tbuckley/cabot-search huggingface dataset:
Adverse Effects of Low-Dose Methotrexate
Authors: Daniel H. Solomon, Jeffrey A Sparks
Journal: Annals of Internal Medicine (2020)

Letters21 July 2020Adverse Effects of Low-Dose MethotrexateDaniel H. Solomon, MD, MPH and Jeffrey A Sparks, MD, MMScDaniel H. Solomon, MD, MPHBrigham and Women's Hospital, Boston, Massachusetts (D.H.S., J.A.S.) and Jeffrey A Sparks, MD, MMScBrigham and Women's Hospital, Boston, Massachusetts (D.H.S., J.A.S.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/L20-0525 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We thank Drs. Robey and Block for their interest in our article as it relates to a possible protective effect of LD-MTX on renal AEs. Because of space limitations in our article, we were unable to report such details as longitudinal changes in eGFR, inflammatory markers, and serum albumin levels. Because LD-MTX is known to be renally cleared, the study excluded patients with advanced stages of chronic kidney disease before randomization. Although the MDRD equation has the limitations described, these limitations are unlikely to explain the difference in eGFR between the groups that were randomly allocated to LD-MTX ... Author, Article, and Disclosure InformationAffiliations: Brigham and Women's Hospital, Boston, Massachusetts (D.H.S., J.A.S.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M19-3369. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAdverse Effects of Low-Dose Methotrexate Daniel H. Solomon , Robert J. Glynn , Elizabeth W. Karlson , Fengxin Lu , Cassandra Corrigan , Josh Colls , Chang Xu , Jean MacFadyen , Medha Barbhaiya , Nancy Berliner , Paul F. Dellaripa , Brendan M. Everett , Aruna D. Pradhan , Sarah P. Hammond , Meredith Murray , Deepak A. Rao , Susan Y. Ritter , Anna Rutherford , Jeffrey A. Sparks , Jackie Stratton , Dong H. Suh , Sara K. Tedeschi , Kathleen M.M. Vanni , Nina P. Paynter , and Paul M Ridker Adverse Effects of Low-Dose Methotrexate R. Brooks Robey and Clay A. Block Metrics Cited byTargeted Mitochondrial Fluorescence Imaging-Guided Tumor Antimetabolic Therapy with the Imprinted Polymer Nanomedicine Capable of Specifically Recognizing Dihydrofolate Reductase 21 July 2020Volume 173, Issue 2Page: 167KeywordsCardiovascular disease riskChronic kidney diseaseDisclosureEstimated glomerular filtration rateInflammationMethotrexateRenal analysisSerum albuminVascular diseases ePublished: 21 July 2020 Issue Published: 21 July 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Neovascularized implantable cell homing encapsulation platform with tunable local immunosuppressant delivery for allogeneic cell transplantation
Authors: Jesus Paez-Mayorga, Simone Capuani, Nathanael Hernandez, Marco Farina, Corrine Ying Xuan Chua, Ryan Blanchard, Antons Sizovs, Hsuan-Chen Liu, Daniel W. Fraga, Jean A. Niles, Hector F. Salazar, Bruna Corradetti, Andrew G. Sikora, Malgorzata Kloc, Xian C. Li, A. Osama Gaber, Joan E. Nichols, Alessandro Grattoni
Journal: Biomaterials (2020)

Cell encapsulation is an attractive transplantation strategy to treat endocrine disorders. Transplanted cells offer a dynamic and stimulus-responsive system that secretes therapeutics based on patient need. Despite significant advancements, a challenge in allogeneic cell encapsulation is maintaining sufficient oxygen and nutrient exchange, while providing protection from the host immune system. To this end, we developed a subcutaneously implantable dual-reservoir encapsulation system integrating in situ prevascularization and local immunosuppressant delivery, termed NICHE. NICHE structure is 3D-printed in biocompatible polyamide 2200 and comprises of independent cell and drug reservoirs separated by a nanoporous membrane for sustained local release of immunosuppressant. Here we present the development and characterization of NICHE, as well as efficacy validation for allogeneic cell transplantation in an immunocompetent rat model. We established biocompatibility and mechanical stability of NICHE. Further, NICHE vascularization was achieved with the aid of mesenchymal stem cells. Our study demonstrated sustained local elution of immunosuppressant (CTLA4Ig) into the cell reservoir protected transcutaneously-transplanted allogeneic Leydig cells from host immune destruction during a 31-day study, and reduced systemic drug exposure by 12-fold. In summary, NICHE is the first encapsulation platform achieving both in situ vascularization and immunosuppressant delivery, presenting a viable strategy for allogeneic cell transplantation.
Long-term mortality after childhood growth hormone treatment: the SAGhE cohort study
Authors: Lars Sävendahl, Rosie Cooke, Anders Tidblad, Dominique Beckers, Gary Butler, Stefano Cianfarani, Peter Clayton, Joël Coste, Anita C S Hokken-Koelega, Wieland Kiess, Claudia E Kuehni, Kerstin Albertsson-Wikland, Annalisa Deodati, Emmanuel Ecosse, Ruth Gausche, Claudio Giacomozzi, Daniel Konrad, Fabienne Landier, Roland Pfaeffle, Grit Sommer, Muriel Thomas, Sally Tollerfield, Gladys R J Zandwijken, Jean-Claude Carel, Anthony J Swerdlow
Journal: The Lancet Diabetes & Endocrinology (2020)
Outcome measures based on digital health technology sensor data: data- and patient-centric approaches
Authors: Kirsten I. Taylor, Hannah Staunton, Florian Lipsmeier, David Nobbs, Michael Lindemann
Journal: npj Digital Medicine (2020)

Digital health technology tools (DHTT) are technologies such as apps, smartphones, and wearables that remotely acquire health-related information from individuals. They have the potential advantages of objectivity and sensitivity of measurement, richness of high-frequency sensor data, and opportunity for passive collection of health-related data. Thus, DHTTs promise to provide patient phenotyping at an order of granularity several times greater than is possible with traditional clinical research tools. While the conceptual development of novel DHTTs is keeping pace with technological and analytical advancements, an as yet unaddressed gap is how to develop robust and meaningful outcome measures based on sensor data. Here, we describe two roadmaps which were developed to generate outcome measures based on DHTT data: one using a data-centric approach and the second a patient-centric approach. The data-centric approach to develop digital outcome measures summarizes those sensor features maximally sensitive to the concept of interest, exemplified with the quantification of disease progression. The patient-centric approach summarizes those sensor features that are optimally relevant to patients’ functioning in everyday life. Both roadmaps are exemplified for use in tracking disease progression in observational and clinical interventional studies, and with a DHTT designed to evaluate motor symptom severity and symptom experience in Parkinson’s disease. Use cases other than disease progression (e.g., case-finding) are considered summarily. DHTT research requires methods to summarize sensor data into meaningful outcome measures. It is hoped that the concepts outlined here will encourage a scientific discourse and eventual consensus on the creation of novel digital outcome measures for both basic clinical research and clinical drug development.
Multiple HLA B*57 alleles, sharing the amino acid residue Valine(97), are associated with drug-induced liver injury due to flucloxacillin in a European population.
Authors: Paola Nicoletti, Guruprasad P. Aithal, Sally Coulthard, Raul Andrade, Bjornsson S. Einar, John Dillon, Anke H. Maitland-van der Zee, Jennifer H. Martin, Mariam Molokhia, Munir Pirmohamed, Mia Wadelius, Aris Floratos, Yufeng Shen, Matthew R. Nelson, Ann K. Daly
Journal: Hepatology (2017)

Multiple HLA B*57 alleles, sharing the amino acid residue Valine(97), are associated with drug-induced liver injury due to flucloxacillin in a European population.
Serum piRNA-54265 is a New Biomarker for early detection and clinical surveillance of Human Colorectal Cancer
Authors: Dongmei Mai, Yanfen Zheng, Huan Guo, Peirong Ding, Ruihong Bai, Mei Li, Ying Ye, Jialiang Zhang, Xudong Huang, Dingxin Liu, Qiaoqi Sui, Ling Pan, Jiachun Su, Junge Deng, Guandi Wu, Rui Li, Shuang Deng, Yansen Bai, Yanan Ligu, Wen Tan, Chen Wu, Tangchun Wu, Jian Zheng, Dongxin Lin
Journal: Theranostics (2020)

Background: Our previous study has demonstrated an oncogenic role of PIWI-interacting RNA-54265 (piR-54265) in colorectal cancer (CRC). Here, we investigate whether it can be a blood biomarker for population screening and clinical applications. Methods: Serum piR-54265 levels were determined by a digital PCR method in 209 cancer-free healthy controls, 725 patients with CRC, 1303 patients with other types of digestive cancer and 192 patients with benign colorectal tumors. A prospective case-control analysis was conducted to assess the predictive value of serum piR-54265 for future CRC diagnosis. Receiver operating characteristic (ROC) curve was constructed to quantify the diagnostic performance of serum piR-54265 levels by assessing its sensitivity, specificity and respective areas under curve (AUC). The odds ratios (ORs) were computed using multivariate logistic regression models. Results: Serum piR-54265 levels were significantly elevated only in patients with CRC compared with controls and patients with other cancer types. The AUC for recognizing CRC was 0.896 (95% CI, 0.874-0.914), with a sensitivity and specificity being 85.7% and 65.1% at 1500 copies/µL as a cut-off value. The serum piR-54265 levels in patients declined substantially after surgery but increased significantly again when tumor relapses. The prediagnostic serum piR-54265 levels were significantly associated with future CRC diagnosis, with the ORs of 7.23, 2.80, 2.45, and 1.24 for those whose CRC was diagnosed within 1, 2, 3 and >3 years. Serum piR-54265 test is more sensitive than other blood CRC markers. Conclusion: Serum piR-54265 may serve as a valuable biomarker for CRC screening, early detection and clinical surveillance.
Inter- and Intra-individual Variation, and Limited Prognostic Utility, of Serum Alkaline Phosphatase in a Trial of Patients With Primary Sclerosing Cholangitis
Authors: Palak J. Trivedi, Andrew J. Muir, Cynthia Levy, Christopher L. Bowlus, Michael P. Manns, Xiaomin Lu, Gerald Crans, Chuhan Chung, G. Mani Subramanian, Robert P. Myers, Zachary Goodman, Naga Chalasani, John M. Vierling, Indra Neil Guha, Gideon M. Hirschfield
Journal: Clinical Gastroenterology and Hepatology (2020)
Debate: What Is Optimal First-Line Therapy for Chronic Lymphocytic Leukemia?
Authors: Mazyar Shadman, Deborah M. Stephens
Journal: Journal of the National Comprehensive Cancer Network (2020)

In the era of newer, highly effective targeted therapies for chronic lymphocytic leukemia (CLL), experts debated whether there is still a role for chemoimmunotherapy in the first-line setting for the treatment of this disease. In general, targeted therapies are preferred as first-line treatment for all patients, with the exception of low-risk patients [younger, fit patients with mutated IGHV who are candidates for fludarabine/cyclophosphamide/rituximab (FCR)]. About 37% of low-risk patients experience long-term durable remissions and remain stable after treatment with FCR for many years. Advantages of FCR over small molecule inhibitors include cost, fixed duration treatment, and long-term survival benefit. Disadvantages are an etimated 5% risk of developing myelodysplastic syndrome or acute myeloid leukemia. Advantages of small molecule inhibitors are improvements in progression-free and overall survival and quality of life when compared with chemoimmunotherapy. Disadvantages of small molecule inhibitors are high cost and the need for continuous treatment. However, studies are underway to develop fixed duration regimens with combinations of small molecule inhibitors that aim to deepen remissions.
PTH-112 Assessing the effect of ethnicity on urinary metabolic profiles in inflammatory bowel disease
Authors: LC Hicks, Str Powles, Lwl Chong, J Swann, E Holmes, Hrt Williams, TR Orchard
Journal: Gut (2017)

Introduction  Urinary metabolic profiling has been shown to distinguish patients with inflammatory bowel disease (IBD) from healthy controls (HC), and also separate ulcerative colitis (UC) from Crohn’s disease (CD) in Caucasian (Cau) cohorts (1). Diet and lifestyle also have an effect on metabolic profiles (2), and these differ in patients from different ethnic backgrounds. Moreover, clinical phenotype varies between Cau and South Asians (SA)(3), however discriminatory metabolites have not been studied in different ethnic populations. The aim of this study was to compare the urinary metabolic profiles of IBD patients and HC from Cau and SA backgrounds.  Method  Samples from 405 IBD patients (283 Cau and 122 SA) and 137 HC (98 Cau and 48 SA) were analysed by H1NMR spectroscopy. Clinical and dietary data were collected. Orthogonal partial least squares discriminant analysis (OPLSDA) was performed to examine whether there were differences in metabolic data between Cau and SA. R2 (variance), Q2 (quality assessment) and p values (validity) for each model were described.  Results  The phenotype of SA CD was not significantly different to Cau CD in this cohort. In the SA UC group there was more pancolitis (p=0.051) and less proctitis (p=0.008). There were more vegetarians in the SA group. OPLSDA was able to separate patients with IBD from HC, and also UC from CD, in the Cau cohort, but this separation could not be replicated in SA (negative Q2 values).  OPLSDA models also separated SA HC from Cau, and SA CD from Cau CD, but in UC no robust model could be made.  Conclusion  The separation between Cau and SA HC may reflect differing lifestyles including diet. Cau IBD patients could be separated from HC, and CD from UC, replicating previous studies. SA IBD patients could not be separated from HC which may be due to lower numbers of SA patients in this study, and specifically less CD patients where stronger discriminating models have been shown in Cau in previous studies. In CD, Cau and SA could be separated, but Cau and SA patients could not be distinguished in the UC cohort, possibly suggesting the metabolic milieu in CD is stronger and less influenced by the impact of ethnicity.  References  . Williams HR, et al. Am J Gastroenterol2009;104(6):1435–44.  . Stella Cet al. J Proteome Res, 2006;5(10):2780–8.  . Walker DG, et al. Am J Gastroenterol2011;106(7):1281–9.  Disclosure of Interest  None Declared
Characteristics and Strength of Evidence of COVID-19 Studies Registered on ClinicalTrials.gov
Authors: Krishna Pundi, Alexander C. Perino, Robert A. Harrington, Harlan M. Krumholz, Mintu P. Turakhia
Journal: JAMA Internal Medicine (2020)

on ClinicalTrials.govThe coronavirus disease 2019 (COVID-19) pandemic has led to a massive activation of clinical research.The methodological strength of these studies is not well characterized but has implications for the quality of evidence produced.We evaluated the characteristics and expected strength of evidence of COVID-19 studies registered on ClinicalTrials.gov.
Commercial Features of Placebo and Therapeutic Efficacy
Authors: Rebecca L Waber, Baba Shiv, Ziv Carmon, Dan Ariely
Journal: JAMA (2008)

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
Identification of Substance-Exposed Newborns and Neonatal Abstinence Syndrome Using ICD-10-CM — 15 Hospitals, Massachusetts, 2017
Authors: Sonal Goyal, Katherine C. Saunders, Chiara S. Moore, Katherine T. Fillo, Jean Y. Ko, Susan E. Manning, Carrie Shapiro-Mendoza, Munish Gupta, Lisa Romero, Kelsey C. Coy, Kendra B. McDow, Amelia A. Keaton, Jennifer Sinatra, Katarina Jones, Charles Alpren, Wanda D. Barfield, Hafsatou Diop
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Opioid use disorder and neonatal abstinence syndrome (NAS) increased in Massachusetts from 1999 to 2013 (1,2). In response, in 2016, the state passed a law requiring birth hospitals to report the number of newborns who were exposed to controlled substances to the Massachusetts Department of Public Health (MDPH)* by mandating monthly reporting of International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic codes related to maternal dependence on opioids (F11.20) or benzodiazepines (F13.20) and to newborns affected by maternal use of drugs of addiction (P04.49) or experiencing withdrawal symptoms from maternal drugs of addiction (P96.1) separately.† MDPH uses these same codes for monthly, real-time crude estimates of NAS and uses P96.1 alone for official NAS state reporting.§ MDPH requested CDC's assistance in evaluating the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of either maternal or newborn codes to identify substance-exposed newborns, and of newborn exposure codes (both exposure [P04.49] or withdrawal [P96.1]) and the newborn code for withdrawal alone (P96.1) to identify infants with NAS cases related to three exposure scenarios: 1) opioids, 2) opioids or benzodiazepines, and 3) any controlled substance. Confirmed diagnoses of substance exposure and NAS abstracted from linked clinical records for 1,123 infants born in 2017 and their birth mothers were considered the diagnostic standard and were compared against hospital-reported ICD-10-CM codes. For identifying substance-exposed newborns across the three exposure scenarios, the newborn exposure codes had higher sensitivity (range = 31%-61%) than did maternal drug dependence codes (range = 16%-41%), but both sets of codes had high PPV (≥74%). For identifying NAS, for all exposure scenarios, the sensitivity for either newborn code (P04.49 or P96.1) was ≥92% and the PPV was ≥64%; for P96.1 alone the sensitivity was ≥79% and the PPV was ≥92% for all scenarios. Whereas ICD-10-CM codes are effective for NAS surveillance in Massachusetts, they should be applied cautiously for substance-exposed newborn surveillance. Surveillance for substance-exposed newborns using ICD-10-CM codes might be improved by increasing the use of validated substance-use screening tools and standardized facility protocols and improving communication between patients and maternal health and infant health care providers.
Nanozyme-assisted sensitive profiling of exosomal proteins for rapid cancer diagnosis
Authors: Huixia Di, Ze Mi, Yan Sun, Xuehui Liu, Xinzhuo Liu, Ang Li, Ying Jiang, Hongmei Gao, Pengfei Rong, Dingbin Liu
Journal: Theranostics (2020)

The proteins expressed on exosomes have emerged as promising liquid-biopsy biomarkers for cancer diagnosis. However, molecular profiling of exosomal proteins remains technically challenging. Herein, we report a nanozyme-assisted immunosorbent assay (NAISA) that enables sensitive and rapid multiplex profiling of exosomal proteins. This NAISA system is based on the installation of peroxidase-like nanozymes onto the phospholipid membranes of exosomes, thus avoiding the need for post-labelling detection antibodies. The exosomal proteins are determined by a sensitive nanozyme-catalyzed colorimetric assay less than 3 h, without the need for multi-step incubation and washing operations. Using NAISA to profile exosomal proteins from different cell lines and clinical samples, we reveal that tumor-associated exosomal proteins can serve as promising biomarkers for accurate cancer diagnosis in a cooperative detection pattern. Methods: Exosomes were engineered with DSPE-PEG-SH through hydrophobic interaction, and then were assembled with gold nanoparticles (2 nm) to produce Exo@Au nanozyme. The proteins on Exo@Au could be selectively captured by their specific antibodies seeded into a 96-well plate. The immobilized Exo@Au shows peroxidase-like activity to perform colorimetric assays by reaction with 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2. The protein levels of exosomes were recorded on a microplate reader. Results: The NAISA platform is capable of profiling multiple exosomal proteins from both cancer cell lines and clinical samples. The expression levels of exosomal proteins, such as CD63, CEA, GPC-3, PD-L1 and HER2, were used to classify different cancer cell lines. Moreover, the protein profiles have been applied to differentiate healthy donors, hepatitis B patients, and hepatic cell carcinoma (HCC) patients with high accuracy. Conclusion: The NAISA nanozyme was allowed to rapidly profile multiple exosomal proteins and could have great promise for early HCC diagnosis and identification of other cancer types.