tbuckley/cabot-search huggingface dataset:
Bullous pemphigoid outcome is associated with CXCL10-induced matrix metalloproteinase 9 secretion from monocytes and neutrophils but not lymphocytes
Authors: Meriem Riani, Sébastien Le Jan, Julie Plée, Anne Durlach, Richard Le Naour, Guy Haegeman, Philippe Bernard, Frank Antonicelli
Journal: Journal of Allergy and Clinical Immunology (2016)
Tumor stroma-containing 3D spheroid arrays: A tool to study nanoparticle penetration
Authors: Dwi L. Priwitaningrum, Jean-Baptiste G. Blondé, Adithya Sridhar, Joop van Baarlen, Wim E. Hennink, Gert Storm, Séverine Le Gac, Jai Prakash
Journal: Journal of Controlled Release (2016)
Ventilator-related causes of lung injury: the mechanical power
Authors: L. Gattinoni, T. Tonetti, M. Cressoni, P. Cadringher, P. Herrmann, O. Moerer, A. Protti, M. Gotti, C. Chiurazzi, E. Carlesso, D. Chiumello, M. Quintel
Journal: Intensive Care Medicine (2016)
Abstract 10337: Using Landiolol During Primary Percutaneous Coronary Intervention Attenuates Myocardial Reperfusion Injury in Patients With ST-segment Elevation Acute Myocardial Infarction
Authors: Masayoshi Kiyokuni, Takayuki Mitsuhashi, Teruyasu Sugano, Tsutomu Endo, Tomoaki Ishigami, Toshiyuki Ishikawa, Satoshi Umemura, Kazuo Kiyokuni
Journal: Circulation (2015)

Introduction: Landiolol is the beta-1 selective receptor blocker and its half-life elimination is 4 minutes. The safety and efficacy of landiolol started before coronary reperfusion in patients with ST-segment elevation acute myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) remains unclear. We assessed the hypothesis that early use of landiolol promotes optimal reperfusion without increasing adverse events for those patients. Methods: We recruited 220 consecutive patients with STEMI performed pPCI. Patients with heart rate&lt;50, Killip class≧2, old myocardial infarction and 2 or 3 degree of AV-block on admission were excluded. 60 patients were non-landiolol group with conventional treatment admitted from October 2010 to September 2012. 55 patients were landiolol group admitted from October 2012 to September 2014. Administration of landiolol was started before pPCI with 3 μg/kg/min and stopped within 12 hours when oral beta-blockers were administered. ST-segment resolution (STR) was defined as more than 70% resolution of sum of ST-segment elevation at the J point between at the time of admission and just after pPCI. Result: Time form admission to stating landiolol was 35±23min in landiolol group. Age, sex, coronary risk factors, culprit lesion, SYNTAX score (19±10vs18±10) and reperfusion time did not differ between the two groups (all NS). The rate of non-sustained ventricular tachycardia (27vs50%, p=0.013), worsening heart failure (0vs8%, p=0.029) and shock (15vs31%, p=0.030) within 12 hours after the admission was lower in landiolol group. Although, at the time of finishing pPCI, systric blood pressure did not differ between the two groups (117±21vs124±24mmHg, p=0.09), heart rate was lower (66±11vs77±14/min, p&lt;0.01) and the rate of STR was higher (61vs42%, p=0.023) in landiolol group. Multivariate analysis showed that landiolol use was an independent predictor of STR (OR2.51, p=0.045). Within 6 months after the admission, the rate of worsening heart failure (0vs7%, p=0.07), target vessel revasculization (5vs10%, p=0.17) was lower in landiolol group. Conclusion: In low risk patients with STEMI, using landiolol during pPCI may attenuate myocardial reperfusion injury and reduce adverse events.
Montelukast Does not Maintain Symptom Remission After Topical Steroid Therapy for Eosinophilic Esophagitis
Authors: Jeffrey A. Alexander, Karthik Ravi, Felicity T. Enders, Debra M. Geno, Lori A. Kryzer, Kristin C. Mara, Thomas C. Smyrk, David A. Katzka
Journal: Clinical Gastroenterology and Hepatology (2016)
PTU-188 Statistical approaches to missing data in trials of irritable bowel syndrome with constipation: experience with linaclotide (constella®): Abstract PTU-188 Table 1
Authors: M Falques, C Díaz, D Vilardell, J Fortea, JM Johnston
Journal: Gut (2015)

<h3>Introduction</h3> Missing data may affect validity and interpretation of clinical trials, as different statistical approaches for handling missing data may lead to different conclusions. As patterns of missing data are often unknown until unblinding, study design should be guided by similar trials. Information on handling missing data in trials in irritable bowel syndrome with constipation (IBS-C) is limited. <h3>Method</h3> This post-hoc analysis compared imputation methods for missing data in 2 pivotal randomised, double-blind, placebo (PBO)-controlled, multicentre Phase 3 clinical trials (Trials 31 and 302) of linaclotide 290 μg once-daily (Constella<sup>®</sup>; LIN) in IBS-C. In both trials, pre-specified European Medicines Agency (EMA)-recommended co-primary endpoints were: 1) 12-week abdominal pain/discomfort responder rate and 2) 12-week IBS degree-of-relief responder rate. These endpoints were analysed using observed cases (OC), last observation carried forward (LOCF), baseline observation carried forward (BOCF), drop-out as non-responder and multiple imputation approaches. <h3>Results</h3> In Trial 302, the different imputation methods for missing data yielded results consistent with the initial OC approach for both co-primary endpoints (Table 1). Results were similar for Trial 31, with statistically significant treatment differences for all imputation methods for both endpoints (<i>P &lt; </i>0.0001 for all except for 12-week abdominal pain/discomfort responder: OC, <i>P = </i>0.0002 and drop-out as non-responder, <i>P = </i>0.0056). <h3>Conclusion</h3> All five imputation methods yielded non-biassed results in both LIN Phase 3 IBS-C trials, supporting the robustness of LIN treatment effects on EMA endpoints. The ‘drop-out as non-responder’ approach could be considered to be the most conservative, as using this method the treatment-effect estimates for both co-primary endpoints were lower than those obtained using other methods. <h3>Disclosure of interest</h3> M. Falques Employee of: Almirall S. A., C. Díaz Employee of: Almirall S. A., D. Vilardell Employee of: Almirall S. A., J. Fortea Employee of: Almirall S. A., J. Johnston Employee of: Ironwood Pharmaceuticals.
Dietary Phosphorus Intake and the Kidney
Authors: Alex R. Chang, Cheryl Anderson
Journal: Annual Review of Nutrition (2017)

Although phosphorus is an essential nutrient required for multiple physiological functions, recent research raises concerns that high phosphorus intake could have detrimental effects on health. Phosphorus is abundant in the food supply of developed countries, occurring naturally in protein-rich foods and as an additive in processed foods. High phosphorus intake can cause vascular and renal calcification, renal tubular injury, and premature death in multiple animal models. Small studies in human suggest that high phosphorus intake may result in positive phosphorus balance and correlate with renal calcification and albuminuria. Although serum phosphorus is strongly associated with cardiovascular disease, progression of kidney disease, and death, limited data exist linking high phosphorus intake directly to adverse clinical outcomes. Further prospective studies are needed to determine whether phosphorus intake is a modifiable risk factor for kidney disease.
Prediction Error Representation in Individuals With Generalized Anxiety Disorder During Passive Avoidance
Authors: Stuart F. White, Marilla Geraci, Elizabeth Lewis, Joseph Leshin, Cindy Teng, Bruno Averbeck, Harma Meffert, Monique Ernst, James R. Blair, Christian Grillon, Karina S. Blair
Journal: American Journal of Psychiatry (2016)

Objective: Deficits in reinforcement-based decision making have been reported in generalized anxiety disorder. However, the pathophysiology of these deficits is largely unknown; published studies have mainly examined adolescents, and the integrity of core functional processes underpinning decision making remains undetermined. In particular, it is unclear whether the representation of reinforcement prediction error (PE) (the difference between received and expected reinforcement) is disrupted in generalized anxiety disorder. This study addresses these issues in adults with the disorder. Method: Forty-six unmedicated individuals with generalized anxiety disorder and 32 healthy comparison subjects group-matched on IQ, gender, and age performed a passive avoidance task while undergoing functional MRI. Data analyses were performed using a computational modeling approach. Results: Behaviorally, individuals with generalized anxiety disorder showed impaired reinforcement-based decision making. Imaging results revealed that during feedback, individuals with generalized anxiety disorder relative to healthy subjects showed a reduced correlation between PE and activity within the ventromedial prefrontal cortex, ventral striatum, and other structures implicated in decision making. In addition, individuals with generalized anxiety disorder relative to healthy participants showed a reduced correlation between punishment PEs, but not reward PEs, and activity within the left and right lentiform nucleus/putamen. Conclusions: This is the first study to identify computational impairments during decision making in generalized anxiety disorder. PE signaling is significantly disrupted in individuals with the disorder and may lead to their decision-making deficits and excessive worry about everyday problems by disrupting the online updating ("reality check") of the current relationship between the expected values of current response options and the actual received rewards and punishments.
Thromboembolic and Hemorrhagic Complications In Adult Patients With Acute Lymphoblastic Leukemia (ALL) Treated With Asparaginase-Containing Combination Chemotherapy: A Single Center Experience
Authors: Jason N. Barreto, Kristen B. Mccullough, Candy S. Peskey, Michelle Elliott, Dennis A. Gastineau, Aref Al-Kali, Louis Letendre, William Hogan, Mark R. Litzow, Mrinal M. Patnaik
Journal: Blood (2013)
Outcomes after radiation therapy for brain metastases from gastrointestinal primaries.
Authors: Keith Robert Unger, Brian Timothy Collins, John Marshall, Michael J. Pishvaian, Ruth He, Sean P. Collins
Journal: Journal of Clinical Oncology (2014)

647 Background: There is limited data regarding outcomes of patients with colorectal cancer (CRC) and other gastrointestinal (GI) cancers metastatic to the brain. The aim of this study is assess intracranial disease control in GI patients treated with radiation therapy (RT) and the likelihood of receiving systemic therapy following the diagnosis of metastatic disease to the brain. Methods: From 1/2007 to 6/2013, 24 consecutive patients with adenocarcinoma of a GI primary were treated with RT for brain metastases. Patients were excluded if they had prior RT to the brain. The majority of patients had CRC (n = 15). Ten patients had resection of at least one brain tumor prior to radiation therapy. Patients were treated with the following RT modalities: stereotactic radiosurgery alone (n = 12), whole brain RT (n = 7), both (n = 1), and partial brain RT (n = 1). Survival and control rates were analyzed by the Kaplan-Meier method. Results: Twenty-one patients had died at the time of analysis and the median overall survival was 5.4 months (range, 0.5 – 58 months). Radiographic follow up was available in 20 patients and 60% (12/20) had intracranial disease progression. The 6- and 12-month control rates for the treated tumors were 60% and 30%, respectively. Seven patients received salvage radiation therapy following intracranial disease progression. Fifty-eight percent (14/24) did not receive further systemic therapy. On univariate analysis, only prior surgical resection predicted for improved survival (3.8 vs. 7.8 months, p = 0.018), while number of lesions, performance status, primary site, chemotherapy after RT, and RT modality were not significant. Conclusions: Survival and intracranial disease control following RT for brain metastasis from GI cancers are poor and many patients do not receive further systemic therapy. In this small series, outcomes are worse than published series for other disease sites metastatic to the brain and further research is warranted.
Psychiatrist admits making sexual advances to medical students he tutored
Authors: Clare Dyer
Journal: BMJ (2016)

A consultant psychiatrist who admitted abusing his position as a tutor to make inappropriate and sexually motivated advances to three medical students at the University of Liverpool has had conditions imposed on his practice for nine months by a medical practitioners’ tribunal.

Vinesh Narayan, a clinical and undergraduate tutor for the Mersey Deanery in addition to his consultant post with 5 Boroughs Partnership NHS Foundation Trust, made comments implying that the students’ marks might depend on pleasing him.

In 2013 and 2014 complaints were made by two female students in the third year and one in the second year, alleging that Narayan had sent them suggestive text messages, arranged to discuss work in pubs, …
P3-102: Effects of gefitinib on peripheral blood lymphocyte subsets in non-small cell lung cancer patients
Authors: Ki Uk Kim, Jin Hoon Cho, Hye Kyung Park, Min Ki Lee, Yun Seong Kim, Soon Kew Park, Sang Yull Lee, I Hoseok, Yeong Dae Kim
Journal: Journal of Thoracic Oncology (2007)
Concomitant pemetrexed/carboplatin chemotherapy and 3D conformal radiotherapy followed by pemetrexed/carboplatin consolidation chemotherapy for locally advanced non-small cell lung cancer: Preliminary results of a phase II study.
Authors: S. Ma, Y. Xu, Y. Ji, X. Sun, J. Cheng, X. Du, Y. Zheng, G. Qiu
Journal: Journal of Clinical Oncology (2010)

7092 Background: Concomitant chemoradiotherapy is the standard treatment of locally advanced, non-resectable, non-small cell lung cancer (NSCLC). However, the optimal chemotherapy regimen is still controversial. The objective of this study was to evaluate the efficacy and toxicity of a concomitant treatment using pemetrexed/carboplatin and radiotherapy followed by pemetrexed/carboplatin consolidation chemotherapy. This report presents preliminary results of 21 patients who have completed treatment in the first stage. Methods: Single-arm design was designed according to the Simon's two-stage version for lung cancer phase II studies. Patients received concomitant pemetrexed 500 mg/m2, carboplatin AUC 5 chemotherapy on day 1 repeated every 3 weeks for 2 cycles and 3-D conformal radiotherapy (Median dose 62 Gy (range: 60-66 Gy) with 2 Gy daily fractions.), followed by pemetrexed (500 mg/m2) and carboplatin (AUC=5) every 3 weeks for 3 cycles as consolidation therapy. The association between histopathology and tumor responses was analyzed using the Chi-square and Fisher's exact test. Results: 21 patients were enrolled between 01/08 and 10/09. Median age was 61 years (range 43-70), M/F 16/5, all proven NSCLC (7 squamous cell carcinoma, 14 adenocarcinoma), stage IIIA/stage IIIB 14/7. The overall response rate (85.7%,95% (CI): 61%-97%) exceeded the goal per study design. Histopathology was predictive factor for the responses found in univariate analysis. Main toxicity (grade 3 or greater, %): neutropenia 6(28.5%); febrile neutropenia 0, thrombocytopenia 2 (9.5%); anaemia 5 (23.8%); esophagitis 1 (4.8%), radiation pneumonitis 1 (4.8%) and fatigue 2 (9.5%). Conclusions: This first-stage data suggests that concomitant treatment with pemetrexed/carboplatin and radiotherapy was well tolerated, with promising activity in locally advanced NSCLC. Better outcomes were observed in patients with adenocarcinoma. Although the data presented herwithin appears promising, second-stage study is needed to further validate this regimen. No significant financial relationships to disclose.
Futility and Avoidance: Medical Professionals in the Treatment of Obesity-Reply
Authors: Arthur Frank
Journal: JAMA (1993)

<h3>In Reply.</h3> —Dr Schachter compares the treatment of obesity with that of other disorders for which treatment protocols have been developed. Perhaps there is a consensus on the management of medical problems for which a single form of therapy is uniquely effective, but the treatment of obesity is still primitive, and as with other diseases in which no form of therapy is clearly advantageous, many forms of treatment have emerged. None is appropriate in all circumstances. Is it fair to hold obesity to a higher set of therapeutic standards than we do those diseases for which no therapeutic consensus, and surely no protocol, has evolved? I agree with the use of a multidisciplinary treatment model as proposed by Dr Roman-Diaz. Obesity is usually best treated in this format. This is not unique; examples of the utility of a therapeutic team include pain management, cancer, arthritis, and diabetes. We would agree
Quality of life (QoL) and overall survival (OS) in patients (pts) with advanced clear-cell renal cell carcinoma (aRCC) treated with nivolumab (NIVI) vs. everolimus (EVE) in the phase III CheckMate 025 study.
Authors: David Cella, Viktor Gruenwald, Paul D. Nathan, Justin Doan, Homa Dastani, Fiona Taylor, Bryan Bennett, Michael DeRosa, Scott Berry, Kristine Broglio, Elmer Berghorn, Robert J. Motzer
Journal: Journal of Clinical Oncology (2016)

4549 Background: In the CheckMate 025 study (NCT01668784), pts treated with nivo had an OS benefit vs eve (hazard ratio=0.73; 98.5% CI, 0.57 to 0.93), and median scores on the Functional Assessment of Cancer Therapy–Kidney Symptom Index–Disease Related Symptoms (FKSI-DRS) scale increased from baseline (BL) and were significantly (P<0.05) improved with nivo vs eve through week 104 (NEJM 2015;373:1803–13). Here we present a full analysis of QoL in relation to OS. Methods: QoL was measured by the kidney-specific FKSI-DRS questionnaire at BL and every 4 weeks. Chi-square analyses were used to assess differences in the proportion of pts who experienced meaningful improvement (2-point change) with nivo vs eve. OS was assessed by subgroups of pts with FKSI-DRS improvement (≥2-point increase), no change (<2-point increase or decrease), and deterioration (≥2-point decrease) at week 8 using the Kaplan–Meier method. Results: BL QoL was collected for 86% of all randomized pts; 361/410 (nivo) and 343/411 (eve). Over the course of the study, 55% of pts experienced meaningful DRS improvement with nivo vs 37% with eve (P<0.001). Median (95% CI) time to improvement in DRS occurred at 4.7 (3.7–7.5) months with nivo and was not estimable (NE) with eve due to the limited number of pts who experienced improvement. Association of change in QoL at week 8 and OS is shown in the table. Results using the EQ-5D questionnaire of general health status will be presented. Conclusions: In this global study of pts with aRCC, treatment with nivo vs eve resulted in a significantly greater proportion of pts experiencing meaningful QoL improvement, and improvement or no change in QoL at 8 weeks was associated with an OS benefit with nivo vs eve. These results suggest that the assessment of QoL may be helpful for evaluating the extent of OS benefit in clinical practice. Clinical trial information: NCT01668784.FKSI-DRS N Nivo median OS (95% CI) N Eve median OS (95% CI) Hazard ratio (95% CI) nivo vs eve Improvement 91 28.1 (23.6–NE) 47 19.3 (14.5–NE) 0.62 (0.37–1.06) No change 122 NE (27.4–NE) 95 NE (19.3–NE) 0.68 (0.44–1.05) Deterioration 89 26.7 (17.3–NE) 128 24.3 (18.7–NE) 0.99 (0.66–1.48)
Opportunities for new CT contrast agents to maximize the diagnostic potential of emerging spectral CT technologies
Authors: Benjamin M. Yeh, Paul F. FitzGerald, Peter M. Edic, Jack W. Lambert, Robert E. Colborn, Michael E. Marino, Paul M. Evans, Jeannette C. Roberts, Zhen J. Wang, Margaret J. Wong, Peter J. Bonitatibus
Journal: Advanced Drug Delivery Reviews (2016)
The GMC is working to improve revalidation
Authors: Niall Dickson
Journal: BMJ (2016)

The research cited in “Revalidation and resignation” in The BMJ ’s Minerva article showed that numerous factors contributed to workload pressure and burnout,1 but it would be wrong to blame all of this on revalidation. In addition, this limited study requires caution—the researchers admitted “uncertainty over the representativeness of the respondents.”

The GMC has commissioned a …
The Role of Interleukin-1 in Inflammatory and Malignant Human Skin Diseases and the Rationale for Targeting Interleukin-1 Alpha
Authors: Mayassa J. Bou-Dargham, Zahraa I. Khamis, Armand B. Cognetta, Qing-Xiang Amy Sang
Journal: Medicinal Research Reviews (2016)

Inflammation plays a major role in the induction and progression of several skin diseases. Overexpression of the major epidermal proinflammatory cytokines interleukin (IL) 1 alpha (IL-1α) and 1 beta (IL-1β) is positively correlated with symptom exacerbation and disease progression in psoriasis, atopic dermatitis, neutrophilic dermatoses, skin phototoxicity, and skin cancer. IL-1β and the interleukin-1 receptor I (IL-1RI) have been used as a therapeutic target for some autoinflammatory skin diseases; yet, their system-wide effects limit their clinical usage. Based on the local effects of extracellular IL-1α and its precursor, pro-IL-1α, we hypothesize that this isoform is a promising drug target for the treatment and prevention of many skin diseases. This review provides an overview on IL-1α and IL-β functions, and their contribution to inflammatory and malignant skin diseases. We also discuss the current treatment regimens, and ongoing clinical trials, demonstrating the potential of targeting IL-1α, and not IL-1β, as a more effective strategy to prevent or treat the onset and progression of various skin diseases.
P2-253: Biweekly docetaxel and gemcitabine as first line chemotherapy in advanced non small cell lung cancer (NSCLC)
Authors: Gaspar Esquerdo, Jose Luis Firvida, Margarita Amenedo, David Orts, Mercedes Salgado, Cristina Llorca, Manolo Ramos, Eva Perez, Jose Manuel Cervera, Jose Abal
Journal: Journal of Thoracic Oncology (2007)