tbuckley/cabot-search huggingface dataset:
Infectious Complications of Chemotherapy in a Protected Environment
Authors: Alexander A. Levitan, Seymour Perry
Journal: New England Journal of Medicine (1967)

NUMEROUS recent studies have pointed out that the most common cause of morbidity and mortality in patients with cancer is not the underlying disease but associated infection and drug toxicity.1 2 3 In an attempt to combat these complications, patient isolator systems§ have been in use on the chemotherapy wards of the National Cancer Institute since September, 1964.4 Their use has been predicated on the belief that it is not only exogenous micro-organisms that can cause infection in malignant states but often the normal flora of the patient's skin and gastrointestinal tract as well.5 The isolator system described below prevents the introduction . . .
THU0028 Cigarette Smoke Triggered Circulating and Infiltrating Neutrophil Extracellular Traps by Autophagy Dependent way in RA Patients
Authors: L. Wang, L. Qian, X. Li
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Cigarette smoking is proved to be an independent risk factor for the development and progression of rheumatoid arthritis (RA). Neutrophil extracellular traps (NETs) are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis. <h3>Objectives</h3> In the current study, we analyzed the formation and magnitude of NETs from circulationg and infiltrating neutrophils, which triggered by smoking in RA patient. <h3>Methods</h3> Circulating neutrophils were separated from peripheral blood of healthy volunteers (n=7) and RA patients (n=15). Infiltrating neutrophils were separated from knee synovial tissue, which were obtained with auto biopsy gun under B ultrasound-guided from smoking and non-smoking RA patients. These neutrophils were incubated with 0, 5, 10% cigarette smoke extract (CSE). The formation of Nets were observed using immunofluorescence (IF), labbed by anti-MPO/anti-H3, then autophagy were inspected by anti-LC3/anti-beclin-1. The magnitude of Nets was detected by fluorescent quantitative assay with PICO green. <h3>Results</h3> Smoking RA patients showed a significant augment of NETs in both neutrophils circulating in peripheral blood and infiltrating in synovial tissues, which is dramatically higher than no-smoking patients and healthy volunteers. Meanwhile, CSE treated neutrophils highly increased NETs in non-smoking RA, but showed much slightly effect in healthy volunteers. Furthermore, synovial tissues demonstrated the colocalization of neutrophils with NETs and autophagy. Additionally, autophagy was idencitified as the orchestrator of NETs formation, as shown by inhibition studies using wortmannin or bafilomycin A1. <h3>Conclusions</h3> Our data show that cigarette smoke probably triggered NETs of both circulating and infiltrating neutrophils by autophagy dependent way in RA patients. <h3>Disclosure of Interest</h3> None declared
Crystal Structure Of Tissue Factor Pathway Inhibitor (TFPI) Kunitz Domain 1 and 2 In Complex With An Inhibitory Cyclic Peptide,
Authors: Michael Dockal, Rudolf Hartmann, Markus Fries, Katerina Prohaska, Robert Pachlinger, Thomas Polakowski, Johannes Brandstetter, Jan Rosing, Friedrich Scheiflinger
Journal: Blood (2013)
Screening for cardiac dysfunction and cardiovascular risk factors in childhood cancer survivors using the Children's Oncology Group (COG) Long-term Follow-up (LTFU) Guidelines.
Authors: S. Armenian, W. Landier, C. Sun, J. Lee, M. Zomorodi, L. Francisco, K. Wilson, S. Bhatia
Journal: Journal of Clinical Oncology (2010)

9034 Background: Childhood cancer survivors are at risk for cardiac dysfunction (CD) due to exposure to anthracyclines and chest radiation. This risk is further compounded by cardiovascular (CV) risk factors (hypertension, dyslipidemia, insulin resistance, overweight/obesity) in this population. COG Guidelines use a consensus-based approach to recommend screening due absence of randomized trials for guidance. The utility and yield of these recommendations need to be evaluated. Methods: Survivors were screened for CD or CV risk factors per COG Guidelines. Screening outcomes: CD (ejection fraction <55%); CV risk factors (dyslipidemia [triglyceride ≥150 mg/dl and/or total cholesterol ≥200 mg/dl]; hypertension [≥130/≥85; <18y: ≥90% age]; insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR) >2.86]; overweight/obese [BMI ≥25kg/m2]). Results: 310 survivors underwent screening (47% female; median age at diagnosis: 11.4 years; at screening: 24.1 years; time from diagnosis: 10.9 years; leukemia [44%], lymphoma [28%], solid tumor [28%]); median anthracycline dose: 225 mg/m2 (25-642). Cardiac dysfunction: among those with ≥2 echocardiograms (n = 129), 18.5% were identified with previously undiagnosed CD (45.8% on first screen, 54.2% on subsequent screening). The prevalence was highest (25.0%) for anthracycline ≥250 mg/m2 with radiation, and lowest (13.3%) for anthracycline <250 mg/m2 without radiation. CV risk factors: 30.1% of survivors screened had ≥2 CV risk factors. Males (OR: 3.5, p<0.01), age at screening (OR: 1.1/yr, p = 0.02), and cranial radiation >18 Gy (OR: 3.1, p = 0.04) were associated with increased risk. Males treated with <18Gy cranial radiation were at highest risk (OR: 17.1, p<0.01). Conclusions: Screening per COG LTFU Guidelines helped identify previously unrecognized CD or CV risk factors in up to 30% of “at risk” survivors, reinforcing the critical need for long-term cardiac surveillance in this population. This study also attempts to refine consensus-based screening recommendations by identifying subgroups with highest or lowest yield per current screening recommendations. No significant financial relationships to disclose.
Ambient Air Pollution and Newborn Size and Adiposity at Birth: Differences by Maternal Ethnicity (the Born in Bradford Study Cohort)
Authors: Anna Schembari, Kees de Hoogh, Marie Pedersen, Payam Dadvand, David Martinez, Gerard Hoek, Emily S. Petherick, John Wright, Mark J. Nieuwenhuijsen
Journal: Environmental Health Perspectives (2015)

Exposure to ambient air pollution has been associated with reduced size of newborns; however, the modifying effect of maternal ethnicity remains little explored among South Asians.We investigated ethnic differences in the association between ambient air pollution and newborn's size.Pregnant women were recruited between 2007 and 2010 for the Born in Bradford cohort study, in England. Exposures to particulate matter (≤ 10 μm, PM10; ≤ 2.5 μm, PM2.5), PM2.5 absorbance, and nitrogen oxides (NOx, NO2) were estimated using land-use regressions models. Using multivariate linear regression models, we evaluated effect modification by maternal ethnicity ("white British" or "Pakistani origin," self-reported) on the associations of air pollution and birth weight, head circumference, and triceps and subscapular skinfold thickness.A 5-μg/m3 increase in mean third trimester PM2.5 was associated with significantly lower birth weight and smaller head circumference in children of white British mothers (-43 g; 95% CI: -76, -10 and -0.28 cm; 95% CI: -0.39, -0.17, respectively), but not in children of Pakistani origin (9 g; 95% CI: -17, 35 and -0.08 cm; 95% CI: -0.17, 0.01, respectively) (p(int) = 0.03 and < 0.001). In contrast, PM2.5 was associated with significantly larger triceps and subscapular skinfold thicknesses in children of Pakistani origin (0.17 mm; 95% CI: 0.08, 0.25 and 0.21 mm; 95% CI: 0.12, 0.29, respectively), but not in white British children (-0.02 mm; 95% CI: -0.14, 0.01 and 0.06 mm; 95% CI: -0.06, 0.18, respectively) (p(int) = 0.06 and 0.11). Patterns of associations for PM10 and PM2.5 absorbance according to ethnicity were similar to those for PM2.5, but associations of the outcomes with NO2 and NOx were mostly nonsignificant in both ethnic groups.Our results suggest that associations of ambient PM exposures with newborn size and adiposity differ between white British and Pakistani origin infants.Schembari A, de Hoogh K, Pedersen M, Dadvand P, Martinez D, Hoek G, Petherick ES, Wright J, Nieuwenhuijsen MJ. 2015. Ambient air pollution and newborn size and adiposity at birth: differences by maternal ethnicity (the Born in Bradford study cohort). Environ Health Perspect 123:1208-1215; http://dx.doi.org/10.1289/ehp.1408675.
Effect of Potassium in Restoring Myocardial Response to a Subthreshold Cardiac Pacemaker
Authors: Weldon J. Walker, John T. Elkins, Laurence W. Wood
Journal: New England Journal of Medicine (1964)

IMPLANTED cardiac pacemakers may become exhausted and no longer produce myocardial response. Pharmacologic means were used in this study to restore responsiveness to partially exhausted pacemakers in 2 patients with complete heart block.Case ReportsCase 1. A 69-year-old woman had been asymptomatic for 20 months after implantation of a cardiac pacemaker for complete heart block and Adams-Stokes attacks. However, 2 weeks before admission, she noted a slower heart rate and after 2 syncopal episodes was returned to Walter Reed General Hospital. An electrocardiogram revealed complete heart block, with idioventricular rhythm. The ventricle responded to the implanted pacemaker only when . . .
Everolimus (Eve) for the Treatment of Advanced Pancreatic Neuroendocrine Tumors (Pnet): Final Overall Survival (Os) Results of a Randomized, Double-Blind, Placebo (Pbo)-Controlled, Multicenter Phase III Trial (Radiant-3)
Authors: J.C. Yao, M. Pavel, C. Lombard-Bohas, E. van Cutsem, D. Lam, T. Kunz, U. Brandt, J. Capdevila, E.G.E. De Vries, T. Hobday, P. Tomassetti, R. Pommier
Journal: Annals of Oncology (2014)
Case 5-1995
Authors: L.R. Caplan, E.T. Hedley-Whyte
Journal: New England Journal of Medicine (1995)

Presentation of CaseA 73-year-old right-handed man was admitted to the hospital because of weakness, drowsiness, headache, and confusion.The patient had been well until four weeks earlier, when fatigue, anorexia, somnolence, confusion, and a severe, constant bilateral frontal headache developed, with pain on the left side of the face and jaw and neck stiffness. Two weeks before admission his vision became blurred, and an ophthalmologist found mild anterior uveitis of the right eye, with cells in the aqueous humor and slightly increased intraocular pressure. Prednisone eyedrops were prescribed, with improvement. One week before admission the patient was seen in . . .
Improving bit rate in an auditory BCI: Exploiting error-related potentials
Authors: Timothy Zeyl, Erwei Yin, Michelle Keightley, Tom Chau
Journal: Brain-Computer Interfaces (2016)

The error-related potential (ErrP) can inform the correction of brain-computer interface (BCI) mistakes, but it has thus far been incorporated only into visual BCIs, with mixed success. Given that ErrPs are thought to have higher impact when BCI accuracy is relatively low, we sought to identify the aurally evoked ErrP and investigate its auto-corrective value in auditory BCIs, which typically yield lower accuracies than visual BCIs. We implemented an auditory P300 BCI with four selectable items. Each of nine typically developed participants attempted to spell letter sequences on two separate days. Erroneous feedback was detected by (i) making use of the ErrP, (ii) assessing BCI selection confidence, and (iii) combining these two pieces of information into a hybrid detector. ErrPs were detected with an average cross-validation area under the curve of 0.946. Simulated automatic correction by reverting to the second-ranked letter improved participant-wise information transfer rate by 2.3 bits/minute when errors were detected by the hybrid method. The results suggest ErrP-based error correction can be used to make a substantial improvement in the performance of auditory BCIs.
Smoking in Relation to Atherosclerosis of the Coronary Arteries
Authors: Oscar Auerbach, E. Cuyler Hammond, Lawrence Garfinkel
Journal: New England Journal of Medicine (1965)

IN numerous studies of male populations it has been found that death rates and incidence rates of coronary heart disease (International List category 420) are higher among cigarette smokers than among nonsmokers and increase with amount of cigarette smoking.1 2 3 4 5 6 However, the epidemiologic evidence does not necessarily indicate an association between cigarette smoking and atherosclerosis of the coronary arteries.7 This paper is concerned with autopsy evidence on the subject.SubjectsBetween January 1, 1955, and December 31, 1960, 2761 men died in the Veterans Administration Hospital, East Orange, New Jersey, and post-mortem examinations were performed on 1972 of them. Several weeks . . .
The Role of Metabolite-Specific Antibodies in Nomifensine-Dependent Immune Hemolytic Anemia
Authors: Abdulgabar Salama, Christian Mueller-Eckhardt
Journal: New England Journal of Medicine (1985)

Nomifensine is an antidepressant drug (widely used in Europe, but not yet available in the United States), which has been linked to intravascular hemolysis. We studied 19 patients (18 women and 1 man) with acute intravascular hemolysis due to nomifensine-dependent antibodies. Transitory renal insufficiency developed in at least seven patients, and four required temporary dialysis. To investigate the antibodies, we used nomifensine, its three main metabolites, and its ex vivo antigens (urine samples from a volunteer collected 1.5 to 16 hours after the ingestion of 100 mg of nomifensine). We found an extraordinary heterogeneity of antibody response. Only five antibodies appeared to be primarily reactive with nomifensine. The remaining antibodies reacted either optimally or exclusively in the presence of one or more of the metabolites. Three of the metabolite-specific antibodies were positive only in the presence of ex vivo antigens, indicating specificity for as-yet-unidentified early and late metabolites of nomifensine. All the antibodies were capable of activating complement and belonged to the IgG or IgM class or both. Two serum samples also contained weak IgA antibodies. In addition to a variable degree of cross-reactivity of the antibodies, at least one serum sample had two drug-dependent red-cell antibodies (IgG against nomifensine and IgM against metabolites), and one sample had a drug-dependent IgM red-cell antibody and an IgG platelet antibody. Despite their serologic heterogeneity, all the antibodies were strongly reactive with ex vivo antigens. We recommend the use of ex vivo antigens as the technique of choice for the detection of nomifensine-dependent (and probably other drug-dependent) antibodies. (N Engl J Med 1985; 313:469–74.)
Case 15-1999
Authors: Craig M. Lilly, Eugene J. Mark
Journal: New England Journal of Medicine (1999)

Presentation of CaseA 77-year-old man was admitted to the hospital because of syncope and hemoptysis.The patient had a long history of type 2 diabetes mellitus, hypertension, coronary artery disease, congestive heart failure, paroxysmal atrial fibrillation, and chronic renal insufficiency ascribed to nephrosclerosis. Two years before the current admission, a leaking abdominal aortic aneurysm had been repaired elsewhere. Ten and a half weeks before the current admission, he was admitted to this hospital because of worsening back pain and was found to have an aneurysm of the descending thoracic aorta, 8.7 cm in diameter; the entire descending thoracic aorta . . .
Yin Yang 1 (YY1) Regulates The Transcription Of The Gene Krüppel-Like Factor 4 (KLF4) In Pediatric Burkitt Lymphoma: Clinical Implications
Authors: Mario I Vega, Alberto Valencia-Hipolito, Miriam Hernandez-Atenogenes, Gabriel G Vega, Hector Mayani, Sara Huerta-Yepez, Benjamin Bonavida, Otoniel Martinez-Maza
Journal: Blood (2013)
P0501 : Reduced T cell activation, regulatory T cell mediated suppression and compromised natural killer cell function characterize immune tolerant phase of chronic HBV infection
Authors: M. Nandi, S. Pal, G. Ray, K. Das, S. Ghosh, S. Banerjee, A. Santra, A. Chowdhury, S. Datta
Journal: Journal of Hepatology (2015)
Bortezomib, melphalan, prednisone, and thalidomide (VMPT) followed by maintenance with bortezomib and thalidomide (VT) for initial treatment of elderly multiple myeloma patients.
Authors: M. Boccadoro, S. Bringhen, G. Gaidano, R. Ria, M. Offidani, F. Patriarca, C. Nozzoli, P. Musto, M. Petrucci, A. P. Palumbo
Journal: Journal of Clinical Oncology (2010)

8013 Background: In newly diagnosed patients (pts) bortezomib-melphalan-prednisone (VMP) was superior to MP. In relapsed-refractory pts the 4 drug combination VMPT induced a high CR rate. Methods: In this phase III trial, 511 pts ≥ 65 years were randomized to receive VMPT followed by VT (N=254) or VMP without maintenance (N=257). The primary end point was PFS. Initially, VMPT consisted of induction with nine 6-week cycles (V: 1.3 mg/m2 d 1,4,8,11,22,25,29,32 in cycles 1-4 and d 1,8,22,29 in cycles 5-9; M: 9 mg/m2 and P: 60 mg/m2 d 1-4 and T: 50 mg d 1-42) followed by maintenance (V: 1.3 mg/m2 every 15 days and T: 50 mg/day); VMP consisted of bortezomib, melphalan and prednisone at the same doses and schedules without maintenance. In March 2007, the protocol was amended: both VMPT and VMP schedules were changed to once-weekly bortezomib infusion. Assuming the hazard ratio (VMP vs. VMPT) of 1.35, the sample size is 500 (250/arm) pts (1- β 80%, 2-side α 0.05). Results: Response rates were superior in VMPT: ≥ PR (89% vs. 81%, p=0.01), ≥ VGPR (59% vs. 50%, p=0.03) and CR (38% vs. 24% p=0.0008), respectively. Maintenance did not increase the response to induction. After a median follow-up of 22 months, the 3-year PFS was 60% in VMPT and 42% in VMP (HR=0.65, 95% CI 0.48-0.89, p=0.007). In both arms, CR significantly prolonged PFS (p<0.01) and chromosomal abnormalities [t(4;14), t(14;16) or del17] did not affect PFS. The 3-year OS was 89% in both groups (p=0.96). VMPT resulted in higher incidence of G3-4 neutropenia (38% vs 28%, p=0.02) and cardiac complications (10% vs. 5%, p=0.04). The incidence of G3-4 peripheral neuropathy (PN) was 8% in VMPT and 5% in VMP (p=0.19). The weekly infusion of bortezomib significantly decreased the incidence of G3-4 PN (from 18-13% to 4-2%, p<0.001), without any significant change in CR rates and PFS. Conclusions: VMPT-VT was superior to VMP for response rates and PFS. The weekly infusion of bortezomib significantly reduced the incidence of PN without affecting outcome. This is the first report showing the superiority of a 4-drug combination followed by maintenance in comparison with the most recent standard therapy, VMP. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene, Janssen-Cilag Celgene, Janssen-Cilag Celgene, Janssen-Cilag
Deaths from low dose paracetamol poisoning
Authors: J. Barnes, M. Abban, P. Howarth, G. Brandon, D P McAliskey, K S Aujla, V M Maclean, J R Richardson, E M Docherty, S H L Thomas, D F D'Costa, M G Cameron, B. Wright, M. Crowe, S Bridger, K Henderson, A J Ellis, E Glucksman, R. Williams, J. Henry
Journal: BMJ (1998)

Costings were inadequateEditor-Comparing the costs of home and acute hospital care, Coast et al address a subject of intense interest to NHS managers. 1The cost of home care in their study was based on a bottom up analysis, in which use of resources was measured on a patient by patient basis.The cost of hospital care, however, was simply the average cost of inpatient care, which includes the use of operating theatres, etc. Patients for whom both sources of care are a viable option, however, are at the lower end of the intensity range for hospital care.The authors recognise this but address the problem by conducting a sensitivity analysis.They imply that assuming a
IMPS-29REFUTING BRAIN IMMUNE PRIVILEGE: LONGITUDINAL MULTIPHOTON IMAGING THROUGH SKULL WINDOWS REVEALS THE IMMUNE SURVEILLANCE OF BRAIN METASTASES AND ITS REGULATION BY FRACTALKINE
Authors: Felix Nwajei, Figen Beceren-Braun, Meenakshi Shanmugasundaram, Anna Zal, Wuenyue Ivy Wu, Amy Heimberger, Tomasz Zal
Journal: Neuro-Oncology (2015)

INTRODUCTION: The  has conventionally been considered to be immune-privileged, which has detracted from the pursuit of immunotherapies for  tumors. However, whether  malignancies remain insulated from the immune system is unclear. T cell migration in tissues is regulated in part by chemokines often in an organ-specific manner. We hypothesized that  tumors are accessible to T cell surveillance, and that this process is regulated by a chemokine called fractalkine, which is highly expressed in the brain. METHODS: Cranial windows for intravital multiphoton microscopy were established in novel transgenic murine models in which T cells, macrophages, microglia, and dendritic cells were distinctly gene-labeled with fluorescent tags. For comparison, multicolor reporter mice deficient in fractalkine receptor (CX3CR1gfp/gfp-KO) were used. Brain metastases (BM) were induced via carotid artery injection of fluorescent MCA fibrosarcoma cells and the immune dynamics at  tumor lesions was imaged longitudinally. RESULTS: BM regressed after initial progression in wild-type (WT) mice, but were lethal in Rag1-KO mice, and importantly also lethal in CX3CR1-KO mice. Intravital microscopy in WT reporter mice revealed hotspots of T cell migration at BM foci followed by tumor fragmentation. In striking contrast, T cells were reduced in BM in CX3CR1-KO reporter mice and exhibited increased meandering and decreased engagement with cancer cells. CONCLUSION: With live imaging, we directly show the existence of robust and effective immune surveillance within the  contrary to the concept of brain immune privilege. Furthermore, we identify the fractalkine/CX3CR1 chemokine-receptor axis as a key regulator of T cell immune surveillance in the malignant brain.
P73 A pilot study to investigate the use of serum inhaled corticosteroid concentration as a potential marker of treatment adherence in severe asthma
Authors: KE George, BG Keevil, G Tavernier, K Hince, DM Ryan, SJ Fowler, RM Niven
Journal: Thorax (2015)

<h3>Background</h3> Inhaled anti-inflammatory therapy is fundamental to asthma management, but adherence is very poor. This increases the risk of exacerbations and poor symptom control. Currently there is no direct way of assessing adherence to inhaled steroids accurately. The primary aim of this project was to determine whether liquid chromatography tandem mass spectrometry could be used to detect fluticasone propionate (FP) in human serum as a potential aid to therapeutic monitoring. The secondary aim was to relate serum levels of FP to markers of asthma severity. <h3>Methods</h3> We collected blood samples over an 8 hr period from inpatients with severe asthma on a stable dose of inhaled FP. Following baseline (trough) sampling, patients were observed using their inhaler, with inhaler technique documented. Subsequent samples were obtained 1, 2s, 4 and 8 hrs post inhalation. Demographic details and spirometry were also recorded. <h3>Results</h3> Thirteen patients were recruited: 8 males, 5 females; age range 22–64 yrs; FEV1 range 53–101% predicted; 10 patients on 1000 mcg/day, and three on 2000 mcg/day FP. The mean concentration of FP at 1 hr post inhaler (peak in 7/13 patients) was 95.5 (SD 89.1) ng/L. The mean pre-dose trough concentration was 32.9 (SD 41.5) ng/L. Two patients were noted to have poor inhaler technique; these patients had some of the lowest serum FP levels recorded. The FEV1% predicted was found to be strongly correlated with the peak serum FP concentration (Pearson’s r = 0.8, p = 0.001). <h3>Conclusion</h3> We have demonstrated that FP can be detected in the blood of patients with severe asthma following directly observed therapy; this could have a potential future application as a direct measure of adherence and perhaps inhaler technique. We also demonstrated a profound effect of reduced lung function predicting low serum FP levels. Future work will explore whether poor absorption reflects relatively poor efficacy in the most severe patients.