tbuckley/cabot-search huggingface dataset:
Abstract 12189: Gender Differences in Intra-Operative Blood Transfusions: Analysis of 54,122 Coronary Artery Bypass (CABG) Procedures
Authors: Samuel Weinstein, Eric Tesdahl, Albert Stammers, Linda B Mongero, Timothy A Dickinson, Yoshiya Toyoda, Rohinton Morris, Michael Firstenberg, Lori J Mosca
Journal: Circulation (2016)

Background/Hypothesis: Women have higher morbidity and mortality associated with CABG procedures than men. The extent intra-operative red blood cell (RBC) transfusions contribute to gender differences in surgical outcomes is not established. We hypothesized that women are at increased risk for RBC transfusions due to lower pre-op hematocrit (Hct) and blood volume, but that other factors may also contribute. Methods: Consecutive, non-reoperative CABG procedures from 189 institutions (2012 -2015) were reviewed. Gender differences and odds ratios for intra-operative transfusion were evaluated with logistic regression models adjusting for age, blood volume (Nadler formula-to normalize for height and weight), procedure acuity, net extracorporeal circuit prime volume, use of retrograde autologous priming, first Hct in OR, nadir Hct on cardiopulmonary bypass (CPB), volume added on CPB, ultra-filtration volume, urine output on CPB, and procedure duration. Results: Among 54,122 patients (25.3% female), 21.9% (n=11,901) received a RBC transfusion. Compared to men, female patients were older (66 yrs vs. 64 yrs, p&lt;.001), had lower blood volumes (4.3L vs. 5.6L, p&lt;.001), and lower pre-op Hct (32.9% vs. 37.2%, p&lt;.001). Transfusion rates were 3-fold higher in women vs. men (45.1% vs 13.7%, p&lt;.001). Even after adjustment for independent predictors of intra-operative transfusion, women remained at increased risk vs men (OR = 1.3, 95% CI = 1.2 -1.4). No gender differences in transfusion rates were observed for Hct 21%-23% (Figure). Conclusions: Women have an increased risk of intra-operative RBC transfusion vs men. After adjusting for height and weight, much of this risk is due to gender differences in pre-op Hct and blood volume, however a residual significant risk remained after adjustment. Perfusion strategies aimed at gender differences may minimize unnecessary transfusions. Future study on the impact of gender on transfusion practice in cardiac surgery is warranted.
Virtual Care as a Specialty
Authors: John F. Pearson, Jorge A. Rodriguez, Charles Safran
Journal: JAMA (2018)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Bortezomib-based induction therapy with high or low-dose dexamethasone in newly diagnosed, transplant-eligible multiple myeloma
Authors: Elias K. Mai, Thomas Hielscher, Uta Bertsch, Jana Schlenzka, Hans J. Salwender, Markus Munder, Christian Gerecke, Ulrich Dührsen, Peter Brossart, Kai Neben, Jens Hillengass, Marc S. Raab, Maximilian Merz, Marc-Andrea Baertsch, Anna Jauch, Dirk Hose, Hans Martin, Hans-Walter Lindemann, Igor W. Blau, Christof Scheid, Katja C. Weisel, Hartmut Goldschmidt
Journal: Leukemia (2018)
Abstract LB-001: Development and evaluation of T-Zap: a novel antibody-drug conjugate for the treatment of Her2 positive breast cancer
Authors: Ricarda M. Hoffmann, Silvia Crescioli, David E. Thurston, Sophia N. Karagiannis
Journal: Cancer Research (2018)

Abstract Background: Breast cancer is the most common type of cancer worldwide and HER2-overexpressing types are especially associated with poor prognosis. Antibody-drug conjugates (ADCs) have been developed as a targeted approach to deliver toxins to cancer cells specifically with the ADC trastuzumab-emtansine (T-DM1) already in clinical use. A novel ADC T-Zap has been developed by linking the antibody trastuzumab to saporin - a ribosome inactivating protein. This study aims to evaluate the novel ADC T-Zap for the treatment of HER2 positive breast cancer. Methods: The plant toxin saporin was linked to the monoclonal antibody tratuzumab via a streptavidin-biotin bridge. Binding kinetics were assessed using flow cytometry, and MTS cell viability assays were performed to compare efficacy to T-DM1. Toxicity towards immune cells was investigated by MTS assays using immune cells. Results: Binding to target cells of T-Zap was confirmed. Comparison of T-Zap efficacy in breast cancer cell lines with and without resistance against trastuzumab showed a trend for higher efficacy of cell killing by T-Zap in trastuzumab resistant cells compared to T-DM1. Toxicity assays revealed no impact of T-Zap on cell viability in immune cells. Conclusions: Cell viability caused by T-Zap was more efficient compared to T-DM1 in the trastuzumab resistant cell line HCC1945. This strengthens the hyposthesis that T-Zap might have potential as new ADC overcoming trastuzumab resistance. Future work will include the development of a specific linker to link trastuzumab to saporin with the aim to develop an ADC that could prove a novel therapeutic agent for the treatment of HER2 positive breast cancer. Citation Format: Ricarda M. Hoffmann, Silvia Crescioli, David E. Thurston, Sophia N. Karagiannis. Development and evaluation of T-Zap: a novel antibody-drug conjugate for the treatment of Her2 positive breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-001.
Exploration of Plasmodium vivax transmission dynamics and recurrent infections in the Peruvian Amazon using whole genome sequencing
Authors: Annie N. Cowell, Hugo O. Valdivia, Danett K. Bishop, Elizabeth A. Winzeler
Journal: Genome Medicine (2018)

Plasmodium vivax poses a significant challenge to malaria elimination due to its ability to cause relapsed infections from reactivation of dormant liver parasites called hypnozoites. We analyzed 69 P. vivax whole genome sequences obtained from subjects residing in three different villages along the Peruvian Amazon. This included 23 paired P. vivax samples from subjects who experienced recurrent P. vivax parasitemia following observed treatment with chloroquine and primaquine. Genomic DNA was extracted from whole blood samples collected from subjects. P. vivax DNA was enriched using selective whole genome amplification and whole genome sequencing. We used single nucleotide polymorphisms (SNPs) from the core P. vivax genome to determine characteristics of the parasite population using discriminant analysis of principal components, maximum likelihood estimation of individual ancestries, and phylogenetic analysis. We estimated the relatedness of the paired samples by calculating the number of segregating sites and using a hidden Markov model approach to estimate identity by descent. We present a comprehensive dataset of population genetics of Plasmodium vivax in the Peruvian Amazonian. We define the parasite population structure in this region and demonstrate a novel method for distinguishing homologous relapses from reinfections or heterologous relapses with improved accuracy. The parasite population in this area was quite diverse with an estimated five subpopulations and evidence of a highly heterogeneous ancestry of some of the isolates, similar to previous analyses of P. vivax in this region. Pairwise comparison of recurrent infections determined that there were 12 homologous relapses and 3 likely heterologous relapses with highly related parasites. To the best of our knowledge, this is the first large-scale study to evaluate recurrent P. vivax infections using whole genome sequencing. Whole genome sequencing is a high-resolution tool that can identify P. vivax homologous relapses with increased sensitivity, while also providing data about drug resistance and parasite population genetics. This information is important for evaluating the efficacy of known and novel antirelapse medications in endemic areas and thus advancing the campaign to eliminate malaria.
Abstract 68: Targeting macrophage that forms a chemotherapy-induced niche significantly reduces cancer stem cells and tumors
Authors: Xi He, Paloma I. Giles, Edward H. Lin, Linheng Li
Journal: Cancer Research (2018)

Abstract Failure in cancer therapy is often caused by relapse resulting largely from chemo-resistant cancer stem cells (CSCs). Most colorectal cancer patients, after receiving chemoradiotherapy, still harbor treatment-resistant residual tumor cells that are akin to colorectal adenoma. We therefore exploited the APCMin adenoma model that allowed us to study the natural and dynamic interaction between CSCs and their microenvironment in vivo following therapeutic stress. We observed that macrophages were directly recruited from blood vessel to the CSC niche in response to chemotherapy, playing a role in protecting and further promoting activation of CSCs. Reduction in the Ly6c-CD11bintCX3CR1+ MHCII+ population of tumor associated macrophages (TAMs) by celecoxib or clodrosome was correlated with a decline in slow-cycling drug-resistant CSCs and tumorigenesis. Molecularly, we found that COX-2 inhibitor celecoxib suppressed Akt and Wnt signaling, downstream of macrophage-dependent PGE2-EP pathway, thus reducing CSC survival and activation. Taken together, in the naturally formed adenoma reflecting human familial adenomatous polyposis, Chemotherapy-induced recruitment of TAMs to the CSC niche protected and promoted activation of surviving CSCs via PGE2-EP mediated Akt-Wnt signaling, leading to tumor regrowth. Targeting the TAMs will benefit clinical treatment of colorectal cancer. Citation Format: Xi He, Paloma I. Giles, Edward H. Lin, Linheng Li. Targeting macrophage that forms a chemotherapy-induced niche significantly reduces cancer stem cells and tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 68.
IL (Interleukin)-10–STAT3–Galectin-3 Axis Is Essential for Osteopontin-Producing Reparative Macrophage Polarization After Myocardial Infarction
Authors: Kohsuke Shirakawa, Jin Endo, Masaharu Kataoka, Yoshinori Katsumata, Naohiro Yoshida, Tsunehisa Yamamoto, Sarasa Isobe, Hidenori Moriyama, Shinichi Goto, Hiroki Kitakata, Takahiro Hiraide, Keiichi Fukuda, Motoaki Sano
Journal: Circulation (2018)

Both osteopontin (OPN) and galectin-3 have been implicated in phagocytic clearance of dead cells and reparative fibrosis during wound healing. CD206+ macrophages are involved in tissue repair through phagocytosis and fibrosis after myocardial infarction (MI). However, the relationship among OPN, galectin-3, and macrophage polarization in the context of MI remains unclear.The time course of Spp1 (encoding OPN) expression in the heart after MI showed a strong activation of Spp1 on day 3 after MI. To identify where in the body and in which cells the transcriptional activity of Spp1 increased after MI, we analyzed EGFP (enhanced green fluorescent protein)- Spp1 knockin reporter mice on day 3 after MI.The transcriptional activity of Spp1 increased only in CD206+ macrophages in the infarct myocardium, and most of CD206+ macrophages have strong transcriptional activation of Spp1 after MI. The temporal expression pattern of Lgal3 (encoding galectin-3) in cardiac macrophages after MI was similar to that of Spp1, and OPN is almost exclusively produced by galectin-3hiCD206+ macrophages. Although both interleukin (IL)-4 and IL-10 were reported to promote CD206+ macrophage-mediated cardiac repair after MI, IL-10- but not IL-4-stimulated CD11b+Ly6G- cells could differentiate into OPN-producing galectin-3hiCD206+ macrophages and showed enhanced phagocytic ability. Inhibition of STAT3 tyrosine phosphorylation suppressed IL-10-induced expression of intracellular galectin-3 and transcriptional activation of Spp1. Knockdown of galectin-3 suppressed their ability to differentiate into OPN-producing cells, but not STAT3 activation. The tyrosine phosphorylation of STAT3 and the appearance rate of galectin-3hiCD206+ cells on cardiac CD11b+Ly6G- cells in Spp1 knockout mice were the same as those in wild-type mice. Spp1 knockout mice showed vulnerability to developing post-MI left ventricular chamber dilatation and the terminal deoxynucleo-tidyltransferase 2'-Deoxyuridine-5'-triphosphate nick-end labeling (TUNEL)-positive cells in the infarcted myocardium after MI remained higher in number in Spp1 knockout mice than in wild-type mice.OPN is almost exclusively produced by galectin-3hiCD206+ macrophages, which specifically appear in the infarct myocardium after MI. The IL-10-STAT3-galectin-3 axis is essential for OPN-producing reparative macrophage polarization after myocardial infarction, and these macrophages contribute to tissue repair by promoting fibrosis and clearance of apoptotic cells. These results suggest that galectin-3 may contribute to reparative fibrosis in the infarct myocardium by controlling OPN levels.
Abstract 4795: Potency of a new ALK/ROS1 inhibitor TPX-0005 to ALK G1202R mutation and ROS1 G2032R mutation
Authors: Satoshi Yoda, Leila Dardaei, Kylie Prutisto-Chang, Jean Cui, Alice T. Shaw, Aaron N. Hata
Journal: Cancer Research (2018)

Abstract ALK rearrangements and ROS1 rearrangements are important therapeutic targets in non-small cell lung cancer (NSCLC). ALK-positive NSCLC is currently treated with the first-generation ALK inhibitor crizotinib followed by more potent, second-generation ALK inhibitors, such as ceritinib, alectinib, or brigatinib, and ROS1-positve NSCLC is currently treated with crizotinib. Even though these drugs produce responses in most patients, drug resistance eventually develops. Notable mechanisms of resistance are kinase domain solvent front mutations, such as ALK G1202R and ROS1 G2032R. Genomic analysis of relapsed cases show ALK G1202R in 21%, 29%, or 43% of ceritinib-, alectinib-, or brigarinib-resistant cases, and ROS1 G2032R in 41% of crizotinib-resistant cases. The novel ALK/ROS1 inhibitor TPX-0005 was designed to overcome clinical resistance mutations, especially solvent front mutations, and is currently being evaluated in a phase 1/2 study. Engineered preclinical models have demonstrated the potency of TPX-0005 against ALK G1202R and ROS1 G2032R. For example, Ba/F3 cells expressing EML4-ALK G1202R or CD74-ROS1 G2032R resistant to second-generation ALK inhibitors or crizotinib, respectively, but were sensitive to TPX-0005. Here we investigate the potency of TPX-0005 to overcome solvent front mutations in resistant patient-derived models. We generated cell lines and patient-derived xenograft mouse models from ALK G1202R and ROS1 G2032R tumors at the time of relapse on second-generation ALK inhibitors or crizotinib, respectively. As expected, these models were resistant to second-generation ALK inhibitors or crizotinib. In contrast, TPX-0005 suppressed ALK or ROS1 phosphorylation, and led to decreased cell viability and tumor regression in vivo. These data demonstrate that TPX-0005 overcomes solvent front mutations in clinically relevant models and provides rationale for the clinical development of TPX-0005 for patients harboring ALK G1202R or ROS1 G2032R resistance mutations. Citation Format: Satoshi Yoda, Leila Dardaei, Kylie Prutisto-Chang, Jean Cui, Alice T. Shaw, Aaron N. Hata. Potency of a new ALK/ROS1 inhibitor TPX-0005 to ALK G1202R mutation and ROS1 G2032R mutation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4795.
Использование количественного определения HBsAg для мониторинга естественного течения хронической HBV-инфекции
Authors: I.A. Zaitsev
Journal: GASTROENTEROLOGY (2020)

В обзорной статье представлены возможности использования количественного определения HBsAg (qHBsAg) для мониторинга естественного течения заболевания. Указана необходимость унификации использования qHBsAg для мониторинга естественного течения заболевания и противовирусной терапии с закреплением рекомендаций в континентальных руководствах по HBV-инфекции.
Variation in antinuclear antibody detection: need for clear expectations and additional studies
Authors: Michael Mahler, Carolina Auza
Journal: Annals of the Rheumatic Diseases (2018)

The recent article by Pisetsky et al 1 showing data derived from a comparison of different antinuclear antibody (ANA) assays in a cohort of patients with established systemic lupus erythematosus triggered significant discussions among experts in ANA testing. In this context, we read with interest the correspondence by van Hoovels et al 2 describing variation in ANA detection by automated indirect immunofluorescence (IIF) analysis. The data presented showed significant variation between manufacturers and also between laboratories and even within the same laboratory, which raised concerns. The majority of laboratories (n=12) used NOVA View (Inova Diagnostics), followed by G-Sight (Menarini, n=9; split into HEp-2 and HEp-2000) and Image Navigator (ImmunoConcepts, n=2).

A similar study has been conducted as part of the regulatory clearance of the NOVA View system, which showed significantly higher consistency. In addition, van Hoovels et al 2 had previously performed a similar study that also reported variability higher than expected.3 However, in this study, the variability could be improved by …
Hermansky-Pudlak syndrome with a novel genetic variant in<i>HPS1</i>and subsequent accelerated pulmonary fibrosis: significance for phenocopy diseases
Authors: Oliver J McElvaney, Marjan Huizing, William A Gahl, Paul O’Donovan, Deirdre Horan, P Mark Logan, Emer P Reeves, Noel G McElvaney
Journal: Thorax (2018)

The Hermansky-Pudlak syndrome (HPS) is a collection of autosomal-recessive disorders characterised by tyrosinase-positive oculocutaneous albinism (OCA), bleeding diatheses and, in selected individuals, early-onset accelerated pulmonary fibrosis, neutropaenia and granulomatous colitis. We describe a young man who presented following a self-directed literature review prompted by severe bleeding complications following minor surgical and dental procedures in the context of OCA. HPS was clinically suspected, with subsequent genetic testing confirming biallelic mutations in the HPS1 gene. Of interest, this is the only described HPS type 1 patient with two different (compound heterozygote) splice site variants in HPS1 In addition to detailing a novel genetic result and outlining the progressive clinical course of disease in this case, we discuss the management of HPS, the prognostic value of subtype analysis and the technical difficulties relating to transplantation in the case of HPS-associated advanced pulmonary fibrosis. This case also illustrates the concept of lung phenocopy relationships and the potential for elucidating the pathogenesis of more common pulmonary disorders by studying genetic diseases that result in similar phenotypes. Furthermore, it re-emphasises the importance of the patient voice, particularly with regard to complex diagnoses and rare diseases.
The accuracy of multiparametric magnetic resonance imaging (mpMRI) using PI-RADS v2 in disease upgrading on re-biopsy among patients with low-risk prostate cancer (PCa) on active surveillance (AS): A Brazilian perspective.
Authors: PÃºblio C. C. Viana, Natally Horvat, Giuliano Guglielmetti, Rafael Coelho, William Carlos Nahas, Rubens Park, Regis Bezerra, Diogo Assed Bastos, Thiana Rodrigues, Hebert Alberto Vargas
Journal: Journal of Clinical Oncology (2017)

5084 Background: The current selection criteria to AS is critical and it becomes even more relevant in Latin America, given the higher proportion of high risk cancers. The objective of this study is to analyze the accuracy of mpMRI using PI-RADS v2 in predicting the risk of upgrading on re-biopsy (UR) in men with low-risk PCa on AS. Methods: In this Institutional Review Board approved prospective study, patients with low-grade PCa selected for AS at our institution underwent mpMRI at least 6 weeks after the baseline 12-core random prostate biopsy (BSB), from March 2014 to March 2016. One blinded abdominal radiologist evaluated the exams regarding presence of dominant lesion and assigned the PI-RADS v2 score. MRI-target transrectal ultrasound-guided re-biopsies were performed in all patients within 6-12 months after the BSB. Standardized 12-core biopsy was performed and additional cores were taken from suspicious areas on mpMRI. Results: One hundred and nine patients were included, 93 (85.3%) patients had a dominant lesion on MRI. mpMRI were classified as PI-RADS 1, 2 or 3 in 67 (61.5%) patients, and as PI-RADS 4 or 5 in 42 (38.5%) patients. UR occurred in 42 (38.5%) patients. Out of these, 39 (92.8%) had radical prostatectomy, 6 (15.4%) T2a, 24 (61.5%) T2b, and 9 (23.1%) T3a. The diagnostic performance of mpMRI for PCa upgrading after re-biopsy was summarized in table 1. Patients assigned as PI-RADS 4 or 5 presented a significantly higher risk for UR compared with patients with PI-RADS 1, 2 or 3 (73.8% vs 16.4%, p &lt; 0.001). Logistic regression analyses demonstrated that PI-RADS 4 or 5 remained a significant predictor of UR (OR: 37.366, p &lt; 0.0001). Conclusions: We demonstrated in our population that mpMRI using PI-RADS v2 is a significant predictor for upgrading on re-biopsy in patients on AS and could be used to guide TRUS biopsy, increasing the accuracy of current clinical criteria for AS. [Table: see text]
Cyclophilin A Function in Mammary Epithelium Impacts Jak2/Stat5 Signaling, Morphogenesis, Differentiation, and Tumorigenesis in the Mammary Gland
Authors: Sonja E. Volker, Shannon E. Hedrick, Yvonne B. Feeney, Charles V. Clevenger
Journal: Cancer Research (2018)

The prolyl isomerase cyclophilin A (CypA) regulates the Jak2/Stat5 pathway, which is necessary for mammary differentiation and the pathogenesis of breast cancer. In this study, we assessed the role of this isomerase during mammary gland development and erbB2-driven tumorigenesis. Genetic deletion of CypA resulted in delayed mammary gland morphogenesis and differentiation with corresponding decrease in Jak2/Stat5 activation; mammary gland cross-transplantation confirmed this defect was epithelial in nature. Analysis of mammary stem and progenitor populations revealed significant disruption of epithelial maturation. Loss of CypA in the erbB2 transgenic mouse model revealed a marked increase in mammary tumor latency that correlated with decreased Stat5 activation, associated gene expression, and reduced epithelial cell proliferation. These results demonstrate an important role for CypA in the regulation of Jak2/Stat5-mediated biology in mammary epithelium, identifying this isomerase as a novel target for therapeutic intervention.Significance: These findings reveal cyclophilin A functions in normal mammary epithelial development and ErbB2-driven mammary tumorigenesis and suggest therapies targeting cyclophilin A may be efficacious for breast cancer treatment.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/14/3877/F1.large.jpg Cancer Res; 78(14); 3877-87. ©2018 AACR.