tbuckley/cabot-search huggingface dataset:
Impact of leucovorin shortage on patient treatment.
Authors: Mina Samir Erian Hanna, Peter Kozuch, Molly Thorn, Janna Roitman, Michael L. Grossbard, Daniel Jacob Becker
Journal: Journal of Clinical Oncology (2013)

e17566 Background: Shortages of intravenous leucovorin were initially reported in late 2008, and availability plummeted nationally and at Continuum Cancer Centers of New York (CCCNY) in late 2011. NCCN guidelines recommend either the use of levoleucovorin or low dose leucovorin during the shortage. The impact of the leucovorin shortage on patient therapy remains unknown. Methods: We reviewed patient charts for all outpatients treated with leucovorin at CCCNY between April and September of 2010, 2011, and 2012. We recorded patient characteristics, and leucovorin use (dose, number of treatments); and calculated descriptive statistics. We classified each dose as either low (20-40 mg/m2) or high (200-500mg/m2) and compared leucovorin use between years with Chi Square and ANOVA tests. We also reviewed pharmacy purchasing data to evaluate the economic effect of the leucovorin shortage. Results: We identified 55 patients treated with 313 doses of leucovorin in 2010, 99 patients treated with 582 doses in 2011 and 118 patients treated with 742 doses in 2012. No patients received levoleucovorin. Patient characteristics, disease and stage were similar between years with colorectal cancer accounting for 78%, 69%, and 70% of patients in 2010, 2011, and 2012 (p=0.87). Low dose leucovorin was used in 30.0% of doses in 2010, 30.4% in 2011, and 99.1% in 2012 (p&lt;0.0001). The mean dose/treatment (SD) was 459 mg (296), 499 mg (328), and 47 mg (89), in 2010, 2011, 2012, respectively (p&lt;0.0001). Among patients treated for colon cancer we found no association between stage (III vs. IV) and use of low dose leucovorin in 2010 or 2011. Quantity of leucovorin purchased at one hospital decreased by 63% from 171.75 g in 2010 and 157.50g in 2011 to 63.00 g in 2012. The price of leucovorin was similar at 0.017 $/mg in 2011 and 0.013 $/mg in 2012. Conclusions: Worsening leucovorin drug shortage was associated with a profound change in leucovorin use at CCCNY between 2011 and 2012. In accordance with NCCN guidelines, physicians used more low dose leucovorin. The price of leucovorin remained constant despite limited supply. Additional patient follow up is warranted to evaluate the outcomes of patients treated during the shortage.
99mTc-MIBI Embolus in the Late Phase of a Parathyroid Scan
Authors: Christos Savvopoulos, Håkan Geijer
Journal: Clinical Nuclear Medicine (2019)

Abstract We report a case of a transient focal MIBI uptake in the late, 90 minutes postinjection phase of a parathyroid scintigraphy in which SPECT/CT imaging proved valuable in delineating the nature of this incidental finding.
Success of Thai cave rescue depended on meticulous planning and rehearsal to minimise risks
Authors: Rebecca Coombes
Journal: BMJ (2019)

The British cave diver who played a leading role in the rescue of 12 Thai boys and their coach last year has spoken of how sedating the children was necessary to complete the mission safely.

John Volanthen, a British cave diver who specialises in rescues, and his colleague Richard Stanton, were the first to find the group who were stranded in the Tham Luang cave in Thailand—a discovery which led to their eventual rescue.

Speaking to a medical audience at the Risky Business conference in London this week, Volanthen told how the rescue wasn’t a “miracle” but the result of meticulous planning, rehearsing each step, and taking calculated risks. All lessons that were translatable to healthcare, he said.

“When the incident commander announced to the world that the boys were …
Inhibition of hyperglycolysis in mesothelial cells prevents peritoneal fibrosis
Authors: Meijun Si, Qianqian Wang, Yin Li, Hongchun Lin, Dan Luo, Wenbo Zhao, Xianrui Dou, Jun Liu, Hui Zhang, Yong Huang, Tanqi Lou, Zhaoyong Hu, Hui Peng
Journal: Science Translational Medicine (2019)

Progressive peritoneal fibrosis affects patients receiving peritoneal dialysis (PD) and has no reliable treatment. The mechanisms that initiate and sustain peritoneal fibrosis remain incompletely elucidated. To overcome these problems, we developed a strategy that prevents peritoneal fibrosis by suppressing PD-stimulated mesothelial-to-mesenchymal transition (MMT). We evaluated single-cell transcriptomes of mesothelial cells obtained from normal peritoneal biopsy and effluent from PD-treated patients. In cells undergoing MMT, we found cellular heterogeneity and intermediate transition states associated with up-regulation of enzymes involved in glycolysis. The expression of glycolytic enzymes was correlated with the development of MMT. Using gene expression profiling and metabolomics analyses, we confirmed that PD fluid induces metabolic reprogramming, characterized as hyperglycolysis, in mouse peritoneum. We found that transforming growth factor β1 (TGF-β1) can substitute for PD fluid to stimulate hyperglycolysis, suppressing mitochondrial respiration in mesothelial cells. Blockade of hyperglycolysis with 2-deoxyglucose (2-DG) inhibited TGF-β1-induced profibrotic cellular phenotype and peritoneal fibrosis in mice. We developed a triad of adeno-associated viruses that overexpressed microRNA-26a and microRNA-200a while inhibiting microRNA-21a to target hyperglycolysis and fibrotic signaling. Intraperitoneal injection of the viral triad inhibited the development of peritoneal fibrosis induced by PD fluid in mice. We conclude that hyperglycolysis is responsible for MMT and peritoneal fibrogenesis, and this aberrant metabolic state can be corrected by modulating microRNAs in the peritoneum. These results could provide a therapeutic strategy to combat peritoneal fibrosis.
Calreticulin mutants as oncogenic rogue chaperones for TpoR and traffic-defective pathogenic TpoR mutants
Authors: Christian Pecquet, Ilyas Chachoua, Anita Roy, Thomas Balligand, Gaëlle Vertenoeil, Emilie Leroy, Roxana-Irina Albu, Jean-Philippe Defour, Harini Nivarthi, Eva Hug, Erica Xu, Yasmine Ould-Amer, Céline Mouton, Didier Colau, Didier Vertommen, Myat Marlar Shwe, Caroline Marty, Isabelle Plo, William Vainchenker, Robert Kralovics, Stefan N. Constantinescu
Journal: Blood (2019)
New preprint server allows earlier sharing of research methods and findings
Authors: Gareth Iacobucci
Journal: BMJ (2019)

A new free online service for archiving and distribution of research article preprints in the medical and health sciences has been announced.

Called medRxiv (pronounced “med-archive”), the preprint server (medRxiv.org) is being launched by The BMJ , Yale University, and Cold Spring Harbor Laboratory, a private, non-profit research institution in Long Island, New York. It is expected to begin accepting manuscripts on 6 June and will be overseen by the three organisations.

Preprints are preliminary versions of research articles that researchers …
Abstract 18104: Impact of Age on the Selection of Nuclear Cardiology Stress Protocols: The INCAPS (IAEA Nuclear Cardiology Protocols) Study
Authors: Mouaz H Al-Mallah, Thomas Pascual, Mathew Mercuri, João V Vitola, Ganesan Karthikeyan, Nathan Better, Madan Rehani, Maurizio Dondi, Diana Paez, Andrew Einstein
Journal: Circulation (2017)

Background: There is growing concern about radiation exposure from nuclear myocardial perfusion imaging (MPI), particularly among younger patients who are more prone to develop untoward effects of ...
Author Correction: GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability
Authors: Joëlle A. Pasman, Karin J. H. Verweij, Zachary Gerring, Sven Stringer, Sandra Sanchez-Roige, Jorien L. Treur, Abdel Abdellaoui, Michel G. Nivard, Bart M. L. Baselmans, Jue-Sheng Ong, Hill F. Ip, Matthijs D. van der Zee, Meike Bartels, Felix R. Day, Pierre Fontanillas, Sarah L. Elson, Harriet de Wit, Lea K. Davis, James MacKillop, Jaime L. Derringer, Susan J. T. Branje, Catharina A. Hartman, Andrew C. Heath, Pol A. C. van Lier, Pamela A. F. Madden, Reedik Mägi, Wim Meeus, Grant W. Montgomery, A. J. Oldehinkel, Zdenka Pausova, Josep A. Ramos-Quiroga, Tomas Paus, Marta Ribases, Jaakko Kaprio, Marco P. M. Boks, Jordana T. Bell, Tim D. Spector, Joel Gelernter, Dorret I. Boomsma, Nicholas G. Martin, Stuart MacGregor, John R. B. Perry, Abraham A. Palmer, Danielle Posthuma, Marcus R. Munafò, Nathan A. Gillespie, Eske M. Derks, Jacqueline M. Vink
Journal: Nature Neuroscience (2019)
Treg lymphocytes and cutaneous viral infections
Authors: S.S. Hampras, M. Tommasino, Y. Zhao, J.L. Messina, A.R. Giuliano, N.A. Fenske, B. Cherpelis, R.S. Hesterberg, A.A. Akuffo, R.P. Amorrortu, J. Balliu, L. Vijayan, T. Gheit, P.K. Epling‐Burnette, D.E. Rollison
Journal: British Journal of Dermatology (2019)

Approximately three million non‐melanoma skin cancers (NMSCs) are diagnosed worldwide each year, although this number is likely an underestimate given that these cancers are not always recorded in cancer registries. Studies have suggested that skin (cutaneous) infections with human papillomaviruses (HPV) and polyomaviruses (HPyV) may play a role in the development of some NMSC types. Suppression of the immune system is also a risk factor for NMSC. This study, from the U.S.A, aimed to understand the relationship between T‐regulatory (Treg) cells, cells which suppress immune response, and cutaneous viral infections. Blood, skin swabs and eyebrow hairs were collected from 352 patients who underwent skin cancer screening and did not have cancer detected. The researchers examined whether the skin swabs (SSW) and eyebrow hairs (EBH) contained genetic material (DNA) corresponding to 98 cutaneous HPV types (including beta HPV and gamma HPV) and 5 HPyV types. The blood samples were analyzed to determine proportions of different types of Treg cell populations in circulation (in the blood). The researchers found no association between total percent of circulating Treg cells and beta HPV or HPyV infection. However, two types of Treg cells were found at lower levels in those that had gamma HPV infection in their EBH and/or SSW. Those two types were CLA+ Treg cells (known to travel to the skin) and effector CD27‐CD45RA‐FOXP3+CD4+ Treg cells (known to become active when exposed to a foreign viral infection). The study results suggest that gamma HPV infection may stimulate Treg cells to move from circulation into the skin tissues.
YES1 Drives Lung Cancer Growth and Progression and Predicts Sensitivity to Dasatinib
Authors: Irati Garmendia, María J. Pajares, Francisco Hermida-Prado, Daniel Ajona, Cristina Bértolo, Cristina Sainz, Amaya Lavín, Ana B. Remírez, Karmele Valencia, Haritz Moreno, Irene Ferrer, Carmen Behrens, Myriam Cuadrado, Luis Paz-Ares, Xosé R. Bustelo, Ignacio Gil-Bazo, Daniel Alameda, Fernando Lecanda, Alfonso Calvo, Enriqueta Felip, Montse Sánchez-Céspedes, Ignacio I. Wistuba, Rocio Granda-Diaz, Juan Pablo Rodrigo, Juana María García-Pedrero, Ruben Pio, Luis M. Montuenga, Jackeline Agorreta
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: The characterization of new genetic alterations is essential to assign effective personalized therapies in non-small cell lung cancer (NSCLC). Furthermore, finding stratification biomarkers is essential for successful personalized therapies. Molecular alterations of YES1, a member of the SRC (proto-oncogene tyrosine-protein kinase Src) family kinases (SFKs), can be found in a significant subset of patients with lung cancer.Objectives: To evaluate YES1 (v-YES-1 Yamaguchi sarcoma viral oncogene homolog 1) genetic alteration as a therapeutic target and predictive biomarker of response to dasatinib in NSCLC.Methods: Functional significance was evaluated by in vivo models of NSCLC and metastasis and patient-derived xenografts. The efficacy of pharmacological and genetic (CRISPR [clustered regularly interspaced short palindromic repeats]/Cas9 [CRISPR-associated protein 9]) YES1 abrogation was also evaluated. In vitro functional assays for signaling, survival, and invasion were also performed. The association between YES1 alterations and prognosis was evaluated in clinical samples.Measurements and Main Results: We demonstrated that YES1 is essential for NSCLC carcinogenesis. Furthermore, YES1 overexpression induced metastatic spread in preclinical in vivo models. YES1 genetic depletion by CRISPR/Cas9 technology significantly reduced tumor growth and metastasis. YES1 effects were mainly driven by mTOR (mammalian target of rapamycin) signaling. Interestingly, cell lines and patient-derived xenograft models with YES1 gene amplifications presented a high sensitivity to dasatinib, an SFK inhibitor, pointing out YES1 status as a stratification biomarker for dasatinib response. Moreover, high YES1 protein expression was an independent predictor for poor prognosis in patients with lung cancer.Conclusions: YES1 is a promising therapeutic target in lung cancer. Our results provide support for the clinical evaluation of dasatinib treatment in a selected subset of patients using YES1 status as predictive biomarker for therapy.
Phase II Evaluation of Aggressive Dose De-Escalation for Adjuvant Chemoradiotherapy in Human Papillomavirus–Associated Oropharynx Squamous Cell Carcinoma
Authors: Daniel J. Ma, Katharine A. Price, Eric J. Moore, Samir H. Patel, Michael L. Hinni, Joaquin J. Garcia, Darlene E. Graner, Nathan R. Foster, Brenda Ginos, Michelle Neben-Wittich, Yolanda I. Garces, Ashish V. Chintakuntlawar, Daniel L. Price, Kerry D. Olsen, Kathryn M. Van Abel, Jan L. Kasperbauer, Jeffrey R. Janus, Mark Waddle, Robert Miller, Satomi Shiraishi, Robert L. Foote
Journal: Journal of Clinical Oncology (2019)

The purpose of this study was to determine if dose de-escalation from 60 to 66 Gy to 30 to 36 Gy of adjuvant radiotherapy (RT) for selected patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma could maintain historical rates for disease control while reducing toxicity and preserving swallow function and quality of life (QOL).
Abstract P122: The Clinical Impact of TC/HDL-C Discordance With LDL-C and Non-HDL-C: 20 Year Follow-up of the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Renato Quispe, Mohamed B Elshazly, Di Zhao, Peter P Toth, Allan D Sniderman, Rishi Puri, Salim S Virani, Seth S Martin, Steven R Jones, Erin D Michos
Journal: Circulation (2017)

Introduction: TheTotal to High-Density Lipoprotein cholesterol (TC/HDL-C) ratio may carry unique prognostic information for atherosclerotic cardiovascular diseases (ASCVD) risk beyond the more commonly used measures of low-density lipoprotein (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C). Information regarding patient-level discordance between these lipid parameters may be clinically relevant in refining risk stratification. Methods: We studied 14,393 ARIC participants free of ASCVD at baseline who were mean age 54 years, 56% women, and 25% black. Lipids were measured at baseline (1987-1989) and at four additional visits. TC/HDL-C discordance with non-HDL-C and LDL-C (defined by categories above/below the median) was updated at each visit. Participants were followed for ASCVD events through end of 2013, with mean follow-up of 20 years. Multivariable-adjusted Cox hazard models were used to estimate for ASCVD risk for each category. Results: Among participants with low LDL-C &lt;median, a discordantly high TC/HDL-C ≥median was associated with a greater ASCVD risk compared to those concordantly low for both TC/HDL-C and LDL-C. Those with low non-HDL but a discordantly high TC/HDL-C also had greater ASCVD risk than those concordantly low for both measures (Table). Conclusions: In a primary prevention population,the TC/HDL-C ratio provides additional prognostic information to non-HDL-C and LDL-C. Individuals who reach low levels of LDL-C or non-HDL-C may still be at high risk of ASCVD if TC/HDL-C is discordantly high.
Methodological Issues in Determining the Accuracy of Automated Office Blood Pressure Readings for Diagnosing Hypertension—Reply
Authors: Michael Roerecke, Janusz Kaczorowski, Martin G. Myers
Journal: JAMA Internal Medicine (2019)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Internal Medicine journal
Cirmtuzumab Inhibits Non-Canonical Wnt Signaling without Enhancing Canonical Wnt/β-Catenin Signaling in Chronic Lymphocytic Leukemia
Authors: Han Zhang, Suping Zhang, Emanuela M. Ghia, Michael Y. Choi, Jieyu Zhang, Liguang Chen, George F. Widhopf II, Laura Z. Rassenti, Thomas J. Kipps
Journal: Blood (2018)
E-cigarettes: Indian government research council recommends “complete prohibition”
Authors: Elisabeth Mahase
Journal: BMJ (2019)

The Indian Council of Medical Research, part of the government’s department of health, has recommended a complete prohibition on e-cigarettes, citing their highly addictive and harmful ingredients among other concerns, in a new white paper.1

The council has claimed that there are documented “adverse effects” of e-cigarette use, including DNA damage, carcinogenesis, and respiratory, cardiovascular, and neurological disorders.

Other problems such as second hand vapour exposure—especially during pregnancy—poisoning from accidental swallowing by children, …
GREY SCALE TEXTURE ANALYSIS OF ENDOBRONCHIAL ULTRASOUND MINI PROBE GUIDE SHEATH IMAGES FOR PREDICTION OF BENIGN OR MALIGNANT AETIOLOGY
Authors: Phan Nguyen, Farzad Bashirzadeh, Justin Hundloe, Olivier Salvado, Nicholas Dowson, Robert Ware, Ian Brent Masters, David Fielding
Journal: Journal of Thoracic Oncology (2013)
Insulin Cost and Underuse in Patients With Diabetes
Authors: Kapil Bhatia, Eric Y. Chang, Muhammad Bilal
Journal: JAMA Internal Medicine (2019)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Internal Medicine journal
Randomized Trial of Lisinopril Versus Carvedilol to Prevent Trastuzumab Cardiotoxicity in Patients With Breast Cancer
Authors: Maya Guglin, Jeffrey Krischer, Roy Tamura, Angelina Fink, Lauren Bello-Matricaria, Worta McCaskill-Stevens, Pamela N Munster
Journal: Journal of the American College of Cardiology (2019)
Endo-lysosomal dysregulations and late-onset Alzheimer’s disease: impact of genetic risk factors
Authors: Zoë P. Van Acker, Marine Bretou, Wim Annaert
Journal: Molecular Neurodegeneration (2019)

Increasing evidence supports that cellular dysregulations in the degradative routes contribute to the initiation and progression of neurodegenerative diseases, including Alzheimer's disease. Autophagy and endolysosomal homeostasis need to be maintained throughout life as they are major cellular mechanisms involved in both the production of toxic amyloid peptides and the clearance of misfolded or aggregated proteins. As such, alterations in endolysosomal and autophagic flux, as a measure of degradation activity in these routes or compartments, may directly impact as well on disease-related mechanisms such as amyloid-β clearance through the blood-brain-barrier and the interneuronal spreading of amyloid-β and/or Tau seeds, affecting synaptic function, plasticity and metabolism. The emerging of several genetic risk factors for late-onset Alzheimer's disease that are functionally related to endocytic transport regulation, including cholesterol metabolism and clearance, supports the notion that in particular the autophagy/lysosomal flux might become more vulnerable during ageing thereby contributing to disease onset. In this review we discuss our current knowledge of the risk genes APOE4, BIN1, CD2AP, PICALM, PLD3 and TREM2 and their impact on endolysosomal (dys)regulations in the light of late-onset Alzheimer's disease pathology.
The intestinal microbiota and cardiovascular disease
Authors: Themistoklis Katsimichas, Alexios S Antonopoulos, Alexandros Katsimichas, Tomohito Ohtani, Yasushi Sakata, Dimitris Tousoulis
Journal: Cardiovascular Research (2019)

The intestinal microbiota of human hosts is the community of microorganisms living in the small and, mainly, the large intestine of humans. This microbial ecosystem has co-evolved with humans across the millennia, has come to play an important interactive role in human physiology and has been aptly called our forgotten organ. Significant properties of the microbiota benefiting its host include energy harvest from food sources indigestible by humans, protection from pathogen colonization, and vitamin synthesis. Mounting evidence has linked changes in the composition or metabolic profiles of the microbiota with human disease, including disorders of the cardiovascular spectrum. Although cause and effect mechanisms are as yet essentially unproven in the relevant literature, the established associations point to the importance of the microbiota in the pathophysiology of cardiovascular disease (CVD). In this review, we first summarize key information on the gut microbial communities and the elaborate tools developed to analyse their structure and metabolic functions. Ecological terms are explained and analytical techniques are simplified, to enhance the understanding of published studies. Statistical methods used in microbial analysis are also described in simple terms. We then present published literature on the association of the compositional and functional changes of the microbiota with CVD, including heart failure, hypertension, and atherosclerosis. Each section of the review deals with the underlying pathophysiology of the relevant associations, connecting the observational and mechanistic aspects. Finally, we discuss the challenges that remain to be met before this field of research can generate knowledge which can impact everyday clinical practice.