tbuckley/cabot-search huggingface dataset:
A survey of intensive care medicine training for respiratory specialist trainees in the United Kingdom
Authors: Syed M.H. Kazmi, Adeel Sahal, Rizwan Ahmed, M.J. Naveed, Lisa Davies, Robert Parker
Journal: European Respiratory Journal (2011)

Introduction: The UK respiratory medicine curriculum requires trainees to spend a minimum of 60 working days in intensive care medicine (ICM) [1]. This should be a dedicated attachment, preferably with ICM on call rather than acute medical duties.

A previous British Thoracic Society survey found that 10% of trainees had inadequate exposure to ICM and just 59% participated in the ICM on call rota [2].

Aims: To assess availability of ICM training, experience offered, quality of placement and trainee satisfaction across UK.

Method: Online questionnaires were sent to respiratory trainees in 4 UK training regions.

Results: The response rate was 56% (121/214). 3 months ICM training was available to all trainees, 47% (57/121) had completed ICM training of whom 16% received 6 months experience, 61% had participated in ICM on-call rotas with just 14% having acute medical on-call commitments. 88% achieved ICM curriculum objectives and 91% were satisfied with their placement. 23% of trainees wished to gain further ICM accreditation.

Conclusions: The availability of dedicated ICM placements has improved. The majority of trainees are able to meet curriculum objectives and are satisfied with their rotation. ICM on call commitment remains regrettably low, as out of hours care provides invaluable learning opportunity. Supporting trainees wishing to pursue a career in ICM will provide challenges to training programmes and workforce planning. We plan to expand this survey across UK to assess ICM training at a national level.

References: 

*   1. Speciality training curriculum for respiratory medicine 2007, JRCPTB.

*   2. Pattani H et al. Critical care as part of respiratory medicine training in the UK. Thorax 2006;61:1013.
Abstract 17491: Impact of Prehospital Administration of Antithrombotic Medications on Infarct-related Artery Patency in ST-elevation Myocardial Infarction: Results from the FAST-MI 2010 Registry
Authors: Etienne Puymirat, Yves Cottin, Gilles Montalescot, Eric Bonnefoy-Cudraz, Laurent Bonello, Loic Belle, Herve Le Breton, Ph Gabriel Steg, Jean Ferrieres, Tabassome Simon, Nicolas Danchin
Journal: Circulation (2014)

Rationale: The role of prehospital (PH) antithrombotic medications in STEMI is debated; real-world data are scarce. We used the FAST-MI 2010 data to assess TIMI flow before PCI, in relation to PH administration of antithrombotic medications and timing of coronary angiography. Methods and Results: FAST-MI is a nationwide French registry including consecutive AMI patients in 213 centers in November 2010. Of 2364 STEMI patients, 2035 had TIMI flow assessed pre-intervention (1458 primary PCI, 289 lysis, 288 no reperfusion therapy); 41% had TIMI flow 2/3. PH use of antithrombotics was: ASA 52%, clopidogrel 37%, prasugrel 7%, GP IIb-IIIa 4%; unfractionated heparin 24%, other anticoagulants 22%. Mean age, risk factors, medical history, GRACE score, location of infarct did not differ between patients with TIMI 2/3 vs 0/1 flow. IRA patency was higher with time from onset to call less than 120min (45% vs 35%, P&lt;0.001), and time from ECG to angio over 120 min (48% vs 33%,P&lt;0.001). In the whole population, % TIMI flow 2/3 was higher with PH lytics (78% vs 42%, P&lt;0.001) and differed according to PH antithrombotic use: no antiplatelet 42%, ASA alone 39%, clopidogrel 53.5%, prasugrel 58%, GPIIb-IIIa 40%; no anticoagulant 43%, UFH 46%, other anticoagulants 55%. Lysis (OR 5.67, 3.67-8.77), and combination of dual antiplatelets and anticoagulants (OR 1.59, 1.20-2.12) were independent correlates of higher patency. In patients with primary PCI, individual medications were not significantly correlated with IRA patency. Combined dual antiplatelet and anticoagulants, however, was a significant correlate of higher TIMI2/3 flow (adjusted OR 1.43, 1.05-1.96), as were shorter duration from onset to call (OR 1.53, 1.13-2.08) and longer time from ECG to angio (OR upper tertile vs lower tertile 1.65, 1.14-2.37). ST-segment resolution, reinfarction, stent thrombosis and TIMI major bleeding did not differ according to PH antithrombotics. Conclusion: In the whole population of STEMI patients (including lytic-treated patients), as in patients with primary PCI, PH administration of combined antiplatelet and anticoagulants is associated with increased IRA patency. In contrast, none of the individual antithrombotic medications significantly improved IRA patency.
The predictive value of HER2 and p53 on outcomes after paclitaxel chemotherapy for metastatic breast cancer: Results from CALGB 9342
Authors: N. U. Lin, G. Broadwater, L. G. Dressler, S. Schnitt, J. Lara, I. Bleiweiss, T. Ngo, A. Miron, E. Winer, L. N. Harris
Journal: Journal of Clinical Oncology (2004)

9562 Background: CALGB 9342 was designed to test the efficacy of three dose levels of paclitaxel in women with advanced breast cancer. We present the results of a correlative study examining the relationship of HER2 and p53 to outcome. Methods: Women with stage IV breast cancer were randomized to paclitaxel 175 mg/m2, paclitaxel 210 mg/m2, or paclitaxel 250 mg/m2, given i.v. every 3 weeks. Tumor tissue was collected from 175 of 474 women enrolled. HER2 immunohistochemistry (IHC) using the CB11 antibody and DAKO HercepTest. was informative in 165 cases; HER2 by FISH (Vysis Pathvysion.) was informative in 114 cases; p53 IHC using the D07 antibody was informative in 150 cases. p53 was sequenced in 160 cases. Because response rates were comparable across the three dose levels, they were combined for the analysis of outcomes by biomarker. Results: Prognostic variables, response rates, time-to-progression (TTP), and overall survival (OS) did not differ between the subset of patients (n=165) with biomarker scores and the remainder of the 9342 population, except for a shorter disease-free interval (19 mo vs 31 mo, p=0.0003). HER2 status by FISH was highly correlated to IHC with CB11 (κ=0.91). The sensitivity of DAKO for CB11 and FISH was high (97–100%); the specificity was lower (85%). HER2 as measured by CB11 showed a trend towards lower response (p=0.06) and shorter TTP (2.34 mo vs 4.15 mo, p=0.067). There was no relationship between HER2 status and OS. p53 IHC was positive in 38% of tumors; p53 mutations were present in 60.6% of tumors. 20% of mutations were found in exon 5 (13.1% of tumors). p53 overexpression by IHC was predictive of worse OS (11.5 mo vs. 14.4 mo, p=0.0002), and there was a trend towards shorter TTP (3.95 mos vs 4.38 mo, p=0.06). The presence of a p53 mutation did not predict response, TTP, or OS. Conclusions: Overexpression of HER2 by FISH and Herceptest did not predict response to paclitaxel. There was a trend toward a lower response and TTP in patients with overexpression of HER2 by CB11. Mutant p53 by IHC correlated with overall survival. Further characterization of the consequences of specific p53 mutations is under way. No significant financial relationships to disclose.
Survival for nasopharyngeal cancer with distant metastatic disease at presentation
Authors: M. A. Dandona, D. Morgensztern, V. Auethavekiat, D. Adkins, W. Thorstad, B. Nussenbaum, Q. Zhang, D. I. Kuperman
Journal: Journal of Clinical Oncology (2009)

e17004 Background: Nasopharyngeal carcinoma (NPC) is a unique form of head and neck cancer, with distinct epidemiology and sensitivity to chemotherapy (CT) and radiation (RT). Long-term survival has been reported for selected patients with metastatic disease. However, given its rarity in the Western Hemisphere, data is limited to case series. We used the Surveillance Epidemiology and End Results (SEER) database to determine factors that correlated with prolonged survival in patients with metastatic NPC at presentation. Methods: The SEER database was searched for patients with NPC who have distant metastatic disease at presentation, defined as extent of disease (EOD10) code 85, aged 20 or older, diagnosed between 1988 and 2003. Survival probability was estimated by Kaplan-Meier method and covariate effects were examined using log-rank tests. Parameters evaluated include age, gender, race, tumor grade, and use of RT. Results: Among the 2,610 patients with NPC in SEER, 177 (6.7%) were identified with distant metastatic disease at presentation. Five patients were excluded from subsequent analysis because RT data was not available. RT was administered to 114 patients (66.3%). Median survival was 9 months (95%CI: 7–13 months) and 5-year overall survival (OS) of 20% (95%CI: 14–26%). Outcomes were significantly improved for patients treated with RT compared to those not receiving it, with the 5-year OS rates of 28% versus 3% (p &lt; 0.0001) respectively. Other factors associated with improved survival included non-white race (p = 0.01) and younger age (p &lt; 0.0001). Conclusions: Although SEER lacks information on performance status, site of metastases, and CT use, our data shows that selected patients with metastatic NPC may achieve prolonged survival, particularly if RT is used. It is unclear whether RT is a determinant of better OS or an epiphenomenon. No significant financial relationships to disclose.
SPARC microenvironment signature (SMS) analysis of a phase II trial of neoadjuvant gemcitabine (G), epirubicin (E), and <i>nab</i>-paclitaxel (<i>nab</i>-P) in locally advanced breast cancer (LABC).
Authors: D. A. Yardley, B. R. Daniel, R. C. Inhorn, E. R. Vazquez, V. N. Trieu, K. Motamed, L. Hwang, H. S. Rugo, N. Desai
Journal: Journal of Clinical Oncology (2010)

10574 Background: SPARC, an albumin-binding protein, may mediate intratumoral accumulation of nab-P and is associated with poor prognosis in many tumors. In tumor microenvironments (M), SPARC is associated with tumor and stromal components. Previous studies examined SPARC in tumor cells and/or fibroblasts. It is unclear if other M components expressing SPARC (inflammatory cells, cellular stroma/matrix, blood vessels, nerve tissue, etc) are of prognostic significance. We examined the impact of a SPARC signature comprised of all SPARC tumor M components, alone and with known risk factors (triple negative [TN], ER-, or PR-), in a LABC trial. Methods: 123 LABC pts were treated with 6 cycles of G 2,000 mg/m2, E 50 mg/m2, and nab-P 175 mg/m2 q14 days followed by surgery. Post op pts received 4 cycles G 2,000 mg/m2 and nab-P 220 mg/m2 q14 days. SPARC IHC component scoring was performed in pretreatment tumor samples. An array analysis program determined the SMS. PFS was correlated with SMS using standard statistical methods. Results: SPARC IHC data were available for 76 pts, with 18/76 (24%) having progression or death. Unique SMS distinguished a low risk (LR) group (n = 35, PFS 81% at 24 mos) from a high risk (HR) group (n = 41, PFS 65% at 24 mos), p = 0.02. There were 3 pCR in the LR group and 5 pCR in the HR group (p = ns). TN, ER-, and PR- were similar between the 2 groups. The prognostic power of SPARC SMS was further improved by combining TN, ER-, PR-: PFS at 24 mos was 93% (n = 24, non-TN, SPARC LR), 93% (n = 21, ER+, SPARC LR), and 92% (n = 20, PR+, SPARC LR) vs 33% (n = 15, TN, SPARC HR), 40% (n = 20, ER-, SPARC HR), and 51% (n = 22, PR-, SPARC HR), p < 0.0001, p = 0.0001, p = 0.002, respectively. Median PFS decreased from 22.7, 30.0, and 22.7 mos for TN, ER-, PR- to 19.5, 24.2, and 14.3 mos when HR SMS was combined with TN, ER-, and PR-. Conclusions: SPARC Microenvironment Signatures (SMS) alone could discriminate between LR and HR groups with respect to PFS in pts with LABC treated with combination chemotherapy. This discrimination was further enhanced when combined with other known risk factors (TN, ER-, and PR-). The clinical application of SMS will be explored in ongoing randomized trials. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abraxis BioScience Abraxis BioScience Abraxis BioScience Lilly Abraxis BioScience
Abstract 15834: Stimulation Within the Scar is Superior to Right Ventricular Stimulation for the Induction of Clinical Arrhythmias in Patients with Post-Infarction Ventricular Tachycardia
Authors: Pasquale Santangeli, Luigi Di Biase, John David Burkhardt, Javier Sanchez, Rodney Horton, Rong Bai, Sanghamitra Mohanty, Agnes Pump, Rachel Xue, Justin Price, Chintan Trivedi, Salwa Beheiry, Richard Hongo, Martina Zucchetti, Corrado Carbucicchio, Antonio Dello Russo, Michela Casella, Claudio Tondo, Andrea Natale
Journal: Circulation (2012)

Introduction. Programmed ventricular stimulation from the right ventricle (RV) is the most commonly adopted induction protocol in patients with post-infarction ventricular tachycardia (VT). Lack of...
Romidepsin and Azacitidine Synergize in their Epigenetic Modulatory Effects to Induce Apoptosis in CTCL
Authors: Sima Rozati, Phil F. Cheng, Daniel S. Widmer, Kazuyasu Fujii, Mitchell P. Levesque, Reinhard Dummer
Journal: Clinical Cancer Research (2015)

Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of malignancies that despite available therapies commonly relapse. The emergence of combination epigenetic therapies in other hematologic malignancies have made investigation of such combinations in CTCL a priority. Here, we explore the synergistic antiproliferative effects of romidepsin, an HDAC inhibitor, and azacitidine, a demethylating agent, combination in CTCL.The growth inhibition under combination treatment and single agent was explored by the MTT cell viability assay and the Annexin V/propidium iodide (PI) apoptosis assay in different CTCL cell lines and tumor cells derived from Sézary syndrome patients. Quantitative analysis of a dose-effect relationship of romidepsin and azacitidine was done by the CompuSyn software. Investigation of mechanism of action was performed by flow cytometry, immunoblotting, qRT-PCR arrays, and chromatin immunoprecipitation. Global CpG methylation sequencing was utilized to study genome methylation alteration under the treatment modalities.The combination of romidepsin and azacitidine exerts synergistic antiproliferative effects and induction of apoptosis involving activation of the caspase cascade in CTCL cell lines and tumor cells derived from Sézary syndrome patients. We identified genes that were selectively induced by the combination treatment, such as the tumor suppressor geneRhoBthat is linked to enhanced histone acetylation at its promoter region in parallel with pronounced expression of p21. Global CpG methylation sequencing in a CTCL cell line and tumor cells demonstrated a subset of genes with a unique change in methylation profile in the combination treatment.The synergistic antiproliferative effects of romidepsin and azacitidine combination treatment justify further exploration in clinical trials for advanced CTCL.
Metastatic prostate cancer at diagnosis: Clinical presentation in the post-PSA era
Authors: R. J. Dickstein, J. E. Kreshover, J. C. Milose, G. A. Gignac
Journal: Journal of Clinical Oncology (2009)

e16159 Background: Prostate cancer (CaP) has varying biologic behavior. Prostate-specific antigen (PSA) screening dramatically diminished the presentation of patients (pts) with metastatic CaP from 5.6% in 1990 to 1.5% in 2003 as evidenced by the CaPSURE database. Our institution has a uniquely diverse demographic and socioeconomic population and we sought to identify pts with metastatic CaP at diagnosis to evaluate contributing factors. Methods: We retrospectively reviewed all pts charts diagnosed with CaP as identified by ICD-9 code (185) between January 1 st 2003 and October 31 st 2008 after cross referencing with the term metastatic. Pts progressing from localized disease were excluded. Data was collected on pts initially presenting with metastases. Results: Sixty-one pts presented initially with metastatic CaP at a median age of 68 years old (45 –90) and a median PSA of 92 ng/mL (4.4 –3463). Digital rectal exam was normal in 8 pts (13%) and abnormal in 43 (70%). Median body mass index was 27.2 (16.9 –46.7) with 26 pts (42%) being smokers and 20 (32%) non-smokers. Thirty-six pts (59%) had a Charlson Comorbidity Index score of 0, 10 (16%) a score of 1, 10 (16%) a score of 2, and 5 (8%) a score of ≥ 3. Fifteen pts (24%) were Caucasian, 42 (68%) black [24 (39%) African American, 10 (16%) Caribbean, 8 (13%) African], 1 (1%) Hispanic, 1 (1%) Asian, 1 (1%) Albanian, and 1 (1%) Indian. Presenting symptoms were comprised of 32 pts (52%) with lower urinary tract symptoms including hematuria, urinary retention, and hydronephrosis, 21 (34%) with bone pain, 3 (4%) with neurologic deficits, and 17 (27%) were asymptomatic. Forty-seven pts (77%) underwent prostate biopsy of which 33 (70%) had high grade (Gleason ≥ 8) tumor. Conclusions: CaP initially presenting as metastatic disease is a rare event in the post-PSA era, but may result from lacking primary health care screening, poor patient compliance, or inherent predisposing factors of tumor biology. Our analysis identifies a predominantly non-Caucasian population of patients, contrasting the CaPSURE database, who are otherwise healthy. We plan on performing comprehensive analyses on all patients with metastatic CaP at Boston Medical Center. No significant financial relationships to disclose.
Brain training games help older adults perform essential tasks, study finds
Authors: Anne Gulland
Journal: BMJ (2015)

Online “brain training” games can improve the cognitive skills of older adults and help them perform day to day tasks such as shopping and managing finances, a study has found.1

Researchers at the Institute of Psychiatry, Psychology and Neuroscience at King’s College London found that playing a daily 10 minute game challenging reasoning and memory skills could benefit for older people.

The double blinded study recruited 6742 adults over the age of 50—some through a BBC television programme, Bang Goes the Theory —and were split into three groups. One group of 2557 participants played games testing problem solving and reasoning, and a second …
Biometric Findings on Cardiac Neurosis
Authors: H. Mayer, Brigitte Stanek, P. Hahn
Journal: Psychotherapy and Psychosomatics (1973)

The introduction of biometric procedures in the examination of psychosomatic illnesses requires an exact analysis of the available parameters. In cardiac neurosis, those characteristics must be emphasized from three points of view: psychoanalysis, test psychology and clinical physiology. Continuous ECG and circulatory measurements were carried out in both upright and tilted positions as a basic test. The results were compared with the findings measured during the psychoanalytical interview. In patients suffering from cardiac neuroses, ST- and T-changes as well as extrasystoles and orthostatic intolerances could be found. These patients also produced characteristic patterns of heart rate.
lymphadenectomy for liver tumors: A safe procedure in a tertiary center which improves the staging of the disease
Authors: M. Ravaioli, G. Ercolani, G. Grazi, M. Cescon, G. Varotti, M. Del Gaudio, G. Vetrone, M. Zanello, F. Tuci, A. Pinna
Journal: Journal of Clinical Oncology (2006)

3622 Background: the role of regional lymphadenectomy for liver metastases and primary liver tumors, but not extra-hepatic bile duct cancer, is debated. Methods: from April ’99 to December ’04, we prospectively evaluated 142 patients treated with liver resections and with the following pre-operative diagnosis: 63 (44.4%) colorectal metastases (M-CR), 48 (33.8%) hepatocellular carcinoma (HCC), 16 (11.3%) non-colorectal metastases (M-NCR) and 15 (10.6%) intra-hepatic cholangiocellular carcinoma (CCC). The regional lymphadenectomy of the hepato-duodenal ligament and of the common hepatic artery was performed in all cases. The incidence and the influence on survival of lymph node metastases were analyzed. Results: 42 “wedge” resection (29.6%), 55 segmentectomies (38.7%) and 45 major hepatectomies (31.7%) were performed. The mean operative time was 292±131 minutes and 96 cases (67.6%) had no blood transfusions during the procedures. Operative mortality (within 30 days) was 3.5%, 48 cases (33.8%) developed post-operative complications and the most common was ascites. The mean hospital stay was 9±5 days. The mean number of nodes (LN) removed were 6.5±5 (range 6–30) and 63 LN (6.5%) had micro-metastases. The incidence of lymph node metastases (LN+) according to the pre-operative diagnosis was: 15.9% M-CR, 4.2% HCC, 37.5% M-NCR and 40% CCC. The mean follow-up was 37.4±22.6 months, 107 patients (75.4%) are alive and 44 (31.7%) developed tumor recurrence, which was more frequent in LN+ (54.2% vs. 27%, p&lt;0.05). The 1-and 3-years patient survival was significantly affected by lymph node metastases: 92% and 85% LN- vs. 79% and 64% LN+, p&lt;0.05. Conclusions: the regional lymphadenectomy for liver tumors is a safe procedure in tertiary referred centers. The presence of lymph node metastases was an important prognostic factor, which should be evaluated to improve the treatment strategies. No significant financial relationships to disclose.
Oral-tolerization Prevents Immune Responses and Improves Transgene Persistence Following Gene Transfer Mediated by Adeno-associated Viral Vector
Authors: Romain Hardet, Benjamin Chevalier, Léa Dupaty, Yassine Naïmi, Gaëtan Riou, Laurent Drouot, Laetitia Jean, Anna Salvetti, Olivier Boyer, Sahil Adriouch
Journal: Molecular Therapy (2015)

Gene therapy represents a feasible strategy to treat inherited monogenic diseases and intramuscular (i.m.) injection of recombinant adeno-associated viral (AAV) vector is now recognized as a convenient and safe method of gene transfer. However, this approach is hampered by immune responses directed against the vector and against the transgenic protein. We used here to reproduce this situation a mouse model where robust immune responses are induced following injection of an AAV vector coding for an immunogenic transgenic protein. We show that prophylactic oral administration of the immunogenic protein before AAV-mediated gene transfer completely prevented antibody formation and cytotoxic CD8(+) T-cell response. Consistently, prophylactic oral-tolerization considerably improved long-term transgene persistence and expression. Mechanistically, inhibition of the cytotoxic immune response involved abortive proliferation of antigen-specific cytotoxic CD8(+) T cells, upregulation of the PD-1 immunoregulatory molecule, downregulation of the Bcl-2 antiapoptotic factor, and their deletion in the context of AAV-mediated gene transfer. Hence, gene therapy may represent an ideal situation where oral-tolerization can be adopted before or at the same time as vector injection to efficiently prevent deleterious immune responses directed against the transgenic protein.