tbuckley/cabot-search huggingface dataset:
THU0463 EXPECTATIONS OF TREATMENT RESULT OF KNEE OSTEOARTHRITIS PATIENTS TREATED WITH A TOTAL KNEE ARTHROPLASTY. THE INFLUENCE OF DEMOGRAPHIC FACTORS, PAIN, PERSONALITY TRAITS, PHYSICAL AND PSYCHOLOGICAL STATUS
Authors: J.J. Tolk, R.P.A. Janssen, T.M. Haanstra, M. (Marieke) C. van der Steen, S.M.A. Bierma-Zeinstra, Max Reijman
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Unrealistic preoperative expectations have a strong influence on the outcome after total knee arthroplasty (TKA). More insight into determinants of the level of expectations is useful in identifying patients at risk for unrealistic expectations. This information can be used in optimizing pre-operative expectation management. <h3>Objectives:</h3> The aim of the current study was to analyze to what extent pre-operative outcome expectations of TKA patients are determined by psychological factors, demographic factors, pain, physical function and general health status. <h3>Methods:</h3> A cross-sectional analysis of 204 patients with symptomatic and radiographic knee OA, scheduled for primary TKA was conducted. Outcome expectations were measured using the Hospital for Special Surgery knee replacement expectations survey. Independent variables included were age, sex, body mass index and patient reported outcome measures for pain, physical function, quality of life, anxiety, depression, catastrophizing, optimism and pessimism. Multiple linear regression analyses were used to evaluate associations between these variables and pre-operative outcome expectations <h3>Results:</h3> The mean overall survey score on the HSS-KRES was 70.9 (SD 17.9). Distribution of expectation scores is shown in Figure 1. Highest expectations were scored for pain relief and improvement of the ability to walk of short and medium distances. Patients had the lowest expectations for improvement in kneeling, squatting, psychological well-being sexual activity and the ability to have paid work. Female sex, higher age, higher depression score and duration of complaints &gt; 50 months showed to be significant predictors of lower expectations for the treatment outcome after TKA. Baseline pain and function scores were not related to the level of pre-operative expectations. <h3>Conclusion:</h3> In conclusion young, male patients with a short duration of complaints might be at risk of having too high expectations of the treatment result. On the contrary patients with depressive symptoms are more likely to have low expectations, with a potential negative influence on their treatment result. The present study aids in identifying patients at risk for having either too high or too low expectations. This knowledge can be utilized in individualized expectation management interventions. <h3>Acknowledgement:</h3> We would like to thank C. van Doesburg and H. Kox for their support in data collection and study procedures. <h3>Disclosure of Interests:</h3> None declared
Biocompatible MoS2/PDA-RGD coating on titanium implant with antibacterial property via intrinsic ROS-independent oxidative stress and NIR irradiation
Authors: Zhang Yuan, Bailong Tao, Ye He, Ju Liu, Chuanchuan Lin, Xinkun Shen, Yao Ding, Yonglin Yu, Caiyun Mu, Peng Liu, Kaiyong Cai
Journal: Biomaterials (2019)

To inhibit bacterial infection in situ and improve osseointegration are essentially important for long-term survival of an orthopedic implant, in particular for infection-associating revision surgery. Herein, we fabricate a functional molybdenum disulfide (MoS2)/polydopamine (PDA)-arginine-glycine-aspartic acid (RGD) coating on titanium (Ti) implant to address above concerns simultaneously. The coating not only improved the osteogenesis of mesenchymal stem cells (MSCs), but also endowed Ti substrates with effective antibacterial ability when exposing to near-infrared (NIR) irradiation. It accelerated glutathione (GSH) oxidation via photothermal energy and induced intrinsic ROS-independent oxidative stress damage deriving from MoS2 nanosheets. The results displayed that RGD-decorated MoS2 nanosheets significantly increased the cellular osteogenic behaviors of MSCs via up-regulating osteogenesis-related genes (ALP, Runx2, Col I and OCN) in vitro. Moreover, the functionalized Ti substrates demonstrated great antibacterial efficiency of over 92.6% inhibition for S. aureus and E. coli under NIR-irradiation. Hyperthermia induced by photothermal effect accelerated the GSH consumption and ROS-independent oxidative stress destroyed the integrity of bacteria membranes, which synergistically led to protein leakage and ATP decrease. Furthermore, co-culture experiment showed that S. aureus contamination was efficiently cleaned from MoS2/PDA-RGD surface after NIR photothermal treatment, while MSCs adhered and proliferated on the MoS2/PDA-RGD surface. In an S. aureus infection model in vivo, MoS2/PDA-RGD modified Ti rods killed bacteria with an efficiency of 94.6% under NIR irradiation, without causing damage to normal tissue. More importantly, the MoS2/PDA-RGD modified Ti implants accelerated new bone formation in comparison with TNT implants in vivo.
PS913 ROLE OF CHOROID PLEXUS STROMA IN TUMOUR CHEMORESISTANCE: A SANCTUARY FOR LEUKAEMIA CELLS IN THE CENTRAL NERVOUS SYSTEM
Authors: L.M. Fernández‐Sevilla, J. Valencia, M.A. Flores, A. Fraile‐Ramos, E. Jiménez, R. Sacedón, M. Ramírez, A. Varas, Á. Vicente
Journal: HemaSphere (2019)

Background: Central Nervous System (CNS) relapses are still one of the main causes of morbimortality in childhood acute lymphoblastic leukaemia (ALL) patients despite the reduction achieved by CNS‐directed prophylactic chemotherapy. Although CNS colonization by ALL cells has been already associated to both increased survival and enhanced chemoresistance of blasts to intrathecal therapy, the mechanisms of protection and tumour cell maintenance in this compartment, as well as the interactions established between ALL and CNS cells, still need to be better understood. Aims: We propose in vivo and in vitro studies aimed at determining the location of leukaemia cells in the choroid plexus (CP) and the relevance of their interaction with stromal fibroblastic cells to create a tumour supportive microenvironment. Also, we explore the contribution of stromal cells to the ALL chemoresistance. Methods: Brain histopathology evaluation of immunodeficient NSG mice transplanted with human primary ALL cells or the Nalm‐6 cell line was performed by using electron and fluorescence microscopy. Leukemic co‐cultures with human CP cells in the presence or absence of different concentrations of chemotherapeutic drugs were used for viability assays. Changes in CP microenvironment were further tested by RT‐qPCR, flow cytometry, ELISA and CBA assays. Results: The histological analysis of a xenograft model of ALL revealed the presence of leukaemic cells not only in the cerebral ventricles floating in the cerebrospinal fluid, but also interacting with the CP epithelium and within the CP stroma of those animals with CNS infiltration. The proximity of ALL cells to CP capillaries suggests they may easily enter through this fenestrated endothelium. Evaluation of interactions between leukaemic cells and stromal cells showed an upregulated expression of very late antigen‐4 (VLA‐4) in ALL cells and vascular cell adhesion molecule (VCAM1) in CP fibroblasts. Furthermore, in these co‐cultures, ALL cells exhibited a reduced cell proliferation and an enhanced cell viability following treatment with chemotherapeutic agents. However, the blockade of VCAM1‐VLA‐4 interaction was found to impair those effects suggesting that VCAM1‐VLA‐4 interactions are, at least in part, responsible of protecting leukemic cells from cell death. Summary/Conclusion: Choroid plexus is proposed as a possible sanctuary for leukemic cells. There, ALL cells may remain attached to fibroblasts in a dormant state and protected from intrathecal chemotherapy treatment, thus favouring later relapses.
Abstract 17557: Two Different Medical Direction for Airway Management in a Single City Did Not Affect Outcome of Out-of-Hospital Cardiac Arrest Patients
Authors: Hiromichi Naito, Tetsuya Yumoto, Hiroki Maeyama, Kohei Tsukahara, Yukihito Okazaki, Takeshi Mikane, Clifton W Callaway, Atsunori Nakao
Journal: Circulation (2017)

Introduction: Advanced airways are used to optimize oxygen delivery during cardiac arrest. However, the effectiveness of advanced airways (endotracheal intubation: ETI or laryngeal tube: LT) over b...
Trends in the Laboratory Detection of Rotavirus Before and After Implementation of Routine Rotavirus Vaccination — United States, 2000–2018
Authors: Benjamin D. Hallowell, Umesh D. Parashar, Aaron Curns, Nicholas P. DeGroote, Jacqueline E. Tate
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Before the introduction of rotavirus vaccine in the United States in 2006, rotavirus infection was the leading cause of severe gastroenteritis among U.S. children (1). To evaluate the long-term impact of rotavirus vaccination on disease prevalence and seasonality in the United States, CDC analyzed national laboratory testing data for rotavirus from laboratories participating in CDC's National Respiratory and Enteric Viruses Surveillance System (NREVSS) during the prevaccine (2000-2006) and postvaccine (2007-2018) periods. Nationally, the median annual percentage of tests positive for rotavirus declined from 25.6% (range = 25.2-29.4) in the prevaccine period to 6.1% (range = 2.6-11.1) in the postvaccine period. When compared with the prevaccine period, the postvaccine period saw declines in the annual peak in rotavirus positivity from a median of 43.1% (range = 43.8-56.3) to a median of 14.0% (range = 4.8-27.3) and in the season duration from a median of 26 weeks (range = 23-27) to a median of 9 weeks (range = 0-18). In the postvaccine period, a biennial pattern emerged, with alternating years of low and high rotavirus activity. Implementation of the rotavirus vaccination program has substantially reduced prevalence of the disease and altered seasonal patterns of rotavirus in the United States; these changes have been sustained over 11 seasons after vaccine introduction. Ongoing efforts to improve coverage and on-time vaccination (2) can help maximize the public health impact of rotavirus vaccination.
The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans
Authors: Pénélope A. Andreux, William Blanco-Bose, Dongryeol Ryu, Frédéric Burdet, Mark Ibberson, Patrick Aebischer, Johan Auwerx, Anurag Singh, Chris Rinsch
Journal: Nature Metabolism (2019)
THU0591 SALIVARY GLAND INVOLVEMENT DISPARITIES IN CLINICAL AND LABORATORY CHARACTERISTICS OF IGG4-RELATED DISEASE: A RETROSPECTIVE STUDY OF 428 PATIENTS
Authors: Yanying Liu, Miao Xue, Zhenfan Wang, Qiaozhu Zeng, Limin Ren, Yanyan Zhang, Shanshan Zhang, Yi Wang, Danhua Shen, Changsheng Xia, Guangyan Yu, LI Zhan-Guo
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> IgG4 related disease (IgG4-RD) is recently recognized as a fibro-inflammatory condition featured by tumefactive lesions in multiple organs, among which salivary gland is one of the most commonly involved sites. Some previous studies have suggested that salivary gland involved IgG4-RD (IgG4-RD SG+) patients may present different features compared to IgG4-RD patients without salivary gland lesions (IgG4-RD SG-), however, only dozens of patients were examined and the comparison has not been studied in detail. <h3>Objectives</h3> We undertook this study to compare detailed demographic, clinical and laboratory characteristics of IgG4-RD patients with salivary gland lesion (IgG4-RD SG+) and salivary gland free IgG4-RD (IgG4-RD SG-) in a large cohort. <h3>Methods</h3> We carried out a retrospective review of the medical records of 428 cases of IgG4-RD diagnosed at Peking University People's hospital between March 2006 and May 2018. <h3>Results</h3> Among 428 patients, 249 had salivary gland affected. IgG4-RD SG+ patients showed younger age at disease onset and diagnosis, and a longer interval between symptom onset and diagnosis. IgG4-RD SG+ group involved more female patients, and allergic diseases were more common in this group. In terms of organ involvement, IgG4-RD SG+ group were more frequently presented with lacrimal gland involvement, while lymph node, retroperitoneal fibrosis, pancreas, biliary system, kidney, and aorta were more prominent in IgG4-RD SG- group. In addition, the serum IgG4 levels, IgG4/IgG ratio and IgE level were significantly higher in IgG4-RD SG+ patients. Patients with eosinophilia were more common in IgG4-RD SG+ group, while elevated ESR, CRP, and positive ANA were more common in IgG4-RD SG- group. <h3>Conclusion</h3> We have revealed demographic, clinical and laboratory differences between IgG4-RD SG+ and SG- patients, which indicated potential differences in pathogenesis and important implications for the diagnosis and management of these two phenotypes. <h3>References</h3> [1] Kamisawa T, Zen Y, Pillai S, Stone JH. IgG4-related disease. Lancet. 2015;385(9976):1460-71. [2] Moriyama M, Ohta M, Furukawa S, Mikami Y, Tanaka A, Maehara T, et al. The diagnostic utility of labial salivary gland biopsy in IgG4-related disease. Mod Rheumatol. 2016;26(5):725-9. [3] Higgs BW, Liu Y, Guo J, Sebastian Y, Morehouse C, Zhu W, et al. High-throughput RNA sequencing reveals distinct gene signatures in active IgG4-related disease. Sci Rep. 2017;7(1):17567. [4] Inoue D, Yoshida K, Yoneda N, Ozaki K, Matsubara T, Nagai K, et al. IgG4-related disease: dataset of 235 consecutive patients. Medicine (Baltimore). 2015;94(15):e680. <h3>Disclosure of Interests</h3> None declared
In older patients with UTIs, deferring or not prescribing antibiotics was linked to adverse outcomes
Authors: John C. O’Horo, Aaron J. Tande
Journal: Annals of Internal Medicine (2019)

Source Citation Gharbi M, Drysdale JH, Lishman H, et al. Antibiotic management of urinary tract infection in elderly patients in primary care and its association with bloodstream infections and all cause mortality: population based cohort study. BMJ. 2019;364:l525. 30814048
PS1200 IDENTIFICATION OF MUTATIONS IN RED CELL MEMBRANOPATHIES USING NGS‐TARGETED SEQUENCING PANEL
Authors: T. More, P. Kedar, P. Warang, R. Devendra, M. Madkaikar
Journal: HemaSphere (2019)

Background: Red cell membranopathies refers to genetically and phenotypically heterogenous disorders due to defects in red cell membrane and skeletal proteins. Phenotypes vary from severe transfusion‐dependent hemolytic anemia to fully compensated hemolysis. Causative genes implicated in RBC membranopathies are numerous, making a gene‐by‐gene approach time consuming, expensive and labor intensive. Use of Next Generation Sequencing (NGS) targeted sequencing panel can expedite the molecular diagnosis after routine laboratory tests. Aims: This study aimed at defining a strategy for effective diagnosis of RBC membrane defects and identification of pathogenic mutations associated with the disease. Methods: Patients with clinical symptoms of hemolytic anemia, jaundice, hepatosplenomegaly and some requiring frequent blood transfusions were recruited in this study. Blood was collected from the patients after informed consent. Peripheral blood smear examination and flow cytometric based EMA binding test were performed and identification of mutations in red cell membrane proteins was done using NGS‐targeted sequencing panel. The relationship between gene mutations and clinical phenotypes was analyzed by In silico prediction tools such as SIFT, Polyphen2. Results: We identified mutations in 21 cases of Hemolytic Anemia (HA) in membrane protein‐coding genes using NGS‐targeted sequencing panel. Five Hereditary Spherocytosis (HS) patients were diagnosed with mutations in ankyrin (ANK1) gene, 3 patients with alpha spectrin (SPTA1) gene and 4 patients with beta spectrin (SPTB) gene. Band 3 (SLC4A1) gene mutations was identified in two HS cases and in 2 with dRTA cases. Five patients showed mutation in PIEZO1 gene causing Hereditary xerocytosis (HX). Twelve novel mutations were found as shown in Table 1. Summary/Conclusion: RBC membranopathies showed highly varied etiology. Our experience demonstrates the high diagnostic yield of NGS for molecular diagnosis of RBC membrane disorders associated with defects in large genes. Timely detection of the disorder not only offers therapeutic benefits for our patients but is likely to help in genetic counseling and future antenatal diagnosis, if required. image
15-Deoxy-Δ12,14-Prostaglandin J<sub>2</sub>Reinforces the Anti-Inflammatory Capacity of Endothelial Cells With a Genetically Determined NO Deficit
Authors: Ivelina Urban, Martin Turinsky, Sviatlana Gehrmann, Jakob Morgenstern, Maik Brune, Moritz R. Milewski, Andreas H. Wagner, Cordula Rumig, Thomas Fleming, Florian Leuschner, Christian A. Gleissner, Markus Hecker
Journal: Circulation Research (2019)

Fluid shear stress (FSS) maintains NOS-3 (endothelial NO synthase) expression. Homozygosity for the C variant of the T-786C single-nucleotide polymorphism of the NOS3 gene, which solely exists in humans, renders the gene less sensitive to FSS, resulting in a reduced endothelial cell (EC) capacity to generate NO. Decreased bioavailability of NO in the arterial vessel wall facilitates atherosclerosis. Consequently, individuals homozygous for the C variant have an increased risk for coronary heart disease (CHD).At least 2 compensatory mechanisms seem to minimize the deleterious effects of this single-nucleotide polymorphism in affected individuals, one of which is characterized herein.Human genotyped umbilical vein ECs and THP-1 monocytes were used to investigate the role of 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) in vitro. Its concentration in plasma samples from genotyped patients with CHD and age-matched CHD-free controls was determined using quantitative ultraperformance LC-MS/MS. Exposure of human ECs to FSS effectively reduced monocyte transmigration particularly through monolayers of CC-genotype ECs. Primarily in CC-genotype ECs, FSS elicited a marked rise in COX (cyclooxygenase)-2 and L-PGDS (lipocalin-type prostaglandin D synthase) expression, which appeared to be NO sensitive, and provoked a significant release of 15d-PGJ2 over baseline. Exogenous 15d-PGJ2 significantly reduced monocyte transmigration and exerted a pronounced anti-inflammatory effect on the transmigrated monocytes by downregulating, for example, transcription of the IL (interleukin)-1β gene (IL1B). Reporter gene analyses verified that this effect is due to binding of Nrf2 (nuclear factor [erythroid-derived 2]-like 2) to 2 AREs (antioxidant response elements) in the proximal IL1B promoter. In patients with CHD, 15d-PGJ2 plasma levels were significantly upregulated compared with age-matched CHD-free controls, suggesting that this powerful anti-inflammatory prostanoid is part of an endogenous defence mechanism to counteract CHD.Despite a reduced capacity to form NO, CC-genotype ECs maintain a robust anti-inflammatory phenotype through an enhanced FSS-dependent release of 15d-PGJ2.
Chromosome 12p Amplification in Triple-Negative/<i>BRCA1-</i>Mutated Breast Cancer Associates with Emergence of Docetaxel Resistance and Carboplatin Sensitivity
Authors: Jorge Gómez-Miragaya, Ander Díaz-Navarro, Raul Tonda, Sergi Beltran, Luis Palomero, Marta Palafox, Lacey E. Dobrolecki, Chen Huang, Suhas Vasaikar, Bing Zhang, Gerburg M. Wulf, Alejandro Collado-Sole, Eva M. Trinidad, Purificación Muñoz, Laia Paré, Aleix Prat, Alejandra Bruna, Carlos Caldas, Joaquín Arribas, María Teresa Soler-Monso, Anna Petit, Judith Balmaña, Cristina Cruz, Violeta Serra, Miguel Angel Pujana, Michael T. Lewis, Xose S. Puente, Eva González-Suárez
Journal: Cancer Research (2019)

Taxanes are the mainstay of treatment in triple-negative breast cancer (TNBC), with
A Missed Opportunity to Address a National Shame
Authors: Gary L. Freed
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Investigating genes and micro-RNAs that may predict clinical benefits of anti-CTLA-4 therapy.
Authors: Jianjun Gao, Hong Chen, Derek Ng Tang, Padmanee Sharma
Journal: Journal of Clinical Oncology (2013)

3043 Background: Blockade of T cell co-inhibitory receptor CTLA-4 with a monoclonal antibody, ipilimumab, has led to augmented anti-tumor immune responses, clinical benefit, and FDA approval of ipilimumab for the treatment of metastatic melanoma. Only a subset of patients benefit from anti-CTLA-4 therapy. In order to identify genes, microRNAs, and signaling pathways that are modulated by anti-CTLA-4, which may be used for potential correlation with clinical outcomes or provide additional targets for therapy, we purified and analyzed CD4 + T cells from patients treated with anti-CTLA-4 for changes in gene and microRNA expression profiles. Methods: On an IRB-approved phase Ia presurgical clinical trial, 6 patients with localized bladder cancer were treated with two doses of ipilimumab at 10 mg/kg at weeks 1 and 4. Pre-therapy and post-therapy blood samples were collected for CD4 + T cell enrichment by using the T cell isolation kit from Miltenyi Biotec (Auburn, CA). RNA and microRNA were isolated from purified CD4 + T cells using Qiagen RNA isolation kits for Affymetrix microarray and micoRNA array analyses. Microarray data were then analyzed using Ingenuity iReport (Redwood City, CA). RT-PCR and Western blot were used to confirm significant changes in genes or pathways identified in microarray analyses. Results: Anti-CTLA-4 treatment resulted in modulation of differentially expressed genes (DEGs). After two doses of treatment, anti-CTLA-4 significantly changed expression of a total of 289 DEGs. Further pathway analyses indicated that anti-CTLA-4 induced a variety of pathways involved in cell proliferation and immune modulation, including PI3K/AKT, MAP/ERK, and IFN/JAK-STAT pathways. We have also identified 9 microRNAs that potentially regulate the expression of genes changed by anti-CTLA-4 therapy. Conclusions: Anti-CTLA-4 treatment results in modulation of multiple genes, microRNAs, and pathways, which likely play important roles in anti-tumor immune responses. We are currently testing a number of these identified genes and microRNAs as potential predictive biomarkers for anti-CTLA-4 therapy in a small cohort of patients who had complete response vs. progression of disease after anti-CTLA-4 therapy.
In normoxemic suspected MI, oxygen therapy did not reduce all-cause mortality or HF hospitalization at 2 years
Authors: Jonathan M. Kirschner, Benton R. Hunter
Journal: Annals of Internal Medicine (2019)

Source Citation Jernberg T, Lindahl B, Alfredsson J, et al; DETO2X-SWEDEHEART Investigators. Long-term effects of oxygen therapy on death or hospitalization for heart failure in patients with suspected acute myocardial infarction. Circulation. 2018;138:2754-62. 30767504