tbuckley/cabot-search huggingface dataset:
Long-Term Exposure to Fine Particulate Matter, Blood Pressure, and Incident Hypertension in Taiwanese Adults
Authors: Zilong Zhang, Cui Guo, Alexis K.H. Lau, Ta-Chien Chan, Yuan Chieh Chuang, Changqing Lin, Wun Kai Jiang, Eng-kiong Yeoh, Tony Tam, Kam S. Woo, Bryan P. Yan, Ly-yun Chang, Martin C.S. Wong, Xiang Qian Lao
Journal: Environmental Health Perspectives (2018)

Background: Long-term exposure to particulate matter (PM) air pollution may increase blood pressure and the risk of hypertension. However, epidemiological evidence is scarce and inconsistent. Objectives: We investigated the associations between long-term exposure to PM with an aerodynamic diameter <2.5μm (PM2.5), blood pressure, and incident hypertension in a large Taiwanese cohort. Methods: We studied 361,560 adults ≥18y old from a large cohort who participated in a standard medical examination program during 2001 to 2014. Among this group, 125,913 nonhypertensive participants were followed up. A satellite-based spatiotemporal model was used to estimate the 2-y average PM2.5 concentrations at each participant's address. Multivariable linear regression was used in the cross-sectional data analysis with the 361,560 participants to investigate the associations between PM2.5 and systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP), and Cox proportional hazard regression was used in the cohort data analysis with the 125,913 participants to investigate the associations between PM2.5 and incident hypertension. Results: Each 10-μg/m3 increment in the 2-y average PM2.5 concentration was associated with increases of 0.45 mmHg [95% confidence interval (CI): 0.40, 0.50], 0.07 mmHg (95% CI: 0.04, 0.11), and 0.38 mmHg (95% CI: 0.33, 0.42) in SBP, DBP, and PP, respectively, after adjusting for a wide range of covariates and possible confounders. Each 10-μg/m3 increment in the 2-y average PM2.5 concentration was associated with an increase of 3% in the risk of developing hypertension [hazard ratio=1.03 (95% CI: 1.01, 1.05)]. Stratified and sensitivity analyses yielded similar results. Conclusions: Long-term exposure to PM2.5 air pollution is associated with higher blood pressure and an increased risk of hypertension. These findings reinforce the importance of air pollution mitigation strategies to reduce the risk of cardiovascular disease. https://doi.org/10.1289/EHP2466
Rogaratinib treatment of patients with advanced urothelial carcinomas prescreened for tumor FGFR mRNA expression.
Authors: Markus Joerger, Philippe Cassier, Nicolas Penel, Richard Cathomas, Heike Richly, Martin Schostak, Andreas Janitzky, Martin Wermke, Lucia Nogova, David Wai-Meng Tai, Cyrus Sayehli, Carsten Grüllich, Enrique Grande, Alejandra Navarro, Se Hoon Park, Silke Gillessen, Hendrik Nogai, Sebastian Bender, Peter Ellinghaus, Martin H. Schuler
Journal: Journal of Clinical Oncology (2018)

494 Background: Activation of FGFR signaling is involved in a variety of malignancies including advanced urothelial cancer (UC). Rogaratinib is an oral pan-FGFR kinase inhibitor. We report here the results from a phase I expansion cohort in UC patients prescreened for FGFR1-3 mRNA expression levels and activating mutations. (NCT01976741) Methods: Patients with advanced urothelial carcinomas were selected based on high FGFR1-3 mRNA expression in biopsy specimens. Selected patients were treated with rogaratinib 800mg twice daily until tumour progression, untolerable toxicity, or withdrawal. Tumor response was assessed by RECIST, v1.1. Adverse events were reported using CTCAE v4.03 criteria. Results: A total of 219 UC patients were prescreened for FGFR1-3 mRNA expression levels and FGFR3 activating mutations, with 99 samples (45%) found to be FGFR-positive. Of those, 87% of samples were positive for FGFR3 mRNA, 5% for FGFR1 mRNA and 8% were double FGFR mRNA-positive (FGFR1/2, 1/3 or 2/3). Frequency of FGFR3 activating mutations in UC samples was 7%, all of which also had high FGFR3 mRNA. Fifty two patients (median prior line of treatment 2) started treatment and 51 were evaluable for response. Rogaratinib was generally well tolerated and AEs manageable with dose modification. The most common AEs were diarrhea (49%) and hyperphosphatemia (49%). Objective response rate (ORR) was 24% (12/51; all PRs) and disease control rate (DCR) was 73% (37/51). Eleven of 12 pts with a PR were positive for FGFR3 mRNA, 5 of whom also had FGFR3 mutations, and one patient was positive for FGFR1 mRNA. Ten FGFR-positive UC patients had prior immuno-oncology (I/O) treatment, 9 of whom had progressive disease as best response. For these 10 patients the ORR was 30% and the DCR 80%. Conclusions: Selection of pts for treatment with rogaratinib based on FGFR mRNA expression levels was feasible and identified drug-sensitive patients with and without underlying DNA alterations. Rogaratinib had a favorable safety profile and showed promising anti-tumor activity in UC patients. Responses and disease stabilization were observed with rogoratinib in UC pts refractory to prior I/O treatment. Clinical trial information: NCT01976741.
Validation of a novel preoperative inflammatory score in localized, clear cell RCC.
Authors: Kevin Richard Melnick, Dattatraya H Patil, Amir Ishaq Khan, Frances Y Kim, Mehmet Asim Bilen, Bradley Curtis Carthon, Omer Kucuk, Christopher Paul Filson, Kenneth Ogan, Haydn T. Kissick, Viraj A. Master
Journal: Journal of Clinical Oncology (2018)

697 Background: A previously created and analyzed composite renal cell carcinoma (RCC) inflammatory score composed of preoperative serum markers was found to be a significant and independent predictor of overall survival in RCC with accuracy at least as good as other established prognostic tools. The aim of our study was therefore to validate the prognostic significance of this novel score in a new, independent cohort of localized clear cell RCC patients. Methods: A new cohort was randomly selected out of our nephrectomy database from a group of patients with localized clear cell RCC, who underwent nephrectomy from March 2007 to June 2017. Biomarker composition, cutoffs, and calculations of the RCC inflammatory score were accurately recreated from the previous publication. The final score was the sum of points accrued for each biomarker, ranging from 0-10, followed by stratification into baseline (0), low (1-3), intermediate (4-6), and high-risk (7-10) groups. ROC and chi-square analysis were performed to compare the prognostic ability of this novel score to SSIGN, UISS, mGPS, and Leibovich Scores. Impact on overall survival was analyzed with multivariate logistic regression analysis. Results: 252 patients were included in the study. On multivariate analysis, after adjusting for confounding variables, a “high-risk” RCC inflammatory score proved to be an independent and significant predictor of increased mortality (HR = 9.65, 95%CI 1.06-87.79, p = 0.044). At median follow up time, only 45% of high-risk score patients were alive compared with 89-98% of all other patients. Chi-square analysis of c-indices for the RCC inflammatory score and current prognostic scores revealed no statistically significant difference in prognostication of overall survival. Conclusions: Concordant with our previous data, this study reveals that a high-risk RCC inflammatory score is an independent and significant predictor of overall survival in localized clear cell RCC with comparable accuracy to accepted prognostic tools. Distinct from the original study, the high-risk group displayed an even greater association than previously shown, but the intermediate-risk group was no longer significantly different from baseline risk.
Combination of Follicular and Epidermal Cell Suspension as a Novel Surgical Approach in Difficult-to-Treat Vitiligo
Authors: Muhammed Razmi T, Ravinder Kumar, Seema Rani, Sendhil M. Kumaran, Sushma Tanwar, Davinder Parsad
Journal: JAMA Dermatology (2018)

<h3>Importance</h3> Epidermal cell suspension (ECS) and follicular cell suspension (FCS) are successful surgical modalities for the treatment of stable vitiligo. However, repigmentation in generalized and acrofacial vitiligo and over acral or bony sites (eg, elbows, knees, iliac crests, and malleoli), which are difficult to treat, is challenging. <h3>Objective</h3> To study the efficacy of transplanting a combination of autologous, noncultured ECS and FCS (ECS + FCS) compared with ECS alone in stable vitiligo. <h3>Design, Setting, and Participants</h3> A prospective, observer-blinded, active-controlled, randomized clinical trial was conducted at a tertiary care hospital, with treatment administered as an outpatient procedure. Thirty participants who had stable vitiligo with symmetrical lesions were recruited between October 18, 2013, and October 28, 2016. All of the lesions were resistant to medical modalities with minimum lesional stability of 1 year. Intent-to-treat analysis was used. <h3>Interventions</h3> ECS + FCS was prepared by mixing equal amounts (in cell number) of FCS with ECS. After manual dermabrasion, ECS was applied to 1 lesion and ECS + FCS was applied to the anatomically based paired lesion of the same patient. No adjuvant treatment was given. <h3>Main Outcomes and Measures</h3> Patients were followed up at 4, 8, and 16 weeks by a blinded observer and extent of repigmentation, color match, pattern of repigmentation, patient satisfaction and complications were noted. Both the visual and the computerized image analysis methods were used for outcome assessment. Cell suspensions were assessed post hoc for OCT4+ stem cell counts using flow cytometry; expression of stem cell factor and basic fibroblast growth factor was evaluated using quantitative relative messenger RNA expression. <h3>Results</h3> Of the 30 patients included in the study, 18 (60%) were women; mean (SD) age was 23.4 (6.4) years. Seventy-four percent of the lesions (62 of 84) were difficult-to-treat vitiligo. ECS + FCS showed superior repigmentation outcomes compared with ECS: extent (76% vs 57%,<i>P</i> &lt; .001), rapidity (48% vs 31%,<i>P</i> = .001), color match (73% vs 61%,<i>P</i> &lt; .001), and patient satisfaction (mean [SD] patient global assessment score, 23.30 [6.89] vs 20.81 [6.61],<i>P</i> = .047). Melanocyte stem cell counts (2% in ECS + FCS vs 0.5% in ECS) as well as expression of basic fibroblast growth factor (11.8-fold) and stem cell factor (6.0-fold) were higher in ECS + FCS suspension (<i>P</i>&lt;.05 for both). <h3>Conclusions and Relevance</h3> The findings from this study establish ECS + FCS as a novel approach in vitiligo surgery for attaining good to excellent repigmentation in a short period with good color match, even in difficult-to-treat vitiligo. <h3>Trial Registration</h3> ctri.nic.in Identifier:CTRI/2017/05/008692
Telemonitoring in Chronic Obstructive Pulmonary Disease (CHROMED). A Randomized Clinical Trial
Authors: Paul P. Walker, Pasquale P. Pompilio, Paolo Zanaboni, Trine S. Bergmo, Kaiu Prikk, Andrei Malinovschi, Josep M. Montserrat, Jo Middlemass, Silvana Šonc, Giulia Munaro, Dorjan Marušič, Ruth Sepper, Roberto Rosso, A. Niroshan Siriwardena, Christer Janson, Ramon Farré, Peter M. A. Calverley, Raffaele L. Dellaca’
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: Early detection of chronic obstructive pulmonary disease (COPD) exacerbations using telemonitoring of physiological variables might reduce the frequency of hospitalization.Objectives: To evaluate the efficacy of home monitoring of lung mechanics by the forced oscillation technique and cardiac parameters in older patients with COPD and comorbidities.Methods: This multicenter, randomized clinical trial recruited 312 patients with Global Initiative for Chronic Obstructive Lung Disease grades II to IV COPD (median age, 71 yr [interquartile range, 66–76 yr]; 49.6% grade II, 50.4% grades III–IV), with a history of exacerbation in the previous year and at least one nonpulmonary comorbidity. Patients were randomized to usual care (n = 158) or telemonitoring (n = 154) and followed for 9 months. All telemonitoring patients self-assessed lung mechanics daily, and in a subgroup with congestive heart failure (n = 37) cardiac parameters were also monitored. An algorithm identified deterioration, triggering a telephone contact to determine appropriate interventions.Measurements and Main Results: Primary outcomes were time to first hospitalization (TTFH) and change in the EuroQoL EQ-5D utility index score. Secondary outcomes included: rate of antibiotic/corticosteroid prescription; hospitalization; the COPD Assessment Tool, Patient Health Questionnaire-9, and Minnesota Living with Heart Failure questionnaire scores; quality-adjusted life years; and healthcare costs. Telemonitoring did not affect TTFH, EQ-5D utility index score, antibiotic prescriptions, hospitalization rate, or questionnaire scores. In an exploratory analysis, telemedicine was associated with fewer repeat hospitalizations (−54%; P = 0.017).Conclusions: In older patients with COPD and comorbidities, remote monitoring of lung function by forced oscillation technique and cardiac parameters did not change TTFH and EQ-5D.Clinical trial registered with www.clinicaltrials.gov (NCT 01960907).
Prognostic Value of the Acute-to-Chronic Glycemic Ratio at Admission in Acute Myocardial Infarction: A Prospective Study
Authors: Giancarlo Marenzi, Nicola Cosentino, Valentina Milazzo, Monica De Metrio, Milena Cecere, Susanna Mosca, Mara Rubino, Jeness Campodonico, Marco Moltrasio, Ivana Marana, Marco Grazi, Gianfranco Lauri, Alice Bonomi, Fabrizio Veglia, Roberto Manfrini, Antonio L. Bartorelli
Journal: Diabetes Care (2018)

OBJECTIVE Acute hyperglycemia is a powerful predictor of poor prognosis in acute myocardial infarction (AMI), particularly in patients without diabetes. This emphasizes the importance of an acute glycemic rise rather than glycemia level at admission alone. We investigated in AMI whether the combined evaluation of acute and chronic glycemic levels, as compared with admission glycemia alone, may have a better prognostic value. RESEARCH DESIGN AND METHODS We prospectively measured admission glycemia and estimated average chronic glucose levels (mg/dL) by the following formula: [(28.7 × glycosylated hemoglobin %) − 46.7], and calculated the acute-to-chronic (A/C) glycemic ratio in 1,553 consecutive AMI patients (mean ± SD age 67 ± 13 years). The primary end point was the combination of in-hospital mortality, acute pulmonary edema, and cardiogenic shock. RESULTS The primary end point rate increased in parallel with A/C glycemic ratio tertiles (5%, 8%, and 20%, respectively; P for trend &amp;lt;0.0001). A parallel increase was observed in troponin I peak value (15 ± 34 ng/mL, 34 ± 66 ng/mL, and 68 ± 131 ng/mL; P &amp;lt; 0.0001). At multivariable analysis, A/C glycemic ratio remained an independent predictor of the primary end point and of troponin I peak value, even after adjustment for major confounders. At reclassification analyses, A/C glycemic ratio showed the best prognostic power in predicting the primary end point as compared with glycemia at admission in the entire population (net reclassification improvement 12% [95% CI 4–20]; P = 0.003) and, particularly, in patients with diabetes (27% [95% CI 14–40]; P &amp;lt; 0.0001). CONCLUSIONS In AMI patients with diabetes, A/C glycemic ratio is a better predictor of in-hospital morbidity and mortality than glycemia at admission.
TH1/17 hybrid CD4+ cells in bronchial alveolar lavage fluid from leukemia patients with checkpoint inhibitor-induced pneumonitis.
Authors: Sang Kim, Vickie Shannon, Ajay Sheshadri, Hagop M. Kantarjian, Guillermo Garcia-Manero, Jin Im, Farhad Ravandi, Aung Naing, Andrew Futreal, Naval Guastad Daver
Journal: Journal of Clinical Oncology (2018)

204 Background: Immune checkpoint inhibitor (ICI)-based therapies are showing encouraging results for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). 20% of AML or MDS patients receiving an ICI develop lung inflammation (herein, pneumonitis), one of fatal immune related adverse events (irAEs). The mechanisms of pneumonitis, the most important step for risk stratification and early detection, remain elusive. Methods: We analyzed bronchial alveolar lavage (BAL) fluid from 8 AML or MDS patients, who received an ICI, developed respiratory symptoms, and underwent a standard-of-care bronchoscopy. As a control, we analyzed BAL fluid from 5 AML or MDS patients who had never received an ICI or had received last ICI more than 16 weeks prior to the bronchoscopy. We also analyzed matched blood within 72 hours after the bronchoscopy. We stained CD4 + cells with lineage specific markers, including CXCR3, CXCR5, CD25, CD127, CCR4, and CCR6. Proportion of the CD4 + cell subsets within total CD4 + lymphocytes in BAL and blood were compared between the pneumonitis and controls. Results: Th1 (CXCR3 hi ) CD4 + cells were expanded in controls in BAL (pneumonitis versus control, 4.2 ± 2.5 % versus 17.2 ± 6.3 % within total CD4 + lymphocytes, P= 0.04) and blood (pneumonitis versus control, 0.5 ± 0.3 % versus 4.0 ± 1.3 % within total CD4 + lymphocytes, P= 0.01). In contrast, Th1/17 (CXCR3 hi CCR6 hi ) hybrid CD4 + cells, known to be pathogenic in autoimmune diseases, were expanded in BAL from the pneumonitis group (pneumonitis versus control, 40.3 ± 8.4 % versus 13.7 ± 4.5 % within total CD4 + lymphocytes, P= 0.03). Th1/17 hybrid CD4 + cells were also PD-1 hi Ki67 hi , suggesting their hyperactive status. Though not reached statistical significance, regulatory T cells were decreased in BAL from pneumonitis group (pneumonitis versus control, 20.8 ± 4.9 % versus 26.2 ± 9.2 % within total CD4 + lymphocytes). Conclusions: These results suggest that Th1/17 hybrid CD4 + cells may play a central role in pneumonitis. Understanding of the Th1/17 hybrid CD4 + cell biology will provide therapeutic targets and reliable biomarkers for pneumonitis.
Shadowing period to be introduced for new foundation year 1 doctors
Authors: Helen Jaques
Journal: BMJ (2012)

Newly qualified doctors in England will have to complete a minimum of four days shadowing their prospective foundation year 1 job before they start in the post this summer, the Department of Health has announced.

The mandatory paid shadowing period will help new doctors to become familiar with the hospital in which they will be working and their specific clinical responsibilities, as well as reduce the level of stress that many newly qualified doctors experience and improve patient safety, said Bruce Keogh, the NHS’s medical director, announcing the change in his letter to final year …
CLINICAL IMPACT OF NEW LEFT BUNDLE BRANCH BLOCK IN INTERMEDIATE RISK PATIENTS UNDERGOING TAVR: AN ANALYSIS OF THE PARTNER II TRIAL AND REGISTRIES
Authors: Tamim Nazif, Isaac George, Jose Dizon, Rebecca T. Hahn, Aaron Crowley, Vasilis Babaliaros, Howard Herrmann, David Brown, Raj Makkar, Richard Smalling, Samir Kapadia, John Webb, Martin B. Leon, Susheel K. Kodali
Journal: Journal of the American College of Cardiology (2018)
Effects of treatment for psoriasis on circulating levels of leptin, adiponectin and resistin: a systematic review and meta-analysis
Authors: A. Kyriakou, A. Patsatsi, D. Sotiriadis, D.G. Goulis
Journal: British Journal of Dermatology (2018)

Metabolic syndrome, a risk factor of cardiovascular disease, is more common in patients with psoriasis than in the general population. Circulating adipokine concentrations are altered in patients with psoriasis and are suggested to represent the pathophysiological link between psoriatic lesions and metabolic alterations. To perform a systematic review of the literature for studies that investigated possible differences in circulating levels of leptin, adiponectin or resistin in patients with psoriasis before and after any treatment intervention, and to meta‐analyse the best evidence available. A search was conducted in three databases (PubMed, Central and Embase). Eligible for the review were studies that assessed leptin, adiponectin or resistin concentrations in patients with psoriasis before and after any topical or systemic treatment. After treatment, blood concentrations of leptin were similar to those before treatment [standardized mean difference (SMD) 0·06, 95% confidence interval (CI) −0·09 to 0·20], with no heterogeneity among studies (I2 = 0%, P = 0·88). After treatment, blood concentrations of adiponectin were similar to those before treatment (SMD −0·14, 95% CI −0·34 to 0·05), with significant heterogeneity among studies (I2 = 36·8%, P = 0·032). After treatment, blood concentrations of resistin were significantly lower than those before treatment (SMD 0·50, 95% CI 0·20–0·79), with significant heterogeneity among studies (I2 = 61·4%, P < 0·001). There is no evidence that treatment for psoriasis modifies leptin and adiponectin concentrations. However, treatment intervention reduces resistin concentrations, a finding that is expected to be of clinical importance.
In defence of gynaecological teaching associates
Authors: Jane Dent
Journal: BMJ (2004)

EDITOR—As a gynaecological teaching associate (GTA) myself, I'd like to respond to some of Syed Sohaib's comments in Lucy Cowdrey's article.1

“Using GTAs is only partially beneficial to students as these women all have normal anatomy. ” The most common criticism of the programme is that we have normal bodies and are unable to teach pathology. I do not think …
Factors associated with underuse of mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction: an analysis of 11 215 patients from the Swedish Heart Failure Registry
Authors: Gianluigi Savarese, Juan‐Jesus Carrero, Bertram Pitt, Stefan D. Anker, Giuseppe M.C. Rosano, Ulf Dahlström, Lars H. Lund
Journal: European Journal of Heart Failure (2018)
I am interested in doing a fellowship in oculoplastics. When is the best time to apply and where?
Authors: Amar Alwitry
Journal: BMJ (2007)

Have a career related problem that needs answering? Can9t find the person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site <b>www.bmjcareers.com/advicezone</b>
Studies on the Biological Action of Malononitriles
Authors: Emery M. Gal, Fung-Haan Fung, David M. Greenberg, Harriet Ezra, Sherburne F. Cook
Journal: Cancer Research (1952)

1.  Malononitriles did not inhibit the rhodanese activity in tissue homogenates, nor did they competitively displace the cyanide.

2.  The rhodanese content of fetal tissue increased in amount with development and at birth. The rhodanese activity of the tissue of the mother was not significantly influenced by pregnancy.

3.  Animals fed 3′-methyl-4-dimethylaminoazobenzene showed a slight decrease in the rhodanese activity coincident with the development of hepatoma. The hepatoma itself showed a significantly damaged rhodanese activity, while the surrounding unimpaired liver tissues continued functioning normally.

4.  The Walker rat carcinoma 256 produced a general lowering of the rhodanese activity in the tissues, which could not be correlated with either loss of weight or a lowered food intake. This was not the case in the tissues of mice with transplanted tumors.

5.  A detailed analysis of different mouse transplanted tumors and the tissues of both the normal and tumor-bearing mice of strains A, C3H, and C57 revealed that the tumors do not have less rhodanese content than their homologous tissues or of some of the vital organs. Liver and kidney, in comparison, possess a disproportionately high activity of rhodanese that well fits in with their function of being the prime sites of cyanide detoxification.

6.  Administration of malononitrile and p -nitrobenzalmalononitrile to C3H-S-bearing mice for a period of 16 days did not influence the rhodanese activity of the tissues or that of the tumors.