No abstract available
https://ift.tt/2l1K3dA
Τρίτη 26 Ιουνίου 2018
Validation study for development of the Japan NBI Expert Team classification of colorectal lesions
Digestive Endoscopy, EarlyView.
https://ift.tt/2KovHCs
Laser‐Enabled Processing of Stretchable Electronics on a Hydrolytically Degradable Hydrogel
Advanced Healthcare Materials, EarlyView.
https://ift.tt/2KlGZ78
PRUNE1‐related disorder: Expanding the clinical spectrum
Clinical Genetics, EarlyView.
https://ift.tt/2KrETTc
Inflammation and fatigue in early, untreated Parkinson's Disease
Acta Neurologica Scandinavica, EarlyView.
https://ift.tt/2tFZiNq
Predicted airway obstruction distribution based on dynamical lung ventilation data: A coupled modeling‐machine learning methodology
International Journal for Numerical Methods in Biomedical Engineering, EarlyView.
https://ift.tt/2tyy77T
Cancers, Vol. 10, Pages 217: Nano-Pulse Stimulation for the Treatment of Pancreatic Cancer and the Changes in Immune Profile
Cancers, Vol. 10, Pages 217: Nano-Pulse Stimulation for the Treatment of Pancreatic Cancer and the Changes in Immune Profile
Cancers doi: 10.3390/cancers10070217
Authors: Siqi Guo Niculina I. Burcus James Hornef Yu Jing Chunqi Jiang Richard Heller Stephen J. Beebe
A Pancreatic cancer is a notorious malignant neoplasm with an extremely poor prognosis. Current standard of care is rarely effective against late-stage pancreatic cancer. In this study, we assessed nanopulse stimulation (NPS) as a local treatment for pancreatic cancer in a syngeneic mouse Pan02 pancreatic cancer model and characterized corresponding changes in the immune profile. A single NPS treatment either achieved complete tumor regression or prolonged overall survival in animals with partial tumor regression. While this is very encouraging, we also explored if this local ablation effect could also result in immune stimulation, as was observed when NPS led to the induction of immune-mediated protection from a second tumor challenge in orthotopic mouse breast and rat liver cancer models. In the Pan02 model, there were insufficient abscopal effects (1/10) and vaccine-like protective effects (1/15) suggesting that NPS-induced immune mechanisms in this model were limited. To evaluate this further, the immune landscape was analyzed. The numbers of both T regulatory cells (Tregs) and myeloid derived suppressor cells (MDSCs) in blood were significantly reduced, but memory (CD44+) T-cells were absent. Furthermore, the numbers of Tregs and MDSCs did not reduce in spleens compared to tumor-bearing mice. Very few T-cells, but large numbers of MDSCs were present in the NPS treated tumor microenvironment (TME). The number of dendritic cells in the TME was increased and multiple activation markers were upregulated following NPS treatment. Overall, NPS treatments used here are effective for pancreatic tumor ablation, but require further optimization for induction of immunity or the need to include effective combinational NPS therapeutic strategy for pancreatic cancer.
https://ift.tt/2yM6rS5
Ibrutinib for Treating Waldenström’s Macroglobulinaemia: An Evidence Review Group Perspective of a NICE Single Technology Appraisal
Abstract
As part of its Single Technology Appraisal (STA) process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer of ibrutinib (Janssen) to submit evidence on the clinical and cost effectiveness of ibrutinib for treating Waldenström's macroglobulinaemia (WM). The School of Health and Related Research Technology Assessment Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical and cost effectiveness of ibrutinib based on the company's submission to NICE. The clinical evidence was derived from one phase II, single-arm, open-label study of ibrutinib in adult patients with WM who had received at least one prior therapy (Study 1118E) and an indirect comparison using a matched cohort from a retrospective European chart review of patients receiving various treatments for WM. The indirect comparison suggested a hazard ratio for progression-free survival (PFS) of 0.25 (95% confidence interval 0.11–0.57). The ERG had concerns regarding the high risk of bias in Study 1118E, the limited generalisability of the study, and the absence of randomised controlled trial evidence. The company's Markov model assessed the cost effectiveness of ibrutinib versus rituximab/chemotherapy for patients with relapsed/refractory (R/R) WM from the perspective of the National Health Service (NHS) and Personal Social Services (PSS) over a lifetime horizon. Based on the company's original Patient Access Scheme (PAS), the company's probabilistic model generated an incremental cost-effectiveness ratio (ICER) for ibrutinib versus rituximab/chemotherapy of £58,905 per quality-adjusted life-year (QALY) gained. Following a critique of the model, the ERG's preferred analysis, which corrected cost errors and used the observed mortality rate from Study 1118E, generated a probabilistic ICER of £61,219 per QALY gained. Based on this amended model, additional exploratory analyses produced ICERs for ibrutinib that were > £60,000 per QALY gained. Subsequently, the company offered to provide ibrutinib at a price that resulted in ibrutinib being cost effective within the Cancer Drugs Fund (CDF). The Committee recommended ibrutinib for use in the CDF as an option for treating WM in adults who have had at least one prior therapy, only if the conditions in the managed access agreement for ibrutinib are followed.
https://ift.tt/2txvW4z
T cell receptor repertoire profiling predicts the prognosis of HBV‐associated hepatocellular carcinoma
Cancer Medicine, EarlyView.
https://ift.tt/2yLIBWv
Impact of altered gingival characteristics on smile esthetics: Laypersons' perspectives by Q sort methodology
Smile esthetics includes the white esthetics related to the teeth and the pink esthetics related to the mucosa. Many surveys have been conducted to evaluate laypersons' perceptions to altered dental characteristics, but few have focused on the soft tissue factors. This study was designed to determine the perceptions of laypeople to variations in soft tissue esthetics during smile.
https://ift.tt/2tzvlPJ
Accuracy of clear aligners: A retrospective study of patients who needed refinement
The purpose of this study was to determine the accuracy of specific tooth movements with Invisalign (Align Technology, Santa Clara, Calif).
https://ift.tt/2N2Wt1O
Hybrid approach for automatic cephalometric landmark annotation on cone-beam computed tomography volumes
Cone-beam computed tomography (CBCT) is commonly used for 3-dimensional (3D) evaluation and treatment planning of patients in orthodontics, where precision and reproducibility of landmark annotation are required. Manual landmarking is a time- and effort-consuming task regardless of the practitioner's experience. We introduce a hybrid algorithm for automatic cephalometric landmark annotation on CBCT volumes.
https://ift.tt/2tynBh0
Childhood body mass index is associated with early dental development and eruption in a longitudinal sample from the Iowa Facial Growth Study
Children with high body mass index (BMI) values have been demonstrated to have precocious dental development. Research has largely focused on cross-sectional data sets, leaving an incomplete understanding of the longitudinal relationship between BMI and dental maturation.
https://ift.tt/2tzvcf9
What we have to offer
It was with great interest that I read the Guest Editorial by Mark Ackerman and Benjamin Burris in the February 2018 issue of the Journal (Ackerman M, Burris B. The way it was, the way it ought to be, the way it is, and the way it will be. Am J Orthod Dentofacial Orthop 2018;153:165-6). I had expected to see some rebuttal or at least some opinions that might have had perhaps a slightly different take on our future. Seeing none, I believe that the void should be filled.
https://ift.tt/2tDdMgI
Three-dimensional evaluation of craniofacial characteristics related to mandibular asymmetries in skeletal Class I patients
Our objective was to analyze the characteristics that affect skeletal Class I adults with mandibular asymmetries using cone-beam computerized tomography.
https://ift.tt/2tyRAoT
No prejudices, please
You truly wish that you could convince your patients to clean their teeth more effectively. Not a day passes when you don't engage in a discussion with a patient or an occasionally overprotective parent about the inadequacy of Junior's oral home care. If only there was a device that could reduce plaque levels for those ambivalent, distracted teenagers who arrive in your office, you're sure that your blood pressure would drop by at least 30 mm of mercury!
https://ift.tt/2yKW6pg
Comparative assessment of treatment efficacy and adverse effects during nonextraction orthodontic treatment of Class I malocclusion patients with direct and indirect bonding: A parallel randomized clinical trial
The objective of this 2-arm parallel trial was to compare the effects of direct and indirect bonding techniques on the orthodontic treatment process and outcomes.
https://ift.tt/2tzv7In
Effects of lactoferrin on bone resorption of midpalatal suture during rapid expansion in rats
The aim of this study was to investigate the effect of lactoferrin (LF) on bone resorption of rats' midpalatal sutures during rapid palatal expansion.
https://ift.tt/2tzv4wb
Time for change
"American Board of Orthodontics: Time for change"1 was published in the March 2018 issue of the AJO-DO. As a former director of the American Board of Orthodontics and one who continues to participate in the Board examination once a year, I strongly support the scenario-based examination that will soon be initiated by the American Board of Orthodontics. My support is based on my 27 years of experience as a director or examiner.
https://ift.tt/2N3y4ck
The sky is not the limit!
I was drawn in by the all-encompassing title of the recent Guest Editorial by Ackerman and Burris (Ackerman M, Burris B. The way it was, the way it ought to be, the way it is, and the way it will be. Am J Orthod Dentofacial Orthop 2018;153:165-6). It is ironic that I am writing this response on a flight home. It's just like the authors described. I'm very happy with my direct and on-schedule flight. I have my favorite seat position—on the aisle, right over the wings. My 300-pound neighbor is Jim, and he's from Wisconsin.
https://ift.tt/2yHxEVQ
Effects of acid etching and calcium chloride immersion on removal torque and bone-cutting ability of orthodontic mini-implants
The 2-fold purpose of this study was to evaluate the effects of acid etching and calcium chloride immersion on removal torque and the bone-cutting ability of orthodontic mini-implants (OMIs).
https://ift.tt/2tyQaL3
Ellen A. BeGole, 1934-2018
Ellen Ann BeGole was born in Detroit in 1934. Her father was an engineer and inventor who held multiple patents. Perhaps not surprisingly, his daughter exhibited a similar knack for mathematics. During the 1950s, women were still generally expected to pursue "less-challenging" careers, if any. Never one to choose the easy road in life, Ellen decided to dedicate hers to mathematics, obtaining a bachelor's degree from the University of Michigan in 1955 and a master's degree from Columbia University in 1969.
https://ift.tt/2yKVQqi
Sleep disordered breathing in children seeking orthodontic care
Our objective was to evaluate the prevalence of high-risk factors for sleep disordered breathing (SDB) in an orthodontic population of children. SDB is a spectrum of breathing disorders ranging from primary snoring to obstructive sleep apnea.
https://ift.tt/2N3JFZ5
A Missense Mutation in the Vacuolar Protein Sorting 11 (VPS11) Gene Is Associated with Neuroaxonal Dystrophy in Rottweiler Dogs
Canine neuroaxonal dystrophy (NAD) is a recessive, degenerative neurological disease of young adult Rottweiler dogs (Canis lupus familiaris) characterized pathologically by axonal spheroids primarily targeting sensory axon terminals. A genome-wide association study of seven Rottweilers affected with NAD and 42 controls revealed a significantly associated region on canine chromosome 5 (CFA 5). Homozygosity within the associated region narrowed the critical interval to a 4.46 Mb haplotype (CFA5:11.28 Mb - 15.75 Mb; CanFam3.1) that associated with the phenotype. Whole-genome sequencing of two histopathologically confirmed canine NAD cases and 98 dogs unaffected with NAD revealed a homozygous missense mutation within the Vacuolar Protein Sorting 11 (VPS11) gene (g.14777774T>C; p.H835R) that was associated with the phenotype. These findings present the opportunity for an antemortem test for confirming NAD in Rottweilers where the allele frequency was estimated at 2.3%. VPS11 mutations have been associated with a degenerative leukoencephalopathy in humans, and VSP11 should additionally be included as a candidate gene for unexplained cases of human NAD.
https://ift.tt/2N1rvXC
On the Relationship Between High-Order Linkage Disequilibrium and Epistasis
A plausible explanation for statistical epistasis revealed in genome wide association analyses is the presence of high order linkage disequilibrium (LD) between the genotyped markers tested for interactions and unobserved functional polymorphisms. Based on findings in experimental data, it has been suggested that high order LD might be a common explanation for statistical epistasis inferred between local polymorphisms in the same genomic region. Here, we empirically evaluate how prevalent high order LD is between local, as well as distal, polymorphisms in the genome. This could provide insights into whether we should account for this when interpreting results from genome wide scans for statistical epistasis. An extensive and strong genome wide high order LD was revealed between pairs of markers on the high density 250k SNP-chip and individual markers revealed by whole genome sequencing in the Arabidopsis thaliana 1001-genomes collection. The high order LD was found to be more prevalent in smaller populations, but present also in samples including several hundred individuals. An empirical example illustrates that high order LD might be an even greater challenge in cases when the genetic architecture is more complex than the common assumption of bi-allelic loci. The example shows how significant statistical epistasis is detected for a pair of markers in high order LD with a complex multi allelic locus. Overall, our study illustrates the importance of considering also other explanations than functional genetic interactions when genome wide statistical epistasis is detected, in particular when the results are obtained in small populations of inbred individuals.
https://ift.tt/2Iw04Sp
Genomic Selection in Preliminary Yield Trials in a Winter Wheat Breeding Program
Genomic prediction (GP) is now routinely performed in crop plants to predict unobserved phenotypes. The use of predicted phenotypes to make selections is an active area of research. Here, we evaluate GP for predicting grain yield and compare genomic and phenotypic selection by tracking lines advanced. We examined four independent nurseries of F3:6 and F3:7 lines trialed at 6 to 10 locations each year. Yield was analyzed using mixed models that accounted for experimental design and spatial variations. Genotype-by-sequencing provided nearly 27,000 high-quality SNPs. Average genomic predictive ability, estimated for each year by randomly masking lines as missing in steps of 10% from 10% to 90%, and using the remaining lines from the same year as well as lines from other years in a training set, ranged from 0.23 to 0.55. The predictive ability estimated for a new year using the other years ranged from 0.17 to 0.28. Further, we tracked lines advanced based on phenotype from each of the four F3:6 nurseries. Lines with both above average genomic estimated breeding value (GEBV) and phenotypic value (BLUP) were retained for more years compared to lines with either above average GEBV or BLUP alone. The number of lines selected for advancement was substantially greater when predictions were made with 50% of the lines from the testing year added to the training set. Hence, evaluation of only 50% of the lines yearly seems possible. This study provides insights to assess and integrate genomic selection in breeding programs of autogamous crops.
https://ift.tt/2N1eYmY
The Role of Next Generation Sequencing in the Differential Diagnosis of Composite Neoplasms
Composite neoplasms (CN) are rare and diagnostically challenging lesions that require differentiating between mixed clonal tumors with divergent phenotypes (MT), collision of two independent tumors adjacent to each other (CT) and tumor-to-tumor metastasis (TTM). To that end, pathologists have traditionally used Immunohistochemistry and limited molecular studies, such as Sanger sequencing. Herein we evaluate the potential application of NGS in the differential diagnosis of these rare neoplasms. Four CNs were included in the study.
https://ift.tt/2Ko1O5i
Clinicopathologic Characterization of Breast Carcinomas in Patients with Non-BRCA Germline Mutations: Results from a Single Institution’s High Risk Population
As multigene panel testing for hereditary cancer syndromes becomes commonplace, germline mutations in genes other than BRCA1/2 are increasingly identified in breast cancer patients. While histopathologic features of BRCA-mutated breast cancers have been well-characterized, less is known about non-BRCA-related hereditary cancers. We herein investigate the clinicopathologic characteristics of breast cancers in women with non-BRCA germline mutations. Out of 612 women who underwent germline testing, 16 (2.6%) of women with 18 cancers had mutations in non-BRCA genes: ATM, CHEK2, PALB2, TP53, BMPR1A, BRIP1, MUTYH, and RAD50.
https://ift.tt/2Mqmoze
Perforated viscus; not always bowel: case report of spontaneous bladder rupture
ANZ Journal of Surgery, EarlyView.
https://ift.tt/2yHlAE2
AMA Adopts Ethical Guidance on Medical Tourism
TUESDAY, June 26, 2018 -- The American Medical Association (AMA) recently adopted new ethical guidelines on medical tourism to help physicians understand their responsibilities when interacting with patients who seek or have received medical care...
https://ift.tt/2MsW8nP
Higher Cancer Rates Confirmed in Women With Dense Breasts
TUESDAY, June 26, 2018 -- Women with dense breasts have a higher rate of recall, higher rates of screen-detected and interval breast cancers, and more lymph node-positive disease, according to a study published online June 26 in Radiology. Nataliia...
https://ift.tt/2KtvAFw
CDC, APhA Create Guide for Community-Clinical Linkages
TUESDAY, June 26, 2018 -- The U.S. Centers for Disease Control and Prevention and the American Pharmacists Association have created a guide that describes community-clinical linkages, which are connections among the community, clinics, and other...
https://ift.tt/2Ks2TFJ
ADA: T1D, T2D, GDM Before 26 Weeks Tied to Higher ASD Risk
TUESDAY, June 26, 2018 -- The risk of autism spectrum disorder (ASD) in offspring is increased in association with type 1 diabetes (T1D), type 2 diabetes (T2D), and gestational diabetes mellitus (GDM) diagnosed by 26 weeks' gestation, according to a...
https://ift.tt/2lD69ne
Authors Explore Overdiagnosis in Cancer Screening
TUESDAY, June 26, 2018 -- Recommendations for defining, estimating, and communicating overdiagnosis in cancer screening are discussed in a special article published online June 25 in the Annals of Internal Medicine. Louise Davies, M.D., from White...
https://ift.tt/2yNUKdw
Corrigendum to “Pericytic mimicry in well-differentiated liposarcoma/atypical lipomatous tumor” (Hum Pathol 2016;54:92–99)
The authors regret that the RGS5 antibody source was published incorrectly. The antibody used for RGS5 detection was an anti-RGS5 antibody (rabbit anti-human, polyclonal, Sigma, HPA001821, Allentown, PA).
https://ift.tt/2KqDgbQ
Correction to: Seroprevalence and determinants of transfusion transmissible infections among voluntary blood donors in Homabay, Kisumu and Siaya counties in western Kenya
Following publication of the original article [1], the authors reported that for two of the authors, Felix Humwa and Vallarie Opollo, an incorrect affiliation has been given. In this Correction the incorrect a...
https://ift.tt/2KkYAfv
Factors affecting development of Clostridium difficile infection in hospitalized pediatric patients in the country Georgia
Main aims of our study were to investigate occurrence of Clostridium difficile among hospitalized pediatric patients in Georgia and examine risk factors for the development of C. difficile infection. During our s...
https://ift.tt/2tuSrXU
Enrichment of rare copy number variation in children with developmental language disorder
Clinical Genetics, EarlyView.
https://ift.tt/2tH1Tqm
Evidence for HNRNPH1 being another gene for Bain type syndromic mental retardation
Clinical Genetics, Volume 0, Issue ja, -Not available-.
https://ift.tt/2N13sYM
IL11RA‐related Crouzon‐like autosomal recessive craniosynostosis in ten new patients: resemblances and differences
Clinical Genetics, Volume 0, Issue ja, -Not available-.
https://ift.tt/2yIbyTm
IFT80 mutations cause a novel complex ciliopathy phenotype with retinal degeneration
Clinical Genetics, Volume 0, Issue ja, -Not available-.
https://ift.tt/2txPpSE
The GBA p.Trp378Gly mutation is a probable French‐Canadian founder mutation causing Gaucher disease and synucleinopathies
Clinical Genetics, Volume 0, Issue ja, -Not available-.
https://ift.tt/2yNvYKG
Genotype‐phenotype correlations of low frequency variants in the complement system in renal disease and age‐related macular degeneration
Clinical Genetics, Volume 0, Issue ja, -Not available-.
https://ift.tt/2txPndu
GPT2 mutations cause developmental encephalopathy with microcephaly and features of complicated hereditary spastic paraplegia
Clinical Genetics, Volume 0, Issue ja, -Not available-.
https://ift.tt/2tvN2Q8
A ZPR1 mutation is associated with a novel syndrome of growth restriction, distinct craniofacial features, alopecia, and hypoplastic kidneys
Clinical Genetics, Volume 0, Issue ja, -Not available-.
https://ift.tt/2yNQavK
Resilience Rather than Medical Factors: How Parents Predict Quality of Life of Their Sick Newborn
To assess the influence of resiliency and stress on parental perspectives of the future quality of life (QOL) of neonatal intensive care unit (NICU) newborns at high risk of neurodevelopmental disability.
https://ift.tt/2tDJ5rX
Blood Glucose and Cerebral Tissue Oxygenation Immediately after Birth—An Observational Study
To assess a possible association of blood glucose concentration with cerebral regional oxygen saturation (crSO2) and cerebral fractional tissue oxygen extraction (cFTOE) in neonates born at term and preterm 15 minutes after birth.
https://ift.tt/2tuH0iW
Selective Serotonin Reuptake Inhibitors Reduce Longitudinal Growth in Risperidone-Treated Boys
To examine whether selective serotonin reuptake inhibitors (SSRIs) inhibit longitudinal growth in children and adolescents, particularly in the early stages of puberty, using a sample of convenience comprising risperidone-treated boys.
https://ift.tt/2tDJ6fv
Peer Relationship Outcomes of School-Age Children Born Very Preterm
To characterize the friendship networks, peer relationships, and bullying experiences of 12-year-old children born extremely preterm (EPT; 23-27 weeks of gestation), very preterm (VPT; 28-32 weeks of gestation), and full term (FT; 38-41 weeks of gestation), and to identify child characteristics placing children at risk of peer problems.
https://ift.tt/2N38aW8
Ambulatory Visits for Otitis Media before and after the Introduction of Pneumococcal Conjugate Vaccination
To examine the long-term trend of otitis media (OM)-associated ambulatory visits from 1997 to 2014 and to evaluate the impact of 7-valent and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13) on OM ambulatory visits.
https://ift.tt/2N3mduH
The Current Status of Drug Discovery and Development as Originated in US Academia: The Influence of Industrial and Academic Collaboration on Drug Discovery and Development
Clinical and Translational Science, Volume 0, Issue ja, -Not available-.
https://ift.tt/2IuWnMW
Population Pharmacokinetic and Exposure‐Dizziness Modeling for a Metabotropic Glutamate Receptor Subtype5 Negative Allosteric Modulator in Major Depressive Disorder Patients
Clinical and Translational Science, Volume 0, Issue ja, -Not available-.
https://ift.tt/2K8LQN3
The Assay Guidance Manual: Quantitative Biology and Pharmacology in Preclinical Drug Discovery
Clinical and Translational Science, Volume 0, Issue ja, -Not available-.
https://ift.tt/2MtESPw
Tutorial on Monoclonal Antibody Pharmacokinetics and its Considerations in Early Development
Clinical and Translational Science, Volume 0, Issue ja, -Not available-.
https://ift.tt/2KaFxIW
Systematic review and meta‐analysis of robotic versus open hepatectomy
ANZ Journal of Surgery, EarlyView.
https://ift.tt/2tHegCv
Text messaging improves preoperative exercise in patients undergoing bariatric surgery
ANZ Journal of Surgery, EarlyView.
https://ift.tt/2twCXTb
Endoscopic papillary large balloon dilation and endoscopic papillary balloon dilation both without sphincterotomy for removal of large bile duct stones: a propensity‐matched analysis
Digestive Endoscopy, Volume 0, Issue ja, -Not available-.
https://ift.tt/2tNmn0L
Secondary gastrointestinal amyloid A amyloidosis possibly caused by hidradenitis suppurativa
Digestive Endoscopy, Volume 0, Issue ja, -Not available-.
https://ift.tt/2yLyi4P
Cannulation method for intra‐diverticular papilla with long oral protrusion using biopsy forceps for axis alignment
Digestive Endoscopy, Volume 0, Issue ja, -Not available-.
https://ift.tt/2lCplkZ
Submucosal tunneling endoscopic resection of a gigantic cardiac leiomyoma
Digestive Endoscopy, Volume 0, Issue ja, -Not available-.
https://ift.tt/2tIdB41
Traction‐assisted endoscopic submucosal dissection for a giant rectal tumor: multiple clip‐and‐threads technique
Digestive Endoscopy, Volume 0, Issue ja, -Not available-.
https://ift.tt/2lDKsDw
The Efficacy and Safety of Pancreatic Juice Cytology by Using Synthetic Secretin in the Diagnosis of Pancreatic Ductal Adenocarcinoma
Digestive Endoscopy, Volume 0, Issue ja, -Not available-.
https://ift.tt/2yIWt3V
Submucosal tunneling endoscopic resection of a large esophageal leiomyoma using endoscopy with near‐focus mode
Digestive Endoscopy, Volume 0, Issue ja, -Not available-.
https://ift.tt/2lDweCw
Retrieval of a large rectal ESD‐specimen using bowel preparation after unsuccessful rectal enema. First report of a novel technique
Digestive Endoscopy, Volume 0, Issue ja, -Not available-.
https://ift.tt/2tNm1Ht
Molecular Endoscopic Imaging in Cancer
Digestive Endoscopy, Volume 0, Issue ja, -Not available-.
https://ift.tt/2lD6q9D
Differentiated‐type predominant mixed‐histology type early gastric cancer is a significant risk factor for endoscopic non‐curative resection regardless of tumor size
Digestive Endoscopy, Volume 0, Issue ja, -Not available-.
https://ift.tt/2lCCPNo
13q deletion is linked to an adverse phenotype and poor prognosis in prostate cancer
Genes, Chromosomes and Cancer, Volume 0, Issue ja, -Not available-.
https://ift.tt/2MYvSmi
Novel intra‐genic large deletions of CTNNB1 gene identified in WT desmoid‐type fibromatosis
Genes, Chromosomes and Cancer, Volume 0, Issue ja, -Not available-.
https://ift.tt/2KqiNR9
DNA methylation profiles of immune response‐related genes in apical periodontitis
International Endodontic Journal, Volume 0, Issue ja, -Not available-.
https://ift.tt/2lCW7CA
Enterococcus faecalis induces apoptosis and pyroptosis of human osteoblastic MG63 cells via the NLRP3 inflammasome
International Endodontic Journal, Volume 0, Issue ja, -Not available-.
https://ift.tt/2yISEf5
3D printed replicas for endodontic education
International Endodontic Journal, Volume 0, Issue ja, -Not available-.
https://ift.tt/2lDHXkC
Use of 0.4‐Tesla static magnetic field to promote reparative dentine formation of dental pulp stems cells through activation of p38 MAPK signaling pathway
International Endodontic Journal, Volume 0, Issue ja, -Not available-.
https://ift.tt/2lz57Zf
Effect of the combination of several irrigants on dentine surface properties, adsorption of chlorhexidine and adhesion of microorganisms to dentine
International Endodontic Journal, Volume 0, Issue ja, -Not available-.
https://ift.tt/2tI8mRT
Porphyromonas endodontalis reactivates latent Epstein‐Barr virus
International Endodontic Journal, Volume 0, Issue ja, -Not available-.
https://ift.tt/2lD2UMt
Orexin‐1 receptors in the rostral ventromedial medulla are involved in the modulation of capsaicin evoked pulpal nociception and impairment of learning and memory
International Endodontic Journal, Volume 0, Issue ja, -Not available-.
https://ift.tt/2yKAE3J
Experimental and theoretical study between cefoxitin and Escherichia coli 5 protein on selection of bioactive molecules against resistant strain
Chemical Biology &Drug Design, Volume 0, Issue ja, -Not available-.
https://ift.tt/2KaeWeR
Selection‐based Design of in silico Dengue Epitope Ensemble Vaccines
Chemical Biology &Drug Design, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Ir4Twl
Identification of a new Pyruvate kinase M2 isoform (PKM2) activator for the treatment of non‐small cell lung cancer (NSCLC)
Chemical Biology &Drug Design, Volume 0, Issue ja, -Not available-.
https://ift.tt/2KngqBP
Preliminary antifungal activity assay of selected chlorine‐containing derivatives of xanthone and phenoxyethyl amines
Chemical Biology &Drug Design, Volume 0, Issue ja, -Not available-.
https://ift.tt/2ItTrQC
Novel 1,3‐oxazine‐tetrazole hybrids as mushroom tyrosinase inhibitors and free radical scavengers: Synthesis, kinetic mechanism and molecular docking studies
Chemical Biology &Drug Design, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Kc4KT1
A Panoptic Uncovering of the Dynamical Evolution of the Zika Virus NS5 Methyltransferase Binding Site Loops– Zeroing in on the Molecular Landscape
Chemical Biology &Drug Design, Volume 0, Issue ja, -Not available-.
https://ift.tt/2MpIS3e
Synthesis and insecticidal activity study of novel anthranilic diamides analogues containing a diacylhydrazine bridge as effective Ca2+ modulators
Chemical Biology &Drug Design, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Ka99G5
Permeation‐Enhancing Effects and Mechanisms of Borneol and Menthol on Ligustrazine: A Multiscale Study using In Vitro and Coarse‐Grained Molecular Dynamics Simulation Methods
Chemical Biology &Drug Design, Volume 0, Issue ja, -Not available-.
https://ift.tt/2IuxWio
Larvicidal study of tetrahydropyrimidine scaffolds against Anopheles arabiensis and structural insight by single crystal X‐ray studies
Chemical Biology &Drug Design, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Kc3mjy
Synthesis and biological evaluation of new tetramethylpyrazine based chalcone derivatives as potential anti‐Alzheimer agents
Chemical Biology &Drug Design, Volume 0, Issue ja, -Not available-.
https://ift.tt/2MrCg4u
The draft genomes and investigation of serotype distribution, antimicrobial resistance of group B Streptococcus strains isolated from urine in Suzhou, China
The group B Streptococcus (GBS) is a human commensal bacterium, which is capable of causing several infectious diseases in infants, and people with chronic diseases. GBS has been the most common cause of infectio...
https://ift.tt/2Kdbmkj
Folic acid supplementation does not attenuate thermoregulatory or cardiovascular strain of older adults exposed to extreme heat and humidity
Experimental Physiology, EarlyView.
https://ift.tt/2tuOySq
Cardiac β‐adrenergic responsiveness of obese Zucker rats: The role of AMPK
Experimental Physiology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2yLn8gt
Membrane potential oscillations are not essential for spontaneous firing generation in L4 Aβ‐afferent neurons after L5 spinal nerve axotomy and are not mediated by HCN channels
Experimental Physiology, EarlyView.
https://ift.tt/2tGKLRw
Improved brachial artery shear patterns and increased flow‐mediated dilation after low‐volume high‐intensity interval training in type 2 diabetes
Experimental Physiology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2N3goxl
Targeted ablation of cardiac sympathetic neurons attenuates adverse post‐infarction remodeling and left ventricle dysfunction
Experimental Physiology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2yHVXDi
Motor cortical and corticospinal function differ during an isometric squat compared to isometric knee extension
Experimental Physiology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2txKuBc
The influence of sex and neonatal stress on medullary microglia in rat pups
Experimental Physiology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2tH2Yy7
Hypoxic pulmonary vasoconstriction in isolated mouse pulmonary arterial vessels
Experimental Physiology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2tuO9zo
Mitochondrial regulation in skeletal muscle: A role for non‐coding RNAs?
Experimental Physiology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2N2FHzU
Intense physical exercise potentiates glucose inhibitory effect over food intake of male Wistar rats
Experimental Physiology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2tE7i1p
Slow wave contraction frequency plateaus in the small intestine are composed of discrete waves of interval increase associated with dislocations
Experimental Physiology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2txxtHy
The emerging fibroblast‐like synoviocyte channelome
Experimental Physiology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2yLqdNx
Differences in the persistence of spatial memory deficits induced by a chronic stressor in adolescents compared to juveniles
Developmental Psychobiology, EarlyView.
https://ift.tt/2Kj6oSn
A three‐dimensional (3D) two‐way coupled fluid‐structure interaction (FSI) study of peristaltic flow in obstructed ureters
International Journal for Numerical Methods in Biomedical Engineering, Volume 0, Issue ja, -Not available-.
https://ift.tt/2ItO7g6
On the Use of Machine Learning Techniques for the Mechanical Characterization of Soft Biological Tissues
International Journal for Numerical Methods in Biomedical Engineering, Volume 0, Issue ja, -Not available-.
https://ift.tt/2N3OyB9
Influence of ageing on human body blood flow and heat transfer: a detailed computational modelling study
International Journal for Numerical Methods in Biomedical Engineering, Volume 0, Issue ja, -Not available-.
https://ift.tt/2KkMa7n
0D lumped approach to incorporate the dynamic part of the pressure at vessel junctions in a 1D wave propagation model
International Journal for Numerical Methods in Biomedical Engineering, Volume 0, Issue ja, -Not available-.
https://ift.tt/2N12oV2
Effects of Nerve Bundle Geometry on Neurotrauma Evaluation
International Journal for Numerical Methods in Biomedical Engineering, Volume 0, Issue ja, -Not available-.
https://ift.tt/2KlXfF3
Investigation of raphe function in the bicuspid aortic valve and its influence on clinical criteria – A patient‐specific finite‐element study
International Journal for Numerical Methods in Biomedical Engineering, Volume 0, Issue ja, -Not available-.
https://ift.tt/2N1yKyT
Evaluating the roles of detailed endocardial structures on right ventricular haemodynamics by means of CFD simulations
International Journal for Numerical Methods in Biomedical Engineering, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Iuc7zA
Nonstandard Finite Difference Approach for Solving Three‐Compartment Pharmacokinetic Models
International Journal for Numerical Methods in Biomedical Engineering, Volume 0, Issue ja, -Not available-.
https://ift.tt/2N1yCiT
Modeling hemodynamics in intracranial aneurysms: Comparing accuracy of CFD solvers based on finite element and finite volume schemes
International Journal for Numerical Methods in Biomedical Engineering, Volume 0, Issue ja, -Not available-.
https://ift.tt/2KsUTVi
Effect of upper airway on tracheobronchial fluid dynamics
International Journal for Numerical Methods in Biomedical Engineering, Volume 0, Issue ja, -Not available-.
https://ift.tt/2txzoMw
Numerical Analysis of Electromagnetic Interactions by a Cell During the Mitosis Phases
International Journal for Numerical Methods in Biomedical Engineering, Volume 0, Issue ja, -Not available-.
https://ift.tt/2IuMxug
IFN‐γ protects from apoptotic neutrophil‐mediated tissue injury during acute Listeria monocytogenes infection
European Journal of Immunology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2N3dI2L
A clinically applicable adjuvant for an atherosclerosis vaccine in mice
European Journal of Immunology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2IubQwy
BATF regulates the expression of Nfil3, Wnt10a and miR155hg for efficient induction of antibody class switch recombination in mice
European Journal of Immunology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2N3dyZd
The immunoproteasome inhibitor ONX‐0914 regulates inflammation and expression of contraction associated proteins in myometrium
European Journal of Immunology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2IwfMwL
Association between levels of synovial anti‐citrullinated peptide antibodies and neutrophil response in patients with rheumatoid arthritis
European Journal of Immunology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2txz0O4
Murine macrophage chemokine receptor CCR2 plays a crucial role in macrophage recruitment and regulated inflammation in wound healing
European Journal of Immunology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2IwfHZZ
Patient‐shared TCRβ‐CDR3 clonotypes correlate with favorable prognosis in chronic hepatitis B
European Journal of Immunology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2txyVKg
Dynamic changes in intrathymic ILC populations during murine neonatal development
European Journal of Immunology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Kqhdii
EWS‐FLI1 regulates a transcriptional program in cooperation with Foxq1 in mouse Ewing sarcoma
Cancer Science, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Koe9Gw
Sex Differences in Early Embryogenesis: Inter‐Chromosomal Regulation Sets the Stage for Sex‐Biased Gene Networks
BioEssays, EarlyView.
https://ift.tt/2MqU2F3
How a System of Checks on Symbiosis Could Become Disastrous
https://ift.tt/2K8Ca5b
Archaea‐First and the Co‐Evolutionary Diversification of Domains of Life
BioEssays, EarlyView.
https://ift.tt/2MtEuR1
Why Do Corals Bleach? Conflict and Conflict Mediation in a Host/Symbiont Community
BioEssays, EarlyView.
https://ift.tt/2KabpNv
Creating Lineage Trajectory Maps Via Integration of Single‐Cell RNA‐Sequencing and Lineage Tracing
BioEssays, EarlyView.
https://ift.tt/2KlS5Jh
Combined neuropathological pathways account for age‐related risk of dementia
Annals of Neurology, EarlyView.
https://ift.tt/2tyDqUG
Collaborative Science Unites Researchers and a Novel Spastic Ataxia Gene
Annals of Neurology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2KrAJL1
Targeted brain proteomics uncover multiple pathways to Alzheimer's dementia
Annals of Neurology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2tuKFgi
Repair after brainstem ischemia involves neurogenesis and the rubrospinal system
Annals of Neurology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2KnQtid
Oligonucleotide therapy mitigates disease in Spinocerebellar Ataxia Type 3 mice
Annals of Neurology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2ty9FDv
Genome sequencing uncovers phenocopies in primary progressive multiple sclerosis
Annals of Neurology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Km0Ra9
Pleural adverse drugs reactions and protein kinase inhibitors: identification of suspicious targets by disproportionality analysis from VigiBase®
British Journal of Clinical Pharmacology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2tyVz4R
Prescription Patterns of Angiotensin‐Converting Enzyme Inhibitors for Various Indications: A UK Population‐based Study
British Journal of Clinical Pharmacology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2KpozlS
A comparative pharmacokinetic study of DRL_BZ, a candidate biosimilar of bevacizumab, with Avastin® (EU and US) in healthy male subjects
British Journal of Clinical Pharmacology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2tyVqOR
Patient‐reported outcome instruments that evaluate adherence behaviours in adults with asthma: a systematic review of measurement properties
British Journal of Clinical Pharmacology, EarlyView.
https://ift.tt/2KpIdhP
Pharmacokinetics and C‐reactive protein modelling of anti‐interleukin‐6 antibody (PF‐04236921) in healthy volunteers and patients with autoimmune disease
British Journal of Clinical Pharmacology, EarlyView.
https://ift.tt/2N0zzId
Effect of tildrakizumab (MK‐3222), a high affinity, selective anti‐IL23p19 monoclonal antibody, on cytochrome P450 metabolism in subjects with moderate to severe psoriasis
British Journal of Clinical Pharmacology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Kp10d9
A Pharmacokinetics Phase 1 Bioequivalence Study of the Trastuzumab Biosimilar MYL‐1401O vs EU‐Trastuzumab and US‐Trastuzumab
British Journal of Clinical Pharmacology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2N0z6pr
MEDI0382, a GLP‐1–glucagon receptor dual agonist, meets safety and tolerability endpoints in a single‐dose, healthy‐subject, randomised, phase 1 study
British Journal of Clinical Pharmacology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2KrAHTp
The challenges of ‘medical cannabis' and mental health: a clinical perspective.
British Journal of Clinical Pharmacology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2txQ5XX
Medicinal Cannabinoids in Palliative Care
British Journal of Clinical Pharmacology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Iux2m5
Coadministration of Probenecid and Cimetidine with Mirogabalin in Healthy Subjects: A Phase 1, Randomized, Open‐Label, Drug‐Drug Interaction Study
British Journal of Clinical Pharmacology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2N0yVuh
New drug controls and reduced hospital presentations due to novel psychoactive substances in Edinburgh
British Journal of Clinical Pharmacology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2KlRhEf
Total flucloxacillin plasma concentrations poorly reflect unbound concentrations in hospitalised patients with Staphylococcus aureus bacteraemia
British Journal of Clinical Pharmacology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2MWfqDf
In vivo affinity and target engagement in skin and blood in a first‐time‐in‐human study of an anti‐oncostatin M monoclonal antibody
British Journal of Clinical Pharmacology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Ko8wFb
Letter: unlikely liver bedfellows—alpha‐1 antitrypsin deficiency and granulomatosis with polyangiitis
Alimentary Pharmacology &Therapeutics, Volume 48, Issue 2, Page 232-233, July 2018.
https://ift.tt/2lypS7s
Letter: direct‐acting anti‐viral (DAA) therapy needs strong safety and efficacy check
Alimentary Pharmacology &Therapeutics, Volume 48, Issue 2, Page 233-234, July 2018.
https://ift.tt/2yLbjXD
Letter: direct‐acting anti‐viral (DAA) therapy needs strong safety and efficacy check—authors’ reply
Alimentary Pharmacology &Therapeutics, Volume 48, Issue 2, Page 235-236, July 2018.
https://ift.tt/2lDCQ3U
Editorial: real‐life data confirm efficacy of elbasvir/grazoprevir in HCV patients with severe kidney disease
Alimentary Pharmacology &Therapeutics, Volume 48, Issue 2, Page 226-227, July 2018.
https://ift.tt/2tN2tD5
Editorial: frequency of surveillance and survival in hepatocellular carcinoma—authors’ reply
Alimentary Pharmacology &Therapeutics, Volume 48, Issue 2, Page 229-230, July 2018.
https://ift.tt/2lCQJzm
Letter: unlikely liver bedfellows—alpha‐1 antitrypsin deficiency and granulomatosis with polyangiitis. Author's reply
Alimentary Pharmacology &Therapeutics, Volume 48, Issue 2, Page 233-233, July 2018.
https://ift.tt/2tI4obK
Letter: impact of HBV genotypes and PC/BCP mutations on serum HBsAg levels in Chinese HBeAg‐negative patients
Alimentary Pharmacology &Therapeutics, Volume 48, Issue 2, Page 236-237, July 2018.
https://ift.tt/2lFzZaJ
Editorial: self‐dilation for refractory oesophageal strictures is worth considering—author's reply
Alimentary Pharmacology &Therapeutics, Volume 48, Issue 2, Page 231-231, July 2018.
https://ift.tt/2tN1UJt
Editorial: frequency of surveillance and survival in hepatocellular carcinoma
Alimentary Pharmacology &Therapeutics, Volume 48, Issue 2, Page 228-229, July 2018.
https://ift.tt/2MmFZAj
The Effect of Addition of Calcium Phosphate Particles to Hydrogel‐Based Composite Materials on Stiffness and Differentiation of Mesenchymal Stromal Cells toward Osteogenesis
Advanced Healthcare Materials, EarlyView.
https://ift.tt/2MYz0yx
Editorial: real‐life data confirm efficacy of elbasvir/grazoprevir in HCV patients with severe kidney disease—Author's reply
Alimentary Pharmacology &Therapeutics, Volume 48, Issue 2, Page 227-227, July 2018.
https://ift.tt/2lCQsfO
Letter: impact of HBV genotypes and PC/BCP mutations on serum HBsAg levels in Chinese HBeAg negative patients—Authors′ reply
Alimentary Pharmacology &Therapeutics, Volume 48, Issue 2, Page 238-239, July 2018.
https://ift.tt/2yNkh6I
Editorial: self‐dilation for refractory oesophageal strictures is worth considering
Alimentary Pharmacology &Therapeutics, Volume 48, Issue 2, Page 230-231, July 2018.
https://ift.tt/2lFzDAV
Issue Information
Alimentary Pharmacology &Therapeutics, Volume 48, Issue 2, Page 111-113, July 2018.
https://ift.tt/2lFzttj
Impact of Graphene on the Efficacy of Neuron Culture Substrates
Advanced Healthcare Materials, EarlyView.
https://ift.tt/2Knjdrg
Hierarchical Biomineralization: from Nature's Designs to Synthetic Materials for Regenerative Medicine and Dentistry
Advanced Healthcare Materials, EarlyView.
https://ift.tt/2Is9i24
Multicombination Approach Suppresses Listeria monocytogenes‐Induced Septicemia‐Associated Acute Hepatic Failure: The Role of iRhom2 Signaling
Advanced Healthcare Materials, EarlyView.
https://ift.tt/2MYyXCR
Mini Review of TiO2‐Based Multifunctional Nanocomposites for Near‐Infrared Light–Responsive Phototherapy
Advanced Healthcare Materials, EarlyView.
https://ift.tt/2KoppPV
Exogenous/Endogenous‐Triggered Mesoporous Silica Cancer Nanomedicine
Advanced Healthcare Materials, EarlyView.
https://ift.tt/2N2ZIX5
Bioinspired Mineral–Organic Bioresorbable Bone Adhesive
Advanced Healthcare Materials, EarlyView.
https://ift.tt/2KqLAVA
Improved quality attributes in soy yogurts prepared from DAG enriched edible oils and edible deoiled soy flour
European Journal of Lipid Science and Technology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2KbTwy8
Durum Wheat Bran By‐Products: Oil and Phenolic Acids to be Valorized by Industrial Symbiosis
European Journal of Lipid Science and Technology, EarlyView.
https://ift.tt/2Ka1wPX
2‐acetyl‐1,3‐diacyl‐sn‐glycerols with unusual acyl composition in seed oils of the genus Polygala
European Journal of Lipid Science and Technology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2MpZeJ9
Recovery of soybean oil containing functional ingredients from Antarctic krill (Euphausia superba) using an improved aqueous enzymatic extraction method
European Journal of Lipid Science and Technology, Volume 0, Issue ja, -Not available-.
https://ift.tt/2MpZkAv
Multilayer Lead‐Free Ceramic Capacitors with Ultrahigh Energy Density and Efficiency
Advanced Materials, EarlyView.
https://ift.tt/2KlFTeN
Flexible Transient Optical Waveguides and Surface‐Wave Biosensors Constructed from Monocrystalline Silicon
Advanced Materials, EarlyView.
https://ift.tt/2MocApy
π‐Phase Tin and Germanium Monochalcogenide Semiconductors: An Emerging Materials System
Advanced Materials, EarlyView.
https://ift.tt/2Kb4JPx
Cold Sintered Ceramic Nanocomposites of 2D MXene and Zinc Oxide
Advanced Materials, EarlyView.
https://ift.tt/2IuJB0W
A Shape‐Induced Orientation Phase within 3D Nanocrystal Solids
Advanced Materials, EarlyView.
https://ift.tt/2KeJso9
Achieving Ultralow Wear with Stable Nanocrystalline Metals
Advanced Materials, EarlyView.
https://ift.tt/2IyfG88
The potential of Olea europaea extracts to prevent TGFβ1-induced epithelial to mesenchymal transition in human nasal respiratory epithelial cells
One of the molecular mechanisms involved in upper airway-related diseases is epithelial-to-mesenchymal transition (EMT). Olea europaea (OE) has anti-inflammatory properties and thus, great potential to prevent EM...
https://ift.tt/2Msctt4
Probiotic fermentation augments the skin anti-photoaging properties of Agastache rugosa through up-regulating antioxidant components in UV-B-irradiated HaCaT keratinocytes
Agastache rugosa (Fisch. & C.A.Mey.) Kuntze (Korean mint) is used to treat diverse types of human disorders in traditional medicine. In recent years, its non-fermented leaf extract (ARE) has been shown to possess...
https://ift.tt/2KkIm9l
The Impact of Maryland's Global Budget Payment Reform on Emergency Department Admission Rates in a Single Health System
Academic Emergency Medicine, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Kn82SR
Reliability of HEARTSMAP as a tool for evaluating psychosocial assessment documentation practices in emergency departments for pediatric mental health complaints
Academic Emergency Medicine, Volume 0, Issue ja, -Not available-.
https://ift.tt/2MsbDfE
Interruptions in emergency medicine: things are not always what they seem
Academic Emergency Medicine, Volume 0, Issue ja, -Not available-.
https://ift.tt/2K8ydNT
The HEART Pathway Randomized Controlled Trial One Year Outcomes
Academic Emergency Medicine, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Mn5guf
Factors Associated with Patient Involvement in Emergency Care Decisions: A Secondary Analysis of the Chest Pain Choice Multicenter Randomized Trial
Academic Emergency Medicine, Volume 0, Issue ja, -Not available-.
https://ift.tt/2KcgOnp
Dissecting the Evidence on Aortic Catastrophe
Academic Emergency Medicine, Volume 0, Issue ja, -Not available-.
https://ift.tt/2IvjiY9
Diagnosing acute aortic dissection : Both an artery and a science
Academic Emergency Medicine, Volume 0, Issue ja, -Not available-.
https://ift.tt/2K8yccN
Patient Preferences regarding Shared Decision‐making in the Emergency Department: Findings from a multi‐site survey
Academic Emergency Medicine, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Ivypkx
First Timers
Academic Emergency Medicine, Volume 0, Issue ja, -Not available-.
https://ift.tt/2KooxxP
Understanding Emergency Medicine Physicians Multitasking Behaviors Around Interruptions
Academic Emergency Medicine, Volume 0, Issue ja, -Not available-.
https://ift.tt/2MtAQXl
Pediatric Emergency Research Canada (PERC): Patient/Family‐Informed Research Priorities for Pediatric Emergency Medicine
Academic Emergency Medicine, Volume 0, Issue ja, -Not available-.
https://ift.tt/2KkexWu
Predictors of Oral Antibiotic Treatment Failure for Non‐Purulent Skin and Soft Tissue Infections in the Emergency Department
Academic Emergency Medicine, Volume 0, Issue ja, -Not available-.
https://ift.tt/2IvjiaB
Author's reply to: Implementation and organization of cancer screening in France
International Journal of Cancer, Volume 0, Issue ja, -Not available-.
https://ift.tt/2MszMTr
Eight‐type human papillomavirus E6/E7 oncoprotein detection as a novel and promising triage strategy for managing HPV‐positive women
International Journal of Cancer, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Kkoh39
Implementation and organization of cancer screening in France
International Journal of Cancer, Volume 0, Issue ja, -Not available-.
https://ift.tt/2KrQzVW
Inhaled corticosteroids in COPD and the risk of lung cancer
International Journal of Cancer, Volume 0, Issue ja, -Not available-.
https://ift.tt/2K9OphQ
Randomized study of HPV prevalence and detection of CIN2+ in vaginal self‐sampling compared to cervical specimens collected by medical personnel
International Journal of Cancer, Volume 0, Issue ja, -Not available-.
https://ift.tt/2KmTteI
Coffee and tea consumption and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition
International Journal of Cancer, Volume 0, Issue ja, -Not available-.
https://ift.tt/2KeWWzZ
Issue Information
International Journal of Cancer, Volume 143, Issue 3, Page 451-458, 1 August 2018.
https://ift.tt/2KlVZln
Issue Information
International Journal of Cancer, Volume 143, Issue 3, Page 724-725, 1 August 2018.
https://ift.tt/2KdFD2g
Bruno Kyewski 1950‐2018
International Journal of Cancer, Volume 143, Issue 3, Page 459-459, 1 August 2018.
https://ift.tt/2MqoqiZ
The current understanding of mesenchymal stem cells as potential attenuators of chemotherapy‐induced toxicity
International Journal of Cancer, Volume 0, Issue ja, -Not available-.
https://ift.tt/2KaNaPq
Somatic late effects in 5‐year survivors of neuroblastoma: A population‐based cohort study within the Adult Life after Childhood Cancer in Scandinavia (ALiCCS) study
International Journal of Cancer, Volume 0, Issue ja, -Not available-.
https://ift.tt/2MqooHT
High turnover of extracellular matrix reflected by specific protein fragments measured in serum is associated with poor outcomes in two metastatic breast cancer cohorts
International Journal of Cancer, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Kama2G
Non‐surgical therapies for resected and unresected pancreatic cancer in Europe and USA in 2003‐2014: A large international population‐based study
International Journal of Cancer, Volume 0, Issue ja, -Not available-.
https://ift.tt/2KphOkj
CIRCULATING TUMOR DNA ANALYSIS ENABLES MOLECULAR CHARACTERIZATION OF PEDIATRIC RENAL TUMORS AT DIAGNOSIS
International Journal of Cancer, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Kko1kH
BMI1 enhancer polymorphism underlies chromosome 10p12.31 association with childhood acute lymphoblastic leukemia
International Journal of Cancer, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Mqonnj
Pre‐diagnostic plasma concentrations of Fibrinogen, sGPIIb/IIIa, sP‐selectin, sThrombomodulin, Thrombopoietin in relation to cancer risk: Findings from a large prospective study
International Journal of Cancer, Volume 0, Issue ja, -Not available-.
https://ift.tt/2KdFBYc
Metastasis directed therapy for liver and lung metastases from colorectal cancer – a population based study
International Journal of Cancer, Volume 0, Issue ja, -Not available-.
https://ift.tt/2KlJMx5
Profiles of Brain Metastases: Prioritization of Therapeutic Targets
International Journal of Cancer, Volume 0, Issue ja, -Not available-.
https://ift.tt/2KdFzzy
Statin use and mortality among endometrial cancer patients: a Danish nationwide cohort study
International Journal of Cancer, Volume 0, Issue ja, -Not available-.
https://ift.tt/2Mtql6r
SOX2‐mediated upregulation of CD24 promotes adaptive resistance towards targeted therapy in melanoma
International Journal of Cancer, Volume 0, Issue ja, -Not available-.
https://ift.tt/2KknYFx
Study Compares Treatment Options for T1a Renal Cancer
TUESDAY, June 26, 2018 -- Percutaneous ablation (PA) is associated with oncologic outcomes that are similar to those of radical nephrectomy (RN) and may be associated with fewer complications than nephron-sparing partial nephrectomy (PN) for...
https://ift.tt/2N3K5hI
Early Preterm Birth Linked to Increased ADHD Symptoms
TUESDAY, June 26, 2018 -- Early preterm birth is associated with a higher level of attention deficit/hyperactivity disorder (ADHD) symptoms in preschool children after accounting for unmeasured genetic and environmental factors, according to a study...
https://ift.tt/2yJHFlr
More Than 2,000 U.S. Campuses Smoke-Free as of Nov. 2017
TUESDAY, June 26, 2018 -- As of November 2017, at least 2,082 U.S. college and university campuses had smoke-free policies, with most of these campuses tobacco-free, prohibiting both smoking and smokeless tobacco products, according to a study...
https://ift.tt/2N0zDYz
Thinner Retinal Nerve Fiber Layer Tied to Worse Cognitive Function
TUESDAY, June 26, 2018 -- For individuals without neurodegenerative disease, a thinner retinal nerve fiber layer (RNFL) is associated with worse cognitive function and increased likelihood of future cognitive decline, according to a study published...
https://ift.tt/2yKyXU9
In Cancer Patients, PTSD May Increase Symptom Burden
TUESDAY, June 26, 2018 -- Post-traumatic stress disorder (PTSD) symptoms among hospitalized patients with cancer are associated with a greater psychological and physical symptom burden as well as a decreased risk of hospital readmissions, according...
https://ift.tt/2txEHLL
ADA: Closed-Loop Insulin Improves Glycemic Control
TUESDAY, June 26, 2018 -- Use of an automated, closed-loop insulin delivery system results in significantly better glycemic control than conventional subcutaneous insulin therapy among patients with type 2 diabetes receiving noncritical care,...
https://ift.tt/2tHk4fg
Cannabis Use Prevalence Up Across Adult Age Groups
TUESDAY, June 26, 2018 -- Across adult age categories, there was an increase in the prevalence of daily cannabis use after 2007, according to a study published online June 13 in the Journal of Studies on Alcohol and Drugs. Pia M. Mauro, Ph.D., from...
https://ift.tt/2MXO2oe
For Pediatric Patients, Wearable Cardioverter Defibrillator Safe
TUESDAY, June 26, 2018 -- For pediatric patients with ventricular arrhythmias at risk for sudden cardiac death (SCD), a wearable cardioverter defibrillator (WCD) seems safe and effective, according to a review published online June 26 in...
https://ift.tt/2yMWQdy
Insulin Glargine 300 Safe, Effective in Seniors With T2DM
TUESDAY, June 26, 2018 -- For older adults, insulin glargine 300 units/mL (Gla-300) is safe and as effective as Gla-100, with a similarly low or lower risk of symptomatic hypoglycemia, according to a study published online June 12 in Diabetes...
https://ift.tt/2ty0we6
New Hospital-at-Home Care Model Tied to Better Outcomes
TUESDAY, June 26, 2018 -- Hospital-at-home (HaH) care, along with 30-day post-acute transitional care, is associated with better patient outcomes and satisfaction with care than inpatient hospitalization, according to a study published online June...
https://ift.tt/2tHk0w2
An Optical Assay for Synaptic Vesicle Recycling in Cultured Neurons Overexpressing Presynaptic Proteins
We describe an optical assay for synaptic vesicle (SV) recycling in cultured neurons. Combining this protocol with double transfection to express a presynaptic marker and protein of interest allows us to locate presynaptic sites, their synaptic vesicle recycling capacity, and determine the role of the protein of interest.
https://ift.tt/2KfEl7a
Exogenous Administration of Microsomes-associated Alpha-synuclein Aggregates to Primary Neurons As a Powerful Cell Model of Fibrils Formation
https://ift.tt/2IqGcQF
Lumbar Epidural Steroid Injections for Herniation and Stenosis: Incidence and Risk Factors of Subsequent Surgery
Publication date: Available online 26 June 2018
Source:The Spine Journal
Author(s): Jayme C.B. Koltsov, Matthew W. Smuck, Alicia Zagel, Todd F. Alamin, Kirkham B. Wood, Ivan Cheng, Serena S. Hu
Background ContextLumbosacral ESIs have increased dramatically despite a narrowing of the clinical indications for use. One potential indication is to avoid or delay surgery, yet little information exists regarding surgery rates after ESI.PurposeThe purpose of this research was to determine the proportion of patients having surgery after lumbar epidural steroid injection (ESI) for disc herniation or stenosis and to identify the timing and factors associated with this progressionStudy Design/SettingThis study was a retrospective review of nationally-representative administrative claims data from the Truven Health MarketScan® databases from 2007 - 2014.Patient SampleThe study cohort was comprised of 179,025 patients (54±15 years, 48% female) having lumbar epidural steroid injections (ESIs) for diagnoses of stenosis and/or herniation.Outcome MeasuresThe primary outcome measure was the time from ESI to surgery.MethodsInclusion criteria were ESI for stenosis and/or herniation, age ≥18 years, and health plan enrollment for 1 year prior to ESI to screen for exclusions. Patients were followed longitudinally until they progressed to surgery or had a lapse in enrollment, at which time they were censored. Rates of surgery were assessed with the Kaplan-Meier survival curves. Demographic and treatment factors associated with surgery were assessed with multivariable Cox proportional hazard models. No external funding was procured for this research and the authors' conflicts of interest are not pertinent to the present work.ResultsWithin 6 months, 12.5% of ESI patients underwent lumbar surgery. By 1 year, 16.9% had surgery, and by 5 years, 26.1% had surgery. Patients with herniation had surgery at rates of up to 5 to 7 fold higher, with the highest rates of surgery in younger patients and those with both herniation and stenosis. Other concomitant spine diagnoses, male sex, previous tobacco use, and residence a rural areas or regions other than the Northeastern United States were associated with higher surgery rates. Medical comorbidities (previous treatment for drug use, CHF, obesity, COPD, hypercholesterolemia, and other cardiac complications) were associated with lower surgery rates.ConclusionsIn the long-term, more than 1 out of every 4 patients undergoing ESI for lumbar herniation or stenosis subsequently had surgery, and nearly 1 of 6 had surgery within the first year. After adjusting for other patient demographics and comorbidities, patients with herniation were more likely have surgery than those with stenosis. The improved understanding of the progression from lumbar ESI to surgery will help to better inform discussions regarding the value of ESI and aid in the shared decision making process.
https://ift.tt/2KqiuWm
Value of standard radiographs, CT and MRI of the lumbar spine in detection of intraoperatively confirmed pedicle screw loosening – a prospective clinical trial
Publication date: Available online 26 June 2018
Source:The Spine Journal
Author(s): José Miguel Spirig, Reto Sutter, Tobias Götschi, Nadja A. Farshad-Amacker, Mazda Farshad
Background ContextPedicle screw loosening is common after spinal fusion and can be associated with pseudoarthrosis and pain. With suspicion of screw loosening on standard radiographs, CT is currently considered the advanced imaging modality of choice. MRI with new metal artifact reduction techniques holds potential to be sensitive in detection of screw loosening. The sensitivity and specificity of either of the imaging modalities are yet clear.PurposeTo evaluate the sensitivity and specificity of three different image modalities (standard radiographs, CT and MRI) for detection of pedicle screw loosening.Study Design/SettingCross-sectional diagnostic studyPatient SampleForty-one patients (159 pedicle screws) undergoing revision surgeries after lumbar spinal fusion between August 2014 and April 2017 with preoperative radiographs, CT and MRI with spinal metal artifact reduction (STIR WARP and TSE high bandwidth sequences).Outcome MeasuresSensitivity and specificity in detection of screw loosening for each imaging modality.MethodsScrew torque force was measured intraoperatively and compared with preoperative screw loosening signs such as peri-screw edema in MRI and peri-screw osteolysis in CT and radiographs. A torque force of less than 60Ncm was used to define a screw as loosened.ResultsSensitivity and specificity in detection of screw loosening was 43.9% and 92.1% for MRI, 64.8% and 96.7% for CT, and 54.2% and 83.5% for standard radiographs, respectively.ConclusionsDespite improvement of MRI with metal artifact reduction MRI technique, CT remains the modality of choice. Even so, CT fails to detect all loosened pedicle screws.
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Sagittal spinal alignment deviation in the general elderly population: A Japanese cohort survey randomly sampled from a basic resident registry
Publication date: Available online 26 June 2018
Source:The Spine Journal
Author(s): Masashi Uehara, Jun Takahashi, Shota Ikegami, Ryosuke Tokida, Hikaru Nishimura, Noriko Sakai, Hiroyuki Kato
Background contextIt is widely recognized that sagittal spinal alignment changes with age. However, there are presently no clear benchmarks for such values or those for the cervical spine in the general population. Quality epidemiological studies are needed to establish standards for spinal alignment deviation.ObjectivesIn this study of an aged Japanese population, we employed random sampling from the basic resident registry of a rural town for subject selection to determine reference values of sagittal spinal alignment including the cervical spine.Study designJapanese resident cohort study based on a municipal registry.Patient sampleA total of 413 aged people randomly sampled from the resident registry of a rural Japanese town.Outcome measuresAll subjects underwent a whole spine lateral radiograph for measurement of sagittal spinal alignment parameters.MethodsRegistered citizens of 50 to 89 years old were targeted for this survey. We established 8 groups based on age (50′s, 60′s, 70′s, and 80′s) and gender (male and female) after random sampling from the resident registry of Obuse town in 2014. A total of 413 people (203 males and 210 females) were enrolled. Radiographic parameters of sagittal spinal alignment of the cohort were measured and analyzed. Funding for this study was provided by the Japan Orthopaedics and Traumatology Research Foundation (10,000 USD), the Japanese Orthopaedic Association (5,000 USD), the Japanese Society for Musculoskeletal Medicine (40,000 USD), and the Nakatomi Foundation (15,000 USD).ResultsGlobal spinal alignments became more misaligned with age for both genders. Sagittal vertical axis (SVA) forward shift was significantly more frequent in 80′s males and 70′s females, and SVA in 80′s females was a mean of 66 mm forward of that of 50′s females. Cervical protrusion was markedly greater in 60′s males onwards. In women, lumbar lordosis and posterior pelvic inclination were noticeable from a younger age than in men. The amount of pelvic tilt misalignment in female subjects was approximately 10 years earlier than their male counterparts.ConclusionsThis first resident cohort of Japanese individuals determined average spinal alignment parameters by age and gender. Spinal balance generally shifts forward as age increases. A forward shift in the upper cervical spine occurs first in men, while lumbopelvic alignment shift occurs first in women.
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Sensitivity and Specificity of Patient-Entered Red Flags for Lower Back Pain
Publication date: Available online 26 June 2018
Source:The Spine Journal
Author(s): John T. Tsiang, Tyler G. Kinzy, Nicolas Thompson, Joseph E. Tanenbaum, Nitya L. Thakore, Tagreed Khalaf, Irene L. Katzan
Background Content: Red flags are questions typically ascertained by providers to screen for serious underlying spinal pathologies. The utility of patient-reported red flags in guiding clinical decision-making for spine care, however, has not been studied.Purpose: The aim of this study was to quantify the sensitivity and specificity of patient-reported red flags in predicting the presence of serious spinal pathologies.Study Design: This was a retrospective nested case-control studyPatient Sample: This study consisted of 120 patients with ICD-9-CM codes for spinal pathologies and 380 randomly selected patients, from a population of 4,313 patients seen at a large tertiary care spine clinic between Oct. 9, 2013 and June 30, 2014.Outcome Measures: The presence of patient-reported red flags and red flags obtained from medical records was verified for chart review. The spinal pathology (i.e., malignancy, fractures, infections, or cauda equina syndrome) was noted for each patient.Methods: The sensitivity and specificity of patient-reported red flags for detecting serious spinal pathologies were calculated from data obtained from the 500 patients. Youden's J was used to rank performance. Agreement between patient-reported red flags and those obtained from medical record review was assessed via Cohen's kappa statistic.Results: "History of cancer" was the best performing patient-reported red flag to identify malignancy [sensitivity=.75 (95%CI .53-.90), specificity=.79 (95%CI .75-.82)]. The best performing patient-reported red flag for fractures was the presence of at least one of the following: "Osteoporosis", "Steroid use", and "Trauma" [sensitivity=.59 (95%CI .44-.72), specificity=.65 (95%CI .60-.69)]. The prevalence of infection and cauda equina diagnoses was insufficient to gauge sensitivity and specificity. Red flags from medical records had better performance than patient-reported red flags. There was poor agreement between patient red flags and those obtained from medical record review.Conclusion: Patient-reported red flags had low sensitivity and specificity for identification of serious pathologies. They should not be used in insolation to make treatment decisions, although they may be useful to prompt further probing to determine if additional investigation is warranted.
https://ift.tt/2Km2E2p
First report on cutaneous infectious granuloma caused by Schizophyllum commune
Schizophyllum commune, a basidiomycetous fungus, is a common invader of rotten wood. This fungus rarely causes mycotic disease in humans, especially cutaneous infection. In this paper, we describe the first case ...
https://ift.tt/2lyDQpE
Seroprevalence and risk factors of recent infection with hepatitis E virus during an acute outbreak in an urban setting in Chad, 2017
From September 2016–April 2017, Am Timan, Chad, experienced a large HEV outbreak in an urban setting with a limited impact in terms of morbidity and mortality. To better understand HEV epidemiology in this con...
https://ift.tt/2tF3tc3
Tracing Gene Expression Through Detection of β-galactosidase Activity in Whole Mouse Embryos
Here we describe the standard protocol for the detection of β-galactosidase activity in early whole mouse embryos and the method for paraffin sectioning and counterstaining. This is an easy and quick procedure to monitor gene expression during development that can also be applied to tissue sections, organs or cultured cells.
https://ift.tt/2KnyYSj
Single-cell Analysis of Immunophenotype and Cytokine Production in Peripheral Whole Blood via Mass Cytometry
Here we describe a single-cell proteomic approach to evaluate immune phenotypic and functional (intracellular cytokine induction) alterations in peripheral whole blood samples, analyzed via mass cytometry.
https://ift.tt/2KpHEEH
Prevalence of antibiotic resistant Escherichia coli isolates from fecal samples of food handlers in Qatar
It is well documented that food handlers harbor and shed enteric foodborne pathogens causing foodborne disease outbreaks. However, little known on enteric antibiotic resistant (AR) bacteria carriage in food ha...
https://ift.tt/2MpzNY9
Recurrent Glioblastoma Treated with Recombinant Poliovirus
https://ift.tt/2K9o1Vg
Preclinical Assessment of the Bioactivity of the Anticancer Coumarin OT48 by Spheroids, Colony Formation Assays, and Zebrafish Xenografts
Here, we present the preclinical screening of anticancer coumarins using 3D culture and zebrafish.
https://ift.tt/2KayakL
Treating Low Back Pain in Failed Back Surgery Patients with Multicolumn-lead Spinal Cord Stimulation
This paper presents a method that uses spinal cord stimulation with a multicolumn lead to treat neuropathic low back pain in failed back surgery patients.
https://ift.tt/2IuICxt
Clonal structures of regionally synchronous gastric adenomas and carcinomas
Purpose: Gastric adenoma (GA) is a premalignant lesion that precedes intestinal-type gastric carcinoma (GC). However, genetic progression mechanisms from GA to GC have not been clarified. Experimental design: We performed whole-exome sequencing-based mutational analyses for 15 synchronous pairs of attached GAs and GCs. Results: There was no significant difference in the number of driver mutations or copy number alterations between GAs and GCs. Well-known mutations of TP53, APC, RNF43, and RPL22 were recurrently detected in synchronous GA/GC pairs. In addition, we discovered novel KDM6A, PREX2, FAT1, KMT2C, GLI3 and RPL22 mutations and hypermutation in GAs, but did not identify recurrent drivers for GA-to-GC progression. Clonal structure analyses revealed that most GA/GC pairs exhibit parallel evolution with early divergence rather than stepwise evolution during GA-to-GC progression. Of note, three cases were identified as clonally non-related GA/GC pairs despite the lack of histologic differences. We found differences in dominant mutational signatures 1, 6, 15, and 17 in GA/GC trunks, GA-branches, and GC-branches. Compared to our previous work on synchronous colon adenoma/carcinoma genome structures, where most drivers were in the trunk with parallel evolution, synchronous GA/GC genomes showed a different model of parallel evolution, with many drivers in the branches. Conclusions: The preferred sequence of mutational events during GA-to-GC progression might be more context-dependent than colon adenoma progression. Our results show that non-clonal synchronous GA/GC is common, and that GA genomes have already acquired distinct genomic alterations, suggesting caution in the diagnosis of synchronous GA and GC, especially in residual or recurrent cases.
https://ift.tt/2KoCada
The light chain IgLV3-21 defines a new poor prognostic subgroup in Chronic Lymphocytic Leukemia: results of a multicenter study
Purpose: Unmutated (UM) immunoglobulin heavy chain variable region (IgHV) status or IgHV3-21 gene usage is associated with poor prognosis in chronic lymphocytic leukemia (CLL) patients. Interestingly, IgHV3-21 is often co-expressed with light chain IgLV3-21, which is potentially able to trigger cell-autonomous BCR-mediated signaling. However, this light chain has never been characterized independently of the heavy chain IgHV3-21. Experimental Design: We performed total RNA sequencing in 32 patients and investigated IgLV3-21 prognostic impact in terms of treatment-free (TFS) and overall (OS) survival in 3 other independent cohorts for a total of 813 patients. IgLV3-21 presence was tested by real-time PCR and confirmed by Sanger sequencing. Results: Using total RNA sequencing to characterize 32 patients with high-risk CLL, we found a high frequency (28%) of IgLV3-21 rearrangements. Gene set enrichment analysis revealed that these patients express higher levels of genes responsible for ribosome biogenesis and translation initiation (P<0.0001) as well as MYC target genes (P=0.0003). Patients with IgLV3-21 rearrangements displayed a significantly shorter TFS and OS (P<0.05), particularly in IgHV-mutated patients. In each of the 3 independent validation cohorts, we showed that IgLV3-21 rearrangements -similar to UM IgHV status- conferred poor prognosis compared to mutated IgHV (P<0.0001). Importantly, we confirmed by multivariate analysis that this was independent of IgHV mutational status or subset #2 stereotyped receptor (P<0.0001). Conclusions: We have demonstrated for the first time that a light chain can impact CLL prognosis and that IgLV3-21 light chain usage defines a new subgroup of CLL patients with poor prognosis.
https://ift.tt/2N0YafT
Characterization of alternative splicing events in HPV negative head and neck squamous cell carcinoma identifies an oncogenic DOCK5 variant
Purpose: Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide and alternative splicing is considered to play important roles in tumor progression. Our study is designed to identify alternative splicing events (ASEs) in HPV negative HNSCC. Experimental Design: RNA sequencing data of 407 HPV negative HNSCC and 38 normal samples were obtained from The Cancer Genome Atlas (TCGA) and splice junctions were discovered using MapSplice. Outlier analysis was used to identify significant splicing junctions between HPV negative HNSCC and normal samples. To explore the functional role of the identified DOCK5 variant, we checked its expression with qRT-PCR in a separate primary tumor validation set and performed proliferation, migration and invasion assays. Results: 580 significant splicing events were identified in HPV negative HNSCC and the most common type of splicing events was an alternative start site (33.3%). The prevalence of a given individual ASE among the tumor cohort ranged from 9.8% and 64.4%. Within the 407 HPV negative HNSCC samples in TCGA, the number of significant ASEs differentially expressed in each tumor ranged from 17 to 290. We identified a novel candidate oncogenic DOCK5 variant confirmed using qRT-PCR in a separate primary tumor validation set. Loss- and gain-of-function experiments indicated that DOCK5 variant promoted proliferation, migration and invasion of HPV negative HNSCC cells, and patients with higher expression of DOCK5 variant showed decreased overall survival. Conclusion: Analysis of ASEs in HPV negative HNSCC identifies multiple alterations likely related to carcinogenesis, including an oncogenic DOCK5 variant.
https://ift.tt/2KnpyTK
Assessing Therapeutic Efficacy of MEK Inhibition in a KRAS G12C-Driven Mouse Model of Lung Cancer
Purpose: Despite the challenge to directly target mutant KRAS due to its high GTP affinity, some agents are under development against downstream signaling pathways, such as MEK inhibitors. However, it remains controversial whether MEK inhibitors can boost current chemotherapy in KRAS-mutant lung tumors in clinic. Considering the genomic heterogeneity among lung cancer patients, it is valuable to test potential therapeutics in KRAS-mutation driven mouse models. Experimental Design: We first compared the pERK1/2 level in lung cancer samples with different KRAS substitutions and generated a new genetically engineered mouse model whose tumor was driven by KRAS G12C, the most common KRAS mutation in lung cancer. Next, we evaluated the efficacy of selumetinib or its combination with chemotherapy, in KRAS G12C tumors compared to KRAS G12D tumors. Moreover, we generated KRAS G12C/p53 R270H model to explore the role of a dominant negative p53 mutation detected in patients in responsiveness to MEK inhibition. Results: We determined higher pERK1/2 in KRAS G12C lung tumors compared to KRAS G12D. Using mouse models, we further identified that KRAS G12C tumors are significantly more sensitive to selumetinib compared with Kras G12D tumors. MEK inhibition significantly increased chemotherapeutic efficacy and progression-free survival of KRAS G12C mice. Interestingly, p53 co-mutation rendered KRAS G12C lung tumors less sensitive to combination treatment with selumetinib and chemotherapy. Conclusions: Our data demonstrate that unique KRAS mutations and concurrent mutations in tumor-suppressor genes are important factors for lung tumor responses to MEK inhibitor. Our preclinical study supports further clinical evaluation of combined MEK inhibition and chemotherapy for lung cancer patients harboring KRAS G12C and wildtype p53 status.
https://ift.tt/2MZFL3f
Molecular Analyses Support the Safety and Activity of Retroviral Replicating Vector Toca 511 in Patients
Purpose: Toca 511 is a gammaretroviral replicating vector encoding cytosine deaminase that selectively infects tumor cells and coverts the antifungal drug 5-fluorocytosine into the antineoplastic drug 5-fluorouracil, which directly kills tumor cells and stimulates anti-tumor immune responses. As part of clinical monitoring of Phase 1 clinical trials in recurrent high grade glioma we have performed extensive molecular analyses of patient specimens in order to track vector fate. Experimental Design: Toca 511 and Toca FC (extended-release 5-fluorocytosine) have been administered to 127 high grade glioma patients across three phase I studies. We measured Toca 511 RNA and DNA levels in available body fluids and tumor samples from patients to assess tumor specificity. We mapped Toca 511 integration sites and sequenced integrated Toca 511 genomes from patient samples with detectable virus. We measured Toca 511 levels in a diverse set of tissue samples from one patient. Results: Integrated Toca 511 is commonly detected in tumor samples and is only transiently detected in blood in a small fraction of patients. There was no believable evidence for clonal expansion of cells with integrated Toca 511 DNA, or preferential retrieval of integration sites near oncogenes. Toca 511 sequence profiles suggest most mutations are caused by APOBEC cytidine deaminases acting during reverse transcription. Tissue samples from a single whole-body autopsy affirm Toca 511 tumor selectivity. Conclusions: Toca 511 and Toca FC treatment was not associated with inappropriate integration sites and clonal expansion. The vector is tumor selective and persistent in patients who received Toca 511 injections.
https://ift.tt/2KojHxB
Talazoparib is a Potent Radiosensitizer in Small Cell Lung Cancer Cell Lines and Xenografts
Purpose: Small cell lung cancer (SCLC) is an aggressive malignancy with a critical need for novel therapies. Our goal was to determine whether PARP inhibition could sensitize SCLC cells to ionizing radiation (IR) and if so, to determine the contribution of PARP trapping to radiosensitization. Methods and Materials: Short-term viability assays and clonogenic survival assays (CSA) were used to assess radiosensitization in six SCLC cell lines. Doses of veliparib and talazoparib with equivalent enzymatic inhibitory activity but differing PARP trapping activity were identified and compared in CSAs. Talazoparib, IR, and their combination were tested in three patient-derived xenograft (PDX) models. Results: Talazoparib radiosensitized 5 of 6 SCLC cell lines in short-term viability assays and confirmed in 3 of 3 cell lines by CSAs. Concentrations of 200 nM talazoparib and 1600 nM veliparib similarly inhibited PAR polymerization; however, talazoparib exhibited greater PARP trapping activity that was associated with superior radiosensitization. This observation further correlated with an increased number of double-stranded DNA breaks induced by talazoparib as compared to veliparib. Finally, a dose of 0.2 mg/kg talazoparib in vivo caused tumor growth inhibition in combination with IR but not as a single agent in 3 SCLC PDX models. Conclusions: PARP inhibition effectively sensitizes SCLC cell lines and PDXs to IR, and PARP trapping activity enhances this effect. PARP inhibitors, especially those with high PARP trapping activity, may provide a powerful tool to improve the efficacy of radiation therapy in SCLC.
https://ift.tt/2MpcFJu
Endoglin expression on cancer-associated fibroblasts regulates invasion and stimulates colorectal cancer metastasis
Purpose: Cancer-associated fibroblasts (CAFs) are a major component of the colorectal cancer (CRC) tumor microenvironment. CAFs play an important role in tumor progression and metastasis, partly through the transforming growth factor-β (TGF-β) signaling pathway. We investigated whether the TGF-β family co-receptor endoglin is involved in CAF-mediated invasion and metastasis. Experimental design: CAF-specific endoglin expression was studied in CRC resection specimens using immunohistochemistry and related to metastases-free survival. Endoglin-mediated invasion was assessed in vitro by transwell invasion, using primary CRC-derived CAFs. Effects of CAF-specific endoglin expression on tumor cell invasion were investigated in a CRC zebrafish model, while liver metastases were assessed in a mouse model. Results: CAFs specifically at invasive borders of CRC express endoglin and increased expression intensity correlated with increased disease stage. Endoglin-expressing CAFs were also detected in lymph node and liver metastases, suggesting a role in CRC metastasis formation. In stage-II CRC, CAF-specific endoglin expression at invasive borders correlated with poor metastasis-free survival. In vitro experiments revealed that endoglin is indispensable for bone morphogenetic protein (BMP)-9-induced signaling and CAF survival. Targeting endoglin using the neutralizing antibody TRC105 inhibited CAF invasion in vitro. In zebrafish, endoglin-expressing fibroblasts enhanced colorectal tumor cell infiltration into the liver and decreased survival. Finally, CAF-specific endoglin targeting with TRC105 decreased metastatic spread of CRC cells to the mouse liver. Conclusions: Endoglin-expressing CAFs contribute to CRC progression and metastasis. TRC105 Treatment inhibits CAF invasion and tumor metastasis, indicating an additional target beyond the angiogenic endothelium, possibly contributing to beneficial effects reported during clinical evaluations.
https://ift.tt/2MXxSLA
Caring for Older Surgical Patients: Contemporary Attitudes, Knowledge, Practices, and Needs of General Surgeons and Residents
Objective: To gain contemporary insights from residents and surgeons regarding the care of older surgical patients. Background Data: With worldwide aging, efforts over the past decade have attempted to increase surgeons' abilities to care for older adults, but a current understanding of attitudes, knowledge, practices, and needs is missing. Methods: Between July 2016 and September 2016 we conducted a national Web-based survey sampling all general surgery residents and academic general surgeons using a questionnaire designed and tested for this purpose. Summative scales within each domain (attitudes, knowledge, practices, and needs) were created and compared between groups. Open-ended responses were analyzed with thematic analysis. Results: Ninety-four of 172 invited residents (55%) and 80 of 243 invited surgeons (33%) across 14 general surgery programs responded with no missing data. Both groups had favorable attitudes (83% vs 68%, P = 0.02). However, 80% of residents and 76% of surgeons had medium-level knowledge test scores, and few had prior training. Most respondents reported only sometimes performing guideline-recommended practices (71% vs 73%, P = 0.55). Gaps in training and care delivery were identified. Residents wanted focused, high-yield materials and case-oriented practical skills training. Respondents reported further improvements may come from building surgeons' capacity, enhancing collaboration including perioperative geriatric services, better preoperative assessment, increased adherence to perioperative guidelines, and greater community-based supports to recovery. Conclusions: Residents and surgeons have favorable attitudes, but only moderate geriatric-specific knowledge and only some guideline-adherent practices. We identified gaps in training and care delivery with targets for future knowledge translation and quality improvement initiatives.https://ift.tt/2l7KDGO
Activity‐dependent vs. neurotrophic modulation of acetylcholine receptor expression: Evidence from rat soleus and extensor digitorum longus muscles confirms the exclusive role of activity
European Journal of Neuroscience, EarlyView.
https://ift.tt/2tC88eY
Bench-to-clinic development of imageable drug-eluting embolization beads: finding the balance
Future Oncology, Ahead of Print.
https://ift.tt/2ItQUpq
Maximizing Utilization in Pancreas Transplantation: Phenotypic Characteristics Differentiating Aggressive from Nonaggressive Transplant Centers
Background Maximizing pancreas utilization requires a balance between judicious donor selection and transplant center aggressiveness. We sought to determine how such aggressiveness affects transplant outcomes. Methods Using the Scientific Registry of Transplant Recipients, we studied 28 487 deceased-donor adult pancreas transplants. Donor and recipient demographic factors indicative of aggressiveness were used to score center aggressiveness. We compared outcomes of low (> 1 SD below mean), medium (+/- 1 SD from mean), and high (> 1 SD above mean) aggressiveness centers using bivariate and multivariable regression. Results Donor and recipient aggressiveness demonstrated a roughly linear relationship (R2 = 0.20). Center volume correlated moderately with donor (rs = 0.433) and recipient (rs = 0.270) aggressiveness. In bivariate analysis, there was little impact of donor selection aggressiveness on graft survival. Further, for simultaneous pancreas and kidney transplants, centers with greater recipient aggressiveness selection had better graft survival. High volume centers had better graft survival than low volume centers. In multivariable analysis, donor aggressiveness did not have an effect on graft survival; whereas graft survival for medium (HR 0. 66, CI 0.53-0.83) and high (HR 0.67, CI 0.51-0.86) recipient aggressiveness performed better than low aggressiveness centers. There was a clear volume effect, with high volume centers (>20 transplants/year, HR 0.69, CI 0.61-0.79) performing better than low volume centers. Conclusions Center practice patterns using higher risk donors and recipients did not negatively affect outcomes. This effect is likely mediated through efficiencies gained with the increased transplant volumes at these centers. Received 26 February 2018. Revision received 23 May 2018. Accepted 12 June 2018. Presented at the 16th International Congress of the International Pancreas and Islet Transplant Association (Oxford, United Kingdom), June 21-24, 2017. Correspondence: Oscar K. Serrano, MD, MBA, University of Minnesota, Division of Transplantation, Department of Surgery, Mayo Mail Code 195, 420 Delaware Street SE, Minneapolis, MN 55455. Email: serra061@umn.edu 1. Authorship: •Participated in research design: Serrano, Vock, Finger. •Participated in the writing of the paper: Serrano, Finger. •Participated in the editing of the paper: Serrano, Vock, Dunn, Kandaswamy, Finger. •Participated in the performance of the research: Serrano, Vock, Dunn, Kandaswamy, Finger. •Contributed new reagents or analytic tools: Vock, Finger •Participated in data analysis: Serrano, Vock, Finger. 2. Disclosure: The authors declare no conflicts of interest. 3. Funding: The authors declare no funding received for this work. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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https://ift.tt/2IsG57c
Efficacy of IgM-Enriched Immunoglobulin for Vasopressor-Resistant Vasoplegic Shock After Liver Transplantation
Background Vasoplegia is a clinical condition typically manifested by cardiovascular instability unresponsive to usual doses of inotropes or vasopressors. It can occur in a variety of clinical settings including liver transplantation (LT). Immunoglobulins have been used to treat sepsis-related vasoplegia. We performed a retrospective study to evaluate the efficacy of IgM-enriched immunoglobulin (IgMIg) on 30-day mortality and its ability to reverse vasoplegia in patients undergoing LT. Methods Between 5/2013 and 11/2017, 473 LT were performed at our institution. We identified 21 patients who received IgMIg for 3 days to treat vasoplegia. Patients included in the study met the criteria for having vasoplegia and required noradrenaline administration greater than 1 μg/kg/min for more than 24 h to maintain a mean arterial pressure (MAP) ≥ 70 mmHg. Procalcitonin (PCT) and interleukin-6 (IL-6) levels were used as surrogate markers for inflammation and were measured at the beginning and end of IgM treatment. Results After IgMIg administration, median noradrenaline infusion rates could be significantly reduced from 1.6 (1.3-2) μg/kg/min to 0.16 (0.08-0.34) μg/kg/min (P
https://ift.tt/2MsiB4f
https://ift.tt/2MsiB4f
Incidence, Outcomes, and Long-Term Immune Response to Tuberculosis in Organ Transplant Recipients
Background Tuberculosis (TB) is a significant opportunistic infection in solid organ transplant recipients (SOTR). There are limited data on TB incidence in transplantation from low prevalence countries as well as on long-term TB specific immune responses. Methods We performed a single-center retrospective review of SOTR diagnosed with active TB between 2000 and 2015 and further contacted the available patients for a study of long-term T cell responses using an interferon-gamma (IFN-γ) release assay and a flow cytometry-based assay. Results We identified 31 SOTR with active TB for an incidence of 62 cases/100,000 patient-years. 19/31 (61.3%) patients were diagnosed within the first year after transplant. Nineteen (61.3%) were born in countries with high TB prevalence and disseminated disease occurred in 22.6%. No patient had been screened for latent TB infection pretransplant. The majority of patients received isoniazid and a rifamycin as part of multidrug regimen. In addition, 13/29 (44.8%) patients received quinolones. One-year mortality in this population was 19.4%. Eight patients were available for long-term immune responses. Of these, all had detectable IFN-γ response by interferon-gamma release assay testing and 7/8 had detectable TB-specific T cells, primarily central and effector T cell responses in the CD4+ compartment and terminally differentiated T cells in the CD8+ compartment. Conclusions TB has high incidence in SOTR even in low-prevalence regions but especially targets patients who originated from TB-endemic countries. Long-term TB-specific T cell responses were found in the majority of patients. Received 26 March 2018. Revision received 22 May 2018. Accepted 16 June 2018. *denotes joint senior authorship CORRESPONDENCE Deepali Kumar MD, Associate Professor of Medicine, Transplant Infectious Diseases & Multi Organ Transplant Program, University Health Network, 585 University Ave., 11-PMB-174, Toronto ON M5G 2N2. Email: deepali.kumar@uhn.ca AUTHOR CONTRIBUTIONS Y.N., A.H. and D.K participated in research design, the writing of the paper, performance of the research and data analysis. V.H.F and S.N. participated in the data analysis and interpretation. S.H., C.R. participated in writing of the paper. DISCLOSURE D.K. has received research funding from Qiagen, and Oxford Immunotec as well as consultancy fees from Qiagen and Oxford Immunotec. A.H. has received research funding from Qiagen. The remaining authors have no conflicts of interest. FUNDING The authors declare no funding for this study. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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https://ift.tt/2IsqBjB
Perioperative Blood Management, Red Cell Recovery (Cell Salvage) Practice in an Australian Tertiary Hospital: A Hospital District Clinical Audit
BACKGROUND: Data on red cell recovery (cell salvage) utilization in Australia are limited and national guidance is based on a single Australian audit conducted at a hospital that excludes cardiothoracic surgery. This clinical audit aimed to analyze the utility of red cell recovery at a tertiary health care facility which includes cardiothoracic surgery. Secondary aims of this study were to identify specific surgical procedures in which red cell recovery is most beneficial and to quantify this benefit. METHODS: Data were collected retrospectively on all adult red cell recovery surgical cases conducted at a 2-campus health care facility over a 2-year period. Case demographic data, including surgical procedure, red blood cell return, and hematocrit levels, were collated and analyzed against national cell salvage guidelines. Average return per procedure was collated into a red cell recovery benefit analysis. RESULTS: A total of 471 red cell recovery cases for 85 surgical procedures met inclusion criteria. Of the 7 surgical subspecialties utilizing red cell recovery, orthopedics utilized the most cases (22.9%, n = 108), followed by urology (19.1%, n = 90) and cardiothoracic surgery (18.3%, n = 86). Radical retropubic prostatectomy (11.7%), revision (7.6%), and primary (6.6%) total hip replacement were the most utilized procedures. Red cell recovery use had a 79% compliance rate with national guidelines. Vascular surgery and urology had the highest average return at 699 mL (interquartile range, 351–1127; CI, 449–852) and 654 mL (interquartile range, 363–860; CI, 465–773), respectively. CONCLUSIONS: Overall, our center demonstrated good compliance with national red cell recovery guidelines. This audit adds to the existing data on red cell recovery practice in Australia and provides a benefit-specific surgical procedure guideline that includes cardiothoracic surgery. Accepted for publication May 5, 2018. Funding: None. The authors declare no conflicts of interest. Gold Coast Health Human Research Ethics Committee number: HREC/17/QGC/130. Reprints will not be available from the authors. Address correspondence to Elizabeth A. Forrest, MD, Department of Anaesthetics, Gold Coast Hospital and Health Service, 1 Hospital Blvd, Southport, QLD 4214, Australia. Address e-mail to elizabeth.forrest3@health.qld.gov.au. © 2018 International Anesthesia Research Society
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https://ift.tt/2N0GZLr
Treating Anemia in the Preanesthesia Assessment Clinic: Results of a Retrospective Evaluation
BACKGROUND: Perioperative anemia is challenging during hospital stay because anemia and red blood cell (RBC) transfusions are associated with an increased morbidity and mortality. With the implementation of patient blood management (PBM), a preanesthesia assessment clinic to screen and treat anemia before elective surgery was institutionalized at Muenster University Hospital, Germany. The main objective of this study was to evaluate the association between treating preoperative anemic patients with intravenous iron (IVI) and (primarily) presurgical hemoglobin levels and (secondarily) use of RBCs and mortality. METHODS: Between April 1, 2014, and July 4, 2016, patients scheduled for elective surgery with a risk for RBC transfusions >10% in 2013 were screened for preoperative anemia and, if indicated, treated with IVI. Patients' data, time span between visit in the anesthesia/PBM clinic and surgery, demographic data, type of surgery, the difference of hemoglobin levels between visit and surgery, RBC transfusion, infectious-related International Classification of Disease codes during hospital stay, and 1-year survival were determined retrospectively by screening electronic data files. In addition, patients were interviewed about adverse events, health-related events, and infections via telephone 30, 90, and 365 days after visiting the anesthesia/PBM clinic. RESULTS: A total of 1101 patients were seen in the anesthesia/PBM clinic between days −28 and −1 (median [Q1–Q3], −3 days [−1, −9 days]) before elective surgery. Approximately 29% of patients presented with anemia, 46.8% of these anemic patients were treated with ferric carboxymaltose (500–1000 mg). In the primary analysis, hemoglobin levels at median were associated with a reduction between the visit in the anesthesia/PBM clinic and the surgery in all nonanemic patients on beginning of medical treatment (nonanemic patients at median −2.8 g/dL [−4, −0.9 g/dL], while anemic patients without IVI presented with median differences of −0.8 g/dL [−2, 0 g/dL] and anemic patients with IVI of 0 g/dL [−1.0, 0.5 g/dL]). Hemoglobin levels raised best at substitution 22–28 days before surgery (0.95 g/dL [−0.35, 1.18 g/dL]). Due to the selection criteria, transfusion rates were high in the cohort. Overall, there was no association between IVI treatment and the use of RBC transfusions (odds ratio for use of RBCs in anemic patients, no IVI versus IVI: 1.14; 95% confidence interval, 0.72–1.82). Patients treated with or without IVI presented a comparable range of International Classification of Disease codes related to infections. Telephone interviews indicated similar adverse events, health-related events, and infections. Cox regression analysis showed an association between anemia and reduced survival, regardless of IVI. CONCLUSIONS: An anemia clinic within the preanesthesia assessment clinic is a feasible and effective approach to treat preoperative anemia. The IVI supplementation was safe but was associated with decreased RBC transfusions in gynecology/obstetric patients only. The conclusions from this retrospective analysis have to be tested in prospective, controlled trials. Accepted for publication May 8, 2018. Funding: This work was supported by an industrial grant for the implementation of patient blood management to H.V.A. (AF 700501). A.U.S. receives funding from the German Research Foundation (DFG-STE1895-4/1). The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). Clinical trial number: The implementation of Patient Blood Management and treatment of anemia was registered at clinicaltrial.gov NCT01820949. I. Ellermann and A. Bueckmann contributed equally and share first authorship. Reprints will not be available from the authors. Address correspondence to Andrea U. Steinbicker, MD, PD, MPH, Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Albert-Schweitzer Campus 1, Bldg A1, Muenster 48149, Germany. Address e-mail to andrea.steinbicker@ukmuenster.de. © 2018 International Anesthesia Research Society
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https://ift.tt/2Mrm17o
Usefulness of the Korean Version of the CAGE-Adapted to Include Drugs Combined With Clinical Predictors to Screen for Opioid-Related Aberrant Behavior
BACKGROUND: As national opioid consumption in South Korea has soared, well-validated screening tools for opioid use disorder (OUD) have become indispensable. The aims of our study were to evaluate OUD using the Korean version of the CAGE-Adapted to Include Drugs (CAGE-AID) and the CAGE-Opioid (an alternative version of the CAGE-AID), and to investigate clinical predictors that might be useful to screen for OUD in conjunction with the CAGE-AID/Opioid questionnaires. METHODS: A single-center, prospective, observational study was performed. After linguistic validation of the Korean version of the CAGE-AID/Opioid questionnaires, we assessed OUD in patients with chronic opioid treatment. Multivariable logistic models of the CAGE-AID/Opioid questionnaires combined with relevant clinical predictors were established. Then, the receiver operating characteristic curve analysis of the multivariable CAGE-AID/Opioid models was conducted to assess diagnostic accuracy to screen for OUD. Next, we calculated predicted probability with >85% sensitivity and >50% specificity in each CAGE-AID and CAGE-Opioid model. Using the optimal value of the predicted probability, a cutoff score of the CAGE-AID/Opioid questionnaires combined with the relevant clinical factors was suggested to screen for OUD. RESULTS: Among 201 participants, 51 patients showed ≥1 OUDs. In the multivariable regression model, male sex, comorbid neuropsychiatric disorder, and current heavy drinking significantly remained as clinical variables to predict OUD combined with the scores of the Korean CAGE-AID/Opioid questionnaire. The area under the curve was 0.77 (95% confidence interval, 0.71–0.83) for the CAGE-AID model and 0.78 (95% confidence interval, 0.71–0.83) for the CAGE-Opioid model. The optimal predicted probability values to screen for OUD in the CAGE-AID/Opioid models were >0.135 (sensitivity, 0.86; specificity, 0.52) and >0.142 (sensitivity, 0.86; specificity, 0.53), respectively. When we used these predictive probabilities, the cutoff score of the CAGE-AID/Opioid questionnaires ranged from 0 to 3, which was dependent on the presence of the relevant clinical variables in each model. CONCLUSIONS: In this study, one fourth of the total participants with chronic opioid treatment showed OUD in the Korean population. The multivariable models of the CAGE-AID/Opioid with sex, comorbid neuropsychiatric disorder, and current heavy drinking are valid parameters to screen for OUD, with the cutoff scores of the CAGE-AID/Opioid questionnaires ranging from 0 to 3 depending on the presence of the clinical variables. Accepted for publication May 8, 2018. Funding: None. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Jee Youn Moon, MD, PhD, FIPP, CIPS, Department of Anesthesiology and Pain Medicine, Seoul National University Hospital College of Medicine, 110 Daehang-ro, Jongno-gu, Seoul 110–744, Korea. Address e-mail to jymoon0901@gmail.com. © 2018 International Anesthesia Research Society
https://ift.tt/2N2tfjh
https://ift.tt/2N2tfjh
Incidence and Epidemiology of Perioperative Transfusion-Related Pulmonary Complications in Pediatric Noncardiac Surgical Patients: A Single-Center, 5-Year Experience
BACKGROUND: Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) are the leading causes of transfusion-related fatalities. While these transfusion-related pulmonary complications (TRPCs) have been well detailed in adults, their burden in pediatric subsets remains poorly defined. We sought to delineate the incidence and epidemiology of pediatric TRPCs after intraoperative blood product transfusion. METHODS: In this retrospective cohort study, we evaluated all consecutive pediatric patients receiving intraoperative blood product transfusions during noncardiac surgeries between January 2010 and December 2014. Exclusion criteria were cyanotic heart disease, preoperative respiratory insufficiency, extracorporeal membrane oxygenation, and American Society of Anesthesiologists physical status VI. Medical records were electronically screened to identify those with evidence of hypoxemia, and in whom a chest x-ray was obtained within 24 hours of surgery. Records were then manually reviewed by 2 physicians to determine whether they met diagnostic criteria for TACO or TRALI. Disagreements were adjudicated by a third senior physician. RESULTS: Of 19,288 unique pediatric surgical patients, 411 were eligible for inclusion. The incidence of TRPCs was 3.6% (95% confidence interval [CI], 2.2–5.9). TACO occurred in 3.4% (95% CI, 2.0–5.6) of patients, TRALI was identified in 1.2% (95% CI, 0.5–2.8), and 1.0% (95% CI, 0.4–2.5) had evidence for both TRALI and TACO. Incidence was not different between males (3.4%) and females (3.8%; P = .815). Although a trend toward an increased incidence of TRPCs was observed in younger patients, this did not reach statistical significance (P = .109). Incidence was comparable across subsets of transfusion volume (P = .184) and surgical specialties (P = .088). Among the 15 patients experiencing TRPCs, red blood cells were administered to 13 subjects, plasma to 3, platelets to 3, cryoprecipitate to 2, and autologous blood to 3. Three patients with TRCPs were transfused mixed blood components. CONCLUSIONS: TRPCs occurred in 3.6% of transfused pediatric surgical patients, with the majority of cases attributable to TACO, congruent with adult literature. The frequency of TRPCs was comparable between genders and across surgical procedures and transfusion volumes. The observed trend toward increased TRPCs in younger children warrants further consideration in future investigations. Red blood cell administration was the associated component for the majority of TRPCs, although platelets demonstrated the highest risk per component transfused. Mitigation of perioperative risk associated with TRPCs in pediatric patients is reliant on further multiinstitutional studies powered to examine patterns and predictors of this highly morbid entity. Accepted for publication May 8, 2018. Funding: D.J.K. receives funding via National Institutes of Health grant R01-HL121232. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Leanne Thalji, BM, MSc, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905. Address e-mail to thalji.leanne@mayo.edu. © 2018 International Anesthesia Research Society
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