tbuckley/cabot-search huggingface dataset:
PTU-244 Audit of 30-day mortality post endoscopy—a tertiary centre experience
Authors: K Kosuri, O Saraj, G Viggars, B Rathbone, S Shah
Journal: Gut (2012)

<h3>Introduction</h3> Post endoscopy mortality is a quality standard for all endoscopy units. Despite the BSG guidelines on endoscopy related mortality in 2006 there has been little published data available for individual trusts. To review all deaths occurring 30 days post Endoscopy performed within the UHL Trust and establish if they are related to the procedure. We also determined an all cause mortality and procedure related mortality for our Trust. <h3>Methods</h3> Deaths that occurred both in hospital and community within 30 days post endoscopy were captured through our local CASE team for a period of 6 months (January–June 2009) and information was obtained on certified cause of death. All patients9 case records were critically reviewed. Data were collected on demographics, principal diagnosis, indication for procedure, nature and type of procedure, immediate complications and cause of death. We made an observation and established if the death was related to endoscopic procedure. Results are analysed using MS excel 2007 and SPSS V.13. <h3>Results</h3> In total 6783 endoscopy procedures were performed during this 6-month period. Of these, 3342 were Gastroscopies, 1645 Flexible Sigmoidoscopies, 1441 Colonoscopies and 355 ERCPs. A total of 87 patients died within 30 days of their Endoscopy procedure, a high proportion of which were inpatients. 56 died during their inpatient stay. 117 (72 OGD, 24 ERCP, 18 FOS, 2 Colons and 1 EUS) procedures completed on these 87 patients were reviewed. Of these, 54 were therapeutic procedures. 53 were male and 34 were female with a median age 74 years. Of these 6 (5%) patients had three or more procedures, 26 (22%) patients had two procedures and 55 (73%) had single procedures. None required reversing agents nor had sedation related complications. One immediate complication of duodenal perforation following ERCP was recorded. Overall four deaths were identified to be causally related to Endoscopy, all of who had therapeutic procedures (One OGD with oesophageal dilatation and three therapeutic ERCP (one of who died following a myocardial infarct)). 14 cardiovascular deaths occurred within 30 days post endoscopy, eight of which were within 8 days. Underlying malignancy was the commonest recorded cause of death in 30. Individual mortality rates 30 days post OGD, FOS, Colonoscopy and ERCP of 1.7%, 0.61%, 0.14% and 7.8% respectively were noted giving an overall mortality rate of 1.3% (1:78). Individual procedure related mortality figures for OGD and ERCP are 0.03% and 0.56% respectively. <h3>Conclusion</h3> Post endoscopy mortality is a safety and quality standard for all units. Our audit serves as a reminder of the appreciable risk associated with therapeutic endoscopy and that cardiovascular complications still account for a significant proportion of endoscopy related morbidity and mortality. <h3>Competing interests</h3> None declared.
480TiP Phase 3, randomised, open-label study of durvalumab (MEDI4736) in combination with tremelimumab versus platinum-based chemotherapy in first-line treatment of patients with advanced or metastatic NSCLC: NEPTUNE
Authors: T. Mok, P. Schmid, O. Arén, O. Arrieta, M. Gottfried, A.R. Jazieh, R. Ramlau, C. Timcheva, C. Martin, L. Zhao, S. McIntosh
Journal: Annals of Oncology (2015)
Abstract 4594: Dual PI3K/mTOR blockade by NVP-BEZ235 sensitizes head and neck squamous cell carcinoma to radiotherapy
Authors: Ming Gao, Chun-Wei Wang, Chun Sheng Fang, Yen-Shen Lu, Ann-Lii Cheng
Journal: Cancer Research (2012)

Abstract Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide accounting for over 500,000 new cases annually. Chemoradiotherapy is a mainstay of treatment. However, long-term survival rate has only improved marginally; and the severe toxicity often associated with chemoradiotherapy advocates a need for better radiosensitization strategies. Akt/mTOR pathway is frequently activated in HNSCC cells. This study sought to explore whether NVP-BEZ235, a novel imidazo [4,5-c] quinoline derivative that inhibits PI3K and mTOR kinase activity, has radiosensitization effect in the treatment of HNSCC. MTT assays revealed that NVP-BEZ235 dose-dependently inhibited the growth of two HNSCC cell lines, SAS and OC3 at low nanomolar concentrations; IC50 values were 27.87 nmol/L in SAS cells and 42.63 nmol/L in OC3 cells. By using clonogenic assay and median effect analysis, we found that dual PI3K/mTOR inhibition effectively sensitized SAS and OC3 cell lines to radiation with CI (combination index) value &amp;lt;1, indicating a synergistic effect. By using flow cytometry analysis, when SAS and OC3 cells were sequentially exposed to NVP-BEZ235 and radiation, an increase in the subG1 population was observed, indicating that NVP-BEZ235 sensitized HNSCC cells to radiation by augmenting apoptotic cell death. In SAS xenograft nude mice model, combination therapy with oral administration of 45mg/kg/day of NVP-BEZ235 and 3 Gy radiation for 5 days was well tolerated and significantly enhanced the antitumor effect of radiation (p=0.005). Our results indicated that dual PI3K/mTOR blockade effectively sensitizes radiotherapy for HNSCC. Clinical trials along this line are warranted. (The study was supported by the grant DOH100-TD-B-111-001) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4594. doi:1538-7445.AM2012-4594
Respiratory-Tract Colonization and a Distinctive Pneumonia Syndrome in Infants Infected with<i>Chlamydia trachomatis</i>
Authors: Marc O. Beem, Evelyn M. Saxon
Journal: New England Journal of Medicine (1977)

To learn if Chlamydia trachomatis causes in young infants a distinctive penumonia characterized by chronic, afebrile course, diffuse lung involvement and elevated serum immunoglobulins G and M, 47 black infants four to 24 weeks of age were examined for nasopharyngeal shedding of C. trachomatis and serum immunofluorescent antibody to lymphogranuloma venereum Type I. Nasopharyngeal C. trachomatis was found in 18 of 20 with the pneumonia syndrome, two of 15 with various other illnesses and 10 of 12 with inclusion conjunctivitis but without lower respiratory illness. Chlamydial antibody titers of infants with the pneumonia syndrome were significantly elevated (geometric mean-1, pneumonia vs. conjunctivitis = 24,833 vs. 1024 P less than 0.001). No other commonly recognized respiratory pathogens were consistently associated with the pneumonia syndrome. We believe these findings demonstrate an association between the distinctive pneumonia syndrome and C. trachomatis. This, in turn, is a particular facet of a more general event consisting of frequent colonization of the respiratory tract by C. trachomatis in natally acquired infection.
SAT0406 Effectiveness of Total Contact Insole on Plantar Fasciitis
Authors: H. V. Oliveira, A. Jones, E. Moreira, F. Jennings, J. Natour
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Plantar fasciitis (PF) in an inflammation of the fascia o on the bottom of the foot, characterized by stiffness in the medial arch and ankle, especially during one's first steps, and can have a significant effect on activities of daily living. An insole is one of the most often employed conservative methods for the treatment of PF. The total contact insole (TCI) is the most recommended, as it redistributes the load uniformly throughout the sole of the foot. However, few studies have demonstrated the effectiveness of this device and there is no consensus on which type of insole is the most adequate. <h3>Objectives</h3> The aim of the present study was to assess the effectiveness of a TCI regarding pain relief in patients with PF. <h3>Methods</h3> Seventy-four patients with plantar fasciitis (33 of whom had pain in both feet) were randomly allocated into a study group (total of 57 feet) using a total contact insole and control group (total of 50 feet) using a sham insole. Evaluations were performed of pain (VAS); quality of life (SF-36); foot function (FFI and FSHQ); walking distance in six-minute walk test and foot pressure analysis using the AM Cube FootWalk Pro program. The groups were evaluated at baseline and after 45, 90 and 180 days by a blinded assessor. Data were analyzed using the intention to treat approach. <h3>Results</h3> The groups were homogeneous regarding the majority of variables at baseline. In the comparisons over time, statistically significant differences between groups were found for pain when walking (p=0.003) and the 6MWT (p=0.006). Improvements occurred in both groups with regard to pain at rest, foot function and some quality of life parameters (functional capacity, bodily pain, vitality and social aspects) without statistically significant differences between groups. No changes in foot pressure were found with the use of the insole. <h3>Image/graph</h3> <h3>Conclusions</h3> Total contact insole can be used to reduce pain when walking and increase walking distance among individuals with plantar fasciitis. <h3>References</h3> Ciconelli RM, Ferraz MB, Santos W, Meinao I, Quaresma MR. Tradução para a língua portuguesa e validação do questionário de avaliação de qualidade de vida SF-36. Rev Bras Reumatol. 1999;39(3):143-50. Ferraz MB, Quaresma MR, Aquino LR, Atra E, Tugwell P, Goldsmith CH. Realiability of pain scales in the assessment of literate and illiterate patients with rheumatoid arthritis. J Rheum. 1990b;17:1022-24. <h3>Acknowledgements</h3> FAPESP and CAPES <h3>Disclosure of Interest</h3> None Declared
EBUS-guided transbronchial biopsy (EBUS-TBNB) with a transbronchial needle forceps (TBNF) – a pilot study
Authors: FJF Herth
Journal: Endoscopy (2011)

One limitation of EBUS TBNA is the size of the available needles, yielding frequently only cells for cytological examination. The aim of this pilot study is to evaluate the efficacy and safety of a newly developed forceps-needle to obtain tissue for the histological diagnosis of enlarged mediastinal lymph nodes.
Abstract 1526: Evaluation of the novel tumor suppressor gene, β-Defensin-1, in colorectal cancer cell line models.
Authors: Austin Layton, Pierre O. Bohanes, Wu Zhang, Heinz-Josef Lenz, Melissa J. Labonte
Journal: Cancer Research (2013)

Abstract Background: Human defensins are antimicrobial linear peptides with broad anti-microbial activity, organized into two classes, α- and β-defensins. Human β-Defensin 1 (hBD-1) is encoded by the DEFB1 gene located on chromosome 8p23 and functions as an antimicrobial peptide involved in the innate immune response. It is most often expressed in epithelial cells, including those in the large intestines. Previous experiments have shown that hBD-1 exhibits tumor suppressor functions in urothelial and kidney cancer cells. Previous evaluation of germline single nucleotide polymorphisms in the promoter region of DEFB1 demonstrated CRC stage specific effects of rs1800972 and rs179946 in predicting time-to-tumor recurrence in CRC patients. This study examined the cancer specific expression of hBD-1 in CRC compared to normal cells and further evaluated the cellular mechanism associated with the effects of hBD-1 expression in CRC proliferation, cell cycle progression and apoptosis. Methods: Twenty-two patients colon tissue samples were subjected to immunohistochemistry (IHC) specific for hBD-1 to examine its expression in both normal and tumor cells. To gain insight into the effects of hBD-1 expression in CRC, CaCo2, HCT116, HT29 and SW620 CRC cell lines were transfected with pCMV6-XL4-DEFB1, alongside a control empty vector, to compare the effect of hBD-1 overexpression on cell viability and apoptosis at 24 and 48 hr. In addition, recombinant hBD-1 was exogenously added to CRC cells and analyzed for the effect on cell viability. Results: Examination of hBD-1 expression from patients’ colon tissue samples by IHC demonstrated that hBD-1 expression was present in the normal colon cells, but its expression was lost in CRC cells. Induction of hBD-1 expression in CRC cell lines resulted in a significant change in cell viability, membrane permeability and induction of apoptosis. Further, the exogenous addition of recombinant hBD-1 to CRC cells resulted in a significant reduction in cell number at 48 hr. Conclusion: These results demonstrate evidence of loss of hBD-1 expression in CRC cells and further provide evidence for hBD-1’s potential role as a tumor suppressor. Further studies are being conducted to determine the pathway of apoptosis that is induced and to better understand the hBD-1 affects in the CRC cells development and progression and further evaluate the potential utility of targeting hBD-1 as a therapeutic strategy. Citation Format: Austin Layton, Pierre O. Bohanes, Wu Zhang, Heinz-Josef Lenz, Melissa J. Labonte. Evaluation of the novel tumor suppressor gene, β-Defensin-1, in colorectal cancer cell line models. [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 1526. doi:10.1158/1538-7445.AM2013-1526
AB1355 Observed dosing and refill compliance in bio-naÏve and bio-experienced psoriatic arthritis patients treated with golimumab
Authors: L. Ellis, S. Haas, S. Bolge, N. Tandon
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Golimumab is a once-monthly, subcutaneously-administered, anti-TNF agent indicated for treatment of active psoriatic arthritis (PsA). Real-world dosing and refill compliance patterns of golimumab use in PsA patients have not been reported previously. <h3>Objectives</h3> This study reports golimumab (GLM) dosing and refill compliance observed in psoriatic arthritis (PsA) patients. <h3>Methods</h3> This retrospective database analysis assessed GLM use in adult PsA patients with ≥2 GLM prescriptions between 4/24/2009 and 12/31/2010; ≥1 PsA diagnosis during the study period; continuous activity in the Source® LX database (≥6 months before; ≥6 months after the index GLM prescription; and a 28-31 day GLM supply. Refill compliance was defined as refills occurring ± 1 week of the expected 28-31 day (d) interval. The percent of compliant GLM refill intervals and the percent of patients demonstrating refill compliance at the 6th GLM dose were assessed in the overall population and in bio-naïve/bio-experienced subgroups. Descriptive statistics were used to characterize the study population (mean ± SD, median, n and %). <h3>Results</h3> A total of 262 PsA patients and 1,489 GLM refill intervals were observed. The sample was 59% female; mean age of 50 years with 72% bio-experienced. A 50 mg GLM dose was found in 97% of all fills. The mean±SD refill interval for the overall population was 35.6±19.8 d with a median of 31 d. Bio-experienced patients had slightly more frequent refill intervals (34.9±18.4 d) as compared to bio-naïve patients (37.4±23.2 d), but the median was 31 d in both subgroups. Refill compliance was observed in 80% of all intervals for the overall population. Refill compliance at the 6th GLM dose was achieved by 84% of patients overall; (87% of bio-naïve and 82% of bio-experienced patients). <h3>Conclusions</h3> In this retrospective analysis of a large national administrative claims database, 97% of GLM doses were 50 mg with approximately once monthly refill intervals. Overall refill compliance was observed in approximately 80% of all GLM refills and in greater than 80% of PsA patients at the sixth GLM dose. Median refill interval and refill compliance appeared similar in bio-experienced and bio-naïve subgroups. Further study of these trends using additional data sources are desired to substantiate these preliminary findings. <h3>Disclosure of Interest</h3> L. Ellis Employee of: Janssen Scientific Affairs, LLC, S. Haas Consultant for: Janssen Scientific Affairs, LLC, S. Bolge Employee of: Janssen Scientific Affairs, LLC, N. Tandon Employee of: Janssen Scientific Affairs, LLC
Diffuse Pulmonary Uptake of Tc-99m MDP in Sarcoidosis
Authors: J Maloof, J Hurst, N Gupta
Journal: Clinical Nuclear Medicine (1996)

A 64-year-old female had nausea, vomiting, anorexia, and fever. She was hypercalcaemic and had a normal serum parathyroid hormone level. Bone marrow biopsy showed granulomatous inflammation, and serum angiotensin converting enzyme was grossly elevated. Tc-99m MDP revealed bilateral diffuse pulmonary uptake, the first reported in a patient with sarcoidosis. Ga-67 scintigraphy showed abnormal pulmonary uptake (corresponding to the bone scan) and increased activity in parotid and lacrimal glands. Calcification was undetected on chest x-ray and CT. Because the mechanism of Ga-67 uptake in sarcoidosis is not well understood, its relationship to pulmonary parenchymal calcification needs further exploration.
Abstract 2244: Internalization of basigin-2, a poor prognosis marker, by a monoclonal antibody
Authors: Douglas A. Lappi, Leonardo Ancheta, Romana A. Nowak
Journal: Cancer Research (2010)

Abstract Basigin-2 (EMMPRIN, CD147) is widely expressed on the surface of numerous tumor types and is associated with poor prognosis. Basigin is an integral membrane glycoprotein also expressed on numerous normal cell types. Several functions have been described for basigin-2 within both normal and malignant tissues. The best characterized is its ability to induce the expression of matrix metalloproteinases in stromal cells. As such, it is suggested to play a role in tumor metastasis. Because of its association with poor prognosis and possible role in metastasis, we examined the ability of basigin-2 to be targeted on the cell surface and internalized as a possible gateway for entry into tumor cells, or for down-regulation for inhibition of metastasis. Belton et al. have documented internalization of basigin-2 by a recombinant soluble protein corresponding to the extracellular domain (ECD) of basigin-2 (J Biol Chem, 2008, 283:17805). We have extended this investigation to examine antibody-mediated endocytosis. A monoclonal antibody to the basigin ECD (also reported in Belton et al.) has been used in an internalization assay using biotinylated antibody mixed with streptavidinylated-saporin (the ribosome-inactivating protein). This complex will eliminate cells only if there is antibody-mediated endocytosis, since saporin has no mechanism of cell entry. HeLa cells, which are known to express basigin-2, were challenged and a potent cytotoxicity was observed: the ED50 of the biotinylated antibody-streptavidin-saporin complex is 370 pM. This is evidence that the antibody internalizes in HeLa cells. Similar data were observed with ovarian carcinoma cells (OVCAR3, SKOV3). Non-tumor cells with low expression have low sensitivity to the complex and there was a correlation between basigin-2 expression on the cell surface and cytotoxicity. We conclude that basigin-2 internalizes in response to antibody binding. Further work is necessary to determine if this can be used for introduction of molecules into basigin-2-expressing cells or if down-regulation would have an effect on metastasis promoted by this poor prognosis molecule. 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 2244.
SP0061 How to treat psoriatic arthritis?
Authors: F. van den Bosch
Journal: Annals of the Rheumatic Diseases (2013)

Psoriatic arthritis (PsA) is an inflammatory rheumatic condition usually associated with skin and/or nail psoriasis. The articular manifestations are quite heterogeneous, with arthritis being the most frequent manifestation, but with enthesitis, dactylitis and/or spondylitis occurring in a relevant proportion of patients. Extra-articular manifestations, such as uveitis or inflammatory bowel disease, also occur in a higher frequency compared to the general population, supporting the inclusion of PsA in the clinical spectrum of spondyloarthritides. It has been shown that PsA can have a profound impact on quality of life, because of the different clinical disease manifestations as well as the psychological and social consequences. All these aspects make PsA a disease which may be difficult to manage in the daily clinic. In the past treatments of PsA were largely based upon therapies "borrowed" from rheumatoid arthritis (RA). Recently EULAR has developed evidence-based guidelines for the management of PsA: these consist of a number of overarching principles, as well as specific recommendations to guide treatment with NSAIDs, synthetic DMARDs and biologicals. The level of evidence supporting each recommendation was graded by a Task Force based upon a systematic review of published literature. Despite the evident lack of well-designed controlled clinical trials, conventional DMARDs such as methotrexate are still widely used by rheumatologists to treat PsA. Upon failure of this therapeutic option, approved anti-TNF agents, such as etanercept, adalimumab, infliximab and golimumab, have been shown to improve dramatically the outcomes for patients, often tackling both the rheumatological and the dermatological aspects of the disease. In case of failure of these treatments, a number of new agents have been studied or are in development for PsA: these include treatments approved for RA (abatacept), psoriasis (ustekinumab), or newer agents targeting e.g. IL-17. Small oral molecules such as apremilast or tofacitinib are also in development. Data on these different options will be discussed, providing an indication of what this could mean for current and future clinical practice. <h3>Disclosure of Interest</h3> None Declared