tbuckley/cabot-search huggingface dataset:
Intravenous busulfan and cyclophosphamide as an autologous transplant conditioning regimen for relapsed non-Hodgkin’s lymphoma
Authors: M. P. Escalon, D. L. Pereira, E. S. Santos, M. Goodman, J. J. Byrnes, H. F. Fernandez
Journal: Journal of Clinical Oncology (2006)

16508 Purpose: High-dose chemotherapy and hematopoietic stem cell transplantation has become the standard of care for chemosensitive relapsed Non-Hodgkin’s Lymphoma. Multiple conditioning regimens including CBV, BEAM, and BEAC have been used in the past with success. Limitations on the supply of carmustine have made it important to find other effective conditioning regimens. Methods: We retrospectively evaluated the use of intravenous Busulfan and Cyclophosphamide (IV Bu/Cy) as a conditioning regimen for autologous stem cell transplantation in Non-Hodgkin’s Lymphoma patients. Patients were given Busulfan 3.2 mg/kg total intravenously on days -7 to -4 (either once daily or in 2 or 4 divided doses) followed by Cyclophosphamide 120 mg/kg intravenously on days -2 and -1. Results: Forty-four patients, ages 20 to 68 years (median 50) were treated from January 2000 to April 2005. Most patients had diffuse large B-cell lymphoma (n = 29). Of the remaining patients, 8 had follicular lymphoma, 4 had mantle cell lymphoma and 3 had peripheral T-cell lymphoma. At the time of transplant, 27 patients had attained a complete response (CR or CRu) to salvage chemotherapy, 13 patients had achieved a partial response, and 4 had stable disease. The patients received a median of 3.0 × 10 6 CD34 + cells/kg (range 1.3–16.6 × 10 6 ). There were 4 treatment-related deaths by day 100: 1 from sepsis, 1 from pneumonia, and 2 from veno-occlusive disease (VOD). With a median follow-up of 42 months, 3-year Kaplan-Meier estimates of event free and overall survival for the entire cohort were 44% and 45%. For the patients that attained a CR or CRu prior to transplant, the EFS and OS were 42% and 53%, respectively. Conclusions: IV Bu/Cy is a safe and effective conditioning regimen. Due to the incidence of VOD, this regimen should be used with caution in patients with pre-existing hepatic dysfunction. Overall, our outcomes are comparable to that of other published regimens. Further investigation of Busulfan with Cyclophosphamide or with other chemotherapy combinations is warranted. No significant financial relationships to disclose.
Preclinical and Early Clinical Development of a GATA-3-Specific Dnazyme Intended for the Treatment of Th2-Driven Asthma
Authors: Agnieszka Turowska, Ursula Homburg, Jens Kuhlmann, Anke Müller, Joachim Bille, Harald E. Renz, Holger Garn
Journal: Journal of Allergy and Clinical Immunology (2013)
Effect of an Enteric-Coated Fish-Oil Preparation on Relapses in Crohn's Disease
Authors: Andrea Belluzzi, Corrado Brignola, Massimo Campieri, Angelo Pera, Stefano Boschi, Mario Miglioli
Journal: New England Journal of Medicine (1996)

Patients with Crohn's disease may have periods of remission, interrupted by relapses. Because fish oil has antiinflammatory actions, it could reduce the frequency of relapses, but it is often poorly tolerated because of its unpleasant taste and gastrointestinal side effects.
S126 Developing Healthy Lifestyle Interventions For Overweight Patients With Obstructive Sleep Apnoea (osa): A Survey Of Patient Attitudes And Current Practice
Authors: I. V. Sanchez, S. Wimpress, C. Brough, S. Singh, R. Evans
Journal: Thorax (2014)

<h3>Background</h3> Current BTS/SIGN guidelines suggest the inclusion of behavioural interventions as part of the management for overweight patients with Obstructive Sleep Apnoea Syndrome (OSAS). Healthy lifestyle interventions are widely available in a variety of settings for other chronic diseases. Our aims were to assess: patients’ views and their experience with weight loss and lifestyle changes. Internet and Information Technology (IT) access to investigate if a web-based lifestyle intervention would be feasible. current clinical practice regarding healthy lifestyle advice. <h3>Methods</h3> A questionnaire was developed to assess patients’ experience with lifestyle changes, their preferences and willingness to take part in a healthy lifestyle intervention, and their internet and IT usage. This was administered to patients with treated OSAS attending a sleep clinic. The MRC dyspnoea scale grade and Veterans Specific Activity Questionnaire (VSAQ)(1) were measured. Current practice regarding lifestyle advice and interventions, and serial weights were assessed by a case-note review of sequential overweight patients with treated OSAS attending a sleep clinic. <h3>Results</h3> 112 patients with treated OSAS completed the survey (results shown in Table 1): 80.5% male, 76% aged 50 to 79 years, mean estimated BMI 35 kg m<sup>-2</sup>, median [IQR] MRC dyspnoea scale 3[2–3] and VSAQ score 5[3–7] indicating being unable to walk briskly. 75% of individuals had access to broadband Internet (Table 1) and over 40% would be interested in a web-based healthy lifestyle intervention. 33 case-notes were reviewed with a mean follow up of 5 years. 27/33 individuals had been given healthy lifestyle advice of which 24/27 was to lose weight. Only two individuals had been recommended to join a leisure programme. Weight remained unchanged over five years after diagnosis, ANOVA p = 0.90. <h3>Conclusions</h3> Breathlessness causing reduced physical activity was commonly reported in overweight patients with OSAS. Weight loss is not currently achieved after simple advice from a healthcare professional, and advice or support regarding increasing physical activity is rarely provided. Further support with healthy lifestyle interventions should be explored, and attitudes and Internet access would favour development of a web-based intervention. <h3>Reference</h3> Myers <i>et al</i>.<i> Am Heart J</i> 2001;14: 1041–1046
Local death rates should be used to calculate public health funding
Authors: M. Limb
Journal: BMJ (2012)

Funds for public health should be allocated to local authorities on the basis of a measure of local death rates, according to interim proposals drawn up for the government.1 A report for the Department of Health says resources should be calculated using the standardised mortality ratio (SMR) for people aged under 75 years.

Under a weighting system, the 10th of areas with the highest number of deaths in people under 75 would receive three times more funding per head than the 10th with the lowest number of deaths.

The interim proposals were drawn up for the government by the Advisory Committee on Resource Allocation, which includes doctors, NHS managers, and academics.

They have the …
FRI0144 Cardiovascular Events in Ankylosing Spondylitis. an Updated Meta-Analysis
Authors: S. Mathieu, M. Soubrier
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid arthritis is associated with increased cardiovascular risk. In the guidelines, ankylosing spondylitis (AS) is considered to have an equally high cardiovascular risk. The literature findings remain controversial. <h3>Objectives</h3> To assess the risk of myocardial infarction (MI) and stroke in AS patients in 2013. <h3>Methods</h3> An updated meta-analysis with a new systematic literature review using PubMed was conducted up to December 2013. Incidence of MI or stroke was calculated by metaproportion. <h3>Results</h3> In addition to the eleven previously included studies, five new studies assessed the occurrence of MI or stroke in AS patients. <i>1. MI:</i> 726 MI were reported in AS patients (N=18,916) over mean follow-up of sixteen years: incidence 5.5% [3.9%, 7.4%], i.e. 0.44/100 pyrs. Seven studies revealed 17,410 MI (2.5% (95% CI [1.8%, 3.4%])) in the control group (N=1,349,964). Meta-analysis of the seven longitudinal studies showed a significant increase in MI (RR=1.46 [1.33, 1.60]) in AS patients. <i>2. Stroke:</i> In ten longitudinal studies (N=43,374), 1,370 strokes were reported in AS patients over 18.5 years of follow-up: incidence 3.4% [1.2%, 6.8%], i.e. 0.1/100 pyrs. Three studies reported 22,899 strokes in controls (N=1,239,041), giving an incidence of 1.78% [1.75%, 1.80%]. A significant increase in stroke (RR=1.50 [1.39, 1.62]) in AS patients was found. <h3>Conclusions</h3> AS patients appear to have a higher risk of MI and stroke. Management of cardiovascular risk factors and control of systemic inflammation should be taken into account in AS. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2063
Oncocytoma of the Parotid Gland Causing False-Positive Result on I-131 Whole-Body Scintigraphy
Authors: Henny Broekhuizen-de Gast, Hans van Isselt, Mark Roef, Marnix Lam
Journal: Clinical Nuclear Medicine (2011)

A 50-year-old patient underwent near-total thyroidectomy in 1997 because of a T1N0M0 follicular carcinoma in the right lobe of the thyroid gland, followed by I-131 ablation (3700 MBq). Follow-up of I-131 whole-body scintigraphy after 9 years showed pathologic uptake at the left side of the neck. Histopathologic analyses of the resected specimen suggested a cystic metastasis within the parotid gland, probably originating from thyroid carcinoma. However, the patient had been disease-free for over 9 years and thyroglobulin was undetectable in plasma. Revision of the specimen with complementary immunohistochemical staining revealed histopathologic aspects more typical of oncocytoma.
Blocking interferon γ reduces expression of chemokines CXCL9, CXCL10 and CXCL11 and decreases macrophage infiltration in ex vivo cultured arteries from patients with giant cell arteritis
Authors: Marc Corbera-Bellalta, Ester Planas-Rigol, Ester Lozano, Nekane Terrades-García, Marco A Alba, Sergio Prieto-González, Ana García-Martínez, Robert Albero, Anna Enjuanes, Georgina Espígol-Frigolé, José Hernández-Rodríguez, Pascale Roux-Lombard, Walter G Ferlin, Jean-Michel Dayer, Marie H Kosco-Vilbois, Maria C Cid
Journal: Annals of the Rheumatic Diseases (2015)

Background Interferon γ (IFNγ) is considered a seminal cytokine in the pathogenesis of giant cell arteritis (GCA), but its functional role has not been investigated. We explored changes in infiltrating cells and biomarkers elicited by blocking IFNγ with a neutralising monoclonal antibody, A6, in temporal arteries from patients with GCA. Methods Temporal arteries from 34 patients with GCA (positive histology) and 21 controls were cultured on 3D matrix (Matrigel) and exposed to A6 or recombinant IFNγ. Changes in gene/protein expression were measured by qRT-PCR/western blot or immunoassay. Changes in infiltrating cells were assessed by immunohistochemistry/immunofluorescence. Chemotaxis/adhesion assays were performed with temporal artery-derived vascular smooth muscle cells (VSMCs) and peripheral blood mononuclear cells (PBMCs). Results Blocking endogenous IFNγ with A6 abrogated STAT-1 phosphorylation in cultured GCA arteries. Furthermore, selective reduction in CXCL9, CXCL10 and CXCL11 chemokine expression was observed along with reduction in infiltrating CD68 macrophages. Adding IFNγ elicited consistent opposite effects. IFNγ induced CXCL9, CXCL10, CXCL11, CCL2 and intracellular adhesion molecule-1 expression by cultured VSMC, resulting in increased PBMC chemotaxis/adhesion. Spontaneous expression of chemokines was higher in VSMC isolated from GCA-involved arteries than in those obtained from controls. Incubation of IFNγ-treated control arteries with PBMC resulted in adhesion/infiltration by CD68 macrophages, which did not occur in untreated arteries. Conclusions Our ex vivo system suggests that IFNγ may play an important role in the recruitment of macrophages in GCA by inducing production of specific chemokines and adhesion molecules. Vascular wall components (ie, VSMC) are mediators of these functions and may facilitate progression of inflammatory infiltrates through the vessel wall.
LA ECOENDOSCOPIA EN EL DIAGNÓSTICO DE TUMORES NEUROENDOCRINOS PANCREÁTICOS: EXPERIENCIA EN NUESTRO CENTRO
Authors: A Ochoa, B Merino Rodríguez, C González Asanza, O Nogales Rincón, L Pérez Carazo, F Díaz Fontenla, A Ahumada, E Cos, P Menchén Fernández Pacheco
Journal: Endoscopy (2012)

Introducción: Los tumores de neuroendocrinos pancreáticos (TNE) son poco comunes. Los datos actuales destacan la importancia de la ultrasonografía endoscópica (USE) con punción en el diagnóstico de estas lesiones. Objetivo: Revisar nuestra experiencia (hospital terciario), en lo que se refiere a presentación clínica y utilidad diagnóstica de la USE con punción. Material y método: Se realizó una revisión prospectiva de las USE identificándose aquellas con sospecha de TNE en el periodo comprendido entre noviembre de 2010 y abril de 2012. Se recogieron datos epidemiológicos, clínicos, pruebas de imagen, resultado de la USE y de la citología/histología. Resultados: Un total de 18 pacientes tuvieron diagnóstico de sospecha de TNE por la imagen obtenida en la USE. El motivo de estudio fue: 39% sospecha de TNE por TC, 11% hallazgo incidental, 5,5% pancreatitis aguda, 28% sospecha de adenocarcinoma pancreático, 5,5% elevación del Ca19.9 sin causa en TC, 11% sospecha de lesión quística pancreática por TC. El diámetro medio de las lesiones fue de 26.5mm (rango 5.9 a 80mm). La localización más frecuente (41%) fue la cabeza del páncreas. La punción clasificó correctamente a 13 pacientes (en 9 casos se confirmó el TNE y en 4 se excluyó por tratarse de adenocarcinomas). En 5 pacientes con punción negativa (ausencia de material suficiente o ausencia de datos de malignidad) se confirmó el diagnóstico de TNE por otros medios (S=64.3%; E 1%; VPP=1%; VPN=44.4) Conclusión: La USE con punción es una modalidad fiable y segura para la caracterización de las lesiones sospechosas y para establecer un diagnóstico definitivo. La obtención de muestras de histología mejora la rentabilidad diagnóstica en este tipo de lesiones.
Abstract LB-023: Caspase-9b directly interacts with cIAP1 to drive agonist-independent NF-κB activation and tumorigenesis in non-small cell lung cancer
Authors: Ngoc T. Vu, Margaret A. Park, Michael D. Shultz, Amy C. Ladd, Charles E. Chalfant
Journal: Cancer Research (2015)

Abstract Caspase-9 has two isoforms with opposing functions, pro-apoptotic caspase-9a (C9a) and anti-apoptotic caspase-9b (C9b). C9b expression has been reported to augment the anchorage-dependent growth (AIG) and tumorigenic capacity of non-small cell lung cancer (NSCLC) cells. The mechanism of this biological observation was revealed in this study. Specifically, C9b was demonstrated to have a dual caspase-9a-independent function in regulating the survival/oncogenic nuclear factor κB (NF-κB) pathway. In particular, C9b was shown to activate the canonical arm and inhibit of the non-canonical arm of the NF-κB pathway by destabilizing NF-κB inhibitor alpha (IκB-α) and NF-κB-inducing kinase (NIK). Importantly, this new role for C9b contributes to the enhanced survival and AIG of NSCLC cells conferred by C9b expression. The link between C9b expression and NF-κB activation was also validated in human NSCLC tumors. Further mechanistic studies revealed a direct association of C9b with the cellular inhibitor of apoptosis 1 (cIAP1), a regulatory factor in both arms of the NF-κB network, via its IAP-binding motif (IBM). Through this interaction, C9b induces the E3 ligase activity of cIAP1, which regulates NF-κB activation, and promotes the viability, AIG and tumorigenicity of NSCLC cells. Hence, C9b/cIAP1 interaction is a new attractive molecular target for developing therapeutics to treat NSCLC. Citation Format: Ngoc T. Vu, Margaret A. Park, Michael D. Shultz, Amy C. Ladd, Charles E. Chalfant. Caspase-9b directly interacts with cIAP1 to drive agonist-independent NF-κB activation and tumorigenesis in non-small cell lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-023. doi:10.1158/1538-7445.AM2015-LB-023
AB0953 Is spinal osteophytosis associated with fatty liver?
Authors: A.P. Rozin, D. Gaitini, K. Toledano, A. Balbir-Gurman
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Lypopolysaccharides (LPS)- induced cartilage damage is widely used as a model to investigate the effectiveness of cartilage protective agents in vitro. Overwhelming liver LPS of intestinal origin break impaired liver barriers, achieve blood stream in low but sustained accounts and spread to joints. That results in lipopolysaccharide (LPS) - binding protein (LBP) - CD14(TLR-4) activation of inflammatory response and development of degenerative joints changes (osteophyte formation and cartilage loss). Easy penetration of LPS into circulation may be a result from liver dysfunction associated with fatty liver. We proposed an analogical in vivo model of bone degenerative changes related to fatty liver. <h3>Objectives</h3> To assess a size of spinal osteophytes in patients with fatty liver in comparison to spinal osteophytes in normal liver control group. <h3>Methods</h3> Ultrasound (US) images of patients admitted to the emergency department for abdominal pain were revised. Two subgroups of patients of similar age and gender were compared: 26 patients (13 male, mean age of 56.2±8.5 years) with US features of fatty liver and 26 patients (13 male, mean age 57.5±8.0 years, p=0.56) without US features of fatty liver. Retrospective analysis of images of the spine (X-ray, CT) in both populations obtained from the hospital imaging data base, was performed. Four maximal size spinal osteophytes were measured. In order to reduce an influence of individual body size factors the spine osteophyte radial length/vertebral width (O/V) ratio was calculated. Correlation between osteophytes' size, patient age, and Body Mass Index (BMI) in both subgroups was assessed. <h3>Results</h3> Spine osteophytes of patients with fatty liver had a bigger size (O/V=0.21±0.06) compared with patients with normal liver (O/V=0.14±0.03, p&lt;0.0001). Fatty liver patients had a higher BMI (32.7±5.4kg/m<sup>2</sup>) compared to normal liver patients (28.0±6.7kg/m<sup>2</sup>, p=0.031). In order to distinguish an influence of BMI and fatty liver on O/V, patients of normal liver group were divided according to increased BMI (&gt;25kg/m<sup>2</sup>) and normal one (&lt;25kg/m<sup>2</sup>). O/V of both groups showed similar values: 0.14±0.03 and 0.13±0.02 respectively (p=0.52). BMI of the groups was significantly different: 31.8±5.4 (&gt;25kg/m<sup>2</sup>) and 21.3±1.7 (normal) (p&lt;0.001). No correlation was found between O/V and BMI in fatty liver group and normal (p=o.81, p=0.51, respectively). In opposite, significant O/V and age correlation was found in normal liver group (p=0.014) and weak correlation in the fatty liver group (p=0.063). <h3>Conclusions</h3> Fatty liver may be considered as a predisposing factor in the pathogenesis of spine osteophytosis. <h3>Disclosure of Interest</h3> None Declared
Abstract 463: Differential cellular localization of programmed death ligand 1 (PD-L1) and enhanced expression of programmed death-1 (PD-1) in melanoma progression.
Authors: Nitin Chakravarti, Roland Bassett, Wen-Jen Hwu, Doina Ivan, Jonathan L. Curry, Victor G. Prieto
Journal: Cancer Research (2013)

Abstract Melanoma is an aggressive malignancy with a relatively high metastatic rate, responsible for almost 60% of lethal skin tumors. Although many human cancers such as melanoma express tumor antigens recognized by T cells, host immune responses often fail to control tumor growth for mostly unexplained reasons. Escaping immune destruction is one of the tenets of tumorigenesis; there have been several studies suggesting an important role of PD-1/PD-L1 (B7-H1) interactions in inhibiting the effector functions of cytotoxic T-lymphocyte in tumor. Ghebeh et al., reported that doxorubicin treatment caused decrease in cytosolic B7-H1 and increased nuclear translocalization in breast carcinoma (Breast Cancer Res. 2010;12(4):R48). It is unknown whether differential cellular expression of PD-L1 contributes to the pathogenesis of melanoma. To address the role of PD-L1 and its receptor PD-1 in different stages of malignant melanoma, we have performed semiquantitative immunohistochemical analysis of PD-L1 and PD-1 in benign nevi (n=59), primary melanomas without metastasis (n=22) or with metastasis (n=17), and melanoma metastases (n=32 cases). Benign nevi had significantly higher levels of nuclear PD-L1 immunopositivity (p=0.004) and low levels of PD-1 protein expression (p=0.002). With progression from benign nevi to primary melanoma there was an increase in cytoplasmic positivity for PD-L1 (p=0.03). Also, a significant positive correlation was observed between the percentage of positive cells (p=0.0007) and intensity (p=0.0009) for PD-1 in primary melanomas. Although there was no significant difference in PD-1 levels in between primaries with or without metastasis, a trend was observed for PD-L1 expression: primaries with metastasis having a larger number of tumor cells with cytosolic localization than primaries without metastasis (p=0.07). Interestingly, primary melanomas without metastasis showed significantly larger number of tumor infiltrating lymphocytes (TILs) cells having intense immunoreactivity for PD-L1 protein than did metastatic melanomas (p=0.03). In conclusion, differential cellular localization of PD-L1 protein and high levels of PD-1 protein correlates with disease progression and high-risk histologic features in melanoma and might partially explain the resistance of melanoma cells against the immune system. Citation Format: Nitin Chakravarti, Roland Bassett, Wen-Jen Hwu, Doina Ivan, Jonathan L. Curry, Victor G. Prieto. Differential cellular localization of programmed death ligand 1 (PD-L1) and enhanced expression of programmed death-1 (PD-1) in melanoma progression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 463. doi:10.1158/1538-7445.AM2013-463
Scleroderma, Fasciitis, and Eosinophilia Associated with the Ingestion of Tryptophan
Authors: Richard M. Silver, Melvyn P. Heyes, John C. Maize, Bonnie Quearry, Michele Vionnet-Fuasset, Esther M. Sternberg
Journal: New England Journal of Medicine (1990)

An association between the ingestion of tryptophan and a syndrome characterized by scleroderma-like skin abnormalities, fasciitis, and eosinophilia has recently been recognized in the United States. We report the clinical and histopathological findings in nine patients and the results of biochemical analyses of tryptophan metabolism in seven patients with this syndrome.
Phase I Trial of RAD001 (Everolimus) in Combination with Radiotherapy in Non-Small Cell Lung Cancer
Authors: E. Deutsch, C. Lepechoux, J.P. Pignon, Y.T. Tao, S. Rivera, B.C. Bourgier, M. Angokai, R. Bahleda, K. Slimane, E. Angevin, B.B. Besse, J.C. Soria
Journal: Annals of Oncology (2013)