tbuckley/cabot-search huggingface dataset:
THU0249 C - reactive protein (CRP) is associated with high disease activity in SSC and ILD. Results from the canadian scleroderma research group (CSRG):
Authors: C. Muangchan, S. Harding, S. Khimdas, A. Bonner, M. Baron, J.E. Pope
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Elevated ESR in SSc is associated with morbidity yet little is known about the predictive value of C-reactive protein (CRP) in SSc. <h3>Objectives</h3> This study was done to determine the associations of CRP in SSc subsets (overall, early, late, dcSSc, lcSSc) and organ associations with CRP. <h3>Methods</h3> The CSRG is a large multi-site dataset comprised of patients with SSc where patient and physician reported measures and lab tests are performed annually. The frequency of elevated CRP and ESR and their relationships to clinical parameters, Scleroderma Disease Activity Score (SDAS), Scleroderma Disease Severity Score (SDSS), Health Assessment Questionnaire (HAQ) and changes between annual follow up were studied. Statistical comparisons were made for CRP in early (≤3 years from 1st non-RP symptom) vs. late SSc, diffuse cutaneous SSc (dcSSc) vs. limited cutaneous (lcSSc). CRP &gt;8mg/L was the cut off for elevated as it was the value for 95th percentile for age and gender matched population norms. <h3>Results</h3> 1,043 patients aged 55.4±12.1 years, female predominant (86.1%), and disease duration of 11.0±9.5 years were analyzed of whom 38% had dcSSc, 62% had lcSSc and 10.6% were early dcSSc. Elevation of CRP occurred in 25.7% and ESR 38.2%. Baseline CRP in dcSSc (11.98±25.41 mg/L) was higher than in lcSSc (8.15±16.09 mg/L); p=0.016. SSc with disease duration ≤3 years had higher CRP (12.89±28.13 mg/L) than that with disease duration &gt;3 years (8.60±17.06 mg/L); p=0.041. Though not be consistent in all subsets, CRP was significantly associated in overall group at p&lt;0.01 for: ESR, MRSS, TLC&lt;80%, FVC&lt;80%, DLCO&lt;75%, disease activity (SDAS), damage (SDSS), and HAQ. In early dcSSc, the frequency of elevated CRP and ESR was 41.5% and 44.2% respectively. CRP seemed to normalize in many SSc patients over time. Adding or withdrawing prednisone did not significantly change CRP but was underpowered. <h3>Conclusions</h3> CRP is elevated in approximately one quarter of SSc patients, especially early disease. It is correlated with disease activity, severity and poor pulmonary function. <h3>Disclosure of Interest</h3> C. Muangchan: None Declared, S. Harding: None Declared, S. Khimdas: None Declared, A. Bonner: None Declared, M. Baron: None Declared, J. Pope Grant/Research support from: Support for the CSRG is from CIHR, Scleroderma Society of Canada, Scleroderma Society of Ontario
P17.27 * HIGH GRADE GLIOMAS IN ELDERLY PATIENTS: RESULTS OF SURGERY AND INFLUENCE ON KARNOFSKY'S PERFORMANCE STATUS
Authors: A. Agnoletti, R. Fornaro, F. M. C. Specchia, D. Garbossa, M. Lanotte, A. Ducati
Journal: Neuro-Oncology (2014)

The management of high grade gliomas (HGG) is complex and multidisciplinar. It has been demonstrated that the extent of resection, achieving gross total volume removal (GTR) has a relevant impact on progression free survival (PFS) and on overall survival (OS). Many strategies have been proven to be effective in achieving GTR such as neuronavigation, fluorescence and intra operative ultra sonography. It is remarkable to say that in multicentric trials, often elderly patients were excluded. Recently the interest in results of surgery in elderly patients has grown, and some studies proved the feasibility and advantages of a surgical resection of HGG in elderly patients. We retrospectively analyzed 73 elderly patients (age at diagnosis at least 70 years old) that were affected by HGG in non eloquent areas, therefore amenable to radical surgical excision, that underwent surgical resection in Our division from January 2008 to December 2012. KPS prior to surgery, post surgery and a month after was assessed. OBJECTIVE: Assess the role of surgery on variation of KPS in elderly patients. Materials and methods: we retrospectively analyzed 73 patients, 42 males (57%), 32 ( 43%) females, age range 70-84, mean age 73.87 years old, that underwent surgical excision of newly diagnosed HGG in Our division from January 2008 to December 2012. KPS assessment was performed prior to surgery, and a month after surgery, before adjuvant therapies administration. RESULTS: From data analysis, mean KPS pre-op was 82.5 (overall); mean KPS post operatory (1 month) was 84.5 (overall). 35/73 (47.9%) patients experienced no change in KPS. 24/73 (32%) improved their KPS score, 14/72 (19%) worsened their KPS score. Of the 14 patients which had a worsening in KPS, one month after surgery (before adjuvant treatment), 8 patients recovered, improving their KPS score, which was similar to pre operatory evaluation. The 35 patients that had stability of KPS after surgery, at 1 month after, did not worse; the same was found for patients that took benefit from surgery. CONCLUSIONS: We observed that surgical intervention in this cohort of elderly patients, lead to a stability or improvement of KPS in 59/72 patients (81,9%). The worsening in KPS was observed in 14/72 patients (19.4%), of which 8/14 recovered after rehabilitative program. Thus, we suggest that surgery for HGG in elderly patients with good KPS should be taken into consideration as a viable option.
OP31 * THE SOUND OF SCIENCE: DEVELOPING THE SPECTRAL LIGHT ORCHESTRA
Authors: K. M. Ashton, A. Brodbelt, C. Davis, T. P. Dawson, R. W. Lea, C. Walker, R. Stables, D. Vicinanza, M. D. Jenkinson, G. Clemens, M. J. Baker
Journal: Neuro-Oncology (2014)

INTRODUCTION: Complete tumour removal during surgery is one of the primary factors for recurrence-free survival. The current process is unable to accurately identify tumour margins and data feedback takes too long for responsive action during surgery. Our recent study has shown the ability of Raman spectroscopy to distinguish between metastatic brain, GBM and normal brain tissue to sensitivities and specificities ranging from 85.71% to 100%. Pushing this result towards the clinic needs an assessment of the data feedback. In a surgery situation, audio feedback of tumour margins would provide a real time response allowing the surgeons visual focus to remain on the patient.Auditory perception of complex, structured information could have several advantages when compared to visual images including the capability of the human ear to detect patterns, recognise timbres and follow different strands at the same time. METHOD: Our method consists of two phases, to compute the relevant variables, we apply feature extraction to the data, extracting band-wise spectral shape descriptors such as centroid, skew and kurtosis. These are then used to modulate parameters of a synthesizer. RESULTS: The method was applied to a dataset of 311 samples, 136 from an uncontrolled and 176 from a controlled group. Based on subjective listening tests taken from around 20 participants, we were able to get manual classification accuracies of up to 83%, using a multi-stimulus technique. CONCLUSION: Raman spectroscopy is able to accurately distinguish between cancerous and non-cancerous tissue. The development of novel data extraction tools has enabled audio feedback of these molecular differences in real time allowing the surgeons visual focus to remain on the patient.
Abstract 2438: Bevacizumab treatment hampers tumor uptake of antibodies in human tumor bearing mice
Authors: Marlous Arjaans, Thijs H. Oude Munnink, Sjoukje F. Oosting, Anton G. T. Terwisscha van Scheltinga, Hetty Timmer-Bosscha, Marjolijn N. Lub- de Hooge, Carolina P. Schröder, Elisabeth G. E. de Vries
Journal: Cancer Research (2012)

Abstract Background: Extensive angiogenesis, defective vascular architecture, impaired lymphatic drainage and increased vascular permeability are characteristics unique for solid tumors. These characteristics result in enhanced tumor permeability and retention (EPR) effect. The EPR effect has been recognized as an important factor for intratumoral delivery of macromolecular drugs, like antibodies. Rapid changes in tumor vasculature and permeability due to antiangiogenic treatment could possibly restrain the EPR effect and thereby lead to a decreased uptake of antibodies. This would have implications for combining antiangiogenic therapy with monoclonal antibodies. We therefore investigated the effect of bevacizumab treatment on the tumor uptake of antibodies by means of immunoPET imaging. Methods: The effect of bevacizumab treatment on the antibody tumor uptake was studied with in vivo PET imaging of 89Zr-trastuzumab, 89Zr-bevacizumab and 89Zr-IgG in a SKOV-3 human xenograft tumor model. PET images were made before and during bevacizumab (5mg/kg; 2qw) or placebo (normal saline) treatment. All animals also received trastuzumab, bevacizumab or IgG labeled with the near-infrared fluorescence dye IRDye 800CW as a co-injection. Immunohistochemistry was performed to determine the mean vascular density (MVD). Immunofluorescence was used to visualize trastuzumab-800CW, bevacizumab-800CW and IgG-800CW and to determine vessel normalization by vessel pericyte coverage. Results: Bevacizumab treatment decreased 89Zr-trastuzumab, 89Zr-bevacizumab and 89Zr-IgG tumor uptake with 41 ± 5% (P&amp;lt;0.0001), 43 ± 4% (P&amp;lt;0.0001) and 28 ± 6% (P=0.0004) respectively. Placebo treatment did not affect tumor uptake of 89Zr-IgG. Immunofluorescence showed less accumulation of IgG-800CW in bevacizumab treated tumor sections compared to placebo treated tumor sections. In all groups, bevacizumab treatment decreased the MVD (P&amp;lt;0.0003). Remaining vessels in bevacizumab treated tumor sections showed an increase in the amount and degree of vessel pericyte coverage compared to placebo. Conclusion: Bevacizumab treatment reduces tumor uptake of trastuzumab, bevacizumab and IgG possibly by restraining the EPR effect through vessel normalization. This deserves attention in the design of clinical trials, when combining antiangiogenic treatment with antibodies. 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 2438. doi:1538-7445.AM2012-2438
Safety, tolerability, and preliminary activity of CUDC-907, a first-in-class, oral, dual inhibitor of HDAC and PI3K, in patients with relapsed or refractory lymphoma or multiple myeloma: an open-label, dose-escalation, phase 1 trial
Authors: Anas Younes, Jesus G Berdeja, Manish R Patel, Ian Flinn, John F Gerecitano, Sattva S Neelapu, Kevin R Kelly, Amanda R Copeland, Amy Akins, Myles S Clancy, Lucy Gong, Jing Wang, Anna Ma, Jaye L Viner, Yasuhiro Oki
Journal: The Lancet Oncology (2016)
OP0293 Increased Nerve Growth Factor in the Synovium of People with Painful Knee Osteoarthritis
Authors: L. A. Stoppiello, P. Mapp, R. Hill, D. Wilson, B. Scammell, D. Walsh
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Pain is the major symptom of knee osteoarthritis (OA) and is usually the reason sufferers first seek clinical assistance; however the precise relationship between tibiofemoral pathology and OA pain is not entirely clear. Although magnetic resonance imaging (MRI) studies have linked pain to synovitis, subchondral changes and meniscal abnormalities, the histopathological features specific to symptoms in OA are not well understood. <h3>Objectives</h3> To identify which histological features are associated with symptomatic human knee OA. Better understanding of pain-associated structural and biochemical modifications is crucial for the development of more targeted and effective analgesic treatments. <h3>Methods</h3> Medial tibial plateaux and synovia were obtained from post-mortem (PM) cases who had not sought help for knee pain and from patients undergoing total knee replacement (TKR) surgery for symptomatic OA. The Academic Rheumatology joint tissue repository (n &gt;2000) was screened to select TKR and PM cases displaying similar macroscopic joint chondropathy (n = 29/group). Tissues were compared to identify which histological features were associated with painful OA, assuming TKR cases experienced greater levels of knee pain than PM. OA changes (Mankin score) and synovitis were histologically graded and CD68-positive macrophages and nerve growth factor (NGF) quantified using immunohistochemistry and computer-assisted image analysis. <h3>Results</h3> Synovitis, loss of cartilage surface integrity, proteoglycan loss, tidemark breaching and subchondral changes were all characteristic features of end-stage OA. In the current study, TKR and PM cases were matched for similar macroscopic chondropathy scores (207 v. 196, respectively, <i>P</i> &gt; 0.05). Total knee replacement cases (median age 68 years, 55% male) were slightly younger (<i>P</i> &lt; 0.05) than post-mortem cases (median age 71 years, 55% male). Synovial fractional area positive for NGF was increased in TKR compared with PM cases (13.9% vs. 9.3%, P = 0.021). Synovitis score and loss of cartilage surface integrity were also greater in the surgical group (P = 0.001 and 0.014, respectively), although CD68 fractional areas did not differ significantly between groups (P = 0.21). Adjusting for age differences did not affect the results. <h3>Conclusions</h3> Symptomatic OA is associated with increased synovial NGF expression, synovitis and loss of cartilage surface integrity compared to PM cases with similar macroscopic joint surface appearances who did not seek TKR. Synovial NGF may be a key inflammatory mediator associated with OA knee pain. Identifying structural, cellular and molecular signatures of symptomatic OA may lead to targeted treatment strategies in the future. <h3>Disclosure of Interest</h3> None Declared
Preoperative capecitabine, oxaliplatin and high-dose pelvic conformal radiotherapy in locally advanced rectal cancer (LARC)
Authors: E. Tucci, R. Algeri, P. C. Giulianotti, A. P. Pecci, G. Schiaroli, F. Sbrana, F. Perillo
Journal: Journal of Clinical Oncology (2004)

3646 Background: Preoperative chemoradiotherapy has proven to improve resectability and local control in LARC. The aim of the present study is to evaluate activity and toxicity of oral capecitabine and oxaliplatin administered concurrently with high dose pelvic conformal radiotherapy as neo-adjuvant treatment of LARC. Methods: Capecitabine 825 mg/sqm bid (days 1 to 40) and oxaliplatin 60 mg/sqm iv every 2 weeks (3 administrations) were given concomitantly with pelvic conformal radiotherapy 1.8 Gy daily up to 45 Gy followed by a 5-fraction boost up to 54 Gy in 6 weeks. From February to November 2003, 16 patients (pts) entered the study: 11 males, 5 females, median age 70 years (range 61–78). Clinical stage, determined by CT, was T3N0–1 in 13, T4N1 in 3 pts. Results: To date 14 pts are fully evaluable (2 too early): a clinical response was observed in 11/14. All pts underwent a R0 surgical resection. Pathological complete response was verified in 4 pts, a minimal microscopic residuum was found in 2 pts. Tumor down-staging by TNM criteria was observed in 10/14 pts. A conservative surgical procedure was performed in 5/9 pts previously planned for abdominoperineal resection. The treatment was well tolerated: no G4 toxicity; G3 diarrhea occurred in 3 pts, G2 leukopenia in 3, G2 anemia in 1. Conclusions: These preliminary data show that the association of capecitabine and oxaliplatin with high dose pelvic conformal radiotherapy as preoperative treatment of LARC is well tolerated and seems active as regards pathological response rate and tumor down-staging, allowing sphincter sparing surgery in pts otherwise candidate to abdominoperineal resection. No significant financial relationships to disclose.
Clinical Value of Grading the Scintigraphic Appearances of Tibial Stress Fractures in Military Recruits
Authors: Jane Dutton, Su E Bromhead, Catherine A Speed, Angus R Menzies, Adrien M Peters
Journal: Clinical Nuclear Medicine (2002)

This study evaluated the relation between the scintigraphic appearances of tibial stress fracture in military recruits and the likelihood that they would complete basic military training.The authors retrospectively reviewed 58 Tc-99m MDP scans of recruits referred for possible tibial stress fracture and graded them according to the criteria of Zwas et al. (1987). Stress fracture appearances were correlated with clinical information such as the duration of rehabilitation and final outcome with regard to completion of the initial basic military training program.Thirty-seven of the 58 patients (64%) had tibial stress fractures, all of which were located in the tibial diaphysis, with most occurring in the middle and lower thirds. Most (23 of 37) patients had stress fractures of grade I or II, and the others had grade III or IV stress fractures. There was no statistical difference in the proportion of patients with bilateral fractures between grades I-II and III-IV. There was no significant difference in the duration of rehabilitation for recruits successfully recovering from grade III-IV fractures compared with grade I-II fracture. There was a greater proportion of patients with lower grade fractures than higher grade fractures (P = 0.0006) who, despite rehabilitation, could not continue training because of unremitting or recurring pain at the fracture site and were medically discharged from military service.Contrary to expectation, recruits with higher-grade stress fractures were not less likely to complete basic military training compared with recruits with lower grade stress fractures.
A1.8 A dual role of MTOR in the rheumatoid mesenchymal tissue response to inflammation
Authors: T Karonitsch, K Dalwigk, J Holinka, B Niederreiter, C W Steiner, M Bilban, A Wanivenhaus, R Windhager, J S Smolen, H P Kiener, G Superti-Furga
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The mechanistic target of rapamycin (mTOR) is known to couple energy and nutrient abundance to the execution of essential cellular processes, such as cellular growth and survival. As such, the unfolding biology of mTOR revealed a crucial role in metabolic diseases and ageing. Now, accumulating evidence suggests that mTOR may have an important role in the modulation of cellular responses to inflammatory cues, such as TNF. Whether or not this applies to rheumatoid fibroblast-like synoviocytes (FLS) remains to be determined. <h3>Methods</h3> To assess mTOR activity in rheumatoid synovitis, immunohistochemistry (IHC) was performed using phosphospecific antibodies to mTOR. For functional <i>in-vitro</i> studies, the specific mTOR inhibitor Torin-1 was applied. The GeneChip<sup>®</sup> PrimeView array™ was used for gene expression profiling. Assessment of regulated genes was determined via SAM analysis. The expression of selected candidates was validated by Q-PCR. Finally, to further evaluate the significance of mTOR activity for the inflammatory mesencyhmal tissue response, a simplified 3-D model of the synovial tissue was used. IL-6 and IL-8 levels in the supernatants of 3-D cultures were measured by ELISA. <h3>Results</h3> IHC revealed that mTOR is activated in RA synovitis, especially in fibroblast-like cells of the hyperplastic synovial lining layer. To determine the effect of mTOR activation for the TNF driven mesenchymal inflammatory response, isolated RA-FLS (n = 5) were exposed to TNF in the presence or the absence of Torin. TNF-stimulation resulted in the increased expression of 587 genes (fold induction&gt;1,5; FDR&lt;0,01). Surprisingly, 141 of those transcripts were further upregulated, when FLS were treated with TNF in the presence of Torin. Importantly, this group contained transcripts that are well known to be involved in RA pathogenesis, including IL-6, IL-8 and MMP1. Stimulation of the 3D synovial organ cultures with TNF resulted in hyperplasia of the lining layer at the surface of the spheres. Strikingly, Torin prevented TNF induced lining layer hyperplasia. In line with the gene expression studies, however, the combination of TNF with Torin resulted in increased production of IL-6 and IL-8, when compared to cultures that were solely exposed to TNF. <h3>Conclusions</h3> These studies provide insight into the regulatory circuits that determine the synovial mesenchymal tissue response to inflammation and suggest a multifaceted regulatory role for the mTOR signalling circuit in rheumatoid synovitis.
Probing for DNA Clues for Cancer Diagnosis, Treatment, And Beyond
Authors: D. Holzman
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Probing for DNA Clues for Cancer Diagnosis, Treatment, And Beyond Get access David Holzman David Holzman Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 22, 15 November 1995, Pages 1663–1664, https://doi.org/10.1093/jnci/87.22.1663 Published: 15 November 1995
Familial Incomplete Male Pseudohermaphroditism, Type 2
Authors: Patrick C. Walsh, James D. Madden, Mary J. Harrod, Joseph L. Goldstein, Paul C. MacDonald, Jean D. Wilson
Journal: New England Journal of Medicine (1974)

Two 46 XY siblings with familial incomplete male pseudohermaphroditism, Type 2, inherited as an apparent autosomal recessive trait, were investigated. The phenotype was distinctive in that male wolffian-duct structures (epididymis, vas deferens and seminal vesicles) were present whereas tissues derived from the urogenital sinus and from the anlage of the external genitalia were female in character. Studies of estrogen and androgen dynamics revealed normal male blood testosterone and estrogen levels, production rates and interconversions. The normal blood luteinizing hormone level and normal estrogen production rate suggest that androgen resistance in this syndrome is different from that in other androgen-resistant states. The demonstration of markedly deficient dihydrotestosterone formation in slices of perineal skin, epididymis and phallus, considered with the fact that dihydrotestosterone is the fetal hormone responsible for male differentiation of the external genitalia, is compatible with the possibility that the fundamental lesion is defective formation of dihydrotestosterone in these genital tissues. (N Engl J Med 291:944–949, 1974)