tbuckley/cabot-search huggingface dataset:
The Dueling Hazards of Incomplete Revascularization and Incomplete Data
Authors: Paul S. Teirstein
Journal: Circulation (2006)

lthough the survival benefit of complete revascularization after bypass surgery is well documented, the importance of opening all stenotic or occluded vessels during percutaneous coronary intervention (PCI) is less certain.On the contrary, much data support targeting only the culprit vessel during PCI.A strategy of "ischemic-driven revascularization" is often the standard of care.Through a potpourri of noninvasive imaging (eg, nuclear imaging, positron emission tomography, stress echocardiography), as well as invasive techniques (eg, fractional flow reserve, intravascular ultrasound measurements, quantitative angiography), much effort has gone into identifying the functional importance of coronary blockages and confining intervention to diseased vessels that significantly limit blood flow to viable myocardium. 1,2Indeed, the phrase oculostenotic reflex was invented to describe the indiscriminate interventionalist, bent on opening any suspicious angiographic blockage.This subcortical reflex has long been considered a liability, and interventionalists are taught to be more cerebral in their decision making.In this issue of Circulation, Hannan et al, in a very provocative report, use data from the New York State reporting system to turn decades of teaching on its ear. 3 Using a database created from a State of New York reporting registry, procedural information was collected on 21 945 patients with Ն2-vessel coronary artery disease undergoing stenting.Then, using patient's Social Security numbers, these in-hospital data were correlated with the New York State Vital Statistics Death File to capture mortality events over a follow-up period of Ϸ3 years.The study found that patients with incomplete revascularization (after adjustment for baseline differences) were 15% more likely to die at follow-up than patients with complete revascularization.This mortality risk increased with the degree of incomplete revascularization.Patients with 1 unopened total occlusion were 35% more likely to die.If Ն2 vessels were incompletely revascularized, and at least 1 of them was totally occluded, the risk of death was 36% higher.A finding of only 1 incompletely revascularized vessel without a total occlusion did not increase the risk of subsequent mortality.The authors conclude that in patients receiving stents, incomplete revascularization results in increased mortality, and therefore cardiologists should consider either "achieving complete revascularization, opting for surgery, or monitoring PCI patients with incomplete revascularization more closely after discharge."
Comparison of spirometric thresholds in diagnosing smoking-related airflow obstruction: authors’ response
Authors: Surya P Bhatt, George R Washko, Mark T Dransfield, Jessica C Sieren, John D Newell, Eric A Hoffman
Journal: Thorax (2014)

We thank Dr Miller for his comments1 on our recent article.2 While we agree that age is an important factor in this longstanding controversy, we would like to debate some of the points he makes. First, contrary to his assertions, strong relationships have been shown between CT measures of emphysema and pathological findings.3 While there has, in the past, been discussion regarding the ‘best’ Hounsfield Unit (HU) threshold to define CT emphysema, our use of −950 HU, correlating with more severe disease, has been used widely to demonstrate the power of CT-based density metrics in identifying COPD phenotypes, monitoring longitudinal changes and reducing the population size needed to power pharmaceutical studies.4 ,5 Second, while we agree with Dr Miller that age may impact the CT-based emphysema score, the effect size is considerably smaller than suggested. Recent data from COPDGene examining normal subjects with a similar age range as our study, with identical scanner protocols, was unable to detect a significant age effect.6 Analyses of data from the Multi-Ethnic Study of Atherosclerosis Lung study, which included a much larger and older population, (n=854) showed a small age effect (0.2% for every 10 years) on CT-emphysema.7 In another large multicentre study, Coxson et al 8 noted that the progression of CT-emphysema with advancing age is low. …
Principles and Practices in the Management of Obesity
Authors: Gary D. Foster
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

It is no surprise to readers of this journal that obesity is associated with impaired respiratory function and is a significant risk factor for obstructive sleep apnea (OSA) (1, 2). Moreover, weight loss appears to be associated with improvements in sleep-disordered breathing (3–6). It is logical then that a consistent clinical recommendation for obese patients with OSA is to lose weight (7, 8). Pack has highlighted the need for pulmonary physicians to treat obesity seriously (9), as for many obese men with OSA, the pulmonary physician may be the first contact with the healthcare system. Treating obesity will not only have effects on sleep apnea but on the many other cardiovascular sequelae that obesity and OSA share, such as hypertension. The purpose of this article is (1) to provide a brief overview of obesity and its assessment; (2) to review the efficacy of behavioral, pharmacologic, and surgical treatments for obesity; and (3) to describe specific steps that physicians can take in the office setting to help patients effectively manage their weight.
Cost-Effectiveness of Dabigatran Compared With Warfarin for Stroke Prevention in Atrial Fibrillation
Authors: James V. Freeman, Ruo P. Zhu, Douglas K. Owens, Alan M. Garber, David W. Hutton, Alan S. Go, Paul J. Wang, Mintu P. Turakhia
Journal: Annals of Internal Medicine (2011)

Background: Warfarin reduces the risk for ischemic stroke in patients with atrial fibrillation (AF) but increases the risk for hemorrhage. Dabigatran is a fixed-dose, oral direct thrombin inhibitor with similar or reduced rates of ischemic stroke and intracranial hemorrhage in patients with AF compared with those of warfarin. Objective: To estimate the quality-adjusted survival, costs, and cost-effectiveness of dabigatran compared with adjusted-dose warfarin for preventing ischemic stroke in patients 65 years or older with nonvalvular AF. Design: Markov decision model. Data Sources: The RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial and other published studies of anticoagulation. The cost of dabigatran was estimated on the basis of pricing in the United Kingdom. Target Population: Patients aged 65 years or older with nonvalvular AF and risk factors for stroke (CHADS2 score ≥1 or equivalent) and no contraindications to anticoagulation. Time Horizon: Lifetime. Perspective: Societal. Intervention: Warfarin anticoagulation (target international normalized ratio, 2.0 to 3.0); dabigatran, 110 mg twice daily (low dose); and dabigatran, 150 mg twice daily (high dose). Outcome Measures: Quality-adjusted life-years (QALYs), costs (in 2008 U.S. dollars), and incremental cost-effectiveness ratios. Results of Base-Case Analysis: The quality-adjusted life expectancy was 10.28 QALYs with warfarin, 10.70 QALYs with low-dose dabigatran, and 10.84 QALYs with high-dose dabigatran. Total costs were $143 193 for warfarin, $164 576 for low-dose dabigatran, and $168 398 for high-dose dabigatran. The incremental cost-effectiveness ratios compared with warfarin were $51 229 per QALY for low-dose dabigatran and $45 372 per QALY for high-dose dabigatran. Results of Sensitivity Analysis: The model was sensitive to the cost of dabigatran but was relatively insensitive to other model inputs. The incremental cost-effectiveness ratio increased to $50 000 per QALY at a cost of $13.70 per day for high-dose dabigatran but remained less than $85 000 per QALY over the full range of model inputs evaluated. The cost-effectiveness of high-dose dabigatran improved with increasing risk for stroke and intracranial hemorrhage. Limitation: Event rates were largely derived from a single randomized clinical trial and extrapolated to a 35-year time frame from clinical trials with approximately 2-year follow-up. Conclusion: In patients aged 65 years or older with nonvalvular AF at increased risk for stroke (CHADS2 score ≥1 or equivalent), dabigatran may be a cost-effective alternative to warfarin depending on pricing in the United States. Primary Funding Source: American Heart Association and Veterans Affairs Health Services Research & Development Service.
The human anti-CD30 antibody 5F11 shows in vitro and in vivo activity against malignant lymphoma
Authors: Peter Borchmann, John F. Treml, Hinrich Hansen, Claudia Gottstein, Roland Schnell, Oliver Staak, Hui-fen Zhang, Thomas Davis, Tibor Keler, Volker Diehl, Robert F. Graziano, Andreas Engert
Journal: Blood (2003)
mTORC2 regulates renal tubule sodium uptake by promoting ENaC activity
Authors: Catherine E. Gleason, Gustavo Frindt, Chih-Jen Cheng, Michael Ng, Atif Kidwai, Priyanka Rashmi, Florian Lang, Michel Baum, Lawrence G. Palmer, David Pearce
Journal: Journal of Clinical Investigation (2014)

The epithelial Na+ channel (ENaC) is essential for Na+ homeostasis, and dysregulation of this channel underlies many forms of hypertension. Recent studies suggest that mTOR regulates phosphorylation and activation of serum/glucocorticoid regulated kinase 1 (SGK1), which is known to inhibit ENaC internalization and degradation; however, it is not clear whether mTOR contributes to the regulation of renal tubule ion transport. Here, we evaluated the effect of selective mTOR inhibitors on kidney tubule Na+ and K+ transport in WT and Sgk1–/– mice, as well as in isolated collecting tubules. We found that 2 structurally distinct competitive inhibitors (PP242 and AZD8055), both of which prevent all mTOR-dependent phosphorylation, including that of SGK1, caused substantial natriuresis, but not kaliuresis, in WT mice, which indicates that mTOR preferentially influences ENaC function. PP242 also substantially inhibited Na+ currents in isolated perfused cortical collecting tubules. Accordingly, patch clamp studies on cortical tubule apical membranes revealed that mTOR inhibition markedly reduces ENaC activity, but does not alter activity of K+ inwardly rectifying channels (ROMK channels). Together, these results demonstrate that mTOR regulates kidney tubule ion handling and suggest that mTOR regulates Na+ homeostasis through SGK1-dependent modulation of ENaC activity.
Second inquiry to be held into Mid Staffordshire trust
Authors: A. O'Dowd
Journal: BMJ (2009)

The Department of Health in England has announced a second inquiry into Mid Staffordshire NHS Foundation Trust, which recently received a highly critical report for its failings in care.

The government is also set to consult on changes to legislation that will allow the health secretary to order the regulatory body, Monitor, to strip any foundation trust of its foundation status in exceptional circumstances.

The health secretary, Andy Burnham, made the announcement as part of several measures from the Department of Health to tackle what he called “exceptional failures” in foundation trusts.

The trust was heavily criticised earlier this year by former regulator the Healthcare Commission after being found to have “appalling” …
DNA repair gene ERCC2 polymorphisms and associations with breast and ovarian cancer risk
Authors: Dominique Bernard-Gallon, Rémy Bosviel, Laetitia Delort, Luc Fontana, Alain Chamoux, Nadège Rabiau, Fabrice Kwiatkowski, Nasséra Chalabi, Samir Satih, Yves-Jean Bignon
Journal: Molecular Cancer (2008)

Abstract Breast and ovarian cancers increased in the last decades. Except rare cases with a genetic predisposition and high penetrance, these pathologies are viewed as a polygenic disease. In this concept, association studies look for genetic variations such as polymorphisms in low penetrance genes, i.e . genes in interaction with environmental factors. DNA repair systems that protect the genome from deleterious endogenous and exogenous damages have been shown to have significantly reduced. In particular, enzymes of the nucleotide excision repair pathway are suspected to be implicated in cancer. In this study, 2 functional polymorphisms in a DNA repair gene ERCC2 were analyzed. The population included 911 breast cancer cases, 51 ovarian cancer cases and 1000 controls. The genotyping of 2 SNP (Single Nucleotide Polymorphism) was carried out on the population with the MGB (Minor Groove Binder) probe technique which consists of the use of the allelic discrimination with the Taqman ® method. This study enabled us to show an increase in risk of breast cancer with no oral contraceptive users and with women exhibiting a waist-to-hip ratio (WHR) &gt; 0.85 for Asn homozygous for ERCC2 312 .
Is the Combination of Sulfonylureas and Metformin Associated With an Increased Risk of Cardiovascular Disease or All-Cause Mortality?
Authors: Ajay D. Rao, Nitesh Kuhadiya, Kristi Reynolds, Vivian A. Fonseca
Journal: Diabetes Care (2008)

OBJECTIVE—Observational studies assessing the association of combination therapy of metformin and sulfonylurea on all-cause and/or cardiovascular mortality in type 2 diabetes have shown conflicting results. We therefore evaluated the effects of combination therapy of sulfonylureas and metformin on the risk of all-cause mortality and cardiovascular disease (CVD) among people with type 2 diabetes. RESEARCH DESIGN AND METHODS—A MEDLINE search (January 1966–July 2007) was conducted to identify observational studies that examined the association between combination therapy of sulfonylureas and metformin on risk of CVD or all-cause mortality. From 299 relevant reports, 9 were included in the meta-analysis. In these studies, combination therapy of metformin and sulfonylurea was assessed, the risk of CVD and/or mortality was reported, and adjusted relative risk (RR) or equivalent (hazard ratio and odds ratio) and corresponding variance or equivalent was reported. RESULTS—The pooled RRs (95% CIs) of outcomes for individuals with type 2 diabetes prescribed combination therapy of sulfonylureas and metformin were 1.19 (0.88–1.62) for all-cause mortality, 1.29 (0.73–2.27) for CVD mortality, and 1.43 (1.10–1.85) for a composite end point of CVD hospitalizations or mortality (fatal or nonfatal events). CONCLUSIONS—The combination therapy of metformin and sulfonylurea significantly increased the RR of the composite end point of cardiovascular hospitalization or mortality (fatal and nonfatal events) irrespective of the reference group (diet therapy, metformin monotherapy, or sulfonylurea monotherapy); however, there were no significant effects of this combination therapy on either CVD mortality or all-cause mortality alone.
Hippo Coactivator YAP1 Upregulates SOX9 and Endows Esophageal Cancer Cells with Stem-like Properties
Authors: Shumei Song, Jaffer A. Ajani, Soichiro Honjo, Dipen M. Maru, Qiongrong Chen, Ailing W. Scott, Todd R. Heallen, Lianchun Xiao, Wayne L. Hofstetter, Brian Weston, Jeffrey H. Lee, Roopma Wadhwa, Kazuki Sudo, John R. Stroehlein, James F. Martin, Mien-Chie Hung, Randy L. Johnson
Journal: Cancer Research (2014)

Cancer stem cells (CSC) are purported to initiate and maintain tumor growth. Deregulation of normal stem cell signaling may lead to the generation of CSCs; however, the molecular determinants of this process remain poorly understood. Here we show that the transcriptional coactivator YAP1 is a major determinant of CSC properties in nontransformed cells and in esophageal cancer cells by direct upregulation of SOX9. YAP1 regulates the transcription of SOX9 through a conserved TEAD binding site in the SOX9 promoter. Expression of exogenous YAP1 in vitro or inhibition of its upstream negative regulators in vivo results in elevated SOX9 expression accompanied by the acquisition of CSC properties. Conversely, shRNA-mediated knockdown of YAP1 or SOX9 in transformed cells attenuates CSC phenotypes in vitro and tumorigenicity in vivo. The small-molecule inhibitor of YAP1, verteporfin, significantly blocks CSC properties in cells with high YAP1 and a high proportion of ALDH1(+). Our findings identify YAP1-driven SOX9 expression as a critical event in the acquisition of CSC properties, suggesting that YAP1 inhibition may offer an effective means of therapeutically targeting the CSC population.
CpG Island Methylator Phenotype–Positive Tumors in the Absence of<i>MLH1</i>Methylation Constitute a Distinct Subset of Duodenal Adenocarcinomas and Are Associated with Poor Prognosis
Authors: Tao Fu, Emmanouil P. Pappou, Angela A. Guzzetta, Jana Jeschke, Ruby Kwak, Pujan Dave, Craig M. Hooker, Richard Morgan, Stephen B. Baylin, Christine A. Iacobuzio-Donahue, Christopher L. Wolfgang, Nita Ahuja
Journal: Clinical Cancer Research (2012)

Little information is available on genetic and epigenetic changes in duodenal adenocarcinomas. The purpose was to identify possible subsets of duodenal adenocarcinomas based on microsatellite instability (MSI), DNA methylation, mutations in the KRAS and BRAF genes, clinicopathologic features, and prognosis.Demographics, tumor characteristics, and survival were available for 99 duodenal adenocarcinoma patients. Testing for KRAS and BRAF mutations, MSI, MLH1 methylation, and CpG island methylator phenotype (CIMP) status was conducted. A Cox proportional hazard model was built to predict survival.CIMP(+) was detected in 27 of 99 (27.3%) duodenal adenocarcinomas and was associated with MSI (P = 0.011) and MLH1 methylation (P < 0.001), but not with KRAS mutations (P = 0.114), as compared with CIMP(-) tumors. No BRAF V600E mutation was detected. Among the CIMP(+) tumors, 15 (55.6%) were CIMP(+)/MLH1-unmethylated (MLH1-U). Kaplan-Meier analysis showed that tumors classified by CIMP, CIMP/MLH1 methylation status, or CIMP/MSI status could predict overall survival (OS; P = 0.047, 0.002, and 0.002, respectively), whereas CIMP/MLH1 methylation status could also predict time-to-recurrence (TTR; P = 0.016). In multivariate analysis, CIMP/MLH1 methylation status showed a significant prognostic value in both OS (P < 0.001) and TTR (P = 0.023). Patients with CIMP(+)/MLH1-U tumors had the worst OS and TTR.Our results showed existence of CIMP in duodenal adenocarcinomas. The combination of CIMP(+)/MLH1-U seems to be independently associated with poor prognosis in patients with duodenal adenocarcinomas. This study also suggests that BRAF mutations are not involved in duodenal tumorigenesis, MSI, or CIMP development.
Immunosuppression for progressive membranous nephropathy: a UK randomised controlled trial
Authors: Andrew Howman, Tracey L Chapman, Maria M Langdon, Caroline Ferguson, Dwomoa Adu, John Feehally, Gillian J Gaskin, David RW Jayne, Donal O'Donoghue, Michael Boulton-Jones, Peter W Mathieson
Journal: The Lancet (2013)
Clinical Evaluation of a Multiple-Gene Sequencing Panel for Hereditary Cancer Risk Assessment
Authors: Allison W. Kurian, Emily E. Hare, Meredith A. Mills, Kerry E. Kingham, Lisa McPherson, Alice S. Whittemore, Valerie McGuire, Uri Ladabaum, Yuya Kobayashi, Stephen E. Lincoln, Michele Cargill, James M. Ford
Journal: Journal of Clinical Oncology (2014)

Multiple-gene sequencing is entering practice, but its clinical value is unknown. We evaluated the performance of a customized germline-DNA sequencing panel for cancer-risk assessment in a representative clinical sample.Patients referred for clinical BRCA1/2 testing from 2002 to 2012 were invited to donate a research blood sample. Samples were frozen at -80° C, and DNA was extracted from them after 1 to 10 years. The entire coding region, exon-intron boundaries, and all known pathogenic variants in other regions were sequenced for 42 genes that had cancer risk associations. Potentially actionable results were disclosed to participants.In total, 198 women participated in the study: 174 had breast cancer and 57 carried germline BRCA1/2 mutations. BRCA1/2 analysis was fully concordant with prior testing. Sixteen pathogenic variants were identified in ATM, BLM, CDH1, CDKN2A, MUTYH, MLH1, NBN, PRSS1, and SLX4 among 141 women without BRCA1/2 mutations. Fourteen participants carried 15 pathogenic variants, warranting a possible change in care; they were invited for targeted screening recommendations, enabling early detection and removal of a tubular adenoma by colonoscopy. Participants carried an average of 2.1 variants of uncertain significance among 42 genes.Among women testing negative for BRCA1/2 mutations, multiple-gene sequencing identified 16 potentially pathogenic mutations in other genes (11.4%; 95% CI, 7.0% to 17.7%), of which 15 (10.6%; 95% CI, 6.5% to 16.9%) prompted consideration of a change in care, enabling early detection of a precancerous colon polyp. Additional studies are required to quantify the penetrance of identified mutations and determine clinical utility. However, these results suggest that multiple-gene sequencing may benefit appropriately selected patients.
Neuropsychological investigation of amateur boxers.
Authors: R J Butler
Journal: British Journal of Sports Medicine (1994)

Amateur boxing is faced with criticism over the potential damage the sport inflicts on those who participate. The most sensitive measure of early neurological dysfunction is neuropsychological investigation. Ten studies employing such assessments on 289 amateur boxers are reviewed. The forms of analysis undertaken include controlled comparison with other sportsmen, of both active and former boxers, detailed pre- and post-bout analysis, analysis of the influence of within-boxing variables, length of career, level of competition and prospective longitudinal investigation. Amateur boxers were found to exhibit no signs of neuropsychological dysfunction in any analysis. However some trends emerged suggesting a long career in amateur boxing might reduce fine motor reactions, although such findings are within the normal range and do not represent central neuropsychological functioning. Thus amateur boxing does not appear to expose individuals to neurological dysfunction.
Shock After Successful Primary Percutaneous Coronary Intervention for Ventricular Fibrillation
Authors: Junji Yamaguchi, Takamichi Miyamoto, Yasunori Arai, Tatsuhiko Hirao, Tomoyuki Umemoto, Yasuteru Yamauchi, Shinichiro Suzaki, Tohru Obayashi
Journal: Circulation (2015)
A Randomized Trial Comparing Intravenous Immune Globulin and Plasma Exchange in Guillain–Barré Syndrome
Authors: F.G.A. van der Meché, P.I.M. Schmitz
Journal: New England Journal of Medicine (1992)

The subacute demyelinating polyneuropathy known as Guillain–Barré syndrome improves more rapidly with plasma exchange than with supportive care alone. We conducted a multicenter trial to determine whether intravenous immune globulin is as effective as the more complicated treatment with plasma exchange.
Erratum to: Fatty acid flux and oxidation are increased by rimonabant in obese women
Authors: K. Backhouse, I. Sarac, F. Shojaee-Moradie, M. Stolinski, M.D. Robertson, G.S. Frost, J.D. Bell, E.L. Thomas, J. Wright, D. Russell-Jones, A.M. Umpleby
Journal: Metabolism (2014)
Asthma: A Study in Prognosis of 1,000 Patients
Authors: A. G. Ogilvie
Journal: Thorax (1962)

It is not easy to find adequate information about the prognosis in asthma. The condition is notoriously liable to spontaneous variation, the disease is not always clearly defined, and most studies have been small, only covering short periods. In this paper I report a follow-up of 1,000 patients with asthma seen by me over a period of more than 25 years at the Royal Victoria Infirmary, Newcastle.