its draining lymph nodes may allow for both the (cross-)priming of T cells and their subsequent homing to effector sites.
New SARS-CoV-2 Variants — Clinical, Public Health, and Vaccine Implications
Authors: Salim S Abdool Karim, Tulio de Oliveira
Journal: New England Journal of Medicine (2021)

The Challenge of SARS-CoV-2 Variants The emergence of the SARS-CoV-2 variants B.1.1.7 (VOC-202012/01), 501Y.V2 (B.1.351), and P.1 (B.1.1.28.1) has aroused many concerns, including worsening Covid-1...
Effect of cabazitaxel on macrophages improves CD47-targeted immunotherapy for triple-negative breast cancer
Authors: Xu Cao, Bolei Li, Jing Chen, Jessica Dang, Siqi Chen, E Gulsen Gunes, Bo Xu, Lei Tian, Sabina Muend, Mustafa Raoof, Christiane Querfeld, Jianhua Yu, Steven T. Rosen, Yingyu Wang, Mingye Feng
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Limited therapeutic options are available for triple-negative breast cancer (TNBC), emphasizing an urgent need for more effective treatment approaches. The development of strategies by targeting tumor-associated macrophages (TAMs) to stimulate their ability of Programmed Cell Removal (PrCR) provides a promising new immunotherapy for TNBC treatment. Methods CD47 is a critical self-protective “don’t eat me” signal on multiple human cancers against macrophage immunosurveillance. Using human and mouse TNBC preclinical models, we evaluated the efficacy of PrCR-based immunotherapy by blocking CD47. We performed high-throughput screens on FDA-approved anti-cancer small molecule compounds for agents potentiating PrCR and enhancing the efficacy of CD47-targeted therapy for TNBC treatment. Results We showed that CD47 was widely expressed on TNBC cells and TAMs represented the most abundant immune cell population in TNBC tumors. Blockade of CD47 enabled PrCR of TNBC cells, but the efficacy was not satisfactory. Our high-throughput screens identified cabazitaxel in enhancing PrCR-based immunotherapy. A combination of CD47 blockade and cabazitaxel treatment yielded a highly effective treatment strategy, promoting PrCR of TNBC cells and inhibiting tumor development and metastasis in preclinical models. We demonstrated that cabazitaxel potentiated PrCR by activating macrophages, independent of its cytotoxicity toward cancer cells. When treated with cabazitaxel, the molecular and phenotypic signatures of macrophages were polarized toward M1 state, and the NF-kB signaling pathway became activated. Conclusion The combination of CD47 blockade and macrophage activation by cabazitaxel synergizes to vastly enhance the elimination of TNBC cells. Our results show that targeting macrophages is a promising and effective strategy for TNBC treatment.
Roxadustat Treatment Corrects Anemia to Hemoglobin (Hb) Values ≥10 g/dL in the Majority of Patients with Non-Dialysis-Dependent Chronic Kidney Disease (NDD-CKD)
Authors: Anjay Rastogi, Roberto Pecoits-Filho, Steven Fishbane, Dustin J. Little, Elise Hardy, Kin-Hung P. Yu, Robert Provenzano
Journal: Journal of the American Society of Nephrology (2020)
Hepatic Arterial Infusion Chemotherapy Combined with Radiation Therapy for Advanced Hepatocellular Carcinoma with Tumor Thrombosis of the Main Trunk or Bilobar of the Portal Vein
Authors: Yumi Kosaka, Tomoki Kimura, Tomokazu Kawaoka, Yutaro Ogawa, Kei Amioka, Kensuke Naruto, Yuki Yoshikawa, Chihiro Kikukawa, Yosuke Suehiro, Kenji Yamaoka, Yuwa Ando, Shinsuke Uchikawa, Kei Morio, Takashi Nakahara, Eisuke Murakami, Shoichi Takahashi, Masataka Tsuge, Akira Hiramatsu, Michio Imamura, Keigo Chosa, Kazuo Awai, Yasushi Nagata, Kazuaki Chayama, Hiroshi Aikata
Journal: Liver Cancer (2021)

Overall survival of patients with advanced hepatocellular carcinoma (HCC) with Vp4 (tumor thrombosis of the main trunk or bilobar of the portal vein) is extremely poor.The purpose of this study is to clarify the prognosis of hepatic arterial infusion chemotherapy (HAIC) combined with radiation therapy (RT) for advanced HCC with Vp4 and to analyze the factors that contribute to the prognosis.In this retrospective cohort study, 51 HCC patients who were treated with HAIC and RT for portal vein tumor thrombosis and met the following criteria were enrolled: (i) with Vp4; (ii) Child-Pugh score of 5-7; (iii) Eastern Cooperative Oncology Group performance status of 0 or 1; (iv) no history of systemic therapy; and (v) from September 2004 to April 2019.Median overall survival and median progression-free survival were 12.1 and 4.2 months, respectively. Multivariate analysis showed >50% of relative tumor volume in the liver (HR, 3.027; p = 0.008) and extrahepatic spread with (HR, 3.773; p = 0.040) as signiﬁcant and independent factors of OS. The total overall response rate (ORR) was 19.6%; ORR in main tumor was 13.7%; and ORR in Vp4 was 51.0%. None of the patients who received HAIC combined with RT for advanced HCC with Vp4 developed hepatic failure. This combination therapy of HAIC with RT was safe and well tolerated in all cases.Combination therapies of HAIC and RT might be good therapy for advanced HCC with Vp4.
CLO21-016: Incidence, Risk Factors, and Prognostic Implications of Peri-Transplant Orthostatic Hypotension in Patients With Multiple Myeloma
Authors: Matthew Ho, Maria Moscvin, Soon Khai Low, Sara Close, Robert Schlossman, Jacob Laubach, Brett Glotzbecker, Paul Richardson, Giada Bianchi
Journal: Journal of the National Comprehensive Cancer Network (2021)

"CLO21-016: Incidence, Risk Factors, and Prognostic Implications of Peri-Transplant Orthostatic Hypotension in Patients With Multiple Myeloma" published on 17 Mar 2021 by National Comprehensive Cancer Network.
Abstract 12186: Performance of a Pre-Procedural Mehran Score to Predict Acute Kidney Injury After Percutaneous Coronary Intervention
Authors: Faisal Rahim, Michelle Nguyen, Steven Quach, Sai Guduru, Khalid Abusaada
Journal: Circulation (2018)

Introduction: Mehran score has been validated for prediction of AKI after PCI. However, its use of contrast volume in score calculation limits its application before the procedure. Hypothesis: To e...
P76.65 CNS Efficacy of AST2818 in Patients with T790M-Positive Advanced NSCLC: Data from a Phase I-II Dose-Expansion Study
Authors: Y. Shi, X. Hu, W. Liao, S. Zhang, Z. Wang, N. Yang, L. Wu, J. Zhou, K. Ying, Z. Ma, J. Feng, L. Liu, S. Qin, J. Fang, X. Zhang, Y. Jiang, N. Ge
Journal: Journal of Thoracic Oncology (2021)
YIA21-001: A Modified Delphi Study to Refine Measures of End-of-Life Care Quality for Children with Cancer
Authors: Prasanna J. Ananth, Sophia Mun, Noora Reffat, Soo Jung Kang, Sarah Pitafi, Xiaomei Ma, Cary P. Gross, Joanne Wolfe
Journal: Journal of the National Comprehensive Cancer Network (2021)
CLO21-014: Impact of Late Dosing on Testosterone Suppression With Two Different Leuprolide Acetate Formulations: In Situ Gel and Microsphere – an Analysis of US Clinical Data
Authors: Lucio N. Gordan, Stuart N. Atkinson, Deborah M. Boldt-Houle, Przemyslaw W. Twardowski
Journal: Journal of the National Comprehensive Cancer Network (2021)

"CLO21-014: Impact of Late Dosing on Testosterone Suppression With Two Different Leuprolide Acetate Formulations: In Situ Gel and Microsphere – an Analysis of US Clinical Data" published on 17 Mar 2021 by National Comprehensive Cancer Network.
Algorithm to Evaluate Abnormal Liver Function Tests in Liver Transplant Patients
Authors: Tom Winter
Journal: JAMA (2021)

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MA09.09 EGFR Mutation Status Is a Risk of Recurrence in pN0–1 Lung Adenocarcinoma When Considering pStage and Histological Subtype
Authors: M. Ito, Y. Miyata, Y. Tsutani, H. Ito, H. Nakayama, K. Imai, N. Ikeda, M. Okada
Journal: Journal of Thoracic Oncology (2021)
Abstract 16904: Hypercoagulability in Pediatric Patients Infected With SARS-Coronavirus 2
Authors: Sirisha Emani, Andrew Torres, Fatoumata Diallo, Mamadou Diallo, Meena Nathan, Juan Ibla, Muhammad Ghbeis, Christina J Vanderpluym, Sitaram Emani
Journal: Circulation (2020)

Introduction: Thrombosis is a complication associated with Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), Corona Virus Disease 2019 (COVID-19). Although, abnormalities in coagulation markers have been reported in adults with COVID-19, coagulopathy in pediatric patients infected with coronavirus has not been elucidated. Hypothesis: In this study, we evaluated the coagulation profile in pediatric patients with COVID-19 using Thromboelastography (TEG). Methods: This is a retrospective study of pediatric (≤18yrs) patients with seropositive COVID-19 (N=35) regardless of symptom status. Coagulation markers including TEG were obtained from review of medical records under an IRB approved study. All TEG parameters were compared between patients with COVID-19 and age matched controls without COVID-19 (N=35). Results: Regardless of symptom status, COVID-19 patients had significantly lower R-time (5.3±2.7 min vs. 6.5±1.5 min; p=0.03 ), K-time (1.1±0.3 min vs. 1.8±1.1 min; p&lt;0.001 ) and fibrinolysis (1.7±1.7% vs. 3.2±3.6%; p=0.04 ); and significantly elevated angle (73.6±4.8 deg vs.66.7±6.2 deg; p&lt;0.001 ), maximum amplitude (68.9±6.1 mm vs. 59.5±8.7 mm; p&lt;0.001 ) and overall clot strength G (11.7±3.3 Kdynes/cm 2 vs. 7.8±2.4 Kdynes/cm 2 ; p&lt;0.001 ). Whereas the standard coagulation tests such as PT/INR, PTT, Thrombin time and Heparin levels were within the normal pediatric reference ranges. D-dimer expression was also higher (0.94 μg/ml) in COVID-19 patients compared to the normal pediatric reference range (&lt;0.4 μg/ml). In patients with COVID-19 undergoing aspirin therapy, all patients responded to the treatment and platelet function was significantly inhibited compared to patients not given aspirin (85% vs. 8% platelet inhibition; p&lt;0.001 ). Conclusions: Abnormal expression of all TEG parameters and D-dimer is consistent with a hypercoagulable profile. TEG may be useful in reducing thrombosis-risk in patients with COVID-19 by guiding anticoagulation management.
Prospective Study of Acute Myeloid Leukemia (AML) Clinical Epidemiology and Cytogenetic Risk Group in Older Adults in the ECOG-ACRIN E2906 Clinical Trial: The Acute Leukemia Epidemiology, Survival and Endpoints (ALESE) Study
Authors: James M. Foran, Yanming Zhang, Michael Heckman, Selina Luger, Cassondra Hulshizer, Emily Vargas, Mark R. Litzow, Jessica K. Altman, Keith Pratz, Ryan Mattison, David F. Claxton, Geoffrey L. Uy, Harry P. Erba, Mohamad A. Cherry, Edward R. Broun, Bayard L. Powell, Hillard M Lazarus, Jacob M. Rowe, Elisabeth Paietta, Richard F. Little, Jen Poynter, Martin S. Tallman, James R. Cerhan
Journal: Blood (2017)
P09.48 Experience and Outcome of COVID-19-Positive Lung Cancer Patients from a Eastern Indian Hospital
Authors: P. Mohapatra, S. Bhuniya, M. Panigrahi, S. Bal, S. Goud, S. Padmaja, S. Ghosh, G. Durgeshwar, V.R. Acharyulu, A. Datta, S. Panigrahi, S. Mitra, M. Sethy, P. Mishra, S. Mohakud, S. Naik, D. Muduly, B. Behera, S. Mohanty, S. Das Majumdar, S. Patra, B. Mishra
Journal: Journal of Thoracic Oncology (2021)
Comparison of Survival Outcomes Among Patients With Breast Cancer With Distant vs Ipsilateral Supraclavicular Lymph Node Metastases
Authors: Hong Pan, Hui Wang, Mengjia Qian, Xinrui Mao, Guojian Shi, Ge Ma, Muxin Yu, Hui Xie, Lijun Ling, Qiang Ding, Kai Zhang, Shui Wang, Wenbin Zhou
Journal: JAMA Network Open (2021)

<h3>Importance</h3> There is a lack of studies exploring whether the survival of patients with distant lymph node metastases (DLNM) is different from that of patients with ipsilateral supraclavicular lymph node metastases (ISLM) and other stage IV breast cancer. <h3>Objective</h3> To assess the survival of patients with DLNM from breast cancer vs ISLM and other stage IV breast cancer. <h3>Design, Setting, and Participants</h3> This cohort study included 2033 patients diagnosed with breast cancer between January 1, 2010, and December 31, 2014, from the Surveillance, Epidemiology and End Results registries database. Three groups of patients were included: (1) patients with ISLM without any distant metastasis, (2) patients with DLNM, and (3) patients with distant metastases (DLNM excluded). Patients younger than 18 years or older than 100 years were excluded. The data were analyzed in February 2020. <h3>Exposures</h3> Surgery for primary tumor, surgery for distant lymph nodes, and radiotherapy. <h3>Main Outcomes and Measures</h3> Overall survival (OS) and breast cancer–specific survival (BCSS). <h3>Results</h3> Of the 2033 women (mean [SD] age, 62.03 [14.62] years [range, 23.00-99.00 years]; 1510 White participants [74.3%]) with breast cancer included in the study, 346 patients (17.0%) had DLNM, 212 (10.4%) had ISLM, and 1475 (72.6%) had distant metastases (DLNM excluded). The 3-year BCSS rates were 63.24% for ISLM, 64.54% for DLNM, and 41.20% for distant metastases. The 3-year OS rates were 53.46% for ISLM, 62.67% for DLNM, and 38.21% for distant metastases. Compared with patients with ISLM, patients with DLNM showed similar BCSS (hazard ratio [HR], 0.81; 95% CI, 0.52-1.25;<i>P</i> = .34) and OS (HR, 0.73; 95% CI, 0.51-1.05;<i>P</i> = .09), whereas patients with distant metastases showed significantly poorer BCSS (HR, 1.99; 95% CI, 1.43-2.78;<i>P</i> &lt; .001) and OS (HR, 1.79; 95% CI, 1.35-2.38;<i>P</i> &lt; .001). Of the 346 patients with DLNM, primary surgery (HR, 0.21; 95% CI, 0.12-0.39;<i>P</i> &lt; .001) and radiotherapy (HR, 0.46; 95% CI, 0.25-0.87;<i>P</i> = .02) were significantly associated with improved OS. <h3>Conclusions and Relevance</h3> The results of this cohort study suggest that DLNM of breast cancer, with similar survival to N3c disease (indicating metastases to the ipsilateral supraclavicular lymph nodes), might be a regional disease, and reassessment of the role of lymph node metastases in breast cancer may be necessary. Given these findings, aggressive locoregional therapies for this disease are recommended, although future studies are still needed to confirm these results.
Second intravenous immunoglobulin dose in patients with Guillain-Barré syndrome with poor prognosis (SID-GBS): a double-blind, randomised, placebo-controlled trial
Authors: Christa Walgaard, Bart C Jacobs, Hester F Lingsma, Ewout W Steyerberg, Bianca van den Berg, Alexandra Y Doets, Sonja E Leonhard, Christine Verboon, Ruth Huizinga, Judith Drenthen, Samuel Arends, Ilona Kleine Budde, Ruud P Kleyweg, Krista Kuitwaard, Marjon F G van der Meulen, Johnny P A Samijn, Frederique H Vermeij, Jan B M Kuks, Gert W van Dijk, Paul W Wirtz, Filip Eftimov, Anneke J van der Kooi, Marcel P J Garssen, Cees J Gijsbers, Maarten C de Rijk, Leo H Visser, Roderik J Blom, Wim H J P Linssen, Elly L van der Kooi, Jan J G M Verschuuren, Rinske van Koningsveld, Rita J G Dieks, H Job Gilhuis, Korné Jellema, Taco C van der Ree, Henriette M E Bienfait, Catharina G Faber, Harry Lovenich, Baziel G M van Engelen, Rutger J Groen, Ingemar S J Merkies, Bob W van Oosten, W Ludo van der Pol, Willem D M van der Meulen, Umesh A Badrising, Martijn Stevens, Albert-Jan J Breukelman, Casper P Zwetsloot, Maaike M van der Graaff, Marielle Wohlgemuth, Richard A C Hughes, David R Cornblath, Pieter A van Doorn, Christa Walgaard, Bart C. Jacobs, Hester F. Lingsma, Ewout W. Steyerberg, Bianca Van den Berg, Alexandra Y. Doets, Sonja E. Leonhard, Christine Verboon, Ruth Huizinga, Judith Drenthen, Samuel Arends, Ilona Kleine Budde, Ruud P. Kleyweg, Krista Kuitwaard, Marjon F.G. Van der Meulen, Johnny P.A. Samijn, Frederique H. Vermeij, Jan B.M. Kuks, Gert W. Van Dijk, Paul W. Wirtz, Filip Eftimov, Anneke J. Van der Kooi, Marcel P.J. Garssen, Cees J. Gijsbers, Maarten C. De Rijk, Leo H. Visser, Roderik J. Blom, Wim H.J.P. Linssen, Elly L. Van der Kooi, Jan J.G.M. Verschuuren, Rinske Van Koningsveld, Rita J.G. Dieks, H. Job Gilhuis, Korné Jellema, Taco C. Van der Ree, Henriette M.E. Bienfait, Karin G. Faber, Harry Lovenich, Baziel G.M. Van Engelen, Rutger J. Groen, Ingemar S.J. Merkies, Bob W. Van Oosten, W. Ludo Van der Pol, Willem D.M. Van der Meulen, Umesh A. Badrising, Martijn Stevens, Albert-Jan J. Breukelman, Casper P. Zwetsloot, Maaike M. Van der Graaff, Marielle Wohlgemuth, Richard A.C. Hughes, David R. Cornblath, Pieter A. Van Doorn, R.B. Althingh van Geusau, C.J.M. Van Boheemen, I.M. Bronner, B. Feenstra, C. Fokke, T.A. Hoogendoorn, R. Van Houten, A. Hovestad, P.J.H.W. Jansen, E. Keuter, J. Krudde, F.H.H. Linn, J. Lion, S.M. Manschot, S.J. Mellema, D.S.M. Molenaar, D.J. Nieuwkamp, D.G. Oenema, J.C.H. Van Oostrom, N.P. Van Orshoven, R.J.O. Van der Ploeg, S. Polman, A. Ruitenberg, L. Ruts, A.J.G.M. Schyns-Soeterboek, R. Trip
Journal: The Lancet Neurology (2021)