tbuckley/cabot-search huggingface dataset:
Higher nurse to patient ratio is linked to reduced risk of inpatient death
Authors: Jacqui Wise
Journal: BMJ (2016)

Death rates in English hospitals where registered nurses cared for six or fewer patients were 20% lower than in those where they cared for more than 10, research published in the online journal BMJ Open has found.1

Researchers looked at the number of beds per registered nurse, doctor, and healthcare support worker in 137 acute care trusts from 2009 to 2011. They also analysed the number of patients per ward nurse in a survey of 2917 registered nurses from a nationally representative subsample of 31 …
P59 TLR4 antagonist in acute liver failure: a novel therapeutic strategy
Authors: N Shah, D Dhar, M Montes de Oca, M Jover-Cobos, N Davies, F Mohamed, R P Mookerjee, R Jalan
Journal: Gut (2010)

Introduction  Acetaminophen (APAP) toxicity is the commonest cause of acute liver failure (ALF) which is characterised by multiorgan failure manifested by rapid acute liver injury, severe brain oedema and renal failure. Without liver transplantation, about 40% patients die and its treatment is an unmet medical need. Unregulated inflammatory response plays an important role in its pathogenesis. A multitude of cytokines are released during ALF with consequent activation of NfKB and progressive liver injury. We hypothesised that Toll-like receptor-4 may be critical in the progression to multiorgan failure.  Aim  The aim of this study was to determine whether administration a novel TLR4 antagonist (STM28) to an APAP model of ALF in mice would prevent liver injury and its deleterious effect on the brain and the kidneys. (STM28 was kindly gifted by Professor Ken-ichi Tanamoto, Division of Microbilogy, National Institute of Health Sciences, Tokyo 158-8501, Japan).  Method  Three groups of Cd1 male mice were studied. Sham, APAP (acetaminophen, 500 mg/kg single dose IP after over night fasting), APAP+TLR4 antagonist (STM28; 20 ug IP, 1 h prior to the administration of APAP and 6 h later). All the mice were hydrated, administered 10% dextrose and kept in temperature controlled environment. Blood was collected for biochemistry and cytokine assay. Liver, kidney and brain were collected for western blotting and cytokine analyses and the brain frontal cortex for brain water. Animals were sacrificed at 12 h after APAP administration.  Results  Administration of APAP led to an increase in the level of liver enzymes, ALT (p=0.004) and AST (p=0.007) in comparison to the Shams, which was significantly reduced (ALT (p=0.01) and AST (p=0.008)) in the TLR4 antagonist group. ALF associated increase in ammonia (p=0.001) and brain water (p=0.04) were significantly reduced (ammonia (p=0.03); brain water (p=0.05)). ALF associated renal failure (p=0.004) was also markedly attenuated (p  Conclusion  The results of this study show for the first time a role for TLR4 in pathogenesis of multiorgan failure in ALF. The data strongly support a potential therapeutic role for TLR4 antagonist in the prevention of progression of ALF.
Bronchial artery embolisation in the management of haemoptysis in pulmonary tuberculosis
Authors: Debajyoti Bhattacharyya, K. Pathak, M.S. Barthwal, C.D.S. Katoch, S. Rohatgi
Journal: European Respiratory Journal (2011)

Introduction:  Bronchial artery embolisation (BAE) is the procedure of selective bronchial angiography with embolisation of abnormal vessels.   Aims and objectives:  To assess the efficacy and safety of BAE in patients with haemoptysis in pulmonary tuberculosis (PTB).   Methods:  This is a retrospective study of all patients of haemoptysis in PTB who underwent BAE between January 2004 and December 2010 in a tertiary care hospital in India. Bronchial arteriography and embolisation was performed using 5 French pigtail catheter and polyvinyl alcohol (PVA) particles ranging from 150 to 1000 micrometers.   Results:  34 patients (21 males and 13 females) of haemoptysis in PTB, underwent 37 BAE procedures during the period of study. 11 (32.3%) of these patients had multidrug resistant tuberculosis. Mean age of patients was 29.4 years (range: 13-69 years). Indication of BAE was: acute major haemoptysis in 11 (32.3%) and chronic recurrent bleeding in 23 (67.7%) patients. Haemoptysis was successfully controlled after the embolisation procedure in 32 (94.1%) patients. Procedure was repeated in three (8.8%) patients within a period of six months because of recurrent haemoptysis. Following arteries were embolised: right bronchial artery (11), left bronchial artery (7), common bronchial trunk (7), intercostal artery (14), right internal mammary artery (1), thyrocervical trunk (1), right intercostobronchial (2), and left intercostobronchial (1). No abnormal vessel was detected in one patient. The only complication encountered was local haematoma in one (2.94%) patient.   Conclusions:  Bronchial artery embolisation is an effective and safe procedure for haemoptysis in pulmonary tuberculosis.
US Surgeons’ Perceptions of Racial/Ethnic Disparities in Health Care
Authors: Breanne V. Britton, Neeraja Nagarajan, Cheryl K. Zogg, Shalini Selvarajah, Maya J. Torain, Ali Salim, Adil H. Haider
Journal: JAMA Surgery (2016)

ticipant recruitment and enrollment; judge the appropriateness of the outcomes; and evaluate dissemination of results.A more immediate measure of success may be the award of funds to carry out the study because demonstration of meaningful engagement is a core aspect of funding.This work was part of a successful application for the Comparing Outcomes of Drugs and Appendectomy study, a pragmatic clinical trial funded by Patient Centered Outcomes Research Institute. 6Patient engagement is increasingly important in surgical research, and we encourage others to share their strategies.Just as dissemination of clinical findings leads to improvements in outcomes, dissemination of engagement strategies may increase the success of future studies.
Hypermethylation of p15INK4B Gene in a Patient With Acute Myelogenous Leukemia Evolved From Paroxysmal Nocturnal Hemoglobinuria
Authors: Toshiki Uchida, Haruhiko Ohashi, Tomohiro Kinoshita, Hidehiko Saito, Ryo Taguchi, Tomomitsu Hotta, Takashi Murate
Journal: Blood (1998)
Sphingosine-1-Phosphate Receptor Agonist Fingolimod Increases Myocardial Salvage and Decreases Adverse Postinfarction Left Ventricular Remodeling in a Porcine Model of Ischemia/Reperfusion
Authors: Carlos G. Santos-Gallego, Torsten P. Vahl, Georg Goliasch, Belen Picatoste, Teresa Arias, Kiyotake Ishikawa, Ida U. Njerve, Javier Sanz, Jagat Narula, Partho P. Sengupta, Roger J. Hajjar, Valentin Fuster, Juan J. Badimon
Journal: Circulation (2016)

Fingolimod, a sphingosine-1-phosphate receptor agonist, is used for the treatment of multiple sclerosis and exerts antiapoptotic properties. We hypothesized that sphingosine-1-phosphate receptor activation with fingolimod during acute myocardial infarction (MI) inhibits apoptosis, leading to increased myocardial salvage, reduced infarct size, and mitigated left ventricular (LV) remodeling in a porcine model of ischemia/reperfusion.Ischemia/reperfusion was induced in pigs by balloon occlusion of the left anterior descending artery, followed by reperfusion. Animals randomly received fingolimod or saline (control). In short-term experiments, fingolimod treatment activated the cardioprotective reperfusion injury salvage kinase and survivor activating factor enhancement pathways in the infarct border zone 24 hours after MI, leading to decreased cardiomyocyte apoptosis and reduced myocardial oxidative stress. These effects were abolished by specific inhibitors of both pathways, demonstrating that fingolimod-induced cardioprotection was mediated by reperfusion injury salvage kinase and survivor activating factor enhancement pathways. In long-term experiments, fingolimod significantly improved myocardial salvage, reduced infarct size, and improved systolic LV function measured by cardiac magnetic resonance 1 week and 1 month after MI. Importantly, fingolimod mitigated the development of adverse post-MI LV remodeling 1 month after MI. Specifically, fingolimod treatment led to a significant reduction in LV mass, LV dilatation, and neurohormonal activation, and it preserved LV geometry. Furthermore, fingolimod decreased interstitial fibrosis, cardiomyocyte hypertrophy, and chronic activation of Akt and extracellular receptor kinase 1/2 in the remote noninfarcted myocardium.Sphingosine-1-phosphate receptor activation with fingolimod during acute MI reduced infarct size via the reperfusion injury salvage kinase and survivor activating factor enhancement pathways, improved systolic LV function, and mitigated post-MI LV remodeling. Our data strongly support a cardioprotective role for sphingosine-1-phosphate receptor activation during MI.
Hypothyroidism as a consequence of intensity-modulated radiation therapy (IMRT) with concurrent taxane-based chemotherapy for locally-advanced head and neck cancer (LAHNC)
Authors: R. Diaz, J. J. Jaboin, S. Stinson, J. Gilbert, C. H. Chung, B. A. Murphy, B. Burkey, J. Netterville, W. G. Yarbrough, P. B. Murphy, A. J. Cmelak
Journal: Journal of Clinical Oncology (2008)

6048 Background: We conducted a retrospective review of 129 consecutively-treated locally advanced head and neck cancer (LAHNC) patients treated with intensity modulated radiotherapy (IMRT)/chemotherapy to determine the rate and potential risk factors for developing hypothyroidism post-treatment. Methods: In order to simplify IMRT planning, a single dose-painting IMRT plan was used: 69.3 Gy (2.1 Gy x 33 fractions) to gross disease and 56.1 Gy (1.7 Gy x 33 fractions) simultaneously to clinically normal nodes down to the clavicles. Fifty percent of the volume of the larynx/trachea/esophagus was limited to ≤25 Gy. Dose-volume histograms (DVHs) were used to determine radiation dose to thyroid, and to correlate dose with parameters predicting the development of hypothyroidism. Comparison to DVHs using 3-D RT using a 2cm wide midline block on the lower neck field was done in the same patients. Weekly paclitaxel 30mg/m2 and carboplatin AUC 1 were given concurrently with IMRT. Results: Patients included male-86%, female-14%; median age was 56.8 years (37–89). Primary site included hypopharynx-4%, larynx-23%, nasopharynx-9%, oral cavity-3%, oropharynx-58%, sinus-2%, unknown primary-2%. Median follow-up was 1.9 years. IMRT doses to thyroid gland had a significantly higher minimum dose (2365 cGy) and volume receiving 20 Gy (V20) (99%), as compared to 3D RT (525 cGy, 89%) (p=0.001, p=0.0003). There was no difference in median dose by IMRT (5026 cGy) than with 3D RT (4775 cGy) (p=0.31). To date, 45 patients (35%) have developed hypothyroidism after median of 1.05 years from IMRT (range 3.9 months to 3.7 years). Comparison to 3D RT (70 Gy) used on ECOG 2399 (with lower neck midline block) in similar patients and with similar chemotherapy shows 4/111 patients (3.6%) developed hypothyroidism at median 3.7 years after treatment (range 1.9–5.2 years) (p<0.001). Conclusions: IMRT for LAHNC results in higher radiation to the thyroid than with conventional 3D RT. Consequently, markedly higher post-treatment hypothyroidism is observed. Furthermore, latency to hypothyroidism onset is shorter with IMRT. Techniques to reduce dose and volume of radiation to thyroid tissue with IMRT are recommended. No significant financial relationships to disclose.
Pharmacokinetics, Efficacy and Safety Of a Recombinant Factor IX (BAX326) In Previously-Treated Pediatric Patients &lt; 12 Years Of Age With Severe Or Moderately Severe Hemophilia B
Authors: Tomasz Urasinski, Oleksandra Stasyshyn, Tatiana Andreeva, Luminita Rusen, Farida Perina, MyungShin Oh, Miranda Chapman, Borislava G Pavlova, Wing Yen Wong, Brigitt E. Abbuehl
Journal: Blood (2013)
Chromatographic and Electrophoretic Analysis of an Antigen in Hodgkin's Disease Tissue Cultures23
Authors: John C. Long, Alan C. Aisenberg, Paul C. Zamecnik
Journal: JNCI Journal of the National Cancer Institute (1977)

An antigen in tissue cultures derived from Hodgkin's disease tumors was investigated by polyacrylamide gel electrophoresis, column chromatography, and isotopic antibody techniques. Fourteen long-term, serially passaged monolayer cultures prepared from tumor nodules of Hodgkin's disease in the spleen were studied; 11 monolayers derived from normal adult spleen and human fetal spleen and thymus were used as controls. Cell-free medium from Hodgkin's disease and normal cultures were centrifuged, and the pellet fractions were sedimented in a discontinuous sucrose gradient, solubilized with sodium dodecyl sulfate, and labeled with radioiodine. Gel filtration and electrophoresis revealed a component in samples prepared from medium of Hodgkin's disease cultures that was not observed in medium from normal cultures. An antiserum made in rabbits against this component reacted by radioiodine-labeled antibody assay with an antigen on the surface of cells from Hodgkin's disease cultures that was present in very small amounts, or in a cryptic state, on normal cultured cells. This antigen, intimately associated with propagation of cells obtained from the tumor in vitro, was not demonstrable in noncultured Hodgkin's disease tissue. The findings suggested that the antigen may be a normal cellular constituent present in greatly increased amounts in Hodgkin's disease cultures, a dedifferentiated tumor neoantigen, or a viral component (either related or unrelated to the etiology of the disorder) whose expression requires prolonged replication of cells in culture.
Kidney disease in moderate-to-severe psoriasis: a critical appraisal
Authors: Z.K. Jabbar-Lopez, S.C. Weatherhead, N.J. Reynolds
Journal: British Journal of Dermatology (2016)

Using a population-based cohort, Wan et al. examined the risk of moderate-to-advanced (stage 3-5) chronic kidney disease (CKD) in patients with psoriasis.A population-based cohort was constructed using The Health Improvement Network (THIN) database. THIN is an electronic primary healthcare records database containing routinely collected medical diagnosis and drug prescribing data on > 9 million patients in the U.K. Data were collected prospectively on 143 883 adults (aged 18-90 years) with psoriasis. Of these, 7354 had severe psoriasis, as defined by prescription codes for systemic medication or treatment codes for phototherapy. Patients with psoriasis were matched with up to five nonpsoriasis age- and practice-matched controls. Patients with a diagnosis of CKD before study entry were excluded. In addition, baseline data from the Incident Health Outcomes and Psoriasis Events (iHOPE) study, a cohort of 8731 primary care patients aged 25-64 years with psoriasis, was included. Psoriasis severity was categorized according to body surface area (BSA) involvement as estimated by general practitioners. A similar method using a patient-reported BSA assessment tool was previously validated by the same group. Patients were matched by age and practice with 10 nonpsoriasis controls.Psoriasis, identified on the basis of a recorded diagnostic code for psoriasis.Incident CKD was defined as the presence of a recorded diagnostic code consistent with moderate-to-advanced (stage 3-5) CKD or laboratory parameters consistent with the diagnosis (estimated glomerular filtration rate < 60 mL min(-1) 1·73 m(-2) ) during follow-up. Prevalent CKD (as defined above) in the cross-sectional data from the iHOPE study.The adjusted hazard ratios for incident CKD were 1·05 [95% confidence interval (CI) 1·02-1·07], 0·99 (95% CI 0·97-1·02) and 1·93 (95% CI 1·79-2·08) in the overall, mild and severe psoriasis groups, respectively. In the nested cross-sectional study (iHOPE) the adjusted prevalence odds ratios for CKD were 0·89 (95% CI 0·72-1·10), 1·36 (95% CI 1·06-1·74) and 1·58 (95% CI 1·07-2·34) in the mild, moderate and severe psoriasis groups, respectively.Moderate-to-severe psoriasis is associated with an increased risk of moderate-to-advanced CKD, independently of traditional risk factors.
Epinephrine Administration and Pediatric In-Hospital Cardiac Arrest—Reply
Authors: Lars W. Andersen, Katherine M. Berg, Michael W. Donnino
Journal: JAMA (2016)

In Reply We do not have data on whether the first epinephrine bolus was administered by an intravenous or intraosseous injection. The variable we used for assessment of epinephrine administration included both intravenous and intraosseous administration but did not distinguish between the two.
A phase I dose-escalation study of IMGN388 in patients with solid tumors.
Authors: D. S. Thompson, A. Patnaik, J. C. Bendell, K. Papadopoulos, J. R. Infante, R. A. Mastico, D. Johnson, A. Qin, J. J. O'Leary, A. W. Tolcher
Journal: Journal of Clinical Oncology (2010)

3058 Background: IMGN388 is a novel antibody-drug conjugate (ADC) composed of an integrin-targeting fully human antibody with the maytansinoid, DM4, attached via a covalent bond. IMGN388 has shown strong activity against human xenograft lung, colon, pancreatic, ovarian and breast tumors in nude rat models. Methods: This is a first-in-human study of IMGN388. New cohorts of patients with advanced solid tumors receive increasing doses of IMGN388, given intravenously, to establish its maximum tolerated dose (MTD). The primary study objectives are to evaluate the safety, MTD and pharmacokinetics (PK) of IMGN388 when given every 3 weeks. Secondary objectives include evaluation of pharmacodynamics, immunogenicity and evidence of activity. Results: 26 patients received a total of 52 cycles of IMGN388 at doses ranging from 5 to 80 mg/m2. IMGN388 was generally well-tolerated. Grade 1/2 toxicities assessed to be treatment related include: fatigue, nausea, anorexia, vomiting, diarrhea, headache and allergic reaction. One dose-limiting toxicity was seen, which was grade 3 headache and confusion 24 hours after the first infusion of IMGN388 at a dose of 45 mg/m2. Prophylactic steroid administration was implemented and no further events have occurred. There has been no evidence of human anti-human antibody formation (data available for doses up to 60 mg/m2). Preliminary IMGN388 PK findings reveal an elimination phase half-life of approximately 28 hours; maximal plasma concentration increases in a generally dose-proportional manner. No evidence of activity was observed at the lowest doses evaluated. At 45 mg/m2, a patient with non-small cell lung carcinoma who previously progressed on two lines of therapy within one year remained on IMGN388 for 6 cycles (18 weeks). Conclusions: IMGN388 has been well tolerated at the doses tested, demonstrating initial evidence of safety in early clinical phase I testing. The MTD has not yet been defined and the study is ongoing. Updated results will be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ImmunoGen ImmunoGen
Evaluation of the effect of systemic corticosteroids for the treatment of immune-related adverse events (irAEs) on the development or maintenance of ipilimumab clinical activity
Authors: A. Amin, V. DePril, O. Hamid, J. Wolchock, M. Maio, B. Neyns, K. Chin, R. Ibrahim, A. Hoos, S. O'Day
Journal: Journal of Clinical Oncology (2009)

9037 Background: Ipilimumab, a fully human monoclonal antibody that inhibits cytotoxic T-lymphocyte antigen-4, has clinical activity at 10 mg/kg in patients (pts) with advanced melanoma. Most grade 3/4 immune-related adverse events (irAEs) associated with ipilimumab can be managed with systemic corticosteroids following established treatment guidelines. However, little has been reported about the effects of corticosteroids used to treat irAEs on ipilimumab antitumor responses. Methods: Across 3 phase II studies with 10 mg/kg ipilimumab monotherapy in advanced melanoma (CA184008, 022, and 007; N=283), 83 pts (29.3%) achieved disease control [complete/partial responses (CR/PR), or stable disease (SD) ≥12 weeks] and 43/83 (52%) received steroids for treatment of irAEs. The pts' ability to develop and maintain disease control in the presence and absence of steroids was analyzed. Disease control was assessed by modified World Health Organization (mWHO) criteria and novel immune-related response criteria (irRC) (Hodi FS, et al. J Clin Oncol 26: 2008 [May 20 suppl; abstr 3008]). The range of follow-up was 5.7–6.3 months. Results: Of 117 pts who received steroids prior to response assessment, 26 pts achieved CR or PR, or maintained SD without disease progression by mWHO, and the remaining 91 pts had PD. Of 166 pts who either never received steroids or received them after response assessment, 31 achieved a CR, PR, or SD (by mWHO). Further, of 26 pts with CR/PR by mWHO, 14 received subsequent steroids and 11 maintained a response, while of 12 pts who received no subsequent steroids, 9 maintained a response. Similar results were obtained if irRC were used (see table ). Conclusions: Systemic corticosteroids for treatment of irAEs do not appear to impact the development or maintenance of ipilimumab clinical activity in advanced melanoma. [Table: see text] [Table: see text]
H1 gets the genome in shape
Authors: Annalisa Izzo, Robert Schneider
Journal: Genome biology (2016)

By performing high-throughput chromosome conformation capture analyses in embryonic stem cells depleted of the linker histone H1, Geeven and colleagues have uncovered exciting new evidence concerning a role for this histone in modulating three-dimensional genome architecture and chromatin organization. Please see link to Research article: http://www.genomebiology.com/2015/16/1/289
Tumor Cell–Driven Extracellular Matrix Remodeling Drives Haptotaxis during Metastatic Progression
Authors: Madeleine J. Oudin, Oliver Jonas, Tatsiana Kosciuk, Liliane C. Broye, Bruna C. Guido, Jeff Wyckoff, Daisy Riquelme, John M. Lamar, Sreeja B. Asokan, Charlie Whittaker, Duanduan Ma, Robert Langer, Michael J. Cima, Kari B. Wisinski, Richard O. Hynes, Douglas A. Lauffenburger, Patricia J. Keely, James E. Bear, Frank B. Gertler
Journal: Cancer Discovery (2016)

Fibronectin (FN) is a major component of the tumor microenvironment, but its role in promoting metastasis is incompletely understood. Here, we show that FN gradients elicit directional movement of breast cancer cells, in vitro and in vivo Haptotaxis on FN gradients requires direct interaction between α5β1 integrin and MENA, an actin regulator, and involves increases in focal complex signaling and tumor cell-mediated extracellular matrix (ECM) remodeling. Compared with MENA, higher levels of the prometastatic MENA(INV) isoform associate with α5, which enables 3-D haptotaxis of tumor cells toward the high FN concentrations typically present in perivascular space and in the periphery of breast tumor tissue. MENA(INV) and FN levels were correlated in two breast cancer cohorts, and high levels of MENA(INV) were significantly associated with increased tumor recurrence as well as decreased patient survival. Our results identify a novel tumor cell-intrinsic mechanism that promotes metastasis through ECM remodeling and ECM-guided directional migration.Here, we provide new insight into how tumor cell:ECM interactions generate signals and structures that promote directed tumor cell migration, a critical component of metastasis. Our results identify a tumor cell-intrinsic mechanism driven by the actin regulatory protein MENA that promotes ECM remodeling and haptotaxis along FN gradients. Cancer Discov; 6(5); 516-31. ©2016 AACR.See related commentary by Santiago-Medina and Yang, p. 474This article is highlighted in the In This Issue feature, p. 461.