tbuckley/cabot-search huggingface dataset:
Effect of atopic skin stressors on natural moisturizing factors and cytokines in healthy adult epidermis
Authors: K.A. Engebretsen, S. Kezic, I. Jakasa, A. Hedengran, A. Linneberg, L. Skov, J.D. Johansen, J.P. Thyssen
Journal: British Journal of Dermatology (2018)

Epidermal deficiency of filaggrin, and the derived natural moisturizing factors (NMFs), is associated with increased risk of atopic dermatitis (AD). While filaggrin gene mutations cause filaggrin deficiency, there is limited insight into the causative environmental factors.To explore the effect of selected exogenous skin stressors on NMF and skin cytokine levels in healthy adult epidermis.Forty healthy volunteers (aged 18-49 years) were exposed to hard, soft and chlorinated water, 0·5% sodium lauryl sulfate, house dust mite, cat allergen, staphylococcal enterotoxin B (SEB), cooling and histamine. Participants were tape-stripped and biophysiological measurements performed. NMF was determined after 24 and 48 h, whereas skin cytokines were measured after 24 h for selected exposures.At 24 h, a significant decrease in NMFs was observed for soft (0·51 ± 0·19 g m-2 h-1 ) and hard water (0·61 ± 0·32 g m-2 h-1 ) compared with occlusion alone (0·71 ± 0·18 g m-2 h-1 ). Hard water led to increased levels of interleukin (IL)-4, interferon (IFN)-γ and IL-10. Exposure to house dust mite and SEB led to a significant decrease in NMFs after 24 h (0·77 ± 0·28 and 0·80 ± 0·28 g m-2 h-1 , respectively) compared with occlusion alone (1·00 ± 0·42 g m-2 h-1 ). House dust mite led to an increase in IFN-γ, IL-2 and IL-4 vs. the nonoccluded control site.Based on experimental exposure to selected atopic skin stressors, we conclude that NMFs levels are decreased along with increased secretion of various skin cytokines in healthy individuals. Our data highlight environmental factors that might play a role in AD pathophysiology.
Abstract P2-12-11: Does conservative surgery treatment for locally advanced breast cancer safe after neoadjuvant treatment?
Authors: G Boufelli, BS Mota, FC Franca, MT Doria, JY Maesaka, MD Ricci, JRM Piato, FBC Rocha, AHG Giribela, R Gonçalves, S Masili-Oku, MS Mano, LF Chala, BM Thompson, EC Baracat, JR Filassi
Journal: Cancer Research (2018)

Abstract BACKGROUND: The aim of this study was to assess the oncological efficacy of breast conserving surgery (BCS) after neoadjuvant chemotherapy in patients with local advanced breast cancer. PATIENTS AND METHODS: A retrospective cohort study was conducted with locally advanced breast cancer invasive (Stage IIb to III) treated at ICESP, an oncologic referral center between 2008 and 2016. Endpoints were disease free survival (DFS), local disease free survival (LDFS) and overall survival (OS). Multivariable analyses were performed using Cox proportional hazards models. RESULTS: 530 patients were included, 26% (138) were stage IIB, 41.9% (222) IIIA, 29.6% (157) IIIB and 2.5% (13) IIIA. 88.8% (470) were invasive ductal carcinoma. The mean age was 51.5(23-95). 95.5% and 4.5% were submitted Neoadjuvant Chemotherapy and Hormone therapy, respectively. The BCS were performed in 24.5% (130) patients versus 75.5% (400) of mastectomies. The mean follow up was 36.4(0.16-80.2) months. There were no differences in local disease free-survival 59 (95%CI 58-61) versus 60 (95%CI 57-60); p=0.4 and overall survival 56.2 (95%CI 52-60) versus 59.3(95%CI 53-65); p= 0.24 for mastectomy and BCS. The disease free survival was lower at mastectomy group 51.4 (95%CI 49-53) versus 56,8 (95%CI 53-59); p=0.01. Logistic regression models were significant only for cancer stage both patterns, although the results were better for masses, particularly when kinetic assessments were included (LR 12.8; p = 0.005) CONCLUSION: In our population, the BCS does not affect the overall and local disease-free survival rates, which seems to be safe to perform in patients who desire to conserve the breast after neoadjuvant treatment. Citation Format: Boufelli G, Mota BS, Franca FC, Doria MT, Maesaka JY, Ricci MD, Piato JRM, Rocha FBC, Giribela AHG, Gonçalves R, Masili-Oku S, Mano MS, Chala LF, Thompson BM, Baracat EC, Filassi JR. Does conservative surgery treatment for locally advanced breast cancer safe after neoadjuvant treatment? [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-12-11.
Mutation, methylation, and gene expression profiles in dup(1q)-positive pediatric B-cell precursor acute lymphoblastic leukemia
Authors: Rebeqa Gunnarsson, Sebastian Dilorenzo, Kristina B Lundin-Ström, Linda Olsson, Andrea Biloglav, Henrik Lilljebjörn, Marianne Rissler, Per Wahlberg, Anders Lundmark, Anders Castor, Mikael Behrendtz, Thoas Fioretos, Kajsa Paulsson, Anders Isaksson, Bertil Johansson
Journal: Leukemia (2018)

High-throughput sequencing was applied to investigate the mutation/methylation patterns on 1q and gene expression profiles in pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL) with/without (w/wo) dup(1q). Sequencing of the breakpoint regions and all exons on 1q in seven dup(1q)-positive cases revealed non-synonymous somatic single nucleotide variants (SNVs) in BLZF1, FMN2, KCNT2, LCE1C, NES, and PARP1. Deep sequencing of these in a validation cohort w (n = 17)/wo (n = 94) dup(1q) revealed similar SNV frequencies in the two groups (47% vs. 35%; P = 0.42). Only 0.6% of the 36,259 CpGs on 1q were differentially methylated between cases w (n = 14)/wo (n = 13) dup(1q). RNA sequencing of high hyperdiploid (HeH) and t(1;19)(q23;p13)-positive cases w (n = 14)/wo (n = 52) dup(1q) identified 252 and 424 differentially expressed genes, respectively; only seven overlapped. Of the overexpressed genes in the HeH and t(1;19) groups, 23 and 31%, respectively, mapped to 1q; 60-80% of these encode nucleic acid/protein binding factors or proteins with catalytic activity. We conclude that the pathogenetically important consequence of dup(1q) in BCP ALL is a gene-dosage effect, with the deregulated genes differing between genetic subtypes, but involving similar molecular functions, biological processes, and protein classes.
How many cores are needed to detect clinically significant prostate cancer on targeted MRI-ultrasound fusion biopsy?
Authors: Amanda Lu, Kamyar Ghabili, Kevin Nguyen, Michael Leapman, Preston Sprenkle
Journal: Journal of Clinical Oncology (2018)

134 Background: The optimal number of MRI-US fusion biopsy cores to adequately sample regions of interest (ROI) remains unknown. To better understand the optimal approach to lesion targeting, we aimed to examine the cancer detection rate based on sequential number of cores obtained. Methods: Of 744 patients undergoing MRI-US fusion biopsy between 2012 and 2016 at our institution, we identified 628 men with targets on multi-parametric MRI (mpMRI) who underwent targeted and systematic fusion biopsy using the Artemis platform for clinical suspicion (n=465) or known history of PCa (n=163). mpMRI studies were reviewed by genitourinary radiologists using a 3-tiered Likert scale and PI-RADS classification schema. Biopsy was performed by two urologists performing a high volume of fusion biopsies (PS and RD). Cores were taken sequentially from each ROI with an even distribution. The primary outcome was the proportion of high-grade (Gleason ≥3+4) cancers missed on a 2-core lesion biopsy. Results: We biopsied 1,233 ROI with a median of 5 cores (IQR 3-5) from each ROI. A total of 581 ROI (47%) were positive for any Gleason grade PCa, in 380 (61%) patients. On a per-lesion basis, 84% of any Gleason score cancers were detected with a two-core biopsy and 77% of Gleason ≥3+4 tumors. Cancer detection rates improved with increasing number of cores (Table 1). For any Gleason grade PCa, additional cores beyond 5 cores had no significance. For G≥3+4 cancer, there was no significance with additional sampling from 3 to 4 cores, but improved detection from 3 to 5 cores (P&lt;0.05). For PI-RADs 4 and 5 lesions, additional sampling up to 4 cores significantly improves G≥3+4 detection, while for PI-RADs 1-3 lesions sampling up to 2 cores improves detection. Conclusions: On a per-lesion basis, sampling two cores of mpMRI-evident lesions at the time of fusion biopsy misses nearly one-quarter of clinically significant PCa that would be detected on additional sampling. [Table: see text]
Euglycemic ketoacidosis, a common and underecognized complication of continuous renal replacement therapy using glucose-free solutions
Authors: Maxime Coutrot, Guillaume Hékimian, Thibaut Moulin, Nicolas Bréchot, Matthieu Schmidt, Sébastien Besset, Ania Nieszkowska, Guillaume Franchineau, Simon Bourcier, Olivier Bourron, Charles-Edouard Luyt, Alain Combes
Journal: Intensive Care Medicine (2018)
Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables
Authors: Emma Ahlqvist, Petter Storm, Annemari Käräjämäki, Mats Martinell, Mozhgan Dorkhan, Annelie Carlsson, Petter Vikman, Rashmi B Prasad, Dina Mansour Aly, Peter Almgren, Ylva Wessman, Nael Shaat, Peter Spégel, Hindrik Mulder, Eero Lindholm, Olle Melander, Ola Hansson, Ulf Malmqvist, Åke Lernmark, Kaj Lahti, Tom Forsén, Tiinamaija Tuomi, Anders H Rosengren, Leif Groop
Journal: The Lancet Diabetes & Endocrinology (2018)
UK should train more generalists and give all trainees full GMC registration, says review
Authors: Abi Rimmer
Journal: BMJ (2013)

The UK should train more generalist doctors and extend full registration with the General Medical Council to all trainee doctors, a major review of postgraduate medical education and training has concluded.

The UK-wide “Shape of Training” review, led by David Greenaway, vice chancellor of Nottingham University, has made a wide range of recommendations on how UK medical training should develop.1 It said that some changes should be implemented immediately, such as forming a UK-wide group to deliver the changes, while others should be completed within two to five years.

The review was jointly sponsored by the Academy of Medical Royal Colleges, the GMC, Health Education England, and the Medical Schools Council, among others. It looked at five areas: the balance of the medical workforce; flexibility of training; breadth and scope of training; balance between service and training; and needs of the patient. …
STAT3 inhibition for gastroenteropancreatic neuroendocrine tumors: Potential for a new therapeutic target?
Authors: Alexandra G Lopez-Aguiar, Lauren McLendon Postlewait, Mohammad Zaidi, Kristen Zhelnin, Alyssa Krasinskas, Maria C. Russell, David A. Kooby, Kenneth Cardona, Bassel F. El-Rayes, Shishir Maithel
Journal: Journal of Clinical Oncology (2018)

340 Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are highly vascular tumors with similar treatments applied to all sites. The expression of pro-angiogenic factors (STAT3, VEGF, and HIF-1α) and their association with known adverse pathologic factors and disease recurrence after resection is not known. Methods: All pts with non-metastatic primary GEP-NETs who underwent curative-intent resection at a single institution from 2000-2013 were included. Immunohistochemistry was performed for STAT3, VEGF, HIF-1α, Ki-67 index, and CD31 using tissue microarrays made in triplicate by a pathologist blinded to other clinicopathologic variables. STAT3, VEGF, and HIF-1α were categorized into high vs low expression; CD31 was dichotomized at the median value. Primary outcome was 3-yr recurrence-free survival (3-yr RFS); secondary outcomes were correlation of STAT3, VEGF, and HIF-1α expression with Ki-67 index, adverse pathologic factors, and CD31 expression, a marker of microvascular density. Results: Of 265 GEP-NETs resected, 144 had tissue for analysis. STAT3 expression was high in 12 (8%) and low in 132 (92%). VEGF expression was high in 19 (13%) and low in 125 (87%), and HIF-1α was high in 1 (1%) and low in 143 (99%). High STAT3 expression was associated with worse 3-yr RFS compared to low expression (55% vs 84%; p = 0.003). High VEGF expression had a 3-yr RFS of 76% compared to 82% for low expression (p = 0.098); HIF-1α expression was not associated with RFS. Ki-67 ≥3% was associated with worse 3-yr RFS (≥3%: 51% vs &lt; 3%: 84%; p &lt; 0.001), as was the presence of lymphovascular invasion (LVI: 72% vs 95%; p = 0.001) and increased microvascular density per µm 2 (CD31 &gt; median: 75% vs CD31 &lt; median: 86%; p = 0.043). High STAT3 expressing tumors were more likely to have a Ki-67≥3% (42% vs 7%; p &lt; 0.001). LVI was present in 82% of high STAT3 tumors compared to only 50% with low STAT3 (p = 0.058). CD31 overexpression was similar between groups (58% vs 49%; p = 0.5). Conclusions: In resected GEP-NETs, high STAT3 expression is associated with an increased Ki-67 index, presence of lymphovascular invasion, and worse 3-yr RFS. STAT3 inhibition may be a novel therapeutic option for patients undergoing resection of high-risk tumors.
Short course of grass allergen peptides immunotherapy over 3 weeks reduces seasonal symptoms in allergic rhinoconjunctivitis with/without asthma: A randomized, multicenter, double‐blind, placebo‐controlled trial
Authors: R. Mösges, C. Bachert, P. Panzner, M. A. Calderon, L. Haazen, S. Pirotton, N. Wathelet, S. R. Durham, M.‐A. Bonny, T. Legon, R. von Frenckell, O. Pfaar, M. H. Shamji
Journal: Allergy (2018)

Abstract Background Immunotherapy with peptide hydrolysates from Lolium perenne ( LPP ) is an alternative treatment for seasonal allergic rhinitis with or without asthma. The aim of this study was to assess the clinical efficacy and safety of a cumulative dose of 170 μg LPP administered subcutaneously over 3 weeks. Methods In a randomized, double‐blind, placebo‐controlled trial, 554 adults with grass pollen rhinoconjunctivitis were randomized (1:2 ratio) to receive 8 subcutaneous injections of placebo or 170 μg LPP administered in increasing doses in 4 visits over 3 weeks. The primary outcome was the combined symptom and medication score ( CSMS ) measured over the peak pollen season. Reactivity to conjunctival provocation test ( CPT ) and quality of life ( QOL ) was assessed as secondary endpoints. Results The mean reduction in CSMS in the LPP vs placebo group was −15.5% ( P = .041) during the peak period and −17.9% ( P = .029) over the entire pollen season. LPP ‐treated group had a reduced reactivity to CPT ( P &lt; .001) and, during the pollen season, a lower rhinoconjunctivitis QOL global score ( P = .005) compared with placebo group. Mostly mild and WAO grade 1 early systemic reaction ( ESR ) were observed ≤30 minutes in 10.5% of LPP ‐treated patients, whereas 3 patients with a medical history of asthma (&lt;1%) experienced a serious ESR that resolved with rescue medication. Conclusion Lolium perenne pollen peptides administered over 3 weeks before the grass pollen season significantly reduced seasonal symptoms and was generally safe and well‐tolerated.
Type I interferons promote the survival and proinflammatory properties of transitional B cells in systemic lupus erythematosus patients
Authors: Mei Liu, Qiang Guo, Chunmei Wu, Delphine Sterlin, Shyamal Goswami, Ying Zhang, Teng Li, Chunde Bao, Nan Shen, Qiong Fu, Xiaoming Zhang
Journal: Cellular and Molecular Immunology (2018)
What is the procedure for overseas doctors wanting to work in Canada?
Authors: Deana Midmer
Journal: BMJ (2005)

Have 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 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. <b>www.bmjcareers.com/advicezone</b>
Factors predicting favourable outcome for recovery of peri-operative neurological deficits in cranio-spinal intrinsic tumours: A single centre experience
Authors: Kishor Choudhari, Shashank Joshi
Journal: Neuro-Oncology (2018)

To review demographic, pathological and surgical factors that minimise long-term neurological deficits in cranio-spinal intrinsic tumours. DESIGN Retrospective analysis. SUBJECTS 33 patients with cranio-spinal intrinsic tumours located in eloquent areas treated at a single centre over a period of five years. From a cohort of 780 neuro-oncology patients, 33 (24 cranial and9 spinal) patients harbouring brain or spinal cord intrinsic tumours in eloquent areas were identified who had significant perioperative neurological deficits but near-complete recovery of the deficits within three months of surgical intervention. In addition to demographic data, technical factors related to surgery and tumour pathology were analysed to determine which factors may influence recovery of deficits. Surgical technical factors were studied for feasibility of gross macroscopic resection. All patients who recovered from their deficits were less than 63 years of age, all except three patients had pathology ranging Gr I-III. In three patients, it wasGr IV. All except three had radical resection of tumour as proven by contrastimaging in the immediate post-operative period and at three months. Age, tumourgrade &amp; extent of surgical resection appeared to be the factors influencingrecovery of neurological deficits. Younger age, lower grade of tumour and grosstotal excision of the tumour at surgery appeared to be favourable factors forrecovery of peri-operative deficits. In a retrospectiveanalysis, younger age, lower grade of tumour and radical surgical excisionappear to be factors predicting favourable outcome for recovery ofperioperative neurological deficits in patients with cranio-spinal intrinsictumours.
LONG-TERM FOLLOW-UP IN 1501 PATIENTS AFTER EXTRACORPOREAL MEMBRANE OXYGENATION THERAPY FOR REFRACTORY CARDIOGENIC SHOCK
Authors: Sven Lehmann, Fabian Emrich, Alexandro Hoyer Sepulveda, Khalil Jawad, Maya Dieterlen, Anna K. Funkat, Jens Garbade, Michael Borger
Journal: Journal of the American College of Cardiology (2018)
Doctors trialling GMC competence tests do not represent the doctors who take them, study finds
Authors: Abi Rimmer
Journal: BMJ (2014)

The doctors trialling the General Medical Council’s (GMC) competence tests are not representative of the doctors who take them, research has found.

The study, carried out by Leila Mehdizadeh and a team of researchers at University College London and published in the Postgraduate Medical Journal , reviewed the reliability of the GMC’s Test of Competence (ToC).1 The test forms part of a performance assessment, which the GMC can undertake during fitness to practise proceedings when concerns have been raised about a …
Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase II Study of Fruquintinib After Two Prior Chemotherapy Regimens in Chinese Patients With Advanced Nonsquamous Non‒Small-Cell Lung Cancer
Authors: Shun Lu, Jianhua Chang, Xiaoqing Liu, Jianhua Shi, You Lu, Wei Li, Jin-ji Yang, Jianying Zhou, Jie Wang, Tongtong An, Lei Yang, Zhe Liu, Xiangdong Zhou, Mo Chen, Ye Hua, Weiguo Su
Journal: Journal of Clinical Oncology (2018)

Purpose Patients with advanced non‒small-cell lung cancer (NSCLC) who fail two lines of chemotherapy have unmet medical needs. The kinase inhibitor fruquintinib selectively targets vascular endothelial growth factor receptors and, hence, tumor angiogenesis and lymphogenesis. This randomized, double-blind, placebo-controlled, multicenter phase II trial evaluated the efficacy and safety of fruquintinib in patients with advanced nonsquamous NSCLC who experienced disease progression after second-line chemotherapy. Patients and Methods Eligible patients were randomly assigned (two to one; stratified by epidermal growth factor receptor status) to receive fruquintinib or placebo, both in combination with best supportive care. Oral fruquintinib (5 mg once daily) was given in 4-week cycles of 3 weeks of treatment followed by 1 week off. Tumor response was assessed using Response Evaluation Criteria in Solid Tumors version 1.1. The primary end point was progression-free survival (PFS) evaluated by a blinded image central review (BICR) committee. Secondary end points included investigator-evaluated PFS, objective response rate, disease control rate, overall survival, and safety. Results Ninety-one patients from 12 hospitals received treatment with fruquintinib (n = 61) or placebo (n = 30). Median PFS was 3.8 months with fruquintinib by both BICR and investigators’ evaluations (hazard ratio by BICR, 0.34; 95% CI, 0.20 to 0.57; P &lt; .001). Three- and 6-month survival rates were 90.2% and 67.2% in the fruquintinib group and 73.3% and 58.8% in the placebo group, respectively. The objective response rate and disease control rate were 13.1% and 60.7% with fruquintinib, compared with 0% and 13.3% with placebo ( P = .041 and &lt; .001), respectively. The most common treatment-emergent adverse events with fruquintinib (≥ grade 3) were hypertension (8.2%), hand-foot syndrome (4.9%), and proteinuria (4.9%). Conclusion Third- and fourth-line fruquintinib for advanced NSCLC was superior to placebo and had an acceptable safety profile.
Embryonic defects induced by maternal obesity in mice derive from Stella insufficiency in oocytes
Authors: Longsen Han, Chao Ren, Ling Li, Xiaoyan Li, Juan Ge, Haichao Wang, Yi-Liang Miao, Xuejiang Guo, Kelle H. Moley, Wenjie Shu, Qiang Wang
Journal: Nature Genetics (2018)
DISCORDANT FINDINGS OF CARDIAC MAGNETIC RESONANCE AND FDG-PET-CT IN A PATIENT WITH CARDIAC SARCOIDOSIS
Authors: Tonusri Nag, Amole Ojo, Adam Horblitt, Jason Jacobson, Anthony Fuisz, Rhadames Rojas, Diwakar Jain, Daniel Frenkel
Journal: Journal of the American College of Cardiology (2018)
Workforce pressure could prevent delivery of new care models, King’s Fund warns
Authors: Abi Rimmer
Journal: BMJ (2015)

NHS workforce pressures, such as staff shortages, could jeopardise plans to deliver new models of care, the King’s Fund has warned.1

In its report the think tank called for a clear plan for the NHS workforce to support proposals set out in NHS England’s Five Year Forward View .2 Such a plan should focus on improving workforce data, strengthening national leadership, improving collaboration, and aligning local and national workforce expectations, it argued.

The report focuses on three key areas: mental health, primary care, …
Stress of working for NHS is killing staff, King’s Fund says
Authors: Abi Rimmer
Journal: BMJ (2016)

The stress of working for the NHS is making healthcare workers ill and killing them, the King’s Fund has said.

Speaking in London on Thursday 14 January, Michael West, head of thought leadership at the think tank, said that stress caused by an increasing workload and a lack of autonomy was deeply affecting NHS staff. “What we know,” he said, “is that stress kills people. It causes heart disease, it causes relationships to break up, it causes poor immune functioning—it is a really clear killer in society.”

He added, “The paradox at the …