tbuckley/cabot-search huggingface dataset:
Pegylated liposomal doxorubicin plus temozolamide in the salvage treatment of brain metastases: The update
Authors: M. Caraglia, R. Addeo, R. Costanzo, L. Montella, V. Faiola, E. Capasso, S. Del Prete
Journal: Journal of Clinical Oncology (2004)

1576 Background: It has been recently demonstrated that pegylated liposomal doxorubicin (Caelyx, PLD) can cross the brain-blood barrier with a consequent accumulation in primitive and secondary brain tumours. Moreover, temozolamide (TMZ) is a new imidazo-tetrazine that accumulates in brain tissue and is used alone or in combination with radiotherapy in the treatment of primary and secondary brain tumours. The two drugs have been already used in combination in a phase I cinical study in the treatment of advanced solid tumours. Methods: We have evaluated the feasibility of the concomitant administration of TMZ and PLD in the treatment of brain mestastases and a preliminary evaluation of the activity was also performed. We have treated 12 consecutive patients (7 F and 5 M, mean age: 62.83 ± 13.9 yrs; median age: 65.5 yrs) affected by brain metastases from different solid tumours (4 breast adenocarcinoma, 6 non small lung cancer, 1 melanoma, 1 ovarian cancer) with TMZ 1000 mg/m2 fractionated in 5 days and PLD 40 mg/m2 day 1 every 28 days. Nine out of 12 pts. have received previous whole brain irradiation plus TMZ. Results: Thirty-four cycles were performed. Three grade II ad 8 grade I neutropenia (CTC), 2 grade II hand and foot syndrome, 8 grade I thrombocytopenia and 9 grade I alopecia were recorded. Nausea and vomiting or liver or renal toxicity were never observed in our series being the schedule well tolerated in all patients. Two CR and two PRs was recorded in the four patients with breast tumours, while a clinical benefit was achieved in other 4 patients (1 with melanoma and 3 with lung cancer). In the long-surviving pt. (overall survival, OS: 27+ months), who achieved CR, also a remission of a neoplastic pleural effusion was observed. Other 2 still alive pts. (breast and NSCLC, respectively), who achieved a PR and a SD, had an OS of 14 and 9 months, respectively. Conclusions: the schedule was a well tolerated treatment (also in elder pts.) and has suggested an encouraging activity in brain metastases from breast. No significant financial relationships to disclose.
An Experimental Study on the Causes of Cor Pulmonale
Authors: Akihiro Ando
Journal: Circulation (1965)

It is considered that cor pulmonale necessarily accompanies pulmonary hypertension, which is caused by the increase of pulmonary vascular resistance, as its occassion, and, as the factors of increasing pulmonary vascular resistance, the existence of some functional factors as well as some organic change in pulmonary blood vessel itself should be taken into consideration. Considerable numbers of experimental studies of acute cor pulmonale caused by disturbance of pulmonary blood vessel have been done, while chronic cor pulmonale caused by disturbance of the lungs coming from airway, which is most frequently seen in clinic, has not been studied very much. In order to find the occasion of cor pulmonale, caused by disturbance of the lungs coming from airway, the present writer produced in adult dogs the experimental pulmonary disturbances by infusing resin into their bronchi, and followed up the changes of circulatory dynamics, ventilatory function and others, in terms of the disturbance part and area as well as of time. And then, comparing these findings with pathological ones, he discusses about them here. Materials and Methods Applying the right cardiac catheterization by a modified Bing-Holt's method to this experiment on twenty-four adult dogs, circulatory dynamics, chiefly residual blood volume and, at the same time, ventilatory dynamics were measured and electrocardiogram was recorded as the pre-experimental values. Then, the dogs were divided into the following four experimental groups after infusing resin in the several areas of their bronchi. Group I : Those dogs, into whose bronchi controlling respectively the right second lobeareas of their lungs and the lowerparts of the left first lobes of their lungs the resin was infused. (the dogs infused in the bronchi controlling the 16% pulmonary area)
PTH-311 The significance of a positive lymph node at the circumferential resection margin in rectal cancer – does it reduce survival?
Authors: N Green, P Sarmah, G Langman, K Chandrakumaran, H Youssef
Journal: Gut (2015)

<h3>Introduction</h3> It is recognised that following rectal cancer resection, a threatened or involved circumferential resection margin (CRM) is associated with increased local recurrence rates. However the significance of a pathological positive lymph node (LN) threatening or involving the CRM remains unclear. The aim of this study was to investigate whether a CRM threatened with a positive lymph node was as significant as for a threatened margin with tumour. The effect of a positive margin on local recurrence, distant recurrence, overall survival and disease-free survival is examined. <h3>Method</h3> From April 2005 to July 2013, a prospectively collected database was used, from a single pathologist with a particular interest in rectal cancer. Data was collected on patients with a threatened or involved CRM, defined as cancer within 1mm of the margin. Data was collected on demographics, type of surgery, lymph node yield, the type of CRM involvement (LN/tumour), local and distant recurrence (LR and DR), overall survival (OS) and disease-free survival (DFS). <h3>Results</h3> From a total of 303 patients, complete data was available for 280 patients: 195male, 86 female; median age 69 (range 23–89). 90 patients had APR and 191 anterior resection. Median LN yield was 41 (range 9–122) 33/281 patients (11.7%) had a positive margin: 16 patients had tumour at the CRM, 13 patients had involved LN and 4 patients involved nerve or blood vessels. Median follow-up was 30 months (range 0–80). In patients with a positive CRM, LR occurred in 6/33 (18.1%) (1 from LN and 5 from tumour) and DR in 12/33 (36.3%) (5 from LN and 7 from tumour). In patients with negative CRM, LR was 17/248 (6.9%) and DR was 26/248 (10.5%). Kaplan Meier predicted 3 and 5-year OS for negative CRM was 84.6 and 75.1% vs. 74.1% and 49.4% for LN at CRM versus 37.5% and 20.0% for tumour at CRM. OS was significantly lower for tumour at CRM than negative CRM (p = 0.001) but no significant difference for LN at CRM (p = 0.209). Kaplan Meier predicted 3 and 5-year DFS for negative CRM was 76.4% and 65.3% vs. 53.8% and 43.1% for LN at CRM versus 25% and 18.8%for tumour at CRM. DFS was significantly lower for tumour at CRM than negative CRM (p = 0.001) but no significant difference for LN at CRM (p = 0.075). <h3>Conclusion</h3> A positive LN at the CRM is not associated with high rates of local recurrence (8%) but did result in distant recurrence in 38% patients. OS and DFS were worse for patients with a positive CRM due to tumour at the margin compared with patients with a negative CRM. However, despite a trend towards lower survival, having a positive LN at the CRM is not associated with significantly reduced OS or DFS. <h3>Disclosure of interest</h3> None Declared.
Anti Etanercept and anti SB4 antibodies detection: impact of the assay method
Authors: Francesca Meacci, Mariangela Manfredi, Maria Infantino, Valentina Grossi, Maurizio Benucci
Journal: Annals of the Rheumatic Diseases (2016)

Anti Etanercept and anti SB4 antibodies detection: impact of the assay methodWe would like to underline the fundamental role of the assay method used to detect anti-drug antibodies.3][4][5] This apparent discrepancy can be explained by the different technical findings of laboratory methods employed in the works.Emery et al employs electrochemiluminescence method (ECL), while most of the authors performed assays on ELISA or Radio Immuno Assay (RIA) platforms.The diagnostic performances of these methods are very dissimilar.ECL is known to have characteristics of excellent sensitivity, high drug tolerance, and minimal influence of sample matrix. 6urthermore, Emery et al's work serum samples were subjected to acid treatment before the analysis to increase the anti-drug antibodies recovery.RIA and ELISA methods have a lower sensitivity and are subjected to drug interference, even though an acid pretreatment of sample can be performed.However, they are much more widely employed worldwide, since they are more standardised and user-friendly than ECL.All these findings could justify the substantial difference in anti-ETN antibodies recovery by ECL, when compared with other methods.Interestingly, in the Emery et al's work, only 0.7% of patients had anti-SB4 antibodies.Since in the ECL method the tagged drug (ETN or SB4) is directly used in a single-step assay, 7 the capability of the assay to detect anti-ETN or anti-SB4 could be identical.Nevertheless, because of the great impact of such new results on clinical management, as also underlined by Moots et al, 8 it would be very interesting to study in depth the different immunogenicity of these two drugs found in the cited study.In particular, some more details on the confirmatory test results to evaluate the specificity of detected ADAs, would be clarifying.A very recently published report comparing the immunogenicity of ETN and biosimilar HD203, found ADAs in 8/147 patients taking HD203 and in 3/147 patients taking ETN. 9 So further studies are needed to better understand factors contributing to different immunogenicity of SB4 than ETN, with a bigger number of patients.
TCTAP A-090 Bioresorbable Vascular Scaffolds Implantation Technique Utilizing Invasive Imaging with Optical Coherence Tomography. Influence on Clinical Outcome
Authors: Ilgiz Gayfullovich Zagitov, Vladimir V. Plechev, Irina E. Nikolaeva, Igor V. Buzaev
Journal: Journal of the American College of Cardiology (2016)
Long Term Efficacy Of Iron Chelation Therapy With Deferasirox On Endocrine Function In Thalassemia Major
Authors: Maddalena Casale, Serena Citarella, Aldo Filosa, Elisa De Michele, Umberto Pugliese, Palmieri Francesco, Alfonso Ragozzino, Amendola Giovanni, Immacolata Tartaglione, Milena Della Rocca, Bruno Nobili, Perrotta Silverio
Journal: Blood (2013)
Do predictive scoring systems have any role in determining treatment strategy for colorectal liver metastases at the individual patient level?
Authors: H. Malik, G. Poston
Journal: Journal of Clinical Oncology (2009)

e15104 Background: the literature contains four prognostic scoring systems from large volume series predicting survival after resection for colorectal liver metastases. Our aim was to directly compare these systems in terms of accuracy in predicting survival, and evaluate the role of such systems in determining therapeutic strategies on intention to treat at the individual patient level. Methods: the original published data were reviewed and the median survivals plotted against each point in the scoring system. The best fit line was drawn and the resultant plots enabled calculation of slope of the linear regression line and the square of the Pearson product moment correlation coefficient through data points allowing all four prognostic scoring systems to be directly compared. Results: when the prognostic scores were compared on a common scale, the R-squared values of all the scoring systems were similar with R-squared values of greater than 0.94 in all cases. The Basingstoke Predictive Index however produced the steepest gradient suggesting it can better distribute patients along a wider range of survival. Conclusions: none of the four scoring systems was perfect in their predictive value. It is not surprising that the risk score from MSKCC and Leeds are not as good as the others since they are meant to be preoperative prognostic scores and postoperative scoring system by their nature of having more information should be better. Clearly, future developments in this field must incorporate advances in our understanding of tumor biology. [Table: see text]
Conflicts of interest among academic dermatologists: freedom or constraint?
Authors: L. Naldi
Journal: British Journal of Dermatology (2016)

Intangible and institutional conflicts of interest can particularly affect academia. Academic scientists have peculiar social responsibilities with respect to education and research. These responsibilities may conflict with the increased presence of industry in academia and commercialization of academic research through patents and royalties. Drug approval is almost entirely dependent worldwide on data produced in studies led by pharmaceutical industries. A reflection of the increasing role of the market in academic research is given by exaggerated claims in press releases by academic institutions. In consideration of the extensive presence of industry in academia, there is a need for a move from individual to institutional conflicts of interest disclosure, defining institutional policies for regulating conflicts of interest and developing an ‘ethically credible partnership’.
Polyhydramnios, Transient Antenatal Bartter’s Syndrome, and<i>MAGED2</i>Mutations
Authors: Kamel Laghmani, Bodo B. Beck, Sung-Sen Yang, Elie Seaayfan, Andrea Wenzel, Björn Reusch, Helga Vitzthum, Dario Priem, Sylvie Demaretz, Klasien Bergmann, Leonie K. Duin, Heike Göbel, Christoph Mache, Holger Thiele, Malte P. Bartram, Carlos Dombret, Janine Altmüller, Peter Nürnberg, Thomas Benzing, Elena Levtchenko, Hannsjörg W. Seyberth, Günter Klaus, Gökhan Yigit, Shih-Hua Lin, Albert Timmer, Tom J. de Koning, Sicco A. Scherjon, Karl P. Schlingmann, Mathieu J.M. Bertrand, Markus M. Rinschen, Olivier de Backer, Martin Konrad, Martin Kömhoff
Journal: New England Journal of Medicine (2016)

Three pregnancies with male offspring in one family were complicated by severe polyhydramnios and prematurity. One fetus died; the other two had transient massive salt-wasting and polyuria reminiscent of antenatal Bartter’s syndrome.
Effect of Dilute Apple Juice and Preferred Fluids vs Electrolyte Maintenance Solution on Treatment Failure Among Children With Mild Gastroenteritis
Authors: Stephen B. Freedman, Andrew R. Willan, Kathy Boutis, Suzanne Schuh
Journal: JAMA (2016)

Gastroenteritis is a common pediatric illness. Electrolyte maintenance solution is recommended to treat and prevent dehydration. Its advantage in minimally dehydrated children is unproven.To determine if oral hydration with dilute apple juice/preferred fluids is noninferior to electrolyte maintenance solution in children with mild gastroenteritis.Randomized, single-blind noninferiority trial conducted between the months of October and April during the years 2010 to 2015 in a tertiary care pediatric emergency department in Toronto, Ontario, Canada. Study participants were children aged 6 to 60 months with gastroenteritis and minimal dehydration.Participants were randomly assigned to receive color-matched half-strength apple juice/preferred fluids (n=323) or apple-flavored electrolyte maintenance solution (n=324). Oral rehydration therapy followed institutional protocols. After discharge, the half-strength apple juice/preferred fluids group was administered fluids as desired; the electrolyte maintenance solution group replaced losses with electrolyte maintenance solution.The primary outcome was a composite of treatment failure defined by any of the following occurring within 7 days of enrollment: intravenous rehydration, hospitalization, subsequent unscheduled physician encounter, protracted symptoms, crossover, and 3% or more weight loss or significant dehydration at in-person follow-up. Secondary outcomes included intravenous rehydration, hospitalization, and frequency of diarrhea and vomiting. The noninferiority margin was defined as a difference between groups of 7.5% for the primary outcome and was assessed with a 1-sided α=.025. If noninferiority was established, a 1-sided test for superiority was conducted.Among 647 randomized children (mean age, 28.3 months; 331 boys [51.1%]; 441 (68.2%) without evidence of dehydration), 644 (99.5%) completed follow-up. Children who were administered dilute apple juice experienced treatment failure less often than those given electrolyte maintenance solution (16.7% vs 25.0%; difference, -8.3%; 97.5% CI, -∞ to -2.0%; P < .001 for inferiority and P = .006 for superiority). Fewer children administered apple juice/preferred fluids received intravenous rehydration (2.5% vs 9.0%; difference, -6.5%; 99% CI, -11.6% to -1.8%). Hospitalization rates and diarrhea and vomiting frequency were not significantly different between groups.Among children with mild gastroenteritis and minimal dehydration, initial oral hydration with dilute apple juice followed by their preferred fluids, compared with electrolyte maintenance solution, resulted in fewer treatment failures. In many high-income countries, the use of dilute apple juice and preferred fluids as desired may be an appropriate alternative to electrolyte maintenance fluids in children with mild gastroenteritis and minimal dehydration.clinicaltrials.gov Identifier: NCT01185054.
Abstract 14763: Discontinuation of Dofetilide or Qt Prolongation is Much More Common in Real-world Setting Than Reported in Clinical Trials
Authors: Vidhu Anand, Kairav Vakil, Selcuk Adabag
Journal: Circulation (2015)

Introduction: Dofetilide is a class III anti-arrhythmic agent approved for achieving and maintaining sinus rhythm in patients with symptomatic atrial fibrillation or flutter (AF). Due to a risk of QT prolongation and ventricular tachycardia (VT) patients initiated on Dofetilide need to be hospitalized for at least 3 days to closely monitor ECG. In large clinical trials 1.8-2.5% of the patients had to discontinue Dofetilide due to QT prolongation. We aimed to evaluate the frequency and correlates of discontinuation of Dofetilide due to QT prolongation (QTc &gt;500 msec) or VT in a real-world, inpatient setting. Methods: We included 100 consecutive patients, hospitalized for Dofetilide initiation at the Minneapolis VA Medical Center from 2011 to 2014. Data was collected retrospectively from electronic medical records. Results: The mean age was 63.8 ± 9.1 years. The indication for Dofetilide was AF (88%) and VT (12%). Dofetilide had to be discontinued in 21% of the patients due to QTc prolongation (17%) or VT (2%) or lack of efficacy (2%). One patient died in the hospital. The mean QTc in patients in whom Dofetilide had to be discontinued was 512±53 msec. In 29% of the cases Dofetilide cardioverted patients to sinus rhythm. Patients who had to discontinue Dofetilide were less likely to have coronary heart disease (CHD) than those who were discharged on Dofetilide (14% vs. 44%, respectively; p= 0.012) (Table). The average number of doses received by patients before discharge was 5.5±0.9 in patients who were discharged on Dofetilde vs. 3.2±1.5 in whom Dofetilide was discontinued because of QTc prolongation (55% discontinued after 2 nd dose). Concomitant QTc prolonging drugs were used in 29% of patients who had to discontinue Dofetilide vs. 24% of those who were discharged on Dofetilide (p=0.78) (Table). Conclusion: The incidence of Dofetilide discontinuation due to high-risk ECG features in the real world setting is remarkably higher than that reported in prior clinical trials.
Lipopolysaccharide induces the rapid tyrosine phosphorylation of the mitogen-activated protein kinases erk-1 and p38 in cultured human vascular endothelial cells requiring the presence of soluble CD14
Authors: RR Schumann, D Pfeil, N Lamping, C Kirschning, G Scherzinger, P Schlag, L Karawajew, F Herrmann
Journal: Blood (1996)
Serotonin transporter variant drives preventable gastrointestinal abnormalities in development and function
Authors: Kara Gross Margolis, Zhishan Li, Korey Stevanovic, Virginia Saurman, Narek Israelyan, George M. Anderson, Isaac Snyder, Jeremy Veenstra-VanderWeele, Randy D. Blakely, Michael D. Gershon
Journal: Journal of Clinical Investigation (2016)

Autism spectrum disorder (ASD) is an increasingly common behavioral condition that frequently presents with gastrointestinal (GI) disturbances. It is not clear, however, how gut dysfunction relates to core ASD features. Multiple, rare hyperfunctional coding variants of the serotonin (5-HT) transporter (SERT, encoded by SLC6A4) have been identified in ASD. Expression of the most common SERT variant (Ala56) in mice increases 5-HT clearance and causes ASD-like behaviors. Here, we demonstrated that Ala56-expressing mice display GI defects that resemble those seen in mice lacking neuronal 5-HT. These defects included enteric nervous system hypoplasia, slow GI transit, diminished peristaltic reflex activity, and proliferation of crypt epithelial cells. An opposite phenotype was seen in SERT-deficient mice and in progeny of WT dams given the SERT antagonist fluoxetine. The reciprocal phenotypes that resulted from increased or decreased SERT activity support the idea that 5-HT signaling regulates enteric neuronal development and can, when disturbed, cause long-lasting abnormalities of GI function. Administration of a 5-HT4 agonist to Ala56 mice during development prevented Ala56-associated GI perturbations, suggesting that excessive SERT activity leads to inadequate 5-HT4–mediated neurogenesis. We propose that deficient 5-HT signaling during development may contribute to GI and behavioral features of ASD. The consequences of therapies targeting SERT during pregnancy warrant further evaluation.
Prognostic marker discordance between breast and axilla in patients with early breast cancer.
Authors: Courtney Porter, Michelle L. Rockey, Dennis Grauer, David W. Henry, Priyanka Sharma, Fang Fan, Qamar J. Khan
Journal: Journal of Clinical Oncology (2015)

e11618 Background: Adjuvant systemic treatment of breast cancer is primarily determined by tumor prognostic markers (ER, PR, HER2) obtained on primary breast cancer. Several studies have shown a discordance of prognostic biomarker status between primary breast cancer and axillary lymph nodes. It is not known whether such discordance is clinically meaningful. The purpose of this study is to determine if testing of prognostic markers on axillary nodes at the time of diagnosis will impact adjuvant therapy recommendations. Methods: Retrospective analysis of prospectively obtained prognostic biomarkers was performed. Pathology reports of 482 patients with non-metastatic primary breast cancer were obtained between August 2007 and August 2014. Subjects with prognostic markers available for both primary breast cancer and ipsilateral axillary lymph nodes were identified. Patients were excluded if ER and PR (by IHC) and HER2 (by IHC and/or FISH) were not available for both primary breast tissue and axillary nodes. Results: A total of214 patients who had all three prognostic markers available for both primary tumor and axillary lymph nodes were included in this analysis. 85% had invasive ductal carcinoma. 50% had grade 2 and 43% had grade 3 cancer. 80% of patients had ER/PR+ disease, 20% were HER2+ and 15% were triple negative. Discordance was identified in at least one of the markers (ER, PR, or HER2) between breast and axillary lymph nodes in 29 (13.6%) patients. One (0.5%) patient was ER/PR+ in breast and ER/PR- in the lymph node. One (0.5%) patient was ER/PR- in breast and ER/PR+ in the lymph node. HER2+ disease in breast and HER2- disease in axilla was identified in 8 (3.7%) patients. Only 2 (0.9%) patients had HER2- disease in the breast and HER2+ disease in the axilla, resulting in addition of trastuzumab to adjuvant chemotherapy. Markers in axilla resulted in change in adjuvant therapy recommendations in only 2 (0.9%) patients. Conclusions: Prognostic marker discordance between primary breast cancer and synchronous lymph nodes is common. However, such discordance rarely results in a change in adjuvant therapy recommendations. Therefore, prognostic marker assessment of ipsilateral axillary lymph nodes is not clinically warranted.