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Τετάρτη 5 Δεκεμβρίου 2018

Impact of Altered Airway Pressure on Intracranial Pressure, Perfusion, and Oxygenation: A Narrative Review

Objectives: A narrative review of the pathophysiology linking altered airway pressure and intracranial pressure and cerebral oxygenation. Data Sources: Online search of PubMed and manual review of articles (laboratory and patient studies) of the altered airway pressure on intracranial pressure, cerebral perfusion, or cerebral oxygenation. Study Selection: Randomized trials, observational and physiologic studies. Data Extraction: Our group determined by consensus which resources would best inform this review. Data Synthesis: In the normal brain, positive-pressure ventilation does not significantly alter intracranial pressure, cerebral oxygenation, or perfusion. In injured brains, the impact of airway pressure on intracranial pressure is variable and determined by several factors; a cerebral venous Starling resistor explains much of the variability. Negative-pressure ventilation can improve cerebral perfusion and oxygenation and reduce intracranial pressure in experimental models, but data are limited, and mechanisms and clinical benefit remain uncertain. Conclusions: The effects of airway pressure and ventilation on cerebral perfusion and oxygenation are increasingly understood, especially in the setting of brain injury. In the face of competing mechanisms and priorities, multimodal monitoring and individualized titration will increasingly be required to optimize care. Drs. Chen, Menon, and Kavanagh helped with conception and design, and drafting the article for important intellectual content. 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/29S62lw). Supported, in part, by research funds (to Dr. Kavanagh) from the Canadian Institutes of Health Research. Dr. Chen is supported by National Natural Science Foundation of China (Grant Number: 81701942). Dr. Menon received support for article research from National Institute for Health Research, United Kingdom. He is a Professorial Fellow, Queens' College, Cambridge, United Kingdom, and a Senior Investigator, National Institute for Health Research, United Kingdom. Dr. Kavanagh disclosed that he has a patent pending for a device for mechanical ventilation. He holds the Dr Geoffrey Barker Chair in Critical Care Research. For information regarding this article, E-mail: brian.kavanagh@utoronto.ca Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Risk Factors for New-Onset Atrial Fibrillation in Patients With Sepsis: A Systematic Review and Meta-Analysis

Objective: Atrial fibrillation frequently develops in patients with sepsis and is associated with increased morbidity and mortality. Unfortunately, risk factors for new-onset atrial fibrillation in sepsis have not been clearly elucidated. Clarification of the risk factors for atrial fibrillation during sepsis may improve our understanding of the mechanisms of arrhythmia development and help guide clinical practice. Data Sources: Medline, Embase, Web of Science, and Cochrane CENTRAL. Study Selection: We conducted a systematic review and meta-analysis to identify risk factors for new-onset atrial fibrillation during sepsis. Data Extraction: We extracted the adjusted odds ratio for each risk factor associated with new-onset atrial fibrillation during sepsis. For risk factors present in more than one study, we calculated pooled odds ratios (meta-analysis). We classified risk factors according to type and quantified the factor effect sizes. We then compared sepsis-associated atrial fibrillation risk factors with risk factors for community-associated atrial fibrillation. Data Synthesis: Forty-four factors were examined as possible risk factors for new-onset atrial fibrillation in sepsis, 18 of which were included in meta-analyses. Risk factors for new-onset atrial fibrillation included demographic factors, comorbid conditions, and most strongly, sepsis-related factors. Sepsis-related factors with a greater than 50% change in odds of new-onset atrial fibrillation included corticosteroid use, right heart catheterization, fungal infection, vasopressor use, and a mean arterial pressure target of 80–85 mm Hg. Several cardiovascular conditions that are known risk factors for community-associated atrial fibrillation were not identified as risk factors for new-onset atrial fibrillation in sepsis. Conclusions: Our study shows that risk factors for new-onset atrial fibrillation during sepsis are mainly factors that are associated with the acute sepsis event and are not synonymous with risk factors for community-associated atrial fibrillation. Our results provide targets for future studies focused on atrial fibrillation prevention and have implications for several key areas in the management of patients with sepsis such as glucocorticoid administration, vasopressor selection, and blood pressure targets. Dr. Bosch takes responsibility for the integrity of the work as a whole, from inception to published article, and he drafted the article. Drs. Bosch and Walkey substantially contributed to the conception and design of this study. Drs. Bosch and Cohen acquired the data. Drs. Bosch, Cohen, and Walkey were involved in the interpretation of data and revised it critically for important intellectual content. 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/29S62lw). Supported, in part, by National Heart, Lung, and Blood Institute grants 5K01HL116768-03 and 1R01HL136660-01 (to Dr. Walkey). Dr. Walkey's institution received funding from the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute; he received royalties from UptoDate; and he received support for article research from the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: nicholas.bosch@bmc.org Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Current Sepsis Mandates Are Overly Prescriptive, and Some Aspects May Be Harmful

No abstract available

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ERBB2 mutation frequency in lobular breast cancer with pleomorphic histology or high‐risk characteristics by molecular expression profiling

Abstract

HER2‐positive breast cancer is defined by amplification or overexpression of the HER2/ERBB2 oncogene and accounts for about 15% of breast cancer (BC) cases. Somatic mutation of ERBB2 is an alternative mechanism, by which activation of HER2 signaling can occur. ERBB2 mutation has been associated with invasive lobular breast cancer (ILBC). This study investigates the frequency and phenotype of ILBC harboring mutated ERBB2.

The ERBB2 mutation status was determined by next generation sequencing and/or pyrosequencing in n = 106 ILBCs, including n = 86 primary or locally recurrent tumors and n = 20 metastases from visceral organs, soft tissue or skin. Immunohistochemical characteristics were determined using tissue microarrays. This series was enriched for ILBCs with pleomorphic histology and/or high‐risk expression profiles (Oncotype DX, recurrence score RS > 25).

Nearly all specimens were E‐cadherin‐negative (99%), estrogen receptor (ER)‐positive (92%), and lacked ERBB2 overexpression (96%). ERBB2 mutations (p.V777 L, p.L755S, p.S310F) were identified in 5/106 (5%) cases. ERBB2‐mutated cases included 2/86 (2%) primary tumors and 3/20 (15%) metastases (P = 0.045). ERBB2‐mutated cases were associated with loss of ER (2/7, 29%, P = 0.035) and histological grade 3 (4/34, 12%, P = 0.023), but not with solid growth (3/31, 10%, P = 0.148) or pleomorphic histology (2/27, 7%, P = 0.599). No ERBB2 mutation was detected in ILBCs with RS > 25 (0/22, 0%). In ten patients with multiple matched specimens (n = 25), the ERBB2 mutational status was always concordant.

In summary, a small subset of ILBCs harbors potentially actionable ERBB2 mutations. In ERBB2‐mutated ILBCs, no association with pleomorphic histology was found.

This article is protected by copyright. All rights reserved.



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The Application of Blockchain Technology in Stroke Rehabilitation

No abstract available

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Pain therapy for the elderly patient: is opioid-free an option?

Purpose of review Chronic noncancer pain is an increasing problem in elderly because of rising life expectancy together with an increase of potentially painful medical conditions. Concomitantly, adequate treatment of elderly is often limited by coexisting diseases and polypharmacy.This review summarizes the most important specifics presented by elderly patients and discusses the pharmacological and nonpharmacological options of pain management. Recent findings A comprehensive pain assessment is a prerequisite for effective pain management. However, this can be a major challenge in patients who are unable to communicate adequately, that is, in patients with dementia. A recently developed electronic tool assessing automated facial expression and clinical behavioral indicators may help to solve this problem. The discussion about benefits and harms of opioids in elderly goes on. Although some authors underline the lack of efficacy together with the potential problems, such as, abuse, others report a beneficial effect in terms of pain relief, functional activities and disability. In addition, opioids have become an important treatment option in patients with restless legs syndrome. Various topical treatment options (i.e. capsaicin patch) and nonpharmacological interventions have been proven to be beneficial in elderly. Summary Adequate pain management of elderly patients constitutes numerous pharmacological options including nonopioids, opioids, coanalgesics and topical agents. Due to age-related characteristics, all systemic analgesics have to be given very cautiously ('start low, go slow'). Whenever possible, treatment should be performed as a multimodal approach based on the biopsychosocial model of chronic pain. Correspondence to Shahnaz Christina Azad, MD, PhD, Department of Anesthesiology and Pain Medicine, Ludwig-Maximilians University Munich, Marchioninistr. 15, 81377 Munich, Germany. Tel: +49 89440074464; fax: +49 89440074469; e-mail: shahnaz.azad@med.uni-muenchen.de Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Correlation Analysis of MRI-based Graft Maturity and Outcomes after Anterior Cruciate Ligament Reconstruction Using IKDC Score

Objective The correlation between the signal/noise quotient (SNQ) values of an anterior cruciate ligament (ACL) graft and the International Knee Documentation Committee (IKDC) Subjective Knee Form 2000 scores after ACL reconstruction was evaluated. Design Magnetic resonance imaging (MRI) and clinical evaluation using IKDC scores were utilized to calculate the signal intensity of the graft maturity at the six-month and twelve-month follow-up points postoperatively. The associations between the SNQ values at the six-month follow-up point and IKDC scores at the twelve-month follow-up point were evaluated. Results A total of 42 male patients completed our trial and returned to normal activity level before the surgery. The mean age of these patients was 29.07 ± 8.11 years (range, 17-47 years). The mean body mass index (BMI) was 26.00 ± 2.59 kg/m2. Notably, the Pearson correlation analysis showed that the IKDC scores obtained at 12 months were significantly associated with the SNQ values measured in the 6th month and 12th month, respectively (r = -0.454, p = 0.003; r = -0.478, p = 0.001). Conclusion According to this study, early measurement of graft maturity might predict the clinical outcome afterwards. The sensitive predictive value of SNQ could be utilized to maximize the patient outcomes. Corresponding author: Nanxin Zhang, Department of Orthopedics, the First Affiliated Hospital of Fujian Medical University, No. 20 Chazhong Road, Fuzhou 350004, Fujian, China. E-mail: zhangnanxin2018@163.com. Tel: 0086-0591-87982113; Fax: 0086-0591-87982113. This study was supported by the Health special funds of Fujian provincial finance department (BPB-LQ2016), the Natural Science Foundation of Fujian provincial science and Technology Department (2017J01283). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Ultrasonographic assessment of carpal tunnel syndrome severity: A systematic review and meta-analysis

OBJECTIVE To investigate the overall estimates of cross-sectional areas (CSA) of the median nerve measured by ultrasonography in accordance with the electrodiagnostic classification of carpal tunnel syndrome (CTS) severity. DESIGN MEDLINE (PubMed), EMBASE (Ovid), and Web of Science were searched for studies reporting the median nerve CSA measured by ultrasonography for mild, moderate and severe CTS based on electrodiagnostic study. CSA values measured at the carpal tunnel inlet were included in the analyses. RESULTS Overall, 866 citations were retrieved and checked for eligibility. Finally, 16 articles were included for meta-analysis. These studies included a total sample of 2,292 wrists including 776 mild, 823 moderate and 693 severe CTS. The pooled analysis revealed a mean CSA of 11.64 mm2 (95% CI: 11.23-12.05 mm2; P

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Response

No abstract available

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Strength reduction in unilateral shoulder pain: Is the healthy side really healthy in rotator cuff disease?

Objective The primary aim was to ascertain if unilateral shoulder pain is implicated in strength reduction both on the ipsilateral and contralateral side. Secondarily, we aimed to determine whether strength was affected by sonographic tendon abnormalities. Design A total of 122 subjects were evaluated. Sixty-six female subjects with unilateral shoulder pain in the dominant arm were recruited. Abduction strength was measured in both the dominant and non-dominant arm. High-resolution ultra-sonography was also conducted on both shoulders. A match-paired control group (n=66) composed of healthy volunteers underwent the same strength and sonography tests. Subjects with any radiographic anomaly were excluded from the control group. A mixed analysis of variance was performed to test the effect of unilateral shoulder pain on abduction strength. The effect of tendinopathy on shoulder strength was investigated using a mixed 2X2 ANOVA. Results ANOVA showed that patients with dominant shoulder pain had lower shoulder strength (11.65±4.05 kg) when compared to controls (14.37±4.00 kg; F=10.454, p=0,002). No statistically significant effects were found when comparing subjects with and without tendinopathy among the study group. Conclusion In patients with unilateral shoulder pain, abduction strength was found to be lower both on the ipsilateral and contralateral side. The presence of tendinopathy did not affect the reduction in strength. Future research is needed to substantiate these findings. Corresponding author: Valerio Sansone: valerio.sansone@unimi.it, IRCCS Istituto Ortopedico Galeazzi, Via Riccardo Galeazzi, 4, 20161 Milan, Italy. telephone: +39 6621 4921 Funding: No funding was received regarding the preparation of this manuscript. Declaration of Interest: The authors whose names are listed above certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Targeting of chondrocyte plasticity via connexin43 modulation attenuates cellular senescence and fosters a pro-regenerative environment in osteoarthritis

Targeting of chondrocyte plasticity via connexin43 modulation attenuates cellular senescence and fosters a pro-regenerative environment in osteoarthritis

Targeting of chondrocyte plasticity via connexin43 modulation attenuates cellular senescence and fosters a pro-regenerative environment in osteoarthritis, Published online: 05 December 2018; doi:10.1038/s41419-018-1225-2

Targeting of chondrocyte plasticity via connexin43 modulation attenuates cellular senescence and fosters a pro-regenerative environment in osteoarthritis

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Variant of SNP rs1317082 at CCSlnc362 (RP11-362K14.5) creates a binding site for miR-4658 and diminishes the susceptibility to CRC

Variant of SNP rs1317082 at CCSlnc362 (RP11-362K14.5) creates a binding site for miR-4658 and diminishes the susceptibility to CRC

Variant of SNP rs1317082 at CCSlnc362 (RP11-362K14.5) creates a binding site for miR-4658 and diminishes the susceptibility to CRC, Published online: 05 December 2018; doi:10.1038/s41419-018-1222-5

Variant of SNP rs1317082 at CCSlnc362 (RP11-362K14.5) creates a binding site for miR-4658 and diminishes the susceptibility to CRC

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Ferritin heavy subunit enhances apoptosis of non-small cell lung cancer cells through modulation of miR-125b/p53 axis

Ferritin heavy subunit enhances apoptosis of non-small cell lung cancer cells through modulation of miR-125b/p53 axis

Ferritin heavy subunit enhances apoptosis of non-small cell lung cancer cells through modulation of miR-125b/p53 axis, Published online: 05 December 2018; doi:10.1038/s41419-018-1216-3

Ferritin heavy subunit enhances apoptosis of non-small cell lung cancer cells through modulation of miR-125b/p53 axis

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Inactivation of Lon protease reveals a link between mitochondrial unfolded protein stress and mitochondrial translation inhibition

Inactivation of Lon protease reveals a link between mitochondrial unfolded protein stress and mitochondrial translation inhibition

Inactivation of Lon protease reveals a link between mitochondrial unfolded protein stress and mitochondrial translation inhibition, Published online: 05 December 2018; doi:10.1038/s41419-018-1213-6

Inactivation of Lon protease reveals a link between mitochondrial unfolded protein stress and mitochondrial translation inhibition

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UBIAD1 suppresses the proliferation of bladder carcinoma cells by regulating H-Ras intracellular trafficking via interaction with the C-terminal domain of H-Ras

UBIAD1 suppresses the proliferation of bladder carcinoma cells by regulating H-Ras intracellular trafficking via interaction with the C-terminal domain of H-Ras

UBIAD1 suppresses the proliferation of bladder carcinoma cells by regulating H-Ras intracellular trafficking via interaction with the C-terminal domain of H-Ras, Published online: 05 December 2018; doi:10.1038/s41419-018-1215-4

UBIAD1 suppresses the proliferation of bladder carcinoma cells by regulating H-Ras intracellular trafficking via interaction with the C-terminal domain of H-Ras

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Long noncoding RNA ATB promotes the epithelial−mesenchymal transition by upregulating the miR-200c/Twist1 axe and predicts poor prognosis in breast cancer

Long noncoding RNA ATB promotes the epithelial−mesenchymal transition by upregulating the miR-200c/Twist1 axe and predicts poor prognosis in breast cancer

Long noncoding RNA ATB promotes the epithelial−mesenchymal transition by upregulating the miR-200c/Twist1 axe and predicts poor prognosis in breast cancer, Published online: 05 December 2018; doi:10.1038/s41419-018-1210-9

Long noncoding RNA ATB promotes the epithelial−mesenchymal transition by upregulating the miR-200c/Twist1 axe and predicts poor prognosis in breast cancer

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LncRNA DANCR upregulates PI3K/AKT signaling through activating serine phosphorylation of RXRA

LncRNA DANCR upregulates PI3K/AKT signaling through activating serine phosphorylation of RXRA

LncRNA <i>DANCR</i> upregulates PI3K/AKT signaling through activating serine phosphorylation of RXRA, Published online: 05 December 2018; doi:10.1038/s41419-018-1220-7

LncRNA DANCR upregulates PI3K/AKT signaling through activating serine phosphorylation of RXRA

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Mast cells are essential intermediaries in regulating IL-33/ST2 signaling for an immune network favorable to mucosal healing in experimentally inflamed colons

Mast cells are essential intermediaries in regulating IL-33/ST2 signaling for an immune network favorable to mucosal healing in experimentally inflamed colons

Mast cells are essential intermediaries in regulating IL-33/ST2 signaling for an immune network favorable to mucosal healing in experimentally inflamed colons, Published online: 05 December 2018; doi:10.1038/s41419-018-1223-4

Mast cells are essential intermediaries in regulating IL-33/ST2 signaling for an immune network favorable to mucosal healing in experimentally inflamed colons

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Cross-sectional and prospective follow-up study to detect early signs of cardiac dysfunction in obesity: protocol of the CARDIOBESE study

Introduction

In view of the increasing occurrence of both obesity and heart failure, a growing overlap of these two clinical entities in the near future is expected. Significant advances in our understanding of the pathophysiological consequences of obesity for the cardiovascular system have been made over the past two decades. However, to optimise management and treatment of obesity patients, further research is required to improve early identification of cardiac dysfunction in obesity and to gain insight in the underlying pathophysiology. The CARdiac Dysfunction In OBesity – Early Signs Evaluation (CARDIOBESE) study has been designed to address these issues.

Methods and analysis

CARDIOBESE is a cross-sectional multicentre study of 100 obesity patients scheduled for bariatric surgery (body mass index (BMI) ≥35 kg/m2) without known cardiovascular disease, and 50 age-matched and gender-matched non-obese controls (BMI <30 kg/m2). Echocardiography, blood and urine biomarkers and Holter monitoring will be used to identify parameters that are able to show cardiac dysfunction at a very early stage in obesity patients (primary objective). Furthermore, a prospective follow-up study of obesity patients before and 1 year after bariatric surgery will be done to gain insight in the pathophysiology of obesity causing cardiac dysfunction (secondary objective).

Ethics and dissemination

The study was approved by the Medical Ethics Committee Toetsingscommissie Wetenschappelijk Onderzoek Rotterdam e.o. (TWOR). Inclusion of patients and controls is almost complete. Analyses of the investigations are currently being performed, and dissemination through peer-reviewed publications and conference presentations is expected from the first quarter of 2019. By identifying early markers of cardiac dysfunction in obesity, and by understanding the underlying pathophysiology of the abnormalities of these markers, the CARDIOBESE study may provide guidance for risk stratification, monitoring and treatment strategies for obesity patients.



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PRedicting Outcomes For Crohns dIsease using a moLecular biomarkEr (PROFILE): protocol for a multicentre, randomised, biomarker-stratified trial

Background

The course of Crohn's disease (CD) varies substantially between individuals, but reliable prognostic markers do not exist. This hinders disease management because patients with aggressive disease are undertreated by conventional 'step-up' therapy (in which treatment is gradually escalated in response to refractory or relapsing disease) while those with more indolent disease would be exposed to unnecessary treatment-related toxicity if a more aggressive 'top-down' approach was indiscriminately used. The Predicting outcomes for Crohn's disease using a molecular biomarker trial will assess whether a prognostic transcriptional biomarker, that we have developed and validated, can improve clinical outcomes by facilitating personalised therapy in CD. This represents the first the biomarker-stratified trial in inflammatory bowel disease.

Methods and analysis

This biomarker-stratified trial will compare the relative efficacy of 'top-down' and 'accelerated step-up' therapy between biomarker-defined subgroups of patients with newly diagnosed CD. 400 participants from ~50 UK centres will be recruited. Subjects within each biomarker subgroup (IBDhi or IBDlo) will be randomised (1:1) to receive one of the treatment strategies until trial completion (48 weeks). The primary outcome is the incidence of sustained surgery and steroid-free remission from the completion of induction treatment through to week 48. Secondary outcomes include mucosal healing, quality-of-life assessments and surrogate measures of disease burden including number of flares, cumulative steroid exposure, number of hospital admissions and number of Crohn's-related surgeries (assessed hierarchically). Analyses will compare the relative benefit of the treatment strategies in each biomarker-defined subgroup, powered as an interaction analysis, to determine whether the biomarker can accurately match patients to the most appropriate therapy.

Ethics and dissemination

Ethical approval has been obtained and recruitment is under way at sites around the UK. Following trial completion and data analysis, the results of the trial will be submitted for publication in peer-reviewed journals and presented at international conferences.

Trial registration number

ISRCTN11808228; Pre-results.



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Opioid Use is Associated with Higher Severity-Adjusted Episode Costs in Patients with Conservatively Managed Degenerative Joint Disease of the Back and Neck

Abstract

Background

Opioid use and misuse are urgent health issues. Previous studies suggest that opioid use increases healthcare resource use but severity adjustment is lacking.

Objective

The objective of this study was to evaluate the severity-adjusted cost difference between opioid users and non-users among patients with conservatively managed degenerative joint disease of the spine within a large commercial health plan population in the United States.

Methods

A retrospective observational study was performed using a national commercial database covering 531,819 patients aged 18–64 years with non-surgically managed cervical or lumbar degenerative spine disease during 2015–6. Patients were grouped based on whether there was evidence for an opioid prescription. Costs for the opioids themselves were excluded. Severity adjustment, on an ascending integer scale from 1 to 4, was performed based on member demographics, clinical comorbidities, disease progression indicators, and complications.

Results

Median episode costs for patients given opioids were approximately twice that for patients not given opioids after severity adjustment. For patients with episodes in both years and stable severity, patients with new prescriptions for opioids in 2016 doubled their median 2015 costs, and patients who had opioids discontinued in 2016 had a 60% cost reduction. Episode costs showed a nearly linear increase based on the length of time taking opioids, as well as with a higher average daily dose. Cost increases with opioids were broad across service categories even when comparing within the same severity-adjusted episodes of care.

Conclusions

The data suggest a clinically and statistically significant increase in episode costs associated with opioid use for degenerative joint disease of the spine, both within and between patients, and higher costs with a longer duration of opioid use as well as with higher daily dosages. Given the health consequences surrounding the overuse of opioids, concerted efforts to move towards a non-opioid pain control strategy are needed.



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Re: “High Altitude and Cancer Mortality” by Thiersch and Swenson (High Alt Med Biol 2018;19:116–123)

High Altitude Medicine &Biology, Ahead of Print.


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Acute Mountain Sickness is Reduced Following 2 Days of Staging During Subsequent Ascent to 4300 m

High Altitude Medicine &Biology, Ahead of Print.


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Special focus issue: ‘innovations in diagnostic and interventional oncology’

Future Oncology, Volume 14, Issue 28, Page 2889-2891, December 2018.


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Applying virtual reality in forensics – a virtual scene walkthrough

Abstract

A major task of forensic investigations is the documentation and interpretation of evidence to reconstruct a forensically relevant incident. To accomplish this task, a scene is documented not only with photographs but also with 3D documentation technologies. The resulting 3D data are used for 3D visualization and to perform 3D reconstructions. In this article, we present an approach for using forensic 3D data in conjunction with virtual reality to perform scene walkthroughs in the context of witness or suspect interrogations. The aim is to provide a method for scene visits showing the original scene even years after the incident. These scene walkthroughs in VR can be reproduced and allow to see through the eyes of a witness by recording their behavior and actions. These recordings allow subsequent examinations and reconstruction to support the investigation and scene understanding and can be used as evidence in court.



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A phase 1b dose-escalation and expansion study of the BCL-2 inhibitor venetoclax combined with tamoxifen in ER and BCL-2-positive metastatic breast cancer [Research Articles]

Venetoclax, a potent and selective BCL-2 inhibitor, synergizes with endocrine therapy in pre-clinical models of ER-positive breast cancer. Using a phase 1b 3+3 dose escalation and expansion study design, 33 patients with ER and BCL-2-positive metastatic disease (mean prior regimens, 2; range 0-8) were treated with daily tamoxifen (20 mg) and venetoclax (200-800 mg). Apart from uncomplicated 'on-target' lymphopenia, no dose-limiting toxicities or high-grade adverse events were observed in the escalation phase (15 patients), and 800 mg was selected as the recommended phase 2 dose (RP2D). In the expansion phase (18 patients), few high-grade treatment-related adverse events were observed. For 24 patients treated at the RP2D, the confirmed radiologic response rate was 54% and clinical benefit rate 75%. Treatment responses were pre-empted by metabolic responses (FDG-PET) at 4 weeks and correlated with serial changes in circulating tumor DNA. Radiologic responses (40%) and clinical benefit (70%) were observed in 10 patients with plasma-detected ESR1 mutations.



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A Very Oil Yellow1 Modifier of the Oil Yellow1-N1989 Allele Uncovers a Cryptic Phenotypic Impact of Cis-regulatory Variation in Maize

Forward genetics determines the function of genes underlying trait variation by identifying the change in DNA responsible for changes in phenotype. Detecting phenotypically-relevant variation outside protein coding sequences and distinguishing this from neutral variants is not trivial; partly because the mechanisms by which DNA polymorphisms in the intergenic regions affect gene regulation are poorly understood. Here we utilized a dominant genetic reporter to investigate the effect of cis and trans-acting regulatory variation. We performed a forward genetic screen for natural variation that suppressed or enhanced the semi-dominant mutant allele Oy1-N1989, encoding the magnesium chelatase subunit I of maize. This mutant permits rapid phenotyping of leaf color as a reporter for chlorophyll accumulation, and mapping of natural variation in maize affecting chlorophyll metabolism. We identified a single modifier locus segregating between B73 and Mo17 that was linked to the reporter gene itself, which we call very oil yellow1 (vey1). Based on the variation in OY1 transcript abundance and genome-wide association data, vey1 is predicted to consist of multiple cis-acting regulatory sequence polymorphisms encoded at the wild-type oy1 alleles. The vey1 locus appears to be a common polymorphism in the maize germplasm that alters the expression level of a key gene in chlorophyll biosynthesis. These vey1 alleles have no discernable impact on leaf chlorophyll in the absence of the Oy1-N1989 reporter. Thus, the use of a mutant as a reporter for magnesium chelatase activity resulted in the detection of expression-level polymorphisms not readily visible in the laboratory.



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Cell-based immunotherapy approaches for multiple myeloma

Cell-based immunotherapy approaches for multiple myeloma

Cell-based immunotherapy approaches for multiple myeloma, Published online: 06 December 2018; doi:10.1038/s41416-018-0346-9

Cell-based immunotherapy approaches for multiple myeloma

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A phase II study of tumor-infiltrating lymphocyte therapy for human papillomavirus-associated epithelial cancers

Purpose: Cellular therapy is an emerging cancer treatment modality, but its application to epithelial cancers has been limited. This clinical trial evaluated tumor-infiltrating lymphocyte (TIL) therapy for the treatment of patients with metastatic human papillomavirus (HPV)-associated carcinomas. Experimental Design: The trial was a phase II design with two cohorts, cervical cancers and non-cervical cancers. Cell infusion was preceded by a lymphocyte-depleting conditioning regimen and followed by systemic high-dose aldesleukin. Results: Objective tumor responses occurred in 5/18 (28%) patients in the cervical cancer cohort and 2/11 (18%) patients in the non-cervical cancer cohort. Two of the responses in cervical cancer were complete and are ongoing 67 and 53 months after treatment. Responses in the non-cervical cancer cohort were in anal cancer and oropharyngeal cancer. The HPV reactivity of the infused T cells correlated with clinical response. Peripheral blood repopulation with HPV-reactive T cells also correlated with clinical response. Conclusions/Discussion: These findings support the concept that cellular therapy can mediate the regression of epithelial cancers, and they suggest the importance of predictive biomarkers and novel treatment platforms for more effective therapies.



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Eradication of central nervous system leukemia of T-cell origin with a brain-permeable LSD1 inhibitor

Purpose: Lysine-specific demethylase 1 (LSD1) regulates several biological processes via the bifunctional modulation of enhancer functions. Recently, we reported that LSD1 overexpression is a founder abnormality of T-cell leukemogenesis and is maintained in fully transformed T-cell acute lymphoblastic leukemia (T-ALL) cells. On the basis of this finding, we attempted to develop novel LSD1 inhibitors effective for T-ALL with central nervous system (CNS) involvement. Experimental design: We chemically modified the prototype LSD inhibitor tranylcypromine (TCP) and screened for cytotoxicity against TCP-resistant T-ALL cell lines. In vivo efficacy of novel LSD1 inhibitors was examined in immunodeficient mice transplanted with luciferase-expressing T-ALL cell lines, which faithfully reproduce human T-ALL with CNS involvement. Results: We found robust cytotoxicity against T-ALL cells, but not normal bone marrow progenitors, for two N-alkylated TCP derivatives, S2116 and S2157. The two compounds induced apoptosis in TCP-resistant T-ALL cells in vitro and in vivo by repressing transcription of the NOTCH3 and TAL1 genes through increased H3K9 methylation and reciprocal H3K27 deacetylation at super-enhancer regions. Both S2116 and S2157 significantly retarded the growth of T-ALL cells in xenotransplanted mice and prolonged the survival of recipients as monotherapy and in combination with dexamethasone. Notably, S2157 could almost completely eradicate CNS leukemia because of its ability to efficiently pass through the blood-brain barrier. Conclusion: These findings provide a molecular basis and rationale for the inclusion of a brain-permeable LSD1 inhibitor, S2157, in treatment strategies for T-ALL with CNS involvement.



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Mitochondrial DNA in the tumour microenvironment activates neutrophils and is associated with worse outcomes in patients with advanced epithelial ovarian cancer

Mitochondrial DNA in the tumour microenvironment activates neutrophils and is associated with worse outcomes in patients with advanced epithelial ovarian cancer

Mitochondrial DNA in the tumour microenvironment activates neutrophils and is associated with worse outcomes in patients with advanced epithelial ovarian cancer, Published online: 06 December 2018; doi:10.1038/s41416-018-0339-8

Mitochondrial DNA in the tumour microenvironment activates neutrophils and is associated with worse outcomes in patients with advanced epithelial ovarian cancer

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FDA Warns of Rare Stroke Risk With Multiple Sclerosis Drug

WEDNESDAY, Dec. 5, 2018 -- A new warning has been added to the multiple sclerosis drug Lemtrada (alemtuzumab) after rare reports of patients suffering strokes and tears in the lining of the arteries in the head and neck, the U.S. Food and Drug...

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J-Shaped Association for Sleep Duration, CV Events and Death

WEDNESDAY, Dec. 5, 2018 -- There is a J-shaped association for total daily sleep duration with all-cause mortality and cardiovascular events, according to a study published online Dec. 5 in the European Heart Journal. Chuangshi Wang, from McMaster...

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Type 2 Diabetes Linked to Colorectal Cancer Risk in Men

WEDNESDAY, Dec. 5, 2018 -- Type 2 diabetes (T2D) is associated with an increased risk for colorectal cancer (CRC), with the association significant for men only, according to a study published online Nov. 7 in the British Journal of Cancer. Yanan...

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SABCS: Delaying Chemo Lowers Survival in Triple-Neg Breast CA

WEDNESDAY, Dec. 5, 2018 -- Delaying initiation of adjuvant chemotherapy in triple-negative breast cancer (TNBC) patients more than 30 days after surgery is associated with a decrease in survival, according to a study presented at the annual San...

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Infections Linked to Increased Later Risk for Mental Disorders

WEDNESDAY, Dec. 5, 2018 -- Infections requiring hospitalization or treatment with anti-infective agents are associated with an increased subsequent risk for mental disorders, according to a study published online Dec. 5 in JAMA Psychiatry. Ole...

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Heterogeneity and Variability in Pressure Autoregulation of Organ Blood Flow: Lessons Learned Over 100+ Years

Objectives: Pressure autoregulation is an organ's intrinsic ability to maintain blood flow despite changes in perfusion pressure. The purpose of this review is to discuss autoregulation's heterogeneity among different organs and variability under different conditions, a very clinically relevant topic. Data Sources: Systematic search of Ovid MEDLINE; nonsystematic search of PubMed, Google Scholar, and reference lists. Study Selection: Animal or human studies investigating the potency or variation of pressure autoregulation of any organs or the association between autoregulation and outcomes. Data Extraction: Two authors screened the identified studies independently then collectively agreed upon articles to be used as the basis for this review. Data Synthesis: Study details, including subjects, organ investigated, methods of blood pressure intervention and blood flow measurement, and values of the lower limit, upper limit, and plateau were examined. Comparative canine studies were used to demonstrate the heterogeneity of pressure autoregulation among different organs and validate the proposed scale for organ categorization by autoregulatory capacity. Autoregulatory variability is discussed per organ. The association between cerebral autoregulation and outcome is summarized. Conclusions: The organs with robust autoregulation are the brain, spinal cord, heart, and kidney. Skeletal muscle has moderate autoregulation. Nearly all splanchnic organs including the stomach, small intestine, colon, liver, and pancreas possess weak autoregulation. Autoregulation can be readily affected by a variety of clinically relevant factors. Organs with weak or weakened autoregulation are at a greater risk of suboptimal perfusion when blood pressure fluctuates. Cerebral autoregulation and outcomes are closely related. These lessons learned over 100+ years are instructive in clinical care. Drs. Meng and Wang planning and study designing the article. All authors writing and revising 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/29S62lw). Support was provided solely from institutional and/or departmental sources. Dr. Meng is a consultant to CAS Medical Systems, and Dr. McDonagh has research support from Lungpacer Medical. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: lingzhong.meng@yale.edu; wangyingwei@yahoo.com Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Clinical Implications of the 2016 International Study Group on Pancreatic Surgery Definition and Grading of Postoperative Pancreatic Fistula on 775 Consecutive Pancreatic Resections

imageObjective: The aim of the present study was to evaluate the clinical implications of the 2016 International Study Group for Pancreatic Surgery (ISGPS) definition and classification of postoperative pancreatic fistula (POPF) using a single high-volume institutional cohort of patients undergone pancreatic surgery. Background: The ISGPS definition and grading system of POPF has been recently updated. Although the rationale for the changes was supported by previous studies, the effect of the new definition and classification scheme on surgical series has not been established. Methods: A total of 775 patients undergone pancreatic surgery in our institute from 2013 to 2015 were reviewed. The parameters modified in the ISGPS classification were analyzed according to postoperative outcomes. Finally the classification was validated by external clinical and economical outcomes. Results: Applying the 2016 scheme, 17.5% of patients changed classification group compared to the 2015 system. Grade B increased from 11.5% to 22.1%, whereas grade C decreased from 15.2% to 4.6%. Biochemical leak occurred in 7% of patients, and it did not differ from the non-POPF condition in terms of surgical outcomes. Non-POPF group, grades B and C POPF differed significantly in terms of intensive care unit staying (P

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Current status of esophageal endoscopy including the evaluation of smoking and alcohol consumption in Japan: an analysis based on the Japan endoscopy database

Abstract

Purpose

The aim was to investigate the current status of esophageal endoscopy, including the evaluation of smoking and alcohol consumption, in Japan.

Methods

A total of 47,441 patients who underwent 69,748 sessions of esophageal endoscopy were registered in the Japan Endoscopy Database between January 2015 and March 2017. The study variables were as follows: (1) methods for monitoring the esophagus and the time required for monitoring and (2) the status of smoking and alcohol consumption in patients with esophageal cancer and head and neck cancer.

Results

Image-enhanced endoscopy was performed in 10.6%, Lugol chromoendoscopy in 4.1%, and magnifying endoscopy in 3.2%. The mean time required for gastrointestinal endoscopy was 10 min 58 s. The mean examination times in patients with or without monitoring of the head and neck were 10 min 51 s and 11 min 13 s, respectively. In 57.0% of the patients with esophageal cancer, the head and neck were monitored at the time of gastrointestinal endoscopy. The proportion of current smokers (esophageal cancer: 16.8–4.7%; head and neck cancer: 24.3–9.3%) and addicted drinkers (esophageal cancer: 52.3–40.8%; head and neck cancer: 50.2–47.3%) were lower at the second or subsequent endoscopy than at the initial endoscopy.

Conclusions

The new strategy for esophageal endoscopy has led to an evolutionary change in Japan. The patients with esophageal cancer and head and neck cancer who underwent a second or subsequent endoscopy had lower incidences of smoking and alcohol consumption, although the incidences remained high.



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Immunohistochemical characteristics of porcine intrahepatic nerves under physiological conditions and after bisphenol A administration

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Background: The neurochemistry of hepatic nerve fibres was investigated in large animal models after dietary exposure to the endocrine disrupting compound known as bisphenol A (BPA).

 

Materials and methods: Antibodies against neuronal peptides were used to study changes in hepatic nerve fibres after exposure to BPA at varying concentrations using standard immunofluorescence techniques. The neuropeptides investigated were substance P (SP), galanin (GAL), pituitary adenylate cyclase activating polypeptide (PACAP), calcitonin gene regulated peptide (CGRP) and cocaine and amphetamine regulated transcript (CART). Immunoreactive nerve fibres were counted in multiple sections of the liver and among multiple animals at varying exposure levels. The data was pooled and presented as mean ± standard error of the mean.

 

Results: It was found that all of the nerve fibres investigated showed upregulation of these neural markers after BPA exposure, even at exposure levels currently considered to be safe. These results show very dramatic increases in nerve fibres containing the above-mentioned neuropeptides and the altered neurochemical levels may be causing a range of pathophysiological states if the trend of over-expression is extrapolated to developing humans.

 

Conclusions: This may have serious implications for children and young adults who are exposed to this very common plastic polymer, if the same trends are occurring in humans.



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Determination and classification of cutaneous innervation of the dorsum of the foot in foetal cadavers

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Background: The aim of this study is to determine cutaneous innervation of the dorsum of the foot on foetal cadavers.

Materials and methods: In this study. 200 limbs from 100 embalmed foetuses (54 males and 46 females) were studied in Anatomy Laboratory. Contributions of medial, lateral and intermediate dorsal cutaneous nerves (MDCN, LDCN and IDCN) of the foot were identified.


Results: Cutaneous innervation of the dorsum of the foot was classified into five types. Type I (75%) where MDCN innervated medial border of the foot and second interdigital cleft; IDCN innervated third, fourth and fifth interdigital clefts; and LDCN innervated the lateral border of the foot. Type II (21%) where MDCN innervated medial border of the foot, second and third interdigital clefts; IDCN innervated fourth and fifth interdigital clefts; and LDCN innervated the lateral border of the foot. Type III (1.5%) where saphenous nerve innervated medial border of the foot; MDCN innervated second and third interdigital clefts; IDCN innervated fourth and fifth interdigital clefts; and LDCN innervated the lateral border of the foot. Type IV (1.5%) was similar to type I, with an extra connection between the MDCN and IDCN on the dorsum of the foot. Type V (1%) where superficial fibular nerve innervated medial border of the foot, and second, third and fourth interdigital clefts; and sural nerve innervated fifth interdigital cleft and
lateral border of the foot.


Conclusions: The present study provides a new classification for the cutaneous innervation of the dorsum of the foot.



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Stress-induced changes in the aged-rat adrenal cortex. Histological and histomorphometric study

Background: Stress exposure exerts direct effects on the morphology and functionality of the adrenal cortex. In addition, ageing effects growth, differentiation, apoptosis and cellularity of the cortex. The missing data is the combined effect of stress and ageing on the adrenal cortex. The aim of this study was to demonstrate the structural changes in the adrenal cortex following the exposure to stress in the adult and aged albino rats.

 

Materials and methods: Forty rats were divided into groups I and II (adult and senile). Each group was further subdivided into subgroups a and b (control and stressed). Light and electron microscopic studies were done. Area per cent of collagen fibres (Masson's trichrome-stained sections), number of proliferating cells (optical density immunoreactivity in the Ki67 stained sections) and thickness of the three adrenal zones were also measured.

 

Results: Lamellar separation of the capsule with subcapsular spindle cell hyperplasia and areas of ghost cells were observed in zona glomerulosa (ZG) and zona fasciculata (ZF) in group I-b. Separation and indentation of the capsule with its lamellar separation were observed in group II-a with the existence of multiple scattered degenerative foci in ZF and zona reticularis (ZR). Similar and aggressive was the architectural pattern of ZF in group II-b with the presence of areas of homogenous degeneration. The nuclei of ZG had marginated chromatin in group I-b and were pyknotic with deformed irregular outlines in group II-b. Multiple lysosomes and vacuolar degeneration mitochondria were also seen in group I-b.

The nuclei of ZF were irregular with condensed marginated heterochromatin in group I-b, irregular with scattered chromatin in group II-a and indented with areas of chromatin destruction in group II-b. Mitochondria with disrupted cristae and cristolysis were also detected in group I-b. Numerous lipofuscin granules and dilated smooth endoplasmic reticulum were revealed in group II-b. The mean collagen fibre area per cent and the mean number of the proliferating cells in group II-b were significantly higher by 39% and 23%. The thickness of ZG decreased significantly by 20% in group I-b. Contrary, the thickness of both ZF and ZR increased significantly by 10% in group I-b.

 

Conclusions: Histological alterations occurred in the adrenal cortex in response to stress, especially when coupled with the advance of age. This was accompanied by increase in the area per cent of collagen fibres and increase in the mean number of the proliferating cells in the adrenal cortex.



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Variability of the vertebral artery origin and transverse foramen entrance level — CT angiographic study

Background: Vertebral artery (VA), the main element of the posterior brain circulation, has many anatomical variations which generally were widely investigated. However, available data vary in wide ranges, reflecting very different sample sizes, lack of data about left-right or sex differences, and about possible ethnic, regionally specific or genetic differences.

 

Materials and methods: Certain new findings suggest possible involvement of some environmental factors in VA variations. Accurate anatomical data about VA variations in different regions of the world, including Balkans countries, are still lacking. Therefore we investigated morphological variability of VA origin and its entrance level into cervical transverse foramina in population of Republika Srpska (Bosnia and Herzegovina), including data about the sex and side.

 

Results: Anatomy of VA was investigated in 112 persons (224 arteries) of both sexes (58 males, 54 females; age 19–83 years), using 64-slice computed tomography (CT) scanner. Origin of VA from subclavian artery (SCA) we found in 95.08% of arteries (52 males, 49 females). Only in 1 (0.45%) male left VA and left SCA had an specific origin from aortic arch (AA), which we named as an "common area of origin". All other observed variations in origin were only of left VA, originating from AA in 4.47% (5 males, 5 females). Left VA most often (usual) entrance level into transverse foramen we found at C6 (87.5%), followed by C5 (8.93%), C4 (3.12%), and in 1 case at level C7 (0.45%). Entry levels at C5, both on right and on the left side, were three times more frequent in males than in females.

 

Conclusions: Wide ranges of differences between the data we obtained on a sample in Republika Srpska (Bosnia and Herzegovina) and the data from many other studies require further and wider investigations.



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Morphometric parameters and histological study of the filum terminale of adult human cadavers and magnetic resonance images

Background: Morphology and histology of filum terminale (FT) has a role in the pathophysiology of tethered cord syndrome (TCS). This research was implemented to investigate the morphometric parameters and histological structure of normal FT in adult human cadavers and magnetic resonance imaging (MRI) scans to correlate them with the pathophysiology of TCS.

 

Materials and methods: Twenty five adult human cadavers (15 males, 10 females) and 100 MRI echo scans of lumbosacral region (50 males and 50 females), were used in this study. MRI patients were divided into 21–40 and 41–60 age groups. The cadavers were dissected at the prone position to explore their fila. The length of FT, filum terminale internum (FTI), filum terminale externum (FTE), vertebral level of beginning, dural piercing and termination of FT, and the initial, midpoint, and mid-FTE diameters were determined. Four segments were excised from lower conus, upper, middle, and lower thirds of FT. The specimens were processed for light microscopic examination. Statistical analysis was done for these parameters.

 

Results: MRI morphometrical parameters of FT, except FTI length, revealed no age effect or sex differences, where length of FTI, FTE, initial diameter, level of conus medullaris termination (CMT) and dural sac termination (DST) were 174.1 ± 16.8, 75.8 ± 9.5, 1.6 ± 0.21, L1-2 and S2U in males and 166.9 ± 18.9, 74.1 ± 9.3, 1.53 ± 0.25, L1-2 and S2M vertebrae in females, respectively. However, non-significant sex difference was observed in morphometric parameters of cadaveric FT, where length of FTI and FTE, initial diameter, CMT and DST levels were 164.2 ± 11.6, 76.7 ± 8.1, 1.7 ± 0.14, L1L and S2U vertebrae in males and 159.2 ± 10.1, 71.02 ± 7.3, 1.6 ± 0.29, L1L and S2U in females, respectively. Moreover, CMT below L2 vertebra was seen in 5% of MRI scans and 8% of cadavers. Also, the initial diameter of FT > 2 mm was recorded in 7% of MRI and 8% of cadaveric cases. Histologically, the structure of FT showed gradual reduction in nervous, glial, and vascular tissues with converse increase in collagen content in FTE compared with those of FTI.

 

Conclusions: Knowledge of the morphometric parameters and the histological structure of FT are necessary for clinicians who dealing with diagnosis or treatment of tethered cord syndrome.



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The superficial palmar branch of the radial artery: a corrosion cast study

Background: Surgical procedures such as thenar flaps and radial artery (RA) harvesting call for an elaborate anatomical study of the RA's superficial palmar branch (SPB). The aim of this study was to describe the branching pattern of this vessel related to the morphometric characteristics and variations of this artery.

 

Materials and methods: Twenty 4% formalin solution-injected hands were dissected. For the morphometric study we used another group of 35 human hands of adult persons, injected with methyl methacrylate fluid into the ulnar and radial arteries. As soon as polymerisation was completed, a 40% solution of potassium hydroxide was applied for corrosion. The vascular arterial casts were examined under the stereoscopic microscope and precise drawings of each specimen were made.

 

Results: In the majority of cases (75%) SPB passed superficially, over the abductor pollicis brevis muscle. The mean diameter of the SPB, very variable depending on its length and field of supply, was 1.52 ± 0.49 mm, ranging from 0.8 to 2.7 mm. Developed SPB type, was present in 31.4% of hands, with the diameter of 1.7 mm and larger (mean 1.95 mm), continuing distally to become the radialis indicis artery, with an average calibre of 1.2 mm, and with important branches to the thumb. In most hands (68.6%), the hypoplastic SPB, was present, with a mean diameter of 1.17 mm, and the field of supply within the thenar area.

 

Conclusions: Knowledge of the SPB dominance and existence of anastomotic vessels in its field of supply are of importance to avoid the risk of possible ischaemic sequelae in the hand associated with harvesting the RA.



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Anatomy of the feeding arteries of the cerebral arteriovenous malformations

Background: Identification and anatomic features of the feeding arteries of the arteriovenous malformations (AVMs) is very important due to neurologic, radiologic, and surgical reasons.

 

Materials and methods: Seventy-seven patients with AVMs were examined by using a digital subtraction angiographic (DSA) and computerised tomographic (CT) examination, including three-dimensional reconstruction of the brain vessels. In addition, the arteries of 4 human brain stems and 8 cerebral hemispheres were microdissected.

 

Results: The anatomic examination showed a sporadic hypoplasia, hyperplasia, early bifurcation and duplication of certain cerebral arteries. The perforating arteries varied from 1 to 8 in number. The features of the leptomeningeal and choroidal vessels were presented. The radiologic examination revealed singular (22.08%), double (32.48%) or multiple primary feeding arteries (45.45%), which were dilated and elongated in 58.44% of the patients. The feeders most often originated from the middle cerebral artery (MCA; (23.38%), less frequently from the anterior cerebral artery (ACA; 12.99%), and the posterior cerebral artery (PCA; 10.39%). Multiple feeders commonly originated from the ACA and MCA (11.69%), the MCA and PCA (10.39%), the ACA and PCA (7.79%), and the ACA, MCA and PCA (5.19%). The infratentorial feeders were found in 9.1% of the AVMs. Contribution from the middle meningeal and occipital arteries was seen in 3.9% angiograms. Two cerebral arteries had a saccular aneurysm. The AVM haemorrhage appeared in 63.6% of patients.

 

Conclusions: The knowledge of the origin and anatomic features of the AVMs feeders is important in the explanation of neurologic signs, and in a decision regarding the endovascular embolisation, neurosurgical and radiosurgical treatments.



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A possible association between medial depression of mandibular ramus and maximum bite force

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Background: Medial depression of the mandibular ramus (MDMR) is an anatomical depression with unknown aetiology and described as a result of a slender mandibular ramus in the area of the mandibular notch. It is suggested that MDMR may be due to variations in muscle functions. The aim of this study is to compare the bite force of patients with and without MDMR detected on panoramic radiographs.

Materials and methods: One hundred and ten patients (55 women and 55 men; mean age 22.69 ± 2.85 years) participated in this study. Patients were divided into two groups based on the presence of MDMR. Bite force of 55 patients with MRMD and 55 patients without MDMR were determined using a bite force sensor. Non-parametric tests were used to assess differences between groups.

Results: Measurements showed statistically significant differences in bite force between genders (p = 0.00) with men having higher values (535.98 ± 187.85 N) than women (363.59 ± 139.56 N). The mean bite force in the sides with and without MDMR was 538.19 ± 196.94 N and 396.22 ± 157.69 N, respectively. There was a statistically significant difference between groups with and without MDMR (p = 0.00). There was no statistically significant difference in bite force between groups according to Angle's classification (p = 0.581).

Conclusions: This study suggests that the presence of MDMR may be an indicator of high muscle activity. Patients with MDMR should be carefully examined for the risk of relapse prior to any surgical intervention.



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Mandibular tori are associated with mandibular bone quality: a case-control study

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Background: Torus mandibularis (TM) is one of the most common oral exostoses. The presence of TMs has been correlated with high skeletal bone mineral density. This study aimed to evaluate the relationship between TM and mandibular bone quality based on the measurement of mandibular cortical index (MCI).

Materials and methods: A case-control study was designed for patients who attended the Department of Dentomaxillofacial Radiology at the University of Hacettepe for routine dental examination. Patients with TMs were defined as cases, and those without TMs were defined as controls. The presence of tori was assessed by visual inspection and digital palpation. MCI assessments were done based on Klemetti's classification. The associations between the presence of TMs, MCI, and the parafunctional activity were assessed.

Results: The sample consisted of 80 subjects with TMs and 80 control subjects. The presence of TMs was strongly associated with the parafunctional activity (p = 0.036) and a non-eroded mandibular cortex (MCI C1, p = 0.001).

Conclusions: Parafunctional activity may be a factor related to the formation or existence of TMs. The association between TMs and mandibular morphology may suggest that subjects with TMs may have a higher mandibular bone quality compared to those without TMs.



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Variations in carotid sinus anatomy and their relevance to carotid interventions

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Background: The carotid sinus (CS) is a dilatation in the carotid bifurcation usually at the origin of proximal internal carotid artery (ICA). It contains baroreceptors which influence blood pressure. Variations in the location of the CS are of importance as atheromatous plaque commonly forms in this area and procedures such as carotid endarterectomy are performed to reduce the risk of stroke. Inadvertent stimulation of the CS baroreceptors during interventions can have profound effects on the patient's haemodynamic status both intra- and postoperatively, causing serious complications. The aim of this study is to determine the inter- and intra-individual variations in the location of the CS.

Materials and methods: Eighty-two carotid arteries were dissected bilaterally from 41 cadavers. The locations of the CS were noted and divided into four potential sites.


Results: The commonest site is the origin of the ICA (74.3%), but the CS can also be found in the distal part of the common carotid artery (CCA) inferior to the bifurcation (17.1%); at the bifurcation involving the distal CCA and origins of both the external carotid artery (ECA) and ICA (7.32%); and at the origin of the ECA (1.22%). In individual cadavers, the CS was located at the origin of the ICA in 97.6% on at least one side. The sites of the CS were asymmetrical in 34.1%.

Conclusions: Clinicians performing carotid interventions should be aware of these anatomical variations to avoid inadvertent stimulation of the CS which can cause profound bradycardia and hypotension.



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Coeliac trunk and common hepatic artery variations in children: an analysis with computed tomography angiography

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Background: Understanding the coeliac trunk (CeT) and hepatic artery anatomy is important not only in preventing iatrogenic injuries but also in planning surgical procedures in children. Therefore, the aim of this study is to analyse the prevalence of CeT and common hepatic artery (CHA) variations in the paediatric population.

 

Materials and methods: One hundred and seventy-four children who underwent abdominal multidetector computed tomography (MDCT) angiography, either because of trauma or liver transplantation, were analysed retrospectively. The patterns of CeT, CHA and their variant branches were revealed and compared with previous studies involving adults.

 

Results: A total of 157 (90.2%) of the 174 patients had normal CeT anatomy, whereas 17 (9.8%) had variations. Five types of CeT variations were identified according to Song's classification in which 'hepatosplenic trunk + left gastric artery + superior mesenteric artery' was the most prevalent. One hundred-twelve (64.4%) of the 174 patients had normal CHA anatomy; however, 62 (35.6%) had variations. Six types of CHA variations were identified according to Michel's and Hiatt's classification. The most common was 'replaced left hepatic artery originating from left gastric artery'.

 

Conclusions: The prevalences of CeT and hepatic artery variations are high in children, as they are in older patients. Awareness of these variations is important in terms of avoiding iatrogenic injury and in promoting surgical procedure planning for liver transplantation or abdominal tumour surgery.



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Tensor fasciae latae muscle in human embryos and foetuses with special reference to its contribution to the development of the iliotibial tract

Background: The human tensor fasciae latae muscle (TFL) is inserted into the iliotibial tract and plays a critical role in lateral stabilisation of the hip joint. We previously described a candidate of the initial iliotibial tract that originated from the gluteus maximus muscle and extended distally.

Materials and methods: This study extended our observations by examining 30 human embryos and foetuses of gestational age (GA) 7–14 weeks (crown-to-rump length 24–108 mm). At GA 7 weeks, the TFL appeared as a small muscle mass floating in the subcutaneous tissue near the origins of the gluteus medius and rectus femoris muscles.


Results: Subsequently, the TFL obtained an iliac origin adjacent to the rectus femoris tendon, but the distal end remained a tiny fibrous mass on the vastus lateralis muscle. Until GA 10 weeks, the TFL muscle fibres were inserted into a vastus lateralis fascia that joined the quadriceps tendon distally. The next stage consisted of the TFL muscle belly "connecting" the vastus fascia and the gluteus fascia, including our previous candidate of the initial iliotibial tract. Until GA 14 weeks, the TFL was sandwiched by two laminae of the connecting fascia.

Conclusions: These findings suggested that, when the vastus lateralis fascia separated from the quadriceps tendon to attach to the tibia, possibly after birth, the resulting iliotibial tract would consist of a continuous longitudinal band from the gluteus maximus fascia, via the vastus fascia, to the tibia. Although it is a small muscle, the foetal TFL plays a critical role in the development of the iliotibial tract.



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Variations of the cephalic vein anterior to the clavicle in humans

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Background: Clinicians should understand that jugulocephalic vein (JCV) variants may be occasionally found. This study aims to classify JCV variants and obtain their frequency.

 

Materials and methods: We investigated anatomical variants of the cephalic vein in 55 human cadavers during a gross anatomy course at our medical school.

 

Results: The percentage of JCVs that pass through the anterior part of the clavicle and anastomose to the jugular vein as per previous studies and our study was 2–5%. Five cases with anastomosis between the cephalic and external jugular veins that pass through the anterior part of the clavicle were found. The courses were classified into 1A, 1B, 2A, and 2B. Type 1 extends beyond the clavicle and anastomoses with the external jugular vein. Type 2 follows the same course as type 1, but anastomoses with the subclavian vein. Subtype A does not have a branch that anastomoses with the axillary vein, whereas subtype B does. We encountered two cases of type 1A and three of type 1B.

 

Conclusions: Four anatomical variants of the cephalic vein around the clavicle were identified. Clinicians' knowledge of these variants is expected to decrease possible complications if venous access via the cephalic vein is needed.



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Evaluation of localisation of mandibular foramen in patients with mandibular third molar teeth using cone-beam computed tomography

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Background: It is important to know the correct anatomical location of the mandibular foramen to obtain successful anaesthesia of inferior alveolar nerve and to prevent injury to the mandibular vessels and nerve, during a variety of oral and maxillofacial surgical procedures. The aim of this study is to evaluate localisation of the mandibular foramen in patients with the third molars using cone-beam computed tomography (CBCT).

Materials and methods: Cone-beam computed tomography was used to determine the location of the mandibular foramen in 67 patients (totally 99 sides) with unilateral or bilateral impacted mandibular third molars.

Results: The distance from the posterior border of the mandibular ramus to mandibular foramen did not differ significantly among the other angulations. But the difference between vertical and horizontal angulation of the impacted
mandibular third molars according to 'fd' values (the shortest distance between mandibular foramen and the posterior border of mandibular ramus) was found to be statistically significant (p < 0.05).

Conclusions: The present study provides new information to the literature concerning relationship between the location of the mandibular foramen and the mandibular third molars.



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Common coeliacomesenteric trunk: a computed tomography radiological study

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Background: There is an increasing trend for administration of invasive radiological interventions, laparoscopic surgery, and transplantation procedures in recent years, and determining the vascular variations prior to these procedures is crucially important. Coeliacomesenteric trunk (CMT) is among these variations. This study aimed to retrospectively evaluate this rare anomaly by computed tomography (CT). Materials and methods: A total of 1000 CT angiography images were analysed retrospectively, and the patients with mesenteric and coeliac arteries arising from the abdominal aorta with a single root were identified. The level that CMT arose, and its branching patterns were determined individually for all patients. Results: Ten patients (6 males and 4 females) with a mean age of 50.2 years (17–87 years) had CMT in CT images. Conclusions: The knowledge of variations in the CMT prior to vascular or laparoscopic interventions will contribute to early intervention in case of a complication, or to avoid from a potential damage.



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Morphology of cranial sutures and radiologic evaluation of the variations of intersutural bones

Background: As far as our literature searches showed us, morphological characteristics of cranium such as sutures, sutural bones and fontanelles had been examined in the skulls in the museums and dry specimens until now. As a modern method, three-dimensional virtual reconstruction of cranial bones by using multidetector computed tomography-computed tomography angiography (MDCT-CTA) can display in vivo morphological characteristics. In our study, we aimed to determine the presence and incidence of these morphological characteristics that can be
clinically significant in our population, by using radiologic methods.

Materials and methods: We examined head and neck regions of 185 patients via MDCT-CTA. We evaluated radiologically detectable variations of the metopic sutures, lambda, bregma, asterion and pterion, which can be very easily confused with fractures. Additionally, the differences between the genders and incidence of coexistence of these variations were evaluated.

Results: According to our study, the incidence of persistent metopic suture was 8.1% and the incidence of lambda variations was 5.9%. Variations were most commonly encountered on the left asterion, and least commonly on the bregma and left pterion. In the evaluation of the coexistence of the parameters and combinations, the Wormian bones located at the right and left asterions were detected. There were no statistically significant differences between genders.

Conclusions: Variations of the sutures and sutural bones can be easily misdiagnosed with the fractures of related bony regions in unconscious patients with multiple traumas. During surgical interventions in these patients, surgeons must take this fact into consideration in order to make differential diagnosis of fractures and intersutural bone variations.



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The triticeous cartilage — redefining of morphology, prevalence and function

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Background: Triticeous cartilage is a small cartilaginous component of the laryngeal skeleton. This cartilage, located in posterior end of the thyrohyoid ligament, presents in different shapes. Radiological studies indicate clinical and anatomical importance of the triticeous cartilage but these studies have limited information due to inadequate inspection method. Computed tomographic angiography is able to evaluate the triticeous cartilage with using three-dimensional images in more detail. The aim of this study is to describe prevalence and morphological properties of the triticeous cartilage.

Materials and methods: We examined computed tomographic angiography images of 746 patients (368 women, 378 men) retrospectively. Shapes, calcification degrees, volumes, lengths and wideness of the triticeous cartilage were evaluated by OsiriX-Lite software.

Results: According to our results, triticeous cartilage presents common in the examined population (68.1%). The prevalence of the triticeous cartilage was higher in men than in women. We also found that the degree of calcification was not related with age and gender.

Conclusions: Clinical importance of the triticeous cartilage is that it could be misdiagnosed with atherosclerosis in common carotid artery because the triticeous cartilage is located almost at same level as the bifurcation of the common carotid artery. Therefore, clinicians should be aware about the triticeous cartilage.



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The posterior epidural ligament in the thoracic region: a cadaveric and histological study

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The existence of posterior epidural ligaments (PEL) has been established in the lumbar region, but they have hitherto not been shown to exist in the thoracic vertebral column. Their identification is of clinical significance in respect to incidental durotomy and the circulation of cerebrospinal fluid (CSF). Fourteen thoracic spine sections were dissected by cutting through the intervertebral disc and separating the ligamentum flavum from the vertebra above. The dural sheath was gently retracted anteriorly to identify macroscopic connections between the ligamentum flavum and the dura. Macroscopic connections observed were dissected out, retaining some dural sheath and ligamentum flavum. Histological
staining with haematoxylin and eosin and Miller's elastin stain was used to investigate cellular connections. Thoracic PELs were positively identified in 5 of the 14 cadavers (35.7%). Histology showed similarities between the thoracic and lumbar
PELs. Fifteen separate PELs were identified within these five thoracic sections. The thoracic PEL has sufficient tensile strength to present a risk to the integrity of the dural sheath during surgery, and surgeons should be aware of these connections when operating on the thoracic spine. PELs may also contribute to the circulation of CSF in the spinal subarachnoid space.



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Autoimmune Thyroid Diseases

2018-11-0382_10-1055-a-0799-5068-1.jpg

Horm Metab Res 2018; 50: 837-839
DOI: 10.1055/a-0799-5068



© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text



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Injectable Bulking Agent to Treat Postprostatectomy Urinary Incontinence: A Safety and Effectiveness Pilot Study

Objectives. To evaluate the safety and effectiveness of the injectable bulking agent Opsys® (Promedon, Cordoba, Argentina) for treating minimal postprostatectomy stress urinary incontinence (SUI). Patients and Methods. Single-centre, pilot study on ten male patients with SUI,

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Integrated Analysis of MicroRNA (miRNA) and mRNA Profiles Reveals Reduced Correlation between MicroRNA and Target Gene in Cancer

Background. Accumulating evidences demonstrated that microRNA-target gene pairs were closely related to tumorigenesis and development. However, the correlation between miRNA and target gene was insufficiently understood, especially its changes between tumor and normal tissues. Objectives. The aim of this study was to evaluate the changes of correlation of miRNAs-target pairs between normal and tumor. Materials and Methods. 5680 mRNA and 5740 miRNA expression profiles of 11 major human cancers were downloaded from the Cancer Genome Atlas (TCGA). The 11 cancer types were bladder urothelial carcinoma, breast invasive carcinoma, head and neck squamous cell carcinoma, kidney chromophobe, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, stomach adenocarcinoma, and thyroid carcinoma. For each cancer type, we firstly obtained differentially expressed miRNAs (DEMs) and genes (DEGs) in tumor and then acquired critical miRNA-target gene pairs by combining DEMs, DEGs and two experimentally validated miRNA-target interaction databases, miRTarBase and miRecords. We collected samples with both miRNA and mRNA expression values and performed a correlation analysis by Pearson method for miRNA-target pairs in normal and tumor, respectively. Results. We totally got 4743 critical miRNA-target pairs across 11 cancer types, and 4572 of them showed weaker correlation in tumor than in normal. The average correlation coefficients of miRNA-target pairs were different greatly between normal (-0.38 ~ -0.61) and tumor (-0.04 ~ -0.26) for 11 cancer type. The pan-cancer network, which consisted of 108 edges connecting 35 miRNAs and 89 target genes, showed the interactions of pairs appeared in multicancers. Conclusions. This comprehensive analysis revealed that correlation between miRNAs and target genes was greatly reduced in tumor and these critical pairs we got were involved in cellular adhesion, proliferation, and migration. Our research could provide opportunities for investigating cancer molecular regulatory mechanism and seeking therapeutic targets.

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Automated, Noncontact Intraocular Pressure Home Monitoring after Implantation of a Novel Telemetric Intraocular Pressure Sensor in Patients with Glaucoma: A Feasibility Study

Purpose. Reliable and regular assessment of intraocular pressure (IOP) is important for the monitoring of patients with glaucoma. The purpose of this study was to evaluate the feasibility of a novel system for the automated, noncontact measurement of IOP. Patients and Methods. A first-generation telemetric IOP sensor was previously implanted in the ciliary sulcus of six patients with open-angle glaucoma during cataract surgery. Using this technology, automated noninvasive tonometry may be performed in a home setting. In the present study, a modified sleep mask and a modified eyepatch with incorporated coil antennae for measurements during nighttime and daytime, respectively, were tested on a single patient. Results. In this feasibility study, the 24 h wear of the prototype measuring apparatus was well tolerated. Three sequences of 24 h IOP measurements with at least 200 IOP measurements per day were performed (Sequence 1: mean 19.6 ± 2.7 mmHg, range 13.4–28.7 mmHg; Sequence 2: mean 21.0 ± 3.0 mmHg, range 13.1–30.5 mmHg; Sequence 3: mean 19.9 ± 2.4 mmHg, range 12.6–27 mmHg). Conclusions. For the first time, repeated and automated 24-hour measurements are possible using a prototype noncontact reading system after implantation of a novel telemetric IOP sensor in patients with glaucoma.

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Molecular Cytogenetics of Pisum sativum L. Grown under Spaceflight-Related Stress

The ontogenesis and reproduction of plants cultivated aboard a spacecraft occur inside the unique closed ecological system wherein plants are subjected to serious abiotic stresses. For the first time, a comparative molecular cytogenetic analysis of Pisum sativum L. (Fabaceae) grown on board the RS ISS during the Expedition-14 and Expedition-16 and also plants of their succeeding (F1 and F2) generations cultivated on Earth was performed in order to reveal possible structural chromosome changes in the pea genome. The karyotypes of these plants were studied by multicolour fluorescence in situ hybridization (FISH) with five different repeated DNA sequences (45S rDNA, 5S rDNA, PisTR-B/1, microsatellite motifs (AG)12, and (GAA)9) as probes. A chromosome aberration was revealed in one F1 plant. Significant changes in distribution of the examined repeated DNAs in karyotypes of the "space grown" pea plants as well as in F1 and F2 plants cultivated on Earth were not observed if compared with control plants. Additional oligo-(GAA)9 sites were detected on chromosomes 6 and 7 in karyotypes of F1 and F2 plants. The detected changes might be related to intraspecific genomic polymorphism or plant cell adaptive responses to spaceflight-related stress factors. Our findings suggest that, despite gradual total trace contamination of the atmosphere on board the ISS associated with the extension of the space station operating life, exposure to the space environment did not induce serious chromosome reorganizations in genomes of the "space grown" pea plants and generations of these plants cultivated on Earth.

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Adolescent social isolation affects parvalbumin expression in the medial prefrontal cortex in the MAM-E17 model of schizophrenia

Abstract

Altered parvalbumin (PV) expression is observed in the prefrontal cortex of subjects with schizophrenia. Environmental context, particularly during adolescence, might regulate PV expression. In the present study, we investigated the effect of adolescent social isolation (SI) on PV expression in the medial prefrontal cortex in a neurodevelopmental model (MAM-E17) of schizophrenia. SI exposure occurred from postnatal day 30 to 40, followed by resocialization until late adolescence or early adulthood. PV mRNA and protein levels, as well as the number of PV cells, were analysed at these ages. Moreover, epigenetic regulation of PV expression by histone methylation was examined by measuring the total and PV gene-bound H3K4me3 levels. MAM only decreased levels of the PV mRNA and protein in adulthood. Decreases in total H3K4me3 levels and its level at the PV gene were also observed at this age. In contrast, in late adolescence, SI induced a decrease in the expression of the PV mRNA in the MAM group that was related to the reduction in total and PV gene-bound H3K4me3 levels. However, at this age, SI increased the levels of the PV protein in both the control and MAM groups. In adulthood, SI did not affect PV mRNA or H3K4me3 levels but decreased levels of the PV protein in both groups. Both MAM and SI failed to change the number of PV cells at any age. The results indicate that adolescent SI accelerated epigenetic impairments of PV expression in MAM-E17 rats; however, subsequent resocialization abolished this dysfunction, but failed to prevent alterations in PV protein.



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Reading the palm with MUNIX: A ‘reversed split hand’ in spinal muscular atrophy

The split hand phenomenon in amyotrophic lateral sclerosis (ALS), first reported by Wilbourn and Sweeney (1994) and Wilbourn (2000), has proved a resilient clinical sign, although it is not always present in ALS (Wilbourn 2000; Menon et al, 2004), and it is occasionally found in other neuromuscular disorders (Wilbourn 2000; Kuwobara et al, 2008). It consists of marked atrophy of the thenar eminence (APB) and first dorsal interosseous (FDI) muscles with relative sparing of the abductor digiti minimi (ADM).

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Mitochondrial DNA in the tumour microenvironment activates neutrophils and is associated with worse outcomes in patients with advanced epithelial ovarian cancer



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Cell-based immunotherapy approaches for multiple myeloma



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Safety and efficacy of hot avulsion as an adjunct to endoscopic mucosal resection (with videos)

Excision of all visible neoplastic tissue is the goal of endoscopic mucosal resection (EMR) of colorectal laterally spreading tumors (LSTs). Flat and fibrotic tissue can resist snaring. Ablation of visible polyps is associated with high recurrence rates. Avulsion is a technique to continue resection when snaring fails.

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The clinicopathological analysis of receptor tyrosine kinases in meningiomas: the expression of VEGFR-2 in meningioma was associated with a higher WHO grade and shorter progression-free survival

Abstract

WHO grade II/III meningiomas recur frequently and there is currently no established molecular target therapy for meningioma. No previous studies have revealed the association between receptor tyrosine kinases (RTKs) and the recurrence of meningiomas. This study aims to elucidate the association between RTKs and the clinicopathological characteristics and recurrence of meningioma. We investigated the immunohistochemical expression of RTKs (VEGFR-1/2/3, PDGFR-alpha/beta and c-Kit) in 81 meningiomas (WHO grade I, n = 64, WHO grade II/III, n = 17) in 74 patients. Immunohistochemistry revealed that 29 WHO grade I (45%), 10 WHO grade II (77%), and 4 WHO grade III (100%) tumors were VEGFR-2-positive, and that the VEGFR-2 expression was significantly correlated with the WHO grade. In univariate analyses to investigate the clinicopathological factors associated with recurrence, Simpson grade IV/V resection, a larger tumor size, a high VEGFR-2 expression level, WHO grade II/III, a high Ki-67 expression level, and the non-expression of PgR were identified as significant factors. Furthermore, patients with VEGFR-2-positive meningiomas showed significantly shorter progression-free survival. In the multivariate analysis, WHO grade II/III and the location were significantly associated with recurrence. In conclusion, our study suggests that VEGFR-2 inhibitors might be one of the best candidates for molecular therapy against recurrent meningiomas.



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Spiritual Experiences of Adults with Advanced Cancer in Outpatient Clinical Settings

Adults who have advanced cancer experience distress, and many use religion and spirituality to cope. Research on the spiritual experiences of advanced cancer patients will help guide the provision of high-quality spiritual care.

https://ift.tt/2EfuWsO

Difference in opinions about continuous deep sedation among cancer patients, bereaved families, and physicians.

Despite recent advances in palliative medicine, some symptoms are refractory to intensive palliative care, and then palliative sedation therapy is sometimes performed 1, 2. Continuous deep sedation until death (CDS) is regarded as one type of palliative sedation therapy, and it has recently become a focus of intense debate 3-8. While dying in one's sleep is regarded as one type of good death in some cultures 9, CDS may be labeled as a continuum of euthanasia, especially when performed for patients with relatively longer predicted survival 3-8, 10.

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Haplotypes of TNFα/β Genes Associated with Sex-Specific Paranoid Schizophrenic Risk in Tunisian Population

Several medical research findings have announced a strong association between the biology of cytokines and various brain activities. Since growing evidences suggest the crucial and complex role of the tumor necrosis factor in the CNS, we have hypothesized that functional genetic variants of the LTA and TNFA genes (LTA +252A/G (rs909253) and TNFA −857C/T (rs1799724) and TNFA −238G/A (rs361525)) may be involved in the predisposition to schizophrenia. This research is based on a case-control study. The RFLP-PCR genotyping was conducted on a Tunisian population composed of 208 patients and 208 controls. We found a strong significant overrepresentation of the minor alleles (G, T, and A, respectively) in all patients compared with controls (,;,; and ,, respectively). This correlation was confirmed for male but not for female patients. Interestingly, the frequencies of the minor alleles were significantly more common among patients with paranoid schizophrenia when compared with controls (,;,; and ,, respectively). This potential association was confirmed by a logistic binary regression analysis only for the development of the paranoid form of schizophrenia (/;/; and /, respectively) and remained not significant for the other subtypes. Moreover, our study showed an important association between GCA haplotype and the development of this pathological form (,). In conclusion, our results proved a significant association between the three polymorphisms and paranoid schizophrenia, at least in the Tunisian population, suggesting a substantially increased risk for paranoid schizophrenia with dominant inheritance of these three minor alleles.

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Trends in Use of Electronic Health Records in Pediatric Office Settings

To determine the prevalence and functionalities of electronic health records (EHRs) and pediatricians' perceptions of EHRs.

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Delineation of the Individual Effects of Vitamin E Isoforms on Early Life Incident Wheezing

To test the hypothesis that maternal plasma alpha-tocopherol levels are associated with protection from childhood wheeze and that this protection is modified by gamma-tocopherol.

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Reply

We thank de Benedictis et al for the opportunity to discuss the widely debated topic of the diagnostic usefulness of lung ultrasound for pediatric community-acquired pneumonia. We and de Benedictis et al agree on the use of lung ultrasound in the detection of pneumonia in clinical settings particularly when chest radiography is not readily available, as reported by Ambroggio et al.1 However, we also believe that more methodologically rigorous studies are necessary to validate lung ultrasound as an alternative to chest radiography for the diagnosis of pediatric community-acquired pneumonia.

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Sedation Management for Critically Ill Children with Pre-Existing Cognitive Impairment

To compare current analgesia and sedation management practices between critically ill children with pre-existing cognitive impairment and critically ill neurotypical children, including possible indicators of therapeutic efficacy.

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Lessons to apply: Welfare check incident became a LODD

NIOSH line of duty death investigation recommendations for conducting welfare checks are applicable to every EMS agency

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Multidisciplinary Assessment of Planning and Resection of Complex Bone Tumor Using Patient-Specific 3D Model

Abstract

Oncological interventions in thoracic cavity have some important problems such as choice of correct operative approaches depending on the tumor, size, extension, and location. In sarcoma surgery, wide resection should be aimed for the curative surgery. Purpose of this study was to evaluate pre-operative planning of patient-specific thoracic cavity model made by multidisciplinary surgeon team for complex tumor mass for oncological procedures. Patient's scans showed a large mass encroaching on the mediastinum and heart, with erosion of the adjacent ribs and vertebral column. Individual model of this case with thoracic tumor was reconstructed from the DICOM file of the CT data. Surgical team including six interdisciplinary surgeons explained their surgical experience of the use of 3D life-size individual model for guiding surgical treatment. Before patients consented to surgery, each surgeon explained the surgical procedure and perioperative risks to her. A questionnaire was applied to 10 surgical residents to evaluate the 3D model's perception. 3D model scans were useful in determining the site of the lesion, the exact size, extension, attachment to the surrounding structures such as lung, aorta, vertebral column, or vascular involvement, the number of involved ribs, whether the diaphragm was involved also in which order surgeons in the team enter the surgery. 3D model's perception was detected statistical significance as < 0.05. Viewing thoracic cavity with tumor model was more efficient than CT imaging. This case was surgically difficult as it included vital structures such as the mediastinal vessels, aorta, ribs, sternum, and vertebral bodies. A difficult pathology for which 3D model has already been explored to assist anatomic visualization was mediastinal osteosarcoma of the chest wall, diaphragm, and the vertebral column. The study helped to establish safe surgical line wherever the healthy tissue was retained and enabled osteotomy of the affected spinal corpus vertically with posterior-anterior direction by preserving the spinal cord and the spinal nerves above and distal the tumor. 3D tumor model helps to transfer complex anatomical information to surgeons, provide guidance in the pre-operative planning stage, for intra-operative navigation and for surgical collaboration purposes. Total radical excision of the bone tumor and reconstructions of remaining structures using life-size model was the key for successful treatment and better outcomes. The recent explosion in popularity of 3D printing is a testament to the promise of this technology and its profound utility in orthopedic oncological surgery.



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Calif. ambulance company owner wins EMT of the Year honors

Medic Ambulance's Jimmy Pierson was among 33 Californians to be honored for their heroic acts and extraordinary contributions to EMS

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History of Partner Violence Tied to Menopause Symptoms

WEDNESDAY, Dec. 5, 2018 -- A history of intimate partner violence (IPV) or sexual assault and current symptoms of posttraumatic stress disorder (PTSD) are associated with an increased risk for menopause symptoms, according to a study published...

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Sympathetic nervous system as a target for aging and obesity-related cardiovascular diseases

Abstract

Chronic sympathetic nervous system overactivity is a hallmark of aging and obesity and contributes to the development of cardiovascular diseases including hypertension and heart failure. The cause of this chronic sympathoexcitation in aging and obesity is multifactorial and centrally mediated. In this mini-review, we have provided an overview of the key and emerging central mechanisms contributing to the pathogenesis of sympathoexcitation in obesity and healthy aging, specifically focusing on hypertension. A clear understanding of these mechanisms will pave way for targeting the sympathetic nervous system for the treatment of cardiovascular diseases in obesity and aging.



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Skin Autofluorescence Predicts T2DM, Heart Disease, Mortality

WEDNESDAY, Dec. 5, 2018 -- Skin autofluorescence predicts incident type 2 diabetes, cardiovascular disease (CVD), and mortality in the general population, according to a study published online Nov. 21 in Diabetologia. Robert P. van Waateringe, from...

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Few Physicians Work in Practices That Use Telemedicine

WEDNESDAY, Dec. 5, 2018 -- Only 15.4 percent of physicians work in practices that use telemedicine for a wide spectrum of patient interactions, with larger practice size being an important correlate of telemedicine use, according to a study...

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ASH: A+CHP Bests CHOP for Peripheral T-Cell Lymphoma

WEDNESDAY, Dec. 5, 2018 -- For patients with CD30-positive peripheral T-cell lymphoma, brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone (A+CHP) is superior to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP),...

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Imaging, Biopsy Often Still Needed After Mastectomy

WEDNESDAY, Dec. 5, 2018 -- Subsequent imaging is required for 10 to 15.5 percent of women who undergo mastectomy, according to a study published in the December issue of the Annals of Surgical Oncology. Soojin Ahn, M.D., from the Icahn School of...

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Migraine With Aura Linked to Increase in Incident A-Fib

WEDNESDAY, Dec. 5, 2018 -- Migraine with aura is associated with an elevated risk for incident atrial fibrillation (AF), according to a study published online Nov. 14 in Neurology. Souvik Sen, M.D., M.P.H., from the University of South Carolina in...

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ASH: Rivaroxaban Prevents Blood Clots in At-Risk Cancer Patients

WEDNESDAY, Dec. 5, 2018 -- Rivaroxaban can prevent venous thromboembolism (VTE) in cancer patients at increased risk, according to a study presented at the annual meeting of the American Society of Hematology, held from Dec. 1 to 4 in San...

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SABCS: T-DM1 Cuts Recurrent Invasive HER2+ Breast CA Risk

WEDNESDAY, Dec. 5, 2018 -- For patients with residual invasive disease after neoadjuvant chemotherapy including a taxane and trastuzumab, substituting trastuzumab emtansine (T-DM1) for adjuvant trastuzumab is associated with a reduced risk for...

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Self-Management Program Beneficial for Patients With COPD

WEDNESDAY, Dec. 5, 2018 -- A three-month intervention, including chronic obstructive pulmonary disease (COPD) self-management support, results in fewer COPD-related acute care events at six months after discharge, according to a study published...

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Machine Learning Models May Predict Emergency Admissions

WEDNESDAY, Dec. 5, 2018 -- Machine learning models incorporated into electronic health records (EHRs) may predict the risk for emergency hospital admissions, according to a study published online Nov. 20 in PLOS Medicine. Fatemeh Rahimian, Ph.D.,...

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Cannabis‐based products for pediatric epilepsy: A systematic review

Summary

Objective

To assess the benefits and harms of cannabis‐based products for pediatric epilepsy.

Methods

We identified in this living systematic review randomized controlled trials (RCTs) and nonrandomized studies (NRSs) involving children with epilepsy treated with cannabis‐based products. We searched MEDLINE, Embase, PsycINFO, Cochrane Library, and gray literature (April 25, 2018). The primary outcome was seizure freedom; secondary outcomes were seizure frequency (total, ≥50% reduction), quality of life, sleep, status epilepticus, death, gastrointestinal adverse events, and visits to the emergency room. Data were pooled by random‐effects meta‐analysis. Risk of bias was assessed for each study, and GRADE was used to assess the quality of evidence for each outcome.

Results

Four RCTs and 19 NRSs were included, primarily involving cannabidiol. All RCTs were at low risk of bias, whereas all NRSs were at high risk. Among RCTs, there was no statistically significant difference between cannabidiol and placebo in seizure freedom (relative risk [RR] = 6.77, 95% confidence interval [CI] = 0.36‐128.38; 1 RCT), quality of life (mean difference = 0.6, 95% CI = −2.6 to 3.9; 3 RCTs), sleep disruption (mean difference = −0.3, 95% CI = −0.8 to 0.2; 3 RCTs), or vomiting (RR = 1.00, 95% CI = 0.51‐1.96; 4 RCTs). There was a statistically significant reduction in the median frequency of monthly seizures with cannabidiol compared with placebo (−19.8%, 95% CI = −27.0% to −12.6%; 3 RCTs) and an increase in the number of participants with at least a 50% reduction in seizures (RR = 1.76, 95% CI = 1.07‐2.88; 1 RCT) and diarrhea (RR = 2.25, 95% CI = 1.38‐3.68; 3 RCTs). Death and status epilepticus were infrequently reported.

Significance

Evidence from high‐quality RCTs suggests that cannabidiol probably reduces seizures among children with drug‐resistant epilepsy (moderate certainty). At this time, the evidence base is primarily limited to cannabidiol, and these findings should not be extended to all cannabis‐based products.



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