tbuckley/cabot-search huggingface dataset:
Ministers' failure to explain the case for "reforms" has left NHS staff without sense of purpose
Authors: M. Limb
Journal: BMJ (2011)

The proposed new NHS Commissioning Board “cannot afford to fail,” NHS Confederation chief executive Mike Farrar told a conference.

Mr Farrar said it was vital that clinical commissioning, a central plank of the government’s health reforms, proved effective as it was “probably the most important part of the system.”

But he said ministers’ failure to make a compelling case for change left many in the NHS without a clear sense of purpose and drive for the next decade.

As a result, it would be up to the NHS Commissioning Board itself to describe how it would work and its vision of what the health service should be. “It needs to be the leader of the …
AB0369 Evaluation of the eurolupus protocol in lupus nephritis treatment in an internal medicine department
Authors: F. Ajili, Y. Ben Ariba, S. Sayehi, M. Maiza, N. Boussetta, N. Ben Abdelhafidh, B. Louzir, J. Laabidi, S. Othmani
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus since it is the major predictor of poor prognosis. Corticosteroids and immunosuppressive treatment has transformed the prognosis of this pathology despite the frequent infectious complications. The Eurolupus protocol is a new regimen using lower doses and shorter treatment durations of intravenous cyclophosphamide that have been advanced to reduce toxicity without sacrificing efficacy of therapy. <h3>Objectives</h3> Our study aims to evaluate this protocol used in patients followed in the internal medicine department of the military hospital of Tunis. <h3>Results</h3> Among 120 patients with SLE, 34 (34,16 %) had LN. Eleven (9,17%) patients were treated according to the Eurolupus protocol (6 fortnightly pulses of 500 mg; cumulative dose 3 gm, followed by azathioprine or mycophenolate monfetil “MMF”). The average age was 38 years, with 2 males and 9 females. Renal biopsy performed in 10 cases showed a LN class III, IV and IV+V in respectively 1, 7 and 2 cases. Histological signs of activity were noted in all cases with signs of chronicity in 2 cases. Maintenance therapy was azathioprine in 5 cases and MMF in 5 cases. The evolution was marked by a complete remission in 7 cases (58%), partial remission in 3 cases (27%) and deterioration of renal function in one case (9%). The average delay of remission was 5 months (1-12months). Renal relapse was noted in 4 cases (38,5%) related to treatment withdrawal, infection and/or pregnancy respectively in three, two and one cases. Infectious complications were observed in 2 cases but no cases of death have been noted. <h3>Conclusions</h3> The Eurolupus protocol leads to similar results as the old regimen of cyclophosphamide with a cumulative dose much smaller and less frequent infectious complications. <h3>References</h3> Updates on the Treatment of Lupus Nephritis. Andrew S. Bomback and Gerald B. Appel. JASN December 1, 2010vol. 21 no. 12 2028-2035 Immunosuppressive Therapy in Lupus Nephritis. The Euro-Lupus Nephritis Trial, a Randomized Trial of Low-Dose Versus High-Dose Intravenous Cyclophosphamide. Frédéric A. Houssiaud al* ARTHRITIS &amp; RHEUMATISM, Vol. 46, No. 8, August 2002, pp 2121–2131 <h3>Disclosure of Interest</h3> None Declared
1021 GLOBAL INVESTIGATION OF THERAPEUTIC DECISIONS IN HEPATOCELLULAR CARCINOMA (HCC) AND OF ITS TREATMENT WITH SORAFENIB (GIDEON): IMPACT OF LIVER DYSFUNCTION ON SORAFENIB TREATMENT IN EUROPE
Authors: P. Mathurin, L. Castells, G. Bodoky, P. Stäal, J.-P. Bronowicki, R. Gerolami, B. Daniele, J.T. Vazquez, F. Serejo, A. Croitoru, A. Hubert, V. Gorbunova, V. Ratziu, C. Papandreou
Journal: Journal of Hepatology (2012)
Abstract LB-350: MicroRNA-301a, elevated in pancreatic cancer, targets tumor suppressor CDKN1A/p21 blocking cellular senescence and promoting invasion of pancreatic epithelial cells
Authors: Jin Wang, Hiroshi Katayama, Aimee B. Leblanc, Marsha L. Frazier, Ann M. Killary, Subrata Sen
Journal: Cancer Research (2010)

Abstract MicroRNAs (miR) are negative regulators of gene expression and have been implicated to play important roles in the carcinogenic processes. Expression of miR-301a is elevated in multiple solid tumors including pancreatic cancer, small cell lung cancer, breast and liver cancer. However, the targets and function of miR-301a remain unknown. Here, we report that miR-301a targets CDKN1A/p21 tumor suppressor gene transcript leading to down regulation of the protein. Luciferase reporter assay of p21 3′UTR construct revealed that p21 is a direct target of miR-301a. Over expression of miR-301a in immortalized non-tumorigenic pancreatic epithelial cells (HPNE and HPDE) by transient transfection of precursor miR-301a resulted in down-regulation of p21 protein level with accompanying accelerated cell proliferation and increase in invasive potential detected in matrigel assays. Conversely, knockdown of miR-301a by antigomir301a resulted in elevated levels of p21 protein in pancreatic ductal adenocarcinoma cells (Panc-1 and Aspc-1). These cells displayed accumulation in G1 cell cycle phase and induction of cellular senescence. The results suggest that the use of synthetic antigomir301a may be a promising approach to pancreatic cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-350.
Giant Pseudoaneurysm of the Left Ventricle Diagnosed by Radionuclide Ventriculography
Authors: AHARON FRIEDENSOHN, TIFHA HORNE, AIDEN ABIDOV
Journal: Clinical Nuclear Medicine (1998)

A 65-year-old woman was hospitalized with an anterior wall myocardial infarction, complicated with congestive heart failure. Three months later, she was rehospitalized with acute pulmonary edema and a new apical holosystolic murmur. Radionuclide ventriculography in the left anterior oblique position showed a giant pseudoaneurysm of the left ventricle that was verified on echocardiography. The patient was transferred to the cardiosurgery center, and a successful aneurysmectomy was performed.
A COMPREHENSIVE SAFETY ANALYSIS OF 6026 PATIENTS FROM PHASE 2 AND 3 SHORT AND LONG TERM CLINICAL TRIALS WITH EVOLOCUMAB (AMG 145)
Authors: Peter P. Toth, Naveed Sattar, Jacques Genest, Olivier S. Descamps, Ricardo Dent, Constantine Djedjos, Jason Legg, Scott Wasserman, Evan Stein
Journal: Journal of the American College of Cardiology (2015)
HIGH RESOLUTION MEASUREMENTS OF MYOCARDIAL BLOOD FLOW WITH TC-99M ALBUMIN MICROSPHERES USING AN ANGER CAMERA.
Authors: Chia-Yao Hung, Robert D. Burow, Benjamin J. Scherlag, Garo P. Basmadjian, Ralph Lazzara
Journal: Clinical Nuclear Medicine (1983)

Hung, Chia-Yao; Burow, Robert D.; Scherlag, Benjamin J.; Basmadjian, Garo P.; Lazzara, Ralph Author Information
PWE-149 Gene expression in oxaliplatin related sinusoidal obstruction syndrome
Authors: S Robinson, J Mann, D Manas, D Mann, S White
Journal: Gut (2012)

<h3>Introduction</h3> Sinusoidal Obstruction Syndrome (SOS) is associated with Oxaliplatin based chemotherapy in patients with colorectal liver metastases (CRLM) and is a cause of concern when undertaking major liver resection. The pathogenesis of SOS is poorly understood however a variety of candidate genes have been identified which may play a role in activating various molecular pathways involved. The aim of this study was to validate these gene expression changes in an independent cohort of patients. <h3>Methods</h3> Patients undergoing liver resection for CRLM, were identified for inclusion and appropriate informed consent obtained. Full clinical information was recorded for each patient including pre-operative chemotherapy use. A biopsy of the non-tumour bearing liver was obtained, prior to parenchymal transection, and stored in RNAlater. Histopathology was reviewed to identify those with SOS. Hepatic gene expression was compared in chemotherapy naive patients (controls) with no evidence of underlying liver disease (n=10) and those who received pre-operative Oxaliplatin either with (n=13) or without (n=9) evidence of SOS by qRT-PCR. Mann–Whitney U test was used to assess statistical significance. <h3>Results</h3> The interval between cessation of chemotherapy and surgery was similar for all patient groups (p=0.45). In contrast to previous studies we were unable to identify changes in extracellular matrix remodelling genes (MMP2, MMP9, TIMP1, TGFβ) thought to be involved in SOS. However there was up regulation of angiogenesis related VEGF-C (1.6-fold, p&lt;0.05) along with the hypoxia induced HIF1α (1.98-fold; p&lt;0.01) in those with SOS. It is suggested that SOS is associated with a pro-thrombotic tendency and in keeping with this there was a non-significant trend towards increased expression of vWF (2.5-fold; p=0.06). We also confirmed up-regulation of CCL20 in those with SOS (3.8-fold; p&lt;0.05) which is chemotactic for colorectal cancer cells. <h3>Conclusion</h3> We were able to confirm up-regulation of genes involved in angiogenesis, hypoxia and thrombogenesis in patients with SOS. It is likely that changes in extracellular matrix re-modelling genes occur early in the development of SOS and but have returned to baseline levels if there is a reasonable duration between stopping chemotherapy and surgical resection. Increased expression of CCL20 may account for the recently reported poorer disease specific survival in patients with SOS. <h3>Competing interests</h3> None declared.
Paris restricts use of cars
Authors: A. Dorozynski
Journal: BMJ (1997)

Parisian police will ban half of the cars in greater Paris during peak pollution days. Cars with an even licence number will be allowed in only on dates of an even number.

The minister of the environment, Corinne Lepage, announced the ban as one of the measures to limit the effects of peak pollution on the population. These traffic flow measures …
SP0018 How to Use MRI in Low Back Pain
Authors: K.G. Hermann
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Back pain is an important problem that affects two-thirds of adults at some time in their lives. One of the leading causes of functional incapacity is spinal degeneration, which is a common source of chronic disability in the working population. Disk degeneration has been linked to mechanical loading, which occurs most typically in the lower cervical and lower lumbar spinal regions. Degeneration of the intervertebral disc can result in annular tears and disc hernation, with compromise or compression of the nerve roots. Dehydration and disintegration of the disc tissue leads to increased segmental mobility. In some patients, instability with symptomatic osteochondrosis develops. Facet joint osteoarthritis can also be responsible for central spinal canal stenosis and stenosis of the recess or narrowing of the neuroforamen. Ganglion cysts are complications of facet joint osteoarthritis, that may lead to further stenosis of the spinal canal.Crystal deposition such as calcium pyrophosphate dihydrate (CPPD) or urate crystals may lead to degeneration of the intervertebral discs, although the latter are less common at the spine. On the other hand, metaplastic ossification of soft tissues such as the annulus fibrosus do occur during mechanically induced degeneration of the discs. This lecture will review important magnetic resonance imaging signs in degenerative spinal disorders and compare those to conventional radiography, and computed tomography, as appropriate. <h3>Disclosure of Interest</h3> K. G. Hermann Conflict with: MSD, AbbVie, UCB, Pfizer <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6347
AB1123 Chilblain-like skin lesions, ILD and immunodeficiency - therapeutic dilemma of immunosuppression vs. restoration of T-cell function
Authors: C. Schuetz, V. Mohr, M. Honig, K.-M. Debatin, W. Friedrich, A. Schulz
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> We report a 13 y/o girl with chronic interstitial lung disease, chilblain-like lesions and a history of severe CMV infection with pneumonitis at 5 months of age. Deterioration of lung function could not be controlled with immunosuppressive regimens resulting in pulmonary hypertension at age 12. <h3>Objectives</h3> Case description and discussion of therapeutic strategies. <h3>Methods</h3> Case report. <h3>Results</h3> The patient is the fourth child of consanguineous parents of Turkish descent. She was referred to us with a chronic recurrent CMV-infection and a history of chilblain-like skin lesions of the ear lobes, cheeks, heels and on thighs. Antiviral therapy resulted in partial resolution of her CMV-infection with ongoing pneumonitis and temporary oxygen requirements. On immunological work-up T- and B-cell numbers were normal with production of specific immunoglobulins, but no antigen-specific T-cell function as well as impairment of stimulated IL-2, IFNg, but not TNFa secretion. Vaccination titers were normal. ANA titers were elevated between 1:320-640, low titers of antiphospholipid antibodies and PR3a antibodies at the upper limit of normal were measured. There was no evidence of cryoglobulins. Lung biopsy showed interstitial lung disease with lymphofollicular changes and predominance of macrophages (ages 2 and 6). Genetic analyses for an underlying primary immunodeficiency including ADA, PNP, JAK-3 deficiencies showed no mutations. Alpha1-antitrypsin deficiency was excluded. No mutations were found in TREX-1, a gene described in the context of both familiar chilblain lupus and SLE. Hematopoietic stem cell transplantation from her HLA-identical sister at 20 months of age without preconditioning regimen had resulted in non-engraftment. Stabilization of her lung function following antiviral treatment and later on hydroxycholorquine and steroid pulses could be achieved. However, over the years, pulmonary function deteriorated leading to pulmonary hypertension. The patient is stable under regular oxygen supply and sildenafil. Her skin lesions are not active, there have never been signs of myositis. <h3>Conclusions</h3> We present a girl with chronic interstitial lung disease, chilblain-like skin lesions and unspecified T-cell deficiency. It is debatable whether stronger immunosuppresive therapy or restoration of immunological function should guide future management of her disease. <h3>Disclosure of Interest</h3> None Declared
S13 Sole use of forced vital capacity as per national institute of health and care excellence criteria disadvantage 2 in 5 people with idiopathic pulmonary fibrosis
Authors: N Chaudhuri, A Duck, M Greaves, CT Leonard
Journal: Thorax (2013)

<h3>Introduction</h3> Pirfenidone has undergone NICE approval and is recommended for patients with IPF if the FVC is 50–80% 1. We hypothesised that the NICE guidance would disadvantage a significant cohort of IPF patients who have moderate reduction in transfer factor despite preserved FVC. <h3>Methods</h3> We retrospectively reassessed the eligibility of fifty IPF patients on the named patient programme using the NICE guidance. Electronic CT and clinical reports were analysed for the presence of coexisting emphysema. <h3>Results</h3> Of fifty patients we identified that 20/50 (40%) would not have been prescribed pirfenidone as per the NICE criteria. The average FVC was significantly higher in the 20 patients that did not meet the NICE criteria compared to those that did (97.6 ± 16.24% vs. 65.48 ± 8.56% (p &lt; 0.001) respectively. In contrast there was no difference in transfer factor between the two groups (42.35 ± 14.66% vs. 44.74 ± 12.29%) respectively. The frequency of emphysema was statistically different between those that met the NICE criteria and those that did not (3 vs. 8 p = 0.0409). Of those patients that had an FVC greater than 80%, 12/20 (60%) had no emphysema visible on CT imaging and 2 (10%), 4 (20%) and 2 (10%) had evidence of mild, moderate and severe emphysema respectively. However, the average transfer factor was not significantly different between those with or without emphysema (35.75% vs. 46.75% respectively). <h3>Conclusion</h3> This retrospective data demonstrates that the sole use of FVC in the NICE criteria for treating IPF disadvantages 40% of patients who demonstrate a significant reduction in transfer factor despite FVC greater than 80%. In this study this reduced transfer factor and preserved FVC can only be attributed to the presence of coexisting emphysema in 8/20 (40%) of patients. 60% of patients had IPF alone with FVC greater than 80% despite an average transfer factor of 47%, which was not statistically different to those with coexisting emphysema. We would therefore advocate the use of both FVC and DLCO when assessing patient suitability for pirfenidone treatment for IPF. The use of FVC alone excludes a substantial cohort of IPF patients who have preserved FVC, reduced DLCO with or without coexisting emphysema.
Phase 1/2 Study of Ap26113 in Patients (PTS) with Advanced Malignancies, Including Anaplastic Lymphoma Kinase (ALK)–Positive Non-Small Cell Lung Cancer (NSCLC): Analysis of Safety and Efficacy at Selected Phase 2 Doses
Authors: R. Rosell, S. Gettinger, L.A. Bazhenova, C.J. Langer, R. Salgia, K. Gold, A.T. Shaw, D.J. Dorer, D. Kerstein, D.R. Camidge
Journal: Annals of Oncology (2015)
Effect of Dietary Intake Before F-18 FDG Positron Emission Tomographic Scanning on the Evaluation of a Solitary Pulmonary Nodule
Authors: BUDDHIWARDHAN OJHA, SCOTT C. BARTLEY, SAI GUNDLAPALLI, JAMES M. MOUNTZ
Journal: Clinical Nuclear Medicine (2001)

The uptake of fluorine-18 fluorodeoxyglucose (F-18 FDG) by a malignant tumor depends on the blood glucose level. The authors present a striking case that illustrates the importance of blood glucose measurement in F-18 FDG positron emission tomographic (PET) imaging in a patient with a solitary pulmonary nodule. With the emergence of freestanding imaging centers, this case emphasizes the importance of using an objective method, such as a glucometer, to measure blood glucose levels before F-18 FDG PET imaging. Results of the initial scan were equivocal (the patient had eaten before the scan), whereas a hypermetabolic focus was clearly identified on a second scan obtained 2 days later.
Minimally invasive treatment of esophageal perforation using a multidisciplinary treatment algorithm: a case series
Authors: K. Ben-David, J. Lopes, S. Hochwald, P. Draganov, C. Forsmark, D. Collins, S. Chauhan, Mihir Wagh, J. Carreras, S. Vogel, G. Sarosi
Journal: Endoscopy (2011)

Esophageal perforation is a dreaded condition with high morbidity and mortality rates. The diagnosis often depends on clinical suspicion, features, and radiographic or endoscopic testing confirming an esophageal leak. The most common cause of esophageal perforation is secondary to an iatrogenic injury but it can also be the result of spontaneous perforation, chemical or foreign body ingestion, and penetrating trauma. Hence, due to mortality rates as high as 20 %, a high index of suspicion and established treatment algorithms are paramount [1].
IT-21 * PD-1 BLOCKADE SHOWS SYNERGISTIC SURVIVAL, ANTI-TUMOR IMMUNE RESPONSE AND LONG-TERM MEMORY WITH INTERSTITIAL BUT NOT SYSTEMIC CHEMOTHERAPY: STUDY IN A MURINE GLIOBLASTOMA MODEL
Authors: D. Mathios, J. Phallen, C.-K. Park, C. Jackson, S. Nicholas, B. Tyler, D. Pardoll, H. Brem, M. Lim
Journal: Neuro-Oncology (2014)

INTRODUCTION: Glioblastoma is the most malignant brain tumor and is characterized by resistance to current therapies. Multi-modal treatment holds potential for complete tumor eradication, however the combination of chemotherapy and immunotherapy has been avoided due to concerns over possible mutually excluding effects. Localized chemotherapy (LC) consisting of biodegradable polymers as the delivery system for the BCNU (BCNU-LC) is FDA approved while treatment with the anti-PD-1 monoclonal antibody (anti-PD-1-mAb) has shown promising early results in clinical trials. Here we report evidence of superior survival and a positive immunological profile resulting from the combination of BCNU-LC + anti-PD-1-mAb in an established murine glioblastoma model. RESULTS: Mice were treated with the following regimens: BCNU-LC + anti-PD-1-mAb, systemic-BCNU + anti-PD-1-mAb, BCNU-LC, systemic-BCNU, anti-PD-1-mAb, untreated. BCNU-LC + anti-PD-1-mAb treated mice showed improved survival compared to mice treated with monotherapies and exhibited enhanced tumor-specific immunity: flow-cytometric analysis of the lymphocytic, myeloid, and microglial compartments in the tumor microenvironment as well as the lymphocytic and myeloid compartments in the periphery showed activation of immune molecules, whereas the mice treated with systemic-BCNU or systemic-BCNU + anti-PD-1-mAb exhibited severe immunosuppression in addition to poor survival. 70% of the BCNU-LC + anti-PD-1-mAb group exhibited long-term survival while the anti-PD-1-mAb, systemic-BCNU and systemic-BCNU + anti-PD-1-mAb groups also produced lower percentages of long-term survivors. Upon tumor re-challenge in the flank or the contralateral brain hemisphere, long-term survivors in the BCNU-LC + anti-PD-1-mAb and anti-PD-1-mAb groups were able to prevent formation of recurrence whereas long-term survivors from the systemic-BCNU and systemic-BCNU + anti-PD-1-mAb groups succumbed to Glioblastoma and were unable to form an immune memory response. CONCLUSIONS: Our results suggest that we rethink our chemotherapy strategies in the setting of immunotherapy. We found that systemic chemotherapy has a cytoreductive effect, and that LC could possibly augment an immunological response and survival benefit.
Case 8-2007
Authors: Gregory D. Lewis, Charles B. Holmes, Godtfred Holmvang, Joan R. Butterton
Journal: New England Journal of Medicine (2007)

A 48-year-old man was admitted to this hospital because of chest pain. An electrocardiogram revealed diffuse ST-segment elevation, and an echocardiographic study was normal. Cardiac arrest with ventricular tachycardia occurred 13 hours after presentation. The patient was successfully resuscitated, and the result of a diagnostic test was received on the fourth hospital day.