tbuckley/cabot-search huggingface dataset:
Systematic Examination of the Updated Framingham Heart Study General Cardiovascular Risk Profile
Authors: Amanda K. Marma, Donald M. Lloyd-Jones
Journal: Circulation (2009)

An updated Framingham risk prediction tool was recently published. It features an expanded end point of general cardiovascular disease and a "vascular age" risk communication analogy.We systematically examined the tool to determine which risk factor combinations allow risk thresholds to be reached and how different risk factor burdens translate into vascular age. We varied risk factor levels in isolation and combination and observed risk output patterns, with high risk defined as > or =20% 10-year predicted risk. As expected, we found that age is the major determinant of 10-year predicted risk for both men and women. Younger individuals tend not to exceed 20% 10-year risk even with multiple risk factors, although with marked risk factor burden, including both smoking and diabetes mellitus, men as young as 35 years of age and women as young as 40 years of age can be classified as high risk. For the risk factor levels we entered, predicted risk ranges from 3.1% to 46.8% for a 45-year-old man and 2.4% to 42.7% for a 55-year-old woman. Likewise, vascular age ranges from 37 to >80 years for a 45-year-old man and 39 to >80 years for a 55-year-old woman.The inclusion of noncoronary end points in this tool expands the range of predicted risks for men and women at all ages studied. Nevertheless, many younger individuals with high risk factor burden have low 10-year predicted risk. Wide ranges of "vascular age" are available for most chronological ages to assist with risk communication.
Randomized Trial of Prophylactic Granulocyte Colony-Stimulating Factor During Rapid COJEC Induction in Pediatric Patients With High-Risk Neuroblastoma: The European HR-NBL1/SIOPEN Study
Authors: Ruth Ladenstein, Dominique Valteau-Couanet, Penelope Brock, Isaac Yaniv, Victoria Castel, Geneviève Laureys, Josef Malis, Vassilios Papadakis, Ana Lacerda, Ellen Ruud, Per Kogner, Miklos Garami, Walentyna Balwierz, Henrik Schroeder, Maja Beck-Popovic, Günter Schreier, David Machin, Ulrike Pötschger, Andrew Pearson
Journal: Journal of Clinical Oncology (2010)

To reduce the incidence of febrile neutropenia during rapid COJEC (cisplatin, vincristine, carboplatin, etoposide, and cyclophosphamide given in a rapid delivery schedule) induction. In the High-Risk Neuroblastoma-1 (HR-NBL1) trial, the International Society of Paediatric Oncology European Neuroblastoma Group (SIOPEN) randomly assigned patients to primary prophylactic (PP) versus symptom-triggered granulocyte colony-stimulating factor (GCSF; filgrastim).From May 2002 to November 2005, 239 patients in 16 countries were randomly assigned to receive or not receive PPGCSF. There were 144 boys with a median age of 3.1 years (range, 1 to 17 years) of whom 217 had International Neuroblastoma Staging System (INSS) stage 4 and 22 had stage 2 or 3 MYCN-amplified disease. The prophylactic arm received a single daily dose of 5 microg/kg GCSF, starting after each of the eight COJEC chemotherapy cycles and stopping 24 hours before the next cycle. Chemotherapy was administered every 10 days regardless of hematologic recovery, provided that infection was controlled.The PPGCSF arm had significantly fewer febrile neutropenic episodes (P = .002), days with fever (P = .004), hospital days (P = .017), and antibiotic days (P = .001). Reported Common Toxicity Criteria (CTC) graded toxicity was also significantly reduced: infections per cycle (P = .002), fever (P < .001), severe leucopenia (P < .001), neutropenia (P < .001), mucositis (P = .002), nausea/vomiting (P = .045), and constipation (P = .008). Severe weight loss was reduced significantly by 50% (P = .013). Protocol compliance with the rapid induction schedule was also significantly better in the PPGCSF arm shown by shorter time to completion (P = .005). PPGCSF did not adversely affect response rates or success of peripheral-blood stem-cell harvest.Following these results, PPG-GSF was advised for all patients on rapid COJEC induction.
Ultrasound-guided pneumothorax induction prior to local anaesthetic thoracoscopy: Table 1
Authors: John P Corcoran, Ioannis Psallidas, Robert J Hallifax, Ambika Talwar, Annemarie Sykes, Najib M Rahman
Journal: Thorax (2015)

Local anaesthetic thoracoscopy (LAT) is performed by a growing number of respiratory physicians in the context of an expanding population with pleural disease. Most LATs occur in patients with moderate to large effusions where the presence of fluid allows safe access to the pleural space. Patients with little or no fluid, but other features concerning for pleural disease, are usually investigated by surgical means. Advanced LAT practitioners can also provide this service through pneumothorax induction, although there is little published data on the safety or efficacy of this technique. We present data from a series of 77 consecutive patients in whom ultrasound-guided pneumothorax induction and LAT were attempted. 67 procedures (87.0%) were successful, with the most common histopathological diagnoses being chronic pleuritis (58.2%) and mesothelioma (16.4%). No adverse events were reported secondary to the procedure. These findings demonstrate the utility of this approach and should inform future practice and guidelines.
Effect of Psychiatric Intervention in Attempted Suicide: A Controlled Study
Authors: S. Greer, C. Bagley
Journal: BMJ (1971)

All patients presenting at the casualty department of King9s College Hospital during the first six months of 1968 with deliberate self-poisoning or self-injury were followed up. Of 211 patients 204 (97%) were traced after a mean interval of 18 months (range one to two years). Despite official hospital policy, 22% had not been seen by a psychiatrist before discharge; these 44 untreated patients were compared with the remaining 160 who had received either brief (one or two interviews) or more prolonged psychiatric and social help. Subsequent suicidal attempts occurred significantly more often among untreated than among treated patients, prolonged treatment being associated with the best prognosis. The same trend was observed in respect of actual suicide, though the numbers were small and differences did not reach statistical significance. These findings held good when the untreated and treated groups were controlled for other variables which were found to be correlated with outcome. These results indicate that psychiatric intervention is associated with a significant reduction in subsequent suicidal behaviour.
Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: preliminary safety results from the CHHiP randomised controlled trial
Authors: David Dearnaley, Isabel Syndikus, Georges Sumo, Margaret Bidmead, David Bloomfield, Catharine Clark, Annie Gao, Shama Hassan, Alan Horwich, Robert Huddart, Vincent Khoo, Peter Kirkbride, Helen Mayles, Philip Mayles, Olivia Naismith, Chris Parker, Helen Patterson, Martin Russell, Christopher Scrase, Chris South, John Staffurth, Emma Hall
Journal: The Lancet Oncology (2011)

Prostate cancer might have high radiation-fraction sensitivity, implying a therapeutic advantage of hypofractionated treatment. We present a pre-planned preliminary safety analysis of side-effects in stages 1 and 2 of a randomised trial comparing standard and hypofractionated radiotherapy.We did a multicentre, randomised study and recruited men with localised prostate cancer between Oct 18, 2002, and Aug 12, 2006, at 11 UK centres. Patients were randomly assigned in a 1:1:1 ratio to receive conventional or hypofractionated high-dose intensity-modulated radiotherapy, and all were given with 3-6 months of neoadjuvant androgen suppression. Computer-generated random permuted blocks were used, with risk of seminal vesicle involvement and radiotherapy-treatment centre as stratification factors. The conventional schedule was 37 fractions of 2 Gy to a total of 74 Gy. The two hypofractionated schedules involved 3 Gy treatments given in either 20 fractions to a total of 60 Gy, or 19 fractions to a total of 57 Gy. The primary endpoint was proportion of patients with grade 2 or worse toxicity at 2 years on the Radiation Therapy Oncology Group (RTOG) scale. The primary analysis included all patients who had received at least one fraction of radiotherapy and completed a 2 year assessment. Treatment allocation was not masked and clinicians were not blinded. Stage 3 of this trial completed the planned recruitment in June, 2011. This study is registered, number ISRCTN97182923.153 men recruited to stages 1 and 2 were randomly assigned to receive conventional treatment of 74 Gy, 153 to receive 60 Gy, and 151 to receive 57 Gy. With 50·5 months median follow-up (IQR 43·5-61·3), six (4·3%; 95% CI 1·6-9·2) of 138 men in the 74 Gy group had bowel toxicity of grade 2 or worse on the RTOG scale at 2 years, as did five (3·6%; 1·2-8·3) of 137 men in the 60 Gy group, and two (1·4%; 0·2-5·0) of 143 men in the 57 Gy group. For bladder toxicities, three (2·2%; 0·5-6·2) of 138 men, three (2·2%; 0·5-6·3) of 137, and none (0·0%; 97·5% CI 0·0-2·6) of 143 had scores of grade 2 or worse on the RTOG scale at 2 years.Hypofractionated high-dose radiotherapy seems equally well tolerated as conventionally fractionated treatment at 2 years.Stage 1 was funded by the Academic Radiotherapy Unit, Cancer Research UK programme grant; stage 2 was funded by the Department of Health and Cancer Research UK.
Predictive Biomarkers for Bevacizumab: Are We There Yet?
Authors: Dipen Maru, Alan P. Venook, Lee M. Ellis
Journal: Clinical Cancer Research (2013)

Therapy targeting VEGF has become the standard of care in several solid malignancies. Early investigations attempting to identify predictive markers for the efficacy of therapy failed to identify any predictive markers that could help oncologists decide who should-and, more importantly, who should not-receive VEGF-targeted therapies. However, interest has been renewed in predictive biomarkers for VEGF-targeted therapies, especially in light of the fact that the U.S. Food and Drug Administration withdrew approval for use of bevacizumab, an antibody to VEGF, in patients with metastatic breast cancer. In a recent publication in the Journal of Clinical Oncology, investigators identified circulating VEGF and tumor neuropilin-1 expression as potential predictive biomarkers for bevacizumab. From this perspective, we provide a critical evaluation of the use of these markers and the need for validation in prospective clinical trials.
Detection of glioblastoma response to temozolomide combined with bevacizumab based on µMRI and µPET imaging reveals [18F]-fluoro-l-thymidine as an early and robust predictive marker for treatment efficacy
Authors: Aurélien Corroyer-Dulmont, Elodie A. Pérès, Edwige Petit, Jean-Sébastien Guillamo, Nathalie Varoqueaux, Simon Roussel, Jérôme Toutain, Didier Divoux, Eric T. MacKenzie, Jérôme Delamare, Méziane Ibazizène, Myriam Lecocq, Andréas H. Jacobs, Louisa Barré, Myriam Bernaudin, Samuel Valable
Journal: Neuro-Oncology (2012)

The individualized care of glioma patients ought to benefit from imaging biomarkers as precocious predictors of therapeutic efficacy. Contrast enhanced MRI and [18F]-fluorodeoxyglucose (FDG)–PET are routinely used in clinical settings; their ability to forecast the therapeutic response is controversial. The objectives of our preclinical study were to analyze sensitive µMRI and/or µPET imaging biomarkers to predict the efficacy of anti-angiogenic and/or chemotherapeutic regimens. Human U87 and U251 orthotopic glioma models were implanted in nude rats. Temozolomide and/or bevacizumab were administered. µMRI (anatomical, diffusion, and microrheological parameters) and µPET ([18F]-FDG and [18F]-fluoro-l-thymidine [FLT]–PET) studies were undertaken soon (t1) after treatment initiation compared with late anatomical µMRI evaluation of tumor volume (t2) and overall survival. In both models, FDG and FLT uptakes were attenuated at t1 in response to temozolomide alone or with bevacizumab. The distribution of FLT, reflecting intratumoral heterogeneity, was also modified. FDG was less predictive for treatment efficacy than was FLT (also highly correlated with outcome, P < .001 for both models). Cerebral blood volume was significantly decreased by temozolomide + bevacizumab and was correlated with survival for rats with U87 implants. While FLT was highly predictive of treatment efficacy, a combination of imaging biomarkers was superior to any one alone (P < .0001 in both tumors with outcome). Our results indicate that FLT is a sensitive predictor of treatment efficacy and that predictability is enhanced by a combination of imaging biomarkers. These findings may translate clinically in that individualized glioma treatments could be decided in given patients after PET/MRI examinations.
The Poxvirus Protein A52R Targets Toll-like Receptor Signaling Complexes to Suppress Host Defense
Authors: Mary T. Harte, Ismar R. Haga, Geraldine Maloney, Pearl Gray, Patrick C. Reading, Nathan W. Bartlett, Geoffrey L. Smith, Andrew Bowie, Luke A.J. O'Neill
Journal: The Journal of Experimental Medicine (2003)

Toll-like receptors (TLRs) are crucial in the innate immune response to pathogens, in that they recognize and respond to pathogen associated molecular patterns, which leads to activation of intracellular signaling pathways and altered gene expression. Vaccinia virus (VV), the poxvirus used to vaccinate against smallpox, encodes proteins that antagonize important components of host antiviral defense. Here we show that the VV protein A52R blocks the activation of the transcription factor nuclear factor κB (NF-κB) by multiple TLRs, including TLR3, a recently identified receptor for viral RNA. A52R associates with both interleukin 1 receptor–associated kinase 2 (IRAK2) and tumor necrosis factor receptor–associated factor 6 (TRAF6), two key proteins important in TLR signal transduction. Further, A52R could disrupt signaling complexes containing these proteins. A virus deletion mutant lacking the A52R gene was attenuated compared with wild-type and revertant controls in a murine intranasal model of infection. This study reveals a novel mechanism used by VV to suppress the host immunity. We demonstrate viral disabling of TLRs, providing further evidence for an important role for this family of receptors in the antiviral response.
Stomach regulates energy balance via acylated ghrelin and desacyl ghrelin
Authors: A Asakawa
Journal: Gut (2004)

The gastric peptide ghrelin, an endogenous ligand for growth-hormone secretagogue receptor, has two major molecular forms: acylated ghrelin and desacyl ghrelin. Acylated ghrelin induces a positive energy balance, while desacyl ghrelin has been reported to be devoid of any endocrine activities. The authors examined the effects of desacyl ghrelin on energy balance.The authors measured food intake, gastric emptying, c-Fos expression in the hypothalamus, and gene expression of hypothalamic neuropeptides in mice after administration of desacyl ghrelin. To explore the effects of long term overexpression of desacyl ghrelin, transgenic mice that overexpressed desacyl ghrelin were created.Administration of desacyl ghrelin decreased food intake and gastric emptying rate through an action on the paraventricular nucleus and the arcuate nucleus in the hypothalamus. Gene expression of anorexigenic cocaine and amphetamine regulated transcript and urocortin in the hypothalamus was increased by desacyl ghrelin. Desacyl ghrelin overexpressing mice exhibited a decrease in body weight, food intake, and fat pad mass weight accompanied by moderately decreased linear growth. Gastric emptying was also decreased in desacyl ghrelin overexpressing mice.These findings indicate that in contrast to acylated ghrelin, desacyl ghrelin induces a negative energy balance by decreasing food intake and delaying gastric emptying. The effect is mediated via the hypothalamus. Although derived from the same precursor, the inverse effects of these two peptides suggest that the stomach might be involved as an endocrine organ in the regulation of the energy balance.
Multilevel atrioventricular block.
Authors: B D Kosowsky, P Latif, A M Radoff
Journal: Circulation (1976)

Arrhythmias displaying conduction disturbances consistent with block at more than one level within the atrioventricular conduction system were seen in 36 patients during a two year period in a community hospital. Two levels of block were postulated in each patient; one patient also demonstrated a third level of block. In 24 patients (Type A), there was an integral conduction ratio at the upper level of block. This pattern was most frequently seen in atrial flutter (mean atrial rate 284 +/- 35 beats/min) with 2:1 block at the upper level and Wenckebach at the lower level. Progression to 2:1 block at the lower level resulted in 4:1 block. Twelve patients (Type B) had a nonintegral conduction ratio of their block at the upper level with a mean atrial rate of 162 +/- 62 beats/min. Their conduction patterns consisted of Wenckebach block at the upper level with either integral (2:1) or nonintegral (Wenckebach) block at the lower level. The presence of multilevel block was not related to specific etiological diagnoses, medications, or electrolyte patterns. It is suggested that multilevel block is a common, frequently transient, conduction pattern seen in a variety of clinical conditions. It is readily recognized from a standard electrocardiogram and, of itself, has no short-term detrimental prognostic implications.
Preserving postischemic reperfusion in the kidney: a role for extracellular adenosine
Authors: Joel M. Weinberg, Manjeri A. Venkatachalam
Journal: Journal of Clinical Investigation (2012)

Several adenosine receptor subtypes on endothelial, epithelial, mesangial, and inflammatory cells have been implicated in ischemic acute kidney injury, a life-threatening condition that frequently complicates the care of hospitalized patients. In this issue of the JCI, Grenz and coworkers provide novel insight into how preservation of postischemic renal perfusion by endothelial cell adenosine A2B receptors is antagonized by adenosine reuptake into proximal tubule cells by equilibrative nucleotide transporter 1, which can be inhibited by dipyridamole. The work suggests that adenosine A2B receptor agonists and inhibition of equilibrative nucleoside transporters by dipyridamole may have therapeutic potential in ischemic acute kidney injury, a condition for which there are currently no specific therapeutic interventions.
Insufficient sensitivity of reagent strips for spontaneous bacterial peritonitis
Authors: Veit Gülberg, Alexander L. Gerbes, Tilman Sauerbruch, Beate Appenrodt
Journal: Hepatology (2007)

We read with interest the study of Nousbaum and colleagues, which reported a low sensitivity of the Multistix 8 reagent strip in the diagnosis of spontaneous bacterial peritonitis (SBP).1 It is noteworthy that overall prevalence of SBP in this study was only 5.5%, significantly lower than in all previous studies focussing on diagnostic accuracy of different reagent strips, where prevalence of SBP ranged between 7% and 23%. Can this simple statistical bias explain the differences in diagnostic sensitivity of different reagent strips? Recently, we terminated a similar study comparing Multistix 10 SG and Combur reagent strips for their diagnostic value of SBP in the inpatient setting at 2 tertiary care centers. We found 16 cases of SBP in 194 paracenteses summing up to a prevalence of SBP of 8.2% in inpatients and comparing well with the subset of inpatients in the study of Nousbaum et al. (9%). Sensitivity of Multistix 10 SG was even worse in our setting (31%) and only slightly better for Combur reagent strips (44%). Although at a different level, this finding is in accordance with the study of Campillo et al.2 who reported better performance of Combur reagent strips. When comparing different parameters between false-negative and true-positive results in our patients with SBP, we found significantly higher mean ascitic protein content in patients with false-negative results than in patients with true-positive results (3.4 versus 2.1 g/dL for Multistix 10 SG and 3.8 versus 2.0 g/dL for Combur reagents strips, respectively). Therefore, we speculate that leukocyte esterase in both test systems may be inhibited by high ascitic protein content thereby decreasing diagnostic sensitivity of SBP. As stated by Nousbaum et al., reagent strips were designed for detecting urinary tract infection. Because proteinuria above 1 g/L is a rare condition, urinary protein content is unlikely to interfere with detection of leukocytes by these reagent strips. In ascites, however, higher protein concentrations may cause insufficient sensitivity of reagent strips to detect SBP. Thus, we fully agree with Nousbaum et al. that it is premature to replace standard ascitic analyses by reagent strips due to their low sensitivity in detecting SBP. Veit Gülberg*, Alexander L. Gerbes*, Tilman Sauerbruch , Beate Appenrodt , * Department of Medicine 2, University of Munich, Germany, Department of Internal Medicine I, General Internal Medicine, University of Bonn, Germany.
Cytotoxic T lymphocytes produce immune interferon in response to antigen or mitogen.
Authors: J R Klein, D H Raulet, M S Pasternack, M J Bevan
Journal: The Journal of Experimental Medicine (1982)

Interferon (IFN) was found to be secreted by cloned lines of murine cytotoxic T lymphocytes in response to mitogenic or antigen specific stimulation. The IFN produced was shown to be of the immune type based on its sensitivity to pH 2.0 and on the ability of an antiserum to immune IFN to neutralize the antiviral activity.
Cancer immunoediting by the innate immune system in the absence of adaptive immunity
Authors: Timothy O’Sullivan, Robert Saddawi-Konefka, William Vermi, Catherine M. Koebel, Cora Arthur, J. Michael White, Ravi Uppaluri, Daniel M. Andrews, Shin Foong Ngiow, Michele W.L. Teng, Mark J. Smyth, Robert D. Schreiber, Jack D. Bui
Journal: The Journal of Experimental Medicine (2012)

Cancer immunoediting is the process whereby immune cells protect against cancer formation by sculpting the immunogenicity of developing tumors. Although the full process depends on innate and adaptive immunity, it remains unclear whether innate immunity alone is capable of immunoediting. To determine whether the innate immune system can edit tumor cells in the absence of adaptive immunity, we compared the incidence and immunogenicity of 3′methylcholanthrene-induced sarcomas in syngeneic wild-type, RAG2−/−, and RAG2−/−x γc−/− mice. We found that innate immune cells could manifest cancer immunoediting activity in the absence of adaptive immunity. This activity required natural killer (NK) cells and interferon γ (IFN-γ), which mediated the induction of M1 macrophages. M1 macrophages could be elicited by administration of CD40 agonists, thereby restoring editing activity in RAG2−/−x γc−/− mice. Our results suggest that in the absence of adaptive immunity, NK cell production of IFN-γ induces M1 macrophages, which act as important effectors during cancer immunoediting.
Feasibility of Open Heart Surgery in a Community Hospital
Authors: A. Hassan Khazei
Journal: JAMA (1975)

A program for open heart surgery in one community hospital was formulated and put into practice. Experience gained indicates that such services are a necessity in hospitals that fulfill certain criteria. The program is safe and inexpensive. A house staff is not a prerequisite. Finally, the analysis of data obtained from the first 100 cases compares very favorably with results in large medical centers, indicating that the patient's recovery is not compromised.