tbuckley/cabot-search huggingface dataset:
ASSOCIATION BETWEEN THE LOW-DENSITY LIPOPROTEIN-CHOLESTEROL/HIGH-DENSITY LIPOPROTEIN-CHOLESTEROL RATIO AND CLINICAL OUTCOMES IN PATIENTS WITH ACUTE CORONARY SYNDROME AND DYSLIPIDEMIA: A SUBANALYSIS OF THE HIJ-PROPER STUDY
Authors: Haruki Sekiguchi, Erisa Kawada-Watanabe, Hiroyuki Arashi, Junichi Yamaguchi, Hiroshi Ogawa, Nobuhisa Hagiwara
Journal: Journal of the American College of Cardiology (2018)
Determinants of monozygotic twinning in ART: a systematic review and a meta-analysis
Authors: Kathrine Vauvert R Hviid, Sara Sofia Malchau, Anja Pinborg, Henriette Svarre Nielsen
Journal: Human Reproduction Update (2018)

The incidence of monozygotic twins (MZT) after ART appears to be higher than the incidence after spontaneous conceptions contradicting the aim of ART to avoid multiple pregnancies because of the associated risks.The aim was to study the frequency of MZT after IVF and ICSI and how it is influenced by the day of embryo transfer, maternal age, zona pellucida manipulation, controlled ovarian stimulation, stimulation protocol, culture media and embryo quality.Original studies and reviews were identified by searching the PubMed, Embase and Cochrane databases up to March 2017. The inclusion criterion was publications focusing on the five study questions related to MZT in our study. The exclusion criteria were articles that did not include blastocyst transfer, were on non-humans, were not published in peer-reviewed journals, and were based only on case studies. All of the articles were categorized according to the Oxford Centre for Evidence-based Medicine's 'Levels of Evidence', and quality and risk of bias assessment was performed with 'The Cochrane Collaboration's Risk of Bias Tools'. A meta-analysis was performed to study the impact of the day of embryo transfer on the MZT rate.The literature search resulted in a total of 42 articles, including 38 original studies, for analysis. The included original studies reported a MZT rate with blastocyst transfer from zero to 13.2%. Our meta-analysis found a higher frequency of MZT after blastocyst transfer compared with cleavage-stage embryos transfer: odds ratio = 2.18, 95% CI: 1.93-2.48 (fixed effect meta-analysis). A younger maternal age may increase the MZT rate, and recent studies regarding the use of zona pellucida manipulating techniques have disagreed with the previous suspicion of a higher MZT rate after the use of these methods. The extended culture to-blastocyst stage is a potential risk factor for MZT, but it is uncertain whether this phenomenon is due to the extended time, culture media or greater likelihood of younger oocytes to reach the blastocyst stage. An increased frequency of MZT following the GnRH-agonist suppression protocol has been suggested, as well as a decreased frequency of MZT with high gonadotrophin doses, which could reflect an age-related effect. Only limited literature has focused on the role of embryo morphology in the MZT rate, therefore, this issue remains unresolved.We found blastocyst transfer to be a risk factor for MZT. Hence, the results of this meta-analysis may weaken the previously proposed view that greater experience with blastocyst transfer and improved culture media could decrease the high rate of MZT after blastocyst transfer. To minimize the rate of MZT and the associated complications, the mechanisms underlying blastocyst transfer and MZT pregnancy must be elucidated.
IMPACT OF CHRONIC TOTAL OCCLUSION ON VENTRICULAR ARRHYTHMIA AND MORTALITY IN ISCHEMIC CARDIOMYOPATHY PATIENT WITH IMPLANTABLE CARDIAC DEFIBRILLATOR: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Wasawat Vutthikraivit, Saranapoom Klomjit, Pattara Rattanawong, Pakpoom Tantrachoti, Pavida Pachariyanon, Awapa Prombandankul, Possawat Vutthikraivit, Mohammad Ansari
Journal: Journal of the American College of Cardiology (2018)
Changes in filaggrin degradation products and corneocyte surface texture by season
Authors: K.A. Engebretsen, S. Kezic, C. Riethmüller, J. Franz, I. Jakasa, A. Hedengran, A. Linneberg, J.D. Johansen, J.P. Thyssen
Journal: British Journal of Dermatology (2018)

During the winter in northern countries, the risk of dermatitis is increased due to low temperature and humidity. Dermatitis is particularly common on weather‐exposed skin such as the cheeks and hands. Recently, increased numbers of unidentified nanosized protrusions on the corneocyte surface were associated with dermatitis and deficiency of natural moisturizing factor (NMF). To investigate the effect of season on NMF levels and corneocyte surface texture in cheek and hand skin of healthy adults. Eighty healthy volunteers (40 male and 40 female) were recruited: 40 aged 18–40 years and 40 aged ≥ 70 years. Cheek and dorsal hand skin was tape stripped in the winter and summer. Analysis for NMF and corneocyte surface texture was done (Dermal Texture Index, DTI). Potential confounders were registered and adjusted for. In cheek skin, NMF levels were reduced and DTI elevated during the winter compared with the summer. Older participants had higher NMF levels than younger participants. In the summer, DTI level was dependent on self‐reported ultraviolet exposure. In hand skin, NMF levels were higher during the winter than in the summer, and female participants had higher NMF levels than male participants. Seasonal effects on NMF and DTI on the cheeks and hands were found, suggesting an influence of climatic factors at the biochemical and ultrastructural levels. Significant variations were also observed regarding age and sex, making it difficult to draw firm conclusions. Our study adds new pieces to the puzzle of seasonal differences in xerosis and dermatitis.
Certificate in Aeromedical Retrieval and Transport
Authors: Pamela Winton
Journal: BMJ (2007)

It was so refreshing to study an area of medicine that I had no prior exposure to. It really fired my interest in the field of aeromedical transport 

FURTHER INFORMATION 

Ms Maureen Gordon, programme officer AVMX, Department of Medicine, Wellington School of Medicine, PO Box 7343, Wellington South, New Zealand. Tel: (+64/0) 4 385 5590, fax (+64/0) 4 389 5427, email deptmed@wnmeds.ac.nz, www.otago.ac.nz/aviation_medicine

Doctors interested in aeromedical transport of patients. It is also suitable for doctors doing air ambulance work, retrieval, or repatriation.

I did it in 2004 while working as an intensive care registrar in New Zealand. I was between …
Defining the Most Appropriate Primary End Point in Phase 2 Trials of Immune Checkpoint Inhibitors for Advanced Solid Cancers
Authors: Georgia Ritchie, Harry Gasper, Johnathan Man, Sally Lord, Ian Marschner, Michael Friedlander, Chee Khoon Lee
Journal: JAMA Oncology (2018)

<h3>Importance</h3> Checkpoint inhibitors have a unique mechanism of action that differs from chemotherapy or targeted therapies. The validity of objective response rate (ORR) as a surrogate for progression-free survival (PFS) and overall survival (OS) in checkpoint-inhibitor trials is uncertain. <h3>Objective</h3> To determine the types of primary end points used in phase 2 checkpoint-inhibitor trials, and to assess the strength of associations for ORR with PFS and OS. <h3>Data Sources</h3> Trials listed in electronic databases from 2000 to 2017 (PREMEDLINE, MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials). <h3>Study Selection</h3> Advanced solid cancers in phase 2 and phase 3 trials. <h3>Data Extraction and Synthesis</h3> Correlations between ORR odds ratios and hazard ratios (HRs) for PFS and OS were examined for randomized comparisons. Within checkpoint-inhibitor treatment arms, correlations for ORR with 6-month PFS and 12-month OS rates were examined. All analyses were weighted by trial size. Multivariable models to predict 6-month PFS and 12-month OS rates from ORR were developed and their performance validated in an independent sample of trials. <h3>Main Outcomes and Measures</h3> Correlation coefficient (<i>r</i>) of ORR with PFS and OS. <h3>Results</h3> Of 87 phase 2 trials identified, ORR was the most common (52 [60%]) primary end point. Twenty randomized clinical trials with 25 treatment comparisons were identified. Checkpoint-inhibitor therapy was associated with pooled ORR of 24% (95% CI, 18%-31%). For randomized comparisons,<i>r</i>between ORR odds ratio and PFS HR was 0.63 (95% CI, 0.35-0.89), ORR odds ratio and OS HR was 0.57 (95% CI, 0.23-0.89), and between PFS HR and OS HR was 0.42 (95% CI, 0.04-0.81). Within the checkpoint-inhibitor arms,<i>r</i>correlation coefficients between ORR with 6-month PFS, ORR with 12-month OS, and 6-month PFS with 12-month OS were 0.37 (95% CI, −0.06 to 0.95), 0.08 (95% CI, −0.17 to 0.70), and 0.74 (95% CI, 0.57-0.92), respectively. In validation, when 6-month PFS was used to predict 12-month OS, there was a good calibration between actual and predicted 12-month OS. When ORR was used to predict 6-month PFS and 12-month OS rates, respectively, the actual vs predicted rates calibrated poorly. <h3>Conclusions and Relevance</h3> In checkpoint-inhibitor trials, ORR correlated poorly with OS. For future phase 2 studies, 6-month PFS rate is recommended as an end point.
What's on the web?
Authors: Haitham Alshafey
Journal: BMJ (2005)

Clinical guidelines (CG) are a simple way to put evidence into practice. As they are not often published in peer reviewed journals, the internet is an ideal way to find them.⇓



To begin searching for a specific CG, look at the website of the relevant royal college (www.rcplondon.ac.uk/general/gen_links.htm). If you get no result there, try the National Institute for Clinical Excellence website (www.nice.org.uk/page.aspx?o=guidelines.completed); you may find the latest formally and systematically produced CG in the United Kingdom. If this is your first visit, have …
Head injury: an integrated approach
Authors: Fahid Rasul
Journal: BMJ (2012)

Head injury: an integrated approach, run by the Royal College of Surgeons of England, deals with the multidisciplinary management of head injuries and focuses on the surgical treatments for head trauma.

The course is aimed at junior neurosurgeons (core trainees year 1-2, specialty trainees year 3), junior consultants, and other doctors and nurses involved in the management of head injuries. Trauma is best treated by a team, and the attendees on day one of the course—including neurosurgeons, intensivists, emergency doctors, orthopaedic surgeons, and nurse specialists—emphasised the multidisciplinary nature of treatment.

At the headquarters of the Royal College of Surgeons of England in Lincoln’s Inn Fields, London. The course convenors were Mark Wilson, a consultant neurosurgeon at St Mary’s Hospital with a specialist interest in neurotrauma, …
Rats in a box: junior doctors and the NHS
Authors: Naaheed Mukadam
Journal: BMJ (2008)

Most people have heard of classic or Pavlovian conditioning, but the recent experience of doctors in the MTAS and MMC debacle raised parallels with another form of conditioning, operant conditioning, famously studied by the US psychologist Frederic Skinner.

Skinner placed hungry rats in a box and observed their behaviour in response to certain stimuli. Rats could press a lever that might lead to a food pellet being dropped into their box. This reward would reinforce the lever pressing behaviour, whereas the delivery of an unpleasant stimulus on pressing the lever led to a reduction in lever presses. Skinner studied the rats’ responses to food rewards given in either a predictable or unpredictable way and found that the most strongly reinforced …
DIRECT COMPARISON OF SAFETY AND EFFECTIVENESS OF THE THREE DIFFERENT DIRECT ORAL ANTICOAGULANTS IN 1785 PATIENTS WITH NONVALVULAR ATRIAL FIBRILLATION
Authors: Yohei Sotomi, Akio Hirata, Tomoaki Nakano, Ryohei Amiya, Nobuhiko Makino, Masao Koide, Takaharu Hayashi, Shimpei Nakatani, Yasuharu Takeda, Yoshiharu Higuchi
Journal: Journal of the American College of Cardiology (2018)
Low-Protein Diet Induces IRE1α-Dependent Anticancer Immunosurveillance
Authors: Camila Rubio-Patiño, Jozef P. Bossowski, Gian Marco De Donatis, Laura Mondragón, Elodie Villa, Lazaro E. Aira, Johanna Chiche, Rana Mhaidly, Cynthia Lebeaupin, Sandrine Marchetti, Konstantinos Voutetakis, Aristotelis Chatziioannou, Florence A. Castelli, Patricia Lamourette, Emeline Chu-Van, François Fenaille, Tony Avril, Thierry Passeron, John B. Patterson, Els Verhoeyen, Béatrice Bailly-Maitre, Eric Chevet, Jean-Ehrland Ricci
Journal: Cell Metabolism (2018)
Vimentin 3 and endothelin in prostate cancer.
Authors: Tobias Kohl, Melanie von Brandenstein, Andreas Stog, Monika Schlosser, Timur H. Kuru, David Pfister, Jochen Fries, Axel Heidenreich
Journal: Journal of Clinical Oncology (2018)

349 Background: An upregulation of vimentin 3, a truncated version of the full length vimentin, with an unknown function, was previously described by our group, in a direct dependency of increased ET-1 levels. We analyzed now vimentin 3 in further genitourinary cancers. Here, we describe our findings how vimentin 3 is part of the signaling pathways from Endothelin-1 (ET-1) and the Endothelin-A-Receptor (ETAR) and how it correlates with aggressive tumor behavior in a PCa cell culture and in human tissue and serum samples from PCa patients. Methods: DU145 cells were cultured. We stimulated with ET-1 with and without artificial downregulation of the ETAR, the ETBR or both receptors. A scratch assay was performed to demonstrate the influence of ET-1. Proteins were then extracted and WB for vimentin full length and vimentin 3 was performed. Additionally we analyzed ET-1 and vimentin 3 in serum from prostate cancer patients using ELISA and we did IF and IHC staining for vimentin 3 in human prostate cancer tissue. Results: Treatment with ET-1 and downregulation of the ETBR lead to a significant increased migration of DU145 cells after 3 and 6 h. The corresponding WB showed increased vimentin 3. ELISA showed increased levels of ET-1 in samples of prostate cancer patients compared to patients with no cancer history. ELISA could also demonstrate elevated levels of vimentin 3 in serum of patients with local disease and significantly elevated values in metastatic prostate cancer patients compared to patients with no cancer history. Conclusions: The data presented shows that ET-1 stimulation leads to overexpression of vimentin 3 in prostate cancer cell cultures and a concomitant aggressive biological behavior. Here we previously described the direct interaction of Vimentin 3 in prostate cancer and the activation mechanism via ET-1 and the ETAR. IHC, IF show an upregulation of the truncated variant Vimentin3 in tissue samples. In an Vimentin 3 ELISA we could show that this truncated variant is increased and therefore represents a potential biomarker. Highest values of vimentin 3 were measured using ELISA in serum of patients with recurrent and metastatic disease also suggesting that vimentin 3 correlates with aggressive tumor behavior.
Persistence of Sexual Harassment and Gender Bias in Medicine Across Generations—Us Too
Authors: Saate Shakil, Megan Lockwood, Deborah Grady
Journal: JAMA Internal Medicine (2018)

We welcome this important perspective on gender bias in medicine by DeFilippis.1 We were struck by how much we can relate to the author's anecdotes, both as attending physicians and as trainees: these experiences, though not novel, continue to be all too familiar.
The Changing Landscape of Pediatric Migraine Therapy
Authors: Carlyn Patterson-Gentile, Christina L. Szperka
Journal: JAMA Neurology (2018)

Migraine is a disabling and prevalent condition that affects the pediatric and adolescent population. This review describes current acute and preventive migraine pharmacologic therapies for the pediatric and adolescent population.Multiple pharmacotherapies that have been used in the treatment of acute headache and prevention in pediatric migraine are reviewed. There have been recent advances in the management of migraines among pediatric and adolescent patients, including US Food and Drug Administration approval of triptans for acute management in children as young as 6 years, and the first prospective, randomized, double-blind, placebo-controlled comparative study of preventive pharmacotherapy in pediatric migraine. A major challenge of evidence-based research in pediatric and adolescent migraine is the significant placebo effect.Although progress is being made in the management of migraines among pediatric and adolescent patients, there remains much work to be done.
11C-4DST PET/CT Imaging of Cardiac Sarcoidosis
Authors: Masatoshi Hotta, Ryogo Minamimoto, Shuji Kubota, Toru Awaya, Yukio Hiroi
Journal: Clinical Nuclear Medicine (2018)

A 75-year-old woman with a history of sarcoidosis presenting with low cardiac output and complete right bundle-branch block underwent 4'-[methyl-C]-thiothymidine (4DST) PET/CT after cardiac MRI and FDG PET/CT for the evaluation of suspected cardiac sarcoidosis (CS) before treatment. Cardiac MRI revealed late gadolinium enhancement on the anterior-to-lateral and posterior wall, indicating CS. FDG uptake was shown on the anterior-to-lateral wall, but not on the posterior wall. In contrast, 4DST uptake was demonstrated on both anterior-to-lateral and posterior walls. Use of 4DST appears promising for detecting CS without dietary restriction, due to the lack of physiological uptake in myocardium.
3D Organoids from Milligrams of Genitourinary Cancer Patients Tissue Retain Key Features of Original Tumors.
Authors: Yue Wang, Glauco R Souza, Robert J. Amato
Journal: Journal of Clinical Oncology (2018)

268 Background: 3D organoid culture, especially that generated from patient samples, is becoming prevalent as 2D cell culture models fail to provide clinical relevance. However, a relatively large amount of starting tissue is still required for this process, and the turnover rate and overall success rate vary greatly if relying solely on spontaneous aggregation. Methods: Here, we report the successful use of magnetic 3D bioprinting to drive organoid formation derived from fresh tumor samples of patients with prostate cancer, renal cell cancer, and urothelial cancer. Results: Only milligrams to tens of milligrams of starting tissues (from fine-needle biopsies, core biopsies, or surgical excision) were used. Most organoids formed overnight, with a very high overall success rate ( &gt; 95%, n = 25). We have demonstrated that these cultures can be maintained, passed, and cryopreserved like conventional 2D cultures. More importantly, we characterized the organoids derived from prostatic adenocarcinomas and neuroendocrine tumors by the means of immunostaining and showed that the organoids expressed the same signature proteins as the originating tumors. This clinical concordance is crucial for downstream translational and biological research. We also showed that these adenocarcinoma cells responded to enzalutamide, an androgen receptor inhibitor that is used clinically to treat prostatic adenocarcinoma. Conclusions: In summary, we have established an efficient and robust system to create patient-derived 3D organoids; molecular characterization shows clinical concordance with original patient tumors; and our system shows great potential in drug screening with patient-derived 3D cultures.
PRESSURE-VOLUME LOOP ANALYSIS DURING MULTI POINT PACING IN CARDIAC RESYNCHRONIZATION THERAPY
Authors: Wouter van Everdingen, Alwin Zweerink, Odette A.E. Salden, Maarten Jan Cramer, Pieter Doevendans, Elien Engels, Albert van Rossum, Frits Prinzen, Kevin Vernooy, Cornelis Allaart, Mathias Meine
Journal: Journal of the American College of Cardiology (2018)
CHALLENGING VOLTAGE MAPPING FOR SCAR DECHANNELING IN A LARGE ANIMAL MODEL OF MYOCARDIAL INFARCTION
Authors: Tobias Plenge, Johannes Terporten, Alexandra Maul, Arian Sultan, Jakob Lueker, Jan van den Bruck, Anja Sterner-Kock, Daniel Steven, Dennis Ladage
Journal: Journal of the American College of Cardiology (2018)
(Meth)acrylate allergy: frequently missed?
Authors: S. Rolls, S. Rajan, A. Shah, J.F. Bourke, M.M. Chowdhury, S.A. Ghaffar, C. Green, G.A. Johnston, D.I. Orton, C. Reckling, N.M. Stone, S.M. Wilkinson, D.A. Buckley
Journal: British Journal of Dermatology (2018)
I am a career paediatrician, have not done any membership exam, but have one year of experience in paediatrics. Now I'm thinking of going for general practice. What should I do?
Authors: Bill Irish
Journal: BMJ (2004)

<i>Got a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.</i>
Are prostate cancer treatments correlated to sleep distress?
Authors: Darryl Mitteldorf, Jerrod Nelms
Journal: Journal of Clinical Oncology (2018)

347 Background: Sleep distress associated with prostate cancer due to emotional issues like anxiety is well documented. But there have been no investigations focused on sleep distress correlated to specific types of prostate cancer treatments. Methods: During a ten day period in July, 2016, 963 men diagnosed with prostate cancer completed an online survey containing demographic and treatment history questions, the Pittsburg Sleep Quality Index (PSQI) and a current state of health self-assessment. The subjects were randomly chosen from the Malecare prostate cancer support network in the United States and completed the survey. 27% of survey subjects reported being initially diagnosed with Gleason 8 or higher. 42% reported using either androgen deprivation therapy, Zofigo, Xtandi or Xofigo within three months of our survey. Only 5% had been continually on active surveillance. We compiled the PSQI Component score and correlated the scores to a specific prostate cancer treatments, adjudicating for pre-existing conditions such as emotional disorders or apnea. We stratified for race, age, sexual orientation and if the subject had a sleep partner. Results: The PSQI handout says that a total score of 5 or greater indicates sleep distress worthy of consultation with a healthcare provider. Our investigation also considered a “4” to indicate poor sleep quality among participants. Only 398 (41.33%) of our participants scored less than 5 on the PSQI, while only 232 (24.09%) scored less than 4. From these statistics, we showed that over 75% of our study sample suffered sleep distress. However, our analysis failed to disclose significant correlations between specific types of prostate cancer treatments and extent of sleep distress. We did not see correlations regarding subject’s age, race, sleep co-habitation, time from diagnosis to survey and other treatment and demographic stratifications. Conclusions: Sleep distress is well established and broadly experienced by prostate cancer patients. Our study showed there is no advantage to any specific prostate cancer treatment in terms of sleep distress. We also found that severity and instances of sleep distress are distributed without significance across age, race, sexual orientation and time to treatment after diagnosis.