tbuckley/cabot-search huggingface dataset:
Longitudinal FGF23 Trajectories and Mortality in Patients with CKD
Authors: Tamara Isakova, Xuan Cai, Jungwha Lee, Dawei Xie, Xue Wang, Rupal Mehta, Norrina B. Allen, Julia J. Scialla, Michael J. Pencina, Amanda H. Anderson, John Talierco, Jing Chen, Michael J. Fischer, Susan P. Steigerwalt, Mary B. Leonard, Chi-yuan Hsu, Ian H. de Boer, John W. Kusek, Harold I. Feldman, Myles Wolf
Journal: Journal of the American Society of Nephrology (2017)

Elevated fibroblast growth factor 23 (FGF23) levels, measured at a single time, are strongly associated with increased risk of mortality in patients with CKD. There are minimal data on serial FGF23 measurements in CKD. In a prospective case-cohort study of the Chronic Renal Insufficiency Cohort, we measured FGF23 at two to five annual time points (mean 4.0±1.2) in a randomly selected subcohort of 1135 participants, of whom 203 died, and all remaining 390 participants who died through mid-2013. Higher FGF23 was independently associated with increased risk of death in multivariable-adjusted analyses of time-varying FGF23 (hazard ratio per 1-SD increase in ln-transformed FGF23, 1.84; 95% CI, 1.67 to 2.03). Median FGF23 was stable over 5 years of follow-up, but its gradually right-skewed distribution suggested a subpopulation with markedly elevated FGF23. Trajectory analysis revealed three distinct trajectories: stable FGF23 in the majority of participants (slope of lnFGF23 per year =0.03, 95% CI, 0.02 to 0.04, n=724) and smaller subpopulations with slowly (slope=0.14, 95% CI, 0.12 to 0.16, n=486) or rapidly (slope=0.46, 95% CI, 0.38 to 0.54, n=99) rising levels. Compared with stable FGF23, participants with slowly rising FGF23 trajectories were at 4.49-fold higher risk of death (95% CI, 3.17 to 6.35) and individuals with rapidly rising FGF23 trajectories were at 15.23-fold higher risk of death (95% CI, 8.24 to 28.14) in fully adjusted analyses. Trajectory analyses that used four or three annual FGF23 measurements yielded qualitatively similar results. In conclusion, FGF23 levels are stable over time in the majority of patients with CKD, but serial measurements identify subpopulations with rising levels and exceptionally high risk of death.
P2.07-013 Efficacy and Safety of Nivolumab in Non-Small Cell Lung Cancer with Preexisting Interstitial Lung Disease
Authors: O. Kanai, Y. Kim, Y. Demura, M. Kanai, K. Fujita, H. Yoshida, M. Akai, T. Mio, T. Hirai
Journal: Journal of Thoracic Oncology (2017)
La importación de ensalada de rúcula, parcialmente responsable del aumento de incidencia de casos de hepatitis A en Suecia, 2000-2001
Authors: K Nygård, Y Andersson, P Lindkvist, C Ancker, I Asteberg, E Dannetun, R Eitrem, L Hellström, M Insulander, L Skedebrant, K Stenqvist, J Giesecke
Journal: Eurosurveillance (2001)

El aumento de la incidencia de hepatitis A autoctona sin una fuente de infeccion evidente en Suecia y el pequeno brote registrado a final de la primavera de 2001, dieron lugar a la realizacion de un estudio de casos y controles. El consumo de ensalada de rucula (conocida tambien como roqueta o arugula) importada fue asociado claramente a la enfermedad (odds ratio=9,1, intervalo de confianza al 95%=1,5 - 69). La importacion de hortalizas desde paises con hepatitis A endemica a paises en los que esta enfermedad no es endemica, sigue constituyendo un problema sanitario.
Utility of Imaging-Based Biomarkers for Glutamate-Targeted Drug Development in Psychotic Disorders
Authors: Daniel C. Javitt, Cameron S. Carter, John H. Krystal, Joshua T. Kantrowitz, Ragy R. Girgis, Lawrence S. Kegeles, John D. Ragland, Richard J. Maddock, Tyler A. Lesh, Costin Tanase, Philip R. Corlett, Douglas L. Rothman, Graeme Mason, Maolin Qiu, James Robinson, William Z. Potter, Marlene Carlson, Melanie M. Wall, Tse-Hwei Choo, Jack Grinband, Jeffrey A. Lieberman
Journal: JAMA Psychiatry (2017)

Despite strong theoretical rationale and preclinical evidence, several glutamate-targeted treatments for schizophrenia have failed in recent pivotal trials, prompting questions as to target validity, compound inadequacy, or lack of target engagement. A key limitation for glutamate-based treatment development is the lack of functional target-engagement biomarkers for translation between preclinical and early-stage clinical studies. We evaluated the utility of 3 potential biomarkers-ketamine-evoked changes in the functional magnetic imaging (fMRI) blood oxygen level-dependent response (pharmacoBOLD), glutamate proton magnetic resonance spectroscopy (1H MRS), and task-based fMRI-for detecting ketamine-related alterations in brain glutamate.To identify measures with sufficient effect size and cross-site reliability to serve as glutamatergic target engagement biomarkers within early-phase clinical studies.This randomized clinical trial was conducted at an academic research institution between May 2014 and October 2015 as part of the National Institute of Mental Health-funded Fast-Fail Trial for Psychotic Spectrum Disorders project. All raters were blinded to study group. Healthy volunteers aged 18 to 55 years of either sex and free of significant medical or psychiatric history were recruited from 3 sites. Data were analyzed between November 2015 and December 2016.Volunteers received either sequential ketamine (0.23 mg/kg infusion over 1 minute followed by 0.58 mg/kg/h infusion over 30 minutes and then 0.29 mg/kg/h infusion over 29 minutes) or placebo infusions.Ketamine-induced changes in pharmacoBOLD, 1H MRS, and task-based fMRI measures, along with symptom ratings. Measures were prespecified prior to data collection.Of the 65 volunteers, 41 (63%) were male, and the mean (SD) age was 31.1 (9.6) years; 59 (91%) had at least 1 valid scan. A total of 53 volunteers (82%) completed both ketamine infusions. In pharmacoBOLD, a highly robust increase (Cohen d = 5.4; P < .001) in fMRI response was observed, with a consistent response across sites. A smaller but significant signal (Cohen d = 0.64; P = .04) was also observed in 1H MRS-determined levels of glutamate+glutamine immediately following ketamine infusion. By contrast, no significant differences in task-activated fMRI responses were found between groups.These findings demonstrate robust effects of ketamine on pharmacoBOLD across sites, supporting its utility for definitive assessment of functional target engagement. Other measures, while sensitive to ketamine effects, were not sufficiently robust for use as cross-site target engagement measures.clinicaltrials.gov Identifier: NCT02134951.
Molecular Ellipticity of Circulating Albumin-Bilirubin Complex Associates With Mortality in Patients With Severe Alcoholic Hepatitis
Authors: Sukanta Das, Jaswinder Singh Maras, Rakhi Maiwall, Saggere M. Shasthry, Shabir Hussain, Shvetank Sharma, Sukriti Sukriti, Tej P. Singh, Shiv Kumar Sarin
Journal: Clinical Gastroenterology and Hepatology (2017)
Abstract 18064: Effect of Fluctuations in Glucose Levels on Vascular Endothelial Dysfunction and Clinical Outcomes in Coronary Artery Disease (CAD) Patients Without Diabetes Mellitus (DM)
Authors: Tomonori Akasaka, Seiji Hokimoto, Hisao Ogawa
Journal: Circulation (2015)

Background: Fluctuations in glucose levels give rise to inflammation and endothelial dysfunction by increasing oxidative stress. Mean amplitude of glycemic excursions (MAGE) is commonly used as a degree of fluctuations in glucose level, and play a significant role in vascular endothelial dysfunction in diabetes mellitus (DM) patients, but not so clear in non-DM patients. Vascular endothelial dysfunction is associated with an increased risk of cardiovascular events. Thus, we examined the impact of MAGE on vascular endothelial dysfunction and clinical outcomes in non-DM patients with CAD. Methods: We analyzed 48 CAD patients following percutaneous coronary intervention (PCI) during 12 months, and assessed the relation among MAGE measured by continuous glucose monitoring (CGM), the level of high-sensitivity CRP (hs-CRP), and reactive hyperemia index (RHI) measured from RH-PAT (reactive hyperemia peripheral arterial tonometry). Cardiovascular events were cardiovascular death, myocardial infarction, unstable angina, and revascularization. Results: In clinical characteristics, HbA1c and MAGE were 5.96±0.40% and 62.5±32.6mg/dl. MAGE correlated with hs-CRP (r=0.426; P=0.003) and RHI (r=–0.403; P=0.007), but not correlated with body mass index (BMI), HbA1c, LDL cholesterol, and systolic blood pressures. In short, high glycemic excursions (high MAGE) is associated with high inflammation (high level of hs-CRP) and vascular endothelial dysfunction (low RHI). When patients were classified into MAGE&lt;65mg/dl (normal glycemic excursions) and MAGE&gt;65mg/dl (high glycemic excursions), group of MAGE&gt;65mg/dl showed significant higher hs-CRP (0.05±0.03 vs 0.15±0.15mg/dl, P&lt;0.001) and lower RHI (1.98±0.45 vs 1.74±0.38, P=0.003) compared with group of MAGE&lt;65mg/dl. Multivariate analysis for clinical outcomes identified high MAGE as predictive factors (OR4.7, P=0.032). In ROC curve, MAGE is predictive index for cardiovascular events (AUC 0.533, P=0.01). Conclusions: Fluctuations in glucose levels are associated with inflammation, endothelial dysfunction, and cardiovascular events. And, MAGE may be good predictive index for cardiovascular events in CAD patients without DM.
Rethinking Eligibility for Experimental Clinical Trials
Authors: Lauren Gibbs
Journal: JAMA Neurology (2017)

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High-Density Lipoprotein Subspecies Defined by Presence of Apolipoprotein C-III and Incident Coronary Heart Disease in Four Cohorts
Authors: Majken K. Jensen, Sarah A. Aroner, Kenneth J. Mukamal, Jeremy D. Furtado, Wendy S. Post, Michael Y. Tsai, Anne Tjønneland, Joseph F. Polak, Eric B. Rimm, Kim Overvad, Robyn L. McClelland, Frank M. Sacks
Journal: Circulation (2017)

Background: The causal role of high-density lipoprotein (HDL) cholesterol in cardioprotection has been questioned by genetic and randomized studies. Novel measures that relate to HDL function may contribute new information to the prediction of cardiovascular risk. Apolipoprotein C-III (apoC-III) is a key regulator of lipoprotein metabolism. We investigated whether subspecies of HDL defined by apoC-III are associated with coronary heart disease (CHD). Methods: We used immunoaffinity chromatography to measure the apoA-I concentrations of HDL that contains and lacks apoC-III in 2 prospective studies of adults free of CHD. In MESA (Multi-Ethnic Study of Atherosclerosis), 5657 participants (52% women, 52–72 years of age) were followed for risk of CHD from 2000 to 2002 through 2013. In a case-cohort study nested within the DCH study (Danish Diet, Cancer, and Health), 3642 participants (47% women, 51–64 years of age) were followed from 1994 to 1997 through 2010. Subsequently, we conducted a meta-analysis that combined these results with the previously published findings from 2 cohort studies that used similar laboratory methodology to measure lipoproteins, totaling 2997 incident cases. Results: ApoC-III was found on 6% to 8% of apoA-I. The 2 HDL subspecies showed opposing associations, with risk of CHD in each of the individual cohorts and in the meta-analysis ( P heterogeneity between the 2 subspecies &lt;0.01). HDL that contains apoC-III was associated with a higher risk of CHD (pooled relative risk per standard deviation, 1.09; 95% confidence interval, 1.01–1.18), whereas HDL that lacks apoC-III was associated with lower risk (relative risk, 0.76; 95% confidence interval, 0.70–0.83). The relative risk for HDL lacking apoC-III was even more negative than the relative risk for total HDL (relative risk, 0.80; 95% confidence interval, 0.74–0.87). Conclusions: Our findings from 4 prospective studies support the hypothesis that apoC-III may mark a subfraction of HDL that is associated with higher risk of CHD. New measures reflecting HDL structure and function may provide novel insights for cardiovascular risk that extend beyond traditional plasma HDL cholesterol concentrations.
Un nuevo relajamiento de los comportamientos preventivos en hombres homosexuales: ¿se puede atribuir a la aparición de tratamientos antirretrovirales de gran actividad?
Authors: A Laporte
Journal: Eurosurveillance (2002)

Todos los articulos publicados en este numero de Eurosurveillance sobre las ultimas tendencias de los comportamientos preventivos en hombres homosexuales en Espana, Suiza y Paises Bajos, coinciden en que se estan relajando las practicas sexuales seguras. Subrayan un aumento de la penetracion anal (en cualquier tipo de pareja), de las relaciones anales sin proteccion y de las orales con eyaculacion en la boca, especialmente con las parejas ocasionales. El aumento de diagnosticos de enfermedades agudas de transmision sexual (como gonorrea y sifilis) en distintos paises europeos –que en este numero se ilustra con los datos de Paises Bajos– es la primera consecuencia tangible de tal relajacion.
Comment prévenir la transmission des SARM dans la population générale
Authors: F Vandenesch, J Etienne
Journal: Eurosurveillance (2004)

Durant les 20 a 30 dernieres annees, les souches de Staphylococcus aureus resistants a la methicilline (SARM) etaient presentes dans les hopitaux et sont devenues une des principales causes des infections nosocomiales. Le taux de resistancea la methicilline des S.aureus est tres variable d'un pays a l'autre, d'une forte prevalence aux Etats-Unis et dans le sud de l'Europe (g20%), a une faible prevalence en Europe du nord (l ou =5%). Les SARM acquis dans la communaute ont emerge dans le monde entier a la fin des annees 1990. Il y a eu une grande confusion dans la litterature entre les infections a SARM associees aux soins survenant dans la population generale chez des patients a risque pour les infections nosocomiales a SARM (tels que les patients ayant ete hospitalises dans le passe, ceux presentant une deficience immunitaire, etc.), et les veritables infections a co-SARM dues a des souches presentes uniquement dans la communaute.
Results of patients of locally advanced nasopharyngeal carcinoma treated with neoadjuvant chemotherapy or upfront concurrent chemoradiotherapy: A regional cancer centre experience
Authors: P.N. Patel, S. Goyal, U. Suryanarayana, A. Anand, H. Panchal, A. Patel, S. Parikh
Journal: Annals of Oncology (2017)
Association of Prognostic Value of Primary Tumor Location in Stage III Colon Cancer With<i>RAS</i>and<i>BRAF</i>Mutational Status
Authors: Julien Taieb, Hampig Raphael Kourie, Jean-François Emile, Karine Le Malicot, Ralyath Balogoun, Josep Tabernero, Enrico Mini, Gunnar Folprecht, Jean-Luc Van Laethem, Claire Mulot, Olivier Bouché, Thomas Aparicio, Pierre Michel, Josef Thaler, John Bridgewater, Eric Van Cutsem, Géraldine Perkins, Come Lepage, Ramon Salazar, Pierre Laurent-Puig
Journal: JAMA Oncology (2017)

We know of no data on the prognostic value of primary tumor location (PTL) according to BRAF, RAS, and microsatellite instability (MSI) status in patients who have undergone resection for colon cancer (CC) and have been treated with current standard adjuvant chemotherapy.To determine the prognostic and predictive value of PTL according to BRAF, RAS, and MSI status in patients with stage III CC receiving adjuvant treatment with FOLFOX (folinic acid [leucovorin calcium], fluorouracil, and oxaliplatin) with or without cetuximab.This post hoc analysis included patients with available tumor blocks of resected stage III colon adenocarcinoma who participated in the Pan-European Trials in Alimentary Tract Cancer (PETACC)-8 phase 3 randomized trial. Among the 2559 patients who underwent randomization, 1900 were screened by next-generation sequencing, which showed that 1869 had full information concerning PTL. We categorized primary tumor site as located proximal (right) or distal (left) to the splenic flexure.The associations between PTL (right- vs left-sided) and disease-free survival (DFS), survival after relapse (SAR), and overall survival (OS) were assessed by Cox models and adjusted for clinical and pathological features, treatment, and MSI, BRAF, and RAS status.Among the 1869 patients (1056 [57%] male; mean [SD] age, 59.4 [9.5] years) with full molecular data analyzed, 755 (40%) had a right-sided tumor, 164 (10%) had MSI, 942 (50%) had RAS mutations, and 212 (11%) had BRAF mutations. Right-sided tumor location was not prognostic for DFS in the whole population but was associated with a shorter SAR (hazard ratio [HR], 1.54; 95% CI, 1.23-1.93; P = .001) and OS (HR, 1.25; 95% CI, 1.02-1.54; P = .03). When looking at DFS in the different molecular subgroups, we found similar results for microsatellite-stable tumors and tumors with MSI; a better DFS in right-sided vs left-sided tumors in patients with RAS mutations (HR, 0.80; 95% CI, 0.64-1.00; P = .046); and a worse DFS in right-sided vs left-sided tumors in patients with RAS and BRAF double wild type (HR, 1.39; 95% CI, 1.01-1.92; P = .04). These results were found independently of the treatment received, and no beneficial effect of cetuximab on DFS or OS was observed in left-sided tumors.Although right-sided tumor location is associated with poor survival in patients with metastatic CC as previously reported, the association with disease recurrence appears to vary for patients with stage III CC and RAS or BRAF mutations vs those with double wild type.
ABC of oxygen: Oxygen transport---2. Tissue hypoxia
Authors: R M Leach, D F Treacher
Journal: BMJ (1998)

Tissues vary considerably in their sensitivity to hypoxia. Neurological cells tolerate hypoxia for only a few minutes whereas bladder smooth muscle may survive for several days without oxygen. This has important implications in the management of oxygen transport and monitoring of tissue hypoxia in critically ill patients.

Regional oxygen transport and cellular use are often neglected but are important in maintaining tissue function and overall survival

### Delivery to organs and tissues 

The mechanisms controlling oxygen distribution are incompletely understood but involve a series of convective and diffusive processes. Convective oxygen transport refers to the bulk movement of oxygen in air or blood and depends on active, energy consuming processes generating flow in the tracheobronchial tree and circulation. Diffusive transport refers to the passive movement of oxygen down its concentration gradient across tissue barriers, including the alveolar-capillary membrane, and across the extracellular matrix between the tissue capillaries and individual cells to mitochondria. The amount of diffusive oxygen movement depends on the oxygen tension gradient and the diffusion distance.



Effect of oxygen tension gradient and diffusion distance on availability of oxygen to cells



In many critically ill patients tissue hypoxia is due to disordered regional distribution of blood flow both between and within organs. Regional and microcirculatory distribution of cardiac output is determined by a complex interaction of endothelial, receptor, neural, metabolic, and pharmacological factors working on small resistance arterioles and precapillary sphincters. In critical illness, particularly sepsis, hypotension and loss of normal autoregulation cause shunting and tissue hypoxia in some organs despite high global oxygen delivery and mixed venous saturation. The perfusion pressure is an important determinant of regional perfusion, but adrenaline or noradrenaline given to maintain systemic blood pressure may reduce regional distribution, particularly to the renal and splanchnic capillary beds.



Severe tissue hypoxia due to capillary microthrombosis in critically ill patient with meningococcal septicaemia …
Novel Predictors of Breast Cancer Survival Derived from miRNA Activity Analysis
Authors: Vasily N. Aushev, Eunjee Lee, Jun Zhu, Kalpana Gopalakrishnan, Qian Li, Susan L. Teitelbaum, James Wetmur, Davide Degli Esposti, Hector Hernandez-Vargas, Zdenko Herceg, Humberto Parada, Regina M. Santella, Marilie D. Gammon, Jia Chen
Journal: Clinical Cancer Research (2017)

Breast cancer is among the leading causes of cancer-related death; discovery of novel prognostic markers is needed to improve outcomes. Combining systems biology and epidemiology, we investigated miRNA-associated genes and breast cancer survival in a well-characterized population-based study.
Aberrant Activation of a Gastrointestinal Transcriptional Circuit in Prostate Cancer Mediates Castration Resistance
Authors: Shipra Shukla, Joanna Cyrta, Devan A. Murphy, Edward G. Walczak, Leili Ran, Praveen Agrawal, Yuanyuan Xie, Yuedan Chen, Shangqian Wang, Yu Zhan, Dan Li, Elissa W.P. Wong, Andrea Sboner, Himisha Beltran, Juan Miguel Mosquera, Jessica Sher, Zhen Cao, John Wongvipat, Richard P. Koche, Anuradha Gopalan, Deyou Zheng, Mark A. Rubin, Howard I. Scher, Ping Chi, Yu Chen
Journal: Cancer Cell (2017)
Sorveglianza su botulismo d'origine alimentare in Polonia: 1960-1998
Authors: A Galazka, A Przybylska
Journal: Eurosurveillance (1999)

Il botulismo umano d'origine alimentare, a differenza delle altre due forme di botulismo (da lesione e infantile), e un'intossicazione che si manifesta in seguito all'ingestione della tossina botulinica formatasi precedentemente. Casi sporadici e focolai familiari o di comunita si verificano quando prodotti alimentari vengono preparati o conservati in maniera non adeguata e immagazzinati in condizioni anaerobiche che permettono al patogeno di germinare, di moltiplicarsi e di produrre la tossina.