tbuckley/cabot-search huggingface dataset:
Incorporation of mutations in five genes in the revised International Prognostic Scoring System can improve risk stratification in the patients with myelodysplastic syndrome
Authors: Hsin-An Hou, Cheng-Hong Tsai, Chien-Chin Lin, Wen-Chien Chou, Yuan-Yeh Kuo, Chieh-Yu Liu, Mei-Hsuan Tseng, Yen-Ling Peng, Ming-Chih Liu, Chia-Wen Liu, Xiu-Wen Liao, Liang-In Lin, Ming Yao, Jih-Luh Tang, Hwei-Fang Tien
Journal: Blood Cancer Journal (2018)

Abstract Gene mutations have not yet been included in the 2016 WHO classification and revised International Prognostic Scoring System (IPSS-R), which are now widely utilized to discriminate myelodysplastic syndrome (MDS) patients regarding risk of leukemia evolution and overall survival (OS). In this study, we aimed to investigate whether integration of gene mutations with other risk factors could further improve the stratification of MDS patients. Mutational analyses of 25 genes relevant to myeloid malignancies in 426 primary MDS patients showed that mutations of CBL, IDH2, ASXL1 , DNMT3A , and TP53 were independently associated with shorter survival. Patients within each IPSS-R or 2016 WHO classification-defined risk group could be stratified into two risk subgroups based on the mutational status of these five genes; patients with these poor-risk mutations had an OS shorter than others in the same risk group, but similar to those with the next higher risk category. A scoring system incorporating age, IPSS-R and five poor-risk mutations could divide the MDS patients into four risk groups ( P &lt; 0.001 for both OS and leukemia-free survival). In conclusion, integration of gene mutations in current IPSS-R improves the prognostication of MDS patients and may help identify high-risk patients for more aggressive treatment in IPSS-R lower risk group.
Abstract 8470: Conditional Deletion of Cardiac Connexin45 Results in Impaired Av-Nodal Conduction Properties
Authors: Jan W Schrickel, Marina Frank, Stefan Offermanns, Angela Wirth, Georg Nickenig, Lars Lickfett, Klaus Willecke
Journal: Circulation (2011)

Introduction: Cx45 has been proposed to maintain basal AV-nodal conduction. The exact function of Cx45 in the adult heart has not yet been identified as Cx45 deficient mice are embryonic lethal. Methods: We generated a transgenic mouse line by breeding floxed Cx45 mice with inducible cardiomyocyte-specific Cre-recombinase-expressing mice. Cardiac Cx45 was conditionally deleted by intraperitoneal administration of tamoxifen in adult mice (Cx45 fl/fl:aMHC-CreERt2). In these mice and control littermates (Cx45 fl/fl), we performed telemetric ECGs (n=5) and in vivo electrophysiological investigations (EPI) using transvenous catheterization to assess standard EPI-parameters (n=10). Results: Holter ECGs showed similar heart rates in the genotypes (590±65 in Cx45 fl/fl:aMHC-CreERt2 vs. 571±72 in Cx45 fl/fl). PQ-intervals were prolonged in Cx45 fl/fl:aMHC-CreERt2 (41.0±2.2ms vs. 36.4±3.1ms; p&lt;0.05) and the P-wave was shorter (8.9±1.6ms vs. 6.6±1.0ms; p&lt;0.05). Under inhalative ansthesia, heart rate was significantly lower in both genotypes (382±43 in Cx45 fl/fl:aMHC-CreERt2; 419±10 in Cx45 fl/fl; p&lt;0.05 vs. spontaneous heart rate), but PQ remained significantly prolonged in the conditional knock-out mice (41.2±4.7ms vs. 37.5±3.5ms; p&lt;0.05). Evaluation of intracardiac electrograms showed no measurable alterations of supra- or infra-Hisian conduction at comparable AH- and HV-intervals. Sinus-nodal recovery period and Wenckebach periodicity were not significantly different among the groups. Conclusions: Our mouse mutants with conditional cardiac deletion of Cx45 represent the first model for evaluation of Cx45 function in the adult heart. Our data show prolonged AV-intervals and no impaired AV-nodal conduction under fast heart rates. These findings support the thesis of Cx45 as a provider of basal AV-nodal conductivity, potentially as a backup system for maintaining AV-nodal conduction under pathological conditions, but with minor importance for AV-nodal conductivity when Cx30.2 and Cx40 are present.
Abstract 13504: Geriatric Nutritional Risk Index Predict Cardiovascular Events in Patients at Risk for Heart Failure
Authors: Masatoshi Minamisawa, Takashi Miura, Hirohiko Motoki, Yasushi Ueki, Tomoaki Mochidome, Yasutaka Oguchi, Hitoshi Nishimura, Soichiro Ebisawa, Jun Koyama, Uichi Ikeda
Journal: Circulation (2016)

Introduction: Geriatric nutritional risk index (GNRI) is a simple nutritional assessment tool for elderly patients. Lower GNRI is associated with a worse prognosis in patients with heart failure (HF) with preserved ejection fraction. However, few data are available regarding the prognostic impact of GNRI value for risk stratification in patients at risk for HF, classified as stage A/B according to the ACC/AHA HF guidelines. Hypothesis: We hypothesized that GNRI values would predict adverse cardiovascular (CV) events, even in patients without prior HF. Methods: We retrospectively enrolled 2258 consecutive patients without prior HF who were hospitalized for CV diseases between 2005 and 2012. GNRI on admission was calculated as follows: 14.89 х serum albumin (g/dL) + 41.7 х body mass index/22. Patients were divided into two groups stratified by GNRI (median value 106.7). The study endpoint was the composite of CV death and hospitalization for worsening HF. Results: Over a 4.6-year median follow-up, adverse events were observed in 139 patients (6.2 %). In Kaplan–Meier analysis, patients with low GNRI (&lt; 106.7, n = 1128) showed worse prognoses than those with high GNRI (≥ 106.7, n = 1130) (8.1 % vs. 4.2 %, P &lt; 0.001). In multivariate Cox proportional hazards analysis after the adjustment for age, sex, estimated glomerular filtration rate, B-type natriuretic peptide, and left ventricular ejection fraction, Low GNRI (&lt;106.7) was significantly associated with the incidence of CV events (hazard ratio: 1.72, 95% confidence interval: 1.26–2.35; P = 0.001). Conclusions: In patients without prior HF, GNRI is an independent predictor of CV events. Simple assessment of GNRI may be useful for predicting CV events in those patients.
Interactions Between Physicians and Skilled Home Health Care Agencies in the Certification of Medicare Beneficiaries' Plans of Care: Results of a Nationally Representative Survey
Authors: Cynthia M. Boyd, Bruce Leff, Julia Bellantoni, Navpreet Rana, Jennifer L. Wolff, David L. Roth, Kim Carl, Orla C. Sheehan
Journal: Annals of Internal Medicine (2018)

Physicians are required to certify a plan of care for patients who receive Medicare skilled home health care (SHHC) services. The Centers for Medicare & Medicaid Services form 485 (CMS-485) is typically used for certification of SHHC plans of care and for interactions between SHHC agencies and physicians. Little is known about how physicians use the CMS-485 or their perceptions of its usefulness with respect to coordinating care with SHHC agencies.To determine how physicians interact with SHHC agencies and use the CMS-485 in care coordination for patients receiving SHHC services.Mailed survey.Nationally representative random sample.Physicians from the American Medical Association Physician Masterfile specializing in family or general medicine (excluding adolescent and sports medicine), geriatrics, geriatric psychiatry, internal medicine, or hospice and palliative medicine.Time spent reviewing the plan of care and experiences with making changes and communicating with SHHC clinicians.The response rate after 3 mailings was 53% (1044 of 1968). Of 1005 respondents who provided patient care, 72% had certified at least 1 plan of care in the past year. Nearly half (47%) reported spending less than 1 minute reviewing the CMS-485 before certification, whereas 21% reported spending at least 2 minutes. Physicians typically interacted with multiple SHHC agencies by fax or mail. Approximately 80% rarely or never changed an order on the CMS-485, and 78.3% rarely or never contacted SHHC clinicians with questions about information. The mean reported ease of contacting the SHHC agency was 4.7 (SD, 2.3) on a scale of 1 (easy) to 10 (difficult).Self-reported data and 53% response rate.The CMS-485 does not meaningfully engage physicians. Physicians spend little time reviewing or acting on the SHHC plan of care. Strategies to enhance meaningful communication between SHHC agencies and physicians are needed.National Institute on Aging and National Institute of Mental Health.
Exome chip analyses identify genes affecting mortality after HLA-matched unrelated-donor blood and marrow transplantation
Authors: Qianqian Zhu, Li Yan, Qian Liu, Chi Zhang, Lei Wei, Qiang Hu, Leah Preus, Alyssa I. Clay-Gilmour, Kenan Onel, Daniel O. Stram, Loreall Pooler, Xin Sheng, Christopher A. Haiman, Xiaochun Zhu, Stephen R. Spellman, Marcelo Pasquini, Philip L. McCarthy, Song Liu, Theresa Hahn, Lara E. Sucheston-Campbell
Journal: Blood (2018)
Tumor-associated macrophages as predictive biomarkers for postoperative adjuvant chemotherapy in patients with stage II colon cancer.
Authors: Jianmin Xu, Qingyang Feng, Wenju Chang, Ye Wei, Li Ren, Guodong He, Yunshi Zhong, Dexiang Zhu, Jingwen Chen, Tuo Yi, Qi Lin, Peng Zheng, Meiling Ji
Journal: Journal of Clinical Oncology (2018)

620 Background: For stage II colon cancer, the effect of postoperative adjuvant chemotherapy is still controversial. It is well known that tumor-associated macrophages (TAMs) play an important role in tumor progression. The aim of this study is to determine the effect of TAMs as predictor for adjuvant chemotherapy for stage II colon cancer. Methods: From July 2009 to June 2012, 521 patients with pathological stage II colon cancer were included. TAMs were detected using tissue microarray and immunohistochemistry (all TAMs detected by CD68; M2 subtype detected by CD206). The density of CD68+ TAMs, CD206+ TAMs and the ratio of CD206+ TAMs / CD68+ TAMs (CD206 / CD68 ratio) were calculated. The cut-off values were defined using X-Tile software. Results: High CD206+ TAMs density and high CD206 / CD68 ratio were significantly associated with reduced disease-free survival (DFS, P &lt; 0.001 and P &lt; 0.001, respectively) and overall survival (OS, P &lt; 0.001 and P &lt; 0.001, respectively). And CD206 / CD68 ratio had a better prognostic power. Furthermore, for patients with low CD206 / CD68 ratio, adjuvant chemotherapy made no benefit. But for high CD206 / CD68 ratio, adjuvant chemotherapy significantly improved DFS and OS (as shown in Table 1). In subgroup analysis, for T3 with high-risk factors or T4 tumors, CD206 / CD68 ratio was also a significant predictor for adjuvant chemotherapy (interaction P = 0.024 in DFS). Conclusions: For stage II colon cancer, CD206 / CD68 ratio was a good prognostic and predictive biomarker for adjuvant chemotherapy. Together with clinicopathological high-risk factors, it might facilitate patient counselling and individualise management. [Table: see text]
Uses of H.P. Acthar Gel in the Clinical Setting
Authors: Tunde Otulana
Journal: JAMA Internal Medicine (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 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
Glucocorticoid-loaded liposomes induce a pro-resolution phenotype in human primary macrophages to support chronic wound healing
Authors: Anne Gauthier, Andreas Fisch, Klaus Seuwen, Birgit Baumgarten, Heinz Ruffner, Alexandra Aebi, Martin Rausch, Fabian Kiessling, Matthias Bartneck, Ralf Weiskirchen, Frank Tacke, Gert Storm, Twan Lammers, Marie-Gabrielle Ludwig
Journal: Biomaterials (2018)
Fighting leukemia with “duel”-targeted therapy
Authors: Tríona Ní Chonghaile
Journal: Science Translational Medicine (2018)

Combining BCL-2 inhibitor venetoclax with monoclonal CD20 antibody rituximab greatly enhances progression-free survival compared with bendamustine-rituximab in a phase 3 trial of relapsed or refractory chronic lymphocytic leukemia patients.
SIRT3 restricts hepatitis B virus transcription and replication through epigenetic regulation of covalently closed circular DNA involving suppressor of variegation 3‐9 homolog 1 and SET domain containing 1A histone methyltransferases
Authors: Ji‐Hua Ren, Jie‐Li Hu, Sheng‐Tao Cheng, Hai‐Bo Yu, Vincent Kam Wai Wong, Betty Yuen Kwan Law, Yong‐Feng Yang, Ying Huang, Yi Liu, Wei‐Xian Chen, Xue‐Fei Cai, Hua Tang, Yuan Hu, Wen‐Lu Zhang, Xiang Liu, Quan‐Xin Long, Li Zhou, Na‐Na Tao, Hong‐Zhong Zhou, Qiu‐Xia Yang, Fang Ren, Lin He, Rui Gong, Ai‐Long Huang, Juan Chen
Journal: Hepatology (2018)

Hepatitis B virus (HBV) infection remains a major health problem worldwide. Maintenance of the covalently closed circular DNA (cccDNA), which serves as a template for HBV RNA transcription, is responsible for the failure of eradicating chronic HBV during current antiviral therapy. cccDNA is assembled with cellular histone proteins into chromatin, but little is known about the regulation of HBV chromatin by histone posttranslational modifications. In this study, we identified silent mating type information regulation 2 homolog 3 (SIRT3) as a host factor restricting HBV transcription and replication by screening seven members of the sirtuin family, which is the class III histone deacetylase. Ectopic SIRT3 expression significantly reduced total HBV RNAs, 3.5-kb RNA, as well as replicative intermediate DNA in HBV-infected HepG2-Na+ /taurocholate cotransporting polypeptide cells and primary human hepatocytes. In contrast, gene silencing of SIRT3 promoted HBV transcription and replication. A mechanistic study found that nuclear SIRT3 was recruited to the HBV cccDNA, where it deacetylated histone 3 lysine 9. Importantly, occupancy of SIRT3 on cccDNA could increase the recruitment of histone methyltransferase suppressor of variegation 3-9 homolog 1 to cccDNA and decrease recruitment of SET domain containing 1A, leading to a marked increase of trimethyl-histone H3 (Lys9) and a decrease of trimethyl-histone H3 (Lys4) on cccDNA. Moreover, SIRT3-mediated HBV cccDNA transcriptional repression involved decreased binding of host RNA polymerase II and transcription factor Yin Yang 1 to cccDNA. Finally, hepatitis B viral X protein could relieve SIRT3-mediated cccDNA transcriptional repression by inhibiting both SIRT3 expression and its recruitment to cccDNA.SIRT3 is a host factor epigenetically restricting HBV cccDNA transcription by acting cooperatively with histone methyltransferase; these data provide a rationale for the use of SIRT3 activators in the prevention or treatment of HBV infection. (Hepatology 2018).
Receptor tyrosine kinases and downstream pathways as druggable targets for cancer treatment: the current arsenal of inhibitors
Authors: Wagner Ricardo Montor, Andrei Ronaldo Oliveira Silva Escar Salas, Fabiana Henriques Machado de Melo
Journal: Molecular Cancer (2018)

Searching for targets that allow pharmacological inhibition of cell proliferation in over-proliferative states, such as cancer, leads us to finely understand the complex mechanisms orchestrating the perfect control of mitosis number, frequency and pace as well as the molecular arrangements that induce cells to enter functional quiescence and brings them back to cycling in specific conditions. Although the mechanisms regulating cell proliferation have been described several years ago, never before has so much light been shed over this machinery as during the last decade when therapy targets have been explored and molecules, either synthetic or in the form of antibodies with the potential of becoming cancer drugs were produced and adjusted for specific binding and function. Proteins containing tyrosine kinase domains, either membrane receptors or cytoplasmic molecules, plus the ones activated by those in downstream pathways, having tyrosine kinase domains or not, such as RAS which is a GTPase and serine/threonine kinases such as RAF, play crucial role in conducting proliferation information from cell surroundings to the nucleus where gene expression takes place. Tyrosine kinases phosphorylate tyrosine residues in an activating mode and are found in important growth factor receptors, such as for ligands from families collectively known as VEGF, PDGF and EGF, to name a few and in intracellular downstream molecules. They all play important roles in normal physiology and are commonly found mutated or overexpressed in neoplastic states. Our objective here is to present such kinases as druggable targets for cancer therapy, highlighting the ones for which the pharmacological arsenal is available, discussing specificity, resistance mechanisms and treatment alternatives in cases of resistance, plus listing potential targets that have not been successfully worked yet.
Avoidance of Severe Cutaneous Adverse Drug Events as a First Step in Precision Neurology
Authors: Yijing He, Lucia Seminario-Vidal, Howard L. McLeod
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
Holding Providers Accountable for Health Care Outcomes
Authors: Jacob Korula
Journal: Annals of Internal Medicine (2018)

Letters3 April 2018Holding Providers Accountable for Health Care OutcomesJacob Korula, MDJacob Korula, MDArcadia, California (J.K.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L17-0707 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Baker and Chassin (1) provide an excellent assessment of the value of outcome measures—the yardstick payers use to evaluate physicians and hospitals accountable for delivering care. This achievement is particularly remarkable, because their commentary seems to be viewed from the perspective of The Joint Commission. I would like to raise some questions to better understand the applicability of the data for accountability programs.First, the authors are correct that the time for each measure defined by diagnosis codes should not be fixed to 30 days. Rather, it should be tailored to specific disease severity. The International Classification ...Reference1. Baker DW, Chassin MR. Holding providers accountable for health care outcomes. Ann Intern Med. 2017;167:418-23. [PMID: 28806793]. doi:10.7326/M17-0691 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Arcadia, California (J.K.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L17-0707. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoHolding Providers Accountable for Health Care Outcomes David W. Baker and Mark R. Chassin Holding Providers Accountable for Health Care Outcomes David W. Baker and Mark R. Chassin Metrics 3 April 2018Volume 168, Issue 7Page: 527KeywordsDiabetes mellitusDisclosureHealth care providersHealth care qualityHeart failureHypertensionPsychologyQuality of life ePublished: 3 April 2018 Issue Published: 3 April 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Automated Reporting of DXA Studies Using a Custom-Built Computer Program
Authors: Joseph R. England, Patrick M. Colletti
Journal: Clinical Nuclear Medicine (2018)

Dual-energy x-ray absorptiometry (DXA) scans are a critical population health tool and relatively simple to interpret but can be time consuming to report, often requiring manual transfer of bone mineral density and associated statistics into commercially available dictation systems. We describe here a custom-built computer program for automated reporting of DXA scans using Pydicom, an open-source package built in the Python computer language, and regular expressions to mine DICOM tags for patient information and bone mineral density statistics. This program, easy to emulate by any novice computer programmer, has doubled our efficiency at reporting DXA scans and has eliminated dictation errors.
An Acquired NRAS Q61K Mutation in BRAF V600E-Mutant Lung Adenocarcinoma Resistant to Dabrafenib Plus Trametinib
Authors: Daniel L. Abravanel, Mizuki Nishino, Lynette M. Sholl, Chiara Ambrogio, Mark M. Awad
Journal: Journal of Thoracic Oncology (2018)