A. Pulido Pérez
Actas Dermosifiliogr.2018;109:295
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Πέμπτη 3 Μαΐου 2018
HIV-associated psoriasis
Morphea in Childhood: An Update
Dermatology and Immunoglobulin Therapy: Who to Treat and How to Administer Immunoglobulins
Quality of Life, Behaviour and Attitudes towards Actinic Keratosis in Spain: The PIQA Study
Photocarcinogenic Risk Associated With Narrowband UV-B Phototherapy: An Epidemiologic Study in a Tertiary Care Hospital
Description of patients excluded for Mohs surgery after pre-surgical evaluation: data from the Regesmohs Spanish registry
V. Ruiz-Salas, J.R. Garcés, T. Alonso-Alonso, M.A. Rodríguez-Prieto, A. Toll-Abelló, E. Eusebio Murillo, R. Miñano, J.L. López-Estebaranz, O. Sanmartín-Jiménez, C. Guillén Barona, I. Allende Markixana, A. Alfaro Rubio, Y. Delgado Jiménez, R. Navarro, L. Barchino Ortiz, P. Lázaro Ochaita, E. Vilarasa, C. Ciudad Blanco, H. Vázquez-Veiga, J.L. Artola Igarza, M.L. Alonso, I. García-Doval, M.A. Descalzo, P. Redondo Bellón
Actas Dermosifiliogr.2018;109:346-50
Abstract - Full text - PDF
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Electrosurgery for the Treatment of Moderate or Severe Rhinophyma
Mucocutaneous Manifestations of Infection by Histoplasma capsulatum in HIV-Negative Immunosuppressed Patients
Painful Ulcer in a Black Man
Umbilicated Papules on the Elbows of a Woman With Systemic Vasculitis
Ulcerative nodules on the perineum
Management of Corticosteroid-Induced Osteoporosis: A Practical Approach for the Dermatologist
Proliferating Pilomatricoma Mimicking a Malignant Tumor
Cutaneous Metastases From Adenocarcinoma of the Prostate
Dermatopathic Lymphadenopathy: Is Our Diagnostic Approach Correct?
Folliculitis Decalvans Caused by Bacterial Superinfection Secondary to Erlotinib
Prevalence of BRCA1/2 large genomic rearrangements in Chinese women with sporadic triple‐negative or familial breast cancer
Clinical Genetics, EarlyView.
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Aldo‐keto reductases‐mediated cytotoxicity of 2‐deoxyglucose: A novel anticancer mechanism
Cancer Science, EarlyView.
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UGT1A polymorphisms associated with worse outcome in colorectal cancer patients treated with irinotecan-based chemotherapy
Abstract
Purpose
To investigate the association between UDP-glucuronosyltransferase (UGT)1A polymorphisms and irinotecan-treatment efficacy in a Chinese population with metastatic colorectal cancer (mCRC).
Methods
The present study was based on a prospective multicenter trial of Chinese mCRC patients treated with irinotecan-based chemotherapy (NCT01282658, registered at http://www.clinicaltrials.gov). Fifteen single-nucleotide polymorphisms (SNPs) in four UGT1A genes were selected for genotyping in 164 patients. Kaplan–Meier and Cox regression analyses were used to assess the association between potential signatures and survival outcome.
Results
We found that UGT1A1*28 variant genotype was significantly associated with decreased progression-free survival (PFS) [adjusted hazard ratio (HR), 1.803; 95% confidence interval (CI), 1.217–2.671] and overall survival (OS) (adjusted HR 1.979; 95% CI 1.267–3.091) compared with wild-type genotype. Patients carrying (TA)7 allele showed a median PFS of 7.5 (95% CI 5.5–9.6) months compared with 9.8 (95% CI 8.6–10.9) months for patients with wild-type genotype. Median OSs were 13.3 (95% CI 10.3–16.2), and 20.8 (95% CI 18.7–23.0) months for (TA)6/7 or (TA)7/7, and (TA)6/6 patients, respectively. Similarly but more significantly, the copy number of haplotype III (composed by rs3755321-T, rs3821242-C, rs4124874-G and rs3755319-C) constructed among the selected SNPs also correlated with survival outcome.
Conclusions
UGT1A polymorphisms are predictive of survival outcome of irinotecan-treated Chinese mCRC patients. After validation, UGT1A polymorphisms might be helpful in facilitating stratification of mCRC patients for individualized treatment options.
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Need a lift? Find out how one tool protects your patients and your back in 3 ways
Binder Lift's torso wrap lifting aid helps prevent injuries, shields EMS providers from fluids and improves patient comfort
https://ift.tt/2HODu88
Use of cyclin-dependent kinase (CDK) 4/6 inhibitors for hormone receptor-positive, human epidermal growth factor receptor 2-negative, metastatic breast cancer: a roundtable discussion by The Breast Cancer Therapy Expert Group (BCTEG)
Abstract
Purpose
To provide an overview of clinical data supporting the use of cyclin-dependent kinases 4 and 6 (CDK 4/6) inhibitors in the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−), metastatic breast cancer (mBC), from the perspective of the practicing oncologist community.
Methods
A recent roundtable discussion was convened by The Breast Cancer Therapy Expert Group (BCTEG) to review existing data on this topic and its impact on their current practice.
Results
Level 1 evidence now supports use of a CDK 4/6 inhibitor in combination with endocrine therapy for patients with HR+, HER2−, mBC. Currently, there are no biomarkers that reliably define patients who will, or will not, benefit from the addition of a CDK 4/6 inhibitor to their endocrine therapy. Additional research is needed to identify the optimal sequencing of CDK 4/6 inhibitors in relation to other therapies as well as the optimal duration of therapy; at present, evidence suggests that use in the upfront setting is better than waiting for a later line of therapy, or adding after endocrine therapy has started.
Conclusions
Thus far, three CDK 4/6 inhibitors—palbociclib, ribociclib, and more recently, abemaciclib—have been approved for use in the setting of HR+, HER2−, mBC. The degrees to which these agents differ in terms of CDK4/6 affinity, side-effect profiles, dosing, degree of central nervous system (CNS) penetration, optimal use in combination with antiestrogen therapy, and across other subsets of breast cancer, remain an active area of investigation.
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Dicer1 downregulation by multiple myeloma cells promotes the senescence and tumor-supporting capacity and decreases the differentiation potential of mesenchymal stem cells
Dicer1 downregulation by multiple myeloma cells promotes the senescence and tumor-supporting capacity and decreases the differentiation potential of mesenchymal stem cells
Dicer1 downregulation by multiple myeloma cells promotes the senescence and tumor-supporting capacity and decreases the differentiation potential of mesenchymal stem cells, Published online: 03 May 2018; doi:10.1038/s41419-018-0545-6
Dicer1 downregulation by multiple myeloma cells promotes the senescence and tumor-supporting capacity and decreases the differentiation potential of mesenchymal stem cellshttps://ift.tt/2HOC7Kq
Repression of Septin9 and Septin2 suppresses tumor growth of human glioblastoma cells
Repression of Septin9 and Septin2 suppresses tumor growth of human glioblastoma cells
Repression of Septin9 and Septin2 suppresses tumor growth of human glioblastoma cells, Published online: 03 May 2018; doi:10.1038/s41419-018-0547-4
Repression of Septin9 and Septin2 suppresses tumor growth of human glioblastoma cellshttps://ift.tt/2rkTAiv
HOXB9 promotes endometrial cancer progression by targeting E2F3
HOXB9 promotes endometrial cancer progression by targeting E2F3
HOXB9 promotes endometrial cancer progression by targeting E2F3, Published online: 03 May 2018; doi:10.1038/s41419-018-0556-3
HOXB9 promotes endometrial cancer progression by targeting E2F3https://ift.tt/2HOjWVp
Loss of Tctn3 causes neuronal apoptosis and neural tube defects in mice
Loss of Tctn3 causes neuronal apoptosis and neural tube defects in mice
Loss of Tctn3 causes neuronal apoptosis and neural tube defects in mice, Published online: 03 May 2018; doi:10.1038/s41419-018-0563-4
Loss of Tctn3 causes neuronal apoptosis and neural tube defects in micehttps://ift.tt/2HPnPcI
IL-3 but not monomeric IgE regulates FcεRI levels and cell survival in primary human basophils
IL-3 but not monomeric IgE regulates FcεRI levels and cell survival in primary human basophils
IL-3 but not monomeric IgE regulates FcεRI levels and cell survival in primary human basophils, Published online: 03 May 2018; doi:10.1038/s41419-018-0526-9
IL-3 but not monomeric IgE regulates FcεRI levels and cell survival in primary human basophilshttps://ift.tt/2rkecYh
WWOX controls hepatic HIF1α to suppress hepatocyte proliferation and neoplasia
WWOX controls hepatic HIF1α to suppress hepatocyte proliferation and neoplasia
WWOX controls hepatic HIF1α to suppress hepatocyte proliferation and neoplasia, Published online: 03 May 2018; doi:10.1038/s41419-018-0510-4
WWOX controls hepatic HIF1α to suppress hepatocyte proliferation and neoplasiahttps://ift.tt/2Kw2uCC
Iron overload promotes mitochondrial fragmentation in mesenchymal stromal cells from myelodysplastic syndrome patients through activation of the AMPK/MFF/Drp1 pathway
Iron overload promotes mitochondrial fragmentation in mesenchymal stromal cells from myelodysplastic syndrome patients through activation of the AMPK/MFF/Drp1 pathway
Iron overload promotes mitochondrial fragmentation in mesenchymal stromal cells from myelodysplastic syndrome patients through activation of the AMPK/MFF/Drp1 pathway, Published online: 03 May 2018; doi:10.1038/s41419-018-0552-7
Iron overload promotes mitochondrial fragmentation in mesenchymal stromal cells from myelodysplastic syndrome patients through activation of the AMPK/MFF/Drp1 pathwayhttps://ift.tt/2rkmjUH
Gallbladder cancer: a journey of a thousand steps
Future Oncology, Ahead of Print.
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A Simple Method for Visualization of Locus-Specific H4K20me1 Modifications in Living Caenorhabditis elegans Single Cells
Recently, advances in next-generation sequencing technologies have enabled genome-wide analyses of epigenetic modifications; however, it remains difficult to analyze the states of histone modifications at a single-cell resolution in living multicellular organisms because of the heterogeneity within cellular populations. Here we describe a simple method to visualize histone modifications on the specific sequence of target locus at a single-cell resolution in living Caenorhabditis elegans, by combining the LacO/LacI system and a genetically-encoded H4K20me1-specific probe, "mintbody". We demonstrate that Venus-labeled mintbody and mTurquoise2-labeled LacI can co-localize on an artificial chromosome carrying both the target locus and LacO sequences, where H4K20me1 marks the target locus. We demonstrate that our visualization method can precisely detect H4K20me1 depositions on the her-1 gene sequences on the artificial chromosome, to which the dosage compensation complex binds to regulate sex determination. The degree of H4K20me1 deposition on the her-1 sequences on the artificial chromosome correlated strongly with sex, suggesting that, using the artificial chromosome, this method can reflect context-dependent changes of H4K20me1 on endogenous genomes. Furthermore, we demonstrate live imaging of H4K20me1 depositions on the artificial chromosome. Combined with ChIP assays, this mintbody-LacO/LacI visualization method will enable analysis of developmental and context-dependent alterations of locus-specific histone modifications in specific cells and elucidation of the underlying molecular mechanisms.
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Amyotrophic lateral sclerosis – time for beta testing?
Recognized from the first descriptions of the disease by Charcot and Joffroy in 1869, amyotrophic lateral sclerosis (ALS) involves the progressive degeneration of lower motor neurons (LMN) from the spinal anterior horns and brainstem, combined with loss of upper motor neurons (UMN) from the primary motor cortex and their axonal projections through the corticospinal tract (CST). Diagnosis remains based around clinical findings of UMN and LMN signs in the same symptomatic region, with accurate detection remaining crucial for timely management of this relentlessly progressive disease.
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Oh surprise! fast ripples on scalp EEG
When I heard of the work of Anatol Bragin (Bragin et al., 1999), the recording of ripples (low amplitude brief oscillations at 80 to 250 Hz) and fast ripples (oscillations at 250 to 600 Hz) with extracellular microelectrodes in experimental epileptic rats and in epileptic patients, I thought that we should look in the human intracerebral EEG to see if such high frequencies and such events could be recorded without the complexity and limitations of microelectrodes. I was not optimistic because I thought that the difference in scale between a microelectrode of 40 micrometers in diameter and a clinical intracerebral EEG electrode having a surface of 1 or 2 mm2, 500 to 1000 times larger, was such that an event as local as the High Frequency Oscillations (HFOs) recorded by Bragin would be not be picked up by the much larger clinical electrodes.
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Normal sensory membrane properties in amyotrophic lateral sclerosis
In this issue of Clinical Neurophysiology, Dr. Matamala and co-authors investigated membrane properties of peripheral sensory myelinated axons in amyotrophic lateral sclerosis (ALS) (Matamala et al., this issue). The study follows the path of a long-standing tradition of renowned Australian neurologists who approach clinical neurological problems by advanced physiological methods, the tradition being started by doctors Lance and McLeod, followed by Dr. Burke (who is one of the co-authors of the paper), and currently continued by Dr.
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Sharply contoured theta waves are the human correlate of ponto-geniculo-occipital waves in the primary visual cortex
Ponto-geniculo-occipital (PGO) waves are the hallmark of REM sleep in certain animal species (Siegel 2011). In the cat, PGO waves have been recorded from the pons (Jouvet et al., 1959), the lateral geniculate nucleus of the thalamus (Mikiten et al., 1961), and the occipital cortex (Mouret et al., 1963), explaining the nomenclature now used. These waves are biphasic sharp field potentials occurring as either singlets during the transition from slow wave sleep to REM sleep (type 1) or in clusters of 3-5 spikes during REM sleep showing a high correspondence to rapid eye movements (type II) (Datta, 1997; Callaway et al., 1987; Nelson et al., 1983).
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Do you define the limits of normalcy from looking at the patient or the healthy subject? – An e-norms reply
I read with great interest Martin Ballegaard's Editorial (Ballegaard 2018) on how you define the limits of normalcy in his discussion of our e-norms paper on the lack of normative data in pediatric EMG that appeared in the March 2018 issue of Clinical Neurophysiology (Pitt and Jabre 2018).
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Tracking the central and peripheral origin of tremor
Human motor control is a highly complex process that requires extraordinary precision to achieve optimal speed and accuracy of each movement. The dysfunction of the motor control system leads to a variety of movement disorders such as parkinsonism, dystonia, and ataxia. How the nervous system governs the movements in both physiological and pathological conditions in real time remains unclear, partly due to the rather complex nature of movements and the corresponding neurophysiology. Tremor is a type of movement with enriched information (phase, frequency, and amplitude) that can be tracked in real time to correlate with oscillatory neuronal activities in the brain, providing a very unique platform to study human motor control (McAuley and Marsden, 2000).
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Reply to “Syncope is associated with electroencephalography changes” and to “Video-EEG during tilt-table testing is an invaluable aid for understanding syncope”
We appreciate the comments from Dr. Heyer (2018) on our recent publication (Muppidi et al., 2018). We acknowledge the work by Heyer et al. on EEG patterns in tilt-induced syncope and in delayed onset tilt-induced hypotension in young patients. In contrast, our retrospective study included mostly adults, with a mean age of 45 years; the youngest patient was 16 years old. In our study population only 3 out of 7 patients with syncope showed visually discernable changes on scalp EEG. This finding was surprising to us as well and the major motivation for its publication.
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Syncope is associated with electroencephalography changes
I read with interest the article by Muppidi et al., titled "The clinical utility of qualitative electroencephalography during tilt table testing" (Muppidi et al., 2018). In a retrospective study, the authors reported qualitative electroencephalography (EEG) findings during tilt-table testing among 87 patients referred for clinical evaluation. Seven patients had neurally-mediated syncope during testing, but only three developed corresponding EEG changes. The loss of consciousness with syncope is caused by impaired cerebral perfusion and consequent neuronal dysfunction.
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Video-EEG during tilt-table testing is an invaluable aid for understanding syncope
Muppidi et al. in their recent publication, addressing the clinical utility of qualitative electroencephalography (EEG) during tilt table testing (TTT), made several statements that deserve critical consideration (Muppidi et al., 2018). Most importantly, the authors stated incorrectly, referring to our work (Van Dijk et al., 2014), that we described 'multiple patterns of EEG changes with syncope' and added, also erroneously, that 'these findings have not been replicated'. In fact, we discussed just two patterns ('slow' and 'slow-flat-slow').
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Lack of correlation between phonetic magnetic mismatch field and plasma d-serine levels in humans
Language processing is crucial for human social life. However, the molecular basis of physiological responses of language processing has remained an essential challenge in the neurobiology of language, because language processing cannot be investigated by animal studies, and invasive human studies are limited by ethical considerations. Language processing ability, in its early stage of information processing, can be neurophysiologically indexed by event-related potentials (ERPs) elicited by change detection of speech sounds, called mismatch negativity (MMN).
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Removal notice to eight abstracts in ‘Abstracts of the 61st Scientific Annual Meeting of the German Society for Clinical Neurophysiology and Functional Imaging (DGKN), Leipzig, Germany, April 27–29, 2017’
These articles have been removed: please see Elsevier Policy on Article Withdrawal (https://ift.tt/2sF4ZfT).
https://ift.tt/2rilKLl
Characteristics of Ictal EEG in Magnetic Seizure Therapy at Various Stimulation Frequencies
Electroconvulsive therapy (ECT) is the most effective treatment for treatment-resistant and severe forms of major depression, with approximately 50-65% of patients achieving response (Coffey 1993; Heijnen et al. 2010). Despite the considerable effectiveness of ECT, only a small percentage of individuals who may benefit from the intervention go on to have treatment, often due to concerns regarding adverse cognitive effects (Chakrabarti et al. 2010).
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IFCN-endorsed practical guidelines for clinical magnetoencephalography (MEG)
These are the first IFCN-endorsed clinical guidelines for magnetoencephalography (MEG). MEG guidelines have been previously published by the American Clinical Magnetoencephalography Society (Bagic et al., 2009; Burgess et al., 2011; Bagic et al., 2017), the Japanese clinical MEG community (Hashimoto et al., 2004), and the MEG research community (Gross et al., 2013a).
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Measuring neuropathy in obese populations: Challenge accepted. Reply to “Diagnostic accuracy of neuropathy tests in obese population remains elusive”
Our manuscript "Better diagnostic accuracy of neuropathy in obesity: A new challenge for neurologists" was performed to address a current gap in our understanding of measuring neuropathy in obese populations (Callaghan et al., 2018). We determined the diagnostic characteristics of several neuropathy measures for three of the most common types of peripheral neuropathy, namely distal symmetric polyneuropathy (DSP), small fiber neuropathy (SFN), and cardiac autonomic neuropathy (CAN). We studied morbidly obese patients prior to them participating in a weight management program and defined neuropathy using the Toronto consensus definition of neuropathy, which requires only clinical information (Dyck et al., 2011).
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Diagnostic accuracy of neuropathy tests in obese population remains elusive
In their article entitled 'Better diagnostic accuracy of neuropathy in obesity' Callaghan et al. pose an intriguing question, namely 'how well do the tools we use work for the actual population in which they are needed?' (Callaghan et al., 2018). With an ever expanding, obese and often diabetic or pre-diabetic population, this question is timely and critically important to answer; however, the methods used in their study and the conclusions are disappointingly flawed.
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An improved methodology for intraoperative monitoring of the lateral spreading response during surgery for hemifacial spasm
Lee and colleagues in their study published in this issue of Clinical Neurophysiology collected an impressive number of 486 patients with hemifacial spasm (Lee et al., this issue). They presented an improved classic method of neurophysiologic detection of the lateral spreading response (LSR), during surgery for microvascular decompression for relieving of hemifacial spasm.
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Review of Economic Value Drivers of the Treatment of Overactive Bladder
Abstract
Overactive bladder (OAB) is a symptom-driven condition with economic burden estimated to be on the order of several hundred dollars or euros per patient in some North American and European countries. This work reviews recently published economic models to evaluate how health states are defined, what cost components are considered, and what utility values are used to estimate the cost effectiveness of OAB pharmacotherapies, botulinum toxin, or sacral neuromodulation. It was found that no clear standard exists for determining OAB health states, although most were defined by some measure of incontinence frequency. Costs of physician visits and incontinence pads were included in nearly all models; however, OAB-associated depression and nursing home costs were rarely included, despite being large cost drivers of global economic burden studies. Utility values used in the models ranged from 0.544 to 0.933, highlighting the uncertainty associated with how OAB patients value health-related quality of life. More research is warranted so that health states providing delineations among OAB symptom severity and quality of life are clinically and economically meaningful as well as meaningful to affected patients.
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SETD2 Haploinsufficiency for Microtubule Methylation is an Early Driver of Genomic Instability in Renal Cell Carcinoma
Loss of the short arm of chromosome 3 (3p) occurs early in >95% of clear cell renal cell carcinoma (ccRCC). Nearly ubiquitous 3p loss in ccRCC suggests haploinsufficiency for 3p tumor suppressors as early drivers of tumorigenesis. We previously reported methyltransferase SETD2, which trimethylates H3 histones on lysine 36 (H3K36me3) and is located in the 3p deletion, to also trimethylate microtubules on lysine 40 (αTubK40me3) during mitosis, with αTubK40me3 required for genomic stability. We now show that mono-allelic, Setd2-deficient cells retaining H3K36me3 but not αTubK40me3 exhibit a dramatic increase in mitotic defects and micronuclei count with increased viability compared to bi-allelic loss. In SETD2-inactivated human kidney cells, rescue with a pathogenic SETD2 mutant deficient for microtubule (αTubK40me3) but not histone (H3K36me3) methylation replicated this phenotype. Genomic instability (micronuclei) was also a hallmark of patient-derived cells from ccRCC. These data show the SETD2 tumor suppressor displays a haploinsufficiency phenotype disproportionately impacting microtubule methylation and serves as an early driver of genomic instability.
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SETD2 is recurrently mutated in whole-exome sequenced canine osteosarcoma.
Osteosarcoma (OSA) is a debilitating bone cancer that affects humans, especially children and adolescents. A homologous form of OSA spontaneously occurs in dogs, and its differential incidence observed across breeds allows for the investigation of tumor mutations in the context of multiple genetic backgrounds. Using whole-exome sequencing and dogs from three susceptible breeds (22 golden retrievers, 21 Rottweilers, and 23 greyhounds), we found that OSA tumors show a high frequency of somatic copy number alterations (SCNA) affecting key oncogenes and tumor suppressor genes. The across-breed results are similar to what has been observed for human OSA, but the disease frequency and somatic mutation counts vary in the three breeds. For all breeds, three mutational signatures (one of which has not been previously reported), and eleven significantly mutated genes were identified. TP53 was the most frequently altered gene (83% of dogs have either mutations or SCNA in TP53), recapitulating observations in human OSA. The second most frequently mutated gene, histone methyltransferase SETD2, has known roles in multiple cancers, but has not previously been strongly implicated in OSA. This study points to the likely importance of histone modifications in OSA and highlights the strong genetic similarities between human and dog OSA, suggesting that canine OSA may serve as an excellent model for developing treatment strategies in both species.
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MIR142 loss-of-function mutations derepress ASH1L to increase HOXA gene expression and promote leukemogenesis
Point mutations in the seed sequence of miR-142-3p are present in a subset of AML and in several subtypes of B cell lymphoma. Here we show that mutations associated with AML result both in loss of miR-142-3p function and in decreased miR-142-5p expression. Mir142 loss altered the hematopoietic differentiation of multipotent hematopoietic progenitors, enhancing their myeloid potential while suppressing their lymphoid potential. During hematopoietic maturation, loss of Mir142 increased Ash1l protein expression and consequently resulted in the aberrant maintenance of Hoxa gene expression in myeloid-committed hematopoietic progenitors. Mir142 loss also enhanced the disease-initiating activity of IDH2 mutant hematopoietic cells in mice. Together these data suggest a novel model in which miR-142, through repression of ASH1L activity, plays a key role in suppressing HOXA9/A10 expression during normal myeloid differentiation. AML-associated loss-of-function mutations of MIR142 disrupt this negative signaling pathway, resulting in sustained HOXA9/A10 expression in myeloid progenitors/myeloblasts and ultimately contributing to leukemic transformation.
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The autotaxin - lysophosphatidic acid axis promotes lung carcinogenesis
Pathogenesis and progression of lung cancer (LC) are governed by complex interactions between the environment and host genetic susceptibility, which is further modulated by genetic and epigenetic changes. Autotaxin (ATX, ENPP2) is a secreted glycoprotein that catalyzes the extracellular production of lysophosphatidic acid (LPA), a growth-factor-like phospholipid which is further regulated by phospholipid phosphatases (PLPP). LPA's pleiotropic effects in almost all cell types are mediated through at least six, G-protein coupled LPA receptors (LPAR) that exhibit overlapping specificities, widespread distribution, and differential expression profiles. Here we use both preclinical models of LC and clinical samples (from patients and healthy controls) to investigate the expression levels, activity and biological role of the above components of the ATX/LPA axis in LC. ENPP2 was genetically altered in 8% of LC patients, while increased ATX staining and activity were detected in patient biopsies and sera, respectively. Moreover, PLPP3 expression was consistently downregulated in LC patients. Comparable observations were made in the two most widely used animal models of LC, the carcinogen urethane (URE) -induced and the genetically engineered K-rasG12D-driven models, where genetic deletion of Enpp2 or Lpar1 resulted in disease attenuation, thus confirming a pro-carcinogenic role of LPA signaling in the lung. Expression profiling data analysis suggested that metabolic rewiring may be implicated in the pro-carcinogenic effects of the ATX/LPA axis in K-ras-G12D-driven LC pathogenesis.
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Five Strategies to Reduce Acute Care for Cancer Patients ID'd
THURSDAY, May 3, 2018 -- Five major strategies exist for reducing acute care for patients with cancer, according to a review published online April 17 in the Journal of Oncology Practice. Nathan R. Handley, M.D., from the University of Pennsylvania...
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Sleep Duration Linked to Health-Related QoL in Kidney Disease
THURSDAY, May 3, 2018 -- Sleep duration is associated with health-related quality of life among patients with chronic kidney disease (CKD), according to a study published online May 3 in the Clinical Journal of the American Society of...
https://ift.tt/2JPKD8B
Systemic Inflammation at Midlife May Up Risk of Later Frailty
THURSDAY, May 3, 2018 -- Those with systemic inflammation during midlife are more likely to have age-related frailty, according to a recent study published in The Journals of Gerontology: Series A. Keenan A. Walker, Ph.D., from Johns Hopkins...
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CTC Status Predicts RT Benefit in Early-Stage Breast Cancer
THURSDAY, May 3, 2018 -- Circulating tumor cell status is predictive of radiotherapy (RT) benefit in early-stage breast cancer, according to a study published online May 3 in JAMA Oncology. Chelain R. Goodman, M.D., Ph.D., from the Northwestern...
https://ift.tt/2JR3C2D
Midlife Transition Tied to Decreasing Stress in Women
THURSDAY, May 3, 2018 -- Self-reported stress decreases for most women as they transition through midlife, according to a recent study published in Women's Midlife Health. Elizabeth Hedgeman, Ph.D., from the University of Michigan in Ann Arbor, and...
https://ift.tt/2reBPlZ
The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology Guidelines for the Management of Patients with Cervical Cancer
Abstract
Background:
Despite significant advances in the screening, detection, and treatment of preinvasive cervical lesions, invasive cervical cancer is the fifth most common cancer in European women. There are large disparities in Europe and worldwide in the incidence, management, and mortality of cervical cancer.
Objective:
The European Society of Gynecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) jointly develop clinically relevant and evidence-based guidelines in order to improve the quality of care for women with cervical cancer across Europe and worldwide.
Methods:
The ESGO/ESTRO/ESP nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of cervical cancer (23 experts across Europe). To ensure that the guidelines are evidence based, the current literature identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 159 international reviewers, selected through ESGO/ESTRO/ESP and including patient representatives.
Results:
The guidelines cover comprehensively staging, management, and follow-up for patients with cervical cancer. Management includes fertility sparing treatment; stage T1a, T1b1/T2a1, clinically occult cervical cancer diagnosed after simple hysterectomy; early and locally advanced cervical cancer; primary distant metastatic disease; cervical cancer in pregnancy; and recurrent disease. Principles of radiotherapy and pathological evaluation are defined.
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Genomic status of MET potentiates sensitivity to MET and MEK inhibition in NF1-related malignant peripheral nerve sheath tumors
Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are highly resistant sarcomas that occur in up to 13% of individuals with Neurofibromatosis Type 1 (NF1). Genomic analysis of longitudinally collected tumor samples in a case of MPNST disease progression revealed early hemizygous microdeletions in NF1 and TP53, with progressive amplifications of MET, HGF, and EGFR. To examine the role of MET in MPNST progression, we developed mice with enhanced MET expression and Nf1 ablation (Nf1fl/KO;lox-stop-loxMETtg/+;Plp-creERTtg/+; referred to as NF1 MET). NF1-MET mice express a robust MPNST phenotype in the absence of additional mutations. A comparison of NF1-MET MPNSTs with MPNSTs derived from Nf1KO/+;p53R172H;Plp-creERTtg/+ (NF1-P53) and Nf1KO/+;Plp-creERTtg/+ (NF1) mice revealed unique Met, Ras, and PI3K signaling patterns. NF1-MET MPNSTs were uniformly sensitive to the highly selective MET inhibitor, capmatinib, whereas a heterogeneous response to MET inhibition was observed in NF1-P53 and NF1 MPNSTs. Combination therapy of capmatinib and the MEK inhibitor trametinib resulted in reduced response variability, enhanced suppression of tumor growth, and suppressed RAS/ERK and PI3K/AKT signaling. These results highlight the influence of concurrent genomic alterations on RAS effector signaling and therapy response to tyrosine kinase inhibitors. Moreover, these findings expand our current understanding of the role of MET signaling in MPNST progression and identify a potential therapeutic niche for NF1-related MPNSTs.
https://ift.tt/2JKLmIa
The paradox of hospice for caregivers of cancer patients
There is a plethora of research noting the challenges of caring for a loved one at the end of life, but is less is known about the timeline of caregivers' quality of life once a family enrolls in hospice care. Our prior work has shown that hospice caregivers can be successful involved in the care planning process, and do benefit from problem solving intervention.1,2 Numerous studies have tried to define and measure QoL, and most have found it to be less than desirable for family caregivers.3-5 The purpose of this study was to examine the trajectory of the QoL of family caregivers of hospice patients.
https://ift.tt/2FFCMba
Current allocation policy is favorable for patients with hepatocellular carcinoma waiting for liver transplantation
Patients with hepatocellular carcinoma (HCC) are a growing population of the transplantation waiting list (WL) for orthotopic liver transplantation (OLT). There is no consensus to prioritize these patients while on the WL.
https://ift.tt/2rkO53o
Randomized Trial of Verubecestat for Mild-to-Moderate Alzheimer’s Disease
Alzheimer's disease is characterized by the deposition of amyloid-beta (Aβ) aggregates and neurofibrillary tangles in the brain. The amyloid cascade hypothesis proposes that Aβ aggregates trigger the spreading of tau-related neurofibrillary tangles and subsequent neuronal degeneration. Aβ is…
https://ift.tt/2ju7hsh
Tolerability of sequential immune therapy and palliative radiotherapy to the cervical and thoracic spine
Abstract
Background
Use of immune therapy in metastatic cancers is rapidly expanding; however, its combination with commonly prescribed palliative radiation fields and doses is not well studied. To investigate this, we evaluated the toxicity of combined immune therapy and palliative cervical or thoracic spine radiotherapy.
Methods
Patients receiving cervical or thoracic spine radiation were evaluated based on administration of immune therapy within 30 days of radiation, use of 3D conformal or simpler techniques, and minimum 1 follow-up from end of treatment.
Results
Thirty patients were evaluable. Median survival following radiotherapy was 87 days. Pembrolizumab was most commonly combined with radiation (11 patients), then nivolumab (10), ipilimumab (3), and atezoliumab (2). Four patients (13.3%) had grade 3 toxicity requiring hospitalization (vomiting, esophagitis) and 12 patients (40%) had grade 2 toxicity (esophagitis, dysphagia). Ten patients (33.3%) had no toxicity. Three of the 4 patients with grade 3 toxicity received concurrent ipilimumab and nivolumab. Median dose was 30 Gy (range, 20–39) and fractions were 10 (range, 5–15). There was a trend toward increased grade 2+ toxicity with greater number of vertebral levels irradiated, 5.7 ± 3.4, vs. 4.0 ± 1.6 for none/grade 1 (P = .086). Seven of 7 patients exposed to ipilimumab developed grade 2+ toxicity vs 39% in the remaining patients (P = .007 for interaction). Radiation dose, fractionation, and timing of immune therapy were not significant contributors.
Conclusions
Combined immune therapy and radiotherapy for palliation of spine metastases suggests increased toxicity when a greater number of vertebral bodies are irradiated, or when combined immune therapy agents are utilized.
https://ift.tt/2waqKqX
Model to Determine the Optimal Dietary Elimination Strategy for Treatment of Eosinophilic Esophagitis
Elimination diets are effective treatments for eosinophilic esophagitis (EoE), but foods that activate esophagitis are identified empirically, via a process that involves multiple esophagogastroduodenoscopies (EGDs). No optimized approach has been developed to identify foods that activate EoE. We aimed to compare clinical strategies to provide data to guide treatment.
https://ift.tt/2ritUUx
(OA10) Patterns of Care and Factors Predictive of Overall Survival In Metastatic Rectal Cancer
We aimed to investigate the patterns of care and overall survival (OS) for metastatic rectal cancer patients treated with chemotherapy, radiation therapy (RT), or with a multimodality approach, utilizing a large national registry of patients.
https://ift.tt/2HMYuAd
(P16) Hyperfractionated Abdominal Reirradiation for Gastrointestinal Malignancies
We sought to determine the role of abdominal reirradiation for patients presenting with recurrent or new primary gastrointestinal (GI) malignancies, as the role of abdominal reirradiation in this setting remains undefined. At our institution, we have established a hyperfractionated, accelerated reirradiation regimen consisting of 39 Gray (Gy) in 26 twice-daily fractions when reirradiation is desired for pelvic malignancies. We sought to determine the toxicity and efficacy of this reirradiation regimen for tumors in the abdomen.
https://ift.tt/2IeT0xt
(P14) Cost Effectiveness of Radiation and Chemotherapy for High-Risk Low Grade Glioma
The standard of care treatment for maximally resected, high risk (≥ 40 years old or sub-totally resected) low grade glioma (LGG) patients was established by RTOG 9802, which showed an overall survival (OS) of 13.3 years for patients treated with radiotherapy (RT) + PCV (procarbazine, lomustine [CCNU], vincristine) chemotherapy compared to 7.8 years for RT alone. In the era of value-based health care, cost-effectiveness analyses (CEA) have the potential to inform coverage decisions and patient care.
https://ift.tt/2HR3uQf
(P18) Is Bigger Better? The effect of Cylinder Diameter on Dosimetric Coverage in Vaginal Cuff Brachytherapy
Vaginal cuff brachytherapy is a common adjuvant treatment in a variety of gynecologic malignancies. Various vaginal cylindrical applicators can be used to perform vaginal brachytherapy; however, the most common approach is to use a vaginal cylinder. As a general principle, radiation oncologists are taught to use the largest diameter that can be comfortably used. The larger the diameter, the more the vagina is thinned facilitating a better dose to the target tissues. A larger diameter also places the target further from the radiation source.
https://ift.tt/2IcduqA
(P15) Rectal Cancer in Patients Less Than 50 Years Old: Presenting Symptoms, Staging and Treatment Decisions in a Single Institution
There is a well-documented increase in rectal cancers among younger patients with little understanding of their clinical presentation, baseline characteristics and treatment strategies. The aim of this study is to characterize the population of young patients (age less than 50) diagnosed with rectal cancer in our institution.
https://ift.tt/2HPYgnT
(OA08) Pathologic Response to Neoadjuvant Chemotherapy and Chemoradiation in Borderline Resectable Adenocarcinoma of the Pancreas
We sought to investigate the efficacy of neoadjuvant chemotherapy (CT) followed by chemoradiation (CRT) followed by surgery in borderline resectable pancreatic cancer (BRPC).
https://ift.tt/2HOfhyC
(OA04) Patterns of Failure After Postoperative Radiation Therapy for Locally Advanced NSCLC: Implications for Shifting Toward More Conformal Radiation Fields
Over the past decade, postoperative radiation therapy (PORT) volumes in locally advanced NSCLC have largely shifted from whole mediastinum to conformal fields as specified in the phase III Lung Adjuvant Radiotherapy Trial (Lung ART) trial. However, limited data is available on how this transition will affect locoregional recurrence rates (LRR) and overall survival (OS). We thus compared patterns of failure, survival outcomes, and toxicity with whole mediastinum (WM) radiation therapy vs. high-risk (HR) conformal fields in the postoperative setting.
https://ift.tt/2HOb2Hg
The Relationship Between Liver Enzymes and Insulin Resistance in Type 2 Diabetes Patients with Nonalcoholic Fatty Liver Disease
Horm Metab Res
DOI: 10.1055/a-0603-7899
Non-alcoholic fatty liver disease (NAFLD) is prevalent worldwide, especially in patients with type 2 diabetes. Liver enzymes are the main warning signs of liver injury and insulin resistance (IR) is critical to NAFLD. This study was aimed to investigate the association between liver enzymes and insulin resistance in type 2 diabetes patients with NAFLD. Data from 212 diabetes patients with NAFLD were analyzed, including 118 males and 94 females who received care from 2014 to 2015. The patients were divided into three groups by severity (mild n=87, moderate n=89, severe n=36). All patients underwent standard clinical and laboratory examinations. Liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transferase (GGT) were measured, serum fasting glucose and serum fasting insulin were obtained. IR was assessed using the homeostasis model assessment insulin resistance index (HOMA-IR). Age, sex, and BMI did not significantly differ in patients (p>0.05). Compared with normal levels, elevated ALT and AST were associated with a higher HOMA-IR (p=0.0035, p=0.0096, respectively). HOMA-IR did not significantly differ (p>0.05) between patients with normal and elevated GGT. HOMA-IR increased as the levels of liver enzymes increased, and each enzyme showed a significant association with HOMA-IR (p=0.0166, p<0.0001, and p <0.0001). HOMA-IR differs between normal and elevated ALT and AST. Liver enzymes are associated with HOMA-IR in type 2 diabetes patients with NAFLD. These findings can help evaluate the degree of IR and hepatocellular steatosis in patients and prevent the progression of type 2 diabetes and NAFLD in clinical practice.
[...]
© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
https://ift.tt/2waewPf
Relationship Between the Brain Natriuretic Peptide (BNP) Level and Prognosis of Diabetic Nephropathy with Microalbuminuria: A 7-Year Follow-Up Study
Horm Metab Res
DOI: 10.1055/a-0603-3792
The aim of the study was to examine the relationship between the brain natriuretic peptide (BNP) level and prognosis of diabetic nephropathy. The subjects were 100 Japanese outpatients with type 2 diabetes mellitus with microalbuminuria. Associations between metabolic parameters at baseline, including BNP, and prognosis of diabetic nephropathy (progression of diabetic nephropathy, cardiovascular events, and death) were examined for 7 years. In Cox proportional hazard analysis, HbA1c, albumin-creatinine ratio (ACR) and BNP were identified as significant factors for progression of diabetic nephropathy (p=0.033, p=0.037, and p=0.044, respectively), BNP was identified as significant factor for cardiovascular events (p=0.046), and estimated glomerular filtration rate (eGFR) and BNP were identified as significant factors for death (p=0.046 and p=0.048, respectively). In Kaplan–Meier analysis, risks of progression of diabetic nephropathy, cardiovascular events, and death were significantly different between patients with a low and a high BNP level (p=0.046, p=0.002, and p=0.025, respectively). ROC curve analysis gave cutoff values for BNP of 14.9 pg/ml for progression of diabetic nephropathy, 16.3 pg/ml for cardiovascular events, and 17.6 pg/ml for death (p=0.047, p=0.035, p=0.018, respectively). In conclusion, the BNP level is associated with prognosis in diabetic nephropathy.
[...]
© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
https://ift.tt/2IfOYVK
Dietary Inflammatory Index and its Association with the Risk of Cardiovascular Diseases, Metabolic Syndrome, and Mortality: A Systematic Review and Meta-Analysis
Horm Metab Res
DOI: 10.1055/a-0596-8204
Findings from previous studies on the association between the Dietary Inflammatory Index (DII) and the risk of chronic diseases and mortality have been inconsistent. We aimed to summarize studies on the association of the DII and the risk for cardiovascular disease (CVD), metabolic syndrome (MetS), and mortality in a systematic review and meta-analysis. We performed a systematic search in PubMed/Medline, Web of Knowledge, and Scopus databases for relevant studies written in English and published until 31 December 2017. Studies that reported the relative risk (RR), odd ratio (OR) or hazard ratio (HR) for the most pro-inflammatory versus the most anti-inflammatory diets were included. Finally, 17 studies [CVD (n=6), MetS (n=5), mortality (n=6)] were included for systematic review and meta-analysis. Findings indicated a trend toward a positive relationship between the DII and the risk for CVD (pooled RR: 1.35; 95% CI: 1.13, 1.60; I2: 28.6%, p=0.21), all-cause mortality (pooled HR: 1.21; 95% CI: 1.09, 1.35; I2: 72.6%, p=0.003), CVD mortality (pooled HR: 1.30, 95% CI: 1.07, 1.57; I2: 74.0%, p=0.009) and cancer mortality (pooled HR: 1.28; 95% CI: 1.07, 1.53; I2: 62.5%, p=0.03). However, no significant association was found between the DII and the risk for MetS (pooled RR: 1.01; 95% CI: 0.82, 1.24; I2: 32.6%, p=0.20). Although in the current meta-analysis the most pro-inflammatory diet versus the most anti-inflammatory diet was not associated with the risk of MetS, we observed a substantial association between the DII and the risk for CVD and all types of mortality. However, further cohort studies in different populations are needed to clarify this association.
[...]
© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
https://ift.tt/2HR4tQq
Mineralocorticoid Receptor Blockers and Aldosterone to Renin Ratio: A Randomized Controlled Trial and Observational Data
Horm Metab Res
DOI: 10.1055/a-0604-3249
Current guidelines recommend to withdraw mineralocorticoid receptor (MR) blocker treatment for at least 4 weeks when measuring the aldosterone to renin ratio (ARR) as a screening test for primary aldosteronism (PA). We aimed to evaluate the effect of MR blocker treatment on ARR and its components, plasma aldosterone concentration (PAC), and direct renin concentration (DRC). First, we performed a post-hoc analysis of the effect of eplerenone on parathyroid hormone levels in primary hyperparathyroidism (EPATH) study, a randomized controlled trial (RCT) in 110 patients with primary hyperparathyroidism (pHPT). Patients were 1:1 randomly assigned to receive either 25 mg eplerenone once daily (up-titration after 4 weeks to 50 mg/day) or placebo for 8 weeks. Second, we measured the ARR in 4 PA patients from the Graz Endocrine Causes of Hypertension Study (GECOH) before and after MR blocker treatment. Ninety-seven participants completed the EPATH trial, and the mean treatment effect (95% confidence interval) for log(e)ARR was 0.08 (–0.32 to 0.48) ng/dl/μU/ml (p=0.694). The treatment effect was 0.71 (0.47 to 0.96; p<0.001) ng/dl for log(e)PAC and 0.64 (0.19 to 1.10; p=0.006) μU/ml for log(e)DRC, respectively. In the 4 PA patients, the ARR decreased from 11.24±3.58 at baseline to 2.70±1.03 (p=0.013) ng/dl/μU/ml after MR blocker treatment. In this study with limited sample size, MR blocker treatment did not significantly alter the ARR in pHPT patients but significantly reduced the ARR in PA patients. Diagnostic utility of ARR and its components for PA diagnostics under MR blocker treatment warrants further study.
[...]
© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
https://ift.tt/2HMYf8h
An international, multicenter, comparative trial of EUS-guided gastrogastrostomy-assisted ERCP versus enteroscopy-assisted ERCP in patients with Roux-en-Y gastric bypass anatomy
ERCP is challenging in patients with Roux-en-Y gastric bypass (RYGB) anatomy. EUS-guided gastrogastrostomy (GG) creation is a promising novel technique to access the excluded stomach in order to facilitate conventional ERCP. We aimed to compare procedural outcomes and adverse events (AEs) between EUS-guided gastrogastrostomy-assisted ERCP (EUS-GG-ERCP) and enteroscopy assisted ERCP (e-ERCP) in patients with RYGB.
https://ift.tt/2wgOWrw
Trends in the timing of inpatient ERCP relative to cholecystectomy: a nationwide database studied longitudinally
ERCP has largely replaced common bile duct exploration for therapy of common bile duct pathology, yet its use as a purely diagnostic test has declined. Among inpatients, we hypothesized that timing between ERCP and cholecystectomy (CCY) have changed. The objectives were to measure temporal trends in the timing between inpatient ERCP and CCY, and to examine factors associated with delays.
https://ift.tt/2JOJdeA
Primary Care and Home Visiting Utilization Patterns among At-Risk Infants
To describe well child care (WCC) utilization in the first year of life among at-risk infants, and the relationship to home visiting enrollment.
https://ift.tt/2FFrQun
"Slime" May Not be so Benign: A Cause of Hand Dermatitis
A 9-year-old girl with no significant past medical history presented with a pruritic hand dermatitis of 5 months' duration. The onset of the dermatitis coincided with her playing with homemade Borax-containing "slime," and as a consequence of this eruption, she switched to detergent-containing slime. Her dermatitis persisted despite frequent emolliation. She was treated empirically for scabies and for culture-positive Staphylococcus aureus infection with a complete course of cephalexin and mupirocin ointment, without complete resolution of her skin findings, which prompted a dermatology referral.
https://ift.tt/2FFlprg
A Giant Ovarian Cyst in an Adolescent
A 12-year-old postmenarchal girl was admitted for evaluation of a 2-month history of increasing abdominal swelling and constipation. On physical examination, a smooth and firm mass filling all the abdomen was palpable. Ultrasound examination showed a giant cystic mass arising from the pelvis; magnetic resonance imaging (Figure) confirmed the finding. Blood tests and tumor markers (β-human choriogonadotropin, CA 19-9, CA-125, and carcinoembryonic antigen) were all within normal range. Suspecting either an ovarian or a paraovarian or a mesenteric cyst, surgical exploration was performed through an umbilical incision.
https://ift.tt/2FFrT9x
Deep Medullary Veins and Brain Injury
A term male neonate appropriate for gestational age was admitted to the neonatal intensive care unit with large bilateral inguinal hernias. He was the first twin of nonconsanguineous parents born by caesarean delivery after an uneventful assisted reproductive technology pregnancy. At day 6 of life he presented with fever, irritability, bulging anterior fontanelle, and seizures while awaiting surgery. A laboratory workup revealed elevated C-reactive protein and pleocytosis, high protein, and low glucose levels in cerebrospinal fluid (CSF).
https://ift.tt/2joNUk6
A Low-Cost and Simple Genetic Screening for Cystic Fibrosis Provided by the Brazilian Public Health System
Cystic fibrosis newborn screening was implemented in Brazil by the Public Health System in 2012. Because of cost, only 1 mutation was tested - p.Phe508del. We developed a robust low-cost genetic test for screening 11 CFTR gene mutations with potential use in developing countries.
https://ift.tt/2KAKOWG
Hyperglycemia in Extremely Preterm Infants—Insulin Treatment, Mortality and Nutrient Intakes
To explore the prevalence of hyperglycemia and the associations between nutritional intakes, hyperglycemia, insulin treatment, and mortality in extremely preterm infants.
https://ift.tt/2FFllI2
Do Functional Gastrointestinal Disorders Affect Growth and Nutrition?
Functional gastrointestinal disorders (FGIDs) are common in children of all ages and dominate pediatric outpatient practice. Symptoms in FGIDs cannot be attributed to structural or biochemical abnormalities; thus, diagnosis relies solely on history, physical examination, and symptom-based criteria.1 The prevalence of FGIDs is increasing in the pediatric population, with infant regurgitation the most common form in infants and functional constipation the most common among toddlers, children, and adolescents.
https://ift.tt/2jsCTOV
The Erythropoietin Promoter Variant rs1617640 Is Not Associated with Severe Retinopathy of Prematurity, Independent of Treatment with Erythropoietin
In this case-control study, the erythropoietin (EPO) promoter variant s1617640, linked to high intravitreal EPO concentrations and increased risk of diabetic retinopathy, was not associated with severe retinopathy of prematurity. This finding was observed both in infants with and without recombinant EPO administration.
https://ift.tt/2KyeXG3
Nintedanib is active in malignant pleural mesothelioma cell models and inhibits angiogenesis and tumor growth in vivo
Purpose: Malignant pleural mesothelioma (MPM) is an aggressive thoracic tumor type with limited treatment options and poor prognosis. The angiokinase inhibitor nintedanib has shown promising activity in the LUME-Meso phase 2 MPM trial and thus is currently being evaluated in the confirmatory LUME-Meso phase 3 trial. However, the anti-MPM potential of nintedanib has not been studied in the preclinical setting. Experimental design: We have examined the antineoplastic activity of nintedanib in various in vitro and in vivo models of human MPM. Results: Nintedanib's target receptors were (co)expressed in all the 20 investigated human MPM cell lines. Nintedanib inhibited MPM cell growth in both short- and long-term viability assays. Reduced MPM cell proliferation and migration and the inhibition of Erk1/2 phosphorylation were also observed upon nintedanib treatment in vitro. Additive effects on cell viability were detected when nintedanib was combined with cisplatin, a drug routinely used for systemic MPM therapy. In an orthotopic mouse model of human MPM, survival of animals receiving nintedanib per os showed a favorable trend, but no significant benefit. Nintedanib significantly reduced tumor burden and vascularization and prolonged the survival of mice when it was administered intraperitoneally. Importantly, unlike bevacizumab, nintedanib demonstrated significant in vivo antivascular and antitumor potential independently of baseline VEGF-A levels. Conclusions: Nintedanib exerts significant antitumor activity in MPM both in vitro and in vivo. These data provide preclinical support for the concept of LUME-Meso trials evaluating nintedanib in patients with unresectable MPM.
https://ift.tt/2KyfFmH
Inside EMS Podcast: Why there are exceptions to every EMS rule
Our co-hosts discuss changing the focus of EMS education in order to teach today's EMT and paramedic students
https://ift.tt/2jqIbdJ
Clinico-pathological Features of PIK3CA Mutation in HER2-Positive Breast Cancer of Indian Population
Abstract
PIK3CA pathway is one of the important signaling pathways in cells, which is involved in cell proliferation, cell survival, motility, and growth. Mutation in PIK3CA gene negatively effects to anti-HER2 therapy in breast cancer patients. PIK3CA gene of HER2-positive breast cancers associated with reduced sensitivity to neoadjuvant therapy. In this study, we assessed the frequency of PIK3CA mutations and influence of PIK3CA mutations on patient survival in a series of HER2-positive breast cancer patients. PIK3CA mutations were assessed by pyrosequencing and next generation sequencing in 107 HER2-positive breast cancer patients of a tertiary Cancer Centre of India from Jan 2012 to Jun 2013 with minimum follow-up of 3 years. We found PIK3CA mutations in 26 tumors (24.2%) of which 5 were in exon 9, 20 were in exon 20, and 1 was in both exon 9 and 20. In exon 9, the mutation c.1634A>G was found in 4 cases and mutation c.1636C>A was found in 2 cases. In exon 20, the mutation c.3140A>G was found in 15 cases and c.3140A>T was found in 6 cases. The outcome between PIK3CA mutated versus PIK3CA wild type was significant showing p value 0.014. Overall survival of mutation and treatment with herceptin, mutation with other chemotherapy treatment in both early breast cancer (EBC), and locally advanced breast cancer (LABC) showed significant p value 0.037 and 0.044 respectively. In conclusion, we identified 24.2% somatic mutation of PIK3CA in HER2-positive breast cancer patients. PIK3CA mutation is significantly associated with ER-positive tumors. The frequency and distribution pattern reported in this study is similar to the global report. Overall survival of PIK3CA mutation is slightly lower but in patients who received herceptin with PIK3CA mutation showed better clinical outcome.
https://ift.tt/2jr0zmH
Mindfulness-Based Interventions for Hematology and Oncology Patients with Pain
Pain is a reality for approximately half of all of patients with cancer and can negatively affect patient cognitive and emotional states, resulting in "total pain." Total pain may not respond to pharmacologic interventions and may pave the way for the onset of suffering, where suffering is defined as physical pain accompanied by negative cognitive interpretations. Mindfulness-based interventions provide an alternate interpretive framework for both pain and suffering and may lessen a patient's experience of pain. Mindfulness-based interventions have the potential to alter a patient's relationship to pain, reducing pain catastrophizing, and enhancing patient reported overall well-being.
https://ift.tt/2KAEChh
Complex Cancer Pain Assessment
Pain is widespread, multidimensional, and one of the most distressing symptoms patients with cancer face. Pain assessment is the foundation to optimal pain management. Despite evidence-based practice guidelines, inadequate pain assessment is a barrier. Patients should be routinely screened for pain at each encounter. If new, worsening, or persistent pain is present, a comprehensive pain assessment and reassessment should be regularly performed and documented to communicate the pain problem. Patient self-report of pain is the gold standard even in those who are nonverbal or cognitively impaired. Clinicians should follow the Hierarchy of Pain Assessment Framework to guide pain assessment approaches.
https://ift.tt/2HLsJHu
Safe Opioid Use
Opioids are highly effective for cancer pain but are associated with multiple adverse effects and risk of addiction. This article provides a synopsis on the management of various opioid-related adverse effects and strategies to minimize aberrant opioid use in patients who have cancer. Many adverse effects can be effectively managed. Some patients on chronic opioid therapy may demonstrate aberrant behaviors suggestive of opioid misuse or diversion. Through intensive education, longitudinal monitoring, early identification, and timely management, clinicians can optimize the risk to benefit ratio to support safe opioid use.
https://ift.tt/2HLD5r8
Interventional Anesthetic Methods for Pain in Hematology/Oncology Patients
This article reviews anesthetic interventional approaches to the management of pain in hematology and oncology patients. It includes a discussion of single interventions including peripheral nerve blocks, plexus injections, and sympathetic nerve neurolysis, and continuous infusion therapy through implantable devices, such as intrathecal pumps, epidural port-a-caths, and tunneled catheters. The primary objective is to inform members of hematology and oncology care teams regarding the variety of interventional options for patients with cancer-related pain for whom medical pain management methods have not been effective.
https://ift.tt/2Ku9nVf
Key Components of Pain Management for Children and Adults with Sickle Cell Disease
Sickle cell disease pain manifests as severe acute pain episodes and a debilitating chronic pain syndrome. Acute pain episodes are the most common reason for health care use; however, acute pain episodes are also frequently managed at home. Chronic pain syndrome develops in 30% to 40% of individuals with sickle cell disease, with an increasing incidence and severity with age. We review the critical aspects of pain management that are integral to the comprehensive approach to sickle cell disease pain and are rooted in the biopsychosocial model. The review focuses on opioid pharmacology and psychosocial comorbidities.
https://ift.tt/2rlwQiv
Oncology Acupuncture for Chronic Pain in Cancer Survivors
Chronic pain syndromes associated with cancer treatment are common but difficult to manage. The American Society of Clinical Oncology recently published a practice guideline to address the unmet needs of cancer survivors, Management of Chronic Pain in Survivors of Adult Cancers, which stresses the importance of implementing integrative therapies including acupuncture. This review focuses on randomized clinical trials of acupuncture for chronic pain in cancer survivors, including its use in chemotherapy-induced peripheral neuropathy, aromatase inhibitor-associated arthralgia, and post neck dissection pain, and provides future directions of oncology acupuncture research in cancer survivorship. The features of oncology acupuncture are also discussed.
https://ift.tt/2Kvul5U
Erratum
In the article on "Emerging Therapies" appearing in the April 2018 issue of Hematology/Oncology Clinics of North America (Volume 32, Issue 2), the following errors were made on page 347 in Table 1:
https://ift.tt/2riGfr7
Spiritual Considerations
Spiritual issues play a prominent role for patients with cancer. Studies have demonstrated a positive connection between a patient's spirituality and health outcomes, including quality of life, depression and anxiety, hopefulness, and the ability to cope with illness. Spiritual or existential distress is prominent in patients with cancer. Models are described that identify ways for clinicians to identify or diagnose spiritual or existential distress, and to attend to that distress. It is critical that all clinicians assess for spiritual distress as part of a routine distress assessment, identify appropriate treatment strategies, and work closely with trained spiritual care professionals.
https://ift.tt/2HNWEyK
Older Adults Agree Sex Is Important Part of Relationships
THURSDAY, May 3, 2018 -- Most older adults agree that sex is an important part of a romantic relationship at any age, according to the National Poll on Healthy Aging. Preeti Malani, M.D., from the University of Michigan in Ann Arbor, and colleagues...
https://ift.tt/2js56Fz
Many Patients Have Unused Opioids After Spine, Joint Surgery
THURSDAY, May 3, 2018 -- Many patients undergoing elective same-day or inpatient joint and spine surgery have unused opioids at one- and six-month follow-up, according to a study published online April 17 in Anesthesia & Analgesia. Mark C....
https://ift.tt/2HP1E2b
No Clinical Benefit Seen for Bath Emollients in Childhood Eczema
THURSDAY, May 3, 2018 -- For children with eczema, there is no clinical benefit for adding emollient bath additives, according to a study published online May 2 in The BMJ. Miriam Santer, M.B.B.Chir., Ph.D., from the University of Southampton in the...
https://ift.tt/2rhlNHR
Mortality Risk Persists for Cancer Tied to Prenatal DES Exposure
THURSDAY, May 3, 2018 -- Diethylstilbestrol (DES)-related clear-cell adenocarcinoma of the vagina and cervix is associated with increased risk of death, even in older women, according to a letter to the editor published in the May 3 issue of the New...
https://ift.tt/2HP1Bn1
Lightning Can Affect Deep Brain Stimulation Devices
THURSDAY, May 3, 2018 -- Lightning, which can result in strong electromagnetic fields (EMFs), can interfere with deep brain stimulation (DBS) devices, according to a case report published online May 1 in the Journal of Neurosurgery. Noting that DBS...
https://ift.tt/2joM1no
Reproductive Markers Associated With Risk of Diabetes
THURSDAY, May 3, 2018 -- Markers of reproductive history, including age of menarche and parity, may be tied to future diabetes risk in women with a body mass index (BMI) ≥25 kg/m², according to a study published in Diabetes, Obesity and...
https://ift.tt/2HP1yaP
Reporting Outcomes Per Surgeon Tied to Drop in CRC Sx Mortality
THURSDAY, May 3, 2018 -- The introduction of public reporting of surgeon specific 90-day postoperative mortality in elective colorectal cancer surgery is associated with a reduction in observed 90-day mortality, according to a study published online...
https://ift.tt/2rofdj9
Gender Disparity Observed in Cancer Genetic Testing in the U.S.
THURSDAY, May 3, 2018 -- Specific demographic groups have lower cancer genetic testing, including unaffected men compared with unaffected women, according to a research letter published online April 26 in JAMA Oncology. Kimberly K. Childers, from...
https://ift.tt/2HRrpiz.
Cystatin C Tied to Cumulative Hearing Impairment
THURSDAY, May 3, 2018 -- Reduced kidney function, estimated using cystatin C, is associated with 20-year cumulative incidence of hearing impairment (HI), according to a study published online April 26 in JAMA Otolaryngology-Head & Neck...
https://ift.tt/2riQfS6
Unit-Dose Packaging Cuts Accidental Peds Opioid Exposures
THURSDAY, May 3, 2018 -- The transition to use of buprenorphine products with unit-dose packaging (UDP) starting in 2010 correlated with a reduction in unintentional pediatric exposures to buprenorphine-naloxone, according to a study published...
https://ift.tt/2HNCSiZ
Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
Cyclin-dependent kinase 1 (Cdk1) is activated in the G2 phase of the cell cycle and regulates many cellular pathways. Here, we present a protocol for an in vitro kinase assay with Cdk1, which allows the identification of Cdk1-specific phosphorylation sites for establishing cellular targets of this important kinase.
https://ift.tt/2FGqz63
Novel Method of Plasmid DNA Delivery to Mouse Bladder Urothelium by Electroporation
We describe a novel method for the delivery of DNA plasmid into the urothelial cells of mouse bladder in vivo through urethra catheterization and electroporation. It offers a fast and convenient way for generating autochthonous mouse models of bladder diseases.
https://ift.tt/2KzuUfl
Chronophin regulates active vitamin B6 levels and transcriptomic features of glioblastoma cell lines cultured under non-adherent, serum-free conditions
Abstract
Background
The phosphatase chronophin (CIN/PDXP) has been shown to be an important regulator of glioma cell migration and invasion. It has two known substrates: p-Ser3-cofilin, the phosphorylated form of the actin binding protein cofilin, and pyridoxal 5′-phosphate, the active form of vitamin B6. Phosphoregulation of cofilin, among other functions, plays an important role in cell migration, whereas active vitamin B6 is a cofactor for more than one hundred enzymatic reactions. The role of CIN has yet only been examined in glioblastoma cell line models derived under serum culture conditions.
Results
We found that CIN is highly expressed in cells cultured under non-adherent, serum-free conditions that are thought to better mimic the in vivo situation. Furthermore, the substrates of CIN, p-Ser3-cofilin and active vitamin B6, were significantly reduced as compared to cell lines cultured in serum-containing medium. To further examine its molecular role we stably knocked down the CIN protein with two different shRNA hairpins in the glioblastoma cell lines NCH421k and NCH644. Both cell lines did not show any significant alterations in proliferation but expression of differentiation markers (such as GFAP or TUBB3) was increased in the knockdown cell lines. In addition, colony formation was significantly impaired in NCH644. Of note, in both cell lines CIN knockdown increased active vitamin B6 levels with vitamin B6 being known to be important for S-adenosylmethionine biosynthesis. Nevertheless, global histone and DNA methylation remained unaltered as was chemoresistance towards temozolomide. To further elucidate the role of phosphocofilin in glioblastoma cells we applied inhibitors for ROCK1/2 and LIMK1/2 to our model. LIMK- and ROCK-inhibitor treatment alone was not toxic for glioblastoma cells. However, it had profound, but antagonistic effects in NCH421k and NCH644 under chemotherapy.
Conclusion
In non-adherent glioblastoma cell lines cultured in serum-free medium, chronophin knockdown induces phenotypic changes, e.g. in colony formation and transcription, but these are highly dependent on the cellular background. The same is true for phenotypes observed after treatment with inhibitors for kinases regulating cofilin phosphorylation (ROCKs and LIMKs). Targeting the cofilin phosphorylation pathway might therefore not be a straightforward therapeutic option in glioblastoma.
https://ift.tt/2JOtzQm
Association of genetic polymorphisms CYP2A6*2 rs1801272 and CYP2A6*9 rs28399433 with tobacco-induced lung Cancer: case-control study in an Egyptian population
Abstract
Background
Several studies have reported the role of CYP2A6 genetic polymorphisms in smoking and lung cancer risk with some contradictory results in different populations. The purpose of the current study is to assess the contribution of the CYP2A6*2 rs1801272 and CYP2A6*9 rs28399433 gene polymorphisms and tobacco smoking in the risk of lung cancer in an Egyptian population.
Methods
A case-control study was conducted on 150 lung cancer cases and 150 controls. All subjects were subjected to blood sampling for Extraction of genomic DNA and Genotyping of the CYP2A6 gene SNPs (CYP2A6*2 (1799 T > A) rs1801272 and CYP2A6*9 (− 48 T > G) rs28399433 by Real time PCR.
Results
AC and CC genotypes were detected in CYP2A6*9; and AT genotype in CYP2A6*2. The frequency of CYP2A6*2 and CYP2A6*9 were 0.7% and 3.7% respectively in the studied Egyptian population. All cancer cases with slow metabolizer variants were NSCLC. Non-smokers represented 71.4% of the CYP2A6 variants. There was no statistical significant association between risk of lung cancer, smoking habits, heaviness of smoking and the different polymorphisms of CYP2A6 genotypes.
Conclusion
The frequency of slow metabolizers CYP2A6*2 and CYP2A6*9 are poor in the studied Egyptian population. Our findings did not suggest any association between CYP2A6 genotypes and risk of lung cancer.
https://ift.tt/2rhAomz
Analysis of cerebral blood flow and intracranial hypertension in critical patients with non-hepatic hyperammonemia
Abstract
Hyperammonemia in adults is generally associated with cerebral edema, decreased cerebral metabolism, and increased cerebral blood flow. The aim of this study was to evaluate the association between non-hepatic hyperammonemia and intracranial hypertension assessed by Doppler flowmetry and measurement of the optic nerve sheath. A prospective cohort study in critically ill patients hospitalized in intensive care units of a University Hospital between March 2015 and February 2016. Clinical data and severity scores were collected and the Glasgow coma scale was recorded. Serial serum ammonia dosages were performed in all study patients. Transcranial Doppler evaluation was carried out for the first 50 consecutive results of each stratum of ammonemia: normal (<35 μmol/L), mild hyperammonemia (≥35 μmol/L and < 50 μmol/L), moderate hyperammonemia (≥50 μmol/L and < 100 μmol/L), and severe hyperammonemia (≥100 μmol/L). The measurement of the optic nerve sheath was performed at the same time as the Doppler examination if the patient scored less than 8 on the Glasgow coma scale. There was no difference in flow velocity in the cerebral arteries between patients with and without hyperammonemia. Patients with hyperammonemia presented longer ICU stay. Optic nerve sheath thickness was higher in the group with severe hyperammonemia and this group presented an association with intracranial hypertension. Higher mortality was observed in the severe hyperammonemia group. There was an association between severe hyperammonemia and signs of intracranial hypertension. No correlation was found between ammonia levels and cerebral blood flow velocity through the Doppler examination.
https://ift.tt/2IaDjHz
National Association of EMS Physicians® recognizes National EMS Week with series of educational opportunities
OVERLAND PARK, Kan. — The National Association of EMS Physicians® (NAEMSP®) will recognize Emergency Medical Services (EMS) Week, May 20-26, to highlight the efforts of all first responders who answer the call, inclusive of more than 1,350 members. EMS Week brings together local communities and medical personnel to promote safety as well as honor the dedication of those who provide the ...
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Automated Slide Scanning and Segmentation in Fluorescently-labeled Tissues Using a Widefield High-content Analysis System
https://ift.tt/2FHo57s
Retroductal Nanoparticle Injection to the Murine Submandibular Gland
https://ift.tt/2KvYYIu
Measuring the Carotid to Femoral Pulse Wave Velocity (Cf-PWV) to Evaluate Arterial Stiffness
This protocol describes a method to standardize the measurements of carotid-femoral pulse wave velocity to evaluate arterial stiffness.
https://ift.tt/2FIpGdy
Association between different acute stroke therapies and development of post stroke seizures
Epilepsy is a major complication of stroke. We aimed to establish whether there is an association between intravenous thrombolysis, intra-arterial thrombolysis and post stroke seizure (PSS) development. Improv...
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Investigation of RNA Synthesis Using 5-Bromouridine Labelling and Immunoprecipitation
https://ift.tt/2KxbNCw
The "Motor" in Implicit Motor Sequence Learning: A Foot-stepping Serial Reaction Time Task
https://ift.tt/2riMnQ6
Sexual risk behaviour, sexual victimisation, substance use and other factors related to depression in men who have sex with men in Wenzhou, China: a cross-sectional study
Objectives
Men who have sex with men (MSM) are a marginalised population at high risk for a variety of mental health problems that may mutually facilitate HIV transmission. We assessed factors associated with depressive symptoms among MSM, which can provide some guidance for future mental health interventions with the MSM population for prevention of HIV infection and transmission.
MethodsA cross-sectional study was conducted in Wenzhou city, China using respondent-driven sampling (RDS) between December 2013 and June 2014. A face-to-face questionnaire survey was employed to collect information about mental and psychosocial health conditions and sexual behaviour characteristics among MSM. Bivariate and multivariable logistic regression analyses were used to identify factors associated with major depressive symptoms.
ResultsOf the 454 participants in the study, prevalence of major depressive symptoms was 34.6%. During the past 6 months, 85% had anal sex with men, and rate of consistent condom use during anal intercourse was 45.1%. Of the respondents, 16.1% reported suicidal ideation, 62.6% had a history of smoking and 41.4% had a history of drinking alcohol, of which 46.3% reported that they were once drunk. Drug use was reported in 3.7% of the sample. Adult sexual violence from same-sex partners was 7.9%, and 5.1% reported childhood sexual abuse. ARDS-weighted multivariable analysis showed that major depressive symptoms among MSM were associated with inconsistent condom use during anal sex with men, multiple oral male sexual partners, suicidal ideation, adult sexual violence from male partners and being once drunk in the past year.
ConclusionWe found high levels of depressive symptoms, unprotected sex and suicidal ideation among MSM. Comprehensive intervention strategies that combine psychological, behavioural and social aspects are needed to address the mental health issues of MSM, with special attention given to suicidality and high-risk behaviours in mental health and HIV prevention interventions.
https://ift.tt/2ricBlT
Light-moderate alcohol consumption and left ventricular function among healthy, middle-aged adults: the HUNT study
Objectives
To investigate the association between alcohol consumption and left ventricular (LV) function in a population with low average alcohol intake.
Design, setting and participantsA total of 1296 healthy participants, free from cardiovascular diseases, were randomly selected from the third wave of the Norwegian HUNT study (2006–2008) and underwent echocardiography. After validation of the inclusion criteria, 30 participants were excluded due to arrhythmias or myocardial or valvular pathology. Alcohol consumption, sociodemographic and major cardiovascular risk factors were assessed by questionnaires and clinical examination in the HUNT3. General linear models were used to analyse the cross-sectional associations between alcohol intake and LV indices.
Primary and secondary outcome measuresLV functional and structural indices were measured with tissue Doppler and speckle tracking echocardiography.
ResultsWe observed no associations between alcohol consumption and multivariable-adjusted LV functional indices. Excluding abstainers who reported regular alcohol consumption 10 years prior to the baseline did not change the results. Alcohol consumption was positively associated with LV mass indices (p<0.01 for linear trend of the means); there was no such association among participants with non-risky drinking characteristics (p=0.67 for linear trend of the means).
ConclusionsWe found no clear evidence that light–moderate alcohol consumption is associated with measures of LV function, although our results indicate that consumption, especially when marked by binge drinking, is progressively associated with greater LV mass.
https://ift.tt/2jrVNFy
Chronic Stress protection for postnatal dEpREssioN prEvention (SERENE): a protocol for an exploratory study
Introduction
The prevalence of postnatal depression (PND) is significant: reaching up to 20% in the general population. In mechanistic terms, the risk of PND lies in an interaction between a maternal psychophysiological vulnerability and a chronic environmental context of stress. On the one hand, repetition of stressor during pregnancy mimics a chronic stress model that is relevant to the study of the allostatic load and the adaptive mechanisms. On the other hand, vulnerability factors reflect a psychological profile mirroring mindfulness functioning (psychological quality that involves bringing one's complete and non-judgemental attention to the present experience on a moment-to-moment basis). This psychological resource is linked to protective and resilient psychic functioning. Thus, PND appears to be a relevant model for studying the mechanisms of chronic stress and vulnerability to psychopathologies.
In this article, we present the protocol of an ongoing study (started in May 2017).
Methods and analysisThe study is being carried out in five maternities and will involve 260 women. We aim to determine the predictive psychobiological factors for PND emergence and to provide a better insight into the mechanisms involved in chronic stress during pregnancy. We use a multidisciplinary approach that encompasses psychological resources and biophysiological and genetic profiles in order to detect relevant vulnerability biomarkers for chronic stress and the development of PND. To do so, each woman will be involved in the study from her first trimester of pregnancy until 12 months postdelivery.
Ethics and disseminationEthics approval was obtained from the Ile de France III Ethics Committee, France (2016-A00887-44). We aim to disseminate the findings through international conferences and international peer-reviewed journals.
Trial registration numberNCT03088319; Pre-results.
https://ift.tt/2HPeHkl
Effectiveness of a computerised system of patient education in clinical practice: a longitudinal nested cohort study
Introduction
Developing electronic health record information systems is an international trend for promoting the integration of health information and enhancing the quality of medical services. Patient education is a frequent intervention in nursing care, and recording the amount and quality of patient education have become essential in the nursing record. The aims of this study are (1): to develop a high-quality Patient Education Assessment and Description Record System (PEADRS) in the electronic medical record (2); to examine the effectiveness of the PEADRS on documentation and nurses' satisfaction (3); to facilitate communication and cooperation between professionals.
Methods and analysisA quasi-experimental design and random sampling will be used. The participants are nurses who are involved in patient education by using traditional record or the PEADRS at a medical centre. A prospective longitudinal nested cohort study will be conducted to compare the effectiveness of the PEADRS, including (1): the length of nursing documentation (2); satisfaction with using the PEADRS; and (3) the benefit to professional cooperation.
Ethics and disseminationPatient privacy will be protected according to Electronic Medical Record Management Practices of the hospital. This study develops a patient education digital record system, which would profit the quality of clinical practice in health education. The results will be published in peer-reviewed journals and will be presented at scientific conferences.
https://ift.tt/2jtPfpH
Measuring outcome differences associated with STEMI screening and diagnostic performance: a multicentred retrospective cohort study protocol
Introduction
Advances in ST-segment elevation myocardial infarction (STEMI) management have involved improving the clinical processes connecting patients with timely emergency cardiovascular care. Screening upon emergency department (ED) arrival for an early ECG to diagnose STEMI, however, is not optimal for all patients. In addition, the degree to which timely screening and diagnosis are associated with improved time to intervention and postpercutaneous coronary intervention outcomes, under more contemporary practice conditions, is not known.
MethodsWe present the methods for a retrospective multicentre cohort study anticipated to include 1220 patients across seven EDs to (1) evaluate the relationship between timely screening and diagnosis with treatment and postintervention clinical outcomes; (2) introduce novel measures for cross-facility performance comparisons of screening and diagnostic care team performance including: door-to-screening, door-to-diagnosis and door-to-catheterisation laboratory arrival times and (3) describe the use of electronic health record data in tandem with an existing disease registry.
Ethics and disseminationThe completion of this study will provide critical feedback on the quality of screening and diagnostic performance within the contemporary STEMI care pathway that can be used to (1) improve emergency care delivery for patients with STEMI presenting to the ED, (2) present novel metrics for the comparison of screening and diagnostic care and (3) inform the development of screening and diagnostic support tools that could be translated to other care environments. We will disseminate our results via publication and quality performance data sharing with each site. Institutional ethics review approval was received prior to study initiation.
https://ift.tt/2jv307X
'Treading water but drowning slowly: what are GPs experiences of living and working with mental illness and distress in England? A qualitative study
Objectives
This paper provides an in-depth account of general practitioners' (GPs) experiences of living and working with mental illness and distress, as part of a wider study reporting the barriers and facilitators to help-seeking for mental illness and burn-out, and sources of stress/distress for GP participants.
DesignQualitative study using in-depth interviews with 47 GP participants. The interviews were audio recorded, transcribed, anonymised and imported into NVivo V.11 to facilitate data management. Data were analysed using a thematic analysis employing the constant comparative method.
SettingEngland.
ParticipantsA purposive sample of GP participants who self-identified as: (1) currently living with mental distress, (2) returning to work following treatment, (3) off sick or retired early as a result of mental distress or (4) without experience of mental distress. Interviews were conducted face to face or over the telephone.
ResultsThe findings report GP participants' in-depth experiences of distress and mental illness with many recollecting their distressing experiences and significant psychological and physical symptoms relating to chronic stress, anxiety, depression and/or burn-out, and a quarter articulating thoughts of suicide. Many talked about their shame, humiliation and embarrassment at their perceived inability to cope with the stresses of their job and/or their symptoms of mental illness.
ConclusionsThese findings paint a concerning picture of the situation affecting primary care doctors, with participants' accounts suggesting there is a considerable degree of mental ill health and reduced well-being among GPs. The solutions are complex and lie in prevention and provision. There needs to be greater recognition of the components and cumulative effect of occupational stressors for doctors, such as the increasing workload and the clinical and emotional demands of the job, as well as the need for a culture shift within medicine to more supportive and compassionate work environments.
https://ift.tt/2HPezkR
Insulin sensitivity assessed using urine C peptide creatinine ratio (UCPCR) in pregnancy: cross-sectional analysis of an English multiethnic cohort
Aims
To assess urinary C peptide creatinine ratio (UCPCR) used in a modified Matsuda equation to measure insulin sensitivity (IS) in pregnancy.
Research and design methodsIn this cross-sectional study, two IS measurements were calculated in 73 pregnant women at ~28 weeks of gestation by two separate methods using modified Matsuda equations. The first using the 0 and 120 min serum C peptide concentration during a 75 g oral glucose tolerance test (OGTT) and the second using the 0 and 120 min UCPCR values. The calculated IS measurements from the two methodologies were evaluated using Person's test and linear regression analysis. The relationship between ISOGTT UCPCR and the fasting second void UCPCR and 120 min UCPCR was assessed using Pearson correlation and linear regression analysis after logarithmic transformation of the variables. Statistical analysis was performed using SPSS V.22.
ResultsThe IS measured using serum C peptide (ISOGTTc-pep) in the modified Matsuda equation correlated with the IS measurement using serum UCPCR (ISOGTT-UCPCR) (r 0.704, p<0.0001). A strong correlation was found between the ISOGTT-UCPCR and the fasting UCPCR (r –0.916, p<0.0001), displaying a hyperbolic relationship.
ConclusionThe UCPCR provides a practical methodology to assess IS and β-cell function in pregnancy.
https://ift.tt/2HRaVqw
Identifying Children with HEreditary Coagulation disorders (iCHEC): a protocol for a prospective cohort study
Introduction
It is challenging to obtain a reliable bleeding history in children who are referred for a suspected inherited bleeding disorder. Bleeding symptoms may be subtle as children face fewer haemostatic challenges compared with adults. In order to standardise bleeding histories, questionnaires have been developed, called bleeding assessment tools (BATs). Although it has been shown that high bleeding scores are associated with the presence of a mucocutaneous bleeding disorder, these BATs lack sensitivity, efficiency and flexibility in the paediatric setting. We developed a new BAT (the iCHEC (identifying Children with HEreditary Coagulation disorders) BAT) to improve on these characteristics. We aim to evaluate the diagnostic accuracy of the iCHEC BAT as a screening tool for children who are suspected for having a bleeding disorder.
Methods and analysisThis is a prospective cohort study. Children (age 0–18 years) suspected for a bleeding disorder who present at tertiary haematology clinics, and/or their parents/guardians, will be asked to complete the iCHEC BAT. Sensitivity was increased by inclusion of paediatric-specific bleeding symptoms and novel qualitative questions per bleeding symptom. Efficiency was improved by developing a self-administered (online) version of the questionnaire. Flexibility for changes in the bleeding phenotype of developing children was improved by including questions that define when the bleeding symptoms occurred in the past. The diagnostic accuracy of the specific bleeding items will be evaluated by receiver operator characteristic curves, using classification based on the results from laboratory assessment as the reference standard. Analysis of the discriminative power of individual bleeding symptoms will be assessed.
Ethics and disseminationThe study has been approved by the medical ethics committees of all participating centres in the Netherlands, Canada and the UK. All paediatric subjects and/or their parents/guardians will provide written informed consent. Study results will be submitted for publication in peer-reviewed journals.
https://ift.tt/2jpe4Dj
Gender disparities in first medical contact and delay in ST-elevation myocardial infarction: a prospective multicentre Swedish survey study
Objectives
Compare gender disparities in ST-elevation myocardial infarction (STEMI) regarding first medical contact (FMC) and prehospital delay times and explore factors associated with prehospital delay in men and women separately.
DesignCross-sectional study based on medical records and a validated questionnaire. Eligible patients were enrolled within 24 hours after admittance to hospital.
SettingPatients were included from November 2012 to January 2014 from five Swedish hospitals with catheterisation facilities 24/7.
Participants340 men and 109 women aged between 31 and 95 years completed the survey.
Main outcome measuresFMC were divided into five possible contacts: primary healthcare centre by phone or directly, national advisory nurse by phone, emergency medical services (EMS) and emergency room directly. Two parts of prehospital delay times were studied: time from symptom onset to FMC and time from symptom onset to diagnostic ECG.
ResultsWomen more often called an advisory nurse as FMC (28% vs 18%, p=0.02). They had a longer delay until FMC, 90 (IQR 39–221) vs 66 (28–161) min, p=0.04 and until ECG, 146 (68–316) vs 103 (61–221) min, p=0.03. Men went to hospital because of believing they were stricken by an MI to a higher extent than women did (25% vs 15%, p=0.04) and were more often recommended to call EMS by bystanders (38% vs 22%, p<0.01). Hesitating about going to hospital and experiencing pain in the stomach/back/shoulders were factors associated with longer delays in women. Believing the symptoms would disappear or interpreting them as nothing serious were corresponding factors in men. In both genders bystanders acting by contacting EMS explained shorter prehospital delays.
ConclusionsIn STEMI, women differed from men in FMC and they had longer delays. This was partly due to atypical symptoms and a longer decision time. Bystanders acted more promptly when men than when women fell ill. Public knowledge of MI symptoms, and how to act properly, still seems insufficient.
https://ift.tt/2HPerBT
Efficacy of bilevel positive airway pressure and continuous positive airway pressure therapy in patients with obesity hypoventilation syndrome: protocol for systematic review and meta-analysis
Introduction
Obesity hypoventilation syndrome (OHS) is a major respiratory complication caused by severe obesity, being associated with significant morbidity, negative impacts on quality of life and reduced survival if not treated appropriately. Positive airway pressure therapy is the first-line treatment for OHS although the optimal modality remains unclear. The goal of this study is to identify the efficacy of home bilevel positive airway pressure therapy by comparison to continuous positive airway pressure therapy and determine the best strategy for patients with OHS.
Methods and analysisThis study will be conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 statement. We will search the following databases: PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials and CINAHL. Ongoing studies will be identified through the ClinicalTrials.gov and WHO International Clinical Trials Registry Platform Search Portal. Grey literature will be recognised through Google Scholar and other search engines. Only randomised controlled trials meeting the eligibility criteria will be included. The risk of bias of the included studies will be evaluated through the Cochrane Collaboration's tool. RevMan V.5.3.5 software will be used for data analysis. The Q statistic and I2 index will be used for investigating heterogeneity, and subgroup analysis or sensitivity analysis will be used to explore the source of heterogeneity. In addition, the Grading of Recommendations Assessment, Development and Evaluation system will be used to inspect the quality of evidence.
Ethics and disseminationEthics approval is not required because this study contains no primary data collected from humans. This systematic review and meta-analysis will be submitted to a peer-reviewed journal for publication.
PROSPERO registration numberCRD42017078369.
https://ift.tt/2rdMr4z
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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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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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