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Παρασκευή 1 Ιουνίου 2018

Knowledge Is Never Just There

Abstract

The belief in a world governed by natural law has meant that our ideas of good thinking have increasingly turned toward formalizable schemes, suitable to support ideas of consistency, accuracy, and disembodied clarity. The idea that thinking might be a bodily thing hasn't been much appreciated among philosophers of this tradition. Yet, we shall pursue this line of thought in this paper. It is suggested that knowledge is not something we have but something created in the very moment of use. The same goes for other essential concepts such as for instance causality. Causality is seen as a human bodily experience (not just a psychological phenomenon, as Hume said, and not a transcendental condition of human existence, as Kant explained). Causality is an experience, and from this fact follows that the Newtonian world must be turned upside down. The laws of gravity are not something "out-there" but something "in-here".



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The role of niraparib for the treatment of ovarian cancer

Future Oncology, Ahead of Print.


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Talking to patients about biosimilars

Future Oncology, Ahead of Print.


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Targeting Rac and Cdc42 GTPases in Cancer

Rac and Cdc42 are small GTPases that have been linked to multiple human cancers and are implicated in epithelial to mesenchymal transition, cell-cycle progression, migration/invasion, tumor growth, angiogenesis, and oncogenic transformation. With the exception of the P29S driver mutation in melanoma, Rac and Cdc42 are not generally mutated in cancer, but are overexpressed (gene amplification and mRNA upregulation) or hyperactivated. Rac and Cdc42 are hyperactivated via signaling through oncogenic cell surface receptors, such as growth factor receptors, which converge on the guanine nucleotide exchange factors that regulate their GDP/GTP exchange. Hence, targeting Rac and Cdc42 represents a promising strategy for precise cancer therapy, as well as for inhibition of bypass signaling that promotes resistance to cell surface receptor-targeted therapies. Therefore, an understanding of the regulatory mechanisms of these pivotal signaling intermediates is key for the development of effective inhibitors. In this review, we focus on the role of Rac and Cdc42 in cancer and summarize the regulatory mechanisms, inhibitory efficacy, and the anticancer potential of Rac- and Cdc42-targeting agents. Cancer Res; 78(12); 1–11. ©2018 AACR.

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Phase 3 Trial of Ibrutinib plus Rituximab in Waldenström’s Macroglobulinemia

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Waldenström's macroglobulinemia, a rare form of B-cell lymphoma, is characterized by elevated serum levels of IgM and infiltration of the bone marrow and other organs by IgM-producing clonal lymphoplasmacytic cells. Treatment is commonly initiated in patients with the disease who have anemia,…

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A functional homologous recombination assay predicts primary chemotherapy response and long-term survival in ovarian cancer patients

Purpose: Homologous recombination deficiency (HRD) correlates with platinum sensitivity in ovarian cancer patients, which clinically is the most useful predictor of sensitivity to PARPi. To date, there are no reliable diagnostic tools to anticipate response to platinum-based chemotherapy, thus we aimed to develop an ex vivo functional HRD detection test that could predict both platinum-sensitivity and patient eligibility to targeted drug treatments. Experimental Design: We obtained a functional HR score by quantifying homologous recombination (HR) repair after ionizing radiation-induced DNA damage in primary ovarian cancer samples (n=32). Samples clustered in 3 categories: HR-deficient, HR-low and HR-proficient. We analysed the HR score association with platinum sensitivity and treatment response, platinum-free interval (PFI) and overall survival (OS), and compared it with other clinical parameters. In parallel, we performed DNA-sequencing of HR genes to assess if functional HRD can be predicted by currently offered genetic screening. Results: Low HR scores predicted primary platinum sensitivity with high statistical significance (p=0.0103), associated with longer PFI (HR-deficient vs HR-proficient: 531 vs 53 days), and significantly correlated with improved OS (HR score <35 vs >=35, hazard ratio=0.08, p=0.0116). At the genomic level, we identified a few unclear mutations in HR genes and the mutational signature associated with HRD, but, overall, genetic screening failed to predict functional HRD. Conclusions: We developed an ex vivo assay that detects tumor functional HRD and an HR score able to predict platinum sensitivity, which holds the clinically relevant potential to become the routine companion diagnostic in the management of ovarian cancer patients.



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Antigen-Specific CD8 Lytic Phenotype Induced by Sipuleucel-T in Hormone-Sensitive or Castration-Resistant Prostate Cancer and Association With Overall Survival

Background: Sipuleucel-T is FDA-approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC) based on the IMPACT trial showing a 4.1-month benefit in median overall survival (OS) for patients receiving sipuleucel-T vs control. Although efficacy of sipuleucel-T is well-established, its mechanism remains incompletely understood. Methods: Patient samples from three sipuleucel-T trials were assessed for peripheral cellular immune responses to the immunogen PA2024 and the target antigen prostatic acid phosphatase (PAP). PAP- and PA2024-specific proliferative and cytolytic responses were characterized to delineate sipuleucel-T-induced immune responses. To quantify potential cytotoxic T lymphocyte (CTL) activity, cell-surface CD107a expression on PAP- or PA2024-specific CD8+ T cells was measured in sipuleucel-T-treated patient and healthy volunteer samples. Results: Increased PA2024-specific CD4+ (p=0.030) and CD8+ (p=0.052) T-cell proliferation from baseline to week 6 was observed (N=14) post-sipuleucel-T, with greater magnitude of PA2024-specific responses compared to PAP. PAP- and PA2024-CTL activity (CD107a positivity) significantly increased at weeks 6 and 26 after sipuleucel-T treatment (p<0.0001; N=22). At 26 weeks post-sipuleucel-T, OS correlated with the magnitude of PAP (Pearson's R, 0.52; p=0.013) or PA2024 (Pearson's R, 0.67; p=0.0006) CTL activity. Higher PA2024-CTL activity at week 26 was significantly associated with longer OS using tertile analysis (p=0.0005; N=22), with PA2024 responses correlating with PAP responses at week 26 (R=0.90; p=1.53E-08). Conclusions: This study is the first to report PAP-specific CD8+ T-cell responses elicited by sipuleucel-T treatment. Increased and persistent potential PA2024-specific CTL activity correlated with PAP-specific CTL activity and associated with improved OS following sipuleucel-T treatment.



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TRPA1-Mediated Ca2+ Influx Protects Tumor Cells from Oxidative Stress [Research Watch]

TRPA1 is upregulated in tumors and increases Ca2+ levels to enhance cell survival in response to ROS.



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p38{alpha} Limits Chromosomal Instability in Breast Cancer Cells [Research Watch]

Inhibiting p38α blocks DNA repair by HR and increases CIN to suppress tumor progression.



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Cholesterol-Induced Conformational Changes Drive Smoothened Activation [Research Watch]

Smoothened and classic G-coupled protein receptors are activated by a similar mechanism.



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3' UTR Shortening Represses Tumor Suppressor Genes in Trans [Research Watch]

3' UTR shortening of ceRNA genes disrupts miRNA binding, freeing miRNAs to repress tumor suppressors.



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Studies ID Impact of U.S. Opioid-Related Mortality, Rx Patterns

FRIDAY, June 1, 2018 -- From 2001 to 2016 there was an increase in the number and percentage of opioid-related deaths; in addition, most patients receiving opioids receive immediate-release (IR) formulations, according to two studies published...

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Higher HDL-C Linked to Better Cognition in Older DM Patients

FRIDAY, June 1, 2018 -- Higher serum high-density lipoprotein cholesterol (HDL-C) is associated with better executive function among older patients with diabetes mellitus (DM), according to a study published online May 19 in the Journal of Diabetes...

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Facial Morphing Program May Deter Young Adults From Tanning

FRIDAY, June 1, 2018 -- A facial morphing intervention may reduce skin cancer risk behaviors among young adults, according to a study published in the June issue of Body Image. Aaron J. Blashill, Ph.D., from San Diego State University, and...

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Knowledge Gaps Found for Non-Drug Therapy in Peds ADHD

FRIDAY, June 1, 2018 -- There are considerable gaps in knowledge relating to the effectiveness of non-pharmacologic treatments for attention-deficit/hyperactivity disorder (ADHD) in pediatric patients, according to a review published online May 30...

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CDC Says E. Coli Outbreak Tied to Romaine Lettuce Is Over

FRIDAY, June 1, 2018 -- This spring's outbreak of Escherichia coli illness tied to tainted Arizona romaine lettuce is likely over, U.S. health officials say, but not before claiming five lives. "Romaine lettuce from the Yuma growing region [of...

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HeartWare HVAD System by Medtronic: Class I Recall - Due to Unintended Intermittent Electrical Disconnection between the Power Source and the Controller

[Posted 06/01/2018] AUDIENCE: Cardiology, Risk Manager, Nursing, Patient ISSUE: Medtronic is recalling the HeartWare HVAD because of the possibility for an interruption to occur in the electrical connection between the system's power source...

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Hormones removal from municipal wastewater using ultrasound

Estrogens are one of the micro-pollutants in the wastewater which have detrimental effects on water living organisms. The aim of this study was to evaluate the efficiency of ultrasound to reduce the estrogen (...

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Lecithin is the key material attribute in soy bean oil affecting filamentous bioprocesses

Complex raw materials are widely used as supplements in biopharmaceutical production processes due to their positive effect on biomass growth and productivity at low cost. However, their use negatively impacts...

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Insights into biomethane production and microbial community succession during semi-continuous anaerobic digestion of waste cooking oil under different organic loading rates

High content of lipids in food waste could restrict digestion rate and give rise to the accumulation of long chain fatty acids in anaerobic digester. In the present study, using waste cooking oil skimmed from ...

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Application of enhanced electronegative multimodal chromatography as the primary capture step for immunoglobulin G purification

In recent studies, electronegative multimodal chromatography with Eshmuno HCX was demonstrated to be a highly promising recovery step for direct immunoglobulin G (IgG) capture from undiluted cell culture fluid...

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HeartWare HVAD System by Medtronic: Class I Recall - Due to Unintended Intermittent Electrical Disconnection between the Power Source and the Controller

[Posted 06/01/2018] AUDIENCE: Cardiology, Risk Manager, Nursing, Patient ISSUE: Medtronic is recalling the HeartWare HVAD because of the possibility for an interruption to occur in the electrical connection between the system's power source...

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Comprehensive evaluation of EMG and biopsy findings supported by computer simulations – preliminary study

Muscle biopsy plays a critical role in the diagnosis of the neuromuscular disorders, along with the clinical examination, electromyography (EMG), laboratory and molecular genetic testing. It provides the diagnostic evidence that either establishes the disease etiology or narrows the differential diagnosis.

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Denosumab

Denosumab is a human monoclonal antibody that binds Receptor Activator of Nuclear factor Kappa β Ligand (RANKL), a cytokine and member of the tumor necrosis factor superfamily. This prevents interaction between RANKL and the RANK receptor on osteoclasts, inhibiting their maturation, function and survival. Consequentially, bone resorption is inhibited. Bisphosphonates also inhibit osteoclast function (via a different mechanism) and thereby have similar effects. Although denosumab and bisphosphonates share indications and undesirable effects, the latter drugs are significantly less expensive.

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Combining Perfusion and High B-value Diffusion MRI to Inform Prognosis and Predict Failure Patterns in Glioblastoma

Advanced imaging modalities such as high b-value diffusion and dynamic contrast enhancement (DCE) MRI have the potential to improve the clinical management of glioblastoma by informing prognosis, predicting sites of progression and guiding dose-escalated radiation to maximize tumor control while minimizing toxicity.

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Validating a predictive atlas of tumor shrinkage for adaptive radiotherapy of locally advanced lung cancer

We generated a predictive atlas that can estimate the spatial distribution of residual tumor in response to radiotherapy, and validated the atlas across independent institutions. Treatment planning guided by the prediction as well as recalibration of the prediction based on imaging surveillance can provide relevant dose escalation to the actual residual tumor, and improve the efficacy compared to the adaptive mid-course replanning approach.

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Localized myxofibrosarcomas: roles of surgical margins and adjuvant radiotherapy

After R0 or R1 resection of limb or superificial trunk myxofibrosarcoma, the 5-year local relapse free survival was only 67%.Three independent prognostic factors influenced the local control: age, R0 resection and adjuvant radiotherapy

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Modeling patient-specific dose-function response using perfusion SPECT/CT for enhanced characterization of personalized functional changes

By quantifying the heterogeneous distribution of lung function prior to treatment, personalized radiotherapies have the potential to limit functional damage and reduce toxicity. However, a limited understanding of the normal tissue response to radiation has hindered the incorporation of functional information in treatment planning. This study applied a patient-specific modeling approach to enhance the characterization of the dose-function response in NSCLC patients treated with conventionally-fractionated RT and SBRT.

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Multi-Center Trial of Stereotactic Body Radiotherapy for Low- and Intermediate-Risk Prostate Cancer: Survival and Toxicity Endpoints

Stereotactic body radiotherapy (SBRT) offers a cost-effective method to escalate dose in early-stage prostate cancer. Although results from single-institutions series are promising, mature data from large multi-center trials are lacking. We treated, across 21 centers, 309 patients with low- and intermediate-risk prostate cancer. With median follow-up exceeding 5 years, rates of grade 3+ toxicities were low (1.3%), and biochemical disease-free survival compared favorably to historical controls. SBRT is a suitable option for early-stage prostate cancer.

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Comparison of patient-reported outcomes after external beam radiation therapy and combined external beam with low-dose rate brachytherapy boost in men with localized prostate cancer

Men with localized prostate cancer treated with combined external beam therapy with low-dose rate brachytherapy prostate boost enrolled in a prospective population-based study reported worse bowel function at one year and worse urinary irritative function through three years compared to men treated with external beam radiation therapy alone. These side effect profiles should be discussed with patients considering combined external beam therapy with low-dose rate brachytherapy prostate boost.

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Image-based data mining to probe dosimetric correlates of radiation-induced trismus

To identify imaged regions in which dose is associated with radiation-induced trismus after head and neck cancer radiotherapy (HNRT) using a novel image-based data mining (IBDM) framework.

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Correlation of Functional Lung Heterogeneity and Dosimetry to Radiation Pneumonitis using Perfusion SPECT/CT and FDG PET/CT Imaging

We apply our previously published framework for extracting dose-volume and dose-function parameters from SPECT/CT perfusion scans to both SPECT/CT and FDG PET/CT scans in an expanded cohort. We offer three perfusion parameters and one FDG PET parameter as candidate predictors of pneumonitis (to be validated in our ongoing functional lung avoidance interventional trial) and an analysis of inter-parameter cross-correlation that we hope will stimulate new discussions on determining optimal anatomic/functional parameter combinations for treatment planning.

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Residual setup errors towards the heart after image guidance linked with poorer survival in lung cancer patients: do we need stricter IGRT protocols?

Image-guided radiotherapy (IGRT) is widely used but data providing evidence of its direct effect on patient outcome is scarce. We related residual patient setup errors from IGRT data to overall survival for NSCLC. The direction of the residual errors was found to be significant, with patients with residual shifts towards the heart having significantly worse overall survival than those with shifts away from the heart. This result was independently validated in an oesophageal cancer cohort.

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Severe PTCH1 deficiency in cancer-prone Gorlin patient cells results in intrinsic radiosensitivity

Gorlin syndrome is a typical case of debated hyper-sensitivity to radiation, although it is well-recognized as a cancer-prone disorder. The present data reveal that only Gorlin cells presenting severe deficiency in PTCH1 gene expression exhibited significantly increased cellular radiosensitivity, and that the PATCHED1 protein had a direct role in regulating intrinsic radiosensitivity, after both high and low radiation doses. This may provide a basis for prognostic screens for radiosensitive Gorlin patients with PTCH1 mutations.

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Su1434 ENDOSCOPIC ULTRASOUND-GUIDED GALLBLADDER DRIANAGE VERSUS ENDOSCOPIC TRANSPAPILLARY GALLBALDDER DRAINAGE FOR ACUTE CHOLECYSTITIS IN HIGH RISK SURGICAL PATIENTS: WHICH IS BETTER?

Endoscopic gallbladder drainage has been performed as an alternative to percutaneous drainage for acute cholecystitis. To date, there was no comparative study between endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) and endoscopic transpapillary gallbladder drainage (ETGBD). The aim of this study was to compare the outcomes of EUS-GBD and ETGBD.

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Interferon-Gamma Release Assay-Based Screening for Pediatric Latent Tuberculosis Infection in an Urban Primary Care Network

To assess outcomes from a QuantiFERON-tuberculosis (TB) Gold (QFT)-based screening for pediatric latent TB infection (LTBI) in the Denver Health Community Health System (CHS), an urban primary-care network in the US.

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Gastric Residual Volume in Feeding Advancement in Preterm Infants (GRIP Study): A Randomized Trial

To evaluate the effect of not relying on prefeeding gastric residual volumes to guide feeding advancement on the time to reach full feeding volumes in preterm infants, compared with routine measurement of gastric residual volumes. We hypothesized that not measuring prefeeding gastric residual volumes can shorten the time to reach full feeds.

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Constipation in Children with Autism Spectrum Disorder Associated with Increased Emergency Department Visits and Inpatient Admissions

To evaluate whether constipation in children with autism spectrum disorder (ASD) is associated with increased emergency department (ED) visits and inpatient admissions compared with constipation in children without ASD.

https://ift.tt/2JpkZLi

Renal Saturation and Acute Kidney Injury in Neonates with Hypoxic Ischemic Encephalopathy Undergoing Therapeutic Hypothermia

To investigate the range of renal near-infrared spectroscopy (NIRS) measures in neonates undergoing therapeutic hypothermia for hypoxic ischemic encephalopathy (HIE) and to determine the association between renal NIRS measures and the development of acute kidney injury (AKI).

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Stiffness, Facial Dysmorphism, and Skeletal Abnormalities: Schwartz-Jampel Syndrome 1A

A 7-year-old boy, first born to healthy nonconsanguineous parents presented with stiffness of both upper and lower limbs, and frequent falls since 2 years of age. Stiffness involving the facial muscles, in the form of inability to open his mouth and poor facial expressions, was noticed since 4 years of age. He also had difficulty in climbing stairs and getting up from a squatting position. On examination, his weight was 13 kg (<−3 z score, World Health Organization [WHO]); height was 94.5 cm (<−3 z score, WHO) and head circumference was 48 cm (−1 to −2 z score, WHO).

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Etiologies and Yield of Diagnostic Testing in Children Presenting to the Emergency Department with Altered Mental Status

To identify etiologies of altered mental status in pediatric patients presenting to the emergency department (ED) and to characterize the yield of diagnostic testing in these patients.

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Two-Year Follow-Up of Impaired Range of Motion in Chronic Fatigue Syndrome

To measure changes in range of motion (ROM) over time in a cohort of 55 adolescents and young adults with chronic fatigue syndrome and to determine whether changes in ROM correlated with changes in health-related quality of life.

https://ift.tt/2LgpaGF

Massive parallel regression: a précis of genetic mechanisms for vision loss in diving beetles

Synopsis
Two tribes of subterranean dytiscid diving beetles independently colonised groundwater systems of the Western Australian arid zone, a habitat transition that was most likely driven by the contraction of surface water bodies following late Neogene aridification of the Australian continent. These 'stygofauna' are now trapped within discrete calcrete aquifers that have formed in palaeodrainage valleys, resulting in the world's most diverse radiations of subterranean dytiscid beetles. Approximately 100 species from three genera exhibit partial or fully regressed visual systems and are essentially blind. This unique study system, with multiple independent transitions to subterranean life enables regressive and adaptive evolutionary processes to be studied in parallel at an unheralded comparative scale. Here we provide an overview of the progression of dytiscid beetle research and undertake a literature survey of published research within the field of regressive evolution as it applies to eye loss. We detail our exploration of insect vision genes for signatures of adaptive and neutral evolutionary mechanisms related to eye regression, largely within photoreceptor and eye pigment genes. Our project makes use of transcriptome data from five representative dytiscid beetle species (two surface and three subterranean) in order to design a customized set of RNA baits for use in a hybrid-capture method to target a pool of vision genes sequenced using high-throughput Illumina platforms. This methodological design permits the assessment of modifications in the genomic sequence of beetle vision genes at a much broader scale than Sanger sequencing, enabling a higher number of both target species and genes to be simultaneously assessed relative to research time-investments. Based on our literature search criteria of the research field ('regressive evolution' + 'eyes'), 81 papers have been published since the late 1980's accruing an h-index of 27 and a mean citation rate of 24.57. Collective annual citations for this field of research have surged over the past five years, an indication that broader scientific community interest is gaining momentum. The majority of publications (75%) have focused on the chordate clade Actinopterygii. Historically, research on variant subterranean taxa have faced difficulties inferring the evolutionary mechanisms of eye regression (and vision loss) using molecular approaches because only a handful of target genes could be feasibly addressed within grant funding cycles. From a comparative phylogenetic perspective, next-generation sequencing approaches applied to stygobiontic dytiscid beetles hold the potential to greatly improve our understanding of the genetic mechanisms underlying regressive evolution generally.

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Extensive uncharted biodiversity: the parasite dimension

Synopsis
Parasites are often hidden in their hosts and exhibit patchy spatial distributions. This makes them relatively difficult to detect and sample. Consequently we have poor knowledge of parasite diversities, distributions and extinction. We evaluate our general understanding of parasite diversity and highlight the enormous bias in research on parasites such as helminths and arthropods that infect vertebrate hosts. We then focus on Myxozoa as an exemplary case for demonstrating uncharted parasite diversity. Myxozoans are a poorly recognised but speciose clade of endoparasitic cnidarians with complex life cycles that have radiated to exploit freshwater, marine and terrestrial hosts by adopting strategies convergent to those of parasitic protists. Myxozoans are estimated to represent some 20% of described cnidarian species – greatly outnumbering the combined species richness of scyphozoans, cubozoans, and staurozoans. We summarise limited understanding of myxozoan diversification and geographical distributions, and highlight gaps in knowledge and approaches for measuring myxozoan diversity. We close by reviewing methods and problems in estimating parasite extinction and concerns about extinction risks in view of the fundamental roles parasites play in ecosystem dynamics and in driving host evolutionary trajectories.

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Inertial Sensing and Encoding of Self-Motion: Structural and Functional Similarities Across Metazoan Taxa



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SGLT2 Inhibition for the Prevention and Treatment of Diabetic Kidney Disease: A Review

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease in the United States and the world alike, and there is a great unmet need for treatments to reduce DKD development and progression. Inhibition of sodium/glucose co-transporter 2 (SGLT2) in the proximal tubule of the kidney has emerged as an effective antihyperglycemic treatment, leading to regulatory approval of several first-generation SGLT2 inhibitors for the treatment of type 2 diabetes. In follow-on clinical trials for the cardiovascular safety of the SGLT2 inhibitors, secondary effects to prevent or reduce albuminuria and decline in estimated glomerular filtration rate spurred further investigation into their potential application in DKD.

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Exome Sequencing for CKD Diagnosis: Coming Soon to a Clinic Near You?

Advances in genetic techniques have opened windows into the human genome that were barely imaginable 17 years ago when the Human Genome Project published its draft sequence.1 The difficult task of making these new tools and the data they generate widely useful to patients and clinicians is only just beginning. Rates of adoption have varied among medical specialties. To date, personalized medicine is a concept much more often talked about than productively used in nephrology.

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GDF-15, Galectin 3, Soluble ST2, and Risk of Mortality and Cardiovascular Events in CKD

Inflammation, cardiac remodeling, and fibrosis may explain in part the excess risk for cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). Growth differentiation factor 15 (GDF-15), galectin 3 (Gal-3), and soluble ST2 (sST2) are possible biomarkers of these pathways in patients with CKD.

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Congophilic Fibrillary Glomerulonephritis: A Case Series

Congo Red positivity with birefringence under polarized light has traditionally permitted classification of organized glomerular deposits as from amyloid or nonamyloid diseases. The absence of congophilia has been used to differentiate fibrillary glomerulonephritis (GN) from amyloidosis. We describe a series of fibrillary GN cases in which the deposits are Congo Red–positive (congophilic fibrillary GN) and discuss the role of DNAJB9 in distinguishing congophilic fibrillary GN from amyloidosis.

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Distant Organ Dysfunction in Acute Kidney Injury: A Review

Acute kidney injury (AKI) is common in critically ill patients and is associated with increased morbidity and mortality. Dysfunction of other organs is an important cause of poor outcomes from AKI. Ample clinical and epidemiologic data show that AKI is associated with distant organ dysfunction in lung, heart, brain, and liver. Recent advancements in basic and clinical research have demonstrated physiologic and molecular mechanisms of distant organ interactions in AKI, including leukocyte activation and infiltration, generation of soluble factors such as inflammatory cytokines/chemokines, and endothelial injury.

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Scientists develop material that could regenerate dental enamel

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Researchers have developed a new way to grow mineralized materials which could regenerate hard tissues such as dental enamel and bone.

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Association of virulence gene expression with colistin-resistance in Acinetobacter baumannii: analysis of genotype, antimicrobial susceptibility, and biofilm formation

Acinetobacter baumannii causes difficult-to-treat nosocomial infections, which often lead to morbidity due to the development of antimicrobial drug resistance and expression of virulence genes. Data regarding the...

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Antibacterial activity and in situ efficacy of Bidens pilosa Linn and Dichrostachys cinerea Wight et Arn extracts against common diarrhoea-causing waterborne bacteria

Bidens pilosa and Dichrostachys cinerea extracts were investigated for the antibacterial properties against waterborne diarrhoeagenic bacteria.

https://ift.tt/2xBNIrC

A 3-dimensional (3D)-printed Template for High Throughput Zebrafish Embryo Arraying

Here, we present a protocol to design and fabricate a zebrafish embryo arraying template, followed by a detailed procedure on the use of such template for high throughput zebrafish embryo arraying into a 96-well plate.

https://ift.tt/2sylMiR

Visualization of Microbiota in Tick Guts by Whole-mount In Situ Hybridization

Here, we present a protocol to spatially and temporally assess the presence of viable microbiota in tick guts using a modified whole-mount in situ hybridization approach.

https://ift.tt/2J2THLw

A Novel Method for the Pentosan Analysis Present in Jute Biomass and Its Conversion into Sugar Monomers Using Acidic Ionic Liquid

We present a protocol for the synthesis of C5 sugars (xylose and arabinose) from a renewable non-edible lignocellulosic biomass (i.e., jute) with the presence of Brønsted acidic ionic liquids (BAILs) as the catalyst in water. The BAILs catalyst exhibited better catalytic performance than conventional mineral acid catalysts (H2SO4 and HCl).

https://ift.tt/2HbiGqi

Advanced magnetic resonance imaging (MRI) techniques of the spine and spinal cord in children and adults

Abstract

In this article, we illustrate the main advanced magnetic resonance imaging (MRI) techniques used for imaging of the spine and spinal cord in children and adults. This work focuses on daily clinical practice and aims to address the most common questions and needs of radiologists. We will also provide tips to solve common problems with which we were confronted. The main clinical indications for each MR technique, possible pitfalls and the challenges faced in spine imaging because of anatomical and physical constraints will be discussed. The major advanced MRI techniques dealt with in this article are CSF, (cerebrosopinal fluid) flow, diffusion, diffusion tensor imaging (DTI), MRA, dynamic contrast-enhanced T1-weighted perfusion, MR angiography, susceptibility-weighted imaging (SWI), functional imaging (fMRI) and spectroscopy.

Teaching Points

DWI is essential to diagnose cord ischaemia in the acute stage.

MRA is useful to guide surgical planning or endovascular embolisation of AVMs.

Three Tesla is superior to 1.5 T for spine MR angiography and spectroscopy.

Advanced sequences should only be used together with conventional morphological sequences.



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Remaining Kidney Health Most Important Concern for Donors

FRIDAY, June 1, 2018 -- Concerns expressed by living kidney donors include kidney failure and function, as well as the surgical, lifestyle, and psychosocial impact of donation, according to a study published online May 31 in the Clinical Journal of...

https://ift.tt/2J235Pv

Male Thyroid Cancer Survivors Face Higher CVD Risk

FRIDAY, June 1, 2018 -- Male thyroid cancer survivors have a nearly 50 percent higher risk of developing cardiovascular disease (CVD) than female survivors within five years of cancer diagnosis, according to a study published online May 29 in the...

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Abortion Not Tied to Significantly Higher Antidepressant Use

FRIDAY, June 1, 2018 -- The likelihood of using antidepressants may be increased for women who have abortions, but the increased use is not attributable to having had an abortion but to differences in risk factors for depression, according to a...

https://ift.tt/2srkwi0

Convolutional Neural Network Tops Clinicians for Melanoma ID

FRIDAY, June 1, 2018 -- The diagnostic performance of a deep learning convolutional neural network (CNN) seems better than that of dermatologists, according to a study published online May 28 in the Annals of Oncology. Holger A. Haenssle, M.D., from...

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Ob-Gyns Should ID Gynecologic Symptoms of Eating Disorders

FRIDAY, June 1, 2018 -- Obstetrician-gynecologists should be aware of the gynecologic concerns and symptoms of eating disorders, according to a committee opinion published in the June issue of Obstetrics & Gynecology. Nancy Sokkary, M.D., from...

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Fever, Rash, Erythema Seen in Most Puerto Rican Kids With Zika

FRIDAY, June 1, 2018 -- Most children with Zika virus (ZIKV) infection have fever, rash, and facial or neck erythema, according to a study published online May 29 in JAMA Pediatrics. Jennifer S. Read, M.D., from the University of Vermont Medical...

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CDC: Death Rate for American Youth Up in Recent Years

FRIDAY, June 1, 2018 -- For persons aged 10 to 19 years, there was a decrease in the total death rate from 1999 to 2013, followed by an increase between 2013 and 2016, according to a report published in the U.S. Centers for Disease Control and...

https://ift.tt/2srkmao

Postmenopausal Sex Hormone Levels Associated With Later CVD

FRIDAY, June 1, 2018 -- In postmenopausal women, higher testosterone/estradiol ratios are associated with increased risks for incident cardiovascular disease (CVD), coronary heart disease (CHD), and heart failure events, according to a study...

https://ift.tt/2xyzTdL

Academic Underachievement With Tourette, Tic Disorders

FRIDAY, June 1, 2018 -- Individuals with Tourette syndrome or chronic tic disorders have lower likelihood of academic achievement, according to a study published online May 29 in JAMA Neurology. Ana Pérez-Vigil, M.D., from the Karolinska Institutet...

https://ift.tt/2snZqB5

Multisensory Interventions Cut Pain in Preterm Infant Eye Exams

FRIDAY, June 1, 2018 -- The addition of multisensory pain-reducing interventions to topical anesthetic (TA) reduces pain in eye examinations of preterm infants, according to research published online June 1 in Pediatrics. Timothy Disher, Ph.D., from...

https://ift.tt/2JaKnkN

May 2018 Briefing - Geriatrics

Here are what the editors at HealthDay consider to be the most important developments in Geriatrics for May 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that are the...

https://ift.tt/2snZjFF

May 2018 Briefing - Cosmetic Surgery

Here are what the editors at HealthDay consider to be the most important developments in Cosmetic Surgery for May 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that...

https://ift.tt/2xBiYXS

May 2018 Briefing - Allergy

Here are what the editors at HealthDay consider to be the most important developments in Allergy for May 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that are the...

https://ift.tt/2J2DLsB

May 2018 Briefing - Gastroenterology

Here are what the editors at HealthDay consider to be the most important developments in Gastroenterology for May 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that...

https://ift.tt/2xA4fwb

May 2018 Briefing - Hematology & Oncology

Here are what the editors at HealthDay consider to be the most important developments in Hematology & Oncology for May 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory...

https://ift.tt/2snZb99

May 2018 Briefing - Pathology

Here are what the editors at HealthDay consider to be the most important developments in Pathology for May 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that are the...

https://ift.tt/2xIuot5

May 2018 Briefing - Diabetes & Endocrinology

Here are what the editors at HealthDay consider to be the most important developments in Diabetes & Endocrinology for May 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory...

https://ift.tt/2spk6sJ

May 2018 Briefing - Surgery

Here are what the editors at HealthDay consider to be the most important developments in Surgery for May 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that are the...

https://ift.tt/2xxYT4F

May 2018 Briefing - Neurology

Here are what the editors at HealthDay consider to be the most important developments in Neurology for May 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that are the...

https://ift.tt/2J5vjJ6

May 2018 Briefing - Rheumatology

Here are what the editors at HealthDay consider to be the most important developments in Rheumatology for May 2018. This roundup includes the latest research news from journal articles, as well as the FDA approvals and regulatory changes that are...

https://ift.tt/2JbxaZ6

Three-dimensional Organotypic Cultures of Vestibular and Auditory Sensory Organs

Three-dimensional organotypic cultures of the murine utricle and cochlea in optically clear collagen I gels preserve innate tissue morphology, allow for mechanical stimulation through adjustment of matrix stiffness, and permit virus-mediated gene delivery.

https://ift.tt/2syuc9F

Adaptation of Hybridization Capture of Chromatin-associated Proteins for Proteomics to Mammalian Cells

This is a method to identify novel DNA-interacting proteins at specific target loci, relying on sequence-specific capture of crosslinked chromatin for subsequent proteomic analyses. No prior knowledge about potential binding proteins, nor cell modifications are required. Initially developed for yeast, the technology has now been adapted for mammalian cells.

https://ift.tt/2kHD6hR

Risk factors and molecular features of sequence type (ST) 131 extended-Spectrum-β-lactamase-producing Escherichia coli in community-onset female genital tract infections

Escherichia coli (E. coli) is known to cause urinary tract infection (UTI) and meningitis in neonates, as well as existing as a commensal flora of the human gut. Extended-spectrum β-lactamase (ESBL)-producing E. ...

https://ift.tt/2J5aXvw

Immune-escape mutations and stop-codons in HBsAg develop in a large proportion of patients with chronic HBV infection exposed to anti-HBV drugs in Europe

HBsAg immune-escape mutations can favor HBV-transmission also in vaccinated individuals, promote immunosuppression-driven HBV-reactivation, and increase fitness of drug-resistant strains. Stop-codons can enhan...

https://ift.tt/2J54PaM

STAT-Check and Medline Manual Resuscitator Bags by SunMed Holdings: Recall - Patient Port May Detach During Use

[Posted 06/01/2018] AUDIENCE: Risk Manager, Nursing, Emergency Medicine, Critical Care Medicine ISSUE: SunMed Holdings initiated a nationwide recall of 18,808 units of STAT-Check and Medline resuscitator bags which were distributed between February...

https://ift.tt/2LPz9nx

Easing Concerns about Giving Research Study Participants Their Genetic Test Results

Do cancer study participants want to receive their genetic test results? A recent study involving women with a history of breast cancer tested an approach for returning genetic research results and evaluated the impact those results had on the women.



https://ift.tt/2J3Hu9l

An Alternative Culture Method to Maintain Genomic Hypomethylation of Mouse Embryonic Stem Cells Using MEK Inhibitor PD0325901 and Vitamin C

56391fig1.jpg

We described in detail two chemical-based protocols for culturing mouse embryonic stem cells. This new method utilizes synergistic mechanisms of promoting Tet-mediated oxidation (by vitamin C) and repressing de novo synthesis of 5-methylcytosine (by PD0325901) to maintain DNA hypomethylation and pluripotency of mouse embryonic stem cells.

https://ift.tt/2sEJKsP

Characterizing Electron Transport through Living Biofilms

A protocol for measuring electrical conductivity of living microbial biofilms under physiologically relevant conditions is presented.

https://ift.tt/2IZNlfM

Which way does the axis tip? IBD increases the risk of Parkinsons disease

In Gut, Villumsen et al1 report a statistically significant association between UC and the risk of parkinsonism in a Danish nested case–control study. Patients with Crohn's disease and UC with at least one inpatient or outpatient encounter for IBD between 1977 and 2014 were compared with age-matched and sex-matched controls (76 477 IBD; 7 548 259 controls). Follow-up started at the time of the first IBD encounter (or the corresponding date for the controls) until the first diagnosis of Parkinson's disease or multiple system atrophy. Parkinsonism was increased among patients with UC (HR 1.35 (95% CI 1.20 to 1.52)), but not Crohn's disease (HR 1.12 (95% CI 0.89 to 1.40)). Parkinson's disease and multiple system atrophy were rare both in patients with IBD (0.4% and 0.02%) and non-IBD patients (0.5% and 0.01%).

These findings are consistent with basic research implicating the link between the central and enteric nervous system, also known as the gut–brain axis,...



https://ift.tt/2xyRB0D

Non-superiority of lumen-apposing metal stents over plastic stents for drainage of walled-off necrosis in a randomised trial

Objective

Although lumen-apposing metal stents (LAMS) are increasingly used for drainage of walled-off necrosis (WON), their advantage over plastic stents is unclear. We compared efficacy of LAMS and plastic stents for WON drainage.

Design

Patients with WON were randomised to endoscopic ultrasound-guided drainage using LAMS or plastic stents. Primary outcome was comparing total number of procedures to achieve treatment success defined as symptom relief in conjunction with WON resolution on CT at 6 months. Secondary outcomes were treatment success, procedure duration, clinical/stent-related adverse events, readmissions, length of hospital stay (LOS) and costs.

Results

60 patients underwent LAMS (n=31) or plastic stent (n=29) placement. There was no significant difference in total number of procedures performed (median 2 (range 2–7) LAMS vs 3 (range 2–7) plastic, p=0.192), treatment success, clinical adverse events, readmissions, LOS and overall treatment costs between cohorts. Although procedure duration was shorter (15 vs 40 min, p<0.001), stent-related adverse events (32.3% vs 6.9%, p=0.01) and procedure costs (US$12 155 vs US$6609, p<0.001) were higher with LAMS. Significant stent-related adverse events were observed ≥3 weeks postintervention in LAMS cohort. Interim audit resulted in protocol amendment where CT scan was obtained at 3 weeks postintervention followed by LAMS removal if WON had resolved. After protocol amendment, there was no significant difference in adverse events between cohorts.

Conclusion

Except for procedure duration, there was no significant difference in treatment outcomes between LAMS and plastic stents. To minimise adverse events with LAMS, patients should undergo follow-up imaging and stent removal at 3 weeks if WON has resolved.

Trial registration number

NCT02685865.



https://ift.tt/2J1NeQZ

STAT-Check and Medline Manual Resuscitator Bags by SunMed Holdings: Recall - Patient Port May Detach During Use

[Posted 06/01/2018] AUDIENCE: Risk Manager, Nursing, Emergency Medicine, Critical Care Medicine ISSUE: SunMed Holdings initiated a nationwide recall of 18,808 units of STAT-Check and Medline resuscitator bags which were distributed between February...

https://ift.tt/2LPz9nx

Whole genome sequence revealed the fine transmission map of carbapenem-resistant Klebsiella pneumonia isolates within a nosocomial outbreak

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a major cause of nosocomial infections worldwide. The transmission route of CRKP isolates within an outbreak is rarely described. This study aimed to reveal th...

https://ift.tt/2xALMjc

Pulmonary Hypertension: Good Intentions, But a Questionable Approach

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Annals of the American Thoracic Society, Volume 15, Issue 6, Page 664-666, June 2018.


https://ift.tt/2kEKnih

Prognostic Significance of Large Airway Dimensions on Computed Tomography in the General Population. The Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study

Annals of the American Thoracic Society, Volume 15, Issue 6, Page 718-727, June 2018.


https://ift.tt/2Ha9X7N

Associations between Neighborhood Walkability and Incident and Ongoing Asthma in Children

Annals of the American Thoracic Society, Volume 15, Issue 6, Page 728-734, June 2018.


https://ift.tt/2kEKbzz

Underreporting of Interstitial Lung Abnormalities on Lung Cancer Screening Computed Tomography

Annals of the American Thoracic Society, Volume 15, Issue 6, Page 764-766, June 2018.


https://ift.tt/2Hc3xVu

Chronic Antibiotic Use in Cystic Fibrosis: A Fine Balance

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Annals of the American Thoracic Society, Volume 15, Issue 6, Page 667-668, June 2018.


https://ift.tt/2J32gWE

Tuberculosis Mortality in the United States: Epidemiology and Prevention Opportunities

Annals of the American Thoracic Society, Volume 15, Issue 6, Page 683-692, June 2018.


https://ift.tt/2ssPMfQ

Environmental Concerns for Children with Asthma on the Navajo Nation

Annals of the American Thoracic Society, Volume 15, Issue 6, Page 745-753, June 2018.


https://ift.tt/2kEJZjP

Signals from an “Alien” Force

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Annals of the American Thoracic Society, Volume 15, Issue 6, Page 760-763, June 2018.


https://ift.tt/2HbyjxG

Development and internal validation of PI-RADs v2-based model for clinically significant prostate cancer

Abstract

Background

Our objective is to build a model based on Prostate Imaging Reporting and Data System version 2 (PI-RADs v2) and assess its accuracy by internal validation.

Methods

Patients who took prostate biopsy from 2014 to 2015 were retrospectively collected to compose training cohort according to the inclusion criteria and patients in 2016 composing validation cohort. Diagnostic performance was evaluated by analyzing the area under the curve (AUC), calibration curves, and decision curves.

Results

Of the 441 patients involved, the clinically significant prostate cancer (csPCa) detection rate were 40.6% (114/281) and 43.8% (70/160) in the training and validation cohort, respectively. Meanwhile, PCa detection rate were 50.2% (141/281) and 53.8% (86/160). Age, prostate-specific antigen density (PSAD)*10 and PI-RADs v2 score composed the model for PCa (model 1) and csPCa (model 2). The area under the curve of models 1 and 2 was 0.870 (95% CI 0.827–0.912) and 0.753 (95% CI 0.717–0.828) in the training cohort, while 0.845 (95% CI 0.786–0.904) and 0.834 (95% CI 0.787–0.882) in the validation cohort. Both models illustrated good calibration, and decision curve analyses showed good performance in predicting PCa or csPCa when the threshold was 0.35 or above.

Conclusions

The model based on age, PSAD*10 and PI-RADs v2 score showed internally validated high predictive value for both PCa and csPCa. It could be used to improve the diagnostic performance of suspicious PCa.



https://ift.tt/2HaJjf0

The amount of calcifications in pseudoxanthoma elasticum patients is underestimated in computed tomographic imaging; a post-mortem correlation of histological and computed tomographic findings in two cases

Abstract

Objectives

Pseudoxanthoma elasticum (PXE) is a rare genetic disorder, characterised by elastic fibre degeneration and calcifications in multiple organ systems. Computed tomography (CT) imaging is a potential method to monitor disease progression in PXE patients; however, this method has not been validated. The aim of this study was to correlate histological and computed tomographic findings in PXE patients to investigate the ability of CT scanning to detect these alterations.

Methods

Post mortem total body CT scans were obtained from two PXE patients (a 69-year-old male and 77-year-old female). Autopsy was performed, and 38 tissue samples of the first and 45 tissue samples of the second patient were extensively investigated histologically. The findings were compared with the CT scans.

Results

Degenerated and calcified elastic fibres and calcifications were histologically found in the skin, subcutaneous fat, heart, arteries and pleura and around the oesophagus. On CT imaging only the intradermal alterations of the skin and the larger vascular calcifications were detected. The smaller PXE-related abnormalities were not visible on CT.

Conclusions

With CT imaging vascular calcifications and skin alterations can be monitored in PXE patients. However, many of the subtle PXE-related abnormalities found in other organ systems during the autopsy were not visualised by CT scans. Furthermore, we extended the current knowledge on the disease location of PXE with subcutaneous, oesophageal and pleural lesions.

Teaching Points

• CT can be used to monitor gross vascular calcifications in PXE patients.

• Many subtle PXE-related abnormalities are not visualised by CT scans.

• PXE-related alterations can also be found in oesophagus, pleura and subcutaneous fat.



https://ift.tt/2Jb4IXi

Treating metastatic prostate cancer with microRNA-145

Abstract

Prostate cancer (PCa) is an incurable disease at the metastatic stage. Although there are different options for treatment, the results are limited. MicroRNAs (miRNAs) are a group of small, noncoding, regulatory RNAs with important roles in regulating gene expression. miR-145 is reported to be a key tumor suppressor miRNA (tsmiR) that controls important oncogenes, such as MYC and RAS. In this study, in vitro studies were performed to show the control of MYC and RAS by miR-145. Flow cytometry was used to analyze cell proliferation and apoptosis. The efficacy of miR-145 in treating metastatic PCa was tested in nude mice using a model of bone metastasis promoted by intraventricular injection of PC-3MLuc-C6 cells. Tumor growth was evaluated by an in vivo bioluminescence system. After the full establishment of metastases on day 21, six animals were treated with three intravenous doses of miR-145 (on days 21, 24 and 27), and six were injected with scramble miRNA as controls. Compared to the controls, tumor growth was significantly reduced in animals receiving miR-145, most importantly on day 7 after the third and last dose of miRNA. After discontinuing the treatment, tumor growth resumed, becoming similar to the group of non-treated animals. A decrease in MYC and RAS expression was observed in all cell lines after treatment with miR-145, although statistical significance was achieved only in experiments with LNCaP and PC3 cell lines, with a decrease in 56% (p = 0.012) and 31% (p = 0.013) of RAS expression, respectively. Our results suggest that miR-145 is a potential molecule to be tested for treatment of metastatic, castration-resistant PCa.



https://ift.tt/2LPxRsw

Apoptosis on the move



https://ift.tt/2xyh0r1

Super-Resolution Imaging Reveals TCTN2 Depletion-Induced IFT88 Lumen Leakage and Ciliary Weakening

The primary cilium is an essential organelle mediating key signaling activities, such as sonic hedgehog signaling. The molecular composition of the ciliary compartment is distinct from that of the cytosol, with the transition zone (TZ) gated the ciliary base. The TZ is a packed and organized protein complex containing multiple ciliopathy-associated protein species. Tectonic 2 (TCTN2) is one of the TZ proteins in the vicinity of the ciliary membrane, and its mutation is associated with Meckel syndrome.

https://ift.tt/2xvFAJq

Reply to Yanagisawa: Treatment of Pulmonary Lymphangioleiomyomatosis during Pregnancy

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 11, Page 1507-1508, June 1, 2018.


https://ift.tt/2spImus

Characterization of the “Frequent Exacerbator Phenotype” in Bronchiectasis

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 11, Page 1410-1420, June 1, 2018.


https://ift.tt/2J6MplO

Lung Transplantation from Hepatitis C Viremic Donors to Uninfected Recipients

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 11, Page 1492-1496, June 1, 2018.


https://ift.tt/2IZqot8

Age Effects on Cerebral Oxygenation and Behavior in Children with Sleep-disordered Breathing

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 11, Page 1468-1477, June 1, 2018.


https://ift.tt/2xyisd9

Disproportionate Right Ventricular Dysfunction and Poor Survival in Group 3 Pulmonary Hypertension

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 11, Page 1496-1499, June 1, 2018.


https://ift.tt/2soLLKj

Targeting of TAM Receptors Ameliorates Fibrotic Mechanisms in Idiopathic Pulmonary Fibrosis

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 11, Page 1443-1456, June 1, 2018.


https://ift.tt/2xzrdUq

Bronchial Epithelial IgA Secretion Is Impaired in Asthma. Role of IL-4/IL-13

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 11, Page 1396-1409, June 1, 2018.


https://ift.tt/2smMnzM

The TAMing of the Idiopathic Pulmonary Fibrosis Myofibroblast. One Step Closer?

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 11, Page 1377-1378, June 1, 2018.


https://ift.tt/2J8h1DA

An Argument for the Protocolized Screening and Management of Post-Extubation Stridor

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 11, Page 1503-1505, June 1, 2018.


https://ift.tt/2J6okQ7

Treatment of Pulmonary Lymphangioleiomyomatosis during Pregnancy

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 11, Page 1506-1507, June 1, 2018.


https://ift.tt/2J8gUrE

Genome-Wide Association Study in African Americans with Acute Respiratory Distress Syndrome Identifies the Selectin P Ligand Gene as a Risk Factor

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 11, Page 1421-1432, June 1, 2018.


https://ift.tt/2so8Ooy

Ivacaftor-treated Patients with Cystic Fibrosis Derive Long-Term Benefit Despite No Short-Term Clinical Improvement

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 11, Page 1483-1486, June 1, 2018.


https://ift.tt/2xzwuLH

Role of Humoral Defense in Severe Asthma

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 11, Page 1369-1371, June 1, 2018.


https://ift.tt/2so8O82

Interventional Pulmonology—Bridging the Gaps through Standardization: Malignant Pleural Effusion, Mediastinal Staging, and Cryobiopsy

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 11, Page 1478-1480, June 1, 2018.


https://ift.tt/2J8SRc7

Long-Term Outcomes after Protocolized Sedation versus Usual Care in Ventilated Pediatric Patients

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 11, Page 1457-1467, June 1, 2018.


https://ift.tt/2spHZQA

Update in Critical Care Medicine 2017

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 11, Page 1382-1388, June 1, 2018.


https://ift.tt/2J8SJJF

Genome-Wide Association Study in Acute Respiratory Distress Syndrome. Finding the Needle in the Haystack to Advance Our Understanding of Acute Respiratory Distress Syndrome

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 11, Page 1373-1374, June 1, 2018.


https://ift.tt/2spHPZu

Bronchial Impaction of Arterial Coil

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 11, Page 1481-1482, June 1, 2018.


https://ift.tt/2J9wjrQ

Reply to Smith et al.: An Argument for the Protocolized Screening and Management of Post-Extubation Stridor

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 11, Page 1505-1506, June 1, 2018.


https://ift.tt/2splR8Z

Reply to Dahm et al., to Shah et al., and to Schünemann and Brożek

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 11, Page 1502-1503, June 1, 2018.


https://ift.tt/2xB677W

Scale-up of Industrial Microbial Processes

Abstract
Scaling up industrial microbial processes for commercial production is a high-stakes endeavor, requiring time and investment often exceeding that for laboratory microbe and process development. Omissions, oversights, and errors can be costly, even fatal to the program. Approached properly, scale-up can be executed successfully. Three guiding principles are provided as a basis: begin with the end in mind; be diligent in the details; prepare for the unexpected. A detailed roadmap builds on these principles. There is a special emphasis on the fermentation step, which is usually the costliest and also impacts downstream processing. Examples of common scale-up mistakes and the recommended approaches are given. It is advised that engineering resources skilled in integrated process development and scale-up be engaged from the very beginning of microbe and process development to guide ongoing R&D, thus ensuring a smooth and profitable path to the large-scale commercial end.

https://ift.tt/2Hc4zRh

Cancers, Vol. 10, Pages 176: Emerging and Established Models of Bone Metastasis

Cancers, Vol. 10, Pages 176: Emerging and Established Models of Bone Metastasis

Cancers doi: 10.3390/cancers10060176

Authors: Alexander H. Jinnah Benjamin C. Zacks Chukwuweike U. Gwam Bethany A. Kerr

Metastasis is the leading cause of cancer-related death and drives patient morbidity as well as healthcare costs. Bone is the primary site of metastasis for several cancers&mdash;breast and prostate cancers in particular. Efforts to treat bone metastases have been stymied by a lack of models to study the progression, cellular players, and signaling pathways driving bone metastasis. In this review, we examine newly described and classic models of bone metastasis. Through the use of current in vivo, microfluidic, and in silico computational bone metastasis models we may eventually understand how cells escape the primary tumor and how these circulating tumor cells then home to and colonize the bone marrow. Further, future models may uncover how cells enter and then escape dormancy to develop into overt metastases. Recreating the metastatic process will lead to the discovery of therapeutic targets for disrupting and treating bone metastasis.



https://ift.tt/2L9TrXF

β-Arrestin-2–Dependent Signaling Promotes CCR4–mediated Chemotaxis of Murine T-Helper Type 2 Cells

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 6, Page 745-755, June 2018.


https://ift.tt/2xzkRo2

Arresting CCR4: A New Look at an Old Approach to Combating Asthma

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 6, Page 673-675, June 2018.


https://ift.tt/2sp0kgV

IL-17 Plays a Role in Respiratory Syncytial Virus–induced Lung Inflammation and Emphysema in Elastase and LPS-injured Mice

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 6, Page 717-726, June 2018.


https://ift.tt/2J7Ugzz

Identification of Drug Candidates to Suppress Cigarette Smoke–induced Inflammation via Connectivity Map Analyses

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 6, Page 727-735, June 2018.


https://ift.tt/2spdkmG

Does Compromised Immune Exclusion Drive Inflammatory Processes in Chronic Obstructive Pulmonary Disease?

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 6, Page 671-672, June 2018.


https://ift.tt/2xynXZp

Characterization of Novel Missense Variants of SERPINA1 Gene Causing Alpha-1 Antitrypsin Deficiency

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 6, Page 706-716, June 2018.


https://ift.tt/2J8Gj4k

PD-1/PD-L1 Pathway Mediates the Alleviation of Pulmonary Fibrosis by Human Mesenchymal Stem Cells in Humanized Mice

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 6, Page 684-695, June 2018.


https://ift.tt/2J4aDkC

Bacterial-derived Neutrophilic Inflammation Drives Lung Remodeling in a Mouse Model of Chronic Obstructive Pulmonary Disease

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 6, Page 736-744, June 2018.


https://ift.tt/2xyo2MH

June Highlights/Papers by Junior Investigators/NIH News

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 6, Page vi-vi, June 2018.


https://ift.tt/2J1muzW

IL-17 Strikes a Chord in Chronic Obstructive Pulmonary Disease Exacerbation

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 6, Page 669-670, June 2018.


https://ift.tt/2soNCPb

Do Mucosa-associated Invariant T Cells Checkmate Streptococcus pneumoniae?

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 6, Page 676-677, June 2018.


https://ift.tt/2J5dfec

Inhibition of Macrophage Complement Receptor CRIg by TRIM72 Polarizes Innate Immunity of the Lung

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 6, Page 756-766, June 2018.


https://ift.tt/2J6iApx

A Phenome-Wide Association Study Uncovers a Role for Autoimmunity in the Development of Chronic Obstructive Pulmonary Disease

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 6, Page 777-779, June 2018.


https://ift.tt/2xzoL09

Bronchiolitis Obliterans and Pulmonary Fibrosis after Sulfur Mustard Inhalation in Rats

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 6, Page 696-705, June 2018.


https://ift.tt/2smCPoM

Riboflavin Metabolism Variation among Clinical Isolates of Streptococcus pneumoniae Results in Differential Activation of Mucosal-associated Invariant T Cells

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 6, Page 767-776, June 2018.


https://ift.tt/2xAYDBS

The Lymphangioleiomyomatosis Lung Cell and Its Human Cell Models

American Journal of Respiratory Cell and Molecular Biology, Volume 58, Issue 6, Page 678-683, June 2018.


https://ift.tt/2smCItm

Phosphodiesterase-5 Inhibitor Therapy for Pulmonary Hypertension in the United States. Actual versus Recommended Use

Annals of the American Thoracic Society, Volume 15, Issue 6, Page 693-701, June 2018.


https://ift.tt/2HaB3vp

Is the “Western Diet” a New Smoking Gun for Chronic Obstructive Pulmonary Disease?

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Annals of the American Thoracic Society, Volume 15, Issue 6, Page 662-663, June 2018.


https://ift.tt/2kGSRpf

Otolaryngology in Critical Care

Annals of the American Thoracic Society, Volume 15, Issue 6, Page 643-654, June 2018.


https://ift.tt/2HcL0Ix

Who Is at Risk? The Role of Airway Imaging in Chronic Lung Disease Risk Assessment

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Annals of the American Thoracic Society, Volume 15, Issue 6, Page 669-670, June 2018.


https://ift.tt/2JlSHkU

Diet Pattern and Respiratory Morbidity in the Atherosclerosis Risk in Communities Study

Annals of the American Thoracic Society, Volume 15, Issue 6, Page 675-682, June 2018.


https://ift.tt/2HaiUhm

The Effect of Defining Chronic Obstructive Pulmonary Disease by the Lower Limit of Normal of the FEV1/FVC Ratio

Annals of the American Thoracic Society, Volume 15, Issue 6, Page 766-767, June 2018.


https://ift.tt/2kGhOAT

Anemia and Adverse Outcomes in a Chronic Obstructive Pulmonary Disease Population with a High Burden of Comorbidities. An Analysis from SPIROMICS

Annals of the American Thoracic Society, Volume 15, Issue 6, Page 710-717, June 2018.


https://ift.tt/2syqRY7

Can the Plateau Be Higher Than the Peak Pressure?

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Annals of the American Thoracic Society, Volume 15, Issue 6, Page 754-759, June 2018.


https://ift.tt/2kIPvlw

Leadership Primer for Current and Aspiring Pulmonary, Critical Care, and Sleep Medicine Academic Division Chiefs

Annals of the American Thoracic Society, Volume 15, Issue 6, Page 655-661, June 2018.


https://ift.tt/2syqFrR

Asthma in Navajo Children: Striving for Health Equity

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Annals of the American Thoracic Society, Volume 15, Issue 6, Page 671-674, June 2018.


https://ift.tt/2kEQLpK

Erratum: Structure and Function Relationships in Diseases of the Small Airways

Annals of the American Thoracic Society, Volume 15, Issue 6, Page 768-768, June 2018.


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Erratum: A Practical Approach to Severe Asthma in Children

Annals of the American Thoracic Society, Volume 15, Issue 6, Page 767-768, June 2018.


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Chronic Azithromycin Use in Cystic Fibrosis and Risk of Treatment-Emergent Respiratory Pathogens

Annals of the American Thoracic Society, Volume 15, Issue 6, Page 702-709, June 2018.


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Inspiratory Muscle Rehabilitation in Critically Ill Adults. A Systematic Review and Meta-Analysis

Annals of the American Thoracic Society, Volume 15, Issue 6, Page 735-744, June 2018.


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Major vessel sealing in laparoscopic surgery for colorectal cancer: a single-center experience with 759 patients

Abstract

Background

Efficient hemostatic techniques are essential in laparoscopic surgery for ideal intraoperative and postoperative results. A variety of advanced devices are available for the sealing of major vascular structures. The aim of this study is to assess effectiveness and safety of major vessel sealing with a radiofrequency device during laparoscopic colorectal resections for cancer based on the experience of a single hospital.

Methods

Early outcomes of a consecutive series of patients who received elective laparoscopic colorectal resections for cancer over a 10-year period (January 2008–September 2017) are analyzed.

In all procedures, the Ligasure® electrothermal bipolar device was used for the closure of the major colonic vessels and the dissection of all the structures. No other products such clips, staplers, hemostatic products, or other devices were used.

Results

Seven-hundred fifty-nine procedures were performed in laparoscopy: 179 rectal resections, 247 sigmoidectomies and left hemicolectomies, 240 right hemicolectomies, 33 resections of the splenic flexure, 35 transverse colonic resections, and 25 other procedures.

In 39 cases, the laparoscopic procedure was converted to open surgery, and in these cases, vessel sealing was also achieved with the radiofrequency device alone.

Vessel dissection and sealing was realized in all cases without any intraoperative or postoperative bleeding. No reoperations for bleeding from major vessels were performed in any patients. One case of reoperation was recorded postoperatively, at 3 h after right hemicolectomy, due to a small bleeding from the fat of the transverse colon stump.

Conclusions

The use of Ligasure® radiofrequency device for sealing and dividing the major colonic vessels is safe, fast, and effective during laparoscopic colorectal resections.



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Pre-operative stromal stiffness measured by shear wave elastography is independently associated with breast cancer-specific survival

Abstract

Introduction

With the increased use of neoadjuvant therapy for breast cancer, there is a need for pre-operative prediction of prognosis. We aimed to assess the prognostic value of tumour stiffness measured by ultrasound shear wave elastography (SWE).

Methods

A consecutive cohort of patients with invasive breast cancer underwent breast ultrasound (US) including SWE. The following were recorded prospectively: US diameter, stiffness at SWE, presentation source, core biopsy grade, oestrogen receptor (ER) status and pre-operative nodal status. Breast cancer-specific survival (BCSS) was analysed with regard to US size and stiffness, tumour grade on core biopsy, ER status, presentation mode and pre-operative nodal status. Analysis used Cox proportional hazards regression.

Results

Of the 520 patients, 42 breast cancer and 53 non-breast cancer deaths were recorded at mean follow-up of 5.4 years. Hazard ratios (HR) for tertiles of stiffness were 1, 4.8 and 8.1 (P = 0.0001). HR for 2 groups based on US size < or ≥ 20 mm were 1 and 5.1 (P < 0.0001). HR for each unit increase in tumour grade on core biopsy was 3.9 (P < 0.0001). The HR for ER positivity compared to ER negativity was 0.21 (P < 0.001). BCSS was also associated with presentation mode and pre-operative nodal status. In a multivariable model, stiffness, US size and ER status were independently associated with BCSS.

Conclusion

Multiple pre-operative factors including stromal stiffness at SWE have independent prognostic significance. A larger dataset with longer follow-up could be used in the future to construct a pre-operative prognostic model to guide treatment decisions.



https://ift.tt/2szfgZ7

The Relationships Between Cold Ischemia Time, Kidney Transplant Length of Stay, and Transplant-Related Costs

BACKGROUND Recent changes in policies guiding allocation of transplant kidneys are predicted to increase sharing between distant geographic regions. The potential exists for an increase in cold ischemia time (CIT) with resulting increases in delayed graft function (DGF) and transplant-related costs (TRC). We sought to explore the impact of CIT on metrics that may influence TRC. METHODS Between 2006 and 2014, 81,945 adult solitary deceased donor kidney transplants (KT) were performed in the United States; 477 (0.6%) at our institution. Regression models were constructed to describe the relationship between CIT on DGF and length of stay (LOS). Using hospital accounting data, we created regression models to evaluate the effect of DGF on LOS and TRC. RESULTS In multivariable models, longer CIT was associated with an increased rate of DGF (odds ratio [OR] 1.41; 95% confidence interval [CI] 1.38-1.44) and increased LOS (1.04; 1.02-1.05). Recipients at our institution who developed DGF had longer LOS (1.71; 1.50-1.95), suggesting that the effect is partially mediated by DGF. After adjusting for LOS, neither CIT nor DGF were independently associated with increased TRC. However, an increased LOS resulted in an increase in TRC by $3422 (95% CI: $3180 - $3664) per additional day, indicating that the effect of CIT on TRC is partially mediated through LOS. CONCLUSION The prolongation of CIT is associated with an increase in DGF rates and LOS, resulting in increased TRC. This study raises the need to balance increased access of traditionally-underserved populations to KT with the inadvertent increase in TRC. Presented at the American Transplant Congress 2016 (Boston, MA). Correspondence: Oscar K. Serrano, MD, Department of Surgery, Division of Transplantation, 420 Delaware Street SE, Mayo Mail Code 195, Minneapolis, MN 55455. Email: serra01@umn.edu Authorship: •Participated in research design: Serrano, Vock, Matas, Finger. •Participated in the writing of the paper: Serrano, Vock, Finger. •Participated in the editing of the paper: Serrano, Vock, Chinnakotla, Dunn, Kandaswamy, Pruett, Feldman, Matas, Finger. •Participated in the performance of the research: Serrano, Chinnakotla, Dunn, Kandaswamy, Pruett, Matas, Finger. •Contributed new reagents or analytic tools: Vock, Feldman •Participated in data analysis: Serrano, Vock, Matas, Finger. Disclosure: The authors declare no conflicts of interest. Funding: The authors declare no funding received for this work. DISCLAIMER The data reported here have been supplied by the Minneapolis Medical Research Foundation (MMRF) as the contractor for the Scientific Registry of Transplant Recipients (SRTR). The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy of or interpretation by the SRTR or the U.S. Government. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Donor Specific Antibody Surveillance and Graft Outcomes in Pediatric Kidney Transplant Recipients

Introduction The development of de novo donor-specific antibodies (dnDSA) has been associated with rejection and graft loss in kidney transplantation, and DSA screening is now recommended in all kidney transplant recipients. However, the clinical significance of dnDSA detected by screening patients with a stable creatinine remains unclear. Methods 103 patients

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Correction to: SEOM clinical guidelines for anaplastic gliomas (2017)

The SEOM/GEINO clinical guidelines provide recommendations for radiological, and molecular diagnosis, treatment and follow-up of adult patients with anaplastic gliomas (AG). We followed the 2016 WHO classification which specifies the major diagnostic/prognostic and predictive value of IDH1/IDH2 missense mutations and 1p/19q codeletions in AG. The diagnosis of anaplastic oligoastrocytoma is discouraged. Surgery, radiotherapy and chemotherapy with PCV or TMZ are the first-line standard of care for AG with slight modifications according to molecular variables. A multidisciplinary team is highly recommended in the management of these tumors.



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New Research From Psychological Science

Read about the latest research published in Psychological Science:

The Political Self: How Identity Aligns Preferences With Epistemic Needs
Christopher M. Federico and Pierce D. Ekstrom

Previous research has suggested that people motivated to quickly get answers and make decisions (i.e., those with high need for closure) tend to affiliate with the political right. However, people who prefer to keep their options open (i.e., those with low need for closure) tend to affiliate with the political left. But how does the extent to which one's political preferences are central to one's self-concept affect these findings? The authors analyzed data from a U.S. representative survey and found that need for closure was related to political ideology only in people who saw their political beliefs as central to their self-concept. In those people, high need for closure was related to conservative political identity and issue attitudes, and low need for closure was related to liberal political identity and issue attitudes. Political identity accounted for the relation between need for closure and issue attitudes. These results show that the relationship between personality and political preferences is complex, and opposing political preferences do not always mean personality differences.

Corepresentation During Joint Action in Marmoset Monkeys (Callithrix jacchus)
Fabia M. Miss and Judith M. Burkart

Humans represent their own actions and their partner's actions while engaging in cooperative behavior, but do other cooperative primate species show such corepresentation? The researchers tested 10 marmosets using an auditory version of the Simon task, which requires participants to make either left-hand or right-hand responses to auditory stimuli. Marmosets performed the task individually and with a partner. Similar to humans, marmosets performed better when the stimulus and the required response were compatible (i.e., they occurred on the same side), a "Simon effect" that was even stronger when the task was performed with a partner. The effect did not occur in the control conditions when one response was not available or when the partner was present but could not collaborate. Results showed that marmosets engaged in mutual gaze before action and looked at their partner more when the partner was collaborating. These results indicate that action corepresentation is not unique to humans and suggest that it does not depend on having a theory of mind.

Evidence of Serial Processing in Visual Word Recognition
Alex L. White, John Palmer, and Geoffrey M. Boynton

Vision begins with the ability to process several elements from the visual field at the same time, in parallel. But what are the limits of this parallel processing? The authors tested whether a serial bottleneck that would allow the visual system to process only one item at a time would constrain visual recognition. They asked participants to fixate on the center of a screen while masked pairs of words were rapidly presented. Participants had to detect target words that belonged to a semantic category or were colored red on one side of the pair (single-task condition) or on both sides (dual-task condition). Results showed that, in the dual-task condition, detection of semantic target words was more impaired than detection of colored words. These results show that the visual system can handle many elements at the same time if only physical features are being processed. When semantic meaning is being processed, a serial bottleneck limits parallel processing. Thus, parallel visual processing is limited by the nature of the task, and semantic recognition requires attention.

Asymmetric Mixtures: Common Conceptual Priorities for Social and Chemical Kinds
Alexander Noyes and Frank C. Keil

People tend to categorize biracial individuals as belonging to the minority category; for example, Black-White biracial individuals are seen as Black instead of White. This phenomenon is called hypodescent. Hypodescent might be caused by a focus of attention on distinctive and dangerous factors that affect general conceptual representations and that are extendable to nonsocial domains. In three experiments, the authors tested this idea by asking participants to categorize mixtures of two liquids. The liquids varied in distinctiveness and dangerousness (water, cranberry juice, apple juice, saline, vodka, Vicodin, urine, and cyanide). The results showed that participants asymmetrically categorized the mixtures as belonging to the distinctive-dangerous category, even when that category's component was less than 50% of the mixture. In another study, participants classified biracial individuals, including categories not usually studied, such as South Asian or Aboriginal Australian. People with Arab and Black ancestry were classified as more Arab and Black, respectively, regardless of their other racial component. Moreover, ratings of danger-potency and distinctiveness predicted liquid and racial hypodescent. These results support the idea that general cognitive factors, rather than social-cognitive factors, create hypodescent.



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Pipeline Embolization for Salvage Treatment of Previously Stented Residual and Recurrent Cerebral Aneurysms

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Introduction: This study assessed the safety and effectiveness of the Pipeline embolization device (PED) for persistent and recurrent aneurysms previously treated with either a vascular reconstruction device (VRD) or a flow diverter (FD). Methods: A prospective, IRB-approved database was analyzed for patients treated with PED for aneurysms previously treated with a stent. Results: Twenty procedures were performed on 18 patients, 11 with prior FD, 7 with VRD, and 2 previously treated with both. Overall, 15 aneurysms were saccular (75%), and size was 13.5 ± 7.6 mm. Location was internal carotid artery (ICA) in 14 cases (70%) and posterior circulation in 6 cases (30%). Average prior treatments were 1.7. Previously FD cases were re-treated at an average of 18.1 months from most recent treatment. Each case used 1 device, 82% with distal coverage and 82% with proximal coverage of prior stent. Balloon remodeling was performed in 3 cases (27%) and no in-stent thrombosis was observed. Previously VRD stent-coiled cases were re-treated at an average of 87.5 months. These cases used on average 1.9 devices, 89% with distal and 100% proximal coverage. Adjunctive coiling was performed in 1 case (11%), balloon remodeling in 5 cases (56%), and 2 cases (28%) developed thrombosis that resolved with abciximab. Re-VRD cases were longer (59.1 vs. 33.7 min, p = 0.02) than re-FD. Angiographic follow-up was available for 16 cases (80%). In re-FD, occlusion was complete in 56% and partial progressive in 33% at 17.1 months digital subtraction angiography. In re-VRD, occlusion was complete in 57% and partial progressive in 27% at 8.1 months. Two complications occurred (10%), including one asymptomatic cervical ICA occlusion and one stent occlusion with associated mortality (5%). Clinical follow-up was 17.8 months on average (range 0.5–51.9). Conclusions: Salvage flow diversion for previously stented aneurysms is technically challenging but offers good prospects of aneurysm obliteration with acceptable complication rates.
Intervent Neurol 2018;7:359–369

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Tissue preservation with mass spectroscopic analysis: Implications for cancer diagnostics

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Breast cancer in an 18-year-old female: A fatal case report and literature review

Volume 19, Issue 7, July 2018, Page 543-548
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Cancers, Vol. 10, Pages 175: Factors Influencing the Clinical Presentation of Breakthrough Pain in Cancer Patients

Cancers, Vol. 10, Pages 175: Factors Influencing the Clinical Presentation of Breakthrough Pain in Cancer Patients

Cancers doi: 10.3390/cancers10060175

Authors: Mercadante Sebastiano Marchetti Paolo Cuomo Arturo Caraceni Augusto Masedu Francesco Aielli Federica on behalf of the IOPS-MS Study Group

Background: The aim of this study was to identify potential variables influencing the clinical presentation of breakthrough cancer pain (BTP). Methods: Cancer patients with a diagnosis of BTP were enrolled. Demographic and clinical characteristics, as well as background pain and BTP characteristics were collected. Multivariate analyses were conducted to assess the correlation between BTP characteristics and the variables examined. Results: Data of 4016 patients were analysed. Average daily number of BTP episodes was 2.4, mean intensity was 7.5, and a mean duration was 43.3 min. A short onset BTP was observed in 68.9% of patients. In 30.5% of patients BTP was predictable. There were 86.0% of participants who reported a marked interference of BTP with their daily activities. Furthermore, 86.8% of patients were receiving opioids for the management of BTP. The average time to meaningful pain relief was 16.5 min and 70.9% of patients were satisfied with their BTP medications. Age, head and neck cancer, Karnofsky, background pain intensity, predictable and fast onset BTP were independently associated with the number of BTP episodes. BTP pain intensity was independently associated with background pain intensity, fast onset BTP, and Karnofsky. Neuropathic pain mechanism was independently associated with unpredictable BTP. Variables independently associated with a longer duration of BTP were age, place of visit, cancer diagnosis, disease-oriented therapy, background pain intensity and mechanism, and unpredictable BTP. Age, Karnofsky, background pain intensity, fast onset, and long duration of BTP were independently associated with interference with daily activity. Conclusions: BTP has a variable presentation depending on interdependent relationships among its different characteristics.



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Mapping of 238 Quadrilateral Plate Fractures with Three-Dimensional Computed Tomography

Publication date: Available online 31 May 2018
Source:Injury
Author(s): Yun Yang, Min Yi, Chang Zou, Zhao-kui Yan, Xin-an Yan, Yue Fang
PurposeThe primary goal of this study is to create a frequency map of a series of the quadrilateral plate fractures, explore the characteristics of fracture map and to further propose a new classification.MethodsWe used a consecutive series of 238 quadrilateral plate fractures to create 3-dimensional reconstruction images, which were superimposed and oriented to fit a model hemipelvis template by aligning specific pelvis landmarks. Fracture lines were identified and traced to create a quadrilateral plate fracture map.ResultsFracture location corresponded with fracture line distribution. Of 238 fractures that met the criteria for inclusion, most fractures involved the "A + B" zone (n = 156; 65%), whereas the remaining minority of the fractures involved the "A" zone (n = 59; 25%) and the "B" zone (n = 23; 10%). Correspondingly the incidence of C-type fracture ("A + B"zone) was significantly higher than that of A-type fracture and B-type fracture. Additionally the most common pattern was demonstrated by coexisting fracture lines; nearly half (48%) of the fractures involved the upper section of the quadrilateral plate traversing both zones, 46% traced almost vertically to the arcuate line, and 25% extended to the posterior aspect. Furthermore, the high fracture line intensity (n = 172; 74%) formed a Gun-shaped pattern, which pointed to the ischial tuberosity.ConclusionsThe map shows that the comminution is prone to traverse the quadrilateral plate in the sagittal direction among nearly two-thirds of all fractures. Moreover, Surgically treated quadrilateral plate fractures display very common patterns. The most common pattern is the upper fracture in nearly half of the fractures. Knowledge of these patterns can aid surgeons during diagnosis, preoperative planning, and execution of surgical strategies.



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Accuracy of Sacroiliac Screw Placement With and Without Intraoperative Navigation and Clinical Application of the Sacral Dysmorphism Score

Publication date: Available online 31 May 2018
Source:Injury
Author(s): Alex Quok An Teo, Jing Hui Yik, Gavin Kane O'Neill
IntroductionPercutaneously-placed sacroiliac (SI) screws are currently the gold-standard fixation technique for fixation of the posterior pelvic ring. The relatively high prevalence of sacral dysmorphism in the general population introduces a high risk of cortical breach with resultant neurovascular damage. This study was performed to compare the accuracy of SI screw placement with and without the use of intraoperative navigation, as well as to externally validate the sacral dysmorphism score in a trauma patient cohort.Patients and methodsAll trauma patients who underwent sacroiliac screw fixation for pelvic fractures at a level 1 trauma centre over a 6 year period were identified. True axial and coronal sacral reconstructions were obtained from their pre-operative CT scans and assessed qualitatively and quantitatively for sacral dysmorphism – a sacral dysmorphism score was calculated by two independent assessors. Post-operative CT scans were then analysed for breaches and correlated with the hospital medical records to check for any clinical sequelae.Results68 screws were inserted in 36 patients, most sustaining injuries from road traffic accidents (50%) or falls from height (36.1%). There was a male preponderance (83.3%) with the majority of the screws inserted percutaneously (86.1%). Intraoperative navigation was used in 47.2% of the patient cohort. 30.6% of the cohort were found to have dysmorphic sacra. The mean sacral dysmorphism scores were not significantly different between navigated and non-navigated groups. Three cortical breaches occurred, two in patients with sacral dysmorphism scores >70 and occurring despite the use of intraoperative navigation. There was no significant difference in the rates of breach between navigated and non-navigated groups. None of the breaches resulted in any clinically observable neurovascular deficit.ConclusionThe sacral dysmorphism score can be clinically applied to a cohort of trauma patients with pelvic fractures. In patients with highly dysmorphic sacra, reflected by high sacral dysmorphism scores, intraoperative navigation is not in itself sufficient to prevent cortical breaches. In such patients it would be prudent to consider instrumentation of the lower sacral corridors instead.



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Outcomes of tibia shaft fractures caused by low energy gunshot wounds

Publication date: Available online 31 May 2018
Source:Injury
Author(s): Charles A. Su, Mai P. Nguyen, Jeffrey A. O'Donnell, Heather A. Vallier
BackgroundThe purpose of this project was to compare the rates of infections, nonunions, malunions, and secondary operations in tibia fractures resultant from low energy GSWs versus those seen in open and closed tibia fractures resultant from blunt trauma. A secondary objective was to assess the utility of using the traditional Gustilo-Anderson classification system for open fractures to describe fractures secondary to low energy GSW.MethodsA retrospective review of 327 patients with tibia shaft fractures was conducted at our level I trauma center. Patients underwent a variety of interventions depending on their injury. Standard fixation techniques were utilized. Outcome measures include: mechanism of injury, rates of superficial and deep infection, nonunion, malunion, and secondary operations.ResultsDeep infection after low energy GSW tibia fractures was uncommon and seen in only 2.3% of patients. Rates of infection after low energy GSWs were similar to low and high energy closed tibia fractures resultant from blunt trauma, but significantly less than that seen in open type II (25%, p < 0.05), type IIIA (19.5%, p < 0.05), and type IIIB fractures (47%, p < 0.01). There were no nonunions following GSW fractures, versus 3.7% after closed tibia fractures from blunt trauma (p = 0.2). Nonunions were more common after open fractures from blunt trauma (11%, p < 0.05) versus GSWs. Differences in infection and nonunion were associated with more secondary operations (18%, p < 0.01) in the open tibia fracture group compared with GSWs (2.3%) and closed fractures (7.9% p = 0.19).ConclusionsWhile GSWs are traditionally thought of as open injuries, low energy GSW tibia fractures had a low rate of infection and no nonunions, and resulted in a reoperation rate similar to closed blunt tibia shaft fractures and significantly lower than open tibia fractures.



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Preventing EMS workplace violence: A mixed-methods analysis of insights from assaulted medics

Publication date: Available online 31 May 2018
Source:Injury
Author(s): Brian J. Maguire, Barbara J. O'Neill, Peter O'Meara, Matthew Browne, Michael T. Dealy
ObjectiveTo describe measures that assaulted EMS personnel believe will help prevent violence against EMS personnel.MethodsThis mixed- methods study includes a thematic analysis and directed content analysis of one survey question that asked the victims of workplace violence how the incident might have been prevented.ResultsOf 1778 survey respondents, 633 reported being assaulted in the previous 12 months; 203 of them believed the incident could have been prevented and 193 of them (95%) answered this question. Six themes were identified using Haddon's Matrix as a framework. The themes included: Human factors, including specialized training related to specific populations and de-escalation techniques as well as improved situational awareness; Equipment factors, such as restraint equipment and resources; and, Operational and environment factors, including advanced warning systems. Persons who could have prevented the violence were identified as police, self, other professionals, partners and dispatchers. Restraints and training were suggested as violence-prevention tools and methodsConclusionsThis is the first international study from the perspective of victimized EMS personnel, to report on ways that violence could be prevented. Ambulance agencies should consider these suggestions and work with researchers to evaluate risks at the agency level and to develop, implement and test interventions to reduce the risks of violence against EMS personnel. These teams should work together to both form an evidence-base for prevention and to publish findings so that EMS medical directors, administrators and professionals around the world can learn from each experience.



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Postoperative Care Handbook of the Massachusetts General Hospital

No abstract available

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Starving Patients Before Cataract Surgery Under Regional Anesthesia: Needed or Not?

No abstract available

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Race/Ethnicity and Sex Both Affect Opioid Administration in the Emergency Room

BACKGROUND: Although racial/ethnic and sex disparities have been examined in health care generally and pain management more specifically, the combined influence of these sociodemographic factors together has not been well documented. The aim of this study was to examine the association between administration of opioid analgesics in the emergency department (ED) and interaction of race/ethnicity and sex. METHODS: We conducted a retrospective cohort study using 2010–2014 Center for Disease Control-National Hospital Ambulatory Medical Care Survey data for patients 12–55 years of age presenting to EDs with a primary diagnosis of appendicitis or gallbladder disease as defined by International Classification of Diseases, Ninth Revision codes. The primary outcome was the receipt of opioid analgesic medications. Secondary outcomes included: receipt of nonopioids, receipt of antiemetic medications, wait time to see a provider, and length of visit in the ED. The association between sex and analgesic receipt within Caucasian non-Hispanic and non-Caucasian groups was evaluated adjusting for pain score on presentation, patient age, emergent status, city/noncity location, number of comorbidities, time of visit (month, day of the week, standard versus nonstandard working hours, year), and US region. RESULTS: After exclusions, a weighted sample of 553 ED visits was identified, representing 2,622,926 unique visits. The sample population was comprised of 1,858,035 (70.8%) females and 1,535,794 (58.6%) Caucasian non-Hispanics. In adjusted models, Caucasian non-Hispanic males 317,427/525,435 (60.4%) were slightly less likely to receive opioids than Caucasian non-Hispanic females 621,638/1,010,360 (61.5), odds ratio = 0.962, 95% CI, 0.955–0.970; P

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Fibrinogen Concentrate in Cardiovascular Surgery: A Meta-analysis of Randomized Controlled Trials

BACKGROUND: Postoperative bleeding remains a frequent complication after cardiovascular surgery and may contribute to serious morbidity and mortality. Observational studies have suggested a relationship between low endogenous plasma fibrinogen concentration and increased risk of postoperative blood loss in cardiac surgery. Although the transfusion of fibrinogen concentrate has been increasing, potential benefits and risks associated with perioperative fibrinogen supplementation in cardiovascular surgery are not fully understood. METHODS: PubMed, Cochrane Library, Ovid MEDLINE, Embase, Web of Science, and China National Knowledge Infrastructure were searched on January 15, 2017, with automated updates searched until February 15, 2018, to identify all randomized controlled trials (RCTs) of fibrinogen concentrate, whether for prophylaxis or treatment of bleeding, in adults undergoing cardiovascular surgery. All RCTs comparing fibrinogen infusion versus any other comparator (placebo/standard of care or another active comparator) in adult cardiovascular surgery and reporting at least 1 predefined clinical outcome were included. The random-effects model was used to calculate risk ratios and weighted mean differences (95% confidence interval [CI]) for dichotomous and continuous variables, respectively. Subgroup analyses by fibrinogen dose and by baseline risk for bleeding were preplanned. RESULTS: A total of 8 RCTs of fibrinogen concentrate in adults (n = 597) of mixed risk or high risk undergoing cardiovascular surgery were included. Compared to placebo or inactive control, perioperative fibrinogen concentrate did not significantly impact risk of all-cause mortality (risk ratio, 0.41; 95% CI, 0.12–1.38; I2 = 10%; P = .15). Fibrinogen significantly reduced incidence of allogeneic red blood cell transfusion (risk ratio, 0.64; 95% CI, 0.49–0.83; I2 = 0%; P = .001). No significant differences were found for other clinical outcomes. Subgroup analyses were unremarkable when analyzed according to fibrinogen dose, time of infusion initiation, mean cardiopulmonary bypass time, and rotational thromboelastometry/fibrinogen temogram use (all P values for subgroup interaction were nonsignificant). CONCLUSIONS: Current evidence remains insufficient to support or refute routine perioperative administration of fibrinogen concentrate in patients undergoing cardiovascular surgery. Fibrinogen concentrate may reduce the need for additional allogeneic blood product transfusion in cardiovascular surgery patients at high risk or with evidence of bleeding. However, no definitive advantage was found for reduction in risk of mortality or other clinically relevant outcomes. The small number of clinical events within existing randomized trials suggests that further well-designed studies of adequate power and duration to measure all-cause mortality, stroke, myocardial infarction, reoperation, and thromboembolic events should be conducted. Future studies should also address cost-effectiveness relative to standard of care. Accepted for publication April 30, 2018. Funding: This work was supported by the Department of Anesthesia and Perioperative Medicine, Western University. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Janet Martin, PharmD, MSc(HTA&M), Department of Anesthesia and Perioperative Medicine, Schulich School of Medicine & Dentistry, Western University, University Hospital, Room C3-412, 339 Windermere Rd, London, ON N6A 5A5, Canada. Address e-mail to jmarti83@uwo.ca. © 2018 International Anesthesia Research Society

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Inhibition of Fatty Acid Amide Hydrolase Improves Depressive-Like Behaviors Independent of Its Peripheral Antinociceptive Effects in a Rat Model of Neuropathic Pain

BACKGROUND: Neuropathic pain is often associated with depression. Enhancing endocannabinoids by fatty acid amide hydrolase (FAAH) inhibitors relieves neuropathic pain and stress-induced depressive-like behaviors in animal models. However, it is unclear whether FAAH inhibitor can relieve neuropathic pain–induced depression by or not by its antinociceptive effects. METHODS: Adult male Wistar rats with chronic constriction injury (CCI) to the sciatic nerve were treated with the systemic FAAH inhibitor URB597 (5.8 mg·kg−1·day−1, intraperitoneally) or peripherally acting FAAH inhibitor URB937 (1.6 mg·kg−1·d−1, intraperitoneally; n = 11–12). The treatment was applied from the 15th day after surgery and continued for 15 days. Mechanical withdrawal threshold was examined by Von Frey test before surgery and on the 28th day after CCI. Depressive-like behaviors were evaluated by forced swimming test (FST) and novelty-suppressed feeding (NSF) after 15-day treatment. The levels of anandamide and 2-arachidonoylglycerol in hippocampus were examined by liquid chromatography and mass spectrometry. Hippocampal neurogenesis including proliferation, differentiation, and survival of newborn cells was assessed by immunohistochemistry. RESULTS: After CCI injury, the rats developed significantly nociceptive and depressive-like behaviors, indicated by persistent mechanical hypersensitivity in Von Frey test, significantly prolonged immobility time in FST (sham: 84.2 ± 13.4 seconds versus CCI: 137.9 ± 18.8 seconds; P

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Resuscitation of Endotheliopathy and Bleeding in Thoracic Aortic Dissections: The VIPER-OCTA Randomized Clinical Pilot Trial

BACKGROUND: Thoracic aorta dissection is an acute critical condition associated with shock-induced endotheliopathy, coagulopathy, massive bleeding, and significant morbidity and mortality. Our aim was to compare the effect of coagulation support with solvent/detergent-treated pooled plasma (OctaplasLG) versus standard fresh frozen plasma (FFP) on glycocalyx and endothelial injury, bleeding, and transfusion requirements. METHODS: Investigator-initiated, single-center, blinded, randomized clinical pilot trial of adult patients undergoing emergency surgery for thoracic aorta dissection. Patients were randomized to receive OctaplasLG or standard FFP as coagulation factor replacement related to bleeding. The primary outcome was glycocalyx and endothelial injury. Other outcomes included bleeding, transfusions and prohemostatics at 24 hours, organ failure, length of stay in the intensive care unit and in the hospital, safety, and mortality at 30 and 90 days. RESULTS: Fifty-seven patients were included to obtain 44 evaluable on the primary outcome. The OctaplasLG group displayed significantly reduced damage to the endothelial glycocalyx (syndecan-1) and reduced endothelial tight junction injury (sVE-cadherin) compared to standard FFP. In the OctaplasLG group compared to the standard FFP, days on ventilator (1 day [interquartile range, 0–1] vs 2 days [1–3]; P = .013), bleeding during surgery (2150 [1600–3087] vs 2750 [2130–6875]; P = .046), 24-hour total transfusion and platelet transfusion volume (3975 mL [2640–6828 mL] vs 6220 mL [4210–10,245 mL]; P = .040, and 1400 mL [1050–2625 mL] vs 2450 mL [1400–3500 mL]; P = .027), and goal-directed use of prohemostatics (7/23 [30.4%] vs 13/21 [61.9%]; P = .036) were all significantly lower. Among the 57 patients randomized, 30-day mortality was 20.7% (6/29) in the OctaplasLG group and 25% (7/28) in the standard FFP group (P = .760). No safety concern was raised. CONCLUSIONS: In this randomized, clinical pilot trial of patients undergoing emergency surgery for thoracic aorta dissections, we found that OctaplasLG reduced glycocalyx and endothelial injury, reduced bleeding, transfusions, use of prohemostatics, and time on ventilator after surgery compared to standard FFP. An adequately powered multicenter trial is warranted to confirm the clinical importance of the findings. Accepted for publication May 8, 2018. Funding: This investigator-initiated trial was funded by internal department funds and an unrestricted research grant from Octapharma AG, the manufacturer of OctaplasLG, paid to and administered by Copenhagen University Hospital, Rigshospitalet, to support the execution of the trial covering expenses to assisting staff, on-call research assistants, blood samples, laboratory analyses, etc. Octapharma AG also supplied the investigational product of the trial free of charge. None of the authors involved have received ­personal income from Octapharma AG, have shares or financial interests in Octapharma AG, and Octapharma AG had no role in the design of this study, its execution, analysis, interpretation of the data, writing of the article, or decision to submit results. Conflicts of Interest: See Disclosures at the end of the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). The trial was registered before patient enrollment at clinicaltrials.gov (NCT02253082, principal investigator: J.S.; date of registration: October 1, 2014). Reprints will not be available from the authors. Address correspondence to Jakob Stensballe, PhD, Section for Transfusion Medicine, Capital Region Blood Bank and Department of Anesthesia, Centre of Head and Orthopedics, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen DK-2100, Denmark. Address e-mail to jakob.stensballe@regionh.dk. © 2018 International Anesthesia Research Society

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