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https://www.readbyqxmd.com/read/28547916/non-shivering-thermogenesis-as-a-mechanism-to-facilitate-sustainable-weight-loss
#1
REVIEW
B F Palmer, D J Clegg
Currently, there is a significant percentage of the population who are or will be classified as obese, necessitating novel strategies to facilitate sustainable weight loss. Reductions in basal metabolic rate occur in the face of weight loss and pose formidable barriers to individuals attempting to sustain meaningful weight reductions. Here, we discuss the mechanisms by which non-shivering thermogenesis may provide insight into metabolic pathways that can become druggable targets to facilitate sustainable weight loss...
May 25, 2017: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28544695/renal-replacement-therapy-in-critically-ill-cirrhotic-patients-a-challenging-balance-between-efficacy-and-futility
#2
EDITORIAL
Enric Reverter, Angels Escorsell, Javier Fernández
No abstract text is available yet for this article.
June 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28541177/when-teachable-moments-become-ethically-problematic
#3
Elizabeth Dzeng
There is frequently tension in medical education between teaching moments that provide skills and knowledge for medical trainees, and instrumentalizing patients for the purpose of teaching. In this commentary, I question the ethical acceptability of the practice of providing cardiopulmonary resuscitation (CPR) and advanced cardiac life support (ACLS) to dying patients who would be unlikely to survive resuscitation, as a teaching opportunity for medical trainees. This practice violates the principle of informed consent, as the patient agreed to resuscitation for the purpose of potentially prolonging life rather than to futile resuscitation as a teaching opportunity...
July 2017: Cambridge Quarterly of Healthcare Ethics: CQ: the International Journal of Healthcare Ethics Committees
https://www.readbyqxmd.com/read/28539226/fecal-calprotectin-as-an-alternative-to-ulcerative-colitis-endoscopic-index-of-severity-to-predict-the-response-to-corticosteroids-of-acute-severe-ulcerative-colitis-a-prospective-observational-study
#4
Tingbin Xie, Chenyan Zhao, Chao Ding, Tenghui Zhang, Xujie Dai, Tengfei Lv, Yi Li, Zhen Guo, Jianfeng Gong, Weiming Zhu
BACKGROUND: Fecal calprotectin (FC) might be an alternative to ulcerative colitis endoscopic index of severity (UCEIS) to predict the response to corticosteroids (CS) in acute severe colitis (ASC). METHODS: One hundred and seventeen ASC patients were prospectively enrolled. Demographic, clinical, laboratory and sigmoidoscopic data were documented. Multivariate and ROC analyses were performed to identify risk factors for non-response to CS, and the predictive accuracy of possible predictors was assessed...
May 3, 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/28535716/extended-two-stage-adaptive-designs-with-three-target-responses-for-phase-ii-clinical-trials
#5
Seongho Kim, Weng Kee Wong
We develop a nature-inspired stochastic population-based algorithm and call it discrete particle swarm optimization to find extended two-stage adaptive optimal designs that allow three target response rates for the drug in a phase II trial. Our proposed designs include the celebrated Simon's two-stage design and its extension that allows two target response rates to be specified for the drug. We show that discrete particle swarm optimization not only frequently outperforms greedy algorithms, which are currently used to find such designs when there are only a few parameters; it is also capable of solving design problems posed here with more parameters that greedy algorithms cannot solve...
January 1, 2017: Statistical Methods in Medical Research
https://www.readbyqxmd.com/read/28506937/bivalirudin-infusion-to-reduce-ventricular-infarction-the-open-label-randomised-bivalirudin-infusion-for-ventricular-infarction-limitation-bival-study
#6
Robert Jan van Geuns, Georgios Sideris, Niels Van Royen, Rami El Mahmoud, Roberto Diletti, Claire Bal Dit Sollier, Jerome Garot, Nina W Van Der Hoeven, Bernardo Cortese, Li Ding, Ilknur Lechthaler, Efthymios N Deliargyris, Prodromos Anthopoulos, Ludovic Drouet
AIMS: The aim of the study was to investigate whether bivalirudin versus unfractionated heparin (UFH) reduces infarct size (IS) for primary percutaneous coronary intervention (PPCI) in large acute myocardial infarction (AMI). METHODS AND RESULTS: This multicentre open-label trial randomised 78 patients undergoing PPCI for large AMI to bivalirudin or UFH. The primary endpoint was IS, assessed by cardiac magnetic resonance (CMR) five days after PPCI. Secondary endpoints included index of microcirculatory resistance (IMR), CMR-assessed microvascular obstruction (MVO) and ejection fraction, and biomarkers for thrombin activity and cell injury...
May 16, 2017: EuroIntervention
https://www.readbyqxmd.com/read/28505999/efficacy-of-a-combined-therapeutic-approach-in-the-management-of-pisa-syndrome
#7
Siria Di Martino, Elisa Unti, Caterina Tramonti, Sonia Mazzucchi, Ubaldo Bonuccelli, Bruno Rossi, Roberto Ceravolo, Carmelo Chisari
BACKGROUND: Pisa syndrome (PS) represents an important source of disability in Parkinson's disease (PD). Currently no consensus has been reached on its definition or diagnostic criteria, and therapeutic approaches are unspecific and often futile. Recently the role of abdominal muscles, and in particular of the external oblique (EO), in the pathogenesis of PS was hypothesized. OBJECTIVES: To evaluate the role of EO and propose a combined therapeutic approach in the management of PS...
May 11, 2017: NeuroRehabilitation
https://www.readbyqxmd.com/read/28501253/resection-of-the-primary-tumor-in-stage-iv-colorectal-cancer-when-is-it-necessary
#8
REVIEW
Leandro Feo, Michael Polcino, Garrett M Nash
Management of metastatic colorectal cancer requires accurate staging and multidisciplinary evaluation, leading to a consensus treatment plan with the ultimate goal of increasing survival and improving the quality of life, while taking into consideration the patient's performance status, disease burden, and goals of care. Since the introduction of multidrug chemotherapeutic regimens, survival of patients with metastatic colorectal cancer has improved. Many patients with unresectable disease are undergoing surgery for asymptomatic primary tumors despite evidence that it is usually a futile intervention...
June 2017: Surgical Clinics of North America
https://www.readbyqxmd.com/read/28501085/staging-in-esophageal-and-gastric-cancers
#9
REVIEW
Thomas Hayes, Elizabeth Smyth, Angela Riddell, William Allum
Gastric and esophageal tumors have a poor prognosis; approximately 15% of patients are alive at 10 years following diagnosis. Surgical resection plus adjunctive chemotherapy or chemoradiotherapy is curative in approximately 50% of patients with operable disease, but is also associated with significant morbidity. Therefore, accurate preoperative staging is required to spare patients unnecessary toxicity and futile surgery. This review evaluates the sensitivity and specificities of the modalities used to stage patients with gastroesophageal cancer...
June 2017: Hematology/oncology Clinics of North America
https://www.readbyqxmd.com/read/28500122/navigating-the-benefits-and-burdens-of-life-saving-treatment-in-severely-decompensated-cirrhosis-an-illustrative-multisourced-narrative
#10
Philip Berry, Kuldeep Cheent, Heather Lewis, Marcus Peck
Severely decompensated cirrhosis presents major challenges in terms of balancing the benefits and burdens of life-extending treatment. Using accounts and interviews with a patient, her mother, consultant hepatologists and a consultant intensivist, this article explores the decision making around a 43-year-old woman with alcoholic liver disease who died after 100 days in a hospital. Particular focus is given to decisions on escalation, recognition of futility, distress associated with therapy and how messages given during end-of-life discussions are processed...
May 12, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28499583/histotype-tailored-neoadjuvant-chemotherapy-versus-standard-chemotherapy-in-patients-with-high-risk-soft-tissue-sarcomas-isg-sts-1001-an-international-open-label-randomised-controlled-phase-3-multicentre-trial
#11
Alessandro Gronchi, Stefano Ferrari, Vittorio Quagliuolo, Javier Martin Broto, Antonio Lopez Pousa, Giovanni Grignani, Umberto Basso, Jean-Yves Blay, Oscar Tendero, Robert Diaz Beveridge, Virginia Ferraresi, Iwona Lugowska, Domenico Franco Merlo, Valeria Fontana, Emanuela Marchesi, Davide Maria Donati, Elena Palassini, Emanuela Palmerini, Rita De Sanctis, Carlo Morosi, Silvia Stacchiotti, Silvia Bagué, Jean Michelle Coindre, Angelo Paolo Dei Tos, Piero Picci, Paolo Bruzzi, Paolo Giovanni Casali
BACKGROUND: Previous trials from our group suggested an overall survival benefit with five cycles of adjuvant full-dose epirubicin plus ifosfamide in localised high-risk soft-tissue sarcoma of the extremities or trunk wall, and no difference in overall survival benefit between three cycles versus five cycles of the same neoadjuvant regimen. We aimed to show the superiority of the neoadjuvant administration of histotype-tailored regimen to standard chemotherapy. METHODS: For this international, open-label, randomised, controlled, phase 3, multicentre trial, patients were enrolled from 32 hospitals in Italy, Spain, France, and Poland...
May 9, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28497761/beyond-the-milan-criteria-for-liver-transplantation-in-children-with-hepatic-tumours
#12
Jean de Ville de Goyet, Rebecka L Meyers, Greg M Tiao, Bruce Morland
The Milan criteria were originally defined in the context of adult liver transplantation for patients with hepatocellular carcinoma and cirrhotic livers. The aim of the criteria was to select patients with small tumours and no disease spread who had a good chance of success, thus avoiding futile transplants. This objective was reached successfully. For the management of selected children with unresectable hepatoblastoma, an almost opposite strategy was proposed and has been implemented in the past two decades, in which transplantation is indicated on the basis of large tumour size and anatomy that precludes the possibility of safe and radical resection...
June 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28497260/a-physiologically-based-pharmacokinetic-perspective-on-the-clinical-utility-of-albumin-based-dose-adjustments-in-critically-ill-patients
#13
Huybrecht T'jollyn, An Vermeulen, Jan Van Bocxlaer, Pieter Colin
INTRODUCTION: In hypo-albuminemia, the extent of albumin binding of a drug decreases. The resulting change in plasma protein binding only rarely leads to clinically relevant changes in unbound drug exposure. Nevertheless, in the critically ill, a tendency to increase dosing of anti-infective therapy is seen in patients experiencing hypo-albuminemia. To reconcile basic pharmacological principles with current clinical practice, this work presents a pharmacologically-based pharmacokinetic simulation study to emphasize the (lack of) effect of altered plasma protein binding on a drug's concentration-time profile and associated pharmacokinetic parameters...
May 11, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28495837/congressing-kinetochores-progressively-load-ska-complexes-to-prevent-force-dependent-detachment
#14
Philip Auckland, Nicholas I Clarke, Stephen J Royle, Andrew D McAinsh
Kinetochores mediate chromosome congression by either sliding along the lattice of spindle microtubules or forming end-on attachments to their depolymerizing plus-ends. By following the fates of individual kinetochores as they congress in live cells, we reveal that the Ska complex is required for a distinct substep of the depolymerization-coupled pulling mechanism. Ska depletion increases the frequency of naturally occurring, force-dependent P kinetochore detachment events, while being dispensable for the initial biorientation and movement of chromosomes...
May 11, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28490559/screening-for-coronary-artery-disease-in-patients-with-type-2-diabetes-a-meta-analysis-and-trial-sequential-analysis
#15
Dimitris V Rados, Lana C Pinto, Cristiane B Leitão, Jorge L Gross
OBJECTIVE: To evaluate the efficacy of coronary artery disease screening in asymptomatic patients with type 2 diabetes and assess the statistical reliability of the findings. METHODS: Electronic databases (MEDLINE, EMBASE, Cochrane Library and clinicaltrials.org) were reviewed up to July 2016. Randomised controlled trials evaluating coronary artery disease screening in asymptomatic patients with type 2 diabetes and reporting cardiovascular events and/or mortality were included...
May 9, 2017: BMJ Open
https://www.readbyqxmd.com/read/28490467/dose-optimization-to-minimize-radiation-risk-for-children-undergoing-ct-and-nuclear-medicine-imaging-is-misguided-and-detrimental
#16
Jeffry A Siegel, Bill Sacks, Charles W Pennington, James S Welsh
A debate exists within the medical community on whether the linear no-threshold (LNT) model of ionizing radiation exposure accurately predicts subsequent radiogenic cancer incidence. We evaluate the evidence that refutes LNT, and its corollary efforts to reduce radiation exposures for CT and nuclear medicine imaging in accord with ALARA (as low as reasonable achievable), particularly for children. Further, we review studies demonstrating that children are not, in fact, more radiosensitive than adults in the radiological imaging dose range, rendering dose reduction for children unjustifiable and counterproductive...
May 10, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28489677/futility-of-imaging-to-stage-melanoma-patients-with-a-positive-sentinel-lymph-node
#17
Lodewijka H J Holtkamp, Rebecca L Read, Louise Emmett, John F Thompson, Omgo E Nieweg
The use of staging imaging in melanoma patients with a positive sentinel lymph node (SLN) has been reported to be of limited value. Improved accuracy resulting from the development of time-of-flight positron emission tomography (PET) and ongoing image quality improvement of computed tomography (CT) may challenge this statement. Our retrospective study assessed the clinical value of routine staging CT and PET/CT imaging in a recent cohort of asymptomatic SLN-positive patients. Between January 2011 and April 2014, 143 patients with a positive SLN were routinely staged using CT of various parts of the body or whole-body PET/CT...
May 4, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28489587/ngs-based-identification-of-mutational-hotspots-for-targeted-therapy-in-anaplastic-thyroid-carcinoma
#18
Vera Tiedje, Saskia Ting, Thomas Herold, Sarah Synoracki, Soeren Latteyer, Lars C Moeller, Denise Zwanziger, Martin Stuschke, Dagmar Fuehrer, Kurt Werner Schmid
CONTEXT: Anaplastic thyroid carcinoma (ATC) represents one of the most aggressive carcinomas with no consistent survival benefit when treated with conventional radiochemotherapy. Approaches targeting "oncogene addiction" of ATC are increasingly explored and first promising results have been reported in single case studies. OBJECTIVE: To determine the prevalence of mutations in known thyroid oncogenes and signalling pathways amendable to targeted therapy in a large cohort of ATC...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28489511/phase-iii-randomized-placebo-controlled-double-blind-trial-of-celecoxib-in-addition-to-standard-chemotherapy-for-advanced-non-small-cell-lung-cancer-with-cyclooxygenase-2-overexpression-calgb-30801-alliance
#19
Martin J Edelman, Xiaofei Wang, Lydia Hodgson, Richard T Cheney, Maria Q Baggstrom, Sachdev P Thomas, Ajeet Gajra, Erin Bertino, Karen L Reckamp, Julian Molina, Joan H Schiller, Kisha Mitchell-Richards, Paula N Friedman, Jon Ritter, Ginger Milne, Olwen M Hahn, Thomas E Stinchcombe, Everett E Vokes
Purpose Tumor overexpression of cyclooxygenase-2 (COX-2) has been associated with worse outcome in non-small-cell lung cancer (NSCLC). In Cancer and Leukemia Group B (CALGB) 30203, we found that the selective COX-2 inhibitor celecoxib in addition to chemotherapy in advanced NSCLC improved progression-free and overall survival in patients with moderate to high COX-2 expression by immunohistochemistry (IHC). CALGB 30801 (Alliance) was designed to prospectively confirm that finding. Patients and Methods Patients with NSCLC (stage IIIB with pleural effusion or stage IV according to American Joint Committee on Cancer [sixth edition] criteria) were preregistered, and biopsy specimens were analyzed for COX-2 by IHC...
May 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28487159/recruitment-failure-and-futility-were-the-most-common-reasons-for-discontinuation-of-clinical-drug-trials-results-of-a-nationwide-inception-cohort-study-in-the-netherlands
#20
Cornelis A van den Bogert, Patrick C Souverein, Cecile T M Brekelmans, Susan W J Janssen, Gerard H Koëter, Hubert G M Leufkens, Lex M Bouter
OBJECTIVE: To identify the reasons for discontinuation of clinical drug trials and to evaluate whether efficacy-related discontinuations were adequately planned in the trial protocol. STUDY DESIGN AND SETTING: All clinical drug trials in the Netherlands, reviewed by Institutional Review Boards (IRBs) in 2007, were followed until December 2015. Data were obtained through the database of the Dutch competent authority (CCMO) and a questionnaire to the principal investigators...
May 6, 2017: Journal of Clinical Epidemiology
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