tbuckley/cabot-search huggingface dataset:
Osmoregulation Performance and Kidney Transplant Outcome
Authors: Manal Mazloum, Jordan Jouffroy, François Brazier, Christophe Legendre, Antoine Neuraz, Nicolas Garcelon, Dominique Prié, Dany Anglicheau, Frank Bienaimé
Journal: Journal of the American Society of Nephrology (2019)

Significance Statement Although hyponatremia is a risk factor for adverse events in CKD and in kidney transplant recipients—who may have impaired urine dilution capability—it is unclear what effects subtler alterations in osmoregulation may have on outcomes in this population. The authors investigated the prevalence of osmoregulation defects in a large, single-center prospective cohort of kidney transplant recipients. They found that a large proportion of the transplant recipients (unlike healthy controls) did not maintain constant plasma sodium in response to sustained moderate water loading. In addition, the magnitude of this osmoregulation defect independently predicted deterioration of kidney function (lower measured GFR at 12 months) and allograft loss. Understanding the basis of defective osmoregulation may provide novel therapeutic targets to prevent kidney allograft dysfunction. Background Kidney transplant recipients have an impaired ability to dilute urine but seldom develop baseline hyponatremia before ESRD. Although hyponatremia is a risk factor for adverse events in CKD and in kidney transplant recipients, it remains unclear whether subtler alterations in osmoregulation performance are associated with outcome. Methods We studied a single-center prospective cohort of 1258 kidney transplant recipients who underwent a water-loading test 3 months after transplant to determine osmoregulation performance. Measured GFR (mGFR) was performed at the same visit. A group of 164 healthy candidates for kidney donation served as controls. We further evaluated the association of osmoregulation performance with transplantation outcomes and subsequent kidney function. Results Unlike controls, most kidney transplant recipients failed to maintain plasma sodium during water loading (plasma sodium slope of −0.6±0.4 mmol/L per hour in transplant recipients versus −0.12±0.3 mmol/L per hour in controls; P &lt;0.001). Steeper plasma sodium reduction during the test independently associated with the composite outcome of all-cause mortality and allograft loss (hazard ratio [HR], 1.73 per 1 mmol/L per hour decrease in plasma sodium; 95% confidence interval [95% CI], 1.23 to 2.45; P =0.002) and allograft loss alone (HR, 2.04 per 1 mmol/L per hour decrease in plasma sodium; 95% CI, 1.19 to 3.51; P =0.01). The association remained significant in a prespecified sensitivity analysis excluding patients with hyperglycemia. In addition, a steeper plasma sodium slope 3 months after transplantation independently correlated with lower mGFR at 12 months ( β =1.93; 95% CI, 0.46 to 3.41; P =0.01). Conclusions Reduced osmoregulation performance occurs frequently in kidney transplant recipients and is an independent predictor of renal outcome.
PF398 KNOCKDOWN OF LASP1 IN CXCR4 EXPRESSING CML CELLS PROMOTES CELL PERSISTENCE, PROLIFERATION AND TKI RESISTANCE
Authors: A.B. Herrmann, M.‐L. Müller, M.F. Orth, J.P. Müller, A. Zernecke, A. Hochhaus, T. Ernst, E. Butt, J.J. Frietsch
Journal: HemaSphere (2019)

Background: Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder characterized by a fusion protein, the constitutively active BCR–ABL tyrosine kinase, leading to expansion of differentiated granulocytes. Although tyrosine kinase inhibitors (TKI) have significantly improved patient care, minimal residual disease (MRD) remains a clinical challenge. Recently, the LIM and SH3 domain protein 1 (LASP1) has been identified as a novel BCR–ABL substrate, which is hyperphosphorylated at Y171 in CML cells. LASP1 is associated with proliferation, migration, tumorigenesis and chemoresistance. Furthermore, the protein can bind to the chemokine receptor 4 (CXCR4), known to be involved in homing of leukemic stem cells and relapse of CML patients. Aims: These two LASP1‐influenced disease promoting effects prompted us to investigate the effect of LASP1 and CXCR4 on processes involved in initiation, progression and maintenance of CML in order to identify and exploit BCR‐ABL‐independent pathways and other extrinsic factors, which may help to eradicate MRD. Methods: Using a CRISPR/Cas9‐based LASP1 knockout system and a lentivirus‐mediated CXCR4 overexpression in the CML cell line K562, the biological influence of CXCR4 and LASP1 was characterized in apoptosis, viability, cell cycle, migration and adhesion assays in the presence of nilotinib. Furthermore, comprehensive transcriptomic microarray data from a public database, immunofluorescence imaging and biochemical analysis were employed to elucidate the roles of LASP1 in CML. Results: Microarray analysis revealed that LASP1 is significantly lower expressed in samples of CML patients not responding to imatinib therapy. The in vitro data indicate that not only the overexpression of CXCR4, but also knockdown of LASP1 contributed to proliferation, reduced apoptosis and impaired cell migration. Additionally, we show that LASP1 depletion leads to decreased cytokine release and reduced natural killer (NK)‐cell mediated cytotoxicity. Finally, we describe a phosphorylation‐dependent loss of direct binding between pLASP1‐Y171 and CXCR4 in CML, which most likely results in receptor destabilization. Summary/Conclusion: Taken together, our results indicate that in CML, reduced levels of LASP1 alone and especially in combination with high CXCR4 expression contribute to TKI resistance and stem cell persistence.
Abstract 19014: Significant Major Complication Occurrence in Extracting Riata Compared to Sprint Fidelis Leads
Authors: Harshal Sheth, Michael Broman, Amit Mehrotra, Dina Sparano, John Shin, Joshua Moss, Hemal Nayak, Martin Burke
Journal: Circulation (2013)

Introduction: Medtronic Sprint Fidelis and St. Jude Medical Riata defibrillator leads have been subject to class I recall. Extraction of these leads is a complex clinical decision with a case by case analysis. We compared the difference in the occurrence of major complications to understand the morbidity and mortality risk extracting either of these leads. Methods: We retrospectively reviewed 86 consecutive cases (59 men, 27 women) of Sprint Fidelis (n = 72) or Riata (n = 14) lead extraction from 2007 to 2012 and compared the rate of major complications between the two. The only exclusion criteria were pocket infection or endocarditis as an indication for extraction. Major complications were defined as death, cardiac/vascular avulsion or tear, cardiac tamponade requiring pericardiocentesis and/or stroke. Minor complications were defined as pericardial effusion not requiring intervention, pneumothorax and/or hematoma at surgical site. Results: The main indications for extraction included lead fracture (n = 36, 42%) and elective removal at pulse generator change (n = 28, 33%). There was a significant difference in occurrence of major complications with extraction of Riata as compared to Sprint Fidelis leads (2/14 vs. 1/72, p = 0.016). All 3 major complications occurred in dual coil leads. Within the Riata family of leads, there was no statistical difference in occurrence of major complications (1500 series 2/7 vs. 7000 series 0/7, p = 0.127). There was also no difference in patients with component failure versus prophylactic extraction (1/36 vs. 2/50, p = 0.76). Conclusions: Major complication occurrences in extraction are higher with Riata as compared with Sprint Fidelis leads based on this large, single-center experience. There was no statistical difference between the 8-Fr 1500 and 7-Fr 7000 Riata series of leads. Further investigation is needed to help guide clinical decision-making for patients presenting with these recalled leads.
Carlos II
Journal: JAMA (1977)

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
Understanding the Nature and Extent of Pharmaceutical Industry Payments to Nonphysician Clinicians
Authors: Emily A. Karanges, Quinn Grundy, Lisa Bero
Journal: JAMA Internal Medicine (2019)

be surprised that many types of expected services (eg, emergency department, cardiology, and neurology) may not be available.Hospitals that provide comprehensive services are more likely to receive "nonelite" ratings, in part because of challenges related to communication and responsiveness among more complex patient populations.The fact that it is difficult for hospitals providing a wider range of services to achieve 5-star ratings may suggest potential limitations to the star rating system as it is currently constructed.
THU0400 COMPLICATIONS OF ANTERIOR UVEITIS ASSOCIATED WITH HLA-B27 ANTIGEN IN PATIENTS WITH AND WITHOUT SPONDYLOARTHRITIS
Authors: Irina Razumova, Alla Godzenko, Irina Guseva
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> HLA-B27- associated anterior uveitis (AU) can be an isolated disease or part of а systemic inflammatory process, such as spondyloarthritis. Differences in the outcome of uveitis with and without spondyloarthritisare still under researh. <h3>Objectives</h3> To compare the incidence of complications in HLA-B27- associated anterior uveitis patients with and without spondyloarthritis (SpA). <h3>Methods</h3> 189 patients with HLA-B27- associated anterior uveitis were observed in Research Institute of Eye Disease for 10 years. The pts were underwent standard ophthalmological examination, and, if necessary, computer perimetry, ultrasound examination (B-scan.), optical coherence tomography of the retina and optic nerve (OCT), fluorescence fundus angiography (FAGD) and electrophysiological studies (EFI). All pts were examined for clinical and imaging signs of SpA: inflammatory back pain, arthritis, enthesitis, sacroiliitis. Different variants of SpA were diagnosed in 108 pts: ankylosing spondylitis – in 48 (44,4%), reactive arthritis – in 9 (8,3%), psoriatic arthritis - in 9 (8,3%), inflammatory bowel disease – in 2(1,9%), juvenile SpA – in 4 (3,7%), undifferented SpA - in 36 (33,3%). In 81 pts SpA was not confirmed: 11 had a viral infection (13,5%), 7- bacterial infection (8,6%), 1 (1,2%)-multiple sclerosis, 3 (3,7%) -psoriasis, 59 (72,8%)- idiopathic AU. <h3>Results</h3> Complications were identified in 74 of 108 (68,5%) pts – 147 eyes in SpA-group and in 39of 81(48,1%) – 110 eyes in group without SpA. Cataract was identified in 89 (60,5%) of 147 eyes in SpA-group and in 35(1,8%) of 110 eyes in group without SpA, p=0,0001;glaucoma – in 28 of 147 eyes (19,0%) in SpA-group and 8 of 110 eyes (7,3%) in group without SpA, p=0,005; synechia - in 24(16,3%) and in 8 (7,3%) respectively, p=0,021;vitreous destruction - in 59(40,1%) and in 26 (23,6%), p=0,005. Maculopathy, оptic atrophy, сorneal degeneration, panuveitis were observed more often in SpA-group, but the differences were not significant. Combinations of several complications were detected in 59 (40,1%) in SpA-group and in 31 (28,2%) in group without SpA, p=0,03. <h3>Conclusion</h3> Complications of HLA-B27- associated AU were identified more often in pts with SpA than without SpA (the majority of which was idiopathic AU). It confirms the effect of systemic inflammatory disease on the severity of uveitis. <h3>Reference</h3> [1] Yang P, Wan W, Du L, et al. Clinical features of HLA-B27-positive acute anterior uveitis with or without ankylosing spondylitis in a Chinese cohort. Br J Ophthalmol. 2018Feb;102(2):215-219. doi: 10.1136/bjophthalmol-2016-309499. Epub 2017 Jun 12 <h3>Disclosure of Interests</h3> None declared
Multiple roles of Bet v 1 ligands in allergen stabilization and modulation of endosomal protease activity
Authors: Wai Tuck Soh, Lorenz Aglas, Geoffrey A. Mueller, Stefanie Gilles, Richard Weiss, Sandra Scheiblhofer, Sara Huber, Tamara Scheidt, Peter M. Thompson, Peter Briza, Robert E. London, Claudia Traidl‐Hoffmann, Chiara Cabrele, Hans Brandstetter, Fatima Ferreira
Journal: Allergy (2019)

Over 100 million people worldwide suffer from birch pollen allergy. Bet v 1 has been identified as the major birch pollen allergen. However, the molecular mechanisms of birch allergic sensitization, including the roles of Bet v 1 and other components of the birch pollen extract, remain incompletely understood. Here, we examined how known birch pollen-derived molecules influence the endolysosomal processing of Bet v 1, thereby shaping its allergenicity.We analyzed the biochemical and immunological interaction of ligands with Bet v 1. We then investigated the proteolytic processing of Bet v 1 by endosomal extracts in the presence and absence of ligands, followed by a detailed kinetic analysis of Bet v 1 processing by individual endolysosomal proteases as well as the T-cell epitope presentation in BMDCs.We identified E1 phytoprostanes as novel Bet v 1 ligands. Pollen-derived ligands enhanced the proteolytic resistance of Bet v 1, affecting degradation kinetics and preferential cleavage sites of the endolysosomal proteases cathepsin S and legumain. E1 phytoprostanes exhibited a dual role by stabilizing Bet v 1 and inhibiting cathepsin protease activity.Bet v 1 can serve as a transporter of pollen-derived, bioactive compounds. When carried to the endolysosome, such compounds can modulate the proteolytic activity, including its processing by cysteine cathepsins. We unveil a paradigm shift from an allergen-centered view to a more systemic view that includes the host endolysosomal enzymes.
Abstract 12708: Similar Risk of Heart Failure Hospitalization in MADIT-RIT Programming Arms
Authors: Robert E Goldstein, Mark C Haigney, Edward M Dwyer, Henry Greenberg, Scott McNitt, Wojciech Zareba, Valentina Kutyifa, Arthur J Moss
Journal: Circulation (2015)

Background: In MADIT-RIT (Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy), we reported a significant reduction in inappropriate ICD therapy and mortality with novel ICD programming, either a high-rate cut-off (VT zone ≥ 200 bpm, Arm B) or 60-sec delayed therapy in the VT zone 170-199 bpm (Arm C), as compared to conventional programming (VT zone&gt;170 bpm, Arm A). However, the effect of novel ICD programming on heart failure (HF) events has not been investigated. Methods: In MADIT-RIT patients (n=1500), we assessed risk of hospitalization with heart failure (HF) in the three programming arms. Brief summaries of each hospitalization were independently reviewed by three experienced cardiologists and HF events identified according to pre-specified criteria. Discrepancies were resolved by a fourth cardiologist. Kaplan-Meier cumulative probabilities and multivariable Cox hazards regression analyses were performed. Results: There was a similar probability of HF hospitalization (p=0.341) and HF hospitalization or death (p=0.207) in all three programming arms in MADIT-RIT (Figure). There were no differences in HF hospitalization in Arm B vs. A (HR=0.91, 95%CI: 0.63-1.33, p=0.629) or Arm C vs. A (HR=1.20, 95%CI: 0.84-1.72, p=0.310) after multivariable adjustments for age, NYHA class, diabetes, ICD vs. CRT-D, ejection fraction, and ischemic vs. non-ischemic cardiomyopathy. Similarly, there were no differences in HF or death in Arm B vs. A (HR=0.78, 95%CI: 0.56-1.10, p=0.154), or in Arm C vs. A (HR=1.06, 95%CI: 0.77-1.45, p=0.723) after multivariable adjustments. Risk of multiple hospitalizations was also the similar in the three programming arms. Conclusions: In MADIT-RIT, the mortality benefit seen with novel ICD programming was not accompanied by reduction in heart failure events. Conversely, greater mortality risk with conventional ICD programming was not associated with increased risk of heart failure hospitalization.
Dual-responsive, Methotrexate-loaded, Ascorbic acid-derived Micelles Exert Anti-tumor and Anti-metastatic Effects by Inhibiting NF-κB Signaling in an Orthotopic Mouse Model of Human Choriocarcinoma
Authors: Lili Wei, Chenyuan Wang, Xianjue Chen, Bing Yang, Kun Shi, Leah R. Benington, Lee Yong Lim, Sanjun Shi, Jingxin Mo
Journal: Theranostics (2019)

Gestational trophoblastic neoplasia (GTN), the most aggressive form of which is choriocarcinoma, can result from over-proliferation of trophoblasts. Treating choriocarcinoma requires high doses of systemic chemotherapeutic agents, which result in nonspecific drug distribution and severe toxicity. To overcome these disadvantages and enhance chemotherapeutic efficacy, we synthesized redox- and pH-sensitive, self-assembling, ascorbic acid-derived (PEG-ss-aAPP) micelles to deliver the drug methotrexate (MTX). Methods: We developed and tested self-assembling PEG-ss-aAPP micelles, which release their drug cargo in response to an intracellular reducing environment and the acidity of the early lysosome or tumoral microenvironment. Uptake into JEG3 choriocarcinoma cancer cells was examined using confocal microscopy and transmission electron microscopy. We examined the ability of MTX-loaded PEG-ss-aAPP micelles to inhibit metastasis in an orthotopic mouse model of human choriocarcinoma. Results: Drug-loaded micelles had encapsulation efficiency above 95%. Particles were spherical based on transmission electron microscopy, with diameters of approximately 229.0 nm based on dynamic light scattering. The drug carrier responded sensitively to redox and pH changes, releasing its cargo in specific environments. PEG-ss-aAPP/MTX micelles efficiently escaped from lysosome/endosomes, and they were effective at producing reactive oxygen species, strongly inducing apoptosis and inhibiting invasion and migration. These effects correlated with the ability of PEG-ss-aAPP/MTX micelles to protect IκBα from degradation, which in turn inhibited translocation of NF-κB p65 to the nucleus. In an orthotopic mouse model of human choriocarcinoma, PEG-ss-aAPP/MTX micelles strongly inhibited primary tumor growth and significantly suppressed metastasis without obvious side effects. Conclusions: Our results highlight the potential of PEG-ss-aAPP micelles for targeted delivery of chemotherapeutic agents against choriocarcinoma.
Abstract 2157: Characteristics of Late Incomplete Stent Apposition: A Comparison between Sirolimus- and Zotarolimus-Eluting Stents
Authors: Katsuhisa Waseda, Junya Ako, Ichizo Tsujino, Masao Yamasaki, Tomomi Koizumi, Akiyoshi Miyazawa, Yoshihisa Shimada, Paul G Yock, Ian Meredith, Peter J Fitzgerald, Yasuhiro Honda
Journal: Circulation (2007)

Background: Characteristics of late incomplete stent apposition (LISA) in different DES have not been systematically compared. The aim of this study was to clarify the morphometric parameters of LI...
Dampening the fire to prevent surgery- and chemotherapy-induced metastasis
Authors: Esra Güç, Jeffrey W. Pollard
Journal: Journal of Clinical Investigation (2019)

In this issue of the JCI, Panigrahy et al. demonstrate that preoperative administration of the antiinflammatory drug ketorolac or specialized proresolving mediators (SPM) called resolvins increases disease-free survival rates and prevents metastasis after surgery and chemotherapy in mouse models of cancer. The antitumor response was partially mediated by tumor-specific T cell immunity and immunological memory.
<i>Notes from the Field:</i> Administration of Expired Injectable Influenza Vaccines Reported to the Vaccine Adverse Event Reporting System — United States, July 2018–March 2019
Authors: Elisabeth M. Hesse, Beth F. Hibbs, Maria V. Cano
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

During July 11, 2018âMarch 29, 2019, in the United States, the Vaccine Adverse Event Reporting System received 125 reports of 192 patients receiving expired inactivated influenza vaccine during the 2018â19 influenza season.
FRI0677 IMPACT OF COMORBIDITY ON THE USE OF BIOLOGICAL AND TARGETED THERAPY IN RHEUMATIC DISEASES IN THE CLINICAL PRACTICE
Authors: Dmitry Karateev, Hava Hamhoeva, Helen Luchihina, Aminat Tangieva
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Comorbid conditions often accompany rheumatic diseases and can influence the prescription of immunosuppressive therapy. Comorbidity seems to be a factor that is still underestimated in actual practice. <h3>Objectives</h3> To study the influence of comorbidity on the prescription of biological and targeted therapies in patients with rheumatic diseases (RD) in clinical practice. <h3>Methods</h3> We perform a retrospective analysis of comorbidity and prescription of biological and targeted immunosuppressors in a group of in-patients with systemic autoimmune RD in rheumatology department. From January 2018 to January 2019, 218 patients with inflammatory RD hospitalized - 146 (67,5%) women, mean age 50.6±14,6 years. Diagnoses: rheumatoid arthritis - 83 patients, spondyloarthritides – 80, systemic lupus erythematosus – 19, systemic scleroderma - 16, ANCA-associated vasculitides – 10, other conditions – 10 patients. Biologics were used in 117 (53,7%) of patients (anti-TNFs – 64 patients, rituximab – 18, tocilizumab – 16, abatacept – 8, secukinumab – 4, ustekinumab – 4, tofacitinib – 3 patients). We examined patients for comorbidities through careful examination of the history, medical records, and general therapeutic laboratory and instrumental screening. The Charlson comorbidity index calculated for every patient. <h3>Results</h3> 174 (79.8%) patients had at least 1 comorbid condition. The most frequent comorbidities were type2 diabetes (19,5% patients), chronic kidney disease (12,6%), cerebrovascular accidental (11,5%), ischemic heart disease and chronic heart failure (11%), chronic liver disease (7,5%). Mean Charlson index was 2,16±2,05 in total group; it was significantly lower in patients who were treated with biological and targeted therapy (1,64±1,8) than in patients who did not received this therapy (2,76±2,1), p&lt;0,01. Biologics were prescribed in 81,8% of patients without comorbidities, in comparison with 55,3% of patients with Charlson comorbidity index 1 or 2, and 36,3% of patients with Charlson index 3 or more. <h3>Conclusion</h3> Comorbidity has a direct impact on the use of biological and targeted therapy in patients with rheumatic diseases in real clinical practice, limiting the ability to control the activity of the disease. It is necessary to develop a general therapeutic strategy for treating comorbid conditions in patients with rheumatic diseases. <h3>References</h3> [1] Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. Journal of Chronic Diseases. 1987; 40 (5): 373–83 <h3>Disclosure of Interests</h3> Dmitry Karateev Speakers bureau: Pfizer, Novartis, Janssen, Abbvie, Biocad, MSD, BMS, Hava Hamhoeva: None declared, Helen Luchihina Speakers bureau: Pfizer, Abbvie, Biocad, Aminat Tangieva: None declared