tbuckley/cabot-search huggingface dataset:
Sudden Death after Intravenous Injection of Mercurial Diuretic
Authors: M. Winternitz
Journal: BMJ (1947)

Sudden Death after Intravenous Injection of Mercurial Diuretic SIR,-A.G. Oettle's case of sudden death after intravenous "neptal " (Oct.4, p. 530) prompts me to a few remarks.Such disasters cannot always be avoided-e.g., if they happen after the first injection to a patient, where there is no reason to expect untoward reactions.Such cases, fortunately, are extremely rare.More often, faulty.choice of the case and an overdose are the cause of toxic reactions.The following rules should help to restrict fatal or toxic reactions.Mercury administration must never be given in excess of the excretory power of the kidneys.Low con- centrating power and poor response to a previous injection are warning signals.The minimal injection-free interval should be three days, except in acute emergencies.Digitalis, strophanthin, urea, and ammonium chloride help to make this possible.The
Immunosuppression Withdrawal in Liver Transplant Recipients on Sirolimus
Authors: Josh Levitsky, Bryna E. Burrell, Sai Kanaparthi, Laurence A. Turka, Sunil Kurian, Alberto Sanchez‐Fueyo, Juan J. Lozano, Anthony Demetris, Andrew Lesniak, Allan D. Kirk, Linda Stempora, Guang‐Yu Yang, James M. Mathew
Journal: Hepatology (2019)

BACKGROUND AND AIMS As conversion from calcineurin inhibitor to sirolimus (SRL), a mechanistic target of rapamycin inhibitor (mTOR‐I), has been shown to enhance immunoregulatory profiles in liver transplant (LT) recipients (LTRs), mTOR‐I therapy might allow for increased success of immunosuppression (IS) withdrawal. Our aim was to determine if operational tolerance could be observed in LTRs withdrawn from SRL and if blood/graft tolerance biomarkers were predictive of successful withdrawal. APPROACH AND RESULTS We performed a prospective trial of SRL monotherapy withdrawal in nonimmune, nonviremic LTRs &gt; 3 years post‐LT. SRL was weaned over ~6 months, and biopsies were performed 12 months postweaning or at concern for acute rejection. Twenty‐one LTRs consented; 6 were excluded due to subclinical acute rejection on baseline biopsy or other reasons, and 15 underwent weaning (age 61.3 ± 8.8 years; LT to SRL weaning 6.7 ± 3 years). Eight (53%) achieved operational tolerance (TOL). Of the 7 who were nontolerant (non‐TOL), 6 had mild acute rejection on biopsy near the end of weaning or at study end; 1 was removed from the trial due to liver cancer recurrence. At baseline preweaning, there were statistically increased blood tolerogenic dendritic cells and cell phenotypes correlating with chronic antigen presentation in the TOL versus non‐TOL groups. A previously identified biopsy gene signature accurately predicted TOL versus non‐TOL in 12/14 LTRs before weaning. At study end, biopsy staining revealed statistically significant increases in antigen‐presenting cell:leukocyte pairings, FOXP3 + /CD4 + T cells, Tbet + /CD8 + T cells, and lobular dendritic cells in the non‐TOL group. CONCLUSIONS This study evaluated IS withdrawal directly from mTOR‐I therapy in LTRs and achieved &gt; 50% operational tolerance. Preweaning gene expression and peripheral blood mononuclear cell profiling may be useful as predictors of successful mTOR‐I therapy withdrawal. NCT02062944.
Growth factors with enhanced syndecan binding generate tonic signalling and promote tissue healing
Authors: Mayumi Mochizuki, Esra Güç, Anthony J. Park, Ziad Julier, Priscilla S. Briquez, Gisela A. Kuhn, Ralph Müller, Melody A. Swartz, Jeffrey A. Hubbell, Mikaël M. Martino
Journal: Nature Biomedical Engineering (2019)
Long Term Discontinuation of Eltrombopag after Remission in Primary Immune Thrombocytopenia: 8-Year Follow-up Data from 15 Spanish Centers
Authors: Tomas Jose Gonzalez-Lopez, Fernando Fernandez-Fuertes, Maria Cristina Pascual Izquierdo, Isabel Caparros, Silvia Bernat, Carmen Pastoriza, Maria Paz Martínez-Badas, Pável E Olivera, Gonzalo Caballero, Jose Angel Hernandez-Rivas, Daniel Martínez-Carballeira, Inmaculada Soto Ortega, Gloria Perez Segura, Isabel Regalado, Blanca Sánchez-González, Isidro Jarque, Luis Javier garcia Frade, Miguel A. Sanz
Journal: Blood (2019)
ACTR-32. NRG ONCOLOGY RTOG 1205: RANDOMIZED PHASE II TRIAL OF CONCURRENT BEVACIZUMAB AND RE-IRRADIATION VS. BEVACIZUMAB ALONE AS TREATMENT FOR RECURRENT GLIOBLASTOMA
Authors: Christina Tsien, Stephanie Pugh, adam Dicker, Jeffrey Raizer, Martha Matuszak, Enrico Lallana, Jiayi Huang, ozer algan, Nicholas Taylor, Lorraine Portelance, John Villano, John T Hamm, Kevin S Oh, Arif N Ali, Michelle Kim, Scott Lindhorst, Minesh Mehta
Journal: Neuro-Oncology (2019)

Abstract This study sought to determine whether re-irradiation (ReRT) and concurrent bevacizumab (BEV) improves overall survival (OS) compared to BEV alone in recurrent glioblastoma (GBM). Patients (pts) were randomized 1:1 to ReRT (35 Gy/10 fractions) plus BEV (IV 10 mg/kg q2 wks) vs. BEV alone. With 160 pts, there was 80% power to detect a 31% reduction in death hazard for BEV+RT at a one-sided significance level of 0.10 using a log rank test. OS and PFS were estimated by Kaplan-Meier and HRs estimated by exact binomial distribution. Objective response was assessed using MacDonald and RANO criteria. From 11/2012 to 4/2016, 182 pts were randomized, with 170 eligible, analyzable pts. 11 pts did not receive protocol treatment. Patient characteristics (age, KPS, re-resection rates) were balanced between arms. Median f/u for censored pts was 12.8 months (mos; min-max, 0.03–52.8). BEV+ReRT did not improve OS vs BEV alone, with median OS of 10.1 vs 9.7 mos, (HR=0.98, 95% CI=0.70–1.38, p=0.46). Median PFS for BEV+RT and BEV was 7.1 vs. 3.8 mos, respectively (HR=0.73, 95% CI=0.53–1.0, p=0.051). BEV+ReRT improved 6-mo PFS rate (PFS6): 54 vs. 29%, (HR=0.42, 95% CI=0.34–0.5, p=0.001). Overall, treatment was well tolerated: 5% acute and 0% delayed grade 3+ treatment-related AE. Most patients died from recurrent GBM. CONCLUSION: RTOG 1205 is the first, prospective, randomized multi-institutional study to evaluate the safety and efficacy of ReRT in recurrent GBM using modern RT techniques. Overall, ReRT was shown to be safe and well tolerated. BEV+ReRT did not demonstrate a benefit in OS but an improved PFS6, and clinically meaningful PFS improvement. Molecular correlates of response analyses are ongoing. Funded by U10CA180868, U10CA180822 from the National Cancer Institute.
Genomic Analysis of Therapy-Related Myeloid Neoplasms and Tracking of the Founder Clone By Circulating Tumor DNA
Authors: Kanya Kondoh, Kazuaki Yokoyama, Nozomi Yusa, Mika Ito, Eigo Shimizu, Sousuke Nakamura, Miho Ogawa, Tomomi Takei, Asako Kobayashi, Rika Kasajima, Yuka Wada, Rui Yamaguchi, Seiya Imoto, Tokiko Nagamura-Inoue, Kaoru Uchimaru, Satoru Miyano, Arinobu Tojo
Journal: Blood (2019)
Fifty sudden deaths may be related to central suppression
Authors: Rokuro Hama
Journal: BMJ (2007)

In his editorial on the association between oseltamivir phosphate (Tamiflu or oseltamivir-P) and neuropsychiatric disturbance in adolescents Maxwell says that the case is not proved but caution is advisable.1 On 16 June 2007 the Japanese Ministry of Health Labour and Welfare announced that by 31 May 2007 it had received 1377 reports of adverse reactions since 2001, when marketing of oseltamivir started in …
R-Loops-Induced ATR Signaling As a Potential Therapeutic Target in Myelodysplastic Syndrome
Authors: Johann-Christoph Jann, Johanna Flach, Antje Knaflic, Eva Altrock, Nanni Schmitt, Alexander Streuer, Justine Danner, Franziska Hofmann, Verena Nowak, Nina Draeger, Julia Obländer, Iris Palme, Patrick Wuchter, Ahmed Jawhar, Georgia Metzgeroth, Florian Nolte, Wolf-Karsten Hofmann, Daniel Nowak
Journal: Blood (2019)
Manufacture of an Allogeneic CAR-T Stem Cell Memory Product Candidate for Multiple Myeloma, P-Bcma-ALLO1, Is Robust, Reproducible and Highly Scalable
Authors: Stacey A Cranert, Maximilian Richter, Min Tong, Leslie Weiss, Yening Tan, Eric M. Ostertag, Julia Coronella, Devon J Shedlock
Journal: Blood (2019)
INNV-11. THE RISK OF HEMORRHAGE ASSOCIATED WITH THROMBOCYTOPENIA IN PATIENTS UNDERGOING OMMAYA RESERVOIR PLACEMENT FOR INTRATHECAL CHEMOTHERAPY: A SINGLE INSTITUTION RETROSPECTIVE ANALYSIS
Authors: Arpan Patel, Surabhi Amar, Salvatore Lettieri, Daniel Gridley, Bikash Bhattarai, Iman Feiz-Erfan
Journal: Neuro-Oncology (2019)

Abstract PURPOSE Ommaya reservoirs are frequently inserted in patients requiring regular delivery of intrathecal medications. The incidence of intracranial hemorrhage following insertion ranges from 1–3% and is typically associated with thrombocytopenia. However, the exact platelet count at which it is considered safe to insert an Ommaya reservoir has not been previously reported. The purpose of this study is to investigate the nature of the relationship between thrombocytopenia and post-operative hemorrhage following insertion of Ommaya reservoirs for intrathecal chemotherapy. METHODS Consecutive patients requiring insertion of an Ommaya reservoir were enrolled in the study with no minimum platelet count as an exclusion criterion. Patients data were retrospectively reviewed with thrombocytopenia defined as platelet count &lt; 100,000. All thrombocytopenic patients received at least one unit of intraoperative platelet transfusion. Post-operative incidence of hemorrhage, determined through CT scan, was compared between the thrombocytopenic group and normal platelet group. RESULTS 53 patients were enrolled within the study with 23 patients determined to be thrombocytopenic at the time of insertion. Thrombocytopenic patients were found to have 18.6 times the odds of post-operative bleeding when compared to patients with normal platelet counts (p&lt; 0.001). However, no patient in the thrombocytopenic group had a clinically significant bleed, defined as being symptomatic or requiring intervention. CONCLUSIONS Although thrombocytopenia increases the risk of post-operative hemorrhage associated with Ommaya reservoir placement, there is no increase in clinically significant bleeding. With concurrent platelet transfusion and use of neuronavigation, Ommaya reservoir may be safely placed in thrombocytopenic patients.
Clinical Activity of Melflufen in Patients with Triple-Class Refractory Multiple Myeloma and Poor-Risk Features in an Updated Analysis of HORIZON (OP-106), a Phase 2 Study in Patients with Relapsed/Refractory Multiple Myeloma Refractory to Pomalidomide and/or Daratumumab
Authors: María-Victoria Mateos, Albert Oriol, Alessandra Larocca, Paula Rodriguez Otero, Joan Bladé, Michele Cavo, Hani Hassoun, Xavier Leleu, Adrián Alegre Amor, Christopher Maisel, Agne Paner, Johan Harmenberg, Catriona Byrne, Sara Thuresson, Hanan Zubair, Paul G. Richardson
Journal: Blood (2019)
Genomic Profiling of Circulating Tumor DNA Reveals Patterns of Response and Refractoriness in Aggressive B-Cell Lymphoma - a Nordic Lymphoma Group Correlative Study
Authors: Leo Meriranta, Amjad Alkodsi, Annika Pasanen, Maija Lepistö, Yngvild Nuvin Blaker, Matias Autio, Judit Jørgensen, Mats Jerkeman, Harald Holte, Pekka Ellonen, Sirpa Leppa
Journal: Blood (2019)
MNGI-07. TRIMETHYLATED H3K27 AND EZH2 EXPRESSION IN MENINGIOMA: CORRELATION WITH TENDENCY TO RECUR
Authors: Chiara Calatozzolo, Monica Patanè, Mariangela Farinotti, Francesco DiMeco, Gaetano Finocchiaro, Bianca Pollo
Journal: Neuro-Oncology (2019)

Abstract Meningiomas are the most frequent primary CNS tumors, usually benign (WHO grade I), but in the 25–30% more aggressive tumors (grade II-III). Histopathological criteria (WHO 2016) are unsatisfactory to recognize meningiomas with tendency to recur. Recent studies have identified some mutations associated with histological features and location (i.e. BAP1 mutation in rhabdoid subtype), while risk stratification schemes based on DNA methylation subgroups have been proposed. Epigenetic modifications of histones play a pivotal role in tumorigenesis, the methylation of lysine 27 (K27) of histone H3 controlled by EZH2 subunit of PRC2 complex. BAP1 could be also involved in epigenetic regulation of PRC2 complex. The deregulation of H3K27 methylation has been found associated with recurrence risk in grade II meningiomas. Aim of the present study was to evaluate histone H3 methylation profile in a group of meningiomas of different grade with follow-up longer than 10 years, comparing non-recurrent to recurrent ones. We performed an immunohistochemical study on 145 meningiomas (50 grade I, 80 grade II and 15 grade III), investigating the expression of trimethylated H3K27 (H3K27me3), EZH2 and BAP1. The results were related to clinical data obtained from our Institutional Tumor Registry and evaluation of clinical reports. We observed a loss of H3K27me3 expression only in grade II and III meningiomas in 18% of cases, without correlation with tendency to recur. EZH2 showed increased percentage of positive nuclei related to the grade. In the group of grade I meningioma EZH2 expression was associated to recurrences. We didn’t observe loss of BAP1 expression. In conclusion, our data suggest that immunohistochemical evaluation of H3K27me3 and EZH2 could be a useful tool to better stratify meningioma with high risk of recurrence. Moreover, EZH2 could be of interest as therapeutic target. Molecular investigations in a larger cohort are needed to confirm these results.
Sickle-Cell Disease Patients' Attitudes Towards Their Treatment with Hydroxycarbamide
Authors: Frédéric Galactéros, Ersi Voskaridou, Anoosha Habibi, Giovanna Cannas, Laure Joseph, Stephanie Ngo, Nathalie Lemonne, Emmanuelle Bernit, Justine Gellen-Dautremer, Gylna Loko
Journal: Blood (2019)
BCL2 Expression Correlates with Refractory and Relapsed Classic Hodgkin Lymphoma. Its Blokeadge As a Promising Directed-Therapy
Authors: Angelica Gamboa-Cedeño, Cristaldo Nancy, Victoria Otero, Natalia Paola Schutz, Dorotea Fantl, Maria Silvana Cugliari, Marta Zerga, Rojas-Bilbao Erica, Hernán García Rivello, Federico Jauk, Myriam Nuñez, Stella Maris Ranuncolo
Journal: Blood (2019)
Bone Marrow Harvest Volume and CD34+ Cell Count in Pediatric Sibling Donors: A Single Centre Retrospective Analysis
Authors: Awatif Alanazi, Amir Nadeem, Khawar Siddiqui, Mouhab Ayas, Ali Abdallah Ahmari, Ibrahim A. Ghemlas, Abdullah Aljefri, Hawazen S. Alsaedi, Amal Al-Seraihy
Journal: Blood (2019)
Lactate Buildup at the Site of Chronic Inflammation Promotes Disease by Inducing CD4+ T Cell Metabolic Rewiring
Authors: Valentina Pucino, Michelangelo Certo, Vinay Bulusu, Danilo Cucchi, Katriona Goldmann, Elena Pontarini, Robert Haas, Joanne Smith, Sarah E. Headland, Kevin Blighe, Massimiliano Ruscica, Frances Humby, Myles J. Lewis, Jurre J. Kamphorst, Michele Bombardieri, Costantino Pitzalis, Claudio Mauro
Journal: Cell Metabolism (2019)

Accumulation of lactate in the tissue microenvironment is a feature of both inflammatory disease and cancer. Here, we assess the response of immune cells to lactate in the context of chronic inflammation. We report that lactate accumulation in the inflamed tissue contributes to the upregulation of the lactate transporter SLC5A12 by human CD4+ T cells. SLC5A12-mediated lactate uptake into CD4+ T cells induces a reshaping of their effector phenotype, resulting in increased IL17 production via nuclear PKM2/STAT3 and enhanced fatty acid synthesis. It also leads to CD4+ T cell retention in the inflamed tissue as a consequence of reduced glycolysis and enhanced fatty acid synthesis. Furthermore, antibody-mediated blockade of SLC5A12 ameliorates the disease severity in a murine model of arthritis. Finally, we propose that lactate/SLC5A12-induced metabolic reprogramming is a distinctive feature of lymphoid synovitis in rheumatoid arthritis patients and a potential therapeutic target in chronic inflammatory disorders.
PET/MRI enables simultaneous <i>in vivo</i> quantification of β-cell mass and function
Authors: Filippo C. Michelotti, Gregory Bowden, Astrid Küppers, Lieke Joosten, Jonas Maczewsky, Volker Nischwitz, Gisela Drews, Andreas Maurer, Martin Gotthardt, Andreas M. Schmid, Bernd J. Pichler
Journal: Theranostics (2019)

Non-invasive imaging of β-cells represents a desirable preclinical and clinical tool to monitor the change of β-cell mass and the loss of function during pre-diabetic stages. Although it is widely accepted that manganese (Mn) ions are actively gated by voltage-dependent calcium channels (VDCC) in response to glucose metabolism, little is known on its specificity in vivo for quantification of islet β-cell function using Mn and magnetic resonance imaging (MRI). On the other hand, glucagon-like-peptide-1 receptor (GLP-1R) represents a validated target for the estimation of β-cell mass using radiolabeled exendin-4 (Ex4) and positron emission tomography (PET). However, a multiparametric imaging workflow revealing β-cell mass and function quantitatively is still missing. Methods: We developed a simultaneous PET/MRI protocol to comprehensively quantify in vivo changes in β-cell mass and function by targeting, respectively, GLP-1R and VDCC coupled with insulin secretion. Differences in the spatial distribution of Mn and radiolabeled Ex4 were monitored overtime in native and transgenic pancreata, characterized by spontaneous pancreatic neuroendocrine tumor development. Follow-up with mass spectrometry imaging (MSI) and autoradiography allowed the ex vivo validation of the specificity of Mn and PET tracer uptake and the detection of endogenous biometals, such as calcium and zinc, throughout the endocrine and exocrine pancreas. Results: Our in vivo data based on a volumetric PET/MRI readout for native pancreata and insulinomas connects uptake of Mn measured at early imaging time points to high non-specific binding by the exocrine tissue, while specific retention was only found 24 h post injection. These results are supported by cross-validation of the spatial distribution of exogenous 55Mn and endogenous 44Ca and 64Zn as well with the specific internalization of the radiolabeled peptide targeting GLP-1R. Conclusion: Simultaneous PET/MR imaging of the pancreas enabled the comprehensive in vivo quantification of β-cell function and mass using Mn and radiolabeled Ex4. Most important, our data revealed that only late time-point measurements reflect the Mn uptake in the islet β-cells, while early time points detect non-specific accumulation of Mn in the exocrine pancreas.
Title: 12 Versus 8 Prophylactic Intrathecal (IT) Chemotherapy Administration Decrease Incidence of Central Nervous System (CNS) Relapse in Patients (pts) with Newly Diagnosed Philadelphia (Ph)-Positive Acute Lymphocytic Leukemia (ALL)
Authors: Shilpa Paul, Koji Sasaki, J Michael Savoy, Adam Dipippo, Nadya Jammal, Kayleigh Marx, Tapan M. Kadia, Guillermo Garcia-Manero, Farhad Ravandi, Hagop M. Kantarjian, Elias Jabbour
Journal: Blood (2019)
Narratives of Patients with Fatal Outcomes During the Phase 2 TITAN and Phase 3 HERCULES Studies
Authors: Spero Cataland, Marie Scully, Flora Peyvandi, Paul Knoebl, Johanna A. Kremer Hovinga, Paul Coppo, Ara Metjian, Javier De La Rubia, Katerina Pavenski, Hilde De Winter, Filip Callewaert
Journal: Blood (2019)
Dual Driver Mutant BCR-ABL1-Negative Myeloid Neoplasms: Multicenter Clinicopathologic and Genomic Analysis
Authors: Zachary D. Epstein-Peterson, Joseph Tripodi, Maria E Arcila, Filiz Sen, Vesna Najfeld, John Mascarenhas, Ronald Hoffman, Rajit K. Rampal
Journal: Blood (2019)
Comprehensive Profiling of Disease-Relevant Copy Number Aberrations Improves Risk Assessment and Unveils the Clonal Origin of Relapse in Pediatric Acute Lymphoblastic Leukemia
Authors: Donát Alpár, Richárd Kiss, Ambrus Gángó, Anne Benard-Slagter, Bálint Egyed, Irén Haltrich, Lajos Hegyi, Karel de Groot, Péter Attila Király, Szilvia Krizsán, Béla Kajtár, Henriett Pikó, László Pajor, Ágnes Vojcek, András Matolcsy, Gábor Kovács, Károly Szuhai, Suvi Savola, Csaba Bödör
Journal: Blood (2019)
Oxygen Poisoning in Man
Authors: J. B. S. Haldane
Journal: BMJ (1947)

Poliomyelitis SIR,-In your leading article on poliomyelitis (July 26, p. 135) you do not mention swimming and diving in sewage-polluted rivers as a cause of infection.'When will the people of this country understand that if they will turn sewage into our rivers and then bathe in thern they must expect trouble.Again and again we see cases of infantile paralysis appearing in farms and villages on the banks of polluted rivers.The virus is present in faeces and then passes through sewage into rivers.Young people bathe in sewage-polluted rivers, and we wonder why they get infantile paralysis.-Iam, etc., New Barnet, Hens.
Gene Expression and Cytokine Analyses Identify Markers of Progression from CLL-like Monoclonal B-Cell Lymphocytosis to Chronic Lymphocytic Leukemia
Authors: Gonzalo Blanco, Anna Puiggros, Barbara Sherry, Lara Nonell, Eulalia Puigdecanet, Pui Yan Chiu, Yasmine Kieso, Gerardo Ferrer, Magdalena Arnal, María Rodríguez-Rivera, Eva Gimeno, Eugenia Abella, Kanti R Rai, Pau Abrisqueta, Xavier Calvo, Francesc Bosch, Ana Ferrer, Nicholas Chiorazzi, Blanca Espinet
Journal: Blood (2019)
Delayed Neutrophil Engraftment in Patients Receiving Daratumumab As Part of Their First Induction Regimen for Multiple Myeloma
Authors: Abdullah S. Al Saleh, M Hasib Sidiqi, Morie A. Gertz, Eli Muchtar, Martha Q. Lacy, Rahma M Warsame, Wilson I Gonsalves, Taxiarchis Kourelis, William J Hogan, Suzanne R. Hayman, Prashant Kapoor, Francis K. Buadi, Angela Dispenzieri, David Dingli, Shaji K. Kumar
Journal: Blood (2019)
REPORTS OF SOCIETIES
Authors: R THOMAS, J H PEEL
Journal: BMJ (1947)

Spinal AnaesthesiaMr. RUFUS THOMAS said that the criteria in anaesthesia for' caesarean section must be primarily the safety of the mother and child and, subject to this, ease of operating for the-surgeon.Nearly all his caesarean sections for nine years had been done under spinal anaesthesia with " nupercaine."He admitted that spinal anaesthesia was not suitable for any and every woman.It was said that the pregnant woman at or near term was susceptible to the influence of cocaine products; " nupercaine," however, was a quinoline product not related to cocaine compounds.It was also said that collapse and death were liable to occur from a sudden drop in blood pressure.This might