tbuckley/cabot-search huggingface dataset:
Randomized control trial of oral arginine therapy for children with sickle cell anemia hospitalized for pain in <scp>Nigeria</scp>
Authors: Richard Onalo, Peter Cooper, Antoinette Cilliers, Barend C. Vorster, Nnebe‐Agumadu Uche, Oniyangi O. Oluseyi, Victoria D. Onalo, Yunusa Zubairu, Alice U. Ayodele‐Kehinde, Oladimeji M. Damilare, Janet Figueroa, Claudia R. Morris
Journal: American Journal of Hematology (2020)

Low arginine bioavailability is associated with vaso-occlusive painful crisis (VOC) severity in sickle cell anemia (SCA) and predicts need for pediatric hospitalization. Intravenous arginine therapy has opioid-sparing effects and was found to significantly decrease pain scores in children hospitalized with SCA-VOC in a phase-two randomized placebo-controlled trial (RCT). Efficacy of oral arginine is unknown. Our objective was to determine the safety and efficacy of oral arginine therapy in Nigerian children with SCA. A double-blind RCT of oral L-arginine-hydrochloride (100 mg/kg TID) was conducted in children with SCA-VOC, aged 5-17 years, hospitalized at two Nigerian sites. The primary outcome measure was analgesic usage, quantified by difference in the mean Analgesic Medication Quantification Scale (MQS). Secondary outcomes included daily pain scores, time-to-crisis-resolution and length-of-hospital-stay. An intention-to-treat analysis was performed. Sixty-eight children (age 5-17 years, mean 10.6 ± 0.4 years; 56% male), were randomized to receive L-arginine (35 patients) or placebo (33 patients). The mean total MQS for the arginine group was 73.4 (95% CI, 62.4-84.3) vs 120.0 (96.7-143.3) for placebo (P < .001). The mean rate of decline in worst pain scores was faster in the arginine arm vs placebo (1.50 [1.23-1.77] vs 1.09 [0.94-1.24] point/d, P = .009). Children receiving arginine had a shorter time-to-crisis-resolution (P = .02), shorter hospital-stay (P = .002) and experienced no serious adverse event. Pain control was more rapid, total analgesic requirement was significantly reduced, and most notably, time-to-crisis-resolution and length-of-hospital-stay were shorter in children with SCA-VOC receiving arginine vs placebo. Given the established safety and low cost, oral arginine is a promising adjuvant therapy for SCA-VOC management.
Carotid Disease and Retinal Optical Coherence Tomography Angiography Parameters in Type 2 Diabetes: The Fremantle Diabetes Study Phase II
Authors: Jocelyn J. Drinkwater, Fred K. Chen, Alison M. Brooks, Brad T. Davis, Angus W. Turner, Timothy M.E. Davis, Wendy A. Davis
Journal: Diabetes Care (2020)

OBJECTIVE To use optical coherence tomography angiography (OCTA) to determine whether retinal microvascular parameters are associated with carotid arterial disease in people with type 2 diabetes. RESEARCH DESIGN AND METHODS Participants (community-based) underwent detailed assessments including carotid ultrasonography and OCTA. Ultrasound images were assessed for mean intima-media thickness (IMT) and the presence of stenosis. OCTA image analysis provided measures of vessel density, foveal avascular zone (FAZ) area, blood flow areas, and retinal thickness. For each OCTA variable, the most parsimonious model was generated using generalized estimating equations, then ipsilateral and contralateral carotid disease–related variables were added to determine their significance. RESULTS A total of 474 eyes from 261 participants (mean ± SD age 72.0 ± 9.3 years, 57.1% males, median diabetes duration 15.4 years [interquartile range 11.1–22.4]) were analyzed. When carotid variables were added to the most parsimonious models, the ipsilateral natural logarithm of common carotid artery IMT (coefficient −2.56 [95% CI −4.76, −0.35], P = 0.023) and presence of any ipsilateral stenosis (−0.82 [−1.48, −0.17], P = 0.014) were statistically significantly associated with a lower parafoveal density in the deep capillary plexus. A mean bifurcation IMT ≥1 mm was associated with a decreased vessel density in the 300-μm ring surrounding the FAZ (coefficient −0.79 [−1.50, −0.08], P = 0.030)). Contralateral carotid disease–related variables were also significantly associated with retinal microvascular parameters. CONCLUSIONS This is the first study to show that carotid disease is an independent associate of retinal microvascular disease assessed by OCTA in type 2 diabetes. Appropriately intensive management of carotid disease may improve the retinal microcirculation.
Obstructive sleep apnoea: latest surgical advances and considerations during the COVID-19 pandemic
Authors: Lucy Williamson
Journal: The Lancet Respiratory Medicine (2020)

Multilevel upper airway surgery could be more effective in reducing the frequency of sleep apnoeas and daytime sleepiness in patients with moderate or severe obstructive sleep apnoea (OSA) compared with medical management (eg, weight loss) according to a study by Stuart MacKay and colleagues. The multicentre, randomised controlled trial is the first of its kind to assess multilevel airway surgery in this patient population. The study provides "arguably the highest quality evidence for surgical therapy of OSA", according to Professor Atul Malhotra from The University of California San Diego (CA, USA).
Letter by Alfonso et al Regarding Article, “Low-Attenuation Noncalcified Plaque on Coronary Computed Tomography Angiography Predicts Myocardial Infarction: Results From the Multicenter SCOT-HEART Trial (Scottish Computed Tomography of the Heart)”
Authors: Fernando Alfonso, Alberto Cecconi, Jesús Jiménez-Borreguero
Journal: Circulation (2020)
Redefining prognostication of de novo cytogenetically normal acute myeloid leukemia in young adults
Authors: Sze P. Tsui, Ho W. Ip, Nicole Y. Saw, Chunxiao Zhang, Arthur K. Cheung, Nelson K. Ng, Cheuk H. Man, Stephen S. Lam, Wing F. Tang, Chi H. Lin, Grace H. Cheng, Chun H. Au, Edmond S. Ma, Tsun L. Chan, Jason C. So, Margaret H. Ng, Kelvin C. Cheng, Kit F. Wong, Lai P. Siu, Sze F. Yip, Shek Y. Lin, June S. Lau, Tsan H. Luk, Harold K. Lee, Chi K. Lau, Bonnie Kho, Joycelyn P. Sim, Yok L. Kwong, Suet Y. Leung, Asif Javed, Anskar Y. Leung
Journal: Blood Cancer Journal (2020)
Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus
Authors: Sheng Chih Jin, Weilai Dong, Adam J. Kundishora, Shreyas Panchagnula, Andres Moreno-De-Luca, Charuta G. Furey, August A. Allocco, Rebecca L. Walker, Carol Nelson-Williams, Hannah Smith, Ashley Dunbar, Sierra Conine, Qiongshi Lu, Xue Zeng, Michael C. Sierant, James R. Knight, William Sullivan, Phan Q. Duy, Tyrone DeSpenza, Benjamin C. Reeves, Jason K. Karimy, Arnaud Marlier, Christopher Castaldi, Irina R. Tikhonova, Boyang Li, Helena Perez Peña, James R. Broach, Edith M. Kabachelor, Peter Ssenyonga, Christine Hehnly, Li Ge, Boris Keren, Andrew T. Timberlake, June Goto, Francesco T. Mangano, James M. Johnston, William E. Butler, Benjamin C. Warf, Edward R. Smith, Steven J. Schiff, David D. Limbrick, Gregory Heuer, Eric M. Jackson, Bermans J. Iskandar, Shrikant Mane, Shozeb Haider, Bulent Guclu, Yasar Bayri, Yener Sahin, Charles C. Duncan, Michael L. J. Apuzzo, Michael L. DiLuna, Ellen J. Hoffman, Nenad Sestan, Laura R. Ment, Seth L. Alper, Kaya Bilguvar, Daniel H. Geschwind, Murat Günel, Richard P. Lifton, Kristopher T. Kahle
Journal: Nature Medicine (2020)
Doxycycline and Growth of Abdominal Aortic Aneurysms
Authors: Antonio V. Sterpetti
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Aggressive PDACs Show Hypomethylation of Repetitive Elements and the Execution of an Intrinsic IFN Program Linked to a Ductal Cell of Origin
Authors: Elisa Espinet, Zuguang Gu, Charles D. Imbusch, Nathalia A. Giese, Magdalena Büscher, Mariam Safavi, Silke Weisenburger, Corinna Klein, Vanessa Vogel, Mattia Falcone, Jacob Insua-Rodríguez, Manuel Reitberger, Vera Thiel, Steffi O. Kossi, Alexander Muckenhuber, Karnjit Sarai, Alex Y.L. Lee, Elyne Backx, Soheila Zarei, Matthias M. Gaida, Manuel Rodríguez-Paredes, Elisa Donato, Hsi-Yu Yen, Roland Eils, Matthias Schlesner, Nicole Pfarr, Thilo Hackert, Christoph Plass, Benedikt Brors, Katja Steiger, Dieter Weichenhan, H. Efsun Arda, Ilse Rooman, Janel L. Kopp, Oliver Strobel, Wilko Weichert, Martin R. Sprick, Andreas Trumpp
Journal: Cancer Discovery (2020)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive desmoplasia, which challenges the molecular analyses of bulk tumor samples. Here we FACS-purified epithelial cells from human PDAC and normal pancreas and derived their genome-wide transcriptome and DNA methylome landscapes. Clustering based on DNA methylation revealed two distinct PDAC groups displaying different methylation patterns at regions encoding repeat elements. Methylationlow tumors are characterized by higher expression of endogenous retroviral transcripts and double-stranded RNA sensors, which lead to a cell-intrinsic activation of an interferon signature (IFNsign). This results in a protumorigenic microenvironment and poor patient outcome. Methylationlow/IFNsignhigh and Methylationhigh/IFNsignlow PDAC cells preserve lineage traits, respective of normal ductal or acinar pancreatic cells. Moreover, ductal-derived KrasG12D/Trp53−/− mouse PDACs show higher expression of IFNsign compared with acinar-derived counterparts. Collectively, our data point to two different origins and etiologies of human PDACs, with the aggressive Methylationlow/IFNsignhigh subtype potentially targetable by agents blocking intrinsic IFN signaling. Significance: The mutational landscapes of PDAC alone cannot explain the observed interpatient heterogeneity. We identified two PDAC subtypes characterized by differential DNA methylation, preserving traits from normal ductal/acinar cells associated with IFN signaling. Our work suggests that epigenetic traits and the cell of origin contribute to PDAC heterogeneity. This article is highlighted in the In This Issue feature, p. 521
24P Is molecular characterization useful for targeted therapy orientation in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) included in early phase clinical trials?
Authors: J-M. Michot, V. Camara-Clayette, C. Quivoron, A. Danu, J. Lazarovici, D. Ghez, J. Rossignol, C. Baldini, P. Martin Romano, C. Sarkozy, A. Varga, S. Cotteret, P. Dartigues, C. Massard, V. Ribrag
Journal: Annals of Oncology (2020)
Dynamic Positron Emission Tomography/Computed Tomography Imaging Correlate of Nonalcoholic Steatohepatitis
Authors: Souvik Sarkar, Karen E. Matsukuma, Benjamin Spencer, Shuai Chen, Kristin A. Olson, Ramsey D. Badawi, Michael T. Corwin, Guobao Wang
Journal: Clinical Gastroenterology and Hepatology (2020)
Brain metastasis detection using machine learning: a systematic review and meta-analysis
Authors: Se Jin Cho, Leonard Sunwoo, Sung Hyun Baik, Yun Jung Bae, Byung Se Choi, Jae Hyoung Kim
Journal: Neuro-Oncology (2020)

Accurate detection of brain metastasis (BM) is important for cancer patients. We aimed to systematically review the performance and quality of machine-learning-based BM detection on MRI in the relevant literature.
Migraine: NICE recommends further prevention option
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Galcanezumab, a new migraine drug, has been recommended by the National Institute for Health and Care Excellence as part of draft guidance.1

Published on 15 October, the guidance said that galcanezumab (marketed by Eli Lilly as Emgality) can be used to prevent migraine in adults who have at least four days with migraine each month and in whom at least three previous preventive treatments …
Covid-19 and net zero for health
Authors: Fiona Godlee
Journal: BMJ (2020)

Nine months ago the world stopped for covid-19. Amid the loss of life, health, and livelihoods there were welcome blue skies and birdsong. People did less flying and driving, more Zooming, walking, and cycling. Consultations between patients and healthcare staff moved online as telemedicine became routine.1 But for the past few months countries have been stumbling back to a semblance of normality, which means that air pollution and traffic noise are back. Rates of new coronavirus infection and long covid are rising alarmingly,2 along with anger about misuse and denial of science and continued government failings,3 and amid increasingly heated debate …
Paediatric Inflammatory Multisystem Syndrome Temporally-Associated with SARS-CoV-2 Infection: An Overview
Authors: Michael J. Carter, Manu Shankar-Hari, Shane M. Tibby
Journal: Intensive Care Medicine (2020)

In spring 2020 paediatricians working across Europe and the USA [1] alerted colleagues to clusters of previously healthy children presenting with unremitting fever, multisystem inflammation and pancarditis.This syndrome, initially termed Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 infection (PIMS-TS), or by its US variation Multisystem Inflammatory Syndrome in Children (MIS-C; Table 1), appears to be a rare complication of (largely) asymptomatic SARS-CoV-2 infection in children [8].However, the overlap with other paediatric inflammatory syndromes such as Kawasaki disease (KD) and optimum treatments remain unknown.We provide a narrative overview of PIMS-TS and highlight important knowledge gaps.
47P Improved treatment outcomes by using patient-specific drug combinations in mTOR activated advanced metastatic cancers
Authors: D. Akolkar, D. Patil, N. Srivastava, V. Datta, S. Schuster, C. Bose, J. Bhatia, A. Ghaisas, C. Sims, R. Patil, S. Patil, S. Apurwa, V. Mhase, S. Pawar, P. Devhare, J. John, R. Gosavi, A. Srinivasan, R. Datar
Journal: Annals of Oncology (2020)
Erratum: Estimation of the total parasite biomass in acute falciparum malaria from plasma PfHRP2 (PLoS Medicine (2005) 2:8 DOI: 10.1371/journal.pmed. 0020204)
Authors: A M Dondorp, V Desakorn, W Pongtavornpinyo, D Sahassananda, K Silamut, K Chotivanich, P N Newton, P Pitisuttithum, A M Smithyman, N J White, Day Npj.
Journal: PLoS Medicine (2005)
Modification of a domiciliary ventilator to increase FiO<sub>2</sub>: an off-label modification which may be of value in COVID-19
Authors: Yoseph Mebrate, Steven Phillips, Debbie Field, Ivy Mumuni, Paul Josse, David Alexander, Rishi Das-Gupta, Richard Trimlett, Michael I Polkey
Journal: Thorax (2020)

Although nasal continuous positive airway pressure or non-invasive ventilation is used to manage some patients with acute lung injury due to COVID-19, such patients also demonstrate increased minute ventilation which makes it hard, if the device is used in line with the manufacturer’s instructions, to achieve adequate oxygen delivery. In addition, if a hospital contains many such patients, then it is possible that the oxygen requirements will exceed infrastructure capacity. Here we describe a simple modification of two exemplar ventilators normally used for domiciliary ventilation, which substantially increased the fraction of inspired oxygen (FiO 2 ) delivered.
Multi-institutional Analysis of Prognostic Factors and Outcomes After Hypofractionated Stereotactic Radiotherapy to the Resection Cavity in Patients With Brain Metastases
Authors: Kerstin A. Eitz, Simon S. Lo, Hany Soliman, Arjun Sahgal, Aimee Theriault, Mark. B. Pinkham, Matthew C. Foote, Andrew J. Song, Wenyin Shi, Kristin J. Redmond, Chengcheng Gui, Aryavarta M. S. Kumar, Mitchell Machtay, Bernhard Meyer, Stephanie E. Combs
Journal: JAMA Oncology (2020)

For brain metastases, the combination of neurosurgical resection and postoperative hypofractionated stereotactic radiotherapy (HSRT) is an emerging therapeutic approach preferred to the prior practice of postoperative whole-brain radiotherapy. However, mature large-scale outcome data are lacking.To evaluate outcomes and prognostic factors after HSRT to the resection cavity in patients with brain metastases.An international, multi-institutional cohort study was performed in 558 patients with resected brain metastases and postoperative HSRT treated between December 1, 2003, and October 31, 2019, in 1 of 6 participating centers. Exclusion criteria were prior cranial radiotherapy (including whole-brain radiotherapy) and early termination of treatment.A median total dose of 30 Gy (range, 18-35 Gy) and a dose per fraction of 6 Gy (range, 5-10.7 Gy) were applied.The primary end points were overall survival, local control (LC), and the analysis of prognostic factors associated with overall survival and LC. Secondary end points included distant intracranial failure, distant progression, and the incidence of neurologic toxicity.A total of 558 patients (mean [SD] age, 61 [0.50] years; 301 [53.9%] female) with 581 resected cavities were analyzed. The median follow-up was 12.3 months (interquartile range, 5.0-25.3 months). Overall survival was 65% at 1 year, 46% at 2 years, and 33% at 3 years, whereas LC was 84% at 1 year, 75% at 2 years, and 71% at 3 years. Radiation necrosis was present in 48 patients (8.6%) and leptomeningeal disease in 73 patients (13.1%). Neurologic toxic events according to the Common Terminology Criteria for Adverse Events grade 3 or higher occurred in 16 patients (2.8%) less than 6 months and 24 patients (4.1%) greater than 6 months after treatment. Multivariate analysis identified a Karnofsky Performance Status score of 80% or greater (hazard ratio [HR], 0.61; 95% CI, 0.46-0.82; P < .001), 22 to 33 days between resection and radiotherapy (HR, 1.50; 95% CI, 1.07-2.10; P = .02), and a controlled primary tumor (HR, 0.69; 95% CI, 0.52-0.90; P = .007) as prognostic factors associated with overall survival. For LC, a single brain metastasis (HR, 0.57; 95% CI, 0.35-0.93; P = .03) and a controlled primary tumor (HR, 0.59; 95% CI, 0.39-0.92; P = .02) were significant in the multivariate analysis.To date, this cohort study includes one of the largest series of patients with brain metastases and postoperative HSRT and appears to confirm an excellent risk-benefit profile of local HSRT to the resection cavity. Additional studies will help determine radiation dose-volume parameters and provide a better understanding of synergistic effects with systemic and immunotherapies.
Abstract 15501: Successes and Ongoing Opportunities in National Efforts to Improve STEMI Care: Mission: Lifeline Update 2010-2018
Authors: Murtuza J Ali, Patricia J Best, Mark Bieniarz, Gregg C Fonarow, William J French, John Gallagher, Abhinav Goyal, Christopher Granger, Timothy D Henry, Lori Hollowell, James Jollis, John Kelly, Michael Redlener, Harper Stone, Jessica Zegre-hemsey, Alice K Jacobs
Journal: Circulation (2019)

Introduction: Since 2007, the American Heart Association Mission: Lifeline program has provided a framework for development of systems of care for ST-elevation myocardial infarct (STEMI) patients. ...
Hyaluronate siRNA nanoparticles with positive charge display rapid attachment to tumor endothelium and penetration into tumors
Authors: Jie Luo, Johannes Schmaus, Mochen Cui, Elisa Hörterer, Ulrich Wilk, Miriam Höhn, Maike Däther, Simone Berger, Teoman Benli-Hoppe, Lun Peng, Ernst Wagner
Journal: Journal of Controlled Release (2020)
Impact of COVID-19 mitigation measures on the incidence of preterm birth: a national quasi-experimental study
Authors: Jasper V Been, Lizbeth Burgos Ochoa, Loes C M Bertens, Sam Schoenmakers, Eric A P Steegers, Irwin K M Reiss
Journal: The Lancet Public Health (2020)

BackgroundPreterm birth is the leading cause of child mortality globally, with many survivors experiencing long-term adverse consequences. Preliminary evidence suggests that numbers of preterm births greatly reduced following implementation of policy measures aimed at mitigating the effects of the COVID-19 pandemic. We aimed to study the impact of the COVID-19 mitigation measures implemented in the Netherlands in a stepwise fashion on March 9, March 15, and March 23, 2020, on the incidence of preterm birth.MethodsWe used a national quasi-experimental difference-in-regression-discontinuity approach. We used data from the neonatal dried blood spot screening programme (2010–20) cross-validated against national perinatal registry data. Stratified analyses were done according to gestational age subgroups, and sensitivity analyses were done to assess robustness of the findings. We explored potential effect modification by neighbourhood socioeconomic status, sex, and small-for-gestational-age status.FindingsData on 1 599 547 singleton neonates were available, including 56 720 births that occurred after implementation of COVID-19 mitigation measures on March 9, 2020. Consistent reductions in the incidence of preterm birth were seen across various time windows surrounding March 9 (± 2 months [n=531 823] odds ratio [OR] 0·77, 95% CI 0·66–0·91, p=0·0026; ± 3 months [n=796 531] OR 0·85, 0·73–0·98, p=0·028; ± 4 months [n=1 066 872] OR 0·84, 0·73–0·97, p=0·023). Decreases in incidence observed following the March 15 measures were of smaller magnitude, but not statistically significant. No changes were observed after March 23. Reductions in the incidence of preterm births after March 9 were consistent across gestational age strata and robust in sensitivity analyses. They appeared confined to neighbourhoods of high socioeconomic status, but effect modification was not statistically significant.InterpretationIn this national quasi-experimental study, initial implementation of COVID-19 mitigation measures was associated with a substantial reduction in the incidence of preterm births in the following months, in agreement with preliminary observations elsewhere. Integration of comparable data from across the globe is needed to further substantiate these findings and start exploring underlying mechanisms.FundingNone.
Discovery and validation of a personalized risk predictor for incident tuberculosis in low transmission settings
Authors: Rishi K. Gupta, Claire J. Calderwood, Alexei Yavlinsky, Maria Krutikov, Matteo Quartagno, Maximilian C. Aichelburg, Neus Altet, Roland Diel, Claudia C. Dobler, Jose Dominguez, Joseph S. Doyle, Connie Erkens, Steffen Geis, Pranabashis Haldar, Anja M. Hauri, Thomas Hermansen, James C. Johnston, Christoph Lange, Berit Lange, Frank van Leth, Laura Muñoz, Christine Roder, Kamila Romanowski, David Roth, Martina Sester, Rosa Sloot, Giovanni Sotgiu, Gerrit Woltmann, Takashi Yoshiyama, Jean-Pierre Zellweger, Dominik Zenner, Robert W. Aldridge, Andrew Copas, Molebogeng X. Rangaka, Marc Lipman, Mahdad Noursadeghi, Ibrahim Abubakar
Journal: Nature Medicine (2020)