tbuckley/cabot-search huggingface dataset:
Exercise-induced pulmonary hypertension in patients with systemic sclerosis: Pilot-study
Authors: Nikolaeva Ekaterina, Ildar Kurmukov, Natalie Yudkina, Alexander Volkov
Journal: European Respiratory Journal (2014)

Patients with systemic sclerosis (SSc) are at risk for developing pulmonary hypertension, which is associated with a poor prognosis.

The aim of this study was to evaluate the comparison between risk factors and clinical parameters of exercise-induced increase in mean PAP in small group patients with SSc.

We selected 19 patients with SSc (age 54 ± 11 years, all female) with normal resting mean PAP (17.2 ± 3.9 mm Hg) who underwent graded bicycle supine exercise right heart catheterization. Pulmonary artery systolic pressure, cardiac output, and other were estimated invasively. Cutoff values of mean PAP ≥30 mm Hg at peak exercise were considered exercise-induced pulmonary hypertension. The risk of PAH development was calculated by DETECT PAH risk calculator. Level of uric acid also was measured in all pts.

Only 10 from 19 pts had a risk factors by DETECT calculator, but we didn't found PH at rest RHC. 9 (47%) patients showed a significant exercise-induced pulmonary hypertension, 7 hadn't changes in pressure follow exercises. 3 pts were excluded with low exercise capacity. We found that patients with EI-PH had significantly higher calculating level of PAH risk in DETECT scale than without (315 ± 20 vs 287 ± 24, p<0,05). Also we found that level of biomarkers were higher in group with EI-PH (uric acid 286±83 vs 182±58, p<0,05)

Conclusion: exercise-induced increase in mean PAP occurs in almost one-half of patients with SSc with normal resting PASP. Detection of interrelation between EI-PH and risk-score and higher biomarkers level could testify that pts without PH now probably will develop it in nearest future and demand the early therapy intervention.
Colorectal cancer screening is appropriate for some adults aged 76 to 85, US panel concludes
Authors: Michael McCarthy
Journal: BMJ (2015)

Adults who are at average risk of colorectal cancer and who do not have a family history of genetic disorders that increases their risk should be screened for the cancer from age 50 and continue until 75, say new draft recommendations.1

Released by the US Preventive Services Task Force on 6 October, the recommendations say that the decision to screen adults 76 or older should be made on an individual basis, on the basis of the patient’s prior history of screening and overall health.

Colorectal cancer is the second leading cause of death from cancer in the United States, causing 50 000 deaths a year, yet about a third of eligible adults in the US have …
Molecular classification of anaplastic oligodendroglioma using next-generation sequencing: a report of the prospective randomized EORTC Brain Tumor Group 26951 phase III trial
Authors: Hendrikus J Dubbink, Peggy N Atmodimedjo, Johan M Kros, Pim J French, Marc Sanson, Ahmed Idbaih, Pieter Wesseling, Roelien Enting, Wim Spliet, Cees Tijssen, Winand N M Dinjens, Thierry Gorlia, Martin J van den Bent
Journal: Neuro-Oncology (2015)

BackgroundHistopathological diagnosis of diffuse gliomas is subject to interobserver variation and correlates modestly with major prognostic and predictive molecular abnormalities. We investigated a series of patients with locally diagnosed anaplastic oligodendroglial tumors included in the EORTC phase III trial 26951 on procarbazine/lomustine/vincristine (PCV) chemotherapy to explore the diagnostic, prognostic, and predictive value of targeted next-generation sequencing (NGS) in diffuse glioma and to assess the prognostic impact of FUBP1 and CIC mutations.
Groups call for “dangerous” trial of doctors’ working hours to stop
Authors: Jeanne Lenzer
Journal: BMJ (2016)

Public Citizen, a US public interest watchdog group, and the American Medical Student Association have issued a renewed call for the Office for Human Research Protections to stop a clinical trial they say is unethical.1

The Individualized Comparative Effectiveness of Models Optimizing Patient Safety and Resident Education (iCOMPARE) study was funded by the National Institutes of Health. It will look at the effects of extended work hours for first year internal medicine resident physicians on patient mortality at 30 days.2 The researchers will compare randomized cluster groups of interns …
The intolerance to functional genetic variation of protein domains predicts the localization of pathogenic mutations within genes
Authors: Ayal B. Gussow, Slavé Petrovski, Quanli Wang, Andrew S. Allen, David B. Goldstein
Journal: Genome biology (2016)

Ranking human genes based on their tolerance to functional genetic variation can greatly facilitate patient genome interpretation. It is well established, however, that different parts of proteins can have different functions, suggesting that it will ultimately be more informative to focus attention on functionally distinct portions of genes. Here we evaluate the intolerance of genic sub-regions using two biological sub-region classifications. We show that the intolerance scores of these sub-regions significantly correlate with reported pathogenic mutations. This observation extends the utility of intolerance scores to indicating where pathogenic mutations are mostly likely to fall within genes.
Abstract 9822: Semi-Automatedly Derived Total Atherosclerotic Plaque Burden by CT Angiography for Predicting Clinically Driven Coronary Artery Revascularization: A Comparison With Expert Stenosis Assessment in the CORE320 Multicenter Study
Authors: Satoru Kishi, Tiago Magalhaes, Rodrigo Cerci, Lisa A Friedman, Yutaka Tanami, Peter Kitslaar, Pedro A Lemos, Hiroyuki Niinuma, Christopher Cox, Johan H Reiber, Joao A Lima, Armin Arbab-Zadeh
Journal: Circulation (2013)

Aims: We investigated the performance of a semi-automated arterial contour algorithm by CT angiography (CTA) for assessing total coronary atheroma burden in patients with suspected coronary artery disease. Methods: A total of 373 patients referred for invasive coronary angiography (ICA) in the CORE320 multicenter study were included in this study. Patients underwent 320-row detector CT scanning for coronary angiography. In addition to quantitative CTA stenosis assessment, a novel arterial contour detection algorithm was used to quantify total coronary atheroma volume by subtracting lumen volume from vessel wall volume for the entire coronary tree using a 19-segment model. Atheroma volume was defined as the difference between vessel and lumen volume. For atheroma burden quantification in each patient, we used three parameters: 1) length normalized total atheroma volume (length normTAV) = total atheroma volume/total coronary length; 2) percent atheroma volume (PAV) = (total atheroma volume/total vessel volume) х 100; 3) Normalized total atheroma volume (TAVnorm) = (total atheroma volume/total coronary length) х mean coronary length in study population. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic accuracy for predicting clinically driven coronary revascularization within 30 days from ICA compared to an assessment based on CTA stenosis evaluation. Results: Of 373 patients, 76 patients underwent coronary revascularization. The median CTA stenosis, length normTAV, PAV, and TAVnorm were 62%, 5.8 m3/m, 54.2%, and 2845.4 mm3, respectively. The AUC of CTA stenosis assessment to predict coronary revascularization was 0.73 (95% CI, 0.69-0.78) compared to 0.69 (95% CI, 0.64-0.73) by PAV (p = 0.11). Accuracy was lower (p = 0.002) for TAVnorm and length norm TAV (AUC, 0.62; 95% CI, 0.57-0.67 for both indices). Interobserver agreement for atheroma volume was high (r = 0.99; p &lt; 0.0001). Conclusions: A semi-automatedly derived index of atheroma volume by CTA performs similarly to expert CTA stenosis assessment for identifying patients who undergo clinically driven coronary revascularization. These results convey promise for a rapid, reliable assessment of clinically relevant coronary artery disease.
Lipid-enveloped zinc phosphate hybrid nanoparticles for codelivery of H-2Kb and H-2Db-restricted antigenic peptides and monophosphoryl lipid A to induce antitumor immunity against melanoma
Authors: Xiangting Zhuang, Tingting Wu, Yongdan Zhao, Xiaomeng Hu, Yuling Bao, Yuanyuan Guo, Qingle Song, Gao Li, Songwei Tan, Zhiping Zhang
Journal: Journal of Controlled Release (2016)
Methotrexate Tissue Distribution: Prediction by a Mathematical Model&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: D. S. Zaharko, R. L. Dedrick, K. B. Bischoff, J. A. Longstreth, V. T. Oliverio
Journal: JNCI Journal of the National Cancer Institute (1971)

A model system, discussed and developed in detail in previous publications, was used to predict the distribution of 3′,5′-tritiated methotrexate (MTX) in several mammalian species. Data from experimental studies showed the predictive capabilities of this model when its parameters are chosen to account for physiological differences among species. Some awareness of the critical factors explaining the complex plasma concentration history of MTX resulted during the development of this model. Important aspects were: a) liver uptake and biliary secretion; b) gastrointestinal reabsorption and transit; c) kidney clearance. Computer simulations of a wide range of doses and a few schedules are presented. Species differences in drug distribution and in drug toxicity are discussed in terms of these model predictions.
A blinded, randomized controlled trial of neo-adjuvant celecoxib in patients with early prostate cancer
Authors: P. Sooriakumaran, P. Macanas-Pirard, S. Fox, H. Coley, G. Bucca, D. Lovell, A. Henderson, C. Smith, S. Langley, R. Laing
Journal: Journal of Clinical Oncology (2006)

4563 Background: Celecoxib inhibits tumorigenesis in many in vitro and in vivo models by anti-angiogenesis, induction of apoptosis, and inhibition of tumour cell proliferation and hypoxia. Methods: 45 cT1–2 prostate cancer patients were block randomized 2:1 to four weeks celecoxib 400mg b.d. or no drug prior to radical prostatectomy (RP). Tumour immunohistochemistry was performed for cell proliferation (Ki-67), angiogenesis (CD-31, VEGF, VEGF-R2), hypoxia (HIF-1), apoptosis (TUNEL), and COX-2. All scoring was performed blind by PS and a random 20% were validated blindly by an immunopathologist (SBF). In 19 patients (12 celecoxib-treated, 7 control), peri-operative peripheral zone biopsies were subjected to cDNA microarray analysis to identify differences in gene expression profiling (GEP) between the groups. Results: There was ‘substantial’ (kappa &gt;0.6) or ‘almost perfect’ (kappa &gt;0.8) inter-observer agreement in immunoscoring for all stains. Baseline scores were not significantly different between the celecoxib and control groups. In the celecoxib group, RP scores were significantly lower for Ki-67 (p = 0.036), and non-significantly lower for hypoxia (p = 0.15), KDR (p = 0.16), COX-2 (p = 0.19), microvessel density (p = 0.53), and VEGF (p = 0.83); tumour apoptosis was non-significantly higher (p = 0.26). MANOVA of the full model of stains showed that the difference between the two groups approached statistical significance (p = 0.058), and this was visualized with principal component analysis. GEP revealed that 76 genes were significantly differentially expressed between the celecoxib and control groups using uncorrected t-tests. In the celecoxib group, the tumour suppressor gene p73 and genes associated with protection against oxidative stress were significantly up-regulated; genes associated with cell adhesion were significantly down-regulated, consistent with a reduction in metastatic potential. Conclusions: Celecoxib appears to have marked anti-cancer effects on prostate tumours, most notably affecting cell cycle regulation, oxidative stress, and cell signalling. It may therefore be a promising agent in the management of prostate cancer and warrants further investigation. No significant financial relationships to disclose.
Delirium symptoms during hospitalization predict long-term mortality in patients with severe pneumonia
Authors: Stefano Aliberti, Giuseppe Bellelli, Mauro Belotti, Alessandro Morandi, Grazia Messinesi, Giorgio Annoni, Alberto Pesci
Journal: European Respiratory Journal (2014)

Delirium represents a common complication in critically ill patients and impacts in-hospital mortality in patients with pneumonia. The aim of the study was to evaluate the prevalence of delirium symptoms during hospitalization in patients with severe pneumonia and their impact on one-year mortality. This was an observational, retrospective, cohort study of consecutive patients admitted to a respiratory high dependency unit with a diagnosis of severe pneumonia. A search through the charts looking for ten key words associated with delirium (confusion, disorientation, altered mental status, delirium, agitation, inappropriate behavior, mental status change, inattention, hallucination, lethargy) was performed. A total of 172 patients were enrolled (78% males; median age: 75 years). At least one delirium symptom was detected in 53 patients (31%) during hospitalization. The prevalence of delirium symptoms during hospitalization was higher among those who died during hospitalization vs. those who survived (44% vs. 27%, p=0.049, respectively). A total of 71 patients (46%) died during one-year follow-up after the diagnosis of pneumonia. At the multivariable logistic regression analysis, after adjustment for age, comorbidities and severe sepsis, the presence of at least one delirium symptom during hospitalization was an independent predictor of one-year mortality (OR: 2.35; 95%CI: 1.13-4.90; p=0.023). Further prospective clinical studies should evaluate delirium as independent predictor of adverse outcomes in patients with pneumonia and include it into risk scores for stratification.
Abstract 103: Analysis of Out-of-Hospital Cardiac Arrest Location and Public Access Defibrillator Placement in Metro Phoenix, Arizona
Authors: Sungwoo Moon, Wes Kortuem, Marvis Kisakye, Madalyn Karamooz, Seungsik Hwang, Bernadette White, Daniel Spaite, Bentley Bobrow
Journal: Circulation (2013)

Background and Objective: Automated external defibrillators (AEDs) improve outcomes from out-of-hospital cardiac arrest (OHCA) but are infrequently used. We sought to compare the locations of OHCAs...
Transcriptional regulation of aquaporin-2 water channel gene by cAMP.
Authors: Y Matsumura, S Uchida, T Rai, S Sasaki, F Marumo
Journal: Journal of the American Society of Nephrology (1997)

Aquaporin-2 (AQP-2) water channel is a key molecule for urinary concentration whose expression is augmented by dehydration in vivo. To elucidate the regulatory mechanism of this phenomenon in vitro, mouse collecting duct cell lines were established from a transgenic mouse harboring temperature-sensitive simian virus 40 large T antigen gene and then screened for the AQP-2 expression, using ribonuclease protection assay. In one cell line designated C4, the endogenous AQP-2 mRNA level measured by ribonuclease protection assay increased fourfold after treatment with chlorophenylthio-cAMP (cpt-cAMP) (400 microM). In contrast, phorbol 12-myristate 13-acetate did not affect the AQP-2 mRNA level. To identify the molecular mechanism(s) of cAMP-induced upregulation of AQP-2 mRNA in C4 cells, luciferase assay was performed using various 5'-flanking regions of the human AQP-2 gene. Luciferase activity in C4 cells transfected with constructs containing approximately 2.8-kbp or 224-bp 5'-flanking region showed a 3.5-fold increase by cpt-cAMP treatment, indicating that the 224-bp 5'-flanking region contains the elements necessary for cAMP-induced regulatory mechanisms. This region contains cAMP-responsive element (CRE), and the deletion of the core sequence of CRE (GACGTCA) or introduction of mutation into CRE (GTGGTCA) completely abolished the responsiveness to cpt-cAMP, confirming the key role of CRE in the cAMP-induced transcriptional activation of the AQP-2 gene. Electrophoretic mobility shift assay revealed the existence of proteins binding to CRE in C4 cells and in rat kidney. The binding of CRE proteins to CRE was increased in the nuclear extract from cpt-cAMP-treated C4 cells and dehydrated rat kidney compared with those from controls. These results demonstrated that the CRE in the AQP-2 gene promoter is a key cis-element for cAMP-mediated transcriptional regulation of this gene and may be important for in vivo regulation of AQP-2 expression in a dehydrated state.
Open versus laparoscopic retroperitoneal lymph node dissection (RPLND) in clinical stage I nonseminomatous germ-cell tumors (NSGCTs): Two contemporary series from a single institution
Authors: N. Nicolai, D. Biasoni, J. Piedra Aguilera, A. Necchi, L. Piva, S. Stagni, T. Torelli, A. Milani, G. Pizzocaro, R. Salvioni
Journal: Journal of Clinical Oncology (2009)

5084 Background: Primary RPLND is our choice for clinical stage I (CSI) NSGCTs. Open RPLND (O-RPLND) has been our standard policy since 1985, while laparoscopic RPLND (L-RPLND) has been introduced since the late-1990s. Methods: Between June 2003-March 2008, 150 consecutive CSI NSGCT patients (pts) have been submitted to O-RPLND (n = 91) or L-RPLND (n = 59). Pts with high risk disease (vascular invasion/embryonal carcinoma &gt; 90% in the primary tumor) were more frequently offered O-RPLND, while pts with low risk disease (none of the 2 above) were usually considered for L-RPLND. We reviewed our data focusing on: complications, operating time (OT), hospital stay (HS), number of removed nodes, occurrence of nodal metastases as well as of metastasis during follow-up and global need of chemotherapy (CT). Results: O-RPLND (91). 59/91 (64.8%) were high-risk patients. Median OT was 140 min (IQR 110–150). Five (5.5%) complications occurred: 4 lymphorrea and 1 hemorrhage. Median HS was 6 days (IQR 5–7). Nodal metastases were found in 24 (26.4%) pts. Median number of removed nodes was 20 (IQR 14–25). L-RPLND (59). 54/59 (91.2%) were low-risk patients. Median OT was 210 min (IQR 180–240). Ten (16.9%) complications occurred: 5 required conversions to open procedure due to intraoperative bleeding (4) or technical impossibility to conclude the procedure (1). Median HS was 4 days (IQR 4–5). Nodal metastases were found in 5 (8.5%) pts: 2 of them received immediate adjuvant CT. Median number of removed nodes was 14 (IQR 11–20). OT and HS were significantly better in O-RPLND and L-RPLND series, respectively (p.0001 at Mann Whitney test). After a median follow-up of 15.1 months (1–52), distant metastases were observed in 10 (0.7%) pts: 7/91 (7.7%) following O-RPLND and 1/59 (1.7%) following L-RPLND. CT was administered to 7 (7.7%) pts following O-RPLND and to 3 (5.1%) pts following L-RPLND. Conclusions: In this large case-series, no excess of recurrences but a higher rate of complications were recorded in L-RPLND pts. O-RPLND had a significant better OT while HS was shorter in L-RPLND series. Both procedures are still being applied: pts are currently offered one of the 2 modalities after counseling. No significant financial relationships to disclose.
Abstract 16412: Aldosterone Blockade Promotes The Stability of the Apoptosis Repressor Arc After Reperfusion Injury - A New Strategy for Management of Ischemic Disease
Authors: Anastasia S Mihailidou, TY Loan Le, Anthony W Ashton
Journal: Circulation (2013)

Apoptosis is an important mechanism of cardiac myocyte loss during ischemia-reperfusion injury and heart failure. We have identified the endogenous myocyte inhibitor of apoptosis ARC (Apoptosis Rep...
Abstract MP073: Combining Multiple Kidney Markers to Predict Future Risk of Clinical Outcomes: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Salman Waheed, Kunihiro Matsushita, Brad C Astor, Josef Coresh
Journal: Circulation (2012)

Background There is substantial interest in investigating how multiple chronic kidney disease (CKD) markers combine to predict risk, in particular using eGFR by cystatin C (eGFR cys ) as a supplement to traditional CKD markers, eGFR by creatinine (eGFR cr ) and albumin: creatinine ratio (ACR). Methods We followed 10,268 participants for a median of 11.2 years. Participants were classified into 8 categories: (1) no CKD by any marker (reference); CKD by either (2) eGFR cr or (3) eGFR cys (&lt;60 ml/min/1.73 m 2 ) or (4) ACR (≥30 mg/g) only; CKD by both (5) eGFR cys and eGFR cr or (6) eGFR cys and ACR or (7) eGFR cr and ACR; and (8) CKD by all 3 markers. Cox proportional hazard models were used to estimate hazard ratios. Results Risk increased with the number of markers indicating CKD. eGFR cr &lt;60 alone (ACR and eGFR cys normal) was associated with increased risk of ESRD but not other outcomes [mortality: 0.95 (0.7, 1.2); coronary heart disease: 0.9 (0.6, 1.2); heart failure: 0.9 (0.6, 1.2); acute kidney injury: 1.3 (0.9, 2.0)] compared to individuals without CKD by any marker. In contrast, eGFR cys &lt;60 alone was associated with increased risk of all outcomes except coronary heart disease. When all three markers were abnormal, risk was higher compared to when combination of eGFR cr and ACR were abnormal, particularly for ESRD [ESRD: 109.2 (66.3, 179.9) vs. 12.2 (4.6, 32.2)]. More markers indicating CKD were associated with higher risk for each of the five outcomes examined after adjustment for covariates (Table). Conclusions Cystatin C is a useful confirmatory marker in those with eGFR cr &lt;60 to predict future risk of mortality, cardiovascular and kidney outcomes, particularly in the absence of albuminuria (i.e., when creatinine is the only criterion used to define CKD). Cystatin C may be used as a supplement to traditional CKD markers when more precise information about risk is needed.
The VIRSTA score, a prediction score to estimate risk of infective endocarditis and determine priority for echocardiography in patients with Staphylococcus aureus bacteremia
Authors: Sarah Tubiana, Xavier Duval, François Alla, Christine Selton-Suty, Pierre Tattevin, François Delahaye, Lionel Piroth, Catherine Chirouze, Jean-Philippe Lavigne, Marie-Line Erpelding, Bruno Hoen, François Vandenesch, Bernard Iung, Vincent Le Moing
Journal: Journal of Infection (2016)
Change in Neutrophil-to-lymphocyte Ratio in Response to Targeted Therapy for Metastatic Renal Cell Carcinoma as a Prognosticator and Biomarker of Efficacy
Authors: Arnoud J. Templeton, Jennifer J. Knox, Xun Lin, Ronit Simantov, Wanling Xie, Nicola Lawrence, Reuben Broom, André P. Fay, Brian Rini, Frede Donskov, Georg A. Bjarnason, Martin Smoragiewicz, Christian Kollmannsberger, Ravindran Kanesvaran, Nimira Alimohamed, Thomas Hermanns, J. Connor Wells, Eitan Amir, Toni K. Choueiri, Daniel Y.C. Heng
Journal: European Urology (2016)