Publication date: Available online 19 November 2018
Source: The Spine Journal
Author(s): Christopher M. Bono
https://ift.tt/2QYAKJR
Τρίτη 20 Νοεμβρίου 2018
Toward stimulating apoptosis in human lung adenocarcinoma cells by novel nano-carmofur compound treatment
Lung cancer is one of the common and most fatal diseases worldwide. It has a high incidence in both men and women, in Turkey. Current antineoplastic drugs are reported to have limitations such as narrow therapeutic index and selectivity, toxicity, and antiproliferative effects on cancer cells. Thus, this study was aimed to investigate the potential cytotoxic, antiproliferative and apoptosis-triggering effects of a newly developed SLN-Carmofur compound on human lung adenocarcinoma A549 cells. The results of this study have shown that SLN-Carmofur significantly decreased the viability of A549 cells in a dose-dependent manner by short-time application. The IC50 value of the agent caused chromatin condensation, fragmentation of the nuclei, and holes on cytoskeleton; moreover, it altered the ultrastructure of the exposed cells with clear signs of apoptosis. Taken all our results together, it is indicated that SLN-Carmofur may be proposed for further research for drug development for cancer therapy, depending on the valuable potential in stimulating apoptosis in cancer cells. Correspondence to Dr Hatice M. Kutlu, Department of Biology, Faculty of Science, Anadolu University, Eskişehir 26470, Turkey Tel: +90 222 335 0580/+90 222 335 4721; e-mail: hmkutlu@anadolu.edu.tr Received May 22, 2018 Accepted November 2, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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https://ift.tt/2Tx3efe
The success of the representation maintenance affects the memory-guided search processing: an ERP study
Abstract
Previous evidence showed that working memory (WM) contents can bias visual selection. However, less is known about how the WM effects change when the WM representation is not held successfully. Here, we investigated this problem using event-related potentials. Subjects maintained a color in WM while performing a search task. The color cue contained the target (valid) or the distractor (invalid). Subjects could either remember the color accurately (correct WM) or not (incorrect WM). An N2-posterior contralateral component and a sustained posterior contralateral negativity (SPCN) were recorded in the valid and incorrect WM condition, while only an attenuated SPCN was elicited in the valid and correct WM condition. No reliable lateralized components were found for the invalid trials. These findings suggest that the WM effects on visual search are affected by the resource interchange between WM and search processes.
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Correction to: ZIKA virus elicits P53 activation and genotoxic stress in human neural progenitors similar to mutations involved in severe forms of genetic microcephaly
Correction to: ZIKA virus elicits P53 activation and genotoxic stress in human neural progenitors similar to mutations involved in severe forms of genetic microcephaly
Correction to: ZIKA virus elicits P53 activation and genotoxic stress in human neural progenitors similar to mutations involved in severe forms of genetic microcephaly, Published online: 20 November 2018; doi:10.1038/s41419-018-1159-8
Correction to: ZIKA virus elicits P53 activation and genotoxic stress in human neural progenitors similar to mutations involved in severe forms of genetic microcephalyhttps://ift.tt/2Ac9tw7
Annexin A1-suppressed autophagy promotes nasopharyngeal carcinoma cell invasion and metastasis by PI3K/AKT signaling activation
Annexin A1-suppressed autophagy promotes nasopharyngeal carcinoma cell invasion and metastasis by PI3K/AKT signaling activation
Annexin A1-suppressed autophagy promotes nasopharyngeal carcinoma cell invasion and metastasis by PI3K/AKT signaling activation, Published online: 20 November 2018; doi:10.1038/s41419-018-1204-7
Annexin A1-suppressed autophagy promotes nasopharyngeal carcinoma cell invasion and metastasis by PI3K/AKT signaling activationhttps://ift.tt/2TuTK4f
Oncolytic Activity of a Novel Influenza A Virus Carrying Granulocyte-Macrophage Colony-Stimulating Factor in Hepatocellular Carcinoma
Human Gene Therapy, Ahead of Print.
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Immunoengineering of the Vascular Endothelium to Silence MHC Expression During Normothermic Ex Vivo Lung Perfusion
Human Gene Therapy, Ahead of Print.
https://ift.tt/2OUmkIE
Application of CRISPR-Cas9 for Long Noncoding RNA Genes in Cancer Research
Human Gene Therapy, Ahead of Print.
https://ift.tt/2zks9ud
Synergistic Antitumor Effect on Bladder Cancer by Rational Combination of Programmed Cell Death 1 Blockade and CRISPR-Cas9-Mediated Long Non-Coding RNA Urothelial Carcinoma Associated 1 Knockout
Human Gene Therapy, Ahead of Print.
https://ift.tt/2OXk1oi
Gene expression profiling in melanoma: past results and future potential
Future Oncology, Ahead of Print.
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Enteral nutrition in esophageal cancer patients treated with radiotherapy: a Chinese expert consensus 2018
Future Oncology, Ahead of Print.
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Wolbachia Infection Associated with Increased Recombination in Drosophila
Wolbachia is a maternally-transmitted endosymbiotic bacteria that infects a large diversity of arthropod and nematode hosts. Some strains of Wolbachia are parasitic, manipulating host reproduction to benefit themselves, while other strains of Wolbachia exhibit obligate or facultative mutualisms with their host. The effects of Wolbachia on its host are many, though primarily relate to host immune and reproductive function. Here we test the hypothesis that Wolbachia infection alters the frequency of homologous recombination during meiosis. We use D. melanogaster as a model system, and survey recombination in eight wild-derived Wolbachia-infected (strain wMel) and Wolbachia-uninfected strains, controlling for genotype. We measure recombination in two intervals of the genome. Our results indicate that Wolbachia infection is associated with increased recombination in one genomic interval and not the other. The effect of Wolbachia infection on recombination is thus heterogenous across the genome. Our data also indicate a reproductive benefit of Wolbachia infection; infected females show higher fecundity than their uninfected genotypic controls. Given the prevalence of Wolbachia infection in natural populations, our findings suggest that Wolbachia infection is likely to contribute to recombination rate and fecundity variation among individuals in nature.
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Genetic Basis of Variation in Heat and Ethanol Tolerance in Saccharomyces cerevisiae
Saccharomyces cerevisiae has the capability of fermenting sugar to produce concentrations of ethanol that are toxic to most organisms. Other Saccharomyces species also have a strong fermentative capacity, but some are specialized to low temperatures, whereas S. cerevisiae is the most thermotolerant. Although S. cerevisiae has been extensively used to study the genetic basis of ethanol tolerance, much less is known about temperature dependent ethanol tolerance. In this study, we examined the genetic basis of ethanol tolerance at high temperature among strains of S. cerevisiae. We identified two amino acid polymorphisms in SEC24 that cause strong sensitivity to ethanol at high temperature and more limited sensitivity to temperature in the absence of ethanol. We also identified a single amino acid polymorphism in PSD1 that causes sensitivity to high temperature in a strain dependent fashion. The genes we identified provide further insight into genetic variation in ethanol and temperature tolerance and the interdependent nature of these two traits in S. cerevisiae.
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Using Maize Chromosome Segment Substitution Line Populations for the Identification of Loci Associated with Multiple Disease Resistance
Southern Leaf Blight (SLB), Northern Leaf Blight (NLB), and Gray Leaf Spot (GLS) caused by Cochliobolus heterostrophus, Setosphaeria turcica, and Cercospora zeae-maydis respectively, are among the most important diseases of corn worldwide. Previously, moderately high and significantly positive genetic correlations between resistance levels to each of these diseases were identified in a panel of 253 diverse maize inbred lines. The goal of this study was to identify loci underlying disease resistance in some of the most multiple disease resistant (MDR) lines by the creation of chromosome segment substitution line (CSSL) populations in multiple disease susceptible (MDS) backgrounds. Four MDR lines (NC304, NC344, Ki3, NC262) were used as donor parents and two MDS lines (Oh7B, H100) were used as recurrent parents to produce eight BC3F4:5 CSSL populations comprising 1,611 lines in total. Each population was genotyped and assessed for each disease in replicated trials in two environments. Moderate to high heritabilities on an entry mean basis were observed (0.32 to 0.83). Several lines in each population were significantly more resistant than the MDS parental lines for each disease. Multiple quantitative trait loci (QTL) for disease resistance were detected for each disease in most of the populations. Seventeen QTLs were associated with variation in resistance to more than one disease (SLB/NLB: 2; SLB/GLS: 7; NLB/GLS: 2 and 6 to all three diseases). For most populations and most disease combinations, significant correlations were observed between disease scores and also between marker effects for each disease. The number of lines that were resistant to more than one disease was significantly higher than would be expected by chance. Using the results from individual QTL analyses, a composite statistic based on Mahalanobis distance (Md) was used to identify joint marker associations with multiple diseases. Across all populations and diseases, 246 markers had significant Md values. However further analysis revealed that most of these associations were due to strong QTL effects on a single disease. Together, these findings reinforce our previous conclusions that loci associated with resistance to different diseases are clustered in the genome more often than would be expected by chance. Nevertheless true MDR loci which have significant effects on more than one disease are still much rarer than loci with single disease effects.
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Towards Identifying Subnetworks from FBF Binding Landscapes in Caenorhabditis Spermatogenic or Oogenic Germlines
Metazoan PUF (Pumilio and FBF) RNA-binding proteins regulate various biological processes, but a common theme across phylogeny is stem cell regulation. In Caenorhabditis elegans, FBF (fem-3 Binding Factor) maintains germline stem cells regardless of which gamete is made, but FBF also functions in the process of spermatogenesis. We have begun to "disentangle" these biological roles by asking which FBF targets are gamete-independent, as expected for stem cells, and which are gamete-specific. Specifically, we compared FBF iCLIP binding profiles in adults making sperm to those making oocytes. Normally, XX adults make oocytes. To generate XX adults making sperm, we used a fem-3(gf) mutant requiring growth at 25°; for comparison, wild-type oogenic hermaphrodites were also raised at 25°. Our FBF iCLIP data revealed FBF binding sites in 1522 RNAs from oogenic adults and 1704 RNAs from spermatogenic adults. More than half of these FBF targets were independent of germline gender. We next clustered RNAs by FBF-RNA complex frequencies and found four distinct blocks. Block I RNAs were enriched in spermatogenic germlines, and included validated target fog-3, while Block II and III RNAs were common to both genders, and Block IV RNAs were enriched in oogenic germlines. Block II (510 RNAs) included almost all validated FBF targets and was enriched for cell cycle regulators. Block III (21 RNAs) was enriched for RNA-binding proteins, including previously validated FBF targets gld-1 and htp-1. We suggest that Block I RNAs belong to the FBF network for spermatogenesis, and that Blocks II and III are associated with stem cell functions.
https://ift.tt/2Qi8DbD
Connection between gut microbiome and brain development in preterm infants
Abstract
Dysbiosis of the gut microbiome in preterm infants predisposes the neonate to various major morbidities including neonatal necrotizing enterocolitis and sepsis in the neonatal intensive care unit, and adverse neurological outcomes later in life. There are parallel early developmental windows for the gut microbiota and the nervous system during prenatal to postnatal of life. Therefore, preterm infants represent a unique population in which optimization of initial colonization and microbiota development can affect brain development and enhance neurological outcomes. In this review, we will first discuss the factors affecting the assembly of neonatal gut microbiota and the contribution of dysbiosis in preterm infants to neuroinflammation and neurodevelopmental disorders. We then will discuss the emerging pathways connecting the gut microbiome and brain development. Further we will discuss the significance of current models for alteration of the gut microbiome (including humanized gnotobiotic models and exposure to antibiotics) to brain development and functions. Understanding the role of early optimization of the microbiome in brain development is of paramount importance for developing microbiome‐targeted therapies and protecting infants from prematurity‐related neurodevelopmental diseases.
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Paternal methyl donor deficient diets during development affect male offspring behavior and memory‐related gene expression in mice
Abstract
It has become increasingly evident that the methylation of DNA, known as an epigenetic marker, affects behavior in animals. In our previous study, a methyl‐donors (folate, methionine, and choline)‐deficient (FMCD) diet during the juvenile period could be shown to affect anxiety‐like behavior and fear memory, accompanied by alteration in some gene expression and their methylations in the hippocampus. One question is whether the fear memory of a parent affects the fear responses of offspring. To explore this question in the present study, C57BL/6 J male (F0) mice were given a FMCD diet from 3 to 12 weeks of age. After confirming the effect of the FMCD diet on the behavior and gene expression of F0 mice, their male offspring (F1‐FMCD mice) were examined using the same behavioral batteries and genetic analysis. F0 diet‐based differences in F1 behavior were observed, accompanied by the differences in the expression of memory‐related genes (Camk2α and PP1) and promoter methylation of the PP1 gene in the hippocampus. Our results add evidence that behavior and gene expression of the F1 generation could be altered due to differences in the father's intake of methyl‐donor nutrients.
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Hyperpolarized MRI visualizes Warburg effects and predicts treatment response to mTOR inhibitors in patient-derived ccRCC xenograft models
The ever-changing tumor-microenvironment constantly challenges individual cancer cells to balance supply and demand, presenting tumor vulnerabilities and therapeutic opportunities. Everolimus and temsirolimus are inhibitors of mTOR (mTORi) approved for treating metastatic renal cell carcinoma (mRCC). However, treatment outcome varies greatly among patients. Accordingly, administration of mTORi in mRCC is diminishing, which could potentially result in missing timely delivery of effective treatment for select patients. Here we implemented a clinically applicable, integrated platform encompassing a single dose of [1-13C] pyruvate to visualize the in vivo effect of mTORi on the conversion of pyruvate to lactate using hyperpolarized MRI. A striking difference that predicts treatment benefit was demonstrated using two preclinical models derived from clear cell RCC (ccRCC) patients who exhibited primary resistance to VEGFRi and quickly succumbed to their diseases within 6 months after the diagnosis of metastasis without receiving mTORi. Our findings suggest that hyperpolarized MRI could be further developed to personalize kidney cancer treatment.
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Histone demethylase KDM4B promotes DNA damage by activating long interspersed nuclear element-1
The histone demethylase KDM4B is frequently overexpressed in various cancer types, and previous studies have indicated that the primary oncogenic function of KDM4B is its ability to demethylate H3K9me3 in different tumors, resulting in altered gene expression and genome instability. A genome-wide analysis to evaluate the effect of KDM4B on the global or local H3K9me3 level has not been performed. In this study, we assess whole-genome H3K9me3 distribution in cancer cells and find that H3K9me3 is largely enriched in long interspersed nuclear element-1 (LINE-1). A significant proportion of KDM4B-dependent H3K9me3 was located in evolutionarily young LINE-1 elements, which likely retain retrotransposition activity. Ectopic expression of KDM4B promoted LINE-1 expression, while depletion of KDM4B reduced it. Furthermore, KDM4B overexpression enhanced LINE-1 retrotransposition efficacy, copy number, and associated DNA damage, presumably via the histone demethylase activity of KDM4B. Breast cancer cell lines expressing high levels of KDM4B also exhibited increased LINE-1 expression and copy number compared with other cell lines. Pharmacological inhibition of KDM4B significantly reduced LINE-1 expression and DNA damage in breast cancer cells with excessive KDM4B. Our study not only identifies KDM4B as a novel regulator of LINE-1, but it also suggests an unexpected oncogenic role for KDM4B overexpression in tumorigenesis, providing clues for the development of new cancer prevention strategies and therapies.
https://ift.tt/2QgkIy0
SACS variants are a relevant cause of autosomal recessive hereditary motor and sensory neuropathy
Abstract
Mutations in the SACS gene have been initially reported in a rare autosomal recessive cerebellar ataxia syndrome featuring prominent cerebellar atrophy, spasticity and peripheral neuropathy as well as retinal abnormalities in some cases (autosomal recessive spastic ataxia of Charlevoix–Saguenay, ARSACS). In the past few years, the phenotypic spectrum has broadened, mainly owing to the availability and application of high-throughput genetic testing methods. We identified nine patients (three sib pairs, three singleton cases) with isolated, non-syndromic hereditary motor and sensory neuropathy (HMSN) who carried pathogenic SACS mutations, either in the homozygous or compound heterozygous state. None of the patients displayed spasticity or pyramidal signs. Ataxia, which was noted in only three patients, was consistent with a sensory ataxia. Nerve conduction and nerve biopsy studies showed mixed demyelinating and axonal neuropathy. Brain MRI scans were either normal or revealed isolated upper vermis atrophy of the cerebellum. Our findings confirm the broad clinical spectrum associated with SACS mutations, including pure polyneuropathy without characteristic clinical and brain imaging manifestations of ARSACS.
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Urinary tract infection caused by a small colony variant form of capnophilic Escherichia coli leading to misidentification and non-reactions in antimicrobial susceptibility tests
Small colony and capnophilic variant cases have been separately reported, but there has been no reports of their simultaneous presence in one isolate. We report a case of Escherichia coli with coexpressed small c...
https://ift.tt/2ziVpBk
USPSTF Suggests Universal HIV Screening, PrEP for High-Risk Patients
TUESDAY, Nov. 20, 2018 -- The U.S. Preventive Services Task Force (USPSTF) recommends HIV screening for individuals aged 15 to 65 years, including all pregnant women, and pre-exposure prophylaxis (PrEP) should be offered to those at high risk of...
https://ift.tt/2FzV4zY
Vaccine-Exempt Students Behind N.C. Chickenpox Outbreak
TUESDAY, Nov. 20, 2018 -- North Carolina's largest chickenpox outbreak in decades is centered in a primary school with a large number of vaccine-exempt students, according to health officials. Thirty-six students at Asheville Waldorf School were...
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FDA: Another E. coli Outbreak Linked to Romaine Lettuce
TUESDAY, Nov. 20, 2018 -- The U.S. Food and Drug Administration and U.S. Centers for Disease Control and Prevention along with health officials from various states are asking American consumers to avoid romaine lettuce due to an outbreak of...
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CDC Announces Acute Flaccid Myelitis Task Force
TUESDAY, Nov. 20, 2018 -- A task force to investigate a rising number of cases of a rare polio-like disease among children in the United States has been created by the U.S. Centers for Disease Control and Prevention. The task force on acute flaccid...
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American College of Allergy, Asthma & Immunology, Nov. 15-19
The 2018 Annual Meeting of the American College of Allergy, Asthma & Immunology The annual meeting of the American College of Allergy, Asthma & Immunology was held from Nov. 15 to 19 in Seattle and attracted approximately 3,500 participants...
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Heterogeneous Presentation of Neonatal Hemochromatosis in Dichorionic Twins
AJP Rep 2018; 08: e332-e334
DOI: 10.1055/s-0038-1675335
Acute liver failure (ALF) in neonates is rare. Although the incidence is reported to be rare, neonatal hemochromatosis (NH) has to be considered as one of the causes of neonatal ALF. We present a pair of dichorionic twin who had a diverse clinical presentation of NH. One twin passed away despite medical treatment with exchange transfusion and intravenous immunoglobulin (IVIg), whereas the other twin suffered from only mildly deranged liver function, which normalized spontaneously. Early identification of liver failure and clinical awareness of this disease entity are essential to its timely diagnosis and treatment. Antenatal management using IVIg prevents the recurrence of NH in subsequent pregnancies.
[...]
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Article in Thieme eJournals:
Table of contents | Abstract | open access Full text
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Points that need attention in auditory N100 gating research in schizophrenia
With great interest, we read the article by Dr. Rosburg, reporting a meta-analysis of the auditory N100 gating studies in schizophrenia patients (Rosburg, 2018). Nevertheless, regarding the conclusion that "Findings are difficult to reconcile with the concept of a N100 gating deficit", we would like to highlight three points, which complement his comments on potential moderators and study limitations.
https://ift.tt/2Qd0qVQ
Proteinase K treatment improves RNA recovery from thyroid cells fixed with liquid-based cytology solution
Fine-needle aspiration biopsy (FNAB), an important diagnostic tool given its simplicity, safety, and cost-effectiveness, is fast becoming a popular procedure in the diagnosis of thyroid diseases. Generally, ce...
https://ift.tt/2Dxc4nT
Job satisfaction and related factors among Iranian intensive care unit nurses
The aim of this study is to determine the levels of job satisfaction and to collect information about the factors affecting job satisfaction of Iranian ICU hospital nurses.
https://ift.tt/2Q7eZKI
Level of job satisfaction and associated factors among health care professionals working at University of Gondar Referral Hospital, Northwest Ethiopia: a cross-sectional study
The main aim of this study was to assess the level of job satisfaction and associated factors among healthcare professionals working at University of Gondar Referral Hospital, Northwest Ethiopia. An institutio...
https://ift.tt/2Dz679Y
Gilenya (fingolimod): Drug Safety Communication - Severe Worsening of Multiple Sclerosis After Stopping the Medicine
Audience: Patient, Health Professional, Neurology, Pharmacy ISSUE: FDA is warning that when the multiple sclerosis (MS) medicine Gilenya (fingolimod) is stopped, the disease can become much worse than before the medicine was started or while it was...
https://ift.tt/2qYENuq
Gilenya (fingolimod): Drug Safety Communication - Severe Worsening of Multiple Sclerosis After Stopping the Medicine
Audience: Patient, Health Professional, Neurology, Pharmacy ISSUE: FDA is warning that when the multiple sclerosis (MS) medicine Gilenya (fingolimod) is stopped, the disease can become much worse than before the medicine was started or while it was...
https://ift.tt/2qYENuq
Cardiac Substructure Segmentation and Dosimetry Using a Novel hybrid MR/CT Cardiac Atlas
Radiation dose to the heart and cardiac substructures has been linked to cardiotoxicities. As cardiac substructures are poorly visualized on treatment planning computed tomography (CT), we employed the superior soft tissue contrast of magnetic resonance (MR) imaging to optimize a hybrid MR/CT atlas for substructure dose assessment using CT.
https://ift.tt/2QcRksa
Structural and mechanistic aspects of S-S bonds in the thioredoxin-like family of proteins
Journal Name: Biological Chemistry
Issue: Ahead of print
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Highlight Issue: Plasma Medicine
Journal Name: Biological Chemistry
Issue: Ahead of print
https://ift.tt/2Tvwu6n
Subjective visual vertical in patients with benign positional paroxysmal vertigo
LETTER
Hippokratia 2017, 21(3):159
Sapountzi Z, Vital V, Psillas G
1st Otolaryngology Department, AHEPA University Hospital, Aristotle's University of Thessaloniki, Thessaloniki , Greece
https://ift.tt/2A8ecz8
Nasopharyngeal angiofibroma in an adult with Proteus syndrome. First reported case
CASE REPORT
Hippokratia 2017, 21(3):147-149
Delides A1, Panayiotides JG2, Kaberos A3, Giotakis I1
12nd Otolaryngology Department, "Attikon" University Hospital, 22nd Department of Pathology, "Attikon" University Hospital, School of Medicine, National & Kapodistrian University of Athens, 3Otolaryngology Department, "Jannio" Hospital of Peireaus, Athens, Greece
https://ift.tt/2TudXar
Daily dose of itraconazole 100 mg to treat allergic bronchopulmonary aspergillosis (ABPA) related eosinophilia: a case report
CASE REPORT
Hippokratia 2017, 21(3):144-146
Konstantinou AE1, Christaki E2, Pitsios C1
1Allergy Outpatient Clinic, 2 Department of Medicine, Medical School, University of Cyprus, Nicosia, Cyprus
https://ift.tt/2TvcRuY
Triage Performance in Emergency Medicine: A Systematic Review
Rapid growth in emergency department (ED) triage literature has been accompanied by diversity in study design, methodology, and outcome assessment. We aim to synthesize existing ED triage literature by using a framework that enables performance comparisons and benchmarking across triage systems, with respect to clinical outcomes and reliability.
https://ift.tt/2DP9IS5
Postdischarge Unplanned Care Events Among Commercially Insured Patients With an Observation Stay Versus Short Inpatient Admission
Observation stays are composing an increasing proportion of unscheduled hospitalizations in the United States, with unclear consequences for the quality of care. This study used a nationally representative data set of commercially insured patients hospitalized from the emergency department (ED) to compare 30-day postdischarge unplanned care events after an observation stay versus a short inpatient admission.
https://ift.tt/2S2XPva
Emergency Department Crowding Is Associated With Delayed Antibiotics for Sepsis
Barriers to early antibiotic administration for sepsis remain poorly understood. We investigated the association between emergency department (ED) crowding and door-to-antibiotic time in ED sepsis.
https://ift.tt/2DORccO
Can S100B Serum Biomarker Testing Reduce Head Computed Tomography Scanning in Children With Mild Traumatic Brain Injury?
The authors identified 1,623 studies; 973 were excluded after review of title and abstract, leaving 57 studies for full-text review, of which 49 were excluded. The 8 included studies comprised 601 children with mild traumatic brain injury who underwent serum S100B biomarker testing compared with head CT or clinical follow-up as the references standard. S100B levels for detecting traumatic intracranial lesions in children with mild traumatic brain injury had a pooled sensitivity of 100% (95% CI 98% to 100%) and negative predictive value of 100% (95% CI 99% to 100%), whereas the pooled specificity was 41% (95% CI 26% to 57%), with significant heterogeneity (I2>50%) that was driven primarily by one study.
https://ift.tt/2S5bOQS
Changes in Reimbursement to Emergency Physicians After Medicaid Expansion Under the Patient Protection and Affordable Care Act
We examine the effect of Medicaid expansion on reimbursement for emergency physicians' professional services.
https://ift.tt/2DQCp1c
Immunomodulatory Effect of Lentinan on Aberrant T Subsets and Cytokines Profile in Non-small Cell Lung Cancer Patients
Abstract
As a purified active component from traditional Chinese medicine, lentinan administration can be applied as beneficial chemo-immunotherapy for anti-tumor. In this study, the immunomodulatory effects of lentinan on aberrant T subsets and cytokines profile were evaluated for non-small cell lung cancer (NSCLC). Of all NSCLC patients treated with NP chemotherapeutic protocol (combination of vinorelbin and cisplatin), 73 cases were recruited in this retrospective cohort trial study, of which 38 cases received additional lentinan. The changes of aberrant T subsets and cytokines profile were compared between two groups (chemotherapy in combination with lentinan vs. conserved single chemotherapy) by flow cytometry and molecular biology. Higher subset ratio of CD3+CD8+ cytotoxic T cells was confirmed in the peripheral blood of NSCLC patients. Chemo-immunotherapy of lentinan resulted in a significant increase of CD3 + CD56+ NKT cells (15.7 ± 3.1%), compared with 8.6 ± 1.4% of NKT cells in single chemotherapy group, and up-regulated CD3+CD8+ and CD3+CD4+ subsets as well, but caused the decrease of CD4+CD25+ Tregs induction, accompanied by significant alleviation of IL-10 and TGF-β1, and elevation of IFN-γ, TNF-α, and IL-12 (P < 0.05). It could be confirmed that lentinan could not only enhance the cellular immunity and promote the beneficial of anti-tumor by associated immunotherapy, but also had the ability to inhibit the expansion of immune suppressive Tregs in the NSCLC patients, in whom there was a raised Tregs induction compared to health control. Lentinan-based chemo-immunotherapy is a promising strategy for anti-tumor via enhancing the proliferation of cytotoxic T cells, followed by the elevation of inflammatory chemokines/cytokines. Meanwhile, the percentage of CD4+ CD25+ Tregs is down-regulated, leading to a shift in the inflammatory status from Th2 to Th1 in NSCLC patients treated with lentinan.
https://ift.tt/2PGBhDB
Molecular characterization of sessile serrated adenoma/polyps with dysplasia/carcinoma based on immunohistochemistry, next-generation sequencing, and microsatellite instability testing: a case series study
Colorectal sessile serrated adenoma/polyps (SSA/Ps) are considered early precursor lesions in the serrated neoplasia pathway. Recent studies have shown associations of SSA/Ps with lost MLH1 expression, a CpG i...
https://ift.tt/2R05LNF
Expression of DENDRIN in several glomerular diseases and correlation to pathological parameters and renal failure - preliminary study
In glomerular injury dendrin translocates from the slit diaphragm to the podocyte nucleus, inducing apoptosis. We analyzed dendrin expression in IgA glomerulonephritis and Henoch Schönlein purpura (IgAN/HSP) v...
https://ift.tt/2PHjWKV
Massive Localized Lymphedema in an Unreported Location (Retroperitoneum)
Massive localized lymphedema (MLL) is a non-neoplastic benign soft tissue lesion that may be confused with sarcomas or other neoplastic proliferations both clinically and morphologically. Most occur in morbidl...
https://ift.tt/2QWcgRm
New remote centre of motion mechanism for robot-assisted minimally invasive surgery
Robot-assisted minimally invasive surgery (RMIS) is promising for improving surgical accuracy and dexterity. As the end effector of the robotic arm, the remote centre of motion mechanism is one of the requisit...
https://ift.tt/2TvsNxx
Salient networks: a novel application to study Alzheimer disease
Extracting fundamental information from data, thus underlining hidden structures or removing noisy information, is one of the most important aims in different scientific fields especially in biological and med...
https://ift.tt/2A7Tqjc
Machine learning in critical care: state-of-the-art and a sepsis case study
Like other scientific fields, such as cosmology, high-energy physics, or even the life sciences, medicine and healthcare face the challenge of an extremely quick transformation into data-driven sciences. This ...
https://ift.tt/2TvYzdv
Modeling hind-limb kinematics using a bio-inspired algorithm with a local search
Laboratory rats play a critical role in research because they provide a biological model that can be used for evaluating the affectation of diseases and injuries, and for the evaluation of the effectiveness of...
https://ift.tt/2A7Thwa
Comprehensive study of instable regions in Pseudomonas aeruginosa and Mycobacterium tuberculosis
Pseudomonas aeruginosa is a common bacterium which is recognized for its association with hospital-acquired infections and its advanced antibiotic resistance mechanisms. Tuberculosis, one of the major causes of m...
https://ift.tt/2TsDVeo
Evaluation of the effect of Lactobacillus reuteri V3401 on biomarkers of inflammation, cardiovascular risk and liver steatosis in obese adults with metabolic syndrome: a randomized clinical trial (PROSIR)
Obesity is characterized by increased fat mass and is associated with the development of insulin resistance syndrome (IRS), usually known as metabolic syndrome. The alteration of the intestinal microbiota comp...
https://ift.tt/2zmLE5h
Determination of the volatile and polyphenol constituents and the antimicrobial, antioxidant, and tyrosinase inhibitory activities of the bioactive compounds from the by-product of Rosa rugosa Thunb. var. plena Regal tea
The phytochemical constituents and biological activities of Rosa rugosa Thunb. var. plena Regal flower cell sap (RFCS) were investigated.
https://ift.tt/2OZ6CfK
Novel Object Recognition and Object Location Behavioral Testing in Mice on a Budget
Here we provide a protocol which includes comprehensive instructions for the economical establishment of murine object location and novel object recognition behavioral testing, including the design, cost, and construction of required equipment as well as execution of behavioral testing, data collection, and analysis.
https://ift.tt/2FHPhIS
Evaluation of Senegal’s prevention of mother to child transmission of HIV (PMTCT) program data for HIV surveillance
With the expansion of Prevention of Mother to Child Transmission (PMTCT) services in Senegal, there is growing interest in using PMTCT program data in lieu of conducting unlinked anonymous testing (UAT)-based ...
https://ift.tt/2PCOeOG
Correlation between antifungal consumption and the distribution of Candida species in different hospital departments of a Lebanese medical Centre
In recent years, there has been a significant increase in the incidence of fungal infections attributed to Candida species worldwide, with a major shift toward non-albicans Candida (NAC). In this study, we have d...
https://ift.tt/2QTGPam
Catheter-associated bacterial flora in patients with benign prostatic hyperplasia: shift in antimicrobial susceptibility pattern
Men with urinary retention secondary to benign prostatic hyperplasia (BPH) are prone to genitourinary infections. Physicians should be aware of the current antimicrobial susceptibility pattern in this populati...
https://ift.tt/2PGtk1m
In Vitro Assay for Studying the Aggregation of Tau Protein and Drug Screening
https://ift.tt/2ziKLuy
Label-Free Imaging of Single Proteins Secreted from Living Cells via iSCAT Microscopy
https://ift.tt/2ORDWoR
Biocytin Recovery and 3D Reconstructions of Filled Hippocampal CA2 Interneurons
The protocol outlined here describes the immunofluorescence analysis, biocytin recovery and high-quality reconstructions of hippocampal CA2 interneurons following the intracellular electrophysiological recordings in vitro, allowing neuronal characterization and ultimately fine neuronal anatomy to be studied.
https://ift.tt/2zfaBzy
Peliosis hepatis associated with follicular lymphoma with a rise in vascular endothelial growth factor and anaemia of inflammation
Emilia Pardal de la Mano, Guillermo Martín-Sánchez, Rosa López López, M Angeles Fernández Galán, Sergio Trinidad Ríos, M José Morán Jiménez, J María García Ruiz de Morales, M Antonia Crespo Santos and Guillermo Martín Núñez
https://ift.tt/2DA8QzP
Corrigendum to “Mast cells improve functional recovery of transected peripheral nerve: A novel preliminary study” [Injury 48/7 (2017) 1480-1485]
Publication date: Available online 20 November 2018
Source: Injury
Author(s): Behrooz Ilkhanizadeh, Leila Zarei, Negin Farhad, Mehran Bahrami-Bukani, Rahim Mohammadi
https://ift.tt/2zismxM
Different tool training induces specific effects on body metric representation
Abstract
Morphology and functional aspects of the tool have been proposed to be critical factors modulating tool use-induced plasticity. However, how these aspects contribute to changing body representation has been underinvestigated. In the arm bisection task, participants have to estimate the length of their own arm by indicating its midpoint, a paradigm used to investigate the representation of the metric properties of the body. We employed this paradigm to investigate the impact of different actions onto tool embodiment. Our findings suggest that a training requiring actions mostly with proximal (shoulder) or distal (wrist) parts induces a different shift in the perceived arm midpoint. This effect is independent of, but enhanced by, the use of the tool during the training and in part influenced by specific demands of the task. These results suggest that specific motor patterns required by the training can induce different changes of body representation, calling for rethinking the concept of tool embodiment, which would be characterized not simply by the morphology of the tools, but also by the actions required for their specific use.
https://ift.tt/2FAY92H
Increased Risk for Oral Cancer With Exposure to High PM2.5
TUESDAY, Nov. 20, 2018 -- Taiwanese men exposed to high concentrations of fine particulate matter 2.5 (PM2.5) have an increased risk for oral cancer, according to a study recently published in the Journal of Investigative Medicine. Yu-Hua Chu, from...
https://ift.tt/2qWSOZB
NPs and PAs Can Effectively Manage Diabetes in Primary Care
TUESDAY, Nov. 20, 2018 -- Diabetes outcomes do not differ for patients treated with a primary care provider who is either a physician, nurse practitioner (NP), or physician assistant (PA), according to a study published online Nov. 20 in the Annals...
https://ift.tt/2FvjkTF
Dementia Tied to Mortality in Older Adults With Down Syndrome
TUESDAY, Nov. 20, 2018 -- Dementia is associated with mortality in most older adults with Down syndrome, according to a study published online Nov. 19 in JAMA Neurology. Rosalyn Hithersay, from King's College London, and colleagues examined the...
https://ift.tt/2qVnBWn
Prenatal Nitric Oxide Exposure Linked to Higher Risk for Autism
TUESDAY, Nov. 20, 2018 -- Prenatal exposure to nitric oxide (NO) is associated with an increased risk for autism spectrum disorder (ASD), according to a study published online Nov. 19 in JAMA Pediatrics. Lief Pagalan, from Simon Fraser University in...
https://ift.tt/2Fz2mUE
RSNA: Ultrasound of Shoulder Muscle May Help Diagnose T2DM
TUESDAY, Nov. 20, 2018 -- The ultrasound appearance of an echogenic deltoid muscle may predict diabetes and prediabetes, according to a study scheduled to be presented at the annual meeting of the Radiological Society of North America, held from...
https://ift.tt/2qVnABN
Performance of AI Dx Tools May Suffer Across Health Systems
TUESDAY, Nov. 20, 2018 -- Artificial intelligence tools trained to detect pneumonia on chest X-rays have decreased performance when tested on data from outside health systems, according to a study published online Nov. 6 in PLOS Medicine. John R....
https://ift.tt/2Fx2uUx
Major Bleeding Up With Frailty in Acute MI Patients
TUESDAY, Nov. 20, 2018 -- Frail acute myocardial infarction (AMI) patients are less likely to undergo cardiac catheterization and have an increased risk for bleeding, according to a study published in the Nov. 26 issue of JACC: Cardiovascular...
https://ift.tt/2qXau79
Immunotherapy Side Effects May Be More Common Than Thought
TUESDAY, Nov. 20, 2018 -- Adverse events for immune checkpoint inhibitors used to treat non-small cell lung cancer (NSCLC) may be more common in real-world settings than reported in the clinical trials that led to U.S. Food and Drug Administration...
https://ift.tt/2FAWPwL
Better Work Environment Tied to Better Patient Safety
TUESDAY, Nov. 20, 2018 -- The results of a recent survey of thousands of nurses and patients show that hospital patient safety remains a serious concern, according to a study published in the November issue of Health Affairs. Linda H. Aiken, R.N.,...
https://ift.tt/2qW7hEQ
Pain Management Telementoring May Cut Opioid Prescribing
TUESDAY, Nov. 20, 2018 -- Military patients whose primary care clinicians participated in a telementoring program, including education on pain management best practices, have larger declines in opioid-related prescriptions than patients whose...
https://ift.tt/2Fx2sfn
Identification of Homologous Recombination Events in Mouse Embryonic Stem Cells Using Southern Blotting and Polymerase Chain Reaction
Here, we present a detailed protocol for identifying homologous recombination events that occurred in mouse embryonic stem cells using Southern blotting and/or PCR. This method is exemplified by the generation of nonmuscle myosin II genetic replacement mouse models using traditional embryonic stem cell-based homologous recombination-mediated targeting technology.
https://ift.tt/2S7Bfl7
Synthesis of 68Ga Core-doped Iron Oxide Nanoparticles for Dual Positron Emission Tomography /(T1)Magnetic Resonance Imaging
Here, we present a protocol to obtain 68Ga core-doped iron oxide nanoparticles via fast microwave-driven synthesis. The methodology renders PET/(T1)MRI nanoparticles with radiolabeling efficiencies higher than 90% and radiochemical purity of 99% in a 20-min synthesis.
https://ift.tt/2DPPyY6
Insights into the regeneration of skin from Acomys, the spiny mouse
Abstract
Members of the Acomys genus, known as spiny mice, are unique among mammals in being perfectly capable of regenerating large areas of skin that have been removed. During this regenerative process hairs, sebaceous glands, erector pili muscles, adipocytes and the panniculus carnosus all regenerate and the dermis does not scar. We review here the processes that the epidermis and the individual components of the dermis undergo in the regeneration process of the spiny mouse, the molecules that have been identified as potentially being important in regeneration and relate this to what has been proposed as playing a role in studies from the lab mouse, Mus musculus. Differences in the immune systems of spiny mice and lab mice are also highlighted as this is suggested to play a part not only in the perfect wound healing that embryos display but also in regeneration in lower vertebrates.
This article is protected by copyright. All rights reserved.
https://ift.tt/2R0s4T5
How chemotherapy and radiotherapy damage the tissue: Comparative biology lessons from feather and hair models
Abstract
Chemotherapy and radiotherapy are common modalities for cancer treatment. While targeting rapidly growing cancer cells, they also damage normal tissues and cause adverse effects. From the initial insult such as DNA double strand break, production of reactive oxygen species (ROS), and a general stress response, there are complex regulatory mechanisms that control the actual tissue damage process. Besides apoptosis, a range of outcomes for the damaged cells are possible including cell cycle arrest, senescence, mitotic catastrophe, and inflammatory responses and fibrosis at the tissue level. Feather and hair are among the most actively proliferating (mini‐)organs, and are highly susceptible to both chemotherapy and radiotherapy damage, thus provide excellent, experimentally tractable model systems for dissecting how normal tissues respond to such injuries. Taking a comparative biology approach to investigate this has turned out to be particularly productive. Started in chicken feather and then extended to murine hair follicles, it was revealed that in addition to p53‐mediated apoptosis, several other previously overlooked mechanisms are involved. Specifically, Shh, Wnt, mTOR, cytokine signaling, and ROS‐mediated degradation of adherens junctions have been implicated in the damage and/or reparative regeneration process. Moreover, we show here that inflammatory responses, which can be prominent upon histological examination of chemo‐ or radiotherapy‐damaged hair follicle, may not be essential for the hair loss phenotype. These studies point to fundamental, evolutionarily conserved mechanisms in controlling tissue responses in vivo, and suggest novel strategies for the prevention and management of adverse effects that arise from chemo‐ or radiotherapy.
This article is protected by copyright. All rights reserved.
https://ift.tt/2PI3da0
Isavuconazole: Case Report and Pharmacokinetic Considerations
Invasive fungal disease (IFD) is one of the major causes of morbidity and mortality in immunocompromised patients. Voriconazole (VCZ) and posaconazole (PCZ) remain the most widely used antifungals for the prophylaxis and treatment of IFD. However, VCZ and PCZ are liable for drug-drug interactions and show a pharmacokinetic variability that requires therapeutic drug monitoring (TDM). Isavuconazole (IVZ) is a newest generation triazole antifungal approved for the treatment of invasive aspergillosis (IA) in adult patients and for the treatment of invasive mucormycosis in adult patients for whom treatment with amphotericin B is inappropriate. In clinical trials, IVZ showed linear pharmacokinetics and little or no evidence for interactions with other drugs. There is only modest evidence on IVZ pharmacokinetics and TDM in real-life settings. Here, we report on IVZ pharmacokinetics in a young adult with Ph chromosome-negative acute lymphoblastic leukemia (ALL) who developed a "probable" IA during induction chemotherapy. The patient was initially treated with VCZ, but she developed a severe hepatic toxicity that was associated to the high plasma levels of VCZ. Therefore, VCZ was discontinued and the patient was switched to IVZ. After a loading dose of VCZ, the patient remained on IVZ for 5 months while also receiving standard maintenance chemotherapy for ALL. At day 65 after the start of IVZ, the patient experienced a significant hepatic toxicity; however, no change in IVZ plasma concentrations was observed in the face of a concomitant administration of many other drugs (cancer drugs, antiemetics, other anti-infectives). Hepatic toxicity resolved after discontinuing maintenance chemotherapy but not IVZ. These results show that (i) IVZ plasma concentrations remained stable throughout and were not affected by concomitant ALL therapy, and (ii) there was no relation between IVZ plasma concentration and hepatic toxicity. Thus, in clinical practice IVZ may not require TDM.
Chemotherapy 2018;63:253–256
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Generating Homo- and Heterografts Between Watermelon and Bottle Gourd for the Study of Cold-responsive MicroRNAs
https://ift.tt/2OV8Igz
Evidence-based Reviews in Surgery: Early Cholecystectomy for Cholecystitis
Question: What are the clinical outcomes of early versus delayed laparoscopic cholecystectomy (LC) in acute cholecystitis with more than 72 hours of symptoms? Design: A randomized controlled trial. Setting: Single center at the University Hospital of Lausanne, Switzerland. Patients: Eighty-six patients were enrolled in the study that had symptoms of acute cholecystitis lasting more than 72 hours before admission. Intervention: Patients were randomly assigned to early LC or delayed LC. Main Outcome: Primary outcome was overall morbidity following initial diagnosis. Secondary outcomes included total length of stay, duration of antibiotic used, cost, and surgical outcome. Results: Overall morbidity was lower in early laparoscopic cholecystectomy (ELC) [6 (14%) vs 17 (39%) patients, P = 0.015]. Median total length of stay (4 vs 7 days, P
https://ift.tt/2Ffjv5H
https://ift.tt/2Ffjv5H
LncRNA MIR31HG targets HIF1A and P21 to facilitate head and neck cancer cell proliferation and tumorigenesis by promoting cell-cycle progression
Abstract
LncRNAs are involved in the initiation and progression of cancer. However, the molecular mechanism and diverse clinical prognosis of MIR31HG in head and neck squamous cell carcinoma (HNSCC) are still unclear. Our previous microarray analysis showed that lncRNA MIR31HG interacted with HIF1A may play an oncogenic role in laryngeal squamous cell cancer (LSCC). To determine whether lncRNA MIR31HG served as a poor prognosis factor and targeted HIF1A to facilitate cell proliferation and tumorigenesis in human HNSCC, we found MIR31HG and HIF1A were overexpressed in LSCC, MIR31HG overexpression or co-expression of HIF1A-positive and p21-negative could serve as a poor prognostic factor for LSCC patients. We further confirmed that MIR31HG promoted cell proliferation, cell cycle progression, and inhibited cell apoptosis in vitro and in vivo. The ingenuity pathway analysis and Western blot indicated that MIR31HG regulated cell cycle progression via HIF1A and p21 in HNSCC. The current results provide evidences for the role of MIR31HG in promoting HNSCC progression and identify MIR31HG as a prognostic biomarker and putative therapeutic target in HNSCC.
https://ift.tt/2FHiGT8
Cancers, Vol. 10, Pages 459: Mutational Evolution in Relapsed Diffuse Large B-Cell Lymphoma
Cancers, Vol. 10, Pages 459: Mutational Evolution in Relapsed Diffuse Large B-Cell Lymphoma
Cancers doi: 10.3390/cancers10110459
Authors: Marcel Nijland Annika Seitz Martijn Terpstra Gustaaf W. van Imhoff Philip M Kluin Tom van Meerten Çiğdem Atayar Léon C. van Kempen Arjan Diepstra Klaas Kok Anke van den Berg
Current genomic models in diffuse large B-cell lymphoma (DLBCL) are based on single tumor biopsies, which might underestimate heterogeneity. Data on mutational evolution largely remains unknown. An exploratory study using whole exome sequencing on paired (primary and relapse) formalin fixed paraffin embedded DLBCL biopsies (n = 14) of 6 patients was performed to globally assess the mutational evolution and to identify gene mutations specific for relapse samples from patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone. A minority of the mutations detected in the primary sample (median 7.6%, range 4.8–66.2%) could not be detected in the matching relapse sample. Relapsed DLBCL samples showed a mild increase of mutations (median 12.5%, range 9.4–87.6%) as compared to primary tumor biopsies. We identified 264 genes possibly related to therapy resistance, including tyrosine kinases (n = 18), (transmembrane) glycoproteins (n = 73), and genes involved in the JAK-STAT pathway (n = 7). Among the potentially resistance related genes were PIM1, SOCS1, and MYC, which have been reported to convey a risk for treatment failure. In conclusion, we show modest temporal heterogeneity between paired tumor samples with the acquisition of new mutations and identification of genes possibly related to therapy resistance. The mutational evolution could have implications for treatment decisions and development of novel targeted drugs.
https://ift.tt/2Bn3BlT
Metastatic or locally advanced breast cancer patients: towards an expert consensus on nab-paclitaxel treatment in HER2-negative tumours—the MACBETH project
Abstract
Introduction
Despite the large use of nab-paclitaxel as a treatment option in metastatic breast cancer (MBC) across different countries, no definitive data are available in particular clinical situations.
Areas covered
Efficacy, safety and schedule issues concerning available literature on nab-paclitaxel in advanced breast cancer and in specific subgroups of patients have been discussed and voted during an International Expert Meeting. Ten expert specialists in oncology, with extensive clinical experience on Nab-P and publications in the field of MBC have been identified. Six scientific areas of interest have been covered, generating 13 specific Statements for Nab-P, after literature review. For efficacy issues, a summary of research quality was performed adopting the GRADE algorithm for evidence scoring. The panel members were invited to express their opinion on the statements, in case of disagreement all the controversial opinions and the relative motivations have been made public.
Expert opinion
Consensus was reached in 30.8% of the Nab-P statements, mainly those regarding safety issues, whereas ones regarding efficacy and schedule still remain controversial areas, requiring further data originated by the literature.
https://ift.tt/2AaUClB
S electing the o ptimal positio n of CDK4/6 i nhibitors in hormone receptor-positive a dvanced breast cancer – the SONIA study: study protocol for a randomized controlled trial
Abstract
Background
Combining cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors with endocrine therapy is an effective strategy to improve progression-free survival in hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. There is a lack of comparative data to help clinicians decide if CDK4/6 inhibitors can best be added to first- or second-line endocrine therapy. Improvement in median progression-free survival in first-line studies is larger than in second-line studies, but CDK4/6 inhibitors have not consistently shown to improve overall survival or quality of life. They do come with added toxicity and costs, and many patients have lasting disease remission on endocrine therapy alone. No subgroup has been identified to select patients who are most likely to benefit from the addition of CDK4/6 inhibition in any line of treatment. Altogether, these factors make that the optimal strategy for using CDK4/6 inhibitors in clinical practice is unknown.
Methods
The SONIA study is an investigator-initiated, multicenter, randomized phase III study in patients with HR+/HER2-negative advanced breast cancer. Patients are randomly assigned to receive either strategy A (first-line treatment with a non-steroidal aromatase inhibitor combined with CDK4/6 inhibition, followed on progression by fulvestrant) or strategy B (first-line treatment with a non-steroidal aromatase inhibitor, followed on progression by fulvestrant combined with CDK4/6 inhibition). The primary objective is to test whether strategy A is more effective than strategy B. The primary endpoint is time from randomization to second objective progression (PFS2). Secondary endpoints include overall survival, safety, quality of life, and cost-effectiveness. Five-hundred seventy-four events yield 89% power to show that strategy A has statistically significant, clinically meaningful superior PFS2 (according to ESMO-MCBS) in a log-rank test at the two-sided 95% confidence level. Given an accrual period of 42 months and an additional 18 months follow-up, inclusion of 1050 evaluable patients is required.
Discussion
This study design represents daily clinical practice, and the results will aid clinicians in deciding when adding CDK4/6 inhibitors to endocrine therapy will benefit their patients most. Additional biomarker analyses may help to optimize patient selection.
Trial registration
http://clinicaltrials.gov: NCT03425838 (8 February 2018). EudraCT-number: 2017–002334-23 (29 September 2017).
https://ift.tt/2PC8Er4
The effects of postoperative radiotherapy on survival outcomes in patients under 65 with estrogen receptor positive tubular breast carcinoma
Abstract
Background
The value of postoperative radiotherapy in tubular breast carcinoma patients under 65 years is uncertain.
Methods
Data on patients with estrogen receptor positive T1N0M0 tubular breast carcinoma who were younger than 65 years and who received breast-conserving surgery between 2000 and 2013 were retrieved from the Surveillance, Epidemiology and End Results database. Demographic, clinicopathologic features, and receipt of postoperative radiotherapy were analyzed to investigate effects on survival.
Results
Data from 2442 patients were analyzed, of whom 2020 (82.7%) received postoperative radiotherapy and 422 (17.3%) did not. The number of patients treated with or without postoperative radiotherapy showed no differences during the study period (p = 0.184). Radiotherapy was more likely to be administered in patients with well differentiated tumors. Multivariate Cox analysis showed that postoperative radiotherapy delivery was significantly correlated with better breast cancer-specific survival (BCSS) (hazard ratio [HR] 0.297, 95% confidence interval [CI] 0.105–0.836, p = 0.022) and overall survival (OS) (HR 0.656, 95% CI 0.441–0.978, p = 0.038). Ten 10-year BCSS was 99.3% in patients who received postoperative radiotherapy and 98.1% in those who did not (p = 0.020), and 10-year OS was 93.4 and 91.0%, respectively (p = 0.029). Postoperative radiotherapy increased BCSS and OS in the subgroups of age < 50 years, non-Hispanic white, well differentiated tumors, and progesterone receptor positive tumors.
Conclusions
Postoperative radiotherapy after breast-conserving surgery improved survival outcomes in tubular breast carcinoma patients aged < 50 years. However, omitting postoperative radiotherapy may not decrease survival in patients aged ≥50 years.
https://ift.tt/2R3d2fG
CAR-T bridging to allo-HSCT as a treatment strategy for relapsed adult acute B-lymphoblastic leukemia: a case report
Abstract
Background
Adults with relapsed acute lymphoblastic leukemia (ALL) have a poor prognosis, especially in patients who relapsed within 6 months of complete remission 1 (CR1). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the treatment of choice. However, this can only be considered after complete remission 2 (CR2) is achieved. Therefore, bridging treatment is urgently needed.
Case presentation
In the present study, we report a relapsed adult B-cell ALL case that achieved CR2 after treatment with CD19-directed chimeric antigen receptor (CAR)-modified T cell (CAR-T) therapy. After subsequent allo-HSCT, the patient acquired 21 months of disease-free survival.
Conclusion
The present results confirm that both CAR-T and allo-HSCT are effective for treating refractory or relapsed B-ALL. However, a novel sequential treatment strategy with these two therapeutic methods may achieve longer disease-free survival time.
https://ift.tt/2zsc99J
CEA clearance pattern as a predictor of tumor response to neoadjuvant treatment in rectal cancer: a post-hoc analysis of FOWARC trial
Abstract
Background
The clinical factors that accurately predict the response to preoperative treatment in rectal cancer were yet unknown. The carcinoembryonic antigen (CEA) clearance pattern during neoadjuvant treatment has been developed and the predictive value explored in rectal cancer patients with elevated CEA levels (> 5 ng/mL).
Methods
The training cohort was derived from the FOWARC prospective phase III trial, and 71/483 eligible patients were included. The validation cohort consisted of 75/587 consecutive rectal cancer patients from Xiangya Hospital between 2014 and 2015. The kinetic changes in serum CEA were measured at different time points during the neoadjuvant treatment. An exponential trend line was drawn using the CEA values. The patients were categorized into two groups based on the R2 value of the trend line, which indicates the correlation coefficient between the exponential graph and measured CEA values: exponential decrease group (0.9 < R2 ≤ 1.0) and non-exponential decrease group (R2 ≤ 0.9).
Results
In multivariate analysis, the patients in the CEA exponential decrease group had significantly high adequate rate of downstaging (ypT0-2N0M0), and pathologic complete response (pCR) rates after neoadjuvant treatment in the training cohort. The predictive values of the CEA clearance pattern for tumor downstaging and pCR were further confirmed in an independent validation cohort.
Conclusions
The CEA clearance pattern was an independent predictor of tumor response to neoadjuvant treatment in patients with rectal cancer. It might serve as an adjunct in the assessment of complete clinical response and guide individualized treatment strategies.
Trial registration
NCT01211210.
https://ift.tt/2OTd7QY
Achieving Thoracic Oncology data collection in Europe: a precursor study in 35 Countries
Abstract
Background
A minority of European countries have participated in international comparisons with high level data on lung cancer. However, the nature and extent of data collection across the continent is simply unknown, and without accurate data collection it is not possible to compare practice and set benchmarks to which lung cancer services can aspire.
Methods
Using an established network of lung cancer specialists in 37 European countries, a survey was distributed in December 2014. The results relate to current practice in each country at the time, early 2015. The results were compiled and then verified with co-authors over the following months.
Results
Thirty-five completed surveys were received which describe a range of current practice for lung cancer data collection. Thirty countries have data collection at the national level, but this is not so in Albania, Bosnia-Herzegovina, Italy, Spain and Switzerland. Data collection varied from paper records with no survival analysis, to well-established electronic databases with links to census data and survival analyses.
Conclusion
Using a network of committed clinicians, we have gathered validated comparative data reporting an observed difference in data collection mechanisms across Europe. We have identified the need to develop a well-designed dataset, whilst acknowledging what is feasible within each country, and aspiring to collect high quality data for clinical research.
https://ift.tt/2zsc85F
Circulating nociceptin and CGRP in medication‐overuse headache
Abstract
Background
Previous studies found low serum levels of nociceptin in migraine patients but high serum levels of calcitonin gene‐related peptide (CGRP). CGRP can elicit migraine‐like headache. Medication‐Overuse Headache (MOH) often has migraine features and can mimic chronic migraine. We therefore hypothesized that as in migraine, serum levels of nociceptin would be lower and CGRP serum levels higher in MOH patients compared with those in healthy volunteers. We hypothesized the serum levels would normalize after detoxification.
Methods
Seventeen MOH patients, hereof 70.6% with chronic migraine and MOH, and 30 sex and age matched headache‐free controls were included. MOH patients underwent a 2‐month out‐patient detoxification program and after six months 10 patients and 19 controls were retested. Blood samples were analyzed blinded.
Results
We found no differences in the levels of nociceptin and CGRP between MOH patients and controls (p=0.65 and p=0.59). The mean headache frequency reduction was 43% and 70% of patients reverted to episodic headache after 6 months, but the levels of nociceptin and CGRP were unchanged (p=0.71 and p=0.82).
Conclusion
In contrast to previous findings in migraine patients, we found normal serum levels of nociceptin and CGRP in MOH patients. Thus, we find no evidence that the increased headache frequency of MOH patients could be caused by altered nociceptin and CGRP levels. This underlines the importance of identifying medication overuse in chronic headache and treating the MOH.
This article is protected by copyright. All rights reserved.
https://ift.tt/2QTbXqE
Olaparib after Initial Treatment Delays Ovarian Cancer Progression
In a recent trial, the PARP inhibitor olaparib substantially delayed ovarian cancer from coming back after the first line of chemotherapy. Could the findings change the standard of care for newly diagnosed ovarian cancer with a BRCA mutation?
https://ift.tt/2OUo70C
Short-term inhibition of spinal reflexes in multiple lower limb muscles after neuromuscular electrical stimulation of ankle plantar flexors
Abstract
Neuromuscular electrical stimulation (NMES) of lower limbs elicits muscle contractions through the activation of efferent fibers and concomitant recruitment of afferent fibers, which can modulate excitability of the central nervous system. However, neural mechanisms of NMES and how unilateral stimulation of the soleus affects spinal reflexes in multiple lower limb muscles bilaterally remains unknown. Twelve able-bodied participants were recruited, and spinal reflex excitability changes were tested after four interventions, each applied for 60 s, on the right plantar flexors: (1) motor-level NMES; (2) sensory-level NMES; (3) voluntary contraction; (4) rest. Spinal reflexes were elicited using single-pulse transcutaneous spinal cord stimulation applied on the lumbar level of the spinal cord to evoke bilateral responses in multiple lower limb muscles, while maximum motor response (Mmax) was tested in the soleus by stimulating the posterior tibial nerve. Spinal reflexes and Mmax before each intervention were compared to immediately after and every 5 min subsequently, for 15 min. Results showed that motor-level NMES inhibited spinal reflexes of the soleus and other studied muscles of the ipsilateral leg, but not the contralateral leg (except vastus medialis) for 15 min, while not affecting soleus muscle properties (Mmax). Voluntary contraction effect lasted less than 5 min, while sensory-level NMES and rest did not produce an effect. Short-term spinal reflex excitability was likely affected because antidromic impulses during motor-level NMES coincided in the spinal cord with afferent inputs to induce spinal neuroplasticity, whereas afferent input alone did not produce short-term effects. Such activation of muscles with NMES could reduce spasticity in individuals with neurological impairments.
https://ift.tt/2Q7xtur
Correction to: Planning comparison of five automated treatment planning solutions for locally advanced head and neck cancer
Following publication of the original article [1], the authors reported that one of the authors' names was processed incorrectly.
https://ift.tt/2FGP602
Rapid tools to gain insights into the interaction dynamics of new 8‐hydroxyquinolines with few fungal lines
Six novel 8‐hydroxyquinoline derivatives were synthesized and evaluated. In addition, this work has used tools to better evaluate the interaction of the most active derivatives with fungal cells. Compounds 5a and 5b showed interesting antimicrobial activity. The EC50 values obtained by combination of time‐kill studies with mathematical model were similar to the minimal inhibitory concentration, which clarify the potential of these compounds. 5a and 5b are highly effective, nonirritant molecules and do not exhibit topical toxicity.
Abstract
The combination of tools such as time‐kill assay with subsequent application of mathematical modeling can clarify the potential of new antimicrobial compounds, since minimal inhibitory concentration (MIC) value does not provide a very detailed characterization of antimicrobial activity. Recently, our group has reported that the 8‐hydroxy‐5‐quinolinesulfonic acid presents relevant antifungal activity. However, its intrinsic acidity could lead to an ionization process, decreasing fungal cell permeability. To overcome this potential problem and enhance activity, the purpose of this study was to synthesize and evaluate a novel series of hybrids between the 8‐hydroxyquinoline core and sulfonamide and to prove their potential using broth microdilution method, obtaining the pharmacodynamic parameters of the most active derivatives combining time‐kill studies and mathematical modeling and evaluating their toxicity. Compound 5a was the most potent, being active against all the fungal species tested, with low toxicity in normal cells. 5a and 5b have presented important antibacterial activity against Staphylococcus aureus strain. The EC50 values obtained by combination of time‐kill studies with mathematical model were similar to those of MIC, which confirms the potential of compounds. In addition, these derivatives are non‐irritant molecules with the absence of topical toxicity. Finally, 5a and 5b are promising candidates for treatment of dermatomycosis and candidiasis.
https://ift.tt/2OT6E8E
Bronchial Asthma and Bronchial Hyperresponsiveness and Their Characteristics in Patients with Common Variable Immunodeficiency
Background: Common variable immunodeficiency (CVID) is one of the most frequent primary immunodeficiencies and is characterized by disturbed immunoglobulin production and dysregulation of the immune system. Results of previous studies suggest a higher prevalence of bronchial asthma (BA) in CVID patients than in the general population. We initiated this study to evaluate lung functions and identify risk factors for BA and bronchial hyperresponsiveness (BHR) in patients with CVID. Methods: Twenty-three patients with CVID were included in this study. In all of them, spirometry and a metacholine bronchoprovocation test were performed. We also investigated the role of atopy, eosinophilic inflammation, and potential risk factors such as gender, age, or immunoglobulin levels at the time of diagnosis. Results: BHR was confirmed in 12 patients (52%), all of whom had normal FEV1 and FEV1/FVC. However, BHR-positive patients had significantly decreased MEF25. BHR-positive patients had also more symptoms related to bronchial obstruction, with 8 of them (35%) being suspected of having BA at the end of the study. A higher prevalence of BHR was found in females, with a relative risk of 2.89. Conclusions: An increased prevalence of BHR and BA was detected in CVID patients compared to the general population. BA may develop despite the disturbed immunoglobulin production, and the majority of patients display nonatopic and noneosinophilic properties. These results suggest a limited role of atopy and eosinophilic inflammation in the pathogenesis of BA in CVID patients.
Int Arch Allergy Immunol
https://ift.tt/2PFutpN
Int Arch Allergy Immunol
https://ift.tt/2PFutpN
Cancers, Vol. 10, Pages 458: Aberrant RNA Splicing in Cancer and Drug Resistance
Cancers, Vol. 10, Pages 458: Aberrant RNA Splicing in Cancer and Drug Resistance
Cancers doi: 10.3390/cancers10110458
Authors: Bi-Dar Wang Norman H. Lee
More than 95% of the 20,000 to 25,000 transcribed human genes undergo alternative RNA splicing, which increases the diversity of the proteome. Isoforms derived from the same gene can have distinct and, in some cases, opposing functions. Accumulating evidence suggests that aberrant RNA splicing is a common and driving event in cancer development and progression. Moreover, aberrant splicing events conferring drug/therapy resistance in cancer is far more common than previously envisioned. In this review, aberrant splicing events in cancer-associated genes, namely BCL2L1, FAS, HRAS, CD44, Cyclin D1, CASP2, TMPRSS2-ERG, FGFR2, VEGF, AR and KLF6, will be discussed. Also highlighted are the functional consequences of aberrant splice variants (BCR-Abl35INS, BIM-γ, IK6, p61 BRAF V600E, CD19-∆2, AR-V7 and PIK3CD-S) in promoting resistance to cancer targeted therapy or immunotherapy. To overcome drug resistance, we discuss opportunities for developing novel strategies to specifically target the aberrant splice variants or splicing machinery that generates the splice variants. Therapeutic approaches include the development of splice variant-specific siRNAs, splice switching antisense oligonucleotides, and small molecule inhibitors targeting splicing factors, splicing factor kinases or the aberrant oncogenic protein isoforms.
https://ift.tt/2A9Kd9M
Cancers, Vol. 10, Pages 457: Advanced Radiation Techniques in the Treatment of Esthesioneuroblastoma: A 7-Year Single-Institution’s Clinical Experience
Cancers, Vol. 10, Pages 457: Advanced Radiation Techniques in the Treatment of Esthesioneuroblastoma: A 7-Year Single-Institution's Clinical Experience
Cancers doi: 10.3390/cancers10110457
Authors: Jakob Liermann Mustafa Syed Thomas Held Denise Bernhardt Peter Plinkert Christine Jungk Andreas Unterberg Stefan Rieken Jürgen Debus Klaus Herfarth Sebastian Adeberg
(1) Background: Esthesioneuroblastoma (ENB) is a rare tumor entity originating from the olfactory neuroepithelium. There is a scarcity of data about different treatment strategies. Intensity modulated radiotherapy (IMRT) and carbon ion radiotherapy (CIRT) are advanced radiation techniques that might improve local tumor control. (2) Methods: This retrospective analysis contained 17 patients with ENB (Kadish stage ≥ C: 88%; n = 15). Four patients had already undergone previous radiotherapy (RT). The treatment consisted of either IMRT (n = 5), CIRT (n = 4) or a combination of both techniques (n = 8). Median follow-up was 29 months. (3) Results: In patients that had not been irradiated before (n = 13), calculated overall survival (OS) and progression free survival (PFS) rates after 48 months were 100% and 81% respectively (Kaplan-Meier estimates). Two of four patients that underwent reirradiation died after RT, presumably due to tumor progression. Besides common toxicities, five patients (30%) showed mostly asymptomatic radiation-induced brain changes, most likely due to a disturbance of the blood-brain barrier. (4) Conclusions: Our results demonstrate that IMRT, CIRT, a combined approach of IMRT and CIRT as well as reirradiation with CIRT seem to be feasible and effective treatment methods in ENB.
https://ift.tt/2TrE1mx
Association between antibiotic consumption and the rate of carbapenem-resistant Gram-negative bacteria from China based on 153 tertiary hospitals data in 2014
This study aimed to investigate the relationship between the rate of carbapenem-resistant Gram-negative bacteria and antibiotic consumption intensity in 153 tertiary hospitals from China in 2014.
https://ift.tt/2QYj0OT
Emergence of high drug resistant bacterial isolates from patients with health care associated infections at Jimma University medical center: a cross sectional study
The rates of resistant microorganisms which complicate the management of healthcare associated infections (HAIs) are increasing worldwide and getting more serious in developing countries. The objective of this...
https://ift.tt/2PEAP8N
Anal canal adenocarcinoma with neuroendocrine features accompanying secondary extramammary Paget disease, successfully treated with modified FOLFOX6: a case report
Abstract
Background
Anal canal cancer occasionally accompanies extramammary Paget disease. Although most of them are squamous cell carcinoma, anal canal adenocarcinoma with neuroendocrine features accompanying secondary extramammary Paget disease has never been reported.
Case presentation
Here, we report a 76-year-old man presented with pruritus in the perianal area. Investigation revealed a fist-sized perianal erythema, diffuse liver tumors, and right inguinal lymph node swelling. Pathological examination of biopsies from the erythema suggested secondary extramammary Paget disease with positive cytokeratin-7 and -20 expressions and negative GCDFP-15 expression. The anal canal tumor was confirmed by digital examination and endoscopy. Biopsies from the anal canal tumor, swollen lymph node, and Paget lesion all showed poorly differentiated adenocarcinoma with neuroendocrine features expressing synaptophysin and chromogranin A. Serum CEA and NSE levels were high, 809.4 ng/ml and 85.8 ng/ml, respectively. After chemotherapy with modified FOLFOX6 for 2 months, the Paget lesion disappeared, and the primary anal canal tumor and liver metastases shrunk remarkably. Serum CEA and NSE levels decreased promptly to within normal ranges.
Conclusions
This is a clinically significant case, as it reveals novel pathological features about anal canal cancer with secondary Paget disease and successfully treated with modified FOLFOX6. Careful pathological investigation and appropriate treatment choice are needed for this rare cancer.
https://ift.tt/2DOZ1Po
Biomechanical and neurocognitive performance outcomes of walking with transtibial limb loss while challenged by a concurrent task
Abstract
Individuals who have sustained loss of a lower limb may require adaptations in sensorimotor and control systems to effectively utilize a prosthesis, and the interaction of these systems during walking is not clearly understood for this patient population. The aim of this study was to concurrently evaluate temporospatial gait mechanics and cortical dynamics in a population with and without unilateral transtibial limb loss (TT). Utilizing motion capture and electroencephalography, these outcomes were simultaneously collected while participants with and without TT completed a concurrent task of varying difficulty (low- and high-demand) while seated and walking. All participants demonstrated a wider base of support and more stable gait pattern when walking and completing the high-demand concurrent task. The cortical dynamics were similarly modulated by the task demand for both groups, to include a decrease in the novelty-P3 component and increase in the frontal theta/parietal alpha ratio power when completing the high-demand task, although specific differences were also observed. These findings confirm and extend prior efforts indicating that dual-task walking can negatively affect walking mechanics and/or neurocognitive performance. However, there may be limited additional cognitive and/or biomechanical impact of utilizing a prosthesis in a stable, protected environment in TT who have acclimated to ambulating with a prosthesis. These results highlight the need for future work to evaluate interactions between these cognitive–motor control systems for individuals with more proximal levels of lower limb loss, and in more challenging (ecologically valid) environments.
https://ift.tt/2OU4ANI
Invasion-related circular RNA circFNDC3B inhibits bladder cancer progression through the miR-1178-3p/G3BP2/SRC/FAK axis
Abstract
Background
Increasing evidence has revealed that circular RNAs (circRNAs) play crucial roles in cancer biology. However, the role and underlying regulatory mechanisms of circFNDC3B in bladder cancer (BC) remain unknown.
Methods
A cell invasion model was established by repeated transwell assays, and invasion-related circRNAs in BC were identified through an invasion model. The expression of circFNDC3B was detected in 82 BC tissues and cell lines by quantitative real-time PCR. Functional assays were performed to evaluate the effects of circFNDC3B on proliferation, migration and invasion in vitro-, and on tumorigenesis and metastasis in vivo. The relationship between circFNDC3B and miR-1178-3p was confirmed by fluorescence in situ hybridization, pull-down assay and luciferase reporter assay.
Results
In the present study, we identified a novel circRNA (circFNDC3B) through our established BC cell invasion model. We found that circFNDC3B was dramatically downregulated in BC tissues and correlated with pathological T stage, grade, lymphatic invasion and patients' overall survival rate. Functionally, overexpression of circFNDC3B significantly inhibited proliferation, migration and invasion both in vitro and in vivo. Mechanistically, circFNDC3B could directly bind to miR-1178-3p, which targeted the 5′UTR of the oncogene G3BP2. Moreover, circFNDC3B acted as a miR-1178-3p sponge to suppress G3BP2, thereby inhibiting the downstream SRC/FAK signaling pathway.
Conclusions
CircFNDC3B may serve as a novel tumor suppressive factor and potential target for new therapies in human BC.
https://ift.tt/2zkvglU
Serum Neurofilament light correlates with CADASIL disease severity and survival
Abstract
Objective
To validate whether serum Neurofilament Light‐chain (NfL) levels correlate with disease severity in CADASIL, and to determine whether serum NfL predicts disease progression and survival.
Methods
Fourty‐one (pre‐) manifest individuals with CADASIL causing NOTCH3 mutations and 22 healthy controls were recruited from CADASIL families. At baseline, MRI‐lesion load and clinical severity was determined and serum was stored. Disease progression was measured in 30/41 patients at 7‐year follow‐up, and survival of all individuals was determined at 17‐year follow‐up. Serum NfL levels were quantified using an ultra‐sensitive molecule array. Generalized estimated equation regression (GEE) was used to analyze association between serum NfL, MRI‐lesion load, disease severity, and disease progression. With GEE‐based Cox regression, survival was analyzed.
Results
At baseline, serum NfL levels correlated with MRI‐lesion load [lacune count (s = 0.64, P = 0.002), brain atrophy (r = −0.50, P = 0.001), and microbleed count (s = 0.48, P = 0.044)], cognition [CAMCOG (s = −0.45, P = 0.010), MMSE (r = −0.61, P = 0.003), GIT (r = −0.61, P < 0.001), TMT‐A (r = 0.70, P < 0.001)) and disability (mRS (r = 0.70, P = 0.002)]. Baseline serum NfL predicted 7‐year changes in disability (B = 0.34, P < 0.001) and cognition (CAMCOG B = −4.94, P = 0.032), as well as 17‐year survival. Higher NfL levels were associated with increased mortality (HR=1.8 per twofold increase in NfL levels, P = 0.006).
Interpretation
Serum NfL levels correlate with disease severity, disease progression and 17‐year survival in CADASIL patients. Serum NfL is a promising biomarker to monitor and predict disease course in CADASIL, as well as potentially assessing therapeutic response in future clinical trials.
https://ift.tt/2QYO94K
ASCO 2018 highlights: metastatic breast cancer
Summary
This article reviews the clinically most relevant presentations at the American Society of Clinical Oncology (ASCO) annual meeting 2018 on the topic of metastatic breast cancer. In the randomized placebo-controlled phase 3 trial MONALEESA-3, testing ribociclib vs. placebo in combination with fulvestrant in postmenopausal women or men with hormone receptor-positive (HR+) and HER2-negative (HER2−) advanced breast cancer (ABC), an increase of median progression-free survival (PFS) from 12.8 months to 20.5 months by the addition of the CDK4/6 inhibitor was reported (HR 0.59; P > 0.01). Taselisib, an alpha specific PI3K inhibitor, was tested in combination with fulvestrant in pretreated HR+/HER2− ABC patients with PIK3CA mutations in the placebo-controlled phase 3 trial SANDPIPER. PFS was significantly longer (7.4 months vs 5.4 months; HR 0.70, P < 0.01) but severe adverse events were more frequent (32% and 9%) in the taselisib group. In triple-negative breast cancer, the AKT inhibitor capivasertib (AZD5363) was combined with paclitaxel as first-line treatment in the placebo-controlled phase 2 trial PAKT. In patients with altered PIK3CA, AKT1 or PTEN, median PFS increased from 3.7 months to 9.3 months (HR 0.30; two-sided P = 0.01). No treatment effect was shown in the non-altered group. The most common adverse events attributed to capivasertib were diarrhea, fatigue and stomatitis. Results of two phase I trials of trastuzumab antibody-drug conjugates (ADCs) indicated HER2 as a non-oncogenic surface target in breast cancer patients expressing HER2.
https://ift.tt/2FwV43R
ASCO Congress 2018: melanoma treatment
Summary
The 2018 ASCO Annual Meeting provided a closer look on the details of studies already presented. In melanoma, the interest was on neoadjuvant treatment options with high pathological response rates as well as updates on large phase III studies in stage IV disease. Further new targets were discussed focusing on additional drugs to a PD-1 backbone treatment.
Another focus was on Merkel cell carcinoma and basal cell carcinomas, giving new data on PD-1 antibody treatments as well as on vismodegib as neoadjuvant therapy.
https://ift.tt/2qXnwSm
Cancers, Vol. 10, Pages 456: Human Glioma Migration and Infiltration Properties as a Target for Personalized Radiation Medicine
Cancers, Vol. 10, Pages 456: Human Glioma Migration and Infiltration Properties as a Target for Personalized Radiation Medicine
Cancers doi: 10.3390/cancers10110456
Authors: Michaela Wank Daniela Schilling Thomas E. Schmid Bernhard Meyer Jens Gempt Melanie Barz Jürgen Schlegel Friederike Liesche Kerstin A. Kessel Benedikt Wiestler Stefanie Bette Claus Zimmer Stephanie E. Combs
Gliomas are primary brain tumors that present the majority of malignant adult brain tumors. Gliomas are subdivided into low- and high-grade tumors. Despite extensive research in recent years, the prognosis of malignant glioma patients remains poor. This is caused by naturally highly infiltrative capacities as well as high levels of radio- and chemoresistance. Additionally, it was shown that low linear energy transfer (LET) irradiation enhances migration and invasion of several glioma entities which might counteract today’s treatment concepts. However, this finding is discussed controversially. In the era of personalized medicine, this controversial data might be attributed to the patient-specific heterogeneity that ultimately could be used for treatment. Thus, current developments in glioma therapy should be seen in the context of intrinsic and radiation-enhanced migration and invasion. Due to the natural heterogeneity of glioma cells and different radiation responses, a personalized radiation treatment concept is suggested and alternative radiation concepts are discussed.
https://ift.tt/2Fy79pm
Validity Evidence for the General Pediatrics Board Certification Examinations: A Practice Analysis
The American Board of Pediatrics (ABP) is responsible for certifying that general pediatricians and pediatric subspecialists have met and continue to meet standards of excellence that lead to the high-quality health care of infants, children, and adolescents. Board certification involves 2 primary components: successfully completing an accredited training program and taking and passing a written examination. The ABP uses a process known as practice analysis to ensure that its exams measure the knowledge required for safe and effective clinical practice.
https://ift.tt/2A529Tb
Corrections
In the article "Early-Onset Acute Recurrent and Chronic Pancreatitis Is Associated with PRSS1 or CTRC Gene Mutations" by Giefer et al (J Pediatr 2017;186:95-100), an error occurred in one of the tables of this article. The correct mutation is c.-147A>G in Table III, line 3 under SPINK1 Mutations. The correct version of the table appears below.
https://ift.tt/2A6sa4l
A difficult decision, illuminated
Parents of children with complex medical problems face many difficult decisions, and these touchpoints persist even after initial diagnosis and stabilization. One of the most fraught is whether to pursue tracheostomy. The context is usually one of worsening clinical status; the caregivers may feel this represents an unanticipated progression of disease or an irrevocable step limiting future options. Many times the child is acutely ill, leading to a sense that there is really no choice at all. In view of this, the study by Nageswaran et al in this volume of The Journal provides invaluable insight into the lived experience of families dealing with this issue.
https://ift.tt/2TtjWvZ
Turning a negative into a positive
In this volume of The Journal, Tester et al described the results of a large study employing whole exome sequencing for rare variants in sudden infant death syndrome (SIDS). These investigators carried out whole exome sequencing on 278 cases of SIDS and compared the results to 973 ethnic-matched controls. One Reviewer remarked, "Many of us have been waiting for this paper after its initial presentation in oral form. There was a sharp intake of breath around the room as an essentially negative report came out." Indeed, while no exome-wide significant differences (P < 2.5 × 10−6) in burden of ultra-rare variants was detected for any genes this is still a notable effort.
https://ift.tt/2TqLUsi
Corrections
In the article "Pulmonary Complications of Down Syndrome during Childhood" by McDowell and Craven (J Pediatr 2011;158:319-25), it should read "left-to-right shunt" instead of "right-to-left shunt" and the revised sentence should read "Children with DS with increased pulmonary blood flow because of an intracardiac left-to-right shunt may have precocious development of pulmonary artery hypertension (PAH)."
https://ift.tt/2A71OiV
50 Years Ago in The Journal of Pediatrics
Bailey DW, and Fenichel G. J Pediatr 1968;73:923-7
https://ift.tt/2A7IGkQ
Lean use of antibiotics in fragile neonates as well as children in the community: we can do better
Studies published in this volume of The Journal show that community prescribing practices for antibiotics according to national guidelines are uneven across provider types, and are not lean enough, and receipt of antibiotic(s) in the early neonatal period in infants born under 33 weeks of gestation is associated with substantial risk of morbidity or even fatal outcome.
https://ift.tt/2TssnI7
50 Years Ago in The Journal of Pediatrics
Pinkel D, Pratt C, Holton C, James D Jr, Wrenn E Jr, Hustu HO. J Pediatr 1968;73(6):928-31
https://ift.tt/2A7IEte
Sleep and obesity
There is an emerging literature on the relationship between sleep and obesity in children and adolescents. Most studies have focused on the duration of sleep, with shorter duration associated with increased risk of obesity. In this volume of The Journal, Jansen et al evaluated both duration of sleep and the variability of duration measured by actigraphy in children from Mexico City. They created 4 sleep categories: sufficient stable, sufficient variable, insufficient stable, and insufficient variable.
https://ift.tt/2TugVvq
Medication reconciliation: ineffective or hard to implement?
In this issue of BMJ Quality & Safety, Schnipper et al evaluate the implementation of a multifaceted medication reconciliation intervention at six hospitals using the MARQUIS medication reconciliation implementation toolkit.1 The planned intervention included the following elements: hiring or reallocating new staff to obtain medication histories, performing both admission and discharge medication reconciliation, improving access to preadmission medication sources, introducing policy, training staff on obtaining medication histories and patient counselling, implementing a gold standard medication reconciliation process including targeting of high-risk patients, improving healthcare information technology and utilising social marketing and community engagement. The study had many methodological strengths, including independent observers for outcome verification, clinical assessment of medication discrepancies, pragmatic implementation in both community and teaching hospitals, mentored implementation and a large randomly selected patient sample with controls and temporal trending. The main result was that potentially harmful discrepancies did not decrease over time beyond baseline...
https://ift.tt/2KhWXA7
Mortality alerts, actions taken and declining mortality: true effect or regression to the mean?
Alerts have become a routine part of our daily lives—from the apps on our phones to an increasing number of 'wearables' (eg, fitness trackers) and household devices. Within healthcare, frontline clinicians have become all too familiar with a barrage of alerts and alarms from electronic medical records and medical devices.
Somewhat less familiar to most clinicians, however, are the alerts received by institutions from regulators and other regional or national bodies monitoring healthcare performance. After the Bristol inquiry in 2001 in the UK,1 research showed that given the available data Bristol could have been detected as an outlier and that it was not simply a matter of the low volume of cases.2 3 Had the cumulative excess mortality been monitored using these routinely collected data, then an alarm could have given for Bristol after the publication of the 1991 Cardiac Surgical Register and...
https://ift.tt/2BjuYwO
Variable effectiveness of stepwise implementation of nudge-type interventions to improve provider compliance with intraoperative low tidal volume ventilation
Background
Identifying mechanisms to improve provider compliance with quality metrics is a common goal across medical disciplines. Nudge interventions are minimally invasive strategies that can influence behavioural changes and are increasingly used within healthcare settings. We hypothesised that nudge interventions may improve provider compliance with lung-protective ventilation (LPV) strategies during general anaesthesia.
MethodsWe developed an audit and feedback dashboard that included information on both provider-level and department-level compliance with LPV strategies in two academic hospitals, two non-academic hospitals and two academic surgery centres affiliated with a single healthcare system. Dashboards were emailed to providers four times over the course of the 9-month study. Additionally, the default setting on anaesthesia machines for tidal volume was decreased from 700 mL to 400 mL. Data on surgical cases performed between 1 September 2016 and 31 May 2017 were examined for compliance with LPV. The impact of the interventions was assessed via pairwise logistic regression analysis corrected for multiple comparisons.
ResultsA total of 14 793 anaesthesia records were analysed. Absolute compliance rates increased from 59.3% to 87.8%preintervention to postintervention. Introduction of attending physician dashboards resulted in a 41% increase in the odds of compliance (OR 1.41, 95% CI 1.17 to 1.69, p=0.002). Subsequently, the addition of advanced practice provider and resident dashboards lead to an additional 93% increase in the odds of compliance (OR 1.93, 95% CI 1.52 to 2.46, p<0.001). Lastly, modifying ventilator defaults led to a 376% increase in the odds of compliance (OR 3.76, 95% CI 3.1 to 4.57, p<0.001).
ConclusionAudit and feedback tools in conjunction with default changes improve provider compliance.
https://ift.tt/2KiH5x3
Effects of a multifaceted medication reconciliation quality improvement intervention on patient safety: final results of the MARQUIS study
Background
Unintentional discrepancies across care settings are a common form of medication error and can contribute to patient harm. Medication reconciliation can reduce discrepancies; however, effective implementation in real-world settings is challenging.
MethodsWe conducted a pragmatic quality improvement (QI) study at five US hospitals, two of which included concurrent controls. The intervention consisted of local implementation of medication reconciliation best practices, utilising an evidence-based toolkit with 11 intervention components. Trained QI mentors conducted monthly site phone calls and two site visits during the intervention, which lasted from December 2011 through June 2014. The primary outcome was number of potentially harmful unintentional medication discrepancies per patient; secondary outcome was total discrepancies regardless of potential for harm. Time series analysis used multivariable Poisson regression.
ResultsAcross five sites, 1648 patients were sampled: 613 during baseline and 1035 during the implementation period. Overall, potentially harmful discrepancies did not decrease over time beyond baseline temporal trends, adjusted incidence rate ratio (IRR) 0.97 per month (95% CI 0.86 to 1.08), p=0.53. The intervention was associated with a reduction in total medication discrepancies, IRR 0.92 per month (95% CI 0.87 to 0.97), p=0.002. Of the four sites that implemented interventions, three had reductions in potentially harmful discrepancies. The fourth site, which implemented interventions and installed a new electronic health record (EHR), saw an increase in discrepancies, as did the fifth site, which did not implement any interventions but also installed a new EHR.
ConclusionsMentored implementation of a multifaceted medication reconciliation QI initiative was associated with a reduction in total, but not potentially harmful, medication discrepancies. The effect of EHR implementation on medication discrepancies warrants further study.
Trial registration numberhttps://ift.tt/2Bk0KtH
Incidence and trends of central line associated pneumothorax using radiograph report text search versus administrative database codes
Background
Central line associated pneumothorax (CLAP) could be a good quality of care indicator because they are objectively measured, clearly undesirable and possibly avoidable. We measured the incidence and trends of CLAP using radiograph report text search with manual review and compared them with measures using routinely collected health administrative data.
MethodsFor each hospitalisation to a tertiary care teaching hospital between 2002 and 2015, we searched all chest radiography reports for a central line with a sensitive computer algorithm. Screen positive reports were manually reviewed to confirm central lines. The index and subsequent chest radiography reports were screened for pneumothorax followed by manual confirmation. Diagnostic and procedural codes were used to identify CLAP in administrative data.
ResultsIn 685 044 hospitalisations, 10 819 underwent central line insertion (1.6%) with CLAP occurring 181 times (1.7%). CLAP risk did not change over time. Codes for CLAP were inaccurate (sensitivity 13.8%, positive predictive value 6.6%). However, overall code-based CLAP risk (1.8%) was almost identical to actual values possibly because patient strata with inflated CLAP risk were balanced by more common strata having underestimated CLAP risk. Code-based methods inflated central line incidence 2.2 times and erroneously concluded that CLAP risk decreased significantly over time.
ConclusionsUsing valid methods, CLAP incidence was similar to those in the literature but has not changed over time. Although administrative database codes for CLAP were very inaccurate, they generated CLAP risks very similar to actual values because of offsetting errors. In contrast to those from radiograph report text search with manual review, CLAP trends decreased significantly using administrative data. Hospital CLAP risk should not be measured using administrative data.
https://ift.tt/2Kko3X4
Investigating the association of alerts from a national mortality surveillance system with subsequent hospital mortality in England: an interrupted time series analysis
Objective
To investigate the association between alerts from a national hospital mortality surveillance system and subsequent trends in relative risk of mortality.
BackgroundThere is increasing interest in performance monitoring in the NHS. Since 2007, Imperial College London has generated monthly mortality alerts, based on statistical process control charts and using routinely collected hospital administrative data, for all English acute NHS hospital trusts. The impact of this system has not yet been studied.
MethodsWe investigated alerts sent to Acute National Health Service hospital trusts in England in 2011–2013. We examined risk-adjusted mortality (relative risk) for all monitored diagnosis and procedure groups at a hospital trust level for 12 months prior to an alert and 23 months post alert. We used an interrupted time series design with a 9-month lag to estimate a trend prior to a mortality alert and the change in trend after, using generalised estimating equations.
ResultsOn average there was a 5% monthly increase in relative risk of mortality during the 12 months prior to an alert (95% CI 4% to 5%). Mortality risk fell, on average by 61% (95% CI 56% to 65%), during the 9-month period immediately following an alert, then levelled to a slow decline, reaching on average the level of expected mortality within 18 months of the alert.
ConclusionsOur results suggest an association between an alert notification and a reduction in the risk of mortality, although with less lag time than expected. It is difficult to determine any causal association. A proportion of alerts may be triggered by random variation alone and subsequent falls could simply reflect regression to the mean. Findings could also indicate that some hospitals are monitoring their own mortality statistics or other performance information, taking action prior to alert notification.
https://ift.tt/2BkonlW
Developing a hospital-wide quality and safety dashboard: a qualitative research study
Background
Several countries have national policies and programmes requiring hospitals to use quality and safety (QS) indicators. To present an overview of these indicators, hospital-wide QS (HWQS) dashboards are designed. There is little evidence how these dashboards are developed. The challenges faced to develop these dashboards in Dutch hospitals were retrospectively studied.
Methods24 focus group interviews were conducted: 12 with hospital managers (n=25; 39.7%) and 12 support staff (n=38; 60.3%) in 12 of the largest Dutch hospitals. Open and axial codings were applied consecutively to analyse the data collected.
ResultsA heuristic tool for the general development process for HWQS dashboards containing five phases was identified. In phase 1, hospitals make inventories to determine the available data and focus too much on quantitative data relevant for accountability. In phase 2, hospitals develop dashboard content by translating data into meaningful indicators for different users, which is not easy due to differing demands. In phase 3, hospitals search for layouts that depict the dashboard content suited for users with different cognitive abilities and analytical skills. In phase 4, hospitals try to integrate dashboards into organisational structures to ensure that data are systematically reviewed and acted on. In phase 5, hospitals want to improve the flexibility of their dashboards to make this adaptable under differing circumstances.
ConclusionThe literature on dashboards addresses the technical and content aspects of dashboards, but overlooks the organisational development process. This study shows how technical and organisational aspects are relevant in development processes.
https://ift.tt/2KknLiW
National hospital mortality surveillance system: a descriptive analysis
Objective
To provide a description of the Imperial College Mortality Surveillance System and subsequent investigations by the Care Quality Commission (CQC) in National Health Service (NHS) hospitals receiving mortality alerts.
BackgroundThe mortality surveillance system has generated monthly mortality alerts since 2007, on 122 individual diagnosis and surgical procedure groups, using routinely collected hospital administrative data for all English acute NHS hospital trusts. The CQC, the English national regulator, is notified of each alert. This study describes the findings of CQC investigations of alerting trusts.
MethodsWe carried out (1) a descriptive analysis of alerts (2007–2016) and (2) an audit of CQC investigations in a subset of alerts (2011–2013).
ResultsBetween April 2007 and October 2016, 860 alerts were generated and 76% (654 alerts) were sent to trusts. Alert volumes varied over time (range: 40–101). Septicaemia (except in labour) was the most commonly alerting group (11.5% alerts sent). We reviewed CQC communications in a subset of 204 alerts from 96 trusts. The CQC investigated 75% (154/204) of alerts. In 90% of these pursued alerts, trusts returned evidence of local case note reviews (140/154). These reviews found areas of care that could be improved in 69% (106/154) of alerts. In 25% (38/154) trusts considered that identified failings in care could have impacted on patient outcomes. The CQC investigations resulted in full trust action plans in 77% (118/154) of all pursued alerts.
ConclusionThe mortality surveillance system has generated a large number of alerts since 2007. Quality of care problems were found in 69% of alerts with CQC investigations, and one in four trusts reported that failings in care may have an impact on patient outcomes. Identifying whether mortality alerts are the most efficient means to highlight areas of substandard care will require further investigation.
https://ift.tt/2BjW8DP
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
