tbuckley/cabot-search huggingface dataset:
Efficacy of immune checkpoint inhibitors in patients with brain metastasis from NSCLC, RCC, and melanoma.
Authors: Adam Lauko, Bicky Thapa, Xuefei Jia, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2018)

214 Background: Immune checkpoint inhibitors are revolutionizing the treatment of multiple advanced malignancies, however, there is limited data on the efficacy of immune checkpoint blockade in brain metastasis. We conducted a study to analyze the overall survival (OS) and progression-free survival (PFS) among patients with brain metastasis from Non-Small Cell Lung Carcinoma (NSCLC), Renal Cell Carcinoma (RCC), and Melanoma treated with either Nivolumab, Pembrolizumab, Ipilimumab or a combination. Methods: After IRB approval, we retrospectively evaluated patients with brain metastasis treated at our tertiary care institution from 2011-2017 who underwent immunotherapy and one or more of the following; whole brain radiation therapy (WBRT), surgery, stereotactic radiosurgery (SRS) or systemic chemotherapy. Univariable and multivariable analysis was utilized to analyze OS and PFS. Volumetric analysis to assess treatment response is ongoing. Results: A total of 128 patients were identified with a median age of 60.6 years. 49% of patients were male; 77% of patients had a good (0 or 1) ECOG performance scores at the time of the brain metastasis; 83 patients had supratentorial brain metastasis, 11 had infratentorial and 24 had both. The prevalence of mutations was 34% in NSCLC patients, 58% in melanoma, and 0% in RCC. The median OS from the start of immunotherapy was not reached for RCC and was 17.1 and 28.9 months for Melanoma and NSCLC respectively. Median PFS was 5.9, 6.7 and 3.6 months for RCC, Melanoma, and NSCLC respectively. On multivariable analysis, SRS, sex and the number of cycles of immunotherapy had statistically significant hazard ratios. Conclusions: Immune checkpoint inhibitors are efficacious in the treatment of brain metastasis. Further analysis including response criteria using volumetric analysis is ongoing and final results will be presented at the meeting. [Table: see text]
How does the femoral cortex depend on bone shape? A methodology for the joint analysis of surface texture and shape
Authors: A.H. Gee, G.M. Treece, K.E.S. Poole
Journal: Medical Image Analysis (2018)

In humans, there is clear evidence of an association between hip fracture risk and femoral neck bone mineral density, and some evidence of an association between fracture risk and the shape of the proximal femur. Here, we investigate whether the femoral cortex plays a role in these associations: do particular morphologies predispose to weaker cortices? To answer this question, we used cortical bone mapping to measure the distribution of cortical mass surface density (CMSD, mg/cm2) in a cohort of 125 females. Principal component analysis of the femoral surfaces identified three modes of shape variation accounting for 65% of the population variance. We then used statistical parametric mapping (SPM) to locate regions of the cortex where CMSD depends on shape, allowing for age. Our principal findings were increased CMSD with increased gracility over much of the proximal femur; and decreased CMSD at the superior femoral neck, coupled with increased CMSD at the calcar femorale, with increasing neck-shaft angle. In obtaining these results, we studied the role of spatial normalization in SPM, identifying systematic misregistration as a major impediment to the joint analysis of CMSD and shape. Through a series of experiments on synthetic data, we evaluated a number of registration methods for spatial normalization, concluding that only those predicated on an explicit set of homologous landmarks are suitable for this kind of analysis. The emergent methodology amounts to an extension of Geometric Morphometric Image Analysis to the domain of textured surfaces, alongside a protocol for labelling homologous landmarks in clinical CT scans of the human proximal femur.
Phase III trial results with blisibimod, a selective inhibitor of B-cell activating factor, in subjects with systemic lupus erythematosus (SLE): results from a randomised, double-blind, placebo-controlled trial
Authors: Joan T Merrill, William R Shanahan, Morton Scheinberg, Kenneth C Kalunian, David Wofsy, Renee S Martin
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Targeted inhibitors of B-cell activating factor (BAFF) have been evaluated in phase III trials in over 4000 patients with systemic lupus erythematosus (SLE). Post hoc analyses of these studies identify greater treatment effect in patients entering with higher disease activity, greater corticosteroid doses, anti double-stranded DNA (dsDNA) and low complement C3 or C4. <h3>Objectives</h3> To evaluate the efficacy and safety of blisibimod, a BAFF inhibitor, in a population of patients with SLE enriched for high disease activity. <h3>Methods</h3> 442 patients with SLE with antinuclear antibodies or anti-dsDNA and Safety of Estrogen in Lupus Erythematosus National Assessment – Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score ≥10 on standard-of-care medications were randomised to receive weekly subcutaneous blisibimod (200 mg) or placebo. Corticosteroid taper was encouraged from week 8. The primary end point was the week 52 SLE Responder Index-6 (SRI-6). <h3>Results</h3> The SRI-6 primary end point was not met. There was a statistically significant steroid-sparing effect, and significantly more blisibimod-treated subjects achieved corticosteroid taper. Increased blisibimod treatment effect on SRI-6 was observed in subjects who achieved a concomitant decrease in corticosteroid dose from baseline. In subjects with baseline urinary protein:creatinine ratio (UPCR) ≥56.5 mg/mmol, significantly higher proportions of blisibimod subjects achieved &gt;50% reduction in UPCR and/or UPCR &lt;56.5 mg/mmol. Reductions in SLE autoantibodies and B cells, and increases in complement C3 and C4 were observed with blisibimod. Blisibimod was well-tolerated. The most common adverse events were upper respiratory tract infection, urinary tract infection, injection site erythema/reaction and diarrhoea. <h3>Conclusions</h3> Although the SRI-6 end point was not met, blisibimod was associated with successful steroid reduction, decreased proteinuria and biomarker responses. <h3>Trial registration number</h3> NCT01395745.
FDG PET/CT in 2 Cases of Hepatic Pseudolymphoma
Authors: Xinping Zhong, Aisheng Dong, Hui Dong, Yang Wang
Journal: Clinical Nuclear Medicine (2018)

Hepatic pseudolymphoma, also known as reactive lymphoid hyperplasia or nodular lymphoid hyperplasia, is a rare benign lymphoproliferative lesion. Preoperative diagnosis of hepatic pseudolymphoma is challenging. We present 2 cases of hepatic pseudolymphoma with focal intense FDG uptake on FDG PET/CT mimicking malignancy. These 2 cases suggest that hepatic pseudolymphoma should be considered as a rare differential diagnosis in patients with focal hypermetabolic hepatic lesion.
Passing PLAB 2
Authors: Kuntal J Patel
Journal: BMJ (2004)

PLAB 2 (the Professional and Linguistic Assessments Board test part 2) consists of 16 objective structured clinical examination (OSCE) stations, which usually include one rest station and one pilot station. Each station is graded from A to E. (www.gmc-uk.org gives further details.) It covers a wide range of tasks including history taking, examination skills, practical skills, use …
Out-of-Hospital Cardiac Arrest Resuscitation Systems of Care: A Scientific Statement From the American Heart Association
Authors: James J. McCarthy, Brendan Carr, Comilla Sasson, Bentley J. Bobrow, Clifton W. Callaway, Robert W. Neumar, Jose Maria E. Ferrer, J. Lee Garvey, Joseph P. Ornato, Louis Gonzales, Christopher B. Granger, Monica E. Kleinman, Chris Bjerke, Graham Nichol
Journal: Circulation (2018)

The American Heart Association previously recommended implementation of cardiac resuscitation systems of care that consist of interconnected community, emergency medical services, and hospital efforts to measure and improve the process of care and outcome for patients with cardiac arrest. In addition, the American Heart Association proposed a national process to develop and implement evidence-based guidelines for cardiac resuscitation systems of care. Significant experience has been gained with implementing these systems, and new evidence has accumulated. This update describes recent advances in the science of cardiac resuscitation systems and evidence of their effectiveness, as well as recent progress in dissemination and implementation throughout the United States. Emphasis is placed on evidence published since the original recommendations (ie, including and since 2010).
Palliative care for people with COPD: effective but underused
Authors: David M.G. Halpin
Journal: European Respiratory Journal (2018)

Nearly 100 000 men and over 65 000 women die from chronic obstructive pulmonary disease (COPD) in Europe each year [1]; more die from one of its comorbidities but face the challenges of living and dying with severe COPD during their last years and months. Globally, COPD is the third most common cause of death worldwide and the Global Burden of Disease project estimated that, in 2015, COPD caused 3.2 million deaths, an increase of 11.6% compared with 1990 [2]. Despite its effectiveness palliative care is underused in the majority of patients with COPD <http://ow.ly/d0YH30hPKeu>
Warning over EU minimum specialty training requirements
Authors: Caroline White
Journal: BMJ (2012)

Concerns have been raised over European parliamentary proposals that would allow EU doctors who have not completed a minimum amount of specialist medical training to practise in other member states.

The internal market committee, which is leading the revision of the mutual recognition of professional qualifications directive, has made several amendments to the original European Commission text in a bid to facilitate the movement of doctors across member states.

The revisions propose that partial exemptions be made to the …
INCIDENTAL CORONARY ARTERY CALCIFICATION ON COMPUTERIZED TOMOGRAPHY IN PATIENTS WITH EARLY STAGE NON-SMALL CELL LUNG CANCER AND OPPORTUNITIES FOR CARDIOVASCULAR RISK OPTIMIZATION
Authors: Sarah Cuddy, David L. Payne, David Murphy, Ruth Dunne, Raphael Bueno, Ron Blankstein, Marcelo Di Carli, Mandeep Mehra, Anju Nohria, John Groarke
Journal: Journal of the American College of Cardiology (2018)
Vascular Smooth Muscle–Specific Progerin Expression Accelerates Atherosclerosis and Death in a Mouse Model of Hutchinson-Gilford Progeria Syndrome
Authors: Magda R. Hamczyk, Ricardo Villa-Bellosta, Pilar Gonzalo, María J. Andrés-Manzano, Paula Nogales, Jacob F. Bentzon, Carlos López-Otín, Vicente Andrés
Journal: Circulation (2018)

Progerin, an aberrant protein that accumulates with age, causes the rare genetic disease Hutchinson-Gilford progeria syndrome (HGPS). Patients who have HGPS exhibit ubiquitous progerin expression, accelerated aging and atherosclerosis, and die in their early teens, mainly of myocardial infarction or stroke. The mechanisms underlying progerin-induced atherosclerosis remain unexplored, in part, because of the lack of appropriate animal models.We generated an atherosclerosis-prone model of HGPS by crossing apolipoprotein E-deficient (Apoe-/-) mice with LmnaG609G/G609G mice ubiquitously expressing progerin. To induce progerin expression specifically in macrophages or vascular smooth muscle cells (VSMCs), we crossed Apoe-/-LmnaLCS/LCS mice with LysMCre and SM22αCre mice, respectively. Progerin expression was evaluated by polymerase chain reaction and immunofluorescence. Cardiovascular alterations were determined by immunofluorescence and histology in male mice fed normal chow or a high-fat diet. In vivo low-density lipoprotein retention was assessed by intravenous injection of fluorescently labeled human low-density lipoprotein. Cardiac electric defects were evaluated by electrocardiography.Apoe-/-LmnaG609G/G609G mice with ubiquitous progerin expression exhibited a premature aging phenotype that included failure to thrive and shortened survival. In addition, high-fat diet-fed Apoe-/-LmnaG609G/G609G mice developed a severe vascular pathology, including medial VSMC loss and lipid retention, adventitial fibrosis, and accelerated atherosclerosis, thus resembling most aspects of cardiovascular disease observed in patients with HGPS. The same vascular alterations were also observed in Apoe-/-LmnaLCS/LCSSM22αCre mice expressing progerin specifically in VSMCs, but not in Apoe-/-LmnaLCS/LCSLysMCre mice with macrophage-specific progerin expression. Moreover, Apoe-/-LmnaLCS/LCSSM22αCre mice had a shortened lifespan despite the lack of any overt aging phenotype. Aortas of ubiquitously and VSMC-specific progerin-expressing mice exhibited increased retention of fluorescently labeled human low-density lipoprotein, and atheromata in both models showed vulnerable plaque features. Immunohistopathological examination indicated that Apoe-/-LmnaLCS/LCSSM22αCre mice, unlike Apoe-/-LmnaG609G/G609G mice, die of atherosclerosis-related causes.We have generated the first mouse model of progerin-induced atherosclerosis acceleration, and demonstrate that restricting progerin expression to VSMCs is sufficient to accelerate atherosclerosis, trigger plaque vulnerability, and reduce lifespan. Our results identify progerin-induced VSMC death as a major factor triggering atherosclerosis and premature death in HGPS.
Caveolin-1, a driver of invasive phenotype in in-vitro 3D-spheroid assays comprised of high grade GBM cells association with an AKT-inhibited phenotype
Authors: Chiara Moriconi, Valentina Palmieri, giusy tornillo, Helen Fillmore, Geoffrey J Pilkington, Mark Gumbleton
Journal: Neuro-Oncology (2018)

Glioblastoma multiforme (GBM) cells display a highly invasive phenotype, a hallmark which counters effective surgical and radiotherapy strategies. Caveolin-1 (Cav-1) is the main structural and functional component of caveolae. The impact of the expression of Cav-1 within a range of tumour and tumour-associated stromal cells is variable with both oncogenic and tumour suppressive roles reported which appear to be both disease-specific and context-dependent. Our hypothesis is that Cav-1 serves as promoter of invasion of GBM cells. To investigate our hypothesis we used a lentiviral shRNA approach to silence Cav-1 in three GBM cell lines (U87, UP007, UP029) derived from adult brain tumours. We employed an in-vitro 3D cell-sprouting invasion assay with GBM cell spheres embedded in Matrigel. Quantification of invasion was undertaken using a novel image analysis tool or 3D systems, INSIDIA (ImageJ Macro for High-throughput Spheroid Invasion Analysis). Parallel migration and invasion studies were performed using a Boyden Chamber approach, as well as cell-cell adhesion assays. Activation of signalling pathways in 2D and 3D cultures were performed by proteomic array and Western Blot analysis. GBM cells expressing Cav-1 (Cav-1 +ve) displayed a higher invasive capacity compared cells where Cav-1 had been silenced Cav-1 –ve), the latter also showing increased cell-cell adhesion. A significant finding from the signalling analysis was an inverse association between Cav-1 silencing and activation of AKT evidenced by increased phosphorylation at both Ser473 and Thr308 sites. Ongoing studies are exploring this signalling axis and its relationship to the invasive phenotype. CM and MG acknowledge Cancer Research Wales support. GP and HF acknowledge Brain Tumour Research support.
Investigating the role of TAM family receptors in Merlin deficient tumours
Authors: Foram Dave
Journal: Neuro-Oncology (2018)

NF2 mutation causes development of multiple benign tumours of the nervous system such as schwannomas, meningiomas and ependymomas. Conventional chemotherapy is ineffective for this group of tumours, and surgery/radiosurgery carries significant risk due to tumour multiplicity and location, thus effective drug therapy is urgently needed. TAM (TYRO3, AXL, MERTK) family of receptor tyrosine kinases are upregulated in several tumours including schwannomas and are shown to be under negative control of a tumour suppressor protein Merlin, encoded by Neurofibromatosis type II (NF2) gene. Our group has also previously shown that AXL contributes to tumour development by increasing cell-proliferation and cell-matrix adhesion in schwannomas. In this study, we’re investigating the role of TYRO3 and MERTK in development of schwannomas and all three receptors in development meningiomas using human primary cells and tissues. Our current data demonstrates that in human primary schwannoma cells, AXL expression is dependent on expression of TYRO3 and MERTK. Confocal microscopy showed co-localisation of AXL, TYRO3 and MERTK in schwannoma cells. However, co-immunoprecipitation experiments revealed the direct interaction only between AXL and TYRO3, and TYRO3 and MERTK. In addition to interact with own members, shRNA knock down experiments confirmed that TYRO3 and MERTK can also cross-talk with other group of receptors such as integrin β1, EGFR and PDGFR in schwannoma. In addition, Western blot experiments with tumour tissue lysates showed overexpression of all three TAM members in grade-I meningiomas, compared to grade II and III meningiomas. High expression and activation/phosphorylation of TYRO3, AXL and MERTK has been also found in NF2-/- grade-I meningioma primary cells and Merlin reintroduction in NF2-/- meningioma primary cells confirmed TAM receptors are negatively regulated by Merlin in meningiomas. Investigating the role of TAM family receptors in pathobiology of schwannoma and meningioma will help to determine the best molecule to target therapeutically for NF2 tumours.
Estimating Treatment Effect With Clinical Interpretation From a Comparative Clinical Trial With an End Point Subject to Competing Risks
Authors: Lihui Zhao, Lu Tian, Brian Claggett, Marc Pfeffer, Dae Hyun Kim, Scott Solomon, Lee-Jen Wei
Journal: JAMA Cardiology (2018)

This study explores using the restricted mean time lost to quantify treatment effects from cardiovascular therapy.
OUTCOMES AFTER TRANSTHORACIC, PERIPHERAL VASCULAR AND TRANSFEMORAL TRANSCATHETER AORTIC VALVE IMPLANTATION: A PROPENSITY ANALYSIS FROM FRANCE TAVI REGISTRY
Authors: Sylvain Beurtheret, Nicole Karam, Noemie Resseguier, Remi Houel, Olivier Com, Richard Gelisse, Jacques Bille, Patrick Joly, Nicolas Barra, Philippe Commeau, Sebastien Armero, Mathieu Pankert, Julien Seitz, Helene Eltchaninoff, Pascal Leprince, Herve Le Breton
Journal: Journal of the American College of Cardiology (2018)
IMPACT OF CORONARY REMODELING ON CORONARY PHYSIOLOGY: A SERIAL CORONARY COMPUTED TOMOGRAPHY STUDY
Authors: Carlos A. Collet, Jeroen Sonck, Yosuke Miyazaki, Taku Asano, Bernard Cosyns, Yoshinobu Onuma, Marcio Bittencourt, Antonio Bartorelli, Daniele Andreini, Charles Taylor, Campbell Rogers, Patrick Serruys
Journal: Journal of the American College of Cardiology (2018)
Disease Management plus Recommended Care versus Recommended Care Alone for Ambulatory Patients with Chronic Obstructive Pulmonary Disease
Authors: Ofra Kalter-Leibovici, Michal Benderly, Laurence S. Freedman, Galit Kaufman, Tchiya Molcho Falkenberg Luft, Havi Murad, Liraz Olmer, Meri Gluch, David Segev, Avi Gilad, Said Elkrinawi, Tali Cukierman-Yaffe, Baruch Chen, Orit Jacobson, Calanit Key, Mordechai Shani, Gershon Fink, Anat Amital, Ahmad Atamna, Michal Benderly, Tali Cukierman-Yaffe, Said Elkrinawi, Laurence S. Freedman, Gershon Fink, Leonardo Fuks, Irena Fomin, Avi Gilad, Meri Gluch, Orit Jacobson, Ofra Kalter-Leibovici, Galit Kaufman, Calanit Key, Havi Murad, Tchiya Molcho Falkenberg Luft, Abdel Rahman Nader, Liraz Olmer, Shmuel Poreh, Mordechai Shani, David Segev, Manuel Szwarcman, Michal Benderly, Gershon Fink, Meri Gluch, Orit Jacobson, Ofra Kalter-Leibovici, Galit Kaufman, Calanit Key, Tchiya Molcho Falkenberg Luft, Mordechai Shani, David Segev, Baruch Chen, Laurence S. Freedman, Tamy Shohat, Michal Benderly, Yaacov Hacham, Vered Yayon, Tali Cukierman-Yaffe, Said ElKrenawi, Avi Gilad, Ofra Kalter-Leibovici, Michal Benderly, Laurence S. Freedman, Ofra Kalter-Leibovici, Havi Murad, Liraz Olmer
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

The efficacy of disease management programs in the treatment of patients with chronic obstructive pulmonary disease (COPD) remains uncertain.
Patients, caregivers and health system costs of home ventilation
Authors: Patrick Brian Murphy, Abdel Douiri
Journal: Thorax (2018)

Long-term ventilation has been a successful part of the management of chronic respiratory failure since the use of the iron lungs was introduced during the polio epidemics in the 1930s and 1940s. The transition from hospital-based therapy to genuine home ventilation was pioneered by a number of physicians and patients including Robert Cavendish whose story was dramatised in the recent biopic ‘Breathe’. Robert Cavendish used his financial backing and engineering contacts to develop the first wheelchair mounted ventilator marking a watershed in the management of ventilator-dependent patients; empowering patients with chronic respiratory failure to live independent of a healthcare environment. Improvements in technology, for example, positive pressure ventilation, have facilitated the move from hospital to community support for complex respiratory patients; however, this comes at a cost to the patient, caregivers and the health system. The cost to the health system is rising as the number of patients’ requiring home mechanical ventilation (HMV) increases1 in line with growing data to demonstrate its effectiveness in chronic respiratory failure secondary to different …
Red Cell Exchange: A Concise Review of Indications and Management
Authors: Elizabeth Biller, Yong Zhao, Lejla Music-Aplenc, Mary Berg, Lisa N Boggio, Theresa Boyd, Kelley Capocelli, Deanna C Fang, Scott A Koepsell, Huy P. Pham, Angela Treml, John Weiss, Geoffrey D. Wool, Beverly W Baron
Journal: Blood (2017)