tbuckley/cabot-search huggingface dataset:
Preliminary Results from a Phase II Study of the Combination of Pevonedistat and Azacitidine in the Treatment of MDS and MDS/MPN after Failure of DNA Methyltransferase Inhibition
Authors: Tamara K Moyo, Justin M. Watts, Barry S. Skikne, Jason H. Mendler, Virginia M. Klimek, Sheau-Chiann Chen, Run Fan, Ingrid A Anderson, Andrew Sochacki, Stephen A. Strickland, Michael T Byrne, Terrence J Bradley, Gregory D Ayers, Sanjay R Mohan, Michael R. Savona
Journal: Blood (2019)
Should Psychiatrists Tell?
Authors: G. Theophilus
Journal: BMJ (1964)

ICARK"a Court of Law and might even involve the psychiatrist who repeats them in a libel action.Freud himself had later to admit that the accusations his female patients made against their fathers which he at first believed were the product of their imagination and dis- torted memory.Every policeman knows how readily people under some emotional strain may accuse themselves of murder or serious crimes they have never committed.However, such subterfuges and treating the legal profession with their own medicine should not be necessary, nor need we wait, as Dr. Spencer suggests, till some psychiatrist is prepared to go to prison.I am sure, Sir, that the whole profession and the common man in the street would wholeheartedly stand behind the B.M.A. or any medical M.P. who would propose to bring the law for the physi- cian (and incidentally the priest) in line with the solicitor, whose communications with his client are legally recognized as privileged.-I am, etc., Leicester.
Phase I/II Study of Carfilzomib, Ruxolitinib and Low-Dose Dexamethasone for Carfilzomib-Refractory Multiple Myeloma (CarJak)
Authors: Shebli Atrash, Myra Robinson, Manisha Bhutani, Jeffrey A. Zonder, Reed Friend, Barry Paul, Daniel Auclair, Jordan Robinsons, Ami P Ndiaye, Kelly Bumgarner, Sarah Norek, James T. Symanowski, Peter M. Voorhees, Saad Z. Usmani
Journal: Blood (2019)
MALDI-TOF Mass Spectrometry in Serum for the Follow-up of Newly Diagnosed Multiple Myeloma Patients Treated with Daratumumab-Based Combination Therapy
Authors: Marion Eveillard, Malin Hultcrantz, Alexander M. Lesokhin, Sham Mailankody, Eric L Smith, Hani Hassoun, Urvi A Shah, Sydney X Lu, Neha Korde, Ola Landgren, Katie Thoren
Journal: Blood (2019)
Annals Story Slam - We're Human
Authors: Sheliza Halani
Journal: Annals of Internal Medicine (2019)

Web Exclusives5 November 2019Annals Story Slam - We're HumanFREESheliza Halani, MDSheliza Halani, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W19-0032 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - We're Human "We're Human," by Sheliza Halani (Duration 5:50)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 5 November 2019Volume 171, Issue 9Page: SS1 ePublished: 5 November 2019 Issue Published: 5 November 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.Loading ...
Heterogeneous Genetic Alterations and Novel Pathogenic Pathways in Relapsed DLBCL Revealed By Whole Exome Sequencing
Authors: Jiao Ma, Kui Nie, Giorgio Inghirami, Kenneth Eng, Olivier Elemento, Rex Au-Yeung, Yajie Shen, Gopesh Srivastava, Jerald Gong, Mina L Xu, Leonard H.C. Tan, Wayne Tam
Journal: Blood (2019)
NCOG-09. TREATMENT DECISION MAKING IN THE SETTING OF ADVANCED CANCER
Authors: Kristen Triebel, Kyler Maulhauser, John Fiveash, Dario Marrotta, Meredith Gammon, David Vance, Louis Nabors
Journal: Neuro-Oncology (2019)

Abstract OBJECTIVE To investigate medical decision-making capacity (MDC) in patients with advanced stage cancer. METHODS Participants were 113 newly diagnosed adults with brain metastases and 41 adults with metastatic cancer without brain metastases who were recruited from an academic medical center and 40 demographically-matched healthy controls recruited from the community. We evaluated MDC using the Capacity to Consent to Treatment Instrument (CCTI) Vignette B and its four clinically relevant consent standards (expressing a treatment choice, appreciation, reasoning, and understanding). Capacity impairment ratings (no impairment, mild/moderate impairment, and severe impairment) on the consent standards were also assigned to each participant using cutoff scores derived statistically from the performance of the control group. RESULTS Both of the metastatic cancer groups (with and without brain metastasis) performed significantly below controls on consent standards of understanding and reasoning. The brain metastasis group performed below the non-metastatic cancer group on understanding. Capacity compromise was defined as performance ≤1.5 standard deviations (SD) below the control group mean. Using this definition, approximately 65% of the participants with brain metastases and 51% of participants with metastatic cancer without brain metastases were impaired on at least one MDC standard. CONCLUSION Over half of participants with metastatic cancer regardless of whether they have brain disease have reduced capacity to make treatment decisions. The finding of impaired MDC in patients without brain metastases is surprising and suggests this group likely exhibits cognitive deficits that impact their ability to understand and reason about different treatment options. This finding suggests that clinicians need to carefully consider the patient’s ability to engage in treatment decision making when they are discussing treatment options for metastatic cancer. These results also indicate a need for the development and investigation of interventions to support MDC in this patient population.
Is Heparin Induced Thrombocytopenia Expert Probability (HEP) Scoring System Superior to 4T'S Scoring in the Diagnosis of Heparin Induced Thrombocytopenia? a Prospective Observational Study from a Tertiary Care Cardiac Centre in India
Authors: Amarnadh Polisetty, Nataraj KS, Hamza Yusuf Dalal, Shilpa Prabhu, Devi Prasad Shetty, Sharat Damodar
Journal: Blood (2019)
GENE-51. ROLE OF TUMOR ENDOTHELIAL MARKER 8 (TEM8) IN PRIMARY AND RECURRENT GLIOBLASTOMA.
Authors: Paramita Kundu, Ruchi Jain, Arivazhagan Arimappamagan, Vani Santosh, Paturu Kondaiah
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma (GBM) is the most common primary malignant tumor of the adult central nervous system. It is highly invasive and almost inevitably recurs; leading to a median survival of 15 months. The recurrent tumor in most cases is radiotherapy and chemotherapy-resistant, making them quite challenging to treat. Several studies have elucidated key driver genes and molecular pathways involved in Gliomagenesis, but genes/pathways that might be involved in aiding relapse are not well elucidated. Interestingly, chemotherapy with Temozolomide and γ-irradiation have been documented to alter the DNA methylome of cells in vitro. A probable hypothesis could be that following surgical resection, therapy alters the epigenome of residual cancer cells giving rise to aggressively resistant recurrent tumors. To examine this possibility, 24 GBM biopsies (11 primary and 13 recurrent GBMs) were subjected to Methylation Bead Array to assess differential methylation of genes in recurrent GBM compared to primary tumors. This was correlated with RNA-seq data for recurrent tumors in TCGA database. A total of 1751 differentially methylated regions (DMRs) were identified, among which 205 differentially methylated genes (74 hypomethylated and 131 hypermethylated) were found to correlate with methylation and RNA-sequencing data of recurrent tumors in TCGA. Among these genes, ANTXR1/TEM8 (Tumor Endothelial Marker 8) was found to be overexpressed in recurrent tumors compared to primary tumors at both transcript and protein levels using RT-PCR and immunohistochemistry, respectively. When overexpressed in Glioma cell lines, TEM8 was found to upregulate phospho-GSK3β, phospho-AKT and lead to β-catenin translocation to the nucleus resulting in activation of Wnt signaling pathway. TEM8 overexpressing cells showed mild enhancement in proliferation and resistance to Temozolomide, Cisplatin and 5-fluoroUracil. Stem cells markers like Oct4 and Nanog are also upregulated. In conclusion, TEM8 may be involved in GBM recurrence and may have a role in conferring chemo- and radioresistance.
EXTH-17. TREATMENT OF MALIGNANT GLIOMAS WITH DRUG-LOADED MICROBUBBLES: CONCEPTION OF A PROMISING FUTURE THERAPEUTIC STRATEGY
Authors: Ellina Schulz, Viviane Mawamba, Volker Sturm, Ralf-Ingo Ernestus, Ulrich Schatzschneider, Mario Löhr, Carsten Hagemann
Journal: Neuro-Oncology (2019)

Abstract The major obstacles for an effective chemotherapy of glioblastomas (GBM) are the blood-brain barrier (BBB) and serious systemic side effects of the cytotoxic drugs. A new promising strategy could be the delivery of the chemotherapeutics across the BBB to the tumor site encapsulated in microbubbles. The microbubbles will shield the drug from detrimental systemic effects. Low intensity focused ultrasound (LIFU) allows opening of the BBB and a targeted release of the drugs within the brain tumor. We synthesized microbubbles ≤ 2 µm in diameter by thin-film hydration of lipids, which could be disintegrated applying LIFU. The toxicity was tested on GBM cell lines and neither the intact bubbles nor the lipids alone showed any toxic effects. Additionally, these cells were treated with 6 platinum(II) and palladium(II) complexes conjugated to lipophilic side chains of different length (C1, C8, C10) for 72 h. Cell viability was evaluated with MTT assay and in real-time utilizing the impedance-based xCELLigence DP-System. EC50 values were calculated from both assays and all six drugs were highly effective. Especially the palladium(II) compound with the C1-chain had a very low EC50 value (&lt; 10 µM), while the longer chains and the platinum(II) compounds were less effective (EC50 10 - 30 µM). The real time proliferation assay of the drugs revealed an early and concentration-dependent onset of the cytotoxic effect, about 30 h after application. The lipophilic side chains of the drugs should allow encapsulating them into the microbubbles to develop an effective drug-delivery system for the treatment of GBM.
How Did I Get Here? Career Choice in Medicine
Authors: Charlie Goldberg
Journal: Annals of Internal Medicine (2019)

On Being a Doctor5 November 2019How Did I Get Here? Career Choice in MedicineCharlie Goldberg, MDCharlie Goldberg, MDUniversity of California, San Diego, School of Medicine, La Jolla, California (C.G.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M19-0030 Audio Reading - “How Did I Get Here? Career Choice in Medicine” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “How Did I Get Here? Career Choice in Medicine” by Charlie Goldberg, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail By January of my second year of residency, I was miserable. It was 1993, and I was a urology resident finishing my second year of general surgery before starting 4 years focused on GU. The hours were long, the work was intense, and I didn't have a moment to consider why I was so unhappy. I ultimately came to realize that I didn't love standing on the right-hand side of the operating table. Being the one performing the procedure (removing diseased tissue, draining infections, restoring blood flow) didn't make me feel particularly satisfied. When surgical friends spoke about the thrill ... Author, Article, and Disclosure InformationAffiliations: University of California, San Diego, School of Medicine, La Jolla, California (C.G.)Corresponding Author: Charlie Goldberg, MD, University of California, San Diego, School of Medicine, 9500 Gilman Drive, No. 0606, La Jolla, CA 92093-0606; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement Audio Reading - “How Did I Get Here? Career Choice in Medicine” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “How Did I Get Here? Career Choice in Medicine” by Charlie Goldberg, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 5 November 2019Volume 171, Issue 9Page: 673-674KeywordsBlood flowFellowshipsInfectious diseasesPatientsResidencySurgeryUrology ePublished: 5 November 2019 Issue Published: 5 November 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Spontaneous Rupture of the Spleen
Authors: A. R. Anscombe, D. J. Crowther
Journal: BMJ (1955)

<b>SUMMARY:</b> Pleomorphic adenomas (PAs), also known as benign mixed tumors, are common tumors of the parotid gland. These tumors occasionally undergo malignant transformation, with potentially devastating consequences. This case report presents the clinical and radiographic features of a rare case of biopsy proved brain and spinal cord metastases arising from carcinoma ex PA of the parotid gland.
EBV microRNA-BHRF1-2-5p targets the 3′UTR of immune checkpoint ligands PD-L1 and PD-L2
Authors: Alexandre S. Cristino, Jamie Nourse, Rachael A. West, Muhammed Bilal Sabdia, Soi C. Law, Jay Gunawardana, Frank Vari, Sally Mujaj, Gayathri Thillaiyampalam, Cameron Snell, Madeline Gough, Colm Keane, Maher K. Gandhi
Journal: Blood (2019)
Development and Validation of a Cancer-Associated Venous Thromboembolism Clinical Risk Prediction (CAT-CR) Model in Newly Diagnosed Cancer Patients Treated with Cheomotherapy
Authors: Piyanuch Kongtim, Kotchanut Litlueangdet, Darunee Emrat, Dhosaporn Charoenjit, Supawee Saengboon, Wasithep Limvorapitak, Nonglak Kanitsap, Hataiwan Ratanabunjerdkul
Journal: Blood (2019)
P53 Pathway Activation Mediated High c-MAF Expression Is Associated with Overall and Post-Progression Survival in Multiple Myeloma
Authors: Eiko Yamane, Tsukasa Oda, Masanobu Sunaga, Yuki Murakami, Rei Ishihara, Yuta Asao, Yuta Masuda, Saki Watanabe, Nobuhiko Kobayashi, Hisashi Takei, Yohei Osaki, Gotoh Nanami, Tetsuhiro Kasamatsu, Hiroaki Shimizu, Takuma Ishizaki, Hiromi Koiso, Makiko Takizawa, Yoshiyuki Ogawa, Akihiko Yokohama, Norifumi Tsukamoto, Takayuki Saitoh, Hirokazu Murakami, Hiroshi Handa
Journal: Blood (2019)
Circulating Tumor DNA in the Peripheral Blood As Early Predictor of Clinical Outcome in Relapsed/ Refractory Multiple Myeloma
Authors: Johannes M. Waldschmidt, Andrew J. Yee, Tushara Vijaykumar, Julia Frede, Praveen Anand, Sayalee Potdar, Monica S. Nair, Antonis Kokkalis, Jake A. Kloeber, Guangwu Guo, Samantha J. Shapiro, Mason L. Mann, Robb S Friedman, Brea C. Lipe, Erica L. Campagnaro, Elizabeth K. O'Donnell, Thomas Guerrero, Jacob P. Laubach, Nikhil C. Munshi, Paul G. Richardson, Kenneth C. Anderson, Noopur S. Raje, Birgit Knoechel, Jens G. Lohr
Journal: Blood (2019)
Blinatumomab in Pediatric Patients with Relapsed/Refractory B-Cell Precursor and Molecularly Resistant Acute Lymphoblastic Leukemia (R/R ALL): Updated Analysis of 110 Patients Treated in an Expanded Access Study (RIALTO)
Authors: Franco Locatelli, Gerhard Zugmaier, Peter Bader, Sima Jeha, Paul-Gerhardt Schlegel, Jean-Pierre Bourquin, Rupert Handgretinger, Benoit Brethon, Claudia Rossig, Christiane Chen-Santel
Journal: Blood (2019)
Reactive Nitrogen Species Induced by Hyperglycemia Suppresses Akt Signaling and Triggers Apoptosis by Upregulating Phosphatase PTEN (Phosphatase and Tensin Homologue Deleted on Chromosome 10) in an LKB1-Dependent Manner
Authors: PingSong, YongWu, JianXu, ZhonglinXie, YunzhouDong, MiaoZhang, Ming-HuiZou
Journal: Circulation (2007)

Background— Oxidative stress plays a causal role in vascular injury in diabetes mellitus, but the mechanisms and targets remain poorly understood. Methods and Results— Exposure of cultured human umbilical vein endothelial cells to either peroxynitrite (ONOO−) or high glucose significantly inhibited both basal and insulin-stimulated Akt phosphorylation at Ser473 and Akt activity in parallel with increased apoptosis, phosphorylation, and activity of phosphatase and tensin homologue deleted on chromosome 10 (PTEN). Furthermore, protein kinase B/Akt inhibition induced by ONOO− or high glucose and apoptosis triggered by high glucose could be abolished by transfection of PTEN-specific small interfering RNA, suggesting that PTEN mediated the Akt inhibition by ONOO−. In addition, exposure of human umbilical vein endothelial cells to ONOO− or high glucose remarkably increased Ser428 phosphorylation of LKB1, a tumor suppressor. Interestingly, the ONOO−-enhanced PTEN phosphorylation and Akt inhibition can be blocked...
Impact of Lab Abnormalities at the Time of Progression in Patients Receiving CD19-Specific CAR T-Cell Therapy for Relapsed/Refractory Large B-Cell Lymphomas
Authors: Ryan C. Lynch, Victor A. Chow, David G. Maloney, Cameron J. Turtle, Stephen D. Smith, Mazyar Shadman, Chaitra S. Ujjani, Ryan D. Cassaday, Brian G. Till, Yolanda D. Tseng, Edus H. Warren, Andrei R Shustov, Manoj P. Menon, Jenna M. Voutsinas, Ted Gooley, Ajay K. Gopal
Journal: Blood (2019)
Bispecific T-Cell Engager (BiTE) Antibody Based Immunotherapy for Treatment of Relapsed Refractory Multiple Myeloma (RRMM): A Systematic Review of Preclinical and Clinical Trials
Authors: Zunairah Shah, Mustafa Nadeem Malik, Syeda Sabeeka Batool, Sravanthi Kotapati, Aisha Akhtar, Owais ur Rehman, Marium Ghani, Maryam Sadiq, Arshia Akbar, Aqsa Ashraf, Arafat Ali Ali Farooqui, Muhammad Abdullah Yousaf, Muhaddis Ejaz Ahmad, Hafiz Muhammad Fazeel, Faiz Anwer
Journal: Blood (2019)
Quadriceps tendon grafts does not cause patients to have inferior subjective outcome after anterior cruciate ligament (ACL) reconstruction than do hamstring grafts: a 2-year prospective randomised controlled trial
Authors: Martin Lind, Torsten Grønbech Nielsen, Ole Gade Soerensen, Bjarne Mygind-Klavsen, Peter Faunø
Journal: British Journal of Sports Medicine (2019)

Objective We performed a randomised controlled trial (RCT) in patients undergoing ACL reconstruction (ACLR) using either quadriceps tendon graft (QT) or semitendinosus/gracilis hamstring (STG) graft. We compared subjective outcome (primary outcome) and knee stability, donor site morbidity and function (secondary outcomes). Methods From 2013 to 2015, we included 99 adults with isolated ACL injuries in the RCT. Fifty patients were randomised to QT grafts and 49 to STG grafts and followed for 2 years. Patient evaluated outcomes were performed by subjective International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome Score, Kujala and Tegner activity scores. Knee laxity was measured with a KT-1000 arthrometer. Donor site morbidity was evaluated by the ‘donor site-related functional problems following ACLR score’. One-leg hop test tested limp strength symmetry. Results At 2-year follow-up, there was no difference between the two graft groups regarding subjective patient outcome, knee stability and reoperations. Also, at 2 years, donor site symptoms were present in 27% of patients in the QT group and 50% of patients in the STG group. The donor site morbidity score was 14 and 22 for the QT and STG, respectively. Hop test demonstrated lower limp symmetry for QT graft than STG graft of 91% and 97% respectively. Conclusion QT graft for ACLR did not result in inferior subjective outcome compared with STG graft. However, QT graft was associated with lower donor site morbidity than STG grafts but resulted in more quadriceps muscle strength deficiency than hamstring grafts. Both graft types had similar knee stability outcome. Trial registration number NCT02173483 .
Ethics of Human Experimentation
Authors: B M BENNETT, E NAKAMURA
Journal: BMJ (1964)

statement on investigations on human subjects (p.178).Leader on this page.Royal College of Psychiatrists: Leader at p. 137.Haemolytic Disease of Newborn: Dr. W. Walker and colleagues assess prognostic signifi- cance of bilirubin, protein, and haemoglobin in amniotic fluid." Examination of liquor . . . is of great practical value " (p
Phase 3 Efficacy Trial of Modified Vaccinia Ankara as a Vaccine against Smallpox
Authors: Phillip R. Pittman, Matthew Hahn, HeeChoon S. Lee, Craig Koca, Nathaly Samy, Darja Schmidt, Joachim Hornung, Heinz Weidenthaler, Christopher R. Heery, Thomas P.H. Meyer, Günter Silbernagl, Jane Maclennan, Paul Chaplin
Journal: New England Journal of Medicine (2019)

Many countries have stockpiled vaccines because of concerns about the reemergence of smallpox. Traditional smallpox vaccines are based on replicating vaccinia viruses; these vaccines have considerable side effects.To evaluate the efficacy of modified vaccinia Ankara (MVA) as a potential smallpox vaccine, we randomly assigned 440 participants to receive two doses of MVA followed by one dose of the established replicating-vaccinia vaccine ACAM2000 (the MVA group) or to receive one dose of ACAM2000 (the ACAM2000-only group). The two primary end points were noninferiority of the MVA vaccine to ACAM2000 with respect to the peak serum neutralizing antibody titers and attenuation of the ACAM2000-associated major cutaneous reaction by previous MVA vaccination, measured according to the maximum lesion area and the derived area attenuation ratio.A total of 220 and 213 participants were randomly assigned and vaccinated in the MVA group and ACAM2000-only group, respectively, and 208 participants received two MVA vaccinations. At peak visits, MVA vaccination induced a geometric mean titer of neutralizing antibodies of 153.5 at week 6, as compared with 79.3 at week 4 with ACAM2000 (a ratio of 1.94 [95% confidence interval {CI}, 1.56 to 2.40]). At day 14, the geometric mean titer of neutralizing antibodies induced by a single MVA vaccination (16.2) was equal to that induced by ACAM2000 (16.2), and the percentages of participants with seroconversion were similar (90.8% and 91.8%, respectively). The median lesion areas of the major cutaneous reaction were 0 mm2 in the MVA group and 76.0 mm2 in the ACAM2000-only group, resulting in an area attenuation ratio of 97.9% (95% CI, 96.6 to 98.3). There were fewer adverse events or adverse events of grade 3 or higher after both MVA vaccination periods in the MVA group than in the ACAM2000-only group (17 vs. 64 participants with adverse events of grade 3 or higher, P<0.001).No safety concerns associated with the MVA vaccine were identified. Immune responses and attenuation of the major cutaneous reaction suggest that this MVA vaccine protected against variola infection. (Funded by the Office of the Assistant Secretary for Preparedness and Response Biomedical Advanced Research and Development Authority of the Department of Health and Human Services and Bavarian Nordic; ClinicalTrials.gov number, NCT01913353.).