tbuckley/cabot-search huggingface dataset:
The 4Kscore to predict the grade and stage of prostate cancer in the radical prostatectomy specimen: Results from a multi-institutional prospective trial.
Authors: Bruno Nahar, Sanoj Punnen, Daniel Sjoberg, Stephen M Zappala, Dipen Parekh
Journal: Journal of Clinical Oncology (2016)

69 Background: A recent prospective validation study confirmed the 4Kscore accurately predicted aggressive prostate cancer on prostate biopsy. We investigated the association between the 4Kscore and pathologic grade and stage at radical prostatectomy, where the entire prostate gland is sampled. Methods: Prospective enrollment of 1,312 men who were referred for prostate biopsy for clinical suspicion of prostate cancer occurred at 26 sites throughout the United States from October 2013 to April 2014. We selected men who were found to have positive prostate cancer biopsies and elected to undergo radical prostatectomy. The 4Kscore is an algorithm that incorporates a panel of 4 Kallikreins (total PSA, free PSA, intact PSA and human kallikrein-2) in addition to age, digital rectal examination, and prior biopsy status. We assessed the concordance between the 4Kscore prior to biopsy and grade of prostate cancer at radical prostatectomy. 4Kscore test results were compared for those with and without non organ-confined tumors at surgery using the Wilcoxon rank-sum. Results: Among the 1,312 men who enrolled in this validation study, 144 were found to have prostate cancer and underwent radical prostatectomy. We saw a significant association between the 4Kscore and grade at surgery with higher scores relating to worse grade. For men with Gleason 6, 7, and 8 or higher cancers in the surgical specimen the median (IQR) 4Kscore was 7% (4, 12), 25% (12, 38), and 47% (24, 66) (p&lt;0.0001).The median 4Kscore among men with non organ-confined cancer was significantly higher then men with cancers confined to the prostate ([36% (IQR 19,58)] vs. [19% (IQR 9, 35)], p=0.002). Conclusions: In a subset of men who underwent radical prostatectomy, the 4Kscore was significantly associated with pathological grade and extracapsular extension in the surgical specimen, with higher scores being linked to higher grade and more aggressive histology. The test can be beneficial to aid in treatment decision making for men who are contemplating observation of their cancer versus immediate treatment.
Adipose-derived stem cell sheets functionalized by hybrid baculovirus for prolonged GDNF expression and improved nerve regeneration
Authors: Mu-Nung Hsu, Han-Tsung Liao, Kuei-Chang Li, Hwei-Hsien Chen, Tzu-Chen Yen, Pavel Makarevich, Yelena Parfyonova, Yu-Chen Hu
Journal: Biomaterials (2017)
Expression of PDL1 (B7-H1) before and after neoadjuvant chemotherapy (NAC) in urothelial carcinoma.
Authors: Ajjai Shivaram Alva, Andrew McDaniel, Tianyu Zhan, Hong Xiao, Arul M. Chinnaiyan, Cheryl T. Lee, Rohit Mehra
Journal: Journal of Clinical Oncology (2015)

313 Background: Expression of the co-stimulatory ligand PDL1 (B7-H1) of the PD-PDL immune checkpoint on tumor cells enables evasion of anti-tumor immunity. The PD-PDL checkpoint is a therapeutic target in UC. We sought to characterize the impact of cytotoxic NAC on PDL1 expression before and after NAC to inform optimal sequencing/combination strategies of immune/cytotoxic therapies. Methods: Immunohistochemical (IHC) staining for PDL1 was performed using a murine anti-B7-H1 monoclonal antibody (clone 5H1) on a tissue microarray with matched pre-NAC T1/T2 transurethral resection (TURBT) samples (T0=2; Tx=1; T1=1; T2=23, T3=11; T4=2) and post-NAC cystectomy samples (pT0N0=15, TisN0=1, T1N0=3, T2N0=6, T3N0=9, T3Nx=1, T4Nx=1, T2N1=1, T3N2, T4N2=1, T3N3=1) from 40 patients (pts) treated from 1999-2011 at the University of Michigan. NAC was cisplatin-based in 13 pts and carboplatin-based in 26 pts. IHC was scored as the product of tumor cell staining intensity (0-3) and percentage of cells positive (0-100). Correlations of T stage at TURBT with the score were analyzed with unpaired t-test and Wilcoxon test. ANOVA analysis and paired t-tests were done to correlate pStage with the score. Results: PDL1 expression was significantly higher in post-NAC cystectomy specimens (mean IHC product score= 217.5) compared to the matched pre-NAC TUR specimens (mean IHC product score= 176.6, p value=0.0196 by Student's paired T test). Among the 21 non-pT0 pts with data at both time-points, PDL1 expression increased after NAC in 16 pts. The % of PDL1 positive cells in the residual tissue increased in 15 pts. The PDL1 expression product score in pre-NAC or post-NAC tissue did not correlate with clinical or pathologic stage, or with recurrence-free or overall survival. Conclusions: PDL1 expression in locally advanced UC in pts receiving NAC did not correlate with clinical outcomes in our small cohort. However, the expression of PDL1 in post-NAC tissue was elevated compared to pre-NAC. The increased PDL1 expression following NAC informs rational combinations and sequencing of cytotoxic chemotherapy with anti-PD1/PDL1 immunotherapies in UC particularly in adjuvant therapy for residual disease after neoadjuvant therapy.
Evaluating Prognostic Value of Patients with Newly Diagnosed Multiple Myeloma By Serum Free Light Chain κ/λ Ratio in Combination with LDH
Authors: Chengcheng Fu, Panfeng Wang, Feiran Gong, Jiazi Zhou, Ying Yao, Yun Xu, Yang Xu, Huirong Chang, Depei Wu
Journal: Blood (2016)
Chromosomal instability in HCC: a key function for checkpoint kinase 2
Authors: Robert Eferl, Michael Trauner
Journal: Gut (2017)

The German cytologist Theodor Boveri proposed about 100 years ago that cancer is caused by an abnormal distribution of microscopic bodies called chromosomes. At that time, researchers had no idea of the cellular component for inheritance and challenged his hypothesis. Meanwhile, genomic instability is viewed as a hallmark of cancer1 and an alternative model for cancer formation was put forward that proposed acquisition of a ‘mutator’ phenotype as the initiating event. Although supported by the vast plasticity of sequence changes and chromosomal aberrations in individual cells of single tumours, these observations did not solve the issue whether the ‘mutator’ phenotype is a precondition or a consequence of tumourigenesis.

The ‘mutator’ phenotype is causative for genomic instability, an umbrella term for small DNA structure variations, microsatellite instability and chromosomal instability (CIN).2 The latter affects chromosome number and structure and is a characteristic feature of many cancer types including hepatocellular carcinoma (HCC).3 It is also associated with the formation of extranuclear bodies that contain damaged chromosome fragments or whole chromosomes. Such micronuclei were identified in regenerative and dysplastic nodules of the liver indicating that CIN can be acquired already in early stage hepatocarcinogenesis.3 Apparently, CIN is linked to certain cancer genotypes because HCC has been originally divided into two major subclasses: one displaying a stable cancer genome and activating β-catenin mutations, and the other with extensive CIN, p53 and Axin …
Is combining gait retraining or an exercise programme with education better than education alone in treating runners with patellofemoral pain?A randomised clinical trial
Authors: Jean-Francois Esculier, Laurent Julien Bouyer, Blaise Dubois, Pierre Fremont, Lynne Moore, Bradford McFadyen, Jean-Sébastien Roy
Journal: British Journal of Sports Medicine (2017)

Design Single-blind randomised clinical trial. Objective To compare the effects of three 8-week rehabilitation programmes on symptoms and functional limitations of runners with patellofemoral pain (PFP). Methods Sixty-nine runners with PFP were randomly assigned to one of three intervention groups: (1) education on symptoms management and training modifications (education); (2) exercise programme in addition to education (exercises); (3) gait retraining in addition to education (gait retraining). Symptoms and functional limitations were assessed at baseline (T 0 ), and after 4, 8 and 20 weeks (T 4 , T 8 and T 20 ) using the Knee Outcome Survey of the Activities of Daily Living Scale (KOS-ADLS) and visual analogue scales (VASs) for usual pain, worst pain and pain during running. Lower limb kinematics and kinetics during running, and isometric strength were also evaluated at T 0 and T 8 . The effects of rehabilitation programmes were assessed using two-way analysis of variance. Results No significant group × time interactions (p&lt;0.447) were found for KOS-ADLS and VASs. All three groups showed similar improvements at T 4 , T 8 and T 20 compared with T 0 (p&lt;0.05). Only the exercises group increased knee extension strength following rehabilitation (group × time: p&lt;0.001) and only the gait retraining group (group × time: p&lt;0.001) increased step rate (+7.0%) and decreased average vertical loading rate (−25.4%). Conclusion Even though gait retraining and exercises improved their targeted mechanisms, their addition to education did not provide additional benefits on symptoms and functional limitations. Appropriate education on symptoms and management of training loads should be included as a primary component of treatment in runners with PFP. Trial registration number ClinicalTrials.gov ( NCT02352909 ).
Imatinib-induced changes in gene expression and the metastatic potential of human breast carcinoma cells
Authors: A. Lorico, F. Anzanello, G. Rappa
Journal: Journal of Clinical Oncology (2009)

1074 Background: Imatinib mesylate (imatinib) is a potent and selective inhibitor of the tyrosine kinases, Bcr-Abl, c-Kit and platelet-derived growth factor receptors (PDGFRs). Since its advent for the successful treatment of chronic myelogenous leukemia in 2001, the clinical efficacy of imatinib has been investigated in many other human malignancies, including breast cancer. Based on recent reports that chemotherapy selects more invasive and metastasizing cells, we have hypothesized that exposure of breast cancer cells to imatinib could enhance their malignant behavior. Methods: MA-11 breast carcinoma cells, originating from bone marrow micrometastases, were exposed to imatinib in vitro for seven days. After four days of recovery in drug-free medium, biological properties and gene expression pattern were compared with those of the parental cell line. In a separate set of experiments, the effects of in vivo administration of imatinib to athymic nude (nu/nu) mice carrying MA-11 tumors were investigated. Results: In vitro, imatinib treatment increased the motility and invasiveness of the breast cancer cells, and induced over-expression of drug transporters and of a set of genes associated with aggressive and metastatic behavior (Table). In vivo, nu/nu mice subcutaneously implanted with MA-11 cells and treated with nine daily intraperitoneal doses of 60 mg/Kg imatinib developed with greater frequency distant organ metastases vs. control mice implanted with MA-11 and treated with the vehicle alone. Conclusions: Our data caution against the clinical use of imatinib in breast cancer; imatinib-selected breast cancer cells represent an important tool to investigate the pro-metastatic role of differentially expressed genes. [Table: see text] No significant financial relationships to disclose.
Consensus statement on concussion in sport—the 5<sup>th</sup>international conference on concussion in sport held in Berlin, October 2016
Authors: Paul McCrory, Willem Meeuwisse, Jiří Dvorak, Mark Aubry, Julian Bailes, Steven Broglio, Robert C Cantu, David Cassidy, Ruben J Echemendia, Rudy J Castellani, Gavin A Davis, Richard Ellenbogen, Carolyn Emery, Lars Engebretsen, Nina Feddermann-Demont, Christopher C Giza, Kevin M Guskiewicz, Stanley Herring, Grant L Iverson, Karen M Johnston, James Kissick, Jeffrey Kutcher, John J Leddy, David Maddocks, Michael Makdissi, Geoff T Manley, Michael McCrea, William P Meehan, Sinji Nagahiro, Jon Patricios, Margot Putukian, Kathryn J Schneider, Allen Sills, Charles H Tator, Michael Turner, Pieter E Vos
Journal: British Journal of Sports Medicine (2017)

The 2017 Concussion in Sport Group (CISG) consensus statement is designed to build on the principles outlined in the previous statements1–4 and to develop further conceptual understanding of sport-related concussion (SRC) using an expert consensus-based approach. This document is developed for physicians and healthcare providers who are involved in athlete care, whether at a recreational, elite or professional level. While agreement exists on the principal messages conveyed by this document, the authors acknowledge that the science of SRC is evolving and therefore individual management and return-to-play decisions remain in the realm of clinical judgement.

This consensus document reflects the current state of knowledge and will need to be modified as new knowledge develops. It provides an overview of issues that may be of importance to healthcare providers involved in the management of SRC. This paper should be read in conjunction with the systematic reviews and methodology paper that accompany it. First and foremost, this document is intended to guide clinical practice; however, the authors feel that it can also help form the agenda for future research relevant to SRC by identifying knowledge gaps.

A series of specific clinical questions were developed as part of the consensus process for the Berlin 2016 meeting. Each consensus question was the subject of a specific formal systematic review, which is published concurrently with this summary statement. Readers are directed to these background papers in conjunction with this summary statement as they provide the context for the issues and include the scope of published research, search strategy and citations reviewed for each question. This 2017 consensus statement also summarises each topic and recommendations in the context of all five CISG meetings (that is, 2001, 2004, 2008, 2012 as well as 2016). Approximately 60 000 published articles were screened by the expert panels for the Berlin …
Novel role for endogenous mitochondrial formylated peptide-driven formyl peptide receptor 1 signalling in acute respiratory distress syndrome
Authors: David A Dorward, Christopher D Lucas, Mary K Doherty, Gavin B Chapman, Emma J Scholefield, Andrew Conway Morris, Jennifer M Felton, Tiina Kipari, Duncan C Humphries, Calum T Robb, A John Simpson, Phillip D Whitfield, Christopher Haslett, Kevin Dhaliwal, Adriano G Rossi
Journal: Thorax (2017)

<h3>Background</h3> Acute respiratory distress syndrome (ARDS) is an often fatal neutrophil-dominant lung disease. Although influenced by multiple proinflammatory mediators, identification of suitable therapeutic candidates remains elusive. We aimed to delineate the presence of mitochondrial formylated peptides in ARDS and characterise the functional importance of formyl peptide receptor 1 (FPR1) signalling in sterile lung inflammation. <h3>Methods</h3> Mitochondrial formylated peptides were identified in bronchoalveolar lavage fluid (BALF) and serum of patients with ARDS by liquid chromatography–tandem mass spectrometry. In vitro, human neutrophils were stimulated with mitochondrial formylated peptides and their effects assessed by flow cytometry and chemotaxis assay. Mouse lung injury was induced by mitochondrial formylated peptides or hydrochloric acid. Bone marrow chimeras determined the contribution of myeloid and parenchymal FPR1 to sterile lung inflammation. <h3>Results</h3> Mitochondrial formylated peptides were elevated in BALF and serum from patients with ARDS. These peptides drove neutrophil activation and chemotaxis through FPR1-dependent mechanisms in vitro and in vivo. In mouse lung injury, inflammation was attenuated in Fpr1−/− mice, effects recapitulated by a pharmacological FPR1 antagonist even when administered after the onset of injury. FPR1 expression was present in alveolar epithelium and chimeric mice demonstrated that both myeloid and parenchymal FPR1 contributed to lung inflammation. <h3>Conclusions</h3> We provide the first definitive evidence of mitochondrial formylated peptides in human disease and demonstrate them to be elevated in ARDS and important in a mouse model of lung injury. This work reveals mitochondrial formylated peptide FPR1 signalling as a key driver of sterile acute lung injury and a potential therapeutic target in ARDS.
Patient access to health records: striving for the Swedish ideal
Authors: Stephen Armstrong
Journal: BMJ (2017)

All patients in Sweden will shortly have access to their full medical records. Stephen Armstrong reports on the the country’s 20 year struggle to achieve this and what the UK can learn

This spring Stockholm, the last of Sweden’s 22 counties to implement patient accessible electronic health records, is rolling out the country’s Journalen patient portal service.1 The portal is part of the national e-health strategy, which states that “all residents from 16 years should by 2020 have access to all information documented in county funded health and dental care.2

Sweden is leading the way in offering all patients universal access to medical records—all its hospitals, primary care centres, and psychiatric facilities already use electronic health records. The figure in Europe is 65% overall and 81% in hospitals.3 By February 2017, 3 773 178 Swedes, or 37.9% of the population, had set up accounts. 

Patients can log in to the Journalen system using either an electronic identifier or their Swedish personal identity number.1 They are able to see notes from all healthcare professionals, a list of prescribed medications, test results, warnings, diagnosis, maternity care records, referrals, and vaccinations as well as a log of everyone who has accessed the record. The can also add comments to notes if, for example, information is incorrect.

The process was long and fraught, necessitating legal changes and research to allay a series of concerns, raised mostly by clinicians.3

The journey began in 1997 in the Uppsala region, a county north of Stockholm, with a project called Sustains 4—an attempt to set up an “internet health account,” much like an online bank account. Sustains was initially hampered by Swedish data protection laws, which did not allow patients to access records.5 It took the introduction of the Patient Data Act in …
Cardiovascular Risk Prediction in Patients With Human Immunodeficiency Virus
Authors: Paolo Raggi, Davide De Francesco, Giovanni Guaraldi
Journal: JAMA Cardiology (2017)

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 Cardiology 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 Cardiology journal
Beta-Blocker Drug Use and Survival among Patients with Pancreatic Adenocarcinoma
Authors: Ruzan Udumyan, Scott Montgomery, Fang Fang, Henrik Almroth, Unnur Valdimarsdottir, Anders Ekbom, Karin E. Smedby, Katja Fall
Journal: Cancer Research (2017)

Preclinical studies have suggested that β-adrenergic signaling is involved in pancreatic cancer progression. Prompted by such studies, we investigated an association between beta-blocker drug use with improved cancer-specific survival in a large, general population-based cohort of patients with pancreatic ductal adenocarcinoma (PDAC). All patients diagnosed with a first primary PDAC in Sweden between 2006 and 2009 were identified through the Swedish Cancer Register (n = 2,394). We obtained information about use of beta-blockers and other medications through linkage with the national Prescribed Drug Register. Cancer-specific mortality was assessed using the Swedish Cause of Death Register. We used multivariable Cox regression adjusted for sociodemographic factors, tumor characteristics, comorbidity score, and other medications to estimate HRs and 95% confidence intervals (CI) for cancer-specific mortality associated with beta-blocker use during the 90-day period before cancer diagnosis. A total of 2,054 (86%) died, with pancreatic cancer recorded as the underlying cause of death during a maximum of 5-year follow-up (median 5 months). Patients who used beta-blockers (n = 522) had a lower cancer-specific mortality rate than nonusers (adjusted HR, 0.79; 95% CI, 0.70-0.90; P < 0.001). This observed rate reduction was more pronounced among patients with localized disease at diagnosis (n = 517; adjusted HR, 0.60; 95% CI, 0.43-0.83; P = 0.002), especially for users with higher daily doses (HR, 0.54; 95% CI, 0.35-0.83; P = 0.005). No clear rate differences were observed by beta-blocker receptor selectivity. Our results support the concept that beta-blocker drugs may improve the survival of PDAC patients, particularly among those with localized disease. Cancer Res; 77(13); 3700-7. ©2017 AACR.
Cardiovascular Risk Prediction in Patients With Human Immunodeficiency Virus—Reply
Authors: Matthew J. Feinstein, Joseph A. Delaney, Heidi M. Crane
Journal: JAMA Cardiology (2017)

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 Cardiology 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 Cardiology journal