tbuckley/cabot-search huggingface dataset:
Should Epidural Analgesia Be Abandoned for Open Pancreatoduodenectomy?
Authors: Renaud Guerin, Karem Slim
Journal: JAMA Surgery (2020)

To the Editor We read with interest the article by Klotz et al1 showing that epidural analgesia (EDA) and intravenous analgesia (IVA) have comparable results, but EDA has more shortcomings. We acknowledge the authors’ work, but this randomized trial deserves 3 comments.
The Imposed Obscurity of Richard W. Lippman, MD (1916–1959), Revered Renal Researcher and Physician
Authors: Franklin G. Strauss, Leon G. Fine
Journal: Journal of the American Society of Nephrology (2020)

In 1948, Richard W. Lippman, MD, was appointed to a research position at the Institute for Medical Research at Cedars of Lebanon Hospital in Los Angeles. His grant support came from the Guggenheim Foundation and the US Public Health Service (USPHS). He was also actively involved in seeing referred
Longitudinal Effect of Luspatercept Treatment on Iron Overload and Iron Chelation Therapy (ICT) in Adult Patients (Pts) with β-Thalassemia in the Believe Trial
Authors: Olivier Hermine, Maria Domenica Cappellini, Ali T. Taher, Thomas D. Coates, Vip Viprakasit, Ersi Voskaridou, Ashutosh Lal, Hong Keng Liew, Silverio Perrotta, Abderrahim Khelif, Antonis Kattamis, Jeevan K. Shetty, George Zhang, Yu (Olivia) Tian, Dimana Miteva, Tatiana Zinger, Derek Tang, Jay T. Backstrom, John B. Porter
Journal: Blood (2020)
Bleeding Cessation in a Mouse Jugular Vein Puncture Wound Model Is Caused By Extravascular Capping, Not Hole Infill
Authors: Brian Storrie, Sung Rhee, Timothy J. Stalker, Irina D Pokrovskaya, Kenny Ling, Yajnesh Vedanaparti, Joshua Cohen, Maria Aronova, Sidney W Whiteheart, Lawrence Brass
Journal: Blood (2020)
Examination of Clinical and Molecular Characteristics and Treatment Patterns of Adolescent and Young Adult (AYA) Patients with Chronic Lymphocytic Leukemia
Authors: Hua-Jay J Cherng, Nadya Jammal, Shilpa Paul, Xuemei Wang, Koji Sasaki, Philip A. Thompson, Jan A. Burger, Alessandra Ferrajoli, Zeev E. Estrov, Susan M. O'Brien, Michael J. Keating, William G. Wierda, Nitin Jain
Journal: Blood (2020)
Not your ‘day-to-day’ colonic polyps
Authors: Jing Liang Ho, Charles Vu, Raymond Liang, Cristine Ding
Journal: Gut (2020)

A 62-year-old man was incidentally found to have a massive splenomegaly during his admission for a right-sided pneumonia. A contrast-enhanced CT of the neck, thorax, abdomen and pelvis revealed a massive splenomegaly that measured 26 cm in the craniocaudal span, with no hepatomegaly, lymphadenopathy or suspicious mass. Thalassaemia screen was negative and peripheral blood film did not show any abnormal cells or spherocytes. A bone marrow examination was normal as well. Liver cirrhosis, though less likely the cause of massive splenomegaly, was excluded by a normal transient elastography.

Full blood count showed microcytic hypochromic anaemia with haemoglobin of 94 g/L. He reported neither gastrointestinal symptoms nor weight loss. Upper gastrointestinal …
An immune cell infiltration-based immune score model predicts prognosis and chemotherapy effects in breast cancer
Authors: Silei Sui, Xin An, Caiming Xu, Zongjuan Li, Yijun Hua, Geya Huang, Sibei Sui, Qian Long, Yanxia Sui, Yuqing Xiong, Micheal Ntim, Wei Guo, Miao Chen, Man Li, Xiangsheng Xiao, Wuguo Deng
Journal: Theranostics (2020)

Background: Immune cells have essential auxiliary functions and influence clinical outcomes in cancer, with high immune infiltration being associated with improved clinical outcomes and better response to treatment in breast cancer (BC). However, studies to date have not fully considered the tumor-infiltrating immune cell (TIIC) landscape in tumors. This study investigated potential biomarkers based on TIICs to improve prognosis and treatment effect in BC. Results: We enrolled 5112 patients for analysis and used cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT), a new computational algorithm, to quantify 22 TIICs in primary BC. From the results of univariate Cox regression, 12 immune cells were determined to be significantly related to the overall survival (OS) of BC patients. Furthermore, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses were applied to construct an immune prognostic model based on six potential biomarkers. By dividing patients into low- and high-risk groups, a significant distinction in OS was found in the training cohort, with 20-year survival rates of 42.6% and 26.3%, respectively. Applying a similar protocol to validation and test cohorts, we found that OS was significantly shorter in the high-risk group than in the low-risk group, regardless of the molecular subtype of BC. Using the immune score model to predict the effect of BC patients to chemotherapy, the survival advantage for the low-risk group was evident among those who received chemotherapy, regardless of the chemotherapy regimen. In evaluating the predictive value of the nomogram, a decision curve showed better predictive accuracy than the standard tumor-node-metastasis (TNM) staging system. Conclusion: The immune cell infiltration-based immune score model can be effectively and efficiently used to predict the prognosis of BC patients as well as the effect of chemotherapy.
The Impact of Anti-Microbial Drug-Drug Interactions on Acute Kidney Injury after Allogeneic Hematopoietic Cell Transplantation
Authors: Fumiya Wada, Yasuyuki Arai, Junya Kanda, Toshio Kitawaki, Masakatsu Hishizawa, Tadakazu Kondo, Kouhei Yamashita, Akifumi Kondo Takaori
Journal: Blood (2020)
Cross-talk between the gut microbiota and monocyte-like macrophages mediates an inflammatory response to promote colitis-associated tumourigenesis
Authors: Yunben Yang, Lili Li, Chunjing Xu, Yunke Wang, Zhen Wang, Mengyao Chen, Zhou Jiang, Jun Pan, Chenghui Yang, Xiaoqian Li, Kai Song, Junfeng Yan, Wanglan Xie, Xianguo Wu, Zhigang Chen, Ying Yuan, Shu Zheng, Jun Yan, Jian Huang, Fuming Qiu
Journal: Gut (2020)

Objective Macrophages are among the most abundant cells in the colon tumour microenvironment, and there is a close relationship among monocytes, macrophages and the gut microbiota. Alterations in the gut microbiota are involved in tumour development, but the underlying mechanisms remain unclear. We aim to elucidate the temporal changes in macrophage subsets and functions, and how these dynamics are regulated by microbial cues in the initiation of colitis-associated cancer. Design A mouse model of colitis-associated tumourigenesis was established to determine macrophage dynamics. The role of monocyte-like macrophage (MLM) was confirmed by targeting its chemotaxis. The effects of the gut microbiota were assessed by antibiotic treatment and faecal microbiota transplantation. Results A selective increase in MLMs was observed in the initial stages of colitis-associated cancer, with an enhanced secretion of inflammatory cytokines. MLM accumulation was regulated by CCL2 expression of colonic epithelial cells, which was influenced by bacteria-derived lipopolysaccharide (LPS). LPS further stimulated interleukin 1β production from MLMs, inducing interleukin-17-producing T-helper cell activation to promote inflammation. These observations were also supported by altered microbial composition associated with human colitis and colorectal cancer, evolving transcriptional signature and immune response during human colitis-associated tumourigenesis. Conclusions The gut microbiota uses LPS as a trigger to regulate MLM accumulation in a chemokine-dependent manner and generate a precancerous inflammatory milieu to facilitate tumourigenesis.
Allogeneic Blood or Marrow Transplantation (BMT) with Post-Transplantation Cyclophosphamide (PTCy) Based Graft Versus Host Disease (GVHD) Prophylaxis for Myelodysplastic Syndrome/ Myeloproliferative Neoplasm-Overlap Syndromes (MDS/MPN)
Authors: Theodoros Karantanos, Hua-Ling Tsai, Lukasz P. Gondek, Mark Levis, Margaret M. Showel, Amy E. DeZern, Ivana Gojo, Ravi Varadhan, Richard J. Jones, Tania Jain
Journal: Blood (2020)
FRI0011 DEVELOPMENT OF A HIGH-DIMENSIONAL FLOW CYTOMETRY PANEL TO ANALYSE NATURAL KILLER CELLS IN SLE
Authors: N. Fewings, S. Schibeci, F. Mckay, S. Swaminathan, M. W. Lin
Journal: Annals of the Rheumatic Diseases (2020)

Background: Natural Killer (NK) cells are an innate immune cell type that has somewhat been overlooked in the context of systemic lupus erythematosus (SLE). SLE patients display a reduced number of NK cells with an activated phenotype and increased capacity to produce IFN-γ, decreased antibody-dependent cellular cytotoxicity (ADCC), and altered natural cytotoxicity (1). NK cell activation is determined by the integration of input from a myriad of activating and inhibitory receptors. Previously, using Nanostring® gene expression technologies, we found our SLE cohort showed decreased gene expression of a number of these receptors (KLRC2, KLRC1, KLRB1, KLRF1, KLRG1, PRF1 and IL2RB) leading us to explore NK cells in SLE in more depth. Objectives: Our aim was to develop a high-dimensional flow cytometry panel to characterise dysregulation of NK cell in SLE, with particular reference to the activating and inhibitory receptors found to be dysregulated in SLE at the gene expression level. Methods: Markers for NK panel were selected to include canonical phenotyping/functional molecules of NK cells with a particular emphasis on receptors found to be lower in our SLE cohort’s gene expression findings. NK panel was designed to minimise spectral overlap, expression and co-expression of markers was taken into consideration. Antibodies were titrated, and voltages optimised to achieve the best separation index for each of the antibodies. The 24-marker panel was run on 52 SLE patients of various disease manifestations, treatments and disease severity. 20 healthy controls were also run for comparison. Results: A 24-marker flow cytometry panel including 19 NK cell antigens was optimised, including basic phenotype (CD3/CD56/CD16/NKp46) and NK differentiation markers (CD57/CD94), activating and inhibitory receptors (NKG2A/NKG2C/NKG2D), costimulatory receptors (CD244/CD226), transcription factors (Eomes/Tbet) and effector molecules (granzyme/perforin). Immunophenotypic high-parameter analysis of SLE and control samples is in progress and results will be presented. Conclusion: Our development of a high-dimensional immunophenotypic panel allows identification of changes in NK cells in SLE including antigen expression levels, subset percentages and potentially of novel subsets. This panel will be used to investigate NK cell changes with disease course/activity, therapeutic response, and to discover potential drug targets for SLE. References: [1]Spada R, Rojas JM, Barber DF. Recent findings on the role of natural killer cells in the pathogenesis of systemic lupus erythematosus. J Leukocyte Biol. 2015;98(4):479-487. doi:10.1189/jlb.4ru0315-081rr Acknowledgments: Westmead Institute for Medical Research Genomics Facility Westmead Institute for Medical Research Flow Cytometry Facility Staff Specialists’ TESL and Trust Fund Committee Disclosure of Interests: None declared
Idecabtagene Vicleucel (ide-cel, bb2121), a BCMA-Directed CAR T Cell Therapy, in Patients with Relapsed and Refractory Multiple Myeloma: Updated Results from Phase 1 CRB-401 Study
Authors: Yi Lin, Noopur S. Raje, Jesus G. Berdeja, David S. Siegel, Sundar Jagannath, Deepu Madduri, Michaela Liedtke, Jacalyn Rosenblatt, Marcela V. Maus, Monica Massaro, Fabio Petrocca, Andrea Caia, Zhihong Yang, Timothy B. Campbell, Kristen Hege, Nikhil C. Munshi, James N. Kochenderfer
Journal: Blood (2020)
Comparing the Efficacy of Cyclophosphamide Versus Lenalidomide in Combination with Bortezomib for Newly Diagnosed Multiple Myeloma Treatment: A Systematic Review
Authors: Muhammad Khawar Sana, Syed Maaz Abdullah, Hamid Ehsan, Sikander Abdullah, Amrat Ehsan, Muhammad Ans Sharif, Sajid Ehsan, Richi Kashyap, Talha Badar, Faiz Anwer
Journal: Blood (2020)
Systematic Review of Phase III Trials of Daratumumab Based Regimens in Relapsed Refractory Multiple Myeloma
Authors: Karun Neupane, Zahoor Ahmed, Rabia Ashraf, Amna Khan, Moazzam Shahzad, Arafat Ali Farooqui, Muhammad Salman Faisal, Syed Maaz Abdullah, Richi Kashyap, Hamid Ehsan, Faiz Anwer
Journal: Blood (2020)
Clinical Significance and Biomarkers to Predict Unsustained Complete Remission in Transplant-Eligible Multiple Myeloma
Authors: Ana Jimenez-Ubieto, Bruno Paiva, Joaquin Martinez Lopez, María Teresa Cedena, Noemi Puig, Albert Oriol, Maria Jesús Blanchard, Rafael Rios, Lucia Lopez-Anglada, Jesús Martín, Rafael Martínez, Anna Sureda Balari, Miguel Hernández, Javier de la Rubia, Isabel Krsnik, Valentin Cabañas, Luis Palomera, Joan Bargay, Jose Maria Moraleda, Laura Rosiñol, María-Victoria Mateos, Jesus F. San-Miguel, Joan Bladé, Juan-José Lahuerta
Journal: Blood (2020)
Presence of a Measurable M-Spike before Autologous Stem Cell Transplantation Is Associated with Shorter Survival in Patients with Light Chain Amyloidosis
Authors: Abdullah S. Al Saleh, Iuliana Vaxman, Harsh Parmar, M Hasib Sidiqi, Eli Muchtar, Francis K. Buadi, David Dingli, Martha Q. Lacy, Rahma M Warsame, Wilson I Gonsalves, Taxiarchis Kourelis, William J Hogan, Prashant Kapoor, Robert Wolf, Angela Dispenzieri, Shaji K. Kumar, Morie A. Gertz
Journal: Blood (2020)
Incidence and Risk Factors for Bleeding in Patients with Acute Myeloid Leukemia Receiving Intensive Induction Chemotherapy
Authors: Jurjen Versluis, Yael Flamand, Erika J. Haydu, Rahul S. Vedula, Anne Charles, Kevin Copson, Ofir Wolach, Pavan Bendapudi, Roger Belizaire, Donna S. Neuberg, Marlise R Luskin, R. Coleman Lindsley
Journal: Blood (2020)
Peripheral Blood Monoclonal B-Cell and/or Plasma Cell Detection By Flow Cytometry in Screening and Monitoring EBV-Positive Post-Transplant Lymphoproliferative Disorders
Authors: Xueying Wu, Hui Wang, Aixian Wang, Xingyu Cao, Meiwei Gong, Junyi Zhen, Man Chen, Qing Du, Peihua Lu
Journal: Blood (2020)
Risk Factors for Overall Survival in Children with High Risk Acute Myeloid Leukemia (HR AML) after Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) with Different Intensity of Conditioning Regimens
Authors: Elena Vladimirovna Semenova, Olesia V Paina, Zhemal Zarifovna Rakhmanova, Polina Valerievna Kozhokar, Anastasia S Frolova, Kirill Alexandrovich Ekushov, Tatiana A Bykova, Anna A. Osipova, Inna Markova, Sergey N. Bondarenko, Boris I Smirnov, Ildar M Barkhatov, Aleksandr Alyanski, Elena V. Babenko, Ivan S. Moiseev, Axel R. Zander, Ludmila S Zubarovskaya
Journal: Blood (2020)
Congenital Muscular Mitral-Aortic Discontinuity Identified in Patients With Obstructive Hypertrophic Cardiomyopathy
Authors: Paolo Ferrazzi, Paolo Spirito, Irene Binaco, Aleksei Zyrianov, Daniele Poggio, Giuseppe Vaccari, Massimiliano Grillo, Laura Pezzoli, Agnese Scatigno, Lucian Dorobantu, Andrea Mortara, Paolo Bruzzi, Luca Boni, Maria Iascone
Journal: Journal of the American College of Cardiology (2020)
PTU-010 Exposure to endotherapy for upper gastrointestinal bleeding at the point of gastroscopy certification – is it sufficient?
Authors: K Siau, P Dunckley, J Anderson, I Beales, R Broughton, M Feeney, N Hawkes, G Johnson, S Thomas-Gibson, R Valori, C Wells, B McKaig
Journal: Gut (2017)

Introduction  Although certification in diagnostic gastroscopy has been established in the UK, there is no formal process for quality assurance (QA) in endotherapy for upper gastrointestinal bleeding (UGIB). Training opportunities are variable, with 11% of gastroenterology ST7s citing inadequate exposure,[1] despite an expectation to independently manage UGIB upon completion of training. Data on endotherapy exposure during endoscopy training is limited. We aimed to assess whether trainees are receiving adequate exposure to endotherapy at the time of gastroscopy certification.  Method  Trainees awarded certification in gastroscopy between September 2009–2016 were identified from the national JETS e-Portfolio. Trainee inputs and formative assessments (DOPS) for UGIB therapy, up to their certification date, were analysed. Only trainees with ³200 procedures were included, thereby excluding those who had submitted baseline information which may have contained therapeutic data. Exposure rates from medical endoscopists (physician and surgical trainees) were compared with non-medical endoscopists (NME).  Results  885 trainee portfolios were analysed (765 medical and 120 NMEs), with a median procedural count of 276 (IQR 124). The median number of therapeutic entries and DOPS were 4 (IQR 11), and 1 (IQR 3) respectively. Overall rates for endotherapy and DOPS were 2.9% and 0.8% per procedure. When stratified by therapy, the median exposure to each therapy was either 0 or 1, with means displayed in Table 1. 25.2% of trainees had no exposure to any type of endotherapy (67.5% of NME and 18.6% of medical endoscopists, p  Conclusion  Training on endotherapy prior to certification is limited. The current UGI certification process does not ensure competency in endotherapy for UGIB. In response, the JAG QA team have recently released new DOPS forms specific to UGIB, and are consulting on introducing formal certification in endotherapy for UGIB.  Reference  GMC National Training Survey Results 2016, Gastroenterology, http://www.gmc-uk.org/education/gastroenterology.asp  Disclosure of Interest  None Declared
Combined Cranial Intraosseous and Cerebral Cavernous Malformations With Pathogenic <i>CCM1 </i>Germline Sequence Variations
Authors: Jian Ren, Yukui Wei, Tao Hong
Journal: JAMA Neurology (2020)

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Sickle Cell Disease Model Mice Lacking 2,3-Dpg Show Reduced RBC Sickling and Improvements in Markers of Hemolytic Anemia
Authors: Kelly M. Knee, Amey Barakat, Lindsay Tomlinson, Lila Ramaiah, Zane Wenzel, Brendon Kapinos, Youngwook Ahn, Nathanael G. Lintner, S. Denise Field, Reema Jasuja, Betty A. Pettersen
Journal: Blood (2020)
Abstract 545: Sex Difference in Right Ventricular Response to Pressure Overload is Associated With Differential Fibrotic Remodeling and Cyclic Guanosine Monophosphate Signaling
Authors: Ilaria Russo, Wen Dun, Swasti Mehta, Christos Tzimas, Emily J Tsai
Journal: Circulation Research (2020)

Background: In HFpEF and PAH, men are more likely than women to develop right ventricular dysfunction (RVD) and die. Mechanisms underlying these sex differences are not well understood. In advanced HF patients, RVD is associated with RV fibrosis. Sex differences in cGMP anti-fibrotic cardioprotection have been reported. Hypothesis: Sex differences in RV response to pressure overload may be due to differential anti-fibrotic cGMP signaling in the RV. Methods: Adult male and female C57BL6/J mice underwent pulmonary artery banding (PAB, 25g) vs. thoracotomy (Sham). RV remodeling was assessed by echocardiography, pressure-volume loop recordings, morphometrics, and histology. Expression of transcripts encoding various cGMP signaling proteins ( Nppa, Nppb, Npr1, Npr2, Npr3, Gucy1a3, Gucy1b3, Pde5, Pde9a, Pkg1a ), the fetal gene program, tissue fibrosis and ECM remodeling ( Ace, Tgfβs, Smads, Ctgf, αSma, Postn, Col1α1, Lum, Igfbp5, Mmp2-3, Timp1-2) were assessed at 9wks. Results: Post-PAB survival rate did not differ between sexes (log-rank HR 1.02, 95% CI 0.30-3.48, P=NS), but median time-to-death was 20 days (IQR 15-32) for M-PAB vs. 35.5 days (IQR 10.8-41.5) for F-PAB. PAB increased RV mass in both sexes (Fulton’s index 0.45±0.07 M-PAB vs 0.21±0.01 M-Sham, P&lt;0.01; 0.49±0.06 F-PAB vs 0.22±0.01 F-Sham, P&lt;0.01). RV myocyte hypertrophy was greater in M-PAB (cardiomyocyte area 592.7±6μm 2 vs 397.7±21.6μm 2 F-PAB, P&lt;0.01). RV dilation and decreased TAPSE and RV S’ were present in all PAB mice. Only M-PAB had depressed RV FAC (29.9±1.9% vs. 38.1±2.4% F-PAB, P=0.02). M-PAB had worse diastolic function than F-PAB (Tau 32.8±2.9ms M-PAB vs 14.2±2.1ms M-Sham, P&lt;0.01; 25.6±5.3ms F-PAB vs 15.0±2.1ms M-Sham, P=NS). In male but not female mice, PAB induced upregulation of Nppa, Nppb, Npr1, Npr2, Npr3, Gucy1a3, Gucy1b3, Pde5 and Pkg1a in the RV. RV transcript levels of Ace, Col1α1, Ctgf, Igfbp5, Mmp2, and Timp2 were also higher in M-PAB than F-PAB. Conclusions: Males have worse RV functional response to PAB than do females. This sex difference was also associated with increased mRNA levels of cGMP signaling mediators and upregulation of pro-hypertrophic and pro-fibrotic genes in male PAB mice. Further studies are needed to elucidate sex-dependent regulation of RV remodeling.
Ibrutinib Off-Target Inhibition Inhibits Antibody-Dependent Cellular Phagocytosis but Not Efferocytosis of CLL Cells
Authors: Charles C. Chu, Jonathan J. Pinney, Sara K. Blick-Nitko, Andrea M. Baran, Derick R. Peterson, Hannah E. Whitehead, Raquel Izumi, Veerendra Munugalavadla, Paul M. Barr, Karl R. VanDerMeid, Michael Rusty Elliott, Clive S. Zent
Journal: Blood (2020)
Decreased Cardiac Ejection Fraction Is Associated with Worse Survival in Patients with Light Chain Amyloidosis Treated with Autologous Stem Cell Transplantation
Authors: Abdullah S. Al Saleh, Iuliana Vaxman, Harsh Parmar, Alissa Visram, M Hasib Sidiqi, Eli Muchtar, Francis K. Buadi, David Dingli, Martha Q. Lacy, Rahma M Warsame, Wilson I Gonsalves, Taxiarchis Kourelis, William J Hogan, Prashant Kapoor, Robert Wolf, Angela Dispenzieri, Shaji K. Kumar, Morie A. Gertz
Journal: Blood (2020)
Jean McIldowie Smellie
Authors: Alan Craft
Journal: BMJ (2020)

Jean McIldowie Smellie was a paediatrician who specialised in the management of children with urinary infection. Her meticulous research was important in developing our current understanding of the condition and substantially reducing the number of investigations and operations to which children were subjected.

She was appointed to a part time post at University College Hospital in London with a remit …
Safety Analysis of Patients Who Received Ruxolitinib for the Treatment of Steroid-Refractory Chronic Graft-Versus-Host Disease in an Expanded Access Program
Authors: Parameswaran Hari, Haris Ali, Yi-Bin Chen, Salman Fazal, Tara K. Gregory, Sarah M. Anand, Ahmad Naim, Dilan Paranagama, Valkal Bhatt, Amy Blithe, John F. DiPersio
Journal: Blood (2020)
Automated Baseline Fluorodeoxyglucose-Positron Emission Tomography Imaging and High BCL2 Expression Provide Orthogonal Prognostic Value in Predicting High-Risk <i>De Novo</i> Diffuse Large B-Cell Lymphoma Patients
Authors: Skander Jemaa, Samuel Tracy, Alessia Bottos, Alex de Crespigny, Thomas Bengtsson, Tina G Nielsen, Joseph N Paulson
Journal: Blood (2020)