tbuckley/cabot-search huggingface dataset:
ARV7/AR ratio and neutrophil-to-lymphocyte ratio (NLR) as predictors of docetaxel benefit in metastatic castration-resistant prostate cancer patients (mCRPC).
Authors: Maria Coral Pérez-Gago, Mercedes Marín-Aguilera, Òscar Reig, Maria Veronica Pereira, Maria Milà, Natalia Jimenez, Iván Victoria, Nuria Chic, Begona Mellado
Journal: Journal of Clinical Oncology (2018)

254 Background: The constitutively active androgen receptor (AR) variant 7 (ARV7) has been associated to AR inhibitors resistance, but its role in taxane-benefit has not been stablished. Moreover, the neutrophil-to-lymphocyte ratio (NLR) has been associated with poor outcome in prostate cancer.The PBMC population may contain circulating tumor cells (CTCs) but is mainly constituted by lymphocytes and monocytes, that also express the AR. Here we studied the expression of ARV7 and AR in peripheral blood mononuclear cells (PBMC) and its correlation with NLR and clinical outcome in mCRPC treated with docetaxel. Methods: ARV7 and AR mRNAs were tested by quantitative reverse-transcription PCR. Baseline neutrophil and lymphocyte values and PBMC samples were prospectively collected before treatment initiation. Patients were stratified according to NLR ratio (low NLR: ≤3; high NLR:&gt;3) and to ARV7/ARFL ratio expression (Maxstat Cutoff 1.99). Correlation between NLR and PSA progression-free (PSA-PFS) and overall survival (OS), were measured from the start of docetaxel treatment and calculated by log rank test. Results: Fifty patients were included:25 (50%) had low NLR. Thirty-eight patients (76%) expressed high ARV7/ARFL. No significant correlation between NLR with ARV7, AR and ARV7/AR was observed. High ARV7/ARF ratio correlated to a better PSA-PFS (median PSA-PFS 7.47; HR 0.38, 95%CI 0.17-0.85; P=0.0179) , but not OS. High NLR was associated to a lower OS [Median OS was 9.2 months versus 30.17 months in those with low NLR (HR 2.19, 95% CI 1.17-4.09, p= 0.01)]. When both parameters were combined, high NLR and low ARV7/ARFL ratio were associated to a worse PSA-PFS in comparison with low NLR and high ARV7/ARFL ratiogroup(median PSA-PFS: 4.9 vs. 7.5; p=0.008 and HR 5.08, 95% CI 1.33-19.41, p= 0.08) and OS (median OS: 7.4 vs. 30.5; p=0.001 and HR 22.79, 95% CI 4.29-121.17, p= 0.00). Conclusions: The combination of low ARV7/ARFL high NLR and ratio evaluated in PBMC prior to docetaxel treatment has a predictive impact on response and survival in mCRPC patients.
Hospitals get new guidance on checking language competency of new staff
Authors: Ingrid Torjesen
Journal: BMJ (2012)

The General Medical Council has welcomed guidance from NHS Employers on how hospitals and other NHS employers should ensure that staff are competent in use of the English language.

The guidance, which aims to ensure that new NHS staff have the language skills needed to provide safe, good quality care to patients, was published in consultation with key partners, including the GMC and the Department of Health.

Niall Dickson, chief executive of the GMC, said, “The General …
Relationship between neutrophil lymphocyte ratio (NLR) and MDSC concentration in localized and metastatic castration resistant prostate cancer (mCRPC) patients.
Authors: Arnab Basu, Kanthi Athreya Kollengode, Ali Rafatnia, Hugh Manoli, Genevieve Danenberg, Eesha Chakravartty, Alan L. Epstein, Jacek K. Pinski
Journal: Journal of Clinical Oncology (2018)

338 Background: Human Myeloid Derived Suppressor Cells (MDSCs) have gained recognition as a significant population of cells that arise in cancer patients to mediate immune tolerance. MDSCs have been validated as a prognostic factor in several tumor types. The Neutrophil-Lymphocyte Ratio (NLR) is an easily obtained marker of inflammation that has also been validated as a prognostic marker in tumors including prostate cancer. We measured and compared MDSC concentrations and NLR in a cohort of patients with prostate cancer and also examined thier relationship with PSA Progression, a validated marker of overall survival. Methods: Blood was collected from patients with localized prostate cancer (n = 14) and mCRPC (n = 44) at 0 and 6 months. The percent CD33+ HLA-DRlow HIF1a+, CD33+ HLADRlow C/EBPb+, CD11b+ HLA-DRlow HIF1a+, and CD11b+ HLA-DRlow C/EBPb+cells as a fraction of PBMC were determined and reported. NLRs were obtained within 4 weeks of MDSC measurements. Patients were followed for a period of 2 years; PSA-Progression (PSA-P) was defined as a PSA doubling time of &lt; 3 months in association with an increase of at least &gt; 5ng/mL from PSA nadir Results: Higher Gleason scores were statistically associated with a NLR of greater than 2 (r = 0.07, p = 0.02, 95% CI [0.01-0.14]). Increasing MDSC% did not correlate with increasing Gleason scores (r = 0.13, p = 0.31) or predict PSA-P at 6 months (p = 0.16). MDSC% in patients with mCRPC (4.25%, 95% CI[3.34-5.17]) were significantly higher than localized prostate cancer (1.7%, 95% CI[1.02-2.37]) . There was a highly statistically significant relationship between the percentage of MDSC in PBMC with the neutrophil lymphocyte ratio (r = 0.68, p = 0.001, 95% CI [0.31-1.05]). Conclusions: MDSC concentrations in metastatic prostate cancer patients are significantly higher than those with localized disease and are associated with an increased neutrophil lymphocyte ratio. Although a trend was detected towards MDSC% predicting PSA-P, in this limited sample it was not statistically significant.
Admitting What We Do Not Know in Rheumatologic Disease
Authors: Megan M. Lockwood, Patrick G. O’Malley
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
PROSPER: A phase 3, randomized, double-blind, placebo (PBO)-controlled study of enzalutamide (ENZA) in men with nonmetastatic castration-resistant prostate cancer (M0 CRPC).
Authors: Maha Hussain, Karim Fizazi, Fred Saad, Per Rathenborg, Neal D. Shore, Eren Demirhan, Katharina Modelska, De Phung, Andrew Krivoshik, Cora N. Sternberg
Journal: Journal of Clinical Oncology (2018)

3 Background: Men with M0 CRPC and rapidly rising prostate-specific antigen (PSA) are at high risk of developing metastatic (M1) CRPC. ENZA improves overall survival (OS) and radiographic progression-free survival in men with M1 CRPC. We hypothesized that ENZA will improve metastasis-free survival (MFS) in men with M0 CRPC. Methods: Eligible men with M0 CRPC, PSA doubling time ≤ 10 mo and PSA ≥ 2 ng/mL at screening continued androgen deprivation therapy (ADT) and were randomized 2:1 to ENZA 160 mg or PBO. The primary endpoint was MFS. Secondary endpoints included time to PSA progression, time to first use of new antineoplastic therapy, OS and safety. Results: In 1401 men, ENZA significantly prolonged median MFS (36.6 mo vs 14.7 mo [ P &lt; .0001]), time to first use of new antineoplastic therapy (39.6 mo vs 17.7 mo [ P &lt; .0001]) and time to PSA progression (37.2 mo vs 3.9 mo [ P &lt; .0001]) compared to PBO (Table). In the first interim analysis of OS there was a trend in favor of ENZA (hazard ratio [HR] = 0.80; P = .1519). Median duration of treatment was 18.4 mo vs 11.1 mo for ENZA vs PBO. Adverse events (AEs) were higher with ENZA vs PBO (any grade: 87% vs 77%; grade ≥ 3: 31% vs 23%; serious: 24% vs 18%); 10% with ENZA discontinued treatment due to AE vs 8% with PBO. Conclusions: In men with M0 CRPC and rapidly rising PSA, ENZA treatment resulted in a clinically meaningful and statistically significant 71% reduction in the risk of developing M1 CRPC. AEs were consistent with the established safety profile of ENZA. Clinical trial information: NCT02003924. [Table: see text]
P078 A genetic variant of IL-32 is associated with the ex vivo cytokine production of ANTI-TNF treated pbmcs isolated from rheumatoid arthritis patients
Authors: C Popa, M Damen, K Schraa, L Tweehuysen, A den Broeder, M Netea, L Joosten
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Since the introduction of biologics in the treatment of rheumatoid arthritis (RA) disease outcome improved. Still, about 40% of RA patients do not respond to therapy with TNFα blockers. Previously, a strong link between TNFα and interleukin (IL)−32 has been reported in RA.<sup>1</sup> <h3>Objectives</h3> We hypothesise that a promoter single nucleotide polymorphism (SNP) in IL-32 can affect clinical responsiveness to anti-TNFα treatment in RA patients, functioning as a new biomarker in treatment of RA.<sup>2</sup> <h3>Methods</h3> Peripheral mononuclear cells (PBMCs) from RA patients and healthy individuals were stimulated with RPMI or recombinant human (rh)TNFα to study the mRNA and protein expression of IL-32 and other pro-inflammatory cytokines. Moreover, disease activity scores (DAS28), '<i>in vitro response</i>' and clinical response to anti-TNFα therapy (etanercept, adalimumab), of RA patients were measured and all were stratified for the IL-32 SNP (C/T). <h3>Results</h3> Stimulation of PBMCs from RA patients was followed by higher IL-32 protein production and a tendency towards higher IL-32β and IL-32γ mRNA expression compared to healthy individuals. When data was stratified for the IL-32 promoter SNP, patients bearing the CC genotype showed higher IL-32 protein expression. Of interest, these patients also produced more cytokines. Even though the DAS28 did not depend on the presence of the promoter SNP, the '<i>ex vivo'</i> cytokine response did have a different pattern in clinical responders depending on the genotype. <h3>Conclusions</h3> IL-32 mRNA and protein production was higher in RA patients compared to healthy individuals, with a trend towards higher concentrations in patients bearing the CC genotype. Regardless of the fact that the promoter SNP was not associated with disease activity, IL-1 beta production in the CC-genotype might predict clinical response to either etanercept or adalimumab. <h3>References</h3> . Heinhuis B, et al. Ann Rheum Dis2011;70:660–7. . Damen MS, et al. Sci Rep2017;7:41629. <h3>Disclosure of interest</h3> None declared
Plasma Connective Tissue Growth Factor (CTGF/CCN2) Levels Predict Myocardial Infarction in the Veterans Affairs Diabetes Trial (VADT) Cohort
Authors: Kelly J. Hunt, Miran A. Jaffa, Sara M. Garrett, Deirdre K. Luttrell, Kenneth E. Lipson, Maria F. Lopes-Virella, Louis M. Luttrell, Ayad A. Jaffa, Maria F. Lopes-Virella, Kelly J. Hunt, Nathaniel L. Baker, Gabriel Virella, Thomas Moritz
Journal: Diabetes Care (2018)

Connective tissue growth factor (CTGF), also known as CCN2, is a potent chemotactic and extracellular matrix-inducing matricellular protein that has been implicated in progression of inflammatory and fibroproliferative disorders. An emerging role of CTGF/CCN2 is that of a prosclerotic factor implicated in the development of cardiac disease. Our objective was to determine the role of CTGF/CCN2 as a predictor of cardiovascular events in type 2 diabetes in the Veterans Affairs Diabetes Trial (VADT) cohort.Levels of CTGF/CCN2 were measured in 952 VADT patients a median of 1.9 years after entry into the study. Participants were followed for an average of 3.3 years for vascular outcomes. CTGF/CCN2 categories were defined as below the detectable limit (referent, 54.5%), lower half of detectable values (22.8%), and upper half of detectable values (22.7%). Hazard ratios (HRs) for cardiovascular end points in relation to CTGF/CCN2 categories were calculated by Cox proportional hazards models.During follow-up, 4.8% had a myocardial infarction (MI), 6.9% had an MI or cardiovascular death, and 6.9% died. After adjustments by conventional risk factors, individuals in the highest category of CTGF/CCN2 were at higher risk of MI (HR 2.43 [95% CI 1.15, 5.14]), MI or cardiovascular death (HR 2.71 [95% CI 1.44, 5.08]), and all-cause mortality (HR 2.70 [95% CI 1.43, 5.08]) relative to individuals with CTGF below the detectable limit.Our study indicates that high levels of CTGF/CCN2 predict future MI and cardiovascular death in patients with type 2 diabetes.
COMPARISON OF PERCUTANEOUS PATENT FORAMEN OVALE CLOSURE AND MEDICAL THERAPY FOR SECONDARY PREVENTION OF CRYPTOGENIC STROKE: A META-ANALYSIS
Authors: Manuel Rivera, Andrew Panakos, Kunal Kapoor, Gilson Fernandes, Gerardo Zablah, Rhanderson Cardoso, Leonardo Kijnik, Eduardo De Marchena
Journal: Journal of the American College of Cardiology (2018)
A third of foundation doctors have not had feedback from a senior doctor, GMC finds
Authors: Abi Rimmer
Journal: BMJ (2014)

Over a third of foundation doctors have rarely or never received feedback on their performance from a senior clinician, the General Medical Council’s national training survey has found.

The GMC’s survey took place between March and May 2013 and received 14 615 responses from doctors in foundation training.1 This represented a 98.5% response rate, but not all respondents answered every question in the survey.

Of the 14 459 foundation doctors who responded to a question on feedback, 39% said that they had rarely or never received informal …
Abstract 12757: The Combination of Dyssynchrony and Global Longitudinal Strain by 3D Speckle Tracking After ST-Elevation Myocardial Infarction is Useful for Prediction of Final Infarct Size and Left Ventricular Remodeling
Authors: Noriaki Iwahashi, Masaomi Gohbara, Shunsuke Kataoka, Eiichi Akiyama, Nobuhiko Maejima, Kengo Tsukahara, Kiyoshi Hibi, Masami Kosuge, Toshiaki Ebina, Satoshi Umemura, Kazuo Kimura
Journal: Circulation (2014)

Background: Left ventricular (LV) global strain estimated immediately after ST elevation AMI (STEMI) was reported as a predictor of LV remodeling. Furthermore, LV dyssynchrony estimated by 2D strain is also a prognosticator. However, strain analysis ideally should be assessed by 3D speckle tracking, in order to avoid through plane motion. We explored the usefulness of these two variable assessed by 3D speckle tracking in patients with a first STEMI. Methods: Consecutive 190 patients (131 men, age 65 years, peak CPK=3169 IU/l) presenting with a first STEMI who underwent primary PCI within 12 hours of onset were enrolled. Within 24 h of PCI, echocardiography was performed by iE33(Philips). 3D speckle tracking was analyzed by 4D LV-Analysis (TOM-TEC, Germany). Global longitudinal strain was calculated (3D-GLS) and the standard deviation (SD) of time to regional peak 3D longitudinal strain (3D-Long-SD) for all 16 segments was assessed as the parameter of dyssynchrony. Final infarct size was defined using Tc99m-sestamibi as the total area of &lt;50%uptake area at 2 weeks. Echocardiography was repeated 12 months later and LV remodeling was defined as an absolute increase in LVEDV of more than 20%. Results: LV remodeling was observed in 52 patients at 12 months. Both 3D-GLS and 3D-Long-SD had significant relationships with infarct size (r2=0.236, 0.169, p&lt;0.0001). Furthermore, both of the worst tertile of them predicted LV remodeling (Odds ratio = 2.634, 95%CI; 1.322-5.308, p&lt;0.001) (Odds ratio = 3.846, 95%CI;1.887-8.011, p&lt;0.001). Table shows logistic regression analysis for LV remodeling and the combination of these indexes was the strongest predictor (Odds ratio = 2.58, 95%CI 1.003-6.723, p=0.04). Conclusions: In patients with a first STEMI, GLS and LV dyssynchrony assessed by 3D speckle tracking echocardiography immediately after PCI can predict final infarct size and LV remodeling. The combination of these parameters was especially useful to predict LV remodeling.
Abstract P6-08-26: Outcomes and prognostic factors in 2000 patients with TNBC: Long-term results covering 10 years
Authors: Z Morante, J Pinto, D Enriquez, J Araujos, R Luque, E Eyzaguirre, A Saavedra, H Fuentes, S Neciosup, H Gomez
Journal: Cancer Research (2018)

Abstract Background: Triple-negative breast cancer (TNBC) is characterized by being a heterogeneous disease with different risk factors and poor survival rates. TNBC have a higher prevalence in the Peruvian population (21.3%) than in Caucasian groups. Our study aims to determine the outcome and identify prognostic factors in Peruvian women with TNBC. Methods: We retrospectively analyzed TNBC patients treated at the “Instituto Nacional de Enfermedades Neoplasicas” between 2000 and 2014. Survival rates and differences were calculated by the Kaplan-Meier method and Log-rank test, respectively. With the Cox regression, in univariate and multivariate analysis, we identified prognostic factors in for our TNBC population. Results: In total, 2007 patients were diagnosed.The mean age was 50 years (range: 19-95 years); 44.8% were premenopausal and 26.2% had obesity at diagnosis. A family history of breast and/or ovarian cancer was present in 266 (28.9%) patients. Regarding the clinical-pathological features, 1860 (93.5%) had ductal invasive carcinoma and 1024 (51.6%) patients were in Stage (S) III. Local relapse and distant metastasis affected to 34.5% and 51.4% of our patients, respectively. Lung (14.5%) and bone (9.7%) were the most frequent sites of metastasis. The median follow-up was 9 years. The 5 and 10 yrs DFS/OS rates are shown in table 1. In the multivariate analysis, adjuvant chemotherapy (ACT) (HR: 0.60, 95%CI: 0.44-0.82, p=0.001) and radiotherapy (RT) (HR:0.72, 95%CI:0.55-0.93, p=0.014) were associated with a reduced risk of recurrence, while nodal involvement were associated to a high recurrence risk. Factors associated to a reduction in the risk of death were ACT (HR:0.73, 95%CI:0.61-0.88, p=0.001), RT (HR: 0.70, 95%CI: 0.60-0.92, p&amp;lt;0.001), and Neoadjuvant CT (HR: 0.61, 95%CI: 0.51-0.73, p&amp;lt;0.001); in contrast, a NLR≥3 (HR:1.60,95%CI: 1.36-1.87, p&amp;lt;0.001), N stage were associated with a higher risk of death. Conclusions: Sociodemographic features of Peruvian patients with TNBC resemble other populations; however, our population is diagnosed at more advanced clinical stages, hence DFS and OS were lower than international reports while prognostic factors were similar to previous studies. Table 1. 5- and 10-years DFS/OS ratesClinical StageIIIIIIIVTotalp (value)DFS (%) &amp;lt;0.0015-years837540-63 10-years696429-52 OS (%) &amp;lt;0.0015-years938239655 10-years837532550 Citation Format: De la Cruz-Ku G, Morante Z, Pinto J, Enriquez D, Araujos J, Luque R, Eyzaguirre E, Saavedra A, Fuentes H, Neciosup S, Gomez H. Outcomes and prognostic factors in 2000 patients with TNBC: Long-term results covering 10 years [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-08-26.
Doctors should seek patient feedback more than once every five years, say MPs
Authors: Helen Jaques
Journal: BMJ (2012)

Doctors undergoing revalidation should seek feedback from patients more often than once every five years to ensure that patients have a genuine opportunity to air their views, MPs have said.

Revalidation regulations require that doctors use questionnaires to seek formal feedback from up to 45 consecutive patients (minimum 34) at least once in every five year cycle.1

However, MPs on …
Margaret McCartney: Medicine must do better on gender
Authors: Margaret McCartney
Journal: BMJ (2018)

Medicine has a shameful history when it comes to sex, gender, and identity. Attempts have been made to “fix” sex, for example, by intervening surgically to “normalise” the genital appearances of intersex people. This happened despite a lack of evidence of benefit and showed disregard for individuals’ feelings over time12—including a lack of full information about their own condition or support, especially regarding fertility. Even well intentioned medicine can do grievous harm.

In recent years terms such as “non-binary” and “gender fluid” have entered the mainstream. The Office for National Statistics may make declaration of sex voluntary in the 2021 census, out of concern that it discriminates against and offends transgender people.3 NHS IT systems don’t respond flexibly: for example, transgender men may …
Divisions, New and Old — Conscience and Religious Freedom at HHS
Authors: Lisa H. Harris
Journal: New England Journal of Medicine (2018)

Interview with Dr. Lisa Harris on HHS's new Conscience and Religious Freedom Division and polarized rhetoric about abortion. (12:11)Download In creating a Conscience and Religious Freedom Division, leaders of the U.S. Department of Health and Human Services have framed "conscience" in a one-sided way, making it yet another issue dividing Americans largely along partisan lines.
EARLY DIASTOLIC STRAIN RATE BY TWO-DIMENSIONAL SPECKLE TRACKING ECHOCARDIOGRAPHY IS A PREDICTOR OF CORONARY ARTERY DISEASE AND CARDIOVASCULAR EVENTS IN STABLE ANGINA PECTORIS
Authors: Rikke Andersen, Soren Hoffmann, Christoffer Hagemann, Philip Brainin, Thomas Fritz-Hansen, Flemming Javier Olsen, Jan Jensen, Tor Biering-Sørensen
Journal: Journal of the American College of Cardiology (2018)