tbuckley/cabot-search huggingface dataset:
PTU-117 Sequential NUC therapy following pegylated interferon provides a greater decline in HBSAG and potentially offers a treatment advantage over current therapies
Authors: US Gill, NK Hansi, L Payaniandy, J Schulz, D Payaniandy, W Alazawi, J Dearden, YN Kallis, P Kooner, R Marley, W Tong, GR Foster, PTF Kennedy
Journal: Gut (2015)

<h3>Introduction</h3> Tenofovir and Entecavir are potent nucleots (t)ide analogues (NUCs) and are the standard of care in the treatment of Chronic Hepatitis B (CHB). Despite this, they have limited ability to reduce HBsAg, thus indefinite or life-long therapy is mandated in the majority of patients. Pegylated-Interferon-Alpha (PegIFNa) is associated with better rates of HBsAg decline, but its effect is limited to a small proportion of patients. In isolation, these therapies are inadequate. By optimising the use of these therapies, delivered in combination or sequentially, better treatment outcomes may be achievable. We report on the treatment response in a cohort of patients treated with sequential NUC therapy. <h3>Method</h3> 31 patients (male = 25); median age 32 (range 18–55), HBeAg positive (n = 20), were treated with PegIFNa; deemed non-responders and treated sequentially with a NUC analogue. Treatment response in this cohort was compared with 58 patients (male = 50); median age 45 (range 21–72), HBeAg positive (n = 25) who were treated with do-novo NUC therapy without previous PegIFNa exposure. Patients in both cohorts were virally suppressed at the time of analysis. Serum ALT, HBV DNA and HBsAg were quantified at baseline and longitudinally in the cohorts. <h3>Results</h3> In the sequential NUC therapy group, baseline median ALT was 102 IU/L (range 24–420) and median HBV DNA 6.93 logIU/ml compared with 43 IU/L and 4.48 logIU/ml respectively for the de-novo NUC group. ALT normalisation and reduction in HBV DNA to undetectable levels was similar in both groups over follow-up (p = n.s). At the time of viral suppression (9–12 months in both cohorts) the decline in HBsAg in the de-novo NUC group overall was 0.02 logIU/ml compared to baseline (p = n.s). In patients receiving sequential NUC therapy there was a significant decline in HBsAg over follow-up compared to baseline (0.70 log IU/ml, p = 0.0001). <h3>Conclusion</h3> Sequential NUC therapy following treatment failure with PegIFNa is associated with greater reductions in HBsAg than PegIFNa alone or NUC monotherapy. This suggests PegIFNa may prime the immune response, even in the context of treatment failure, leading to better outcomes with sequential NUC therapy. We have identified an immune phenotype associated with HBsAg decline in sequential NUC therapy. Further studies are required to confirm this finding and the applicability of an immune marker to predict treatment response in clinical practice. <h3>Disclosure of interest</h3> None Declared.
Dendritic cell therapy in glioblastoma multiforme
Authors: J. Nesselhut, T. Nesselhut, R. Chang, D. Marx, W. Brockmann, I. Wilke, C. Matthes, D. Lorenzen, W. Stücker, H. Peters, W. Lüke
Journal: Journal of Clinical Oncology (2007)

3065 Background: Malignant brain tumors belong to the tumors with unfavorable prognosis. The most aggressive form, glioblastoma multiforme (GBM WHO grade IV glioma), is categorized as incurable with median survivals less than 12–18 months and 90–95% of patients surviving less than 2 years. Here we show that immunotherapy with monocyte-derived dendritic cells (MoDC) can induce a clinical response in advanced GMB, especially when combined with the non human pathogenic oncolytic virus NDV (New Castle Disease Virus). Methods: After isolating monocytes from peripheral blood of n=21 patients dendritic cells were generated ex vivo in the presence of recombinant cytokines (IL-4, GM-CSF) and 2,5% autologous serum. If tumor tissue was available the MoDC were primed on day 5 with tumor- lysate and co-cultured with poly:IC and IFN-alpha. The MoDC were harvested on day 7 of culture and administered to the patients, intradermally. In 5 patients NDV was added to the MoDC for one hour prior to administration. These patients received an infusion with NDV one day before vaccination. Results: We were able to induce a clinical response in 33% (n=7) of the treated patients. The median survival after onset of DC-therapy was 10 months. With respect to primary diagnosis the median survival was 19 months with 1- and 2-years survival rates of 81% and 14%, respectively. Improvement of the clinical response can be observed by combination of NDV. None of the 5 patients treated with this combination therapy died of the disease (9–19 months after primary diagnosis). Three of them (60%) show a response with 2 clear partial remissions (40%). Conclusions: Taken together, a dendritic-cell based therapy can be successful in the treatment of GBM. Enhancement of the therapeutically outcome can be induced by a combination therapy with New Castle Disease Virus leading to the suggestion that there may be an interaction between the dendritic cells and the NDV. No significant financial relationships to disclose.
Modulation of liver tolerance by conventional and nonconventional antigen-presenting cells and regulatory immune cells
Authors: Andrea Kristina Horst, Katrin Neumann, Linda Diehl, Gisa Tiegs
Journal: Cellular and Molecular Immunology (2016)

The liver is a tolerogenic organ with exquisite mechanisms of immune regulation that ensure upkeep of local and systemic immune tolerance to self and foreign antigens, but that is also able to mount effective immune responses against pathogens. The immune privilege of liver allografts was recognized first in pigs in spite of major histo-compatibility complex mismatch, and termed the “liver tolerance effect”. Furthermore, liver transplants are spontaneously accepted with only low-dose immunosuppression, and induce tolerance for non-hepatic co-transplanted allografts of the same donor. Although this immunotolerogenic environment is favorable in the setting of organ transplantation, it is detrimental in chronic infectious liver diseases like hepatitis B or C, malaria, schistosomiasis or tumorigenesis, leading to pathogen persistence and weak anti-tumor effects. The liver is a primary site of T-cell activation, but it elicits poor or incomplete activation of T cells, leading to their abortive activation, exhaustion, suppression of their effector function and early death. This is exploited by pathogens and can impair pathogen control and clearance or allow tumor growth. Hepatic priming of T cells is mediated by a number of local conventional and nonconventional antigen-presenting cells (APCs), which promote tolerance by immune deviation, induction of T-cell anergy or apoptosis, and generating and expanding regulatory T cells. This review will focus on the communication between classical and nonclassical APCs and lymphocytes in the liver in tolerance induction and will discuss recent insights into the role of innate lymphocytes in this process.
SAT0300 Teriparatide Inhibits Bone Loss and Improves Hyperalgesia in Ovariectomized Mice
Authors: S. Kato, H. Wakabayashi, T. Nakagawa, Y. Naito, A. Sudo
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Osteoporosis may cause not only fractures but also chronic back pain in elderly women. Bente et al reported that postmenopausal women with severe osteoporosis who were prescribed teriparatide (TPTD) in standard clinical practice had a reduction in back pain. However, there have been no reports regarding the effect of TPTD on pain in animal models of osteoporosis. <h3>Objectives</h3> In this study, we investigated the effect of TPTD on pain-related behavior in ovariectomized mice. <h3>Methods</h3> 8-week-old female ddY mice were ovariectomized (OVX) and assigned to 3groups; SHAM-operated mice treated with vehicle (SHAM), OVX mice treated with vehicle (OVX-V), OVX mice treated with TPTD (OVX-TPTD). Starting immediately after surgery, vehicle or 40μg/kg TPTD was injected subcutaneously 5 times a week for 4 weeks. The bilateral proximal tibial metaphyses were analyzed three-dimensionally by μCT 4 weeks after surgery (each group; 4 mice). Mechanical sensitivity was tested using von Frey filaments 4 weeks after surgery. To evaluate the 50% withdrawal threshold, nine von Frey filaments with forces of 0.02, 0.04, 0.07, 0.16, 0.4, 0.6, 1.0, 1.4 and 2.0 g were applied to the middle of the plantar surface. Testing was initiated with the 0.6 g filament. In the absence of a clear paw withdrawal response, increasingly stronger filaments were presented consecutively, until one of them was found to elicit such a response. If the 0.6 g filament elicited a response, filaments with decreasing strength were presented until determination of the first one which failed to cause paw withdrawal. Data was collected using the up-down method to calculate the 50% mechanical paw withdrawal threshold <h3>Results</h3> μCT analysis of the proximal tibial metaphysis (Fig. 1) showed that bone volume/tissue volume (BV/TV) and trabecular number (Tb.N) were significantly less in the OVX-V group than in the SHAM group, whereas trabecular separation (Tb.Sp) was significantly greater in the OVX-V group than in the SHAM group. In the OVX-TPTD group, BV/TV and Tb.N were significantly greater than in the OVX-V group, whereas Tb.Sp was significantly less than in the OVX-V group. The 50% withdrawal threshold was significantly lower in the OVX group than in the SHAM group, whereas it was higher in the OVX-TPTD group than in the OVX-V group,but there was not significant. <h3>Conclusions</h3> In this study,TPTD prevented ovariectomy-induced bone loss. Mechanical hyperalgesia in hindlimbs tended to be decreased in OVX group compered with OVX-TPTD group.TPTD may be usefull for treatment of the postmenopausal osteoporotic pain. <h3>Disclosure of Interest</h3> None declared
Children are still transferred by non-specialist teams
Authors: A. Sharples, M. O'Neill, O. Dearlove
Journal: BMJ (1996)

paediatric transfer by non-specialists,3 surely they are too non-specific to assess the performance of a specialist team.A study by Edge et al,4 in which a specialist retrieval team did not seem to reduce physiological deterioration during transfer as assessed by these criteria, may be criticised on the grounds that the two groups were not comparable.The patients transferred by a non-specialist team were significantly older and included a higher proportion of victims of trauma.The diagnoses in the patients transferred by a specialist team were not stated.Also, although physiological deterioration occurred in 11% of the patients transferred by the specialist teams and 12% of the patients transferred by the non-specialist teams, the data from the two groups were pooled together, making further analysis impossible.It would be interesting if Britto and colleagues' study was repeated, with more sensitive criteria being used to assess morbidity during transfer, perhaps by the inclusion of a specified percentage deterioration in physiological variables before transfer.
Choi Vs. Recist Assessment of Tumor Response in a Retrospective Analysis of Patients (Pts) Receiving Trabectedin (T) for Advanced Soft Tissue Sarcomas (Asts)
Authors: S. Taieb, E. Saada, E. Tresch, T. Ryckewaert, E. Bompas, A. Italiano, C. Guillemet, C. Peugniez, S. Piperno-Neumann, A. Thyss, S. Clisant, A. Cassar, D. Nommay, N. Penel
Journal: Annals of Oncology (2014)
Abstract 540: Effects Of Altered Levels Of Adenylyl Cyclase Type 5 In Cardiac Myocytes From Chimeric Mice
Authors: Che-Lin Hu, Shumin Gao, Chull Hong, Jing Liu, Heather Reinhardt, Eric Holle, Thomas E Wagner, Dorothy E Vatner, Stephen F Vatner
Journal: Circulation (2007)

The role of adenylyl cyclase (AC) isoforms in the heart has remained controversial in regards to their ability to enhance or impair cardiac function. We examined the effects of chronic pressure overload (aortic banding) in transgenic (TG) mice with cardiac overexpressed AC isoform type 5 (AC5TG), a major cardiac AC isoform. In AC5TG, the hypertrophic response, as assessed by LV/tibia length (TL), was greater, p&lt;0.05, in AC5TG (6.6±0.2) than wildtype (WT) (5.1±0.2). In addition, cardiac decompensation occurred, as reflected by decreased LV ejection fraction and increased lung/body weight, which could exert systemic effects through reflexes and hormones. We sought to examine whether the effects of overexpressed AC5 on the response to pressure overload is due to the affects on the myocyte or its environment. Chimeric mice from fusion between embryos from the transgenic overexpressed AC5 parents and the Rosa26 parents, which ubiquitously express beta-galactosidase in all tissues and can be identified histologically with X-gal staining, were developed. The proportion of the AC5TG (FVB background) cells in the myocardium ranged from 2% to 75% (n=9). We subjected these animals to 2 wk aortic banding at 4 – 6 months of age and examined the physiological and histological changes in the heart. There was a direct correlation (r= 0.91) between the percentage of AC5OE cells and LV hypertrophy index (LV weight/BW) including LV end diastolic and systolic wall thickness (r=0.98 and 0.92, respectively). We then determined the myocyte cross-sectional cell size from different cell origin micrographically. After 2wk banding, myocytes originating from the Rosa26 (C57/BL6) and FVB background were similar in size, but myocytes overexpressing AC5 were significantly larger (33%, p&lt;0.05). Conversely, there was a negative correlation between the amount of AC5OE cells and heart function: LV ejection fraction and contractility decreased in mice with a higher percentage of AC5OE myocytes (r = −0.89 and r = −0.81, respectively). Thus, overexpression of AC5 even in only a small fraction of total myocytes in the heart induced myocyte hypertrophy independent of any systemic influences.
Platelet-Mediated Thrombosis
Authors: Paul A. Gurbel, Young-Hoon Jeong, Eliano P. Navarese, Udaya S. Tantry
Journal: Circulation Research (2016)

The pivotal role that platelets play in thrombosis and resultant ischemic event occurrences in patients with high-risk coronary artery disease is well established. This role provides the fundamental basis for the current wide implementation of dual antiplatelet therapy with aspirin and a P2Y12 receptor inhibitor. The development of user friendly point-of-care methods to assess platelet reactivity to adenosine diphosphate has increased the frequency of platelet function testing in clinical practice. Recent large observational studies have established an independent relation between the results of point-of-care platelet function testing and clinical event occurrence in patients undergoing coronary artery stenting. However, prospective, randomized trials have failed to demonstrate that personalized antiplatelet therapy based on point-of-care assessment of platelet function is effective in reducing ischemic event occurrences. Important limitations were associated with these trials. In addition, the concept of a therapeutic window of P2Y12 receptor reactivity with an upper threshold associated with ischemic event occurrence and a lower threshold associated with bleeding has also been proposed. In the absence of strong prospective evidence to support personalized antiplatelet therapy, clinical decision making about antiplatelet therapy rests on the large body of observational data and the fundamental importance of platelet physiology in catastrophic event occurrence in patients with high-risk coronary artery disease.
18F-Fluorocholine PET/CT Finding of a Vertebral Hemangioma
Authors: Giordano Savelli, Valentina Perotti, Edoardo Rosso, Claudio Pizzocaro, Silvia Magnaldi
Journal: Clinical Nuclear Medicine (2016)

The uptake of 18F-fluorocholine (FCH), a radiopharmaceutical used to study patients with prostate cancer, follow both the phosphorylcholine and acetylcholine synthesis. FCH uptake is not specific of neoplastic cells because phospholipids are a structural constituent of the membrane of all cells. Thus, PET/CT with FCH show several areas of physiologic uptake. The skeleton concentrates only mild amounts of FCH, thus a diffuse faint uptake of the radiopharmaceutical is present at a PET/CT study. Herein we present the case of a patient in which PET/CT evidenced a sharply defined vertebral “cold” area of reduced FCH uptake corresponding to a vertebral hemangioma.
Prostate cancer in men under the age of 50: A comparison of race and outcomes.
Authors: P. M. Parker, K. R. Rice, Y. Chen, D. G. McLeod, S. A. Brassell
Journal: Journal of Clinical Oncology (2010)

4654 Background: Controversy exists as to what age to undergo prostate cancer screening, outcomes for early intervention, and whether there are differences in tumor biology as one ages. We compared clinicopathologic features as well as survival outcomes for men under the age of 50 (<50) in relation to other age groups stratified by race to further define these differences. Methods: After a multi- institutional review of 12,081 patient records of men diagnosed with prostate cancer from 1989-2009, 543 (4.5%) were found to be <50. Patients were then stratified by age and race. Clinic-pathological features were compared across age groups using chi square test. Biochemical recurrence-free and overall survival curves across age groups were compared using Kaplan-Meier survival analysis and log-rank test. Multivariate Cox proportional hazard analysis was used to evaluate the prediction value of age on biochemical recurrence and overall survival adjusted by other clinic-pathological features. Results: A higher percentage of African American men diagnosed with prostate cancer were <50 compared to Caucasians (8.3% vs. 3.3%, P<.0001). Positive family history was more prevalent in the <50 cohort (36.1% vs. 22.0%, P<.0001). Despite these findings both racial subgroups for men < 50 demonstrated a lower PSA at diagnosis, PSA velocity, biopsy Gleason sum, incidence of extracapsular extension, positive surgical margins, and pathologic Gleason sum. Furthermore, both Kaplan-Meier survival analysis and multivariate Cox proportional hazard analysis showed that the < 50 cohort had a lower incidence of biochemical recurrence and improved overall survival. Conclusions: Race and family history appear to play a significant role in the incidence of prostate cancer in younger men. Early diagnosis of disease is associated with more favorable oncologic outcomes and indicates that population-based screening at younger ages could potentially lead to improved survival. No significant financial relationships to disclose.
Soundings: Publish and be praised
Authors: James Owen Drife
Journal: BMJ (2000)

It is the distinction awards season. All over Britain hospital doctors are hand delivering envelopes marked “Strictly private and confidential.” Inside are computer generated forms that never quite manage to position themselves correctly on the page.

The completed forms contain lists of achievements, something of which most people would be proud. Doctors, however, are oddly furtive about them. We sidle up to one another like Michelle of the Resistance, “Listen carefully, I shall photocopy this only once.”

But this is not a subject for levity. Merit awards, like natural functions, should not be discussed in public. Writing this is a breach of protocol. It is un-British, like analysing the honours system.

I should say that I am not one of the decision makers. In this era of open.gov.uk it is probably easy to find out who sits on the important committees, but most of us rely on hearsay. We take the process seriously but not that seriously. Nevertheless, I have seen many completed forms over the years. It is quite a feat to compress a lifetime of service into two sides of A4, even using font size 8. A tiny typeface gets in more information but may be unwise, considering the seniority of the people who have to read it.

What always strikes me is how little doctors know about one another—even close colleagues. Reading other people's CVs is a humbling experience. All those publications. All those committees.

There is something illogical about a system that expects doctors to work flat out all week and then rewards those who do more. Nevertheless, it is popular among doctors, who are naturally competitive, and among health economists, who know it is cost effective. So much medical advice for the NHS, most of it free at the point of use. Patients may be less impressed with a system that encourages overwork. “Busy doctor” and “busy hospital” are popular cliches with NHS staff. Patients might prefer “relaxed, easy going doctors” and “quiet, efficiently run hospitals.”

Whatever you think of the system, it does provide extra motivation to type A personalities. Its flaw is its secrecy. The names of award holders are published but their completed CV forms should be too. That would be an effective riposte to accusations of nepotism, and I think that the public would be impressed.
Heterotopic Intrathoracic Liver
Authors: B. T. Le Roux
Journal: Thorax (1961)

Accessory hepatic tissue, unlike accessory splenic and pancreatic tissue, is rare, and has a limited and almost exclusively subdiaphragmatic distribution (Willis, 1958).Only one example of supradiaphragmatic heterotopic liver has been found in the literature (Hansbrough and Lipin, 1957).A second example of this unusual anomaly is described, and is similar in nearly every detail to the case mentioned above.This very similarity suggests that the developmental aberration which results in hepatic tissue lodging above the diaphragm is reproducible, and that other cases are likely to be found.The lesion is symptomless and harmless, and if further examples are found that follow a pattern similar to the two known cases, awareness of the occurrence of the lesion may ultimately obviate the need for diagnostic thoracotomy.
Patterns and predictive factors of recurrences after complete resection for fibrolamellar hepatocellular carcinoma
Authors: G. El Maalouf, C. Le Tourneau, V. Paradis, F. Degos, O. Farges, A. Cortes, E. Raymond, J. Belghiti, S. Faivre
Journal: Journal of Clinical Oncology (2007)

15071 Background: Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare subtype of primary HCC which often arises in young patients without underlying hepatic disease or viral infection. Clinical and pathological factors of prognosis are warranted. Methods: Descriptive, univariate and multivariate analysis of survival parameters were analyzed in a monocenter cohort of FL-HCC patients completely resected. Main variables were WHO-PS, age, AJCC stage, AFP level and detailed pathological features including EGFR, p- AKT, and PTEN expression. Results: 23 consecutive patients (median age: 30, M/F:6/17) with pathologically reviewed FL-HCC were analyzed. Median tumor size was 11 cm (range 4–23) and 6 patients had AFP&gt;200ng/ml. two patients had respectable metastasis (lung or peritoneum), 5 patients had vascular invasion and 3 patients had lymph node metastasis achieving the following AJCC staging: I (70%), III (22%) and IV (8%). With median follow-up of 36 months, 3-year survival was 76% . Median time of recurrence was 23 months. Sites of first recurrence were hepatic in 5 patients, extra-hepatic in 4 patients, and both in 3 of 12 patients who recurred (52%). Metastasis occurred in lung, peritoneum, bone, skin and lymph nodes. Expression of EGFR, p-AKT, and PTEN was found in 94%, 69% and 0% of patients, respectively. None of the clinical parameters including AJCC staging predicted survival. In multivariate analysis, bad prognostic factors of recurrence were satellite micro-nodules (p=0.04) and micro-vascular tumor invasion (p=0.03) on pathological specimens. There was a trend toward a better survival in patients with &lt;30% EGFR expression (p=0.06). Conclusions: FL-HCC patients with primary complete resection may develop extra-hepatic metastasis (58%) or isolated intra-hepatic recurrence (42%) within a median follow-up of 2 years. Prognostic factors of survival are pathological satellite nodules and micro-vascular tumor invasion. No significant financial relationships to disclose.