tbuckley/cabot-search huggingface dataset:
Successful treatment of severe psoriasis relapse with secukinumab (interleukin 17 A inhibitor) after abrupt brodalumab (interleukin 17 receptor inhibitor) discontinuation: A retrospective study evaluating long-term efficacy and safety
Authors: Abdallah Khemis, Awatef Kelati, Henri Montaudié, Jean-Philippe Lacour, Thierry Passeron
Journal: Journal of the American Academy of Dermatology (2018)
SOCIAL NETWORK CHARACTERISTICS OF PATIENTS WITH HYPERTENSION AND DIABETES IN WESTERN KENYA
Authors: Samuel Ruchman, Allison DeLong, Winnie Matelong, Evon Okidi, Vitalis Orango, Jemima Kamano, Gerald Bloomfield, Joseph Hogan, Carol Horowitz, Violet Naanyu, Sonak Pastakia, Valentin Fuster, Thomas Valente, Rajesh Vedanthan
Journal: Journal of the American College of Cardiology (2018)
CRTH2 expression on T cell subsets in asthma
Authors: Teerapol Chantveerawong, Panitan Pradubpongsa, Sarawut Jindarat, Wat Mitthamsiri, Rattanaporn Fuengthong, Atik Sangasapaviliya, Tadech Boonpiyathad
Journal: Journal of Allergy and Clinical Immunology (2018)
Musculoskeletal clinical examination course
Authors: Robbie Ray
Journal: BMJ (2008)

This is a one day clinical examination course run by the team who maintain the Orthoteers website, a popular web based resource for orthopaedic trainees. It is a completely practical course without any formal lectures, and the emphasis is on learning slick, reproducible examination techniques. The areas covered are shoulder, elbow, wrist, hand, spine, hip, knee, ankle, and foot.

Originally, Orthoteers ran as a revision course for senior orthopaedic trainees preparing for their exit exams, but there was a lot of interest from junior orthopaedic trainees, sports medicine doctors, rheumatologists, and physiotherapists. To accommodate this, …
European parliament votes through directive on movement of doctors
Authors: Caroline White
Journal: BMJ (2013)

The European parliament has given the go ahead to plans to facilitate the movement of doctors and other healthcare professionals among EU countries.1

The vote on the revised directive on mutual recognition of professional qualifications confirms an informal agreement reached by EU decision makers earlier this summer.2

The revisions are expected to be formally approved by the European Council within the next few weeks, after which member states …
Safety and feasibility of immuno-cryotherapy.
Authors: Junaid Raja, Anish Ghodadra, Scott N. Gettinger, Harriet M. Kluger, Mario Sznol, Kurt Alex Schalper, Hyun S. "Kevin" Kim
Journal: Journal of Clinical Oncology (2018)

34 Background: To investigate the safety and feasibility of image guided immuno-cryotherapy in patients with immune checkpoint inhibitor failure. Methods: Consecutive patients with primary or acquired failure to immune checkpoint inhibitor therapy were studied following treatment with concomitant image-guided cryotherapy and immune checkpoint inhibition. In addition to demographic features, type of malignancy, size of targeted metastatic lesion, number of cycles of cryotherapy, systemic immunotherapy, and adverse events in a 90 day post procedural window were extracted. The primary end point was safety and adverse events stratified by the common terminology for adverse events (CTCAE) criteria. As a secondary endpoint, efficacy of the cryotherapy was assessed by iRECIST. Results: Ten patients underwent combined image-guided cryotherapy and checkpoint immunotherapy between 2015 and 2017. Five patients received CTLA 4 blockade with cryotherapy, and 8 patients received PD1 axis blockade and cryotherapy. Six patients had metastatic non-small cell lung cancer and 4 had metastatic melanoma. Immunoprofiling demonstrated one patient each with a mutation in NRAS (G12C), NRAS (Q61R), KRAS (G12C), and ALK; and 2 with aBRAF V600E mutation. Cryotherapy was performed in immunotherapy failure sites, including liver (5) and adrenal glands (3), lymph node and muscle. The median size of targeted lesions was 4.5 cm (standard deviation 3.7cm). There were no grade 3 or higher adverse event, though 6 patients had grade 1 and 2 adverse effects in the periprocedural period which included fatigue, local pain, and poor appetite, isolated cases of diarrhea, colitis, pneumothorax, and procedural site hematoma. Regarding therapeutic response: 5 patients demonstrated partial response, 1 stable response, and 1 progression of disease. Two patients died in the followup period from non-treatment induced causes and 1 is awaiting follow-up. Disease control rate was 85.7%. Conclusions: Immuno-cryotherapy with immune checkpoint therapy in patients with immune checkpoint inhibitor resistance is safe and feasible in metastatic NSCLC and melanoma. There were no grade 3 or above adverse events.
Postgraduate certificate in allergy
Authors: Shyla Chacko Jehangir
Journal: BMJ (2011)

Imperial College London’s allergy programme offers the option to study for a postgraduate certificate in allergy or a full masters degree. The certificate (PG Cert Allergy) can be done in nine months of part time study, while the MSc is a two or three year programme.

The certificate course is a blended direct teaching and e-learning course for healthcare professionals who deal with people who have allergies: doctors (whether hospital based or general practitioners), nurses, dietitians, and scientists from the UK and worldwide. Applicants would normally have a degree in medicine or an upper second class honours degree in a healthcare related subject, typically nursing, dietetics, immunology or physiology, or biomedicine. …
Plans to restrict access to drugs will put vulnerable patients at risk, BMA argues
Authors: Gareth Iacobucci
Journal: BMJ (2018)

Proposals to restrict access to drugs that can be bought over the counter for minor, short term conditions will put vulnerable patients at risk, the BMA has warned.

NHS England is consulting on plans to issue national guidance to clinical commissioning groups (CCGs) on limiting GPs’ prescribing of over-the-counter products for 35 minor or self limiting conditions, as part of a push to save money and tackle unwarranted variation in prescribing.12

But in its response to the consultation, which closes on 14 March, the BMA said that the proposals would …
A new 50-gene molecular subtype classifier: An evaluation of subtype stability and association with response to neoadjuvant chemotherapy in muscle-invasive bladder cancer.
Authors: Woonyoung Choi, Elizabeth R. Plimack, Arlene O. Siefker-Radtke, Colin P.N. Dinney, David James McConkey
Journal: Journal of Clinical Oncology (2018)

519 Background: The bladder cancer basal and luminal molecular subtypes have been associated with differential progression patterns and responses to neoadjuvant chemotherapy. However, they are typically identified by whole transcriptome expression profiling, which may be impractical for most academic centers. To make subtype classification more accessible, we developed a 50-gene basal and luminal subtype classifier and examined its performance in matched tumor specimens, including pretreatment biopsies from patients treated with neoadjuvant chemotherapy. Methods: We refined a 50-gene subtype classifier derived from a oneNN classifier containing &gt;~2000 genes that we previously developed using unsupervised methods. We compared its accuracy against calls made using the original oneNN classifier, including 148 tumors from a neoadjuvant chemotherapy meta dataset. To test subtype stability, tumors in 2 different datasets (30 sets of matched primary and lymph node tumors and 43 sets of matched pre- and post-chemotherapy tumors) were assigned using 50-gene subtype classifier with Linear Discriminator Analysis (LDA) prediction algorithms. Results: In the NAC cohort, patients with tumors assigned to the basal subtype by the 50-gene classifier had better survival outcomes compared to the luminal tumors, consistent with the conclusion generated with the parent classifier (p&lt;0.05). Basal subtype assignments were stable in 62.5 % of pairs, whereas luminal tumors displayed 100% stability. In matched pre- and post-chemotherapy tumors, basal tumors displayed 78% stability while luminal tumors showed 94% stability. Conclusions: Based on these preliminary data, it appears that basal tumors display higher plasticity than luminal tumors with these specific contexts. This plasticity may interfere with precise subtype predictions with tumors assigned to the basal subtype at biopsy.
Association of Changes in Plasma Neurofilament Light and Tau Levels With Anesthesia and Surgery
Authors: Lisbeth Evered, Brendan Silbert, David A. Scott, Henrik Zetterberg, Kaj Blennow
Journal: JAMA Neurology (2018)

Anesthesia and surgery are believed to act on the central nervous system by a fully reversible mechanism innocuous to nerve cells. Evidence that neurological sequelae may follow would challenge this belief and would thereby suggest a need to reassess theories of the mechanism of anesthetic action or the response of the central nervous system to surgery.To measure 2 biomarkers of neurological injury (neurofilament light and tau) in plasma in a series of timed collections before and after anesthesia and surgery.These 2 related observational studies (CAPACITY and ARCADIAN) recruited patients 60 years and older who were undergoing general anesthesia for surgeries performed within a tertiary hospital. Blood samples were taken immediately before surgical anesthesia was administered and then sequentially after surgery at 30-minute, 6-hour, 24-hour, and 48-hour intervals. Sampling took place from January 2014 to August 2015. Data analysis took place from October 2016 to February 2017.Plasma neurofilament light and tau.A total of 30 patients were enrolled (13 from the CAPACITY study and 17 from the ARCADIAN study). The mean (SD) age was 69.1 (7.0) years, and 18 members (59%) of the participant group were female; 22 (73%) were undergoing joint arthroplasty. Mean neurofilament light increased at each measurement from a combined baseline mean (SD) of 22.3 (20.4) pg/mL to a maximal combined mean (SD) level of 35.1 (28.7) pg/mL, a maximum increase of 67% (95% CI, 45%-89%; P < .001), at 48 hours postoperatively. The level of tau increased significantly from baseline at every measurement, from a combined baseline mean (SD) of 3.1 (1.3) pg/mL to a maximal combined mean (SD) of 10.8 (9.5) pg/mL, a peak increase of 257% (95% CI, 154%-361%; P < .001), at 6 hours postoperatively. After 6 hours, the mean level began to return to baseline but remained elevated after 48 hours.Neurofilament light is a specific marker of axonal injury and has been shown to indicate neuronal damage in a number of diseases. Tau proteins are an integral component of axonal integrity, and increased tau indicates neuronal damage. The increases in both neurofilament light and tau over 48 hours after surgery suggest that general anesthesia and surgery may be associated with neuronal damage in the short term. Further investigations will be required to study any association with clinical outcomes. These preliminary findings demand that we question the prevailing assumption that anesthesia and surgery are innocuous, transient, and without injurious changes to the central nervous system.
Abstract 136: A Case of Complex Congenital Heart Disease with Postoperative Complications of Impaired Consciousness and Several Arrhythmias due to Encephalitis in the Acute Stage of Kawasaki Disease
Authors: Naomi Nakagawa, Masahiro Kamada, Yukiko Ishiguchi, Yuji Moritoh, Kenji Okamoto
Journal: Circulation (2015)

Background: In addition to muscular and medium arteries, Kawasaki disease causes inflammation in nerves and the myocardium. However, arrhythmia severe enough to be problematic is rare. Patient: At age 1 day, the patient was in a state of shock and was diagnosed with Taussig-Bing anomaly and aortic arch coarctation. At age 4 days, he underwent aortic arch reconstruction and pulmonary arterial banding. At age 2 months, he underwent arterial switch operation and ventricular septal defect closure. No significant arrhythmias were observed. At age 5 years 6 months, he had a fever, and 5 days later, he developed rash, conjunctival hyperemia, and redness of the lips and fingertips. Kawasaki disease was diagnosed on day 7 after symptom onset. The patient presented with disorientation, so electroencephalography and magnetic resonance imaging were performed and revealed overall slow-wave activity and cerebral edema, respectively, indicating complicated encephalitis. Sinoatrial block and sinus arrest were also observed. The patient received ultrahigh-dose γ-globulin therapy and steroid pulse therapy for encephalitis. The fever resolved at a total γ-globulin dose of 4 g/kg. The other main Kawasaki disease symptoms also disappeared. By day 18, his consciousness completely recovered but the sinus arrest remained. On day 20, an atrial flutter developed from tachycardia that was treated with electric shocks. Sinus arrest at a maximum of 5.7 s was observed at that time, and bradycardia-tachycardia syndrome was suspected. On the same day, the sinus arrest improved gradually and largely disappeared 3 days later. The atrial flutter also disappeared. Discussion: Severe arrhythmia that requires treatment is rare in Kawasaki disease. Our patient underwent surgery for a complex cardiac anomaly. Thus, the requisites for arrhythmia were present when the Kawasaki disease caused myocardial inflammation, which is thought to cause severe symptoms.
<i>ADCY9</i> Genetic Variants and Cardiovascular Outcomes With Evacetrapib in Patients With High-Risk Vascular Disease
Authors: Steven E. Nissen, Sreekumar G. Pillai, Stephen J. Nicholls, Kathy Wolski, Jeffrey S. Riesmeyer, Govinda J. Weerakkody, Wendra M. Foster, Ellen McErlean, Lin Li, Pallav Bhatnagar, Giacomo Ruotolo, A. Michael Lincoff
Journal: JAMA Cardiology (2018)

A pharmacogenetic analysis of dalcetrapib, a cholesteryl ester transfer protein inhibitor, reported an association between a single-nucleotide polymorphism (SNP) in the ADCY9 gene (rs1967309) and reduction in major adverse cardiovascular events despite a neutral result for the overall trial.To determine whether the association between the SNP in the ADCY9 gene and a reduction in major adverse cardiovascular events could be replicated for another cholesteryl ester transfer protein inhibitor, evacetrapib, in patients with high-risk vascular disease.A nested case-control study examining the rs1967309 SNP in 1427 cases and 1532 matched controls selected from the 12 092-patient Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition with Evacetrapib in Patients at a High Risk for Vascular Outcomes (ACCELERATE) trial, a randomized, double-blind, placebo-controlled phase 3 trial conducted in patients with high-risk vascular disease randomized from October 2012 through December 2013. The genotyping was conducted from January 2017 to March 2017, and the data analyses were conducted from July 2017 to November 2017.Evacetrapib, 130 mg, or matching placebo.The primary analyses used a conditional logistic regression model to assess the odds ratio (OR) for major adverse cardiovascular events for evacetrapib compared with placebo for each genotype. The basic model included adjustment for age, sex, and the top 5 principal components. An additional model included cardiovascular risk factors to adjust for potential bias in selecting control patients. The primary major adverse cardiovascular event end point was the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina.For patients with the AA genotype reported to demonstrate a beneficial effect from dalcetrapib, the OR for evacetrapib compared with placebo was 0.88 (95% CI, 0.69-1.12). For patients with the AG genotype, the OR was 1.04 (95% CI, 0.90-1.21). For patients with the GG genotype reported to show evidence for a harmful effect from dalcetrapib, the OR for evacetrapib was 1.18 (95% CI, 0.98-1.41). The interaction P value among the 3 genotypes was P = .17 and the trend P value was P = .06. When adjusted for cardiovascular risk factors, the OR for evacetrapib was 0.93 (95% CI, 0.73-1.19) for the AA genotype, 1.05 (95% CI, 0.91-1.22) for the AG genotype, and 1.02 (95% CI 0.85-1.24) for the GG genotype; interaction P = .71 and trend P = .59.Pharmacogenetic analysis did not show a significant association between the ADCY9 SNP (rs1967309) and cardiovascular benefit or harm for the cholesteryl ester transfer protein inhibitor evacetrapib.
18F-methylcholine PET/CT, in vivo magnetic resonance spectroscopy imaging and tissue enzyme biomarkers of choline metabolism in primary brain gliomas
Authors: Matthew Grech-Sollars, Katherine Ordidge, Babar Vaqas, Lesley Honeyfield, Sophie Camp, Sameer Khan, David Towey, David Peterson, Federico Roncaroli, Kevin O’Neill, Tara Barwick, Adam Waldman
Journal: Neuro-Oncology (2018)

Pilot C-11/ F-18 choline PET studies show differential uptake between benign and malignant tumours, however the cellular and molecular basis of this uptake and MRS-visible choline containing compounds (Cho) is not well understood. Choline kinase-α phosphorylates choline, an essential step in membrane synthesis, and is expressed by malignant tumours; it presents a potential novel therapeutic target. We investigate the relationship between choline metabolism detected in vivo using MRS and PET, CKα expression and proliferation in anatomically-defined locations within gliomas. Prospective pilot study. 14 patients with suspected primary glioma underwent multimodal 3T MRI (including multi-voxel MRS) and dynamic 18F-FMC PET/CT prior to surgery. Co-registered PET and MRI data were used to identify regions of high and low choline, and targeted biopsies were performed using a surgical planning tool. Immunohistochemistry for CKα expression was performed on these samples. All tumours showed increased tracer uptake relative to contralateral white matter. Significant differences in TBR were found between WHO grade IV and WHO grades I, II &amp; III tumours in 18F-FMC uptake and between WHO grades IV&amp;III and WHO grades I&amp;II using Cho/Cr ratios on MRS. Combining PET and MRS data showed spatial concordance between regions of high PET uptake and highest Cho/Cr ratio, however there was no correlation between the actual levels of uptake (TBR) and the Cho/Cr ratio in these regions. Furthermore, regions of contrast enhancement on MRI showed high uptake on PET. CKα expression assays showed no simple relationship with imaging parameters. Combining 18F-FMC uptake and Cho/Cr ratio on MRS may help stratify aggressive glioma phenotypes. Establishing the relationship between imaging-derived choline biomarkers markers and CKα expression is challenging, and may be confounded by both physiological and technical factors.
Accelerated Estimation of Frequency Classes in Site-Heterogeneous Profile Mixture Models
Authors: Edward Susko, Léa Lincker, Andrew J Roger
Journal: Molecular Biology and Evolution (2018)

As a consequence of structural and functional constraints, proteins tend to have site-specific preferences for particular amino acids. Failing to adjust for heterogeneity of frequencies over sites can lead to artifacts in phylogenetic estimation. Site-heterogeneous mixture-models have been developed to address this problem. However, due to prohibitive computational times, maximum likelihood implementations utilize fixed component frequency vectors inferred from sequences in a database that are external to the alignment under analysis. Here, we propose a composite likelihood approach to estimation of component frequencies for a mixture model that directly uses the data from the alignment of interest. In the common case that the number of taxa under study is not large, several adjustments to the default composite likelihood are shown to be necessary. In simulations, the approach is shown to provide large improvements over hierarchical clustering. For empirical data, substantial improvements in likelihoods are found over mixtures using fixed components.
IDENTIFYING FAMILIAL HYPERCHOLESTEROLEMIA USING A BLOOD DONOR SCREENING PROGRAM: RESULTS FROM &gt;200,000 DONORS
Authors: Candace Wu, Stephen J. Eason, Zahid Ahmad, Colby Ayers, M. Odette Gore, Darren McGuire, Merlyn Sayers, Amit Khera
Journal: Journal of the American College of Cardiology (2018)
Correlation of IL-17 with immune suppression involving MDSC, malnutrition, and prognosis in patients with gastric and colorectal cancer.
Authors: Kenji Gonda, Masahiko Shibata, Daisuke Ujiie, Mai Ashizawa, Tomohiro Kikuchi, Hirokazu Okayama, Shoutarou Fujita, Wataru Sakamoto, Takahiro Nakajima, Hisahito Endo, Motonobu Saito, Tomoyuki Monma, Zenichiro Saze, Shinji Ohki, Koji Kono, Seiichi Takenoshita
Journal: Journal of Clinical Oncology (2018)

83 Background: Although a causal relationship linking inflammation and cancer immunity is more widely accepted today, precise cell mechanisms mediating this relationship have not been elucidated. IL-17, a pro-inflammatory cytokine primarily secreted by T helper (Th)17 cells, has previously been associated with inflammatory processes in autoimmune disease. The presence of IL-17 and Th17 cells has been confirmed in various invasive cancers and recently linked to immunosuppression in cancer patients. We investigated systemic inflammation, immune suppression, malnutrition, and prognosis associated with IL-17 in patients with gastric and colorectal cancer. Methods: We measured IL-17 in 106 patients, including 43 with gastric and 63 with colorectal cancer, Production of IL-17 stimulated by PHA was measured by ELISA. MDSC (myeloid-derived suppressor cells), which significantly contribute to immunosuppression, were measured by flow cytometry (CD11b+CD14-CD33+). Neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) were used as inflammatory markers. Production of IL-12 and the SI (stimulation index) of lymphocytes’ blastogenic response were used as markers of cell-mediated immune response. Results: Production of IL-17 increased in advanced stages of gastric and colorectal cancer. IL-17 positively correlated with levels of MDSC, serum concentrations of VEGF, NLR, and levels of CRP, and was inversely correlated with IL-12 production, SI, and nutritional markers including prealbumin and retinol binding protein. Patient cohorts were divided into two groups with IL-17 level (540 pg/ml) and OS (overall survival) of patients with stages III and IV gastric or colorectal cancer both significantly worse in patients with high production of IL-17 than in those with low IL-17, although the differences were not significant in patients at stages I and II. Conclusions: The present study suggests that IL-17 may reflect an inflammatory impact on the advancement and progression of cancer, and it may serve as useful marker of immune suppression involving MDSC, malnutrition, and poor prognosis in patients with gastric and colorectal cancer.