tbuckley/cabot-search huggingface dataset:
Longitudinal Cytokine Expression during IMRT for Prostate Cancer and Acute Treatment Toxicity
Authors: Eva Christensen, Melania Pintilie, Kenneth R. Evans, Michelle Lenarduzzi, Cynthia Ménard, Charles N. Catton, Eleftherios P. Diamandis, Robert G. Bristow
Journal: Clinical Cancer Research (2009)

Proteomic profiling of patients undergoing intensity-modulated radiotherapy (IMRT) for prostate cancer can identify unique biomarkers that reflect acute toxicity in normal tissues. Our objectives were to measure inflammatory cytokine proteins during IMRT and assess the variability of individual proteomic signatures.Forty-two patients with intermediate-risk prostate cancer were recruited as follows: group 1, definitive IMRT (78 Gy in 39 fractions, n = 22), and group 2, IMRT postprostatectomy (66 Gy in 33 fractions, n = 20). Blood/urine samples were collected at baseline and weekly during IMRT. Acute toxicity was graded weekly during radiotherapy using CTC-AE v3.0 criteria. Multiplexed immunoassays were used to quantify cytokines including granulocyte macrophage colony-stimulating factor, IFN-gamma, tumor necrosis factor-alpha, interleukin (IL)-1alpha, IL-2, IL6, IL-8, IL-10, and IL-12p70.We observed positive correlations between cytokine expression between serum and plasma, but not between serum/plasma and urine. The Mann-Whitney test showed a significant increase in IFN-gamma and IL-6 during IMRT (P = 0.0077, 0.0035). Increasing IL-2 and IL-1 expression were associated with increased probability of acute gastrointestinal and genitourinary toxicity, respectively.Determination of radiation-response signatures is feasible using multiplexed immunoassays and is a promising predictive early biomarker of toxicity outcomes.
Exercise training reverses exertional oscillatory ventilation in heart failure patients
Authors: Marzena Zurek, Ugo Corrà, Massimo F. Piepoli, Ronald K. Binder, Hugo Saner, Jean-Paul Schmid
Journal: European Respiratory Journal (2012)

Exertional oscillatory ventilation (EOV) is an ominous prognostic sign in chronic heart failure (CHF), but little is known about the success of specific therapeutic interventions. Our aim was to study the impact of an exercise training on exercise capacity and cardiopulmonary adaptation in stable CHF patients with left ventricular systolic dysfunction and EOV. 96 stable CHF patients with EOV were included in a retrospective analysis (52 training versus 44 controls). EOV was defined as follows: 1) three or more oscillatory fluctuations in minute ventilation (V'(E)) during exercise; 2) regular oscillations; and 3) minimal average ventilation amplitude ≥5 L. EOV disappeared in 37 (71.2%) out of 52 patients after training, but only in one (2.3%) out of 44 without training (p<0.001). The decrease of EOV amplitude correlated with changes in end-tidal carbon dioxide tension (r= -0.60, p<0.001) at the respiratory compensation point and V'(E)/carbon dioxide production (V'(CO(2))) slope (r=0.50, p<0.001). Training significantly improved resting values of respiratory frequency (f(R)), V'(E), tidal volume (V(T)) and V'(E)/V'(CO(2)) ratio. During exercise, V'(E) and V(T) reached significantly higher values at the peak, while f(R) and V'(E)/V'(CO(2)) ratio were significantly lower at submaximal exercise. No change was noted in the control group. Exercise training leads to a significant decrease of EOV and improves ventilatory efficiency in patients with stable CHF.
Keep calm and carry on: miR-1298 prevents up-regulation of Cx43 and secures a quiescent vascular smooth muscle cell: Figure 1
Authors: Kjestine Schmidt, Cor de Wit
Journal: Cardiovascular Research (2015)

This editorial refers to ‘MicroRNA-1298 is regulated by DNA methylation and affects vascular smooth muscle cell function by targeting connexin 43’ by W. Hu et al. , pp. 534–545. 

Atherosclerosis constitutes the leading cause of cardiovascular disease resulting in ischaemia of dependent organs due to arterial occlusion. It affects not only heart and brain, but also limbs and other organs with fatal consequences for the individuum. The process invokes profound remodelling of the entire vascular wall driven by inflammation, which affects endothelial cells and promotes the activation of vascular smooth muscle cells (VSMCs). In healthy vessels, VSMCs retain a quiescent, contractile state but in response to environmental cues (chemical and mechanical) they adopt an activated, synthetic state characterized also by proliferation and migration. This remarkable plasticity is achieved through a substantial change in gene expression profile, which is likely governed by epigenetic and/or transcriptional control mechanisms.

In addition to transcriptional regulation, non-coding, single-stranded, small RNAs (typically ∼22 nucleotides) contribute substantially to the phenotypic modulation of VSMCs through post-transcriptional regulation of gene expression (mRNA degradation or translational repression).1,2 These so-called microRNAs (miRNAs/miRs) promote or inhibit the switch of VSMCs to the synthetic state. For example, the miR-143/145 cluster supports a contractile state and was down-regulated by vascular injury, implicating that its lack fosters the synthetic state.3,4 Conversely, other miRNAs (miR-21, miR-221/222) were found to promote the synthetic …
Predictive Effects of Urinary Liver-Type Fatty Acid–Binding Protein for Deteriorating Renal Function and Incidence of Cardiovascular Disease in Type 2 Diabetic Patients Without Advanced Nephropathy
Authors: Shin-ichi Araki, Masakazu Haneda, Daisuke Koya, Takeshi Sugaya, Keiji Isshiki, Shinji Kume, Atsunori Kashiwagi, Takashi Uzu, Hiroshi Maegawa
Journal: Diabetes Care (2012)

To improve prognosis, it is important to predict the incidence of renal failure and cardiovascular disease in type 2 diabetic patients before the progression to advanced nephropathy. We investigated the predictive effects of urinary liver-type fatty acid-binding protein (L-FABP), which is associated with renal tubulointerstitial damage, in renal and cardiovascular prognosis.Japanese type 2 diabetic patients (n = 618) with serum creatinine ≤1.0 mg/dL and without overt proteinuria were enrolled between 1996 and 2000 and followed up until 2011. Baseline urinary L-FABP was measured with an enzyme-linked immunosorbent assay. The primary end points were renal and cardiovascular composites (hemodialysis, myocardial infarction, angina pectoris, stroke, cerebral hemorrhage, and peripheral vascular disease). The secondary renal outcomes were the incidence of a 50% decline in estimated glomerular filtration rate (eGFR), progression to an eGFR <30 mL/min/1.73 m(2), and the annual decline rate in eGFR.During a 12-year median follow-up, 103 primary end points occurred. The incidence rate of the primary end point increased in a stepwise manner with increases in urinary L-FABP. In Cox proportional hazards analysis, the adjusted hazard ratio in patients with the highest tertile of urinary L-FBAP was 1.93 (95% CI 1.13-3.29). This relationship was observed even when analyzed separately in normoalbuminuria and microalbuminuria. Patients with the highest tertile of urinary L-FABP also demonstrated a higher incidence of the secondary renal outcomes.Our results indicate that urinary L-FABP may be a predictive marker for renal and cardiovascular prognosis in type 2 diabetic patients without advanced nephropathy.
Survey of joint mobility and in vivo skin elasticity in London schoolchildren.
Authors: S Silverman, L Constine, W Harvey, R Grahame
Journal: Annals of the Rheumatic Diseases (1975)

A survey of joint mobility was conducted in 295 healthy children between the ages of 5 and 10 years who attended a London primary school. Estimates of the commonly used measurements, that is passive dorsiflexion of the wirsts and ankles, passive hypertension of the elbows and knee, were too insensitive to detect any age effect. However, a method of estimating extensibility of the 5th metacarpophalangeal joint in response to a standard load detected a highly significant inverse correlation between joint mobility and age in the samples significant inverse correlation between joint mobility and age in the samples tested ( r = -0.586; P less than 0.0001). There was no apparement sex difference. Skinfold thickness using the Harpenden caliper over the 3rd metacarpal bone and the in vivo skin elasticity measured using a suction cup device performed on a sample of 78 of the children revealed no influence of either age or sex on these parameters. This is in sharp contradistinction to the effect of both age and sex in these two parameters in adults...
Systematic Urokinase-Activated Anthrax Toxin Therapy Produces Regressions of Subcutaneous Human Non–Small Cell Lung Tumor in Athymic Nude Mice
Authors: Yunpeng Su, Janelle Ortiz, Shihui Liu, Thomas H. Bugge, Ravibhushan Singh, Stephen H. Leppla, Arthur E. Frankel
Journal: Cancer Research (2007)

Abstract The novel recombinant anthrax toxin, PrAgU2/FP59, composed of the urokinase-activated protective antigen and a fusion protein of Pseudomonas exotoxin and lethal factor was tested for anti–lung cancer efficacy in an in vivo human tumor model. Male athymic nude mice (age 4–6 weeks) were inoculated s.c. with 10 million H1299 non–small cell lung cancer (NSCLC) cells in the left flank. When tumor volumes reached 200 mm3 (6–8 days), i.p. injection of 100 μL saline or different ratios and doses of PrAgU2/FP59 in 100 μL saline were given every 3 days for four doses and an additional dose at day 29. Animals were monitored twice daily and tumor measurements were made by calipers. The maximum tolerated doses of PrAgU2/FP59 differed dependent on the ratios of PrAgU2 to FP59 over the range of 3:1 to 25:1, respectively. At tolerated doses, tumor regressions were seen in all animals. Complete histologic remission lasting 60 days occurred in 30% of animals. PrAgU2/FP59 showed dramatic anti-NSCLC efficacy and warrants further clinical development for therapy of patients with advanced NSCLC. [Cancer Res 2007;67(7):3329–36]
Crisis in Hospital-Acquired, Healthcare-Associated Infections
Authors: David P. Calfee
Journal: Annual Review of Medicine (2011)

Healthcare-associated infections (HAIs) cause significant morbidity and mortality. Recognition of the burden, cost, and preventability of HAIs has resulted in new initiatives to encourage adherence to recommended infection prevention practices and new research to better understand the pathogenesis of HAIs and to develop novel approaches to prevention. Although substantial progress in HAI prevention has been made over the past decade, many opportunities for improvement remain and new challenges continue to arise. Optimal protection of patients from the harms associated with HAIs will require not only allocation of adequate financial resources and additional scientific research, but also a strong commitment to excellence among all healthcare providers, including consistent use of proven prevention practices and appropriate use of antimicrobial agents. Although it is a daunting task, there has never been a better opportunity for the healthcare system to make the changes necessary to achieve the goal of elimination of HAIs.
Relationship Between Hospital Readmission and Mortality Rates for Patients Hospitalized With Acute Myocardial Infarction, Heart Failure, or Pneumonia
Authors: Harlan M Krumholz, Zhenqiu Lin, Patricia S Keenan, Jersey Chen, Joseph S Ross, Elizabeth E Drye, Susannah M Bernheim, Yun Wang, Elizabeth H Bradley, Lein F Han, Sharon-Lise T Normand
Journal: JAMA (2013)

<h3>Importance</h3>The Centers for Medicare &amp; Medicaid Services publicly reports hospital 30-day, all-cause, risk-standardized mortality rates (RSMRs) and 30-day, all-cause, risk-standardized readmission rates (RSRRs) for acute myocardial infarction, heart failure, and pneumonia. The evaluation of hospital performance as measured by RSMRs and RSRRs has not been well characterized.<h3>Objective</h3>To determine the relationship between hospital RSMRs and RSRRs overall and within subgroups defined by hospital characteristics.<h3>Design, Setting, and Participants</h3>We studied Medicare fee-for-service beneficiaries discharged with acute myocardial infarction, heart failure, or pneumonia between July 1, 2005, and June 30, 2008 (4506 hospitals for acute myocardial infarction, 4767 hospitals for heart failure, and 4811 hospitals for pneumonia). We quantified the correlation between hospital RSMRs and RSRRs using weighted linear correlation; evaluated correlations in groups defined by hospital characteristics; and determined the proportion of hospitals with better and worse performance on both measures.<h3>Main Outcome Measures</h3>Hospital 30-day RSMRs and RSRRs.<h3>Results</h3>Mean RSMRs and RSRRs, respectively, were 16.60% and 19.94% for acute myocardial infarction, 11.17% and 24.56% for heart failure, and 11.64% and 18.22% for pneumonia. The correlations between RSMRs and RSRRs were 0.03 (95% CI, −0.002 to 0.06) for acute myocardial infarction, −0.17 (95% CI, −0.20 to −0.14) for heart failure, and 0.002 (95% CI, −0.03 to 0.03) for pneumonia. The results were similar for subgroups defined by hospital characteristics. Although there was a significant negative linear relationship between RSMRs and RSRRs for heart failure, the shared variance between them was only 2.9% (r<sup>2</sup> = 0.029), with the correlation most prominent for hospitals with RSMR &lt;11%.<h3>Conclusion and Relevance</h3>Risk-standardized mortality rates and readmission rates were not associated for patients admitted with an acute myocardial infarction or pneumonia and were only weakly associated, within a certain range, for patients admitted with heart failure.
Immunopathology of fatal soybean dust-induced asthma
Authors: M Synek, JM Anto, R Beasley, AJ Frew, L Holloway, FC Lampe, JL Lloreta, J Sunyer, A Thornton, ST Holgate
Journal: European Respiratory Journal (1996)

A hypothesis was postulated that the characteristic clinical course of fatal soybean asthma may be reflected by specific immunopathological findings. Seven cases of fatal soybean dust-induced asthma from Barcelona, Spain were compared with 25 fatal asthma cases from New Zealand. Sections of lung tissue were stained by monoclonal antibodies using standard streptavidin-biotin peroxidase technique. The following cell types were identified: mast cells, "activated" eosinophils, neutrophils, monocytes/macrophages, CD3+ T-cells and CD8+ T-cells. The positively staining cells were counted in the epithelium and the submucosa and their numbers expressed per mm and mm2, respectively. The airways were divided into larger (internal perimeter (Pi) &gt; 2 mm) and smaller (Pi &lt; 2 mm). Firstly, all airways were studied together; and subsequently, larger and smaller airways were studied separately. Differences in the numbers of mast cells, eosinophils, neutrophils and monocytes/macrophages between the two groups were not significant. The numbers of CD3+ and CD8+ T-cells were significantly reduced in fatal soybean asthma when all airways were taken together. In larger airways, the difference was not significant in the epithelium, but was significant in the submucosa for CD3+ cells. CD8+ cells were significantly reduced in fatal soybean asthma both in the epithelium and the submucosa. The cell counts in smaller airways were not significantly different either in the epithelium or in the submucosa for CD3+ cells. The numbers of CD8+ cells were not different in the epithelium, but were significantly reduced in the submucosa of fatal soybean asthma cases. We conclude that the numbers of CD3+ and CD8+ T-cells are substantially reduced in fatal soybean asthma. These data together with the clinical features of the fatal attack suggest a different mechanism(s) from that described for most asthma deaths, probably involving anaphylaxis.
Mid Staffs hospital is fined 200 000 over "avoidable" death of diabetic patient in 2007
Authors: C. Dyer
Journal: BMJ (2014)

Mid Staffordshire NHS Foundation Trust has been fined £200 000 (€243 000; $336 000) and ordered to pay more than £27 000 in costs after it was prosecuted by the Health and Safety Executive over the “wholly avoidable” death of Gillian Astbury, a diabetic patient who died after nurses failed to give her insulin.

Sentencing the trust at Stafford Crown Court Mr Justice Haddon-Cave said, “This was a wholly avoidable and tragic death of a vulnerable patient who was admitted to hospital for care, but who …
Streptococcal Toxic Shock Syndrome Caused by Streptococcus suis Serotype 2
Authors: Jiaqi Tang, Changjun Wang, Youjun Feng, Weizhong Yang, Huaidong Song, Zhihai Chen, Hongjie Yu, Xiuzhen Pan, Xiaojun Zhou, Huaru Wang, Bo Wu, Haili Wang, Huamei Zhao, Ying Lin, Jianhua Yue, Zhenqiang Wu, Xiaowei He, Feng Gao, Abdul Hamid Khan, Jian Wang, Guo-Ping Zhao, Yu Wang, Xiaoning Wang, Zhu Chen, George F Gao
Journal: PLoS Medicine (2006)

Streptococcus suis serotype 2 (S. suis 2, SS2) is a major zoonotic pathogen that causes only sporadic cases of meningitis and sepsis in humans. Most if not all cases of Streptococcal toxic shock syndrome (STSS) that have been well-documented to date were associated with the non-SS2 group A streptococcus (GAS). However, a recent large-scale outbreak of SS2 in Sichuan Province, China, appeared to be caused by more invasive deep-tissue infection with STSS, characterized by acute high fever, vascular collapse, hypotension, shock, and multiple organ failure.We investigated this outbreak of SS2 infections in both human and pigs, which took place from July to August, 2005, through clinical observation and laboratory experiments. Clinical and pathological characterization of the human patients revealed the hallmarks of typical STSS, which to date had only been associated with GAS infection. Retrospectively, we found that this outbreak was very similar to an earlier outbreak in Jiangsu Province, China, in 1998. We isolated and analyzed 37 bacterial strains from human specimens and eight from pig specimens of the recent outbreak, as well as three human isolates and two pig isolates from the 1998 outbreak we had kept in our laboratory. The bacterial isolates were examined using light microscopy observation, pig infection experiments, multiplex-PCR assay, as well as restriction fragment length polymorphisms (RFLP) and multiple sequence alignment analyses. Multiple lines of evidence confirmed that highly virulent strains of SS2 were the causative agents of both outbreaks.We report, to our knowledge for the first time, two outbreaks of STSS caused by SS2, a non-GAS streptococcus. The 2005 outbreak was associated with 38 deaths out of 204 documented human cases; the 1998 outbreak with 14 deaths out of 25 reported human cases. Most of the fatal cases were characterized by STSS; some of them by meningitis or severe septicemia. The molecular mechanisms underlying these human STSS outbreaks in human beings remain unclear and an objective for further study.
Hospice Admissions for Cancer in the Final Days of Life: Independent Predictors and Implications for Quality Measures
Authors: Nina R. O'Connor, Rong Hu, Pamela S. Harris, Kevin Ache, David J. Casarett
Journal: Journal of Clinical Oncology (2014)

To define patient characteristics associated with hospice enrollment in the last 3 days of life, and to describe adjusted proportions of patients with late referrals among patient subgroups that could be considered patient-mix adjustment variables for this quality measure.Electronic health record-based retrospective cohort study of patients with cancer admitted to 12 hospices in the Coalition of Hospices Organized to Investigate Comparative Effectiveness network.Of 64,264 patients admitted to hospice with cancer, 10,460 (16.3%) had a length of stay ≤ 3 days. There was significant variation among hospices (range, 11.4% to 24.5%). In multivariable analysis, among patients referred to hospice, patients who were admitted in the last 3 days of life were more likely to have a hematologic malignancy, were more likely to be male and married, and were younger (age < 65 years). Patients with Medicaid or self-insurance were less likely to be admitted to hospice within 3 days of death.Quality measures of hospice lengths of stay should include patient-mix adjustments for type of cancer and site of care. Patients with hematologic malignancies are at especially increased risk for late admission to hospice.
Increase in hospital admissions for childhood asthma: trends in referral, severity, and readmissions from 1970 to 1985 in a health region of the United Kingdom.
Authors: H R Anderson
Journal: Thorax (1989)

Admissions to hospital for childhood asthma have continued to increase, but the reasons are unknown. Because the incidence of acute asthmatic attacks in the community greatly exceeds the admission rate, this increase could be a result of changes in medical practice shifting the balance of care towards the hospital without there being any underlying change in morbidity. In the South West Thames Region (population 2.9 million) over the eight years 1978-85 the number of hospital admissions among those aged 0-4 and 5-14 rose by 186% and 56%. A random sample of case notes from all hospitals in the region was examined for evidence of changes in mode of referral, severity on admission (duration of episode, vital signs on admission), and readmission ratio. The findings indicate that there has been no reduction in severity on admission or increase in readmission rate since 1978. The findings for the 5-14 age group contrast with those from an earlier study (1970-8) in the same region, in which a substantial increase in self referral was observed together with an increase in readmissions and a reduction in the duration of the attack; pulse and respiration rates on admission have, however, remained unchanged over the 16 year period. Overall, these findings indicate that the increase in admissions cannot be satisfactorily explained by changes in medical practice alone and may be due to an increase in the number of asthmatic children experiencing severe attacks. This points to a change in the epidemiology of childhood asthma.
Inflammatory Interaction Between LIGHT and Proteinase-Activated Receptor-2 in Endothelial Cells
Authors: Wiggo J. Sandberg, Bente Halvorsen, Arne Yndestad, Camilla Smith, Kari Otterdal, Frank R. Brosstad, Stig S. Frøland, Peder S. Olofsson, Jan K. Damås, Lars Gullestad, Göran K. Hansson, Erik Øie, Pål Aukrust
Journal: Circulation Research (2008)

The interaction between inflammatory cytokines and endothelial cells is a critical step in atherogenesis leading to endothelial dysfunction and inflammation. We have previously reported that the tumor necrosis factor superfamily member LIGHT could be involved in atherogenesis through its ability to promote vascular inflammation. In the present study we identified proteinase-activated receptor (PAR)-2 as an inflammatory mediator that was markedly enhanced by LIGHT in endothelial cells. We also found that LIGHT acted synergistically with PAR-2 activation to promote enhanced release of the proatherogenic chemokines interleukin-8 and monocyte chemoattractant protein-1, underscoring that the interaction between LIGHT and PAR-2 is biologically active, promoting potent inflammatory effects. We showed that the LIGHT-mediated upregulation of PAR-2 in endothelial cells is mediated through the HVEM receptor, involving Jun N-terminal kinase signaling pathways. A LIGHT-mediated upregulation of PAR-2 mRNA levels was also found in human monocytes when these cells were preactivated by tumor necrosis factor alpha. We have previously demonstrated increased plasma levels of LIGHT in unstable angina patients, and here we show a similar pattern for PAR-2 expression in peripheral blood monocytes. We also found that LIGHT, LIGHT receptors, and PAR-2 showed enhanced expression, and, to some degree, colocalization in endothelial cells and macrophages, in the atherosclerotic plaques of ApoE(-/-) mice, suggesting that the inflammatory interaction between LIGHT and PAR-2 also may be operating in vivo within an atherosclerotic lesion. Our findings suggest that LIGHT/PAR-2-driven inflammation could be a pathogenic loop in atherogenesis potentially representing a target for therapy in this disorder.