tbuckley/cabot-search huggingface dataset:
Response to sunitinib malate (SM) in alveolar soft part sarcoma (ASPS)
Authors: S. Stacchiotti, E. Tamborini, R. Bertulli, C. Piovesan, A. Marrari, C. Morosi, F. Crippa, S. Pilotti, A. Gronchi, P. G. Casali
Journal: Journal of Clinical Oncology (2008)

10592 Background: ASPS is a rare soft tissue sarcoma, with high metastatic potential but indolent growth pattern and prolonged survival with metastatic disease. It is generally resistant to chemotherapy. ASPS has a characteristic translocation t (17-X) resulting in the fusion protein ASPS-TFE3, which is shared with one subtype of "pediatric" renal carcinoma. This fusion protein acts as aberrant transcription factor causing strong MET autophosphorylation and activation of downstream signaling in the presence of HGF. Moreover HGF has been reported as a potent stimulator of the vascular endothelial cell proliferation and capillary-tube organization. On the contrary, VEGFR and PDGFR do not seem to be activated in ASPS. SM (SU11248) is a known tyrosine-kinase inhibitor (rTKI) approved for treatment of GIST and renal cancer. No data have been reported about SM activity in ASPS or against MET. Since SM and SU5416, an rTKI shown to inhibit activation of HGF/MET in hepatocarcinoma, are chemically related with similar functional groups, the activity of SM in ASPS might be due to HGF/MET downsignaling switch off more than to VEGF/PDGF inhibition. Methods: Since July 2007, 2 patients (pts) with progressive widespread metastatic ASPS (Pt A: male, 27 yrs, PS1, 3 yrs from diagnosis - Pt B: male, 57 yrs, PS2, 7 yrs from diagnosis) have been treated with continuous SM 37.5 mg/day, on an individual use basis. Before starting SM, they both progressed under Interferon beta, anthracycline + ifosfamide (IF), high dose IF, gemcitabine + docetaxel, etoposide. Both pts are evaluable for response. Morphologically, both tumors showed typical organoid pattern and nuclear immunostaining for TFE3. Biochemical analysis was performed on cryopreserved material to assess MET status and its downstream signaling. 3 more pts are starting SM. Results: Both pts are still on treatment (5 and 4 mos). Treatment has been well tolerated (no G3–4 toxicity). After 3 months of treatment, both pts had RECIST PR, along with subjective improvement in breathing (Pt A) and pain (Pt B). Pt B also had a PET response after 2 months, confirmed after 4 months (PET not done in Pt A). Both primary tumors showed expression/activation of AKT, MAPK and S6K proteins. Assessment of MET status is ongoing. Conclusions: SM seems to have antitumor activity in ASPS. Results will be updated. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Oncology Pfizer Oncology
Effectiveness of Remote Patient Monitoring After Discharge of Hospitalized Patients With Heart Failure
Authors: Michael K. Ong, Patrick S. Romano, Sarah Edgington, Harriet U. Aronow, Andrew D. Auerbach, Jeanne T. Black, Teresa De Marco, Jose J. Escarce, Lorraine S. Evangelista, Barbara Hanna, Theodore G. Ganiats, Barry H. Greenberg, Sheldon Greenfield, Sherrie H. Kaplan, Asher Kimchi, Honghu Liu, Dawn Lombardo, Carol M. Mangione, Bahman Sadeghi, Banafsheh Sadeghi, Majid Sarrafzadeh, Kathleen Tong, Gregg C. Fonarow
Journal: JAMA Internal Medicine (2016)

It remains unclear whether telemonitoring approaches provide benefits for patients with heart failure (HF) after hospitalization.To evaluate the effectiveness of a care transition intervention using remote patient monitoring in reducing 180-day all-cause readmissions among a broad population of older adults hospitalized with HF.We randomized 1437 patients hospitalized for HF between October 12, 2011, and September 30, 2013, to the intervention arm (715 patients) or to the usual care arm (722 patients) of the Better Effectiveness After Transition-Heart Failure (BEAT-HF) study and observed them for 180 days. The dates of our study analysis were March 30, 2014, to October 1, 2015. The setting was 6 academic medical centers in California. Participants were hospitalized individuals 50 years or older who received active treatment for decompensated HF.The intervention combined health coaching telephone calls and telemonitoring. Telemonitoring used electronic equipment that collected daily information about blood pressure, heart rate, symptoms, and weight. Centralized registered nurses conducted telemonitoring reviews, protocolized actions, and telephone calls.The primary outcome was readmission for any cause within 180 days after discharge. Secondary outcomes were all-cause readmission within 30 days, all-cause mortality at 30 and 180 days, and quality of life at 30 and 180 days.Among 1437 participants, the median age was 73 years. Overall, 46.2% (664 of 1437) were female, and 22.0% (316 of 1437) were African American. The intervention and usual care groups did not differ significantly in readmissions for any cause 180 days after discharge, which occurred in 50.8% (363 of 715) and 49.2% (355 of 722) of patients, respectively (adjusted hazard ratio, 1.03; 95% CI, 0.88-1.20; P = .74). In secondary analyses, there were no significant differences in 30-day readmission or 180-day mortality, but there was a significant difference in 180-day quality of life between the intervention and usual care groups. No adverse events were reported.Among patients hospitalized for HF, combined health coaching telephone calls and telemonitoring did not reduce 180-day readmissions.clinicaltrials.gov Identifier: NCT01360203.
Raynaud's phenomenon in patients treated with cisplatin, vinblastine, and bleomycin for germ cell cancer: measurement of vasoconstrictor response to cold.
Authors: S W Hansen, N Olsen
Journal: Journal of Clinical Oncology (1989)

The prevalence of Raynaud's phenomenon (RP) was studied in patients treated with cisplatin, vinblastine, and bleomycin. Thirty-two patients with germ cell cancer were followed for a median of 78 months (range, 49 to 106 months). All had obtained complete remission during treatment; none had relapsed at last follow-up examination. All blood samples, including serum magnesium, were normal. The arterial vasoconstrictor response to cold in the finger was measured by cuff- and strain-gauge techniques at 30, 15, and 10 degrees C. Blood pressure (BP) was measured auscultatorily, using a 12-cm broad cuff on the ipsilateral upper arm. Fourteen patients (44%) had developed anamnestic RP, and all showed an exaggerated response to cold; arterial closure was provoked in nine patients. Eighteen patients (56%) were without finger symptoms. These patients had an exaggerated response to cold in comparison with controls, and in two patients, RP was provoked. None of the patients had an increased systolic pressure gradient from arm to finger when compared with a control group. Thus, an exaggerated cold response was found to be a prolonged vasospastic side effect not only in patients with RP, but also in patients without finger symptoms.
원저 : 만성 간질환에 대한 Diphenyl - dimethyl - dicarboxylate 의 안전성 및 효과
Authors: 김형식, 이수택, 김대곤, 안득수 ( Hyoung Sik kim), Soo Taek Lee, Dae Gon kim, Deuk Soo Ahn
Journal: Clinical and Molecular Hepatology (1996)

Background/Aims: The spectrum of clinical features of chronic liver disease bas wide range from asymptomatic cases to hepatic failure, The natural course and long-term prognosis of chronic liver disease also varies greately, and this diversity makes it diflicult to predict the clinical course of individual patient. The two majar approaches to the treatment of chronic liver disease are 1) directed toward the eradication of the virus and 2)designed to modulate cellular and humeral immunity. Progress has been made in the development of antiviral chernotherapeutic agents for hepatitis. But as yet no safe and reliably effective treatment or combination of treatrnents is available. In tkis study, we performed trial of diphenyl-dimethyl-dicarboxylate to evaluate the therapeutic effect and safety of it. Methods: The ciinical trials of DDB(complex capsule of diphenyl dimethyl dicarboxylate 7.5mg and polysorbate 80 1,5mg and polyethylene glycol 6000 66mg) were carried out in 30 patients with chronic liver disease for 6 months. All patients had abnormal liver function test ouer a period of 6 months. Results:In selected groups mean serum aspartate aminotransferase and alanine aminotrans- ferase dropped from pretreatment level of' 115.9+ 74.1 IU/L and 201.6+ 173.0 1U/L to posttreatment level of46.6+ 21.6 UU/L and 28.7- 15.4IU/L, respectively(p<0.01). There was no significant hernatological and biochemical change after administration of DDB. Untoward side effects were easily controlled by discontinuing the drugs, Conclusions:Administration of DDB(for 6 months) appears to be effective for decrement of transaminase level and safe for the treatment of patients with chronic liver disease.
Fatigue: A symptom of asthma in children?
Authors: Ghislaine van der Zande, W.B. Vreede, H. Heneweer
Journal: European Respiratory Journal (2012)

Introduction: In children with symptoms of fatigue asthma is frequently diagnosed. However fatigue is not mentioned as a symptom in definitions of asthma in children.

Aim of the study: Exploration of the consistency between the symptom fatigue and the diagnosis asthma in children. Consequently asthma can be diagnosed earlier and faster and the care for these patients will improve.

Method: A retrospective analysis of the files of 440 patients between the age of 5 and 18 years with the diagnose Asthma de Novo between May 15th 2009 and May 15th 2011. The data of patient characteristics, pulmonary function tests and symptoms were analyzed.

View this table:

Patients characteristics





Results: There was an uneven distribution between boys (58%) and girls. The boys had a average age of 9.9 years, the girls of 11.0 years. In both groups the various pulmonary function parameters were abnormal. 52% of the patients complained of fatigue. The distribution of symptoms in boys and girls is equally.

![Figure][1] 



Conclusion: Fatigue is the most frequently mentioned symptom of asthma in children, after complaints during exercise, dyspnea and coughing. Fatigue is not a specific symptom. The results can therefore only be an assumption. It is recommended to involve asthma in the differential diagnosis of unexplained fatigue in children.

 [1]: pending:yes
Purifying Selection on Exonic Splice Enhancers in Intronless Genes
Authors: Rosina Savisaar, Laurence D. Hurst
Journal: Molecular Biology and Evolution (2016)

Exonic splice enhancers (ESEs) are short nucleotide motifs, enriched near exon ends, that enhance the recognition of the splice site and thus promote splicing. Are intronless genes under selection to avoid these motifs so as not to attract the splicing machinery to an mRNA that should not be spliced, thereby preventing the production of an aberrant transcript? Consistent with this possibility, we find that ESEs in putative recent retrocopies are at a higher density and evolving faster than those in other intronless genes, suggesting that they are being lost. Moreover, intronless genes are less dense in putative ESEs than intron-containing ones. However, this latter difference is likely due to the skewed base composition of intronless sequences, a skew that is in line with the general GC richness of few exon genes. Indeed, after controlling for such biases, we find that both intronless and intron-containing genes are denser in ESEs than expected by chance. Importantly, nucleotide-controlled analysis of evolutionary rates at synonymous sites in ESEs indicates that the ESEs in intronless genes are under purifying selection in both human and mouse. We conclude that on the loss of introns, some but not all, ESE motifs are lost, the remainder having functions beyond a role in splice promotion. These results have implications for the design of intronless transgenes and for understanding the causes of selection on synonymous sites.
Pomalidomide Plus Low-Dose Dexamethasone In Relapsed Or Refractory Multiple Myeloma (RRMM) With Deletion (del)17p and/Or Translocation t(4;14)
Authors: Xavier Leleu, Lionel Karlin, Margaret Macro, Cyrille Hulin, Laurent Garderet, Murielle Roussel, Bertrand Arnulf, Brigitte Pegourie, Brigitte Kolb, Anne-Marie Stoppa, Sabine Brechiniac, Mauricette Michallet, Gerald Marit, Claire Mathiot, Anne Banos, Laurence Lacotte, Mourad Tiab, Mamoun Dib, Jean-Gabriel Fuzibet, Marie-Odile Petillon, Philippe Rodon, Marc Wetterwald, Bruno Royer, Laurence Legros, Lotfi Benboubker, Olivier Decaux, Denis Caillot, Martine Escoffre-Barbe, Jean Paul Fermand, Philippe Moreau, Michel Attal, Hervé Avet-Loiseau, Thierry Facon
Journal: Blood (2013)
Phylogenetic relationships of reverse transcriptase and RNase H sequences and aspects of genome structure in the gypsy group of retrotransposons.
Authors: M S Springer, R J Britten
Journal: Molecular Biology and Evolution (1993)

The gypsy group of long-terminal-repeat retrotransposons contains elements having the same order of enzyme domains in the pol gene as do retroviruses. Elements in the gypsy group are now known from yeast, filamentous fungi, plants, insects, and echinoids. Reverse transcriptase and RNase H amino acid sequences from elements in the gypsy group--including the recently described SURL elements, TED, Cft1, and Ulysses,--were aligned and analyzed by using parsimony and bootstrapping methods, with plant caulimoviruses and/or retroviruses as outgroups. Clades supported at the 95% level after bootstrapping include (1) 17.6 with 297 and (2) all of the SURL elements together. Other likely relationships supported at lower bootstrap confidence intervals include (1) SURL elements with mag, (2) 17.6 and 297 with TED, and this collective group with 412 and gypsy, (3) Tf1 with Cft1, (4) IFG7 with Del, and (5) all of the retrotransposons in the gypsy group together, to the exclusion of Ty3. In contrast with an earlier analysis, our results place mag within the gypsy group rather than outside of a cluster that contains gypsy group retrotransposons and plant caulimoviruses. Several features of retrotransposon genomes provide further support for some of the aforementioned relationships. The union of SURL elements with mag is supported by the presence of two RNA binding sites in the nucleocapsid protein. Location of the tRNA primer binding site and the presence of a long open reading frame 3' to the pol gene support the 17.6-297-TED-412-gypsy cluster.
The Shape of the Heart
Authors: Arpan K Banerjee
Journal: BMJ (2001)

Pierre Vinken 

Elsevier, £12.82, pp 206

ISBN 0 444 82987 3

Rating: ![Graphic][1] ![Graphic][2] ![Graphic][3] 

Have you ever wondered why the iconographic representation of the heart differs from its true anatomical shape? This question has intrigued Dr Pierre Vinken, a former neurosurgeon turned publisher, who explores this intellectual conundrum in this historical monograph.

In 1962 the art historian Erwin Panofsky was similarly perplexed. He noted that the valentine heart shape has been used since prehistoric times and was seen in Palaeolithic cave paintings in Spain. …

 [1]: /embed/inline-graphic-1.gif
 [2]: /embed/inline-graphic-2.gif
 [3]: /embed/inline-graphic-3.gif
Response to Dr Forestier's eLetter on EULAR recommendations for the non-pharmacological core management of hip and knee osteoarthritis
Authors: T P Vliet Vlieland, L Fernandes, J W Bijlsma, K B Hagen
Journal: Annals of the Rheumatic Diseases (2013)

Dear Editor,

We thank Forestier and Erol for their response on our paper on Eular recommendations for the non-pharmacological core management of hip and knee osteoarthritis (OA). We agree that balneotherapy is a relevant non-pharmacological intervention in hip and knee OA and has been properly evaluated by means of randomised clinical trials, with the evidence summarised in systematic reviews. The topics to be included in the recommendations …
Prognostic significance of CD44s expression in bile duct carcinomas
Authors: K. Lee, Y. Shim, S. Lee, M. Cho, Y. Mun, C. Seong, S. Lee
Journal: Journal of Clinical Oncology (2006)

14071 Background: CD44 is a surface glycoprotein and has a key role for surface hyaluronan receptor, which is associated with adhesion and metastasis in many solid tumors. There are CD44 standard isoform (CD44s) and ten variant isoforms (CD44v1–10). CD44s and CD44 variant 6 (CD44v6) were evaluated to clarify the applicable prognostic factor in patients with bile duct carcinomas. Methods: A retrospective study was performed in bile duct carcinomas. Immunohistochemical stain was done with primary antibodies for CD44 (Novocastra, Newcastle upon Tyne, UK) and CD44v6 (Novocastra) using automated machine (Vision Biosystems, Mount Waverley, VIC, Australia) and bond polymer detection system with counterstain (Vision Biosystems) in paraffin embedded tissues. The extent of staining categorized as 0% (none), &lt;10% (weak), 10%-50% (moderate), and &gt;50% (strong). Clinical characteristics including age, sex, stage, grade and overall survival were reviewed. Results: Ninety six patients (M:F=35:61) were evaluated and the median age of these patients was 64 years old (37∼86). The rate of overexpression (&gt;10%) of CD44s was 50% and the rate of CD44v6 expression was 16.9%. With median 34.2 months of follow up, the overall survival of total 96 patients was 12.2 months. The Cox proportional hazards test identified CD44s overexpression. (HR:2.379, 95% CI:1.195–4.736, p=0.014) and the stage as prognostic factors. But the expression of CD44v6 (weak vs. moderate to strong, HR:3.983, 95%CI:0.295–1.588, p=0.377) showed no prognostic significance on overall survival. Conclusion: CD44s overexpression can be a poor prognostic marker in bile duct carcinomas. And there is a potential to apply postoperative investigational or aggressive therapy in this poor prognostic group. No significant financial relationships to disclose.
Abstract 15975: Atrial Fibrillation Triggers From Non-PV, Non-SVC Foci: Assessment of Incidence, Characteristics and Efficacy of Catheter Ablation in a Single Center, High Volume Series
Authors: Kiyoshi Otomo, Kaname Takizawa, Naoto Inoue, Taiichiro Meguro
Journal: Circulation (2014)

Backgrounds: The electrical isolation of the thoracic veins to eliminate triggers of atrial fibrillation (AF) is the mainstay of catheter ablation (CA) for AF. AF is sometimes triggered by repetitive firings from the non-PV, non-SVC (nPVnSVC) foci, and their characteristics have not been fully elucidated. Purposes: To elucidate the incidence, characteristics and efficacy of CA of the nPVnSVC foci in AF patients (pts). Methods: Consecutive 1491 pts who received CA for AF (1080 males, age: 64±10 years, paroxysmal: 995, non-paroxysmal: 496) were included in this study. In index procedures, PV and SVC isolation were performed in all pts without subsequent provocation of nPVnSVC triggers. In repeat procedures, high dose isoproterenol (up to 400μg/hr) and boluses of adenosine triphosphate were given to provoke AF initiation by nPVnSVC triggers and focal ablation of all AF triggers was performed. Results: Among 2097 procedures in all 1491 pts, 58 AF triggers from nPVnSVC foci were provoked in 55 pts (3.7%; 30 paroxysmal and 25 non-paroxysmal AF pts) during 57 procedures (12 index and 45 repeat procedures). The pts with nPVnSVC triggers were significantly more likely to be females (42 vs 28%; P=0.03). The trigger foci were localized in the RA (20 foci; CS os in 8, crista terminalis in 7, IVC os in 3 and tricuspid annulus in 2), LA (24 foci; anterior (6), inferior (3) and posterior wall (3), roof in 3, mitral annulus in 3, Marshall vein in 5 and appendage in 1) and septum (14 foci; left (7) and right side (2) of fossa ovalis, high right septum in 4 and non-coronary cusp of the aortic sinus in 1). All AF triggers were eliminated in 46 pts (84%), while in the others they were not. During follow-up after the last procedure (284±218 days), recurrence-free survival was similar in those with and without nPVnSVC triggers (91 vs 95%; P=0.05), although mean procedure number was significantly larger in those with nPVnSVC triggers than in those without (2.1±0.6 vs 1.4±0.6 times/pt; P&lt;0.0001). Conclusions: The nPVnSVC triggers were observed in 3.7% of all AF pts. The location of the triggers could be clustered to the several anatomical regions. Successful elimination of nPVnSVC triggers contributed to high post-ablation recurrence-free survival that was similar to that in those without nPVnSVC triggers.
Phase I dose-escalation study of thoracic radiotherapy in combination with gefitinib in patients with IIIB/IV non-small cell lung cancer (NCT00497250)
Authors: M. Fan, L. Xie, X. Xu, G. Zhang, J. Chen, X. Fu, X. Zhou, W. Li, G. Jiang
Journal: Journal of Clinical Oncology (2009)

e14581 Background: Cinical studies have confirmed that gefitinib, an EGFR-TKI, is effective for some advanced NSCLC patients. Patients with Asian ethnicity are reported to have a higher response rate with gefitinib monotherapy. However, a higher incidence of interstitial lung disease, sometimes lethal, is also found. The combination of gefitinib and radiotherapy has been observed to have a synergistic, anti-proliferative effect against NSCLC in vitro. This phase I study assessed the safety, clinical feasibility and optimally tolerated regimen (OTR) of this combination in patients with pretreated locally advanced or metastatic (IIIB/IV) NSCLC. Methods: Patients with stage IIIB or selected stage IV, failure of platinum-based chemotherapy regimen NSCLC were eligible. Four Cohorts of eight patients each were planned to be treated with escalating doses from 54 to 60 Gy of conformal or intensity- modulated radiotherapy (2Gy/Fx) administered in combination with gefitinib 250mg daily during RT and 60 days after the completion of RT to determine the OTR. Results: Since June 2007, 2 cohorts, a total of 16 patients, were enrolled and treated: 8 stage IIIB and 8 stage IV; 2 squamous-cell carcinoma and 14 adenocarcinoma; 8 smokers and 8 nonsmokers. Prior-chemotherapy regimen was consisted of NP, GP and TP for a median of 3.5 cycles (range, 1–5). Median follow-up time was seven months. Mean progression-free survival time was 5.2 months (median, 3.9; range, 1.7–12.3). Overall, adverse events were mild to moderate in severity. The most frequent grade 2 events included pneumonitis (31%) and dysphagia (19%). There were one treatment-related grade 3 event, which was nausea, and no grade 4 events. Most of the failure patterns were out-of-field (11/13) and the most common distant metastasis organ was the lungs. Three patients are progression-free to date. Conclusions: Thoracic radiotherapy up to 56 Gy concurrent with gefitinib 250 mg daily was well tolerated and clinically active in this group of pretreated Chinese NSCLC patients, including nonsmokers with adenocarcinoma. Accrual is continuing. Sponsorship: This work was partly supported by Program for New Century Excellent Talents in University (NCET), Ministry of Education. No significant financial relationships to disclose.