Αρχειοθήκη ιστολογίου

Τετάρτη 28 Ιουνίου 2017

Tuberculous meningoencephalitis associated with brain tuberculomas during pregnancy: a case report

Tuberculous meningitis is globally highly prevalent and is commoner in resource-limited countries and in patients with immunosuppression. Central nervous system tuberculosis is one of the severest forms of ext...

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Fluorescein sodium-guided surgery of parotid gland tumors as a technical advance

Complete tumor removal and preservation of the facial nerve are essential in parotid gland surgery. A technical adjunct that potentially enhances the contrast between the facial nerve and the adherent tumor ti...

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Partenij Pavlovich revisited



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Rivals and Collaborators. The Image of the West in Albanian Anti-Soviet Propaganda



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Rapid response to clinical symptoms in early psoriatic onycho-pachydermo-periostitis treated with infliximab



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Dermatological learning needs among aboriginal health workers in rural and remote Australia: A cross-sectional survey



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Lepromatous leprosy with Lucio's phenomenon



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Maculopapular type drug eruption caused by garenoxacin mesilate hydrate: A case report and literature review



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Necrobiosis lipoidica following Q-switched laser tattoo removal



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Pyoderma gangrenosum arising during treatment of psoriasis with adalimumab: Effectiveness of ustekinumab



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Febrile headache and leg weakness as the initial symptoms of tickborne encephalitis

Description

A 61-year-old woman presented to the emergency department (ED) with a 1-week fever associated with progressive headache. She also reported weakness and paraesthesias in both legs. In the ED, the patient had normal vital parameters and reported no other medical history. Clinical examination showed a slight neck stiffness; the rest of the examination was normal. Laboratory findings showed a mild inflammatory syndrome. The patient had a lumbar punction; the cerebrospinal fluid (CSF) showed moderate pleocytosis (140 leucocytes/μL with a mononuclear cell dominance). After a normal CT scan, an MRI examination was performed (figures 1and 2). Several days later, intrathecal IgM and IgG antibodies came back positive.

Figure 1

T2-weighted transverse MRI. Localised hyperintense band involving the tegmentum pontis (arrow heads) and the cerebellar vermis (arrow).

Figure 2

Coronal MRI, fluid attenuation inversion recovery...



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Critical Ischemia Times and The Effect of Novel Preservation Solutions HTK-N and TiPROTEC on Tissues of a Vascularized Tissue Isograft.

Background: We herein investigate critical ischemia times and the effect of novel preservation solutions HTK-N and TiProtec on the individual tissues of a rat limb isograft. Methods: Orthotopic hind-limb transplantations were performed in male Lewis rats following 2h, 6h or 10h of cold ischemia. Limbs were flushed and stored in either HTK-N, TiProtec, HTK or saline solution. Muscle, nerve, vessel, skin and bone samples were procured on day 10 for histology, immunohistochemistry, confocal and electron microscopy and RTqPCR analysis. Results: Histomorphology of the muscle showed a mainly perivascular inflammatory infiltrate, fibrotic degeneration and neovascularization after 6h and 10h of cold ischemia. However, centrally aligned nuclei observed in muscle fibers suggest for muscle regeneration in these samples. In addition to Wallerian degeneration, nerve injury was significantly (p=0.032) aggravated after prolonged cold ischemia. Proinflammatory and regulatory cytokines were most significantly upregulated after 2h cold ischemia. Our data suggest no superiority of novel perfusates HTK-N and TiProtec in terms of tissue preservation, compared to HTK and saline. Conclusions: Limiting cold ischemia time below 6h is the most significant factor to reduce tissue damage in vascularized tissue transplantation. Signs of muscle regeneration give rise that ischemic muscle damage in limb transplantation might be reversible to a certain extent. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Targeted Next-generation Sequencing in Brazilian Children With Nephrotic Syndrome Submitted to Renal Transplant.

Background: The aims of this study were to identify the genetic mutations profile in Brazilian children with nephrotic syndrome and to determine a genotype-phenotype correlation in this disease. Methods: Next generation sequencing (NGS) and mutation analysis were performed on 24 genes related to nephrotic syndrome in a cross-sectional study involving 95 children who underwent kidney transplantation due to nephrotic syndrome, excluding congenital cases. Results: A total of 149 variants were identified in 22 out of 24 sequenced genes. The mutations were classified as pathogenic, likely pathogenic, likely benign and benign per the chance of causing the disease. NPHS2 was the most common mutated gene. We identified 8 patients (8.4%) with hereditary NS and 5 patients (5%) with probably genetically caused NS. COL4A3-5 variants were found as well, but it is not clear whether they should be considered isolated FSGS or simply a misdiagnosed type of the Alport spectrum. Considering the clinical results, hereditary NS patients presented a tendency to early disease onset when compared to the other groups (p=0.06) and time to end stage renal disease (ESRD) was longer in this group (p=0.03). No patients from hereditary NS group had NS recurrence after transplantation. Conclusions: This is the first study in children with steroid resistant nephrotic syndrome who underwent kidney transplantation using NGS. Considering our results, we believe this study has shed some light to the uncertainties of genotype-phenotype correlation in NS, where several genes cooperate to produce or even to modify the course of the disease. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Pharmacokinetics and Clinical Outcomes of Generic Tacrolimus (Hexal) Versus Branded Tacrolimus in De Novo Kidney Transplant Patients: A Multicenter, Randomized Trial.

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Background: Scrupulous comparison of the pharmacokinetic and clinical characteristics of generic tacrolimus formulations versus the reference drug (Prograf) is essential. Pharmacokinetics of the TacHexal formulation are similar to Prograf in stable renal transplant patients but data in de novo patients is lacking. Methods: De novo kidney transplant patients were randomized to generic tacrolimus (Tacrolimus Hexal [TacHexal]) or Prograf in a 6-month open-label study. Results: The primary endpoint, the dose-normalized AUC0-12h ratio at month 1 posttransplant, was similar with TacHexal or Prograf: back-transformed geometric means of adjusted log-transformed values (ANOVA) were 18.99 ng*h/L (TacHexal) and 20.48 ng*h/L (Prograf) (ratio 1.08 [90% CI 0.84; 1.38]; p=0.605). The dose-normalized peak concentration (Cmax) geometric means at month 1 was also comparable between treatments (ratio 1.16 [90% CI 0.88; 1.54], p=0.377). There were no relevant differences in other pharmacokinetic parameters at month 1, or in AUC0-4 and trough concentration when measured at months 3 and 6. The adjusted change in mean estimated GFR from baseline to month 6 (Nankivell) was noninferior for TacHexal versus Prograf using observed values (47.7 versus 38.6mL/min/1.73m2, p

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Tacrolimus Trough Concentration Variability and Disparities in African American Kidney Transplantation.

Background: Low tacrolimus concentrations have been associated with higher risk of acute rejection, particularly within African-American (AA) kidney transplant recipients; little is known about intrapatient tacrolimus variabilities impact on racial disparities. Methods: Ten year, single-center, longitudinal cohort study of kidney recipients. Intrapatient tacrolimus variability was assessed using the coefficient of variation (CV) measured between 1 month posttransplant and the clinical event, with a comparable period assessed in those without events. Pediatrics, nontacrolimus/mycophenolate regimens and nonrenal transplants were excluded. Multivariable Cox regression models were used to analyze data. Results: 1411 recipients were included (54.4% AA) with 39 521 concentrations utilized to assess intrapatient tacrolimus CV. Overall, intrapatient tacrolimus CV was higher in AAs vs non-AAs (39.9+/-19.8 % vs. 34.8+/-15.8% p40%) was a significant explanatory variable for disparities in AAs; the crude relative risk of acute rejection in AAs was reduced by 46% when including tacrolimus variability in modeling and reduced by 40% for graft loss. Conclusions: These data demonstrate that intrapatient tacrolimus variability is strongly associated with acute rejection in AAs and graft loss in all patients. Tacrolimus variability is a significant explanatory variable for disparities in AA recipients. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Necrotising coronaritis with fatal outcome

A 56-year-old woman presented with acute onset of typical chest pain. She was diagnosed with acute coronary syndrome with ST-segment elevation myocardial infarction. Although significant obstructive coronary artery disease was ruled out by coronary angiography, cardiac MRI showed transmural necrosis of the lateral free wall with extensive microvascular obstruction consistent with ischaemic heart disease. Within 48 hours after initial presentation, the patient suddenly arrested due to pulseless electrical activity with futile resuscitation efforts. Autopsy revealed myocardial perforation with extensive haematothorax due to pericardial laceration, caused by the mechanical chest compressions. Eventually, histology identified diffuse necrotising coronary vasculitis as a rare cause of ischaemic heart disease.



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Pattern of skin diseases among patients attending an outpatient dermatology clinic in a tertiary hospital in urban Malaysia



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Infundibulocystic basal cell carcinoma of the eyelid



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Clinical and dermoscopic features of targetoid haemosiderotic naevus: A peculiar melanoma simulator



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Bilateral inner ear damage after electrical injury: A case report

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Publication date: Available online 28 June 2017
Source:Auris Nasus Larynx
Author(s): George Psillas, Marios Stavrakas, Ioanna Petrou, Dimitrios Rachovitsas, Konstantinos Markou
Electrical injury occurs as a result of direct contact with an electrical source. We present the case of a 62-year-old male patient, an electrician by profession, who was hit by a high-voltage electrical current while working with cables in proximity to a wet floor. The patient suffered from immediate loss of consciousness and five days later he started complaining of slight hearing loss, persistent vertigo, instability and bilateral tinnitus. A thorough audiological and vestibular examination revealed an extensive bilateral vestibulocochlear dysfunction. The exact pathogenetic mechanisms of inner ear dysfunction after electrical injury have not been fully elucidated, although it is believed that there is significant improvement with time. Long-term follow-up, medical assistance and psychological support are crucial factors for the patient management.



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Ultrasound Risk Categories for Thyroid Nodules and Cytology Results: A Single Institution’s Experience after the Adoption of the 2016 Update of Medical Guidelines by the American Association of Clinical Endocrinologists and Associazione Medici Endocrinologi

Objectives. In 2016, the American Association of Clinical Endocrinologists (AACE) and Associazione Medici Endocrinologi (AME) released updated guidelines for the diagnosis and management of thyroid nodules. The aim of this study was to evaluate the AACE/AME recommendations for FNA in clinical practice, by comparing the (US) stratification risk and indications for FNA with cytologic results. Methods. From May to December 2016, we collected the cytologic results from FNAs of nodules that were classified using a three-tier US category system (low, intermediate, and high risk). Results. We obtained 859 FNAs from 598 patients: 341 (39.7%) from low, 489 (56.9%) from intermediate, and 29 (3.4%) from high risk nodules. Of these, 88.5% and 74.9% of low and intermediate risk nodules, respectively, were cytologically benign, whereas 84.6% of high risk nodules had a moderate-to-elevated risk of malignancy or were malignant. If FNAs had been limited to intermediate risk nodules >20 mm, we would have missed 13/17 (76.5%) nodules that had moderate-to-elevated risk of malignancy or were malignant (11/13 were malignant based on histology). Conclusions. A nonnegligible number of cytologically malignant nodules or nodules that were suspected to be malignant would be missed if intermediate US risk nodules

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Retrospective study of intranasal dexmedetomidine as a prophylactic against emergence delirium in pediatric patients undergoing ear tube surgery

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Publication date: September 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 100
Author(s): Lisgelia Santana, Katherine Mills
ObjectivesThis study evaluated the effect of intranasal dexmedetomidine on emergence delirium (ED) in pediatric patients who underwent ear tube surgeries. Due to the brief nature of the surgery and low levels of pain experienced, an IV is rarely needed, limiting the medications available to anesthesiologists to manage postoperative delirium that may arise during recovery from inhalational anesthesia. Intravenous dexmedetomidine is an alpha-2 agonist anesthetic that is used in pediatric patients for the management of ED in various surgical procedures. However, intranasal medication has not been evaluated specifically in ear tube surgeries for ED prevention.MethodsWe conducted a retrospective chart review of pediatric patients at Nemours Children's Hospital who had undergone ear tube insertion or removal surgery between 2013 and 2015, controlling for confounding variables such as age, surgery duration, and anesthesiologist. We used the post anesthesia emergence delirium (PAED) tool, an instrument created to assess ED in the clinical setting. We analyzed the data for significant differences in PAED score and time in the post anesthesia care unit (PACU) between patients treated with intranasal dexmedetomidine and the control group that did not receive the medication.ResultsWe found no significant difference between the PAED scores of those patients treated with intranasal dexmedetomidine prior to ear tube surgeries and those who did not receive the medication, and no difference in the duration of PACU stay.ConclusionThese results conflict with other research on intranasal dexmedetomidine and its potential to prevent ED in pediatric patients. This information should prompt further prospective investigation into the most efficacious use of dexmedetomidine for ED prevention, both in terms of timing and dosage required.



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Comparison of home sleep apnea testing versus laboratory polysomnography for the diagnosis of obstructive sleep apnea in children

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Publication date: September 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 100
Author(s): Nicholas Scalzitti, Shana Hansen, Stephen Maturo, Joshua Lospinoso, Peter O'Connor
IntroductionObstructive sleep apnea (OSA) affects 1–5% of pediatric patients. Laboratory polysomnography is expensive, not always available, and is inconvenient for patients. Our study investigates the diagnostic ability of an unattended ambulatory monitor for the diagnosis of pediatric OSA.MethodsA prospective study was conducted in children, ages 2–17. Subjects completed in-lab polysomnography simultaneously with ambulatory monitoring. Caregivers attempted home studies on two subsequent nights to compare the home monitor and the laboratory polysomnogram (PSG).ResultsThirty-three subjects completed simultaneous laboratory polysomnogram with portable monitoring. Twenty patients completed home studies, with 16 completing 2 nights of monitoring. The measurement of AHI by the portable monitor was different than that obtained by the PSG with statistical significance for the comparisons of PSG vs. In-Lab (p = 0.0026), PSG vs. Home 1 (p = 0.033), and PSG vs. Home 2 (p = 0.033). The sensitivity of the portable monitor for diagnosing OSA was best for the In-lab use at 81%, but only 69% and 70% for the uses at home on the 2 nights respectively. Interestingly, the comparison of AHI and lowest oxygen saturation measurements from the home sleep test in children age 6 and older did not differ significantly from the PSG.ConclusionsThis pilot study demonstrated differences between home sleep testing and in-lab polysomnography for the diagnosis of pediatric sleep apnea. These differences were predominantly found to exist in younger children. Larger prospective studies are needed prior to widespread use, but home studies may alleviate issues of access to care and higher costs of laboratory polysomnography.



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Autoinflammatory keratinization diseases

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Publication date: Available online 28 June 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Masashi Akiyama, Takuya Takeichi, John A. McGrath, Kazumitsu Sugiura




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A clustering approach to identify and characterize the asthma and chronic obstructive pulmonary disease overlap phenotype

Abstract

Background

Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases. The phenotypes that have clinical features of both asthma and COPD are still incompletely understood.

Objective

To clarify the best discriminators of the asthma-COPD overlap phenotype from asthma and COPD subgroups using a clustering approach.

Methods

This study assessed pathophysiological parameters, including mRNA expression levels of T helper cell-related transcription factors, namely, TBX21 (Th1), GATA3 (Th2), RORC (Th17), and FOXP3 (Treg), in peripheral blood mononuclear cells in asthma patients (n = 152) and in COPD patients (n = 50). Clusters were determined using k-means clustering. Exacerbations of asthma and COPD were recorded during the 1-year follow-up period.

Results

The cluster analysis revealed four biological clusters: cluster 1, predominantly patients with COPD; cluster 2, patients with an asthma-COPD overlap phenotype; cluster 3, patients with non-atopic and late-onset asthma; and cluster 4, patients with early-onset atopic asthma. Hazard ratios for exacerbation were 2.5 (95% confidence interval [CI], 1.1–5.6) in cluster 1 and 2.3 (95% CI, 1.0–5.0) in cluster 2 compared with patients in other clusters. Cluster 2 was discriminated from other clusters by total serum IgE level ≥ 310 IU/mL, blood eosinophil counts ≥ 280 cells/μL, a higher ratio of TBX21/GATA3, FEV1/FVC ratio < 0.67, and smoking ≥ 10 pack-years with an area under the curve of 0.94 (95% CI, 0.90–0.98) in the receiver operating characteristic analysis.

Conclusions & Clinical Relevance

The asthma-COPD overlap phenotype was characterized by peripheral blood eosinophilia and higher levels of IgE despite the Th2-low endotype.

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Novel Somatic RET Mutation Questioning the Causality of the RET I852M Germline Sequence Variant in Multiple Endocrine Neoplasia 2A

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Thyroid , Vol. 0, No. 0.


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Double chin: Causes and how to get rid of one

Excess fat under the chin can be caused by a number of factors, including age, weight, and genetics. Learn how to reduce the appearance of a double chin.

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Whitish Papules and Scars on a Patient With Bowel Perforation

A woman in her 30s with a 1-year history of unintentional weight loss, mild diffuse abdominal pain, and occasional episodes of vomiting after bowel perforation 3 years prior had a 24-hour history of intense abdominal pain, fever, and loose stools. What is your diagnosis?

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Isotretinoin and Timing of Cutaneous Surgery Procedural Interventions

This systematic review analyzes the evidence behind the medical dictum prohibiting procedural interventions in the setting of isotretinoin therapy.

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Human Papillomavirus Vaccination and Keratinocyte Carcinomas—Reply

In Reply We appreciate Dr Mayer's interest in our article as well as his comments highlighting the inherent limitations of a small case series. We reported 2 cases of immunocompetent patients with a history of multiple keratinocyte carcinomas (KCs) and observed a substantial reduction of both squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs) subsequent to the quadrivalent human papillomavirus (HPV) vaccine.

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Human Papillomavirus Vaccination and Keratinocyte Carcinomas

To the Editor I enjoyed reading the article by Nichols et al on using the human papillomavirus (HPV) vaccine for the prevention of keratinocyte carcinomas (KCs). They found that 2 patients given the HPV vaccine had a large decrease in both squamous cell carcinomas (SCCs) (about 65%) and basal cell carcinomas (BCCs) (100%). However, further study details are needed to clarify whether the HPV vaccine is indeed a magic bullet or if the results are due to selection bias.

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Misspelling of Coauthor Surname

In the article titled "Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Standard Reporting and Evaluation Guidelines: Results of a National Institutes of Health Working Group," published online March 15, 2017, Dr Tassaneeyakul's surname was misspelled in the byline. This article has been corrected online. This article was also corrected in April 2017 for typographical errors and missing table footnote.

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Correlation Among Cancer Mortality Rates and Internet Searches

This cross-sectional analysis of Google seach volume index data investigates whether internet search volumes are correlated with registry recorded incidences and mortalities of common cancers

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Immediate moxifloxacin hypersensitivity: is there more than currently meets the eye?

Abstract

Immediate drug hypersensitivity reactions (IDHR) to moxifloxacin constitute a pathomechanistic conundrum and a diagnostic challenge. Our objective was to study whether simultaneous phenotyping and quantification of histamine release might add to our knowledge about the basophil activation properties of moxifloxacin and constitute a reliable diagnostic aid. Fifteen patients with an IDHR to moxifloxacin and 9 moxifloxacin challenged controls were selected. All had a basophil activation test (BAT) with moxifloxacin. Flow cytometric analysis of basophil responses implied labeling for CD63, CD203c and intracellular histamine. Unlike tolerant challenged controls, basophilic upregulation of CD203c in response to moxifloxacin was observed in 7/15 patients. Only 2 of these 7 patients demonstrated appearance of CD63 and release of histamine. In the remainder 8 patients no basophil responses were demonstrable. In conclusion, immediate hypersensitivity to moxifloxacin might involve mechanisms difficult to capture by traditional CD63/CD203c-based BAT. Deciphering the complexity of quinolone IDHR seems mandatory.

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Delayed type hypersensitivity reactions induced by proton pump inhibitors: a clinical and in vitro T cell reactivity study

Abstract

Background

Proton pump inhibitors (PPI) has been known to induce type I hypersensitivity reactions. However, severe delayed type hypersensitivity reactions (DHR) induced by PPI, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug rash with eosinophilia and systemic symptoms (DRESS), are rarely reported. We conducted a study of a large series of PPI-related DHR, followed up their tolerability to alternative anti-ulcer agents, and investigated the T cell reactivity to PPI in PPI-related DHR patients.

Methods

We retrospectively analyzed patients with PPI-related DHR from multiple medical centers in Taiwan during the study period January 2003 to April 2016. We analyzed the causative PPI, clinical manifestations, organ involvement, treatment, and complications. We also followed up the potential risk of cross-hypersensitivity or tolerability to other PPI after their hypersensitivity episodes. Drug lymphocyte activation test (LAT) was conducted by measuring granulysin and interferon-γ to confirm the causalities.

Results

There were 69 cases of PPI-related DHR, including SJS/TEN (n=27) and DRESS (n=10). The LAT by measuring granulysin showed a sensitivity of 59.3% and specificity of 96.4%. Esomeprazole was the most commonly involved in PPI-related DHR (51%). Thirteen patients allergic to one kind of PPI could tolerate other structurally different PPI without cross-hypersensitivity reactions, whereas three patients developed cross-hypersensitivity reactions to alternative structurally similar PPI. The cross-reactivity to structurally similar PPI was also observed in LAT assay.

Conclusions

PPIs have the potential to induce life-threatening DHR. In patients when PPI is necessary for treatment, switching to structurally different alternatives should be considered.

This article is protected by copyright. All rights reserved.



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The in vitro mucolytic effect of xylitol and dornase alfa on chronic rhinosinusitis mucus

Background

The overproduction and stagnation of purulent mucus impair mucociliary clearance and exacerbate the symptoms of chronic rhinosinusitis (CRS). There is a clinical need for effective topical mucolytic agents to facilitate removal of mucus and improve postoperative outcomes.

Methods

The effects of xylitol (5%) and dornase alfa (1 mg/mL) on mucus and mucus crusts were investigated. Viscoelasticity and viscosity of wet mucus derived from 30 CRS patients was measured with a plate rheometer. Postoperative dried mucus crust dissolution was measured by examining peripheral transparency, central transparency, and border definition of treated crust samples from 17 CRS patients.

Results

Xylitol and dornase alfa reduced wet mucus viscoelasticity at a frequency of 0.1 Hz significantly more than the saline control. Treatments also produced significantly lower viscosities than saline at a shear rate of 10 and 100 seconds−1. Xylitol and dornase alfa significantly decreased mucus crust border definition relative to saline.

Conclusion

Xylitol and dornase alfa may be efficacious mucolytics, encouraging the breakdown of postoperative mucus crusts and the reduction of viscoelasticity and viscosity of wet mucus. In vivo study is required to evaluate the potential of these agents in treating recalcitrant CRS.



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Assessment of acquired mucociliary clearance defects using micro-optical coherence tomography

Background

Dehydration of airway surface liquid (ASL) disrupts normal mucociliary clearance (MCC) in sinonasal epithelium, which may lead to chronic rhinosinusitis (CRS). Abnormal chloride (Cl) transport is one such mechanism that contributes to this disorder and can be acquired secondary to environmental perturbations, such as hypoxia at the tissue surface. The objective of this study was to assess the technological feasibility of the novel micro-optical coherence tomography (μOCT) imaging technique for investigating acquired MCC defects in cultured human sinonasal epithelial (HSNE) cells.

Methods

Primary HSNE cell cultures were subjected to a 1% oxygen environment for 12 hours to induce acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. Ion transport characteristics were assessed with pharmacologic manipulation in Ussing chambers. ASL, periciliary fluid (PCL), and ciliary beat frequency (CBF) were evaluated using μOCT.

Results

Amiloride-sensitive transport (ΔISC) was greater in cultures exposed to hypoxia (hypoxia: −13.2 ± 0.6 μA/cm2; control: −6.5 ± 0.1 μA/cm2; p < 0.01), whereas CFTR-mediated anion transport was significantly diminished (hypoxia: 28.6 ± 0.3 μA/cm2; control: 36.2 ± 1.6 μA/cm2; p < 0.01), consistent with acquired CFTR dysfunction and sodium hyperabsorption. Hypoxia diminished all markers of airway surface function microanatomy as observed with μOCT, including ASL (hypoxia: 5.0 ± 0.4 μm; control: 9.0 ± 0.9 μm; p < 0.01) and PCL depth (hypoxia: 2.5 ± 0.1 μm; control: 4.8 ± 0.3 μm; p < 0.01), and CBF (hypoxia: 8.7 ± 0.3 Hz; control: 10.2 ± 0.3 Hz; p < 0.01).

Conclusion

Hypoxia-induced defects in epithelial anion transport in HSNE led to predictable effects on markers of MCC measured with novel μOCT imaging. This imaging method represents a technological leap forward and is feasible for assessing acquired defects impacting the airway surface.



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Platelet activation by crushed and uncrushed muscle: a flow cytometry analysis

Background

Crushed autologous muscle is used in skull base surgery in the acute phase of major arterial hemorrhage to stop bleeding. The mechanism of this is not yet clear, but is thought to involve the formation of a platelet plug, which seals the vessel wall defect but still allows ongoing blood flow to the brain.

Methods

In this study we use flow cytometry to replicate the in-vivo actions of crushed muscle on platelets in whole blood. We compare the ratio of activation of platelets exposed to crushed and uncrushed muscle supernatant in control patients and in patients on antiplatelet agents.

Results

Crushed muscle activated platelets to a higher degree than uncrushed muscle: 5.18-fold greater in control blood (p = 0.002); 6.53-fold greater in aspirin-exposed blood (p < 0.0001); and 9.4-fold greater in clopidogrel-exposed blood (p < 0.0001).

Conclusion

Crushed muscle caused a consistently increased ratio of platelet activation when compared with uncrushed muscle across all groups, adding to the evidence that at least part of its clinical effect is the result of platelet activation.



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A call for critical examination of endoscopically guided cultures in chronic rhinosinusitis



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Expression of Metabolic Syndrome in Women with Severe Obesity

Metabolic Syndrome and Related Disorders , Vol. 0, No. 0.


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Association between preoperative pulse pressure and perioperative myocardial injury: an international observational cohort study of patients undergoing non-cardiac surgery

Abstract
Background. The management of elevated blood pressure before non-cardiac surgery remains controversial. Pulse pressure is a stronger predictor of cardiovascular morbidity in the general population than systolic blood pressure alone. We hypothesized that preoperative pulse pressure was associated with perioperative myocardial injury.Methods. This is a secondary analysis of the Vascular Events in Non-cardiac Surgery Patients Cohort Evaluation (VISION) international cohort study. Participants were aged ≥45 yr and undergoing non-cardiac surgery at 12 hospitals in eight countries. The primary outcome was myocardial injury, defined using serum troponin concentration, within 30 days after surgery. The sample was stratified into quintiles by preoperative pulse pressure. Multivariable logistic regression analysis explored associations between pulse pressure and myocardial injury. We accounted for potential confounding by systolic blood pressure and other co-morbidities known to be associated with postoperative cardiovascular complications.Results. One thousand one hundred and ninety-one of 15 057 (7.9%) patients sustained myocardial injury, which was more frequent amongst patients in the highest two preoperative pulse pressure quintiles {63–75 mm Hg, risk ratio (RR) 1.14 [95% confidence interval (CI): 1.01–1.28], P=0.03; >75 mm Hg, RR 1.15 [95% CI: 1.03–1.29], P=0.02}. After adjustment for systolic blood pressure, preoperative pulse pressure remained the dominant predictor of myocardial injury (63–75 mm Hg, RR 1.20 [95% CI: 1.05–1.37], P<0.01; >75 mm Hg, RR 1.25 [95% CI: 1.06–1.48], P<0.01). Systolic blood pressure >160 mm Hg was not associated with myocardial injury in the absence of pulse pressure >62 mm Hg (RR 0.67 [95% CI: 0.30–1.44], P=0.31).Conclusions. Preoperative pulse pressure >62 mm Hg was associated with myocardial injury, independent of systolic blood pressure. Elevated pulse pressure may be a useful clinical sign to guide strategies to reduce perioperative myocardial injury.

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Some light in the grey zone?

Treatment of shock is not a new concern in intensive care medicine. The highest priority in patients with shock is the restoration of oxygen delivery. Fluid resuscitation is the very first goal of increasing cardiac output and oxygen delivery in patients with acute circulatory insufficiency. First, based on the simple physiology of the Frank–Starling mechanism, fluid loading should increase cardiac output (CO) by increasing preload and subsequently increasing left ventricular (LV) stroke volume.1 However, fluid overload, especially in patients with pre-existing or developing cardiac failure, can end in only a fractional increase of stroke volume and negative effects like pulmonary venous congestion can predominate. It is therefore a daily task for each intensivist to identify those patients who will respond to and benefit from volume expansion (e.g. acute shock) and to avoid fluid overload in those who are no longer fluid responsive but are at risk for increased mortality by further fluid therapy (e.g. protracted sepsis, acute respiratory distress syndrome, acute kidney injury). Thus the therapeutic conflict between hypovolaemia and hypervolaemia needs to be addressed wisely. Consequently, precise monitoring of preload could be helpful in this clinical scenario (Fig. 1).

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Hypotension during induction of anaesthesia is neither a reliable nor a useful quality measure for comparison of anaesthetists’ performance

Abstract
Background. Identification of statistically reliable outcomes for comparison among anaesthetists is challenging. Time-weighted intraoperative mean arterial pressure <65 mm Hg (AUC65) is associated with increased odds for myocardial damage. We explored retrospectively whether such hypotension before incision was statistically reliable for peer comparison.Methods. We retrieved electronic data between 2006 and 2015 at a tertiary care, academic hospital in the USA for patients at risk for myocardial damage (inpatient after surgery, ASA physical status ≥III, ≥50 yr of age, and case duration ≥60 min). We determined the percentage of anaesthetists comparable based on caseload and case-mix. The AUC65 was compared amongst anaesthetists supervising ≥100 cases involving at-risk patients during the last 12 months.Results. Only 14.1% [95% confidence interval (CI) 13.6–14.5%] of cases involved patients who were 'at risk' during the 10 yr study period. A yearly average of 49 (sd 6) anaesthetists supervised ≥100 cases of any type, of whom only 52% (95% CI 47.1–56.0%) supervised ≥100 cases involving at-risk patients. Thus, nearly half the anaesthetists would have been excluded from peer comparison. During the last 12 months, there were two outliers among 34 evaluable anaesthetists (P<0.05, controlling for false discovery). However, their contribution to total hypotension amongst cases for all patients was small, because hypotension was widely distributed (e.g. 80% of hypotension attributable to 61.8% of anaesthetists, 95% CI 59.8–63.7%). There was no relationship between the AUC65 and propofol induction dose.Conclusions. The AUC65 of time-weighted pre-incision hypotension is not a suitable metric for comparing anaesthetists. There were few at-risk patients, half the anaesthetists were not evaluable because of their case-mix and caseload, and hypotension was widely distributed.

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The spectrum of spontaneous coronary artery dissection: illustrated review of the literature



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Cohort study of preoperative blood pressure and risk of 30-day mortality after elective non-cardiac surgery

British Journal of Anaesthesia, 119(1): 65–77 (2017), DOI 10.1093/bja/aex056

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Quality metrics: hard to develop, hard to validate

In this issue of the British Journal of Anaesthesia, Epstein and colleagues1 report their findings surrounding the proposed use of intraoperative hypotension as a quality metric for comparison of anaesthetists. The authors analysed a retrospective data set derived from 10 yr of data from their anaesthesia information management system, focusing specifically on a cohort of patients undergoing surgery at an increased risk of postoperative myocardial injury. The availability of electronic health records has enabled big data approaches for quality improvement and outcomes research in anaesthesia.23 Anaesthetists performing these procedures were compared based on the time-weighted area under the curve for postinduction hypotension (defined as a mean arterial pressure of <65 mm Hg) over 2 month intervals. Recent evidence reviewed by Epstein and colleagues1 has implicated intraoperative hypotension in adverse outcomes after cardiac and non-cardiac surgery, and additional relevant studies will appear in the British Journal of Anaesthesia.45 The authors showed, convincingly, that because of the wide distribution of hypotension across providers and time epochs, intraoperative hypotension cannot be used alone as a quality metric to compare anaesthetists.

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Predictor of fluid responsiveness in the ‘grey zone’: augmented pulse pressure variation through a temporary increase in tidal volume

Abstract
Background: Pulse pressure variation (PPV) is widely used as a predictor of fluid responsiveness. However, a previous study has suggested a 'grey zone' between 9 and 13% in which PPV would be inconclusive to predict fluid responsiveness. Considering PPV is based on cardiopulmonary interactions, we evaluated whether an augmented PPV using a temporary increase in tidal volume (VT) from 8 to 12 ml kg−1 has the predictability for fluid responsiveness in patients within the grey zone.Methods: Adult patients requiring general anaesthesia were enrolled. During the period when PPV was within the range of 9–13%, haemodynamic variables such as stroke volume index (SVI) and PPV with an 8 ml kg−1 tidal volume ventilation (PPV8) were obtained before and after volume expansion (6 ml kg−1) under mechanical ventilation. Augmented PPV induced by 2-min ventilation with a VT of 12 ml kg−1 (PPV12) was also recorded immediately before volume loading. The patients whose SVI increased ≥10% after volume expansion were considered responders.Results: In 38 enrolled patients, 20 were responders. Receiver operating characteristic curve analysis showed PPV12 had an excellent predictability for fluid responsiveness {area under the curve [AUC]=0.935 [95% confidence interval (CI) 0.805–0.989]; sensitivity 95%; specificity 72%; P<0.0001}. The optimal threshold for PPV12 was >17%. However, PPV8 failed to show significant predictability [AUC=0.668 (95% CI 0.497–0.812); sensitivity 65%; specificity 61%; P=0.06].Conclusion: In mechanically ventilated patients, our augmented PPV successfully predicted fluid responsiveness in the previously suggested grey zone.Clinical trial registration: ClinicalTrials.gov, NCT02653469.

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Predicting postoperative morbidity in adult elective surgical patients using the Surgical Outcome Risk Tool (SORT)

Abstract
Background. The Surgical Outcome Risk Tool (SORT) is a risk stratification instrument used to predict perioperative mortality. We wanted to evaluate and refine SORT for better prediction of the risk of postoperative morbidity.Methods. We analysed prospectively collected data from a single-centre cohort of adult patients undergoing major elective surgery. The data set was split randomly into derivation and validation samples. We used logistic regression to construct a model in the derivation sample to predict postoperative morbidity as defined using the validated Postoperative Morbidity Survey (POMS) assessed at 1 week after surgery. Performance of this 'SORT-morbidity' model was then tested in the validation sample and compared against the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM).Results. The SORT-morbidity model was constructed using a derivation sample of 1056 patients and validated in a further 527 patients. SORT-morbidity was well calibrated in the validation sample, as assessed using calibration plots and the Hosmer–Lemeshow test (χ2=4.87, P=0.77). It showed acceptable discrimination by receiver operating characteristic curve analysis [area under the receiver operating characteristic curve (AUROC)=0.72, 95% confidence interval: 0.67–0.77]. This compared favourably with POSSUM (AUROC=0.66, 95% confidence interval: 0.60–0.71), whilst being simpler to use. Linear shrinkage factors were estimated, which allow the SORT-morbidity model to predict a range of alternative morbidity outcomes with greater accuracy, including low- and high-grade morbidity, and POMS at later time points.Conclusions. SORT-morbidity can be used before surgery, with clinical judgement, to predict postoperative morbidity risk in major elective surgery.

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Sleep deprived and unprepared

Recent UK government policy initiatives concerning 24/7 care have once again put the spotlight on work after hours. The unavoidable night shift confronts us on a regular basis with the physical, psychological, social, and emotional impacts of acute sleep deprivation and fatigue. Although the function of sleep is still not fully understood, it is undoubtedly vital for our good health and well-being. Regardless, on average we are sleeping less now than we ever did before. As a result, there is endless debate about the dangers of long working hours vs the benefits of continuity of care. Intriguingly, very little is actually known about the impact of delaying sleep on our behaviour as a team member in an unpredictable environment such as the emergency room, operating room, or intensive care unit.

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Supplemental oxygen and surgical site infection: getting to the truth

Surgical site infection (SSI) remains one of the most serious and expensive postoperative complications.1 Infected patients are twice as likely to need admission to critical care and twice as likely to die.2 The primary defence against SSI is oxidative killing by neutrophils, and molecular oxygen is the substrate.3 Resistance to infection is thus a strong function of tissue oxygen partial pressure over the clinical range. One might thus expect that supplemental perioperative oxygen (∼80%) would reduce infection risk when compared with more traditional inspired oxygen concentrations (∼30%) during anaesthesia and surgery. Despite some early evidence supporting the role of supplemental oxygen in reducing the risk of SSI,4 there have since been conflicting results from numerous randomized clinical trials. The most compelling data come from the PROXI trial,5 a large, multicentre, randomized trial enrolling 1400 patients undergoing abdominal surgery. This trial found no evidence of any beneficial effect of supplemental oxygen; SSI occurred in 131 of 685 patients (19%) receiving 80% oxygen and in 141 of 701 (20%) receiving 30% oxygen [odds ratio 0.94 (95% confidence interval 0.72–1.22), P=0.64]. Indeed, a long-term follow-up study (median 2.3 years after surgery) found poorer survival in the supplemental oxygen group.6

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Continuous monitoring and feedback of quality of recovery indicators for anaesthetists: a qualitative investigation of reported effects on professional behaviour

Abstract
Background: Research suggests that providing clinicians with feedback on their performance can result in professional behaviour change and improved clinical outcomes. Departments would benefit from understanding which characteristics of feedback support effective quality monitoring, professional behaviour change and service improvement. This study aimed to report the experience of anaesthetists participating in a long-term initiative to provide comprehensive personalized feedback to consultants on patient-reported quality of recovery indicators in a large London teaching hospital.Methods: Semi-structured interviews were conducted with 13 consultant anaesthetists, six surgical nursing leads, the theatre manager and the clinical coordinator for recovery. Transcripts were qualitatively analysed for themes linked to the perceived value of the initiative, its acceptability and its effects upon professional practice.Results: Analysis of qualitative data from participant interviews suggested that effective quality indicators must address areas that are within the control of the anaesthetist. Graphical data presentation, both longitudinal (personal variation over time) and comparative (peer-group distributions), was found to be preferable to summary statistics and provided useful and complementary perspectives for improvement. Developing trust in the reliability and credibility of the data through co-development of data reports with clinical input into areas such as case-mix adjustment was important for engagement. Making feedback specifically relevant to the recipient supported professional learning within a supportive and open collaborative environment.Conclusions: This study investigated the requirements for effective feedback on quality of anaesthetic care for anaesthetists, highlighting the mechanisms by which feedback may translate into improvements in practice at the individual and peer-group level.

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Hypotension during induction of anaesthesia is neither a reliable nor a useful quality measure for comparison of anaesthetists’ performance

Abstract
Background. Identification of statistically reliable outcomes for comparison among anaesthetists is challenging. Time-weighted intraoperative mean arterial pressure <65 mm Hg (AUC65) is associated with increased odds for myocardial damage. We explored retrospectively whether such hypotension before incision was statistically reliable for peer comparison.Methods. We retrieved electronic data between 2006 and 2015 at a tertiary care, academic hospital in the USA for patients at risk for myocardial damage (inpatient after surgery, ASA physical status ≥III, ≥50 yr of age, and case duration ≥60 min). We determined the percentage of anaesthetists comparable based on caseload and case-mix. The AUC65 was compared amongst anaesthetists supervising ≥100 cases involving at-risk patients during the last 12 months.Results. Only 14.1% [95% confidence interval (CI) 13.6–14.5%] of cases involved patients who were 'at risk' during the 10 yr study period. A yearly average of 49 (sd 6) anaesthetists supervised ≥100 cases of any type, of whom only 52% (95% CI 47.1–56.0%) supervised ≥100 cases involving at-risk patients. Thus, nearly half the anaesthetists would have been excluded from peer comparison. During the last 12 months, there were two outliers among 34 evaluable anaesthetists (P<0.05, controlling for false discovery). However, their contribution to total hypotension amongst cases for all patients was small, because hypotension was widely distributed (e.g. 80% of hypotension attributable to 61.8% of anaesthetists, 95% CI 59.8–63.7%). There was no relationship between the AUC65 and propofol induction dose.Conclusions. The AUC65 of time-weighted pre-incision hypotension is not a suitable metric for comparing anaesthetists. There were few at-risk patients, half the anaesthetists were not evaluable because of their case-mix and caseload, and hypotension was widely distributed.

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Association between preoperative pulse pressure and perioperative myocardial injury: an international observational cohort study of patients undergoing non-cardiac surgery

Abstract
Background. The management of elevated blood pressure before non-cardiac surgery remains controversial. Pulse pressure is a stronger predictor of cardiovascular morbidity in the general population than systolic blood pressure alone. We hypothesized that preoperative pulse pressure was associated with perioperative myocardial injury.Methods. This is a secondary analysis of the Vascular Events in Non-cardiac Surgery Patients Cohort Evaluation (VISION) international cohort study. Participants were aged ≥45 yr and undergoing non-cardiac surgery at 12 hospitals in eight countries. The primary outcome was myocardial injury, defined using serum troponin concentration, within 30 days after surgery. The sample was stratified into quintiles by preoperative pulse pressure. Multivariable logistic regression analysis explored associations between pulse pressure and myocardial injury. We accounted for potential confounding by systolic blood pressure and other co-morbidities known to be associated with postoperative cardiovascular complications.Results. One thousand one hundred and ninety-one of 15 057 (7.9%) patients sustained myocardial injury, which was more frequent amongst patients in the highest two preoperative pulse pressure quintiles {63–75 mm Hg, risk ratio (RR) 1.14 [95% confidence interval (CI): 1.01–1.28], P=0.03; >75 mm Hg, RR 1.15 [95% CI: 1.03–1.29], P=0.02}. After adjustment for systolic blood pressure, preoperative pulse pressure remained the dominant predictor of myocardial injury (63–75 mm Hg, RR 1.20 [95% CI: 1.05–1.37], P<0.01; >75 mm Hg, RR 1.25 [95% CI: 1.06–1.48], P<0.01). Systolic blood pressure >160 mm Hg was not associated with myocardial injury in the absence of pulse pressure >62 mm Hg (RR 0.67 [95% CI: 0.30–1.44], P=0.31).Conclusions. Preoperative pulse pressure >62 mm Hg was associated with myocardial injury, independent of systolic blood pressure. Elevated pulse pressure may be a useful clinical sign to guide strategies to reduce perioperative myocardial injury.

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Prolonged concurrent hypotension and low bispectral index (‘double low’) are associated with mortality, serious complications, and prolonged hospitalization after cardiac surgery

Abstract
Background: Low bispectral index (BIS) and low mean arterial pressure (MAP) are associated with worse outcomes after surgery. We tested the hypothesis that a combination of these risk factors, a 'double low', is associated with death and major complications after cardiac surgery.Methods: We used data from 8239 cardiac surgical patients from two US hospitals. The primary outcomes were 30-day mortality and a composite of in-hospital mortality and morbidity. We examined whether patients who had a case-averaged double low, defined as time-weighted average BIS and MAP (calculated over an entire case) below the sample mean but not in the reference group, had increased risk of the primary outcomes compared with patients whose BIS and/or MAP were at or higher than the sample mean. We also examined whether a prolonged cumulative duration of a concurrent double low (simultaneous low MAP and BIS) increased the risk of the primary outcomes.Results: Case-averaged double low was not associated with increased risk of 30-day mortality {odds ratio [OR] 1.73 [95% confidence interval (CI) 0.94–3.18] vs reference; P=0.01} or the composite of in-hospital mortality and morbidity [OR 1.47 (95% CI 0.98–2.20); P=0.01] after correction for multiple outcomes. A prolonged concurrent double low was associated with 30-day mortality [OR 1.06 (95% CI 1.01–1.11) per 10-min increase; P=0.001] and the composite of in-hospital mortality and morbidity [OR 1.04 (95% CI 1.01–1.07), P=0.004].Conclusions: A prolonged concurrent double low, but not a case-averaged double low, was associated with higher morbidity and mortality after cardiac surgery.

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Intraoperative fraction of inspired oxygen: bringing back the focus on patient outcome

Over the last two decades, several randomized controlled trials (RCTs) have investigated the clinical impact of a higher fraction of inspired oxygen (FiO2) administered in the perioperative period. Setting FiO2 in the operating theatre and after surgery is one of the daily tasks of every anaesthetist, and in elective surgery in uncomplicated patients is often based on the clinician's habits, training, and local clinical practice, rather than on evidence-based guidelines.

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Supraglottic jet oxygenation and ventilation enhances oxygenation during upper gastrointestinal endoscopy in patients sedated with propofol: a randomized multicentre clinical trial

Abstract
Background. Hypoventilation is the main reason for hypoxia during upper gastrointestinal endoscopy procedures with sedation. The key to preventing hypoxia is to maintain normal ventilation during the procedure. We introduced supraglottic jet oxygenation and ventilation (SJOV) through a new Wei nasal jet tube (WNJ) to reduce the incidence of hypoxia in patients sedated with propofol during upper gastrointestinal endoscopy procedures.Methods. In a multicentre, prospective randomized single-blinded study, 1781 outpatients undergoing routine upper gastrointestinal endoscopy who were sedated with propofol by an anaesthetist were randomized into the following three groups: the supplementary oxygen via nasal cannula group [nasal cannula oxygen: O2 (2 litres min−1) was administered via a nasal cannula]; the supplementary oxygen via WNJ group [WNJ oxygen: O2 (2 litres min−1) was administered through a WNJ]; and the SJOV via WNJ group (WNJ SJOV: SJOV was administered via WNJ) at three centres from March 2015 to July 2016. The primary outcome of interest was the incidence of hypoxia (peripheral oxygen saturation of 75–89%). Other adverse events were also recorded.Results. Supraglottic jet oxygenation and ventilation decreased the incidence of hypoxia from 9 to 3% (P<0.0001). No severe hypoxia occurred in the WNJ SJOV group, one instance occurred in the WNJ oxygen group, and two instances were observed in the nasal cannula oxygen supply control group. Supraglottic jet oxygenation and ventilation-related minor adverse events increased significantly within 1 min after the procedure but decreased 30 min later.Conclusions. The use of SJOV during upper gastrointestinal endoscopy for patients who are sedated with propofol reduces the incidence of hypoxia, with minor and tolerable adverse events. Supraglottic jet oxygenation and ventilation has a favourable risk-to-benefit ratio and may improve patient safety.Clinical trial registration. NCT02436018.

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Methodology in systematic reviews of goal-directed therapy: improving but not perfect

There has been a recent tsunami of articles on goal-directed (fluid) therapy, haemodynamic optimization and validation of cardiovascular monitoring devices. This has been followed by a wave of systematic reviews, in particular over the last five years, trying to summarize and derive conclusions and recommendations from many of these studies.119 Terminology for systematic reviews and meta-analyses is frequently used incorrectly. A systematic review refers to a rigorous scientific process of reviewing relevant literature whereas meta-analysis refers to a statistical method of pooling data from multiple studies to derive a summary effect estimate. Any well-conducted scientific process needs to comply with quality standards. Likewise, systematic reviews need to meet quality criteria before qualifying for the highest level of evidence (http://ift.tt/17HmMli, accessed May 29, 2017), including a sufficiently detailed published protocol, full search strategy in multiple databases, outcome selection following GRADE20 (http://ift.tt/YgVdNI, accessed May 29, 2017), assessment of risks of bias, assessment of risks of random errors, and reporting results following PRISMA21 and GRADEpro. Producing pooled estimates is always tempting whereas frequently not pooling data because of large heterogeneity might be much wiser. Eventually, only a few systematic reviews qualify for Level 1A evidence.

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Some light in the grey zone?

Treatment of shock is not a new concern in intensive care medicine. The highest priority in patients with shock is the restoration of oxygen delivery. Fluid resuscitation is the very first goal of increasing cardiac output and oxygen delivery in patients with acute circulatory insufficiency. First, based on the simple physiology of the Frank–Starling mechanism, fluid loading should increase cardiac output (CO) by increasing preload and subsequently increasing left ventricular (LV) stroke volume.1 However, fluid overload, especially in patients with pre-existing or developing cardiac failure, can end in only a fractional increase of stroke volume and negative effects like pulmonary venous congestion can predominate. It is therefore a daily task for each intensivist to identify those patients who will respond to and benefit from volume expansion (e.g. acute shock) and to avoid fluid overload in those who are no longer fluid responsive but are at risk for increased mortality by further fluid therapy (e.g. protracted sepsis, acute respiratory distress syndrome, acute kidney injury). Thus the therapeutic conflict between hypovolaemia and hypervolaemia needs to be addressed wisely. Consequently, precise monitoring of preload could be helpful in this clinical scenario (Fig. 1).

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The Goldilocks principle as it applies to perioperative blood pressure: what is too high, too low, or just right?

In this issue of the British Journal of Anaesthesia, Professor Venkatesan and colleagues,1 using data from the large UK Clinical Practice Research Datalink (CPRD) database, found a significant association between low preoperative arterial blood pressure (BP) values and increased postoperative mortality, but only in an elderly population of patients. The risk thresholds started at a preoperative systolic BP of 119 mm Hg and diastolic BP of 63 mm Hg compared with a reference BP of 120 mm Hg. Elevated diastolic, but not systolic BP, was also associated with increased mortality in the entire cohort of patients. These BP readings are considered within the normal, in fact optimal, ranges of acceptable BP for long-term control. Readers should not be surprised that elevated BP was associated with adverse outcomes. However, the findings that only elevated diastolic readings, not systolic hypertension, and 'low' (though the adjective 'lower' would likely be more descriptive of the actual findings) BP are associated with mortality are novel findings. The findings regarding low BP add weight to a growing body of observational data suggesting intraoperative hypotension is associated with adverse outcome. This article challenges us to perhaps be as concerned about low BP readings as we are about elevated BP in the preoperative as well as intraoperative periods.

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Impact of sleep deprivation on anaesthesia residents’ non-technical skills: a pilot simulation-based prospective randomized trial

Abstract
Background. Sleep deprivation is common in anaesthesia residents, but its impact on performance remains uncertain. Non-technical skills (team working, situation awareness, decision making, and task management) are key components of quality of care in anaesthesia, particularly in crisis situations occurring in the operating room. The impact of sleep deprivation on non-technical skills is unknown. We tested the hypothesis that in anaesthesia residents sleep deprivation is associated with impaired non-technical skills.Methods. Twenty anaesthesia residents were randomly allocated to undergo a simulation session after a night shift [sleep-deprived (SLD) group, n=10] or after a night of rest [rested (R) group, n=10] from January to March 2015. The simulated scenario was a situation of crisis management in the operating room. The primary end point was a composite score of anaesthetists' non-technical skills (ANTS) assessed by two blinded evaluators.Results. Non-technical skills were significantly impaired in the SLD group [ANTS score 12.2 (interquartile range 10.5–13)] compared with the R group [14.5 (14–15), P<0.02]. This difference was mainly accounted for by a difference in the team working item. On the day of simulation, the SLD group showed increased sleepiness and decreased confidence in anaesthesia skills.Conclusions. In this randomized pilot trial, sleep deprivation was associated with impaired non-technical skills of anaesthesia residents in a simulated anaesthesia intraoperative crisis scenario.Trial registration. NCT02622217.

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Rising sudden death among anaesthesiologists in China

Editor—Anaesthesiologists in China are currently suffering from work overload, and sudden death is increasing dramatically. A recent sudden death of a young anaesthesiologist in a local hospital followed an overnight of on-duty work; the second sudden death of a young anaesthesiologist this spring. In 2014, a young anaesthesiologist had a cardiac arrest after working 70 hours per week before the incident. More than 10 anaesthesiologists aged 30–45 yr had a cardiac arrest due to a heavy workload in China from 2013 to 2014.1 Sadly, this number has been increasing in recent years.2 The occupational status of anaesthesiologists was recently examined in a survey conducted by the New Youth Anaesthesia Forum, the largest web site of anaesthesiologists in China.3 The survey was also supported by the Chinese Society of Anaesthesiology and the Chinese Association of Anaesthesiology.

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Premedication with salbutamol prior to surgery does not decrease the risk of perioperative respiratory adverse events in school-aged children

Abstract
Background: Perioperative respiratory adverse events (PRAE) remain the leading cause of morbidity and mortality in the paediatric population. This double-blinded randomized control trial investigated whether inhaled salbutamol premedication decreased the occurrence of PRAE in children identified as being at high risk of PRAE.Methods: Children with at least two parentally reported risk factors for PRAE undergoing elective surgery were eligible for recruitment. They were randomized to receive either salbutamol (200 µg) or placebo prior to their surgery and PRAE (bronchospasm, laryngospasm, airway obstruction, desaturation, coughing and stridor) were recorded.Results: Out of 470 children (6–16 yr, 277 males, 59%) recruited, 462 were available for an intention-to-treat analysis. Thirty-two (14%) and 27 (12%) children from the placebo and salbutamol groups experienced PRAE. This difference was not significant [odds ratio (OR): 0.83, 95% confidence interval (CI): 0.48–1.44, P: 0.51]. Oxygen desaturation [14/232 (6%) vs 14/230 (6%), OR: 1.01, 95% CI: 0.47–2.17, P: 0.98] and severe coughing [12/232 (5%) vs 10/230 (4%), OR: 0.83, 95% CI: 0.35–1.97, P: 0.68] were the most common PRAE, but did not significantly differ between the groups. The occurrence of PRAE was slightly lower in children with respiratory symptoms who received salbutamol compared with placebo [16/134 (12%) vs 21/142 (15%), OR: 0.93, 95% CI: 0.38–2.26, P: 0.87], but was not significantly different.Conclusions: Premedication with salbutamol to children aged between 6 and 16 years and at high risk of PRAE prior to their surgery did not reduce their risk of PRAE.Trial registration number: ACTRN12612000626864 (www.anzctr.org.au).

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ISO (Infraclavicular–SubOmohyoid) block: a single-puncture technique for diaphragm- and opioid-sparing shoulder anaesthesia

Editor—The shoulder joint and its muscles are entirely supplied by the brachial plexus and can be anaesthetized simply using the interscalene block. However, this proximal placement of local anaesthetic results in spread to many crucial neural structures (especially the phrenic nerve). To bypass this complication, distal block of the shoulder innervation is recommended.1 Distally, the shoulder nerves are discrete, so multiple injections are usually required to achieve adequate analgesia. Blocking the axillary nerve and suprascapular nerve can provide adequate analgesia for minor shoulder surgery, but for major surgery both infraclavicular and suprascapular nerve blocks are required.1 To minimize block time and patient discomfort, we perform both infraclavicular and suprascapular nerve blocks through a single-puncture technique (the ISO block).

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Lip, tooth, and pharyngeal injuries during tracheal intubation at a teaching hospital

EditorA non-negligible number of patients suffer injury to the lips, teeth, or pharynx during tracheal intubation,12 but the incidence of such injuries at teaching hospitals has not been clarified. This prospective observational study surveyed the occurrence of lip, tooth, and pharyngeal injuries associated with tracheal intubation by trainee doctors at a teaching hospital (Osaka Medical College, Japan) to compare incidence rates during the early and late training stages.

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Reports of Adverse Reactions With Cosmetics Increasing


Reuters Health Information

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Large Study Finds No Link Between Eczema, Cardiovascular Disease

Atopic dermatitis (AD) is unlikely to be associated with cardiovascular disease, new research shows.
Reuters Health Information

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An Unusually Large Carbuncle of the Temporofacial Region

How was this extensive carbuncle over the temporofacial region effectively managed?
Wounds

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Fluorescein sodium-guided surgery of parotid gland tumors as a technical advance

Abstract

Background

Complete tumor removal and preservation of the facial nerve are essential in parotid gland surgery. A technical adjunct that potentially enhances the contrast between the facial nerve and the adherent tumor tissue and allows to identify residual tumor tissue could be Fluorescein Sodium.

Methods

Retrospective chart analysis on 7 patients with benign parotid gland lesions that were operated using Fluorescein Sodium intravenously and the application of the YELLOW 560 nm filter of the operating microscope. Safety and feasibility were evaluated.

Results

All tumors showed fluorescence and the rating ´contrast-enhancing´ was assigned in all cases. In 2 patients, satellite nodules were identified and resected meaning that the fluorescence staining of the tumor margins was significantly better than under white light.

Conclusion

The use of Fluorescein Sodium in parotidectomy is promising. In two cases residual tumor was detected that would have been left behind under white light. Further research in parotid gland surgery and other head and neck tumor procedures is warranted.



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Silver(I)-Induced Higher-Ordered Structure Based on Planar Chiral Tetrasubstituted [2.2]Paracyclophane

Chem. Commun., 2017, Accepted Manuscript
DOI: 10.1039/C7CC03615A, Communication
Masayuki Gon, Yasuhiro Morisaki, Yoshiki Chujo
Optically active phenylene-ethynylene dimers with pyridine groups based on a planar chiral 4,7,12,15-tetrasubstituted [2.2]paracyclophane were synthesized. The chiral conformation was controlled by pyridine-Ag(I) coordinations. After Ag(I) coordination, the resulting higher-ordered...
The content of this RSS Feed (c) The Royal Society of Chemistry


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Understanding atypical sepsis

Paramedics Australasia WA describe presentations of atypical sepsis.

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School Gender Composition, Laddish School Culture and the Ethnic Prejudice of Flemish Pupils.



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Next generation deep sequencing corrects diagnostic pitfalls of traditional molecular approach in a patient with prenatal onset of Pompe disease

Pompe disease is a rare inherited metabolic disorder of glycogen metabolism caused by mutations in the GAA gene, encoding the acid α-1,4 glucosidase. Successful diagnosis of Pompe disease is achieved by clinical and biochemical evaluation followed by confirmation with DNA testing. Here, we report a male infant with a prenatal onset of cardiac symptoms and enzyme testing consistent with Pompe disease, but DNA testing by Sanger sequencing revealed no pathogenic variants. Due to the strong indication from clinical, enzymatic, and histological studies (despite the absence of molecular confirmation by traditional Sanger sequencing), enzyme replacement therapy (ERT) for Pompe disease was initiated. Reanalysis of the patient's DNA sample using next generation sequencing (NGS) of a panel of target genes causing glycogen storage disorders demonstrated compound heterozygosity for a point mutation and an exonic deletion in the GAA gene. This case illustrates the value of astute clinical judgement in patient management as well as the power of target capture deep NGS in the simultaneous detection of both a point mutation and a heterozygous exonic deletion by correcting pitfalls of the traditional PCR based sequencing, namely; allele dropout and the inability to detect exonic deletions.



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Shared Care of Childhood Cancer Survivors: A Telemedicine Feasibility Study

Journal of Adolescent and Young Adult Oncology , Vol. 0, No. 0.


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FOXC1 haploinsufficiency due to 6p25 deletion in a patient with rapidly progressing aortic valve disease

6p25 deletion is a rare but well-known entity. The main clinical features include an abnormal facial appearance, developmental delay, and ocular anomalies. Cardiac anomalies are frequently seen but remain poorly delineated. We describe a 4-year-old girl with 6p25.3 deletion, which includes the FOXC1 gene, typical dysmorphic features associated with developmental delay and oculo-motor anomalies. Aortic valve dysplasia was diagnosed early in life. The cardiac lesion progressed very rapidly between the age of 3 and 4 years requiring aortic valve replacement. Genomic analysis of blood and excised valve tissue showed down-regulation of FOXC1 but also FOXC2 expression in the diseased aortic valve. This allows us to speculate on the potential role of FOXC1 in aortic valve anomalies.



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The Impact of Coverage Restrictions on Antipsychotic Utilization Among Low-Income Medicare Part D Enrollees

Abstract

Prior research demonstrates substantial access problems associated with utilization management and formulary exclusions for antipsychotics in Medicaid, but the use and impact of coverage restrictions for these medications in Medicare Part D remains unknown. We assess the effect of coverage restrictions on antipsychotic utilization in Part D by exploiting a unique natural experiment in which low-income beneficiaries are randomly assigned to prescription drug plans with varying levels of formulary generosity. Despite considerable variation in use of coverage restrictions across Part D plans, we find no evidence that these restrictions significantly deter utilization or reduce access to antipsychotics for low-income beneficiaries.



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Recommendations of the Fertility Preservation Working Group in Oncological, Hematological and Other Patients Treated With Gonadotoxic Therapies “ONCOFERTILITY” (GROF) of the Polish Society of Oncological Gynecology

Journal of Adolescent and Young Adult Oncology , Vol. 0, No. 0.


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Glucose uptake in human brown adipose tissue is impaired upon fasting-induced insulin resistance

Human brown adipose tissue (BAT) has recently emerged as a potential target in the treatment of type 2 diabetes, owing to its capacity to actively clear glucose from the circulation-at least upon cold exposure. The effects of insulin resistance on the capacity of human BAT to take up glucose are unknown. Prolonged fasting is known to induce insulin resistance in peripheral tissues in order to spare glucose for the brain. We studied the effect of fasting-induced insulin resistance on the capacity of BAT to take up glucose during cold exposure as well as on cold-stimulated thermogenesis. BAT glucose uptake was assessed by means of cold-stimulated dynamic 2-deoxy-2-[F-18]fluoro-d-glucose positron emission tomography/computed tomography ([F-18]FDG-PET/CT) imaging. We show that a 54 h fasting period markedly decreases both cold-induced BAT glucose uptake and nonshivering thermogenesis (NST) during cold stimulation. In vivo molecular imaging and modelling revealed that the reduction of glucose uptake in BAT was due to impaired cellular glucose uptake and not due to decreased supply. Interestingly, decreased BAT glucose uptake upon fasting was related to a decrease in core temperature during cold exposure, pointing towards a role for BAT in maintaining normothermia in humans. Cold-stimulated glucose uptake in BAT is strongly reduced upon prolonged fasting. When cold-stimulated glucose uptake in BAT is also reduced under other insulin-resistant states, such as diabetes, cold-induced activation of BAT may not be a valid way to improve glucose clearance by BAT under such conditions. Trial registration: www.trialregister.nl NTR3523 Funding: This work was supported by the EU FP7 project DIABAT (HEALTH-F2-2011-278373 to WDvML) and by the Netherlands Organization for Scientific Research (TOP 91209037 to WDvML).

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Flow Cytometric Single-Cell Identification of Populations in Synthetic Bacterial Communities

Bacterial cells can be characterized in terms of their cell properties using flow cytometry. Flow cytometry is able to deliver multiparametric measurements of up to 50,000 cells per second. However, there has not yet been a thorough survey concerning the identification of the population to which bacterial single cells belong based on flow cytometry data. This paper not only aims to assess the quality of flow cytometry data when measuring bacterial populations, but also suggests an alternative approach for analyzing synthetic microbial communities. We created so-called in silico communities, which allow us to explore the possibilities of bacterial flow cytometry data using supervised machine learning techniques. We can identify single cells with an accuracy > 90% for more than half of the communities consisting out of two bacterial populations. In order to assess to what extent an in silico community is representative for its synthetic counterpart, we created so-called abundance gradients, a combination of synthetic ( i. e., in vitro) communities containing two bacterial populations in varying abundances. By showing that we are able to retrieve an abundance gradient using a combination of in silico communities and supervised machine learning tech-niques, we argue that in silico communities form a viable representation for synthetic bacte-rial communities, opening up new opportunities for the analysis of synthetic communities and bacterial flow cytometry data in general.

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Translation of clinical problems in osteoarthritis into pathophysiological research goals



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Understanding atypical sepsis

Paramedics Australasia WA describe presentations of atypical sepsis.

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Helminth Products Potently Modulate Experimental Autoimmune Encephalomyelitis by Downregulating Neuroinflammation and Promoting a Suppressive Microenvironment

A negative correlation between the geographical distribution of autoimmune diseases and helminth infections has been largely associated in the last few years with a possible role for such type of parasites in the regulation of inflammatory diseases, suggesting new pathways for drug development. However, few helminth-derived immunomodulators have been tested in experimental autoimmune encephalomyelitis (EAE), an animal model of the human disease multiple sclerosis (MS). The immunomodulatory activities of Taenia crassiceps excreted/secreted products (TcES) that may suppress EAE development were sought for. Interestingly, it was discovered that TcES was able to suppress EAE development with more potency than dexamethasone; moreover, TcES treatment was still effective even when inoculated at later stages after the onset of EAE. Importantly, the TcES treatment was able to induce a range of Th2-type cytokines, while suppressing Th1 and Th17 responses. Both the polyclonal and the antigen-specific proliferative responses of lymphocytes were also inhibited in EAE-ill mice receiving TcES in association with a potent recruitment of suppressor cell populations. Peritoneal inoculation of TcES was able to direct the normal inflammatory cell traffic to the site of injection, thus modulating CNS infiltration, which may work along with Th2 immune polarization and lymphocyte activation impairment to downregulate EAE development.

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The novel compound PBT434 prevents iron mediated neurodegeneration and alpha-synuclein toxicity in multiple models of Parkinson’s disease

Abstract

Elevated iron in the SNpc may play a key role in Parkinson's disease (PD) neurodegeneration since drug candidates with high iron affinity rescue PD animal models, and one candidate, deferirpone, has shown efficacy recently in a phase two clinical trial. However, strong iron chelators may perturb essential iron metabolism, and it is not yet known whether the damage associated with iron is mediated by a tightly bound (eg ferritin) or lower-affinity, labile, iron pool. Here we report the preclinical characterization of PBT434, a novel quinazolinone compound bearing a moderate affinity metal-binding motif, which is in development for Parkinsonian conditions. In vitro, PBT434 was far less potent than deferiprone or deferoxamine at lowering cellular iron levels, yet was found to inhibit iron-mediated redox activity and iron-mediated aggregation of α-synuclein, a protein that aggregates in the neuropathology. In vivo, PBT434 did not deplete tissue iron stores in normal rodents, yet prevented loss of substantia nigra pars compacta neurons (SNpc), lowered nigral α-synuclein accumulation, and rescued motor performance in mice exposed to the Parkinsonian toxins 6-OHDA and MPTP, and in a transgenic animal model (hA53T α-synuclein) of PD. These improvements were associated with reduced markers of oxidative damage, and increased levels of ferroportin (an iron exporter) and DJ-1. We conclude that compounds designed to target a pool of pathological iron that is not held in high-affinity complexes in the tissue can maintain the survival of SNpc neurons and could be disease-modifying in PD.



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A finite element study of traditional Chinese cervical manipulation

Abstract

Purpose

Traditional Chinese cervical manipulation (TCCM) has been claimed as an effective treatment for diseases of the cervical spine, but its biomechanical effects on the vertebral body and intervertebral discs remain unclear. The aim of this study was to develop and validate a detailed finite element model of cervical spine, which was then used to investigate the biomechanical response of the cervical spine to TCCM.

Methods

The model of a C2–T1 cervical spine was constructed based on CT images of a healthy male volunteer and validated against published in vitro studies under different loading conditions. The detailed force–time data of TCCM were measured on the same volunteer through dynamometric diaphragms. The data were applied on the validated finite element model to simulate TCCM.

Results

The current model could offer potentials to effectively reflect the behavior of human cervical spine suitable for biomechanics studies of TCCM. Under simulated TCCM condition, the stress distributions in cervical spine and intervertebral discs could not be completely explained through the traditional theory.

Conclusion

Spinal manipulation, or TCCM, might play no role in reducing intradiscal pressure for treating cervical spondylosis. It could cause less stress concentration in intervertebral discs while operating spinal manipulation or TCCM when the adjustment points was chosen near the root of spinous process than the top of spinous process.



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Granulome annulaire élastolytique à cellules géantes : étude anatomoclinique

Publication date: Available online 27 June 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): F. Margerin, B. Cribier
IntroductionLe rare granulome annulaire élastolytique à cellules géantes (GAECG), décrit en 1979, est très proche du granulome actinique (GA) de O'Brien, décrit en 1975. Depuis, de nombreux cas ont été publiés sous l'un ou l'autre nom. Nous avons effectué une étude anatomoclinique monocentrique afin d'en préciser les caractéristiques et de déterminer s'il existait une différence entre GAECG et GA.Matériel et méthodesLes cas classés GAECG ou GA au laboratoire de dermatopathologie de Strasbourg ont été inclus et analysés avec les colorations hématoxyline-éosine, orcéine et bleu alcian. Le diagnostic était retenu lorsqu'il existait un granulome riche en cellules géantes multinucléées et une diminution ou une disparition du tissu élastique. Les renseignements cliniques ont été collectés à partir des demandes d'analyse et des dossiers cliniques.RésultatsNous avons retenu 73 cas : 12 classés GAECG et 61 GA. L'âge moyen était de 60,5 ans et le sex-ratio de 0,55. La durée d'évolution variait de 8jours à 17 ans. Il s'agissait d'une lésion unique dans 52 % des cas et de lésions multiples dans les autres cas. Leur taille variait de 0,3 à 10cm. Elles siégeaient avec prédilection dans les zones photo-exposées, majoritairement la tête, le cou et les membres supérieurs. Il s'agissait le plus souvent de lésions à bordure érythémateuse annulaire et à centre clair, de croissance centrifuge lente. Le diagnostic n'avait été proposé que dans 5,5 % des cas par le clinicien. Ces granulomes étaient de siège dermique superficiel et moyen, rarement profond, comportaient de nombreuses cellules géantes avec un contingent lymphocytaire constant, mais aussi plasmocytaire dans la moitié des cas. La coloration à l'orcéine montrait une diminution nette ou une disparition totale du tissu élastique au sein de la zone granulomateuse et presque toujours des images d'élastophagocytose. De manière plus rare, des images de nécrobiose, d'organisation palissadique de granulome, d'atteinte vasculaire ou encore de corps astéroïdes orcéinophiles étaient observées. Il n'y avait pas de différence clinique ou histologique notable entre les cas initialement classés comme GAECG ou GA.DiscussionLe GAECG est une entité unique distincte du granulome annulaire, qui doit être assimilée au granulome actinique d'O'Brien. Le rôle central des fibres élastiques semble clair mais celui des ultraviolets est plus débattu. Le terme de granulome annulaire élastolytique à cellules géantes apparaît plus approprié car plus descriptif et sans implication physiopathologique. Le lien avec une sarcoïdose ou un diabète semble significatif dans une minorité de cas, justifiant leur dépistage.BackgroundAnnular elastolytic giant cell granuloma (AEGCG), a rare entity first described in 1979, is very similar to O'Brien actinic granuloma (AG), first described in 1975. Since then, many cases have been published under one or other of the two names. We performed a single-centre histopathology study to identify the distinguishing features and determine whether there was any objective difference between AEGCG and AG.Patients and methodsCases classed as AEGCG or AG at the dermatopathology laboratory in Strasbourg were included and analysed using haematoxylin-eosin, orcein and Alcian blue staining. The diagnosis was made in the event of granuloma rich in multi-nucleated giant cells and reduction or disappearance of elastic tissue. Clinical data were collected from the analysis requests and clinical files.ResultsWe identified 73 cases: 12 classed as AEGCG and 61 classed as AG. Mean age was 60.5 years with a sex ratio of 0.55. The duration of the disease ranged from 8 days to 17 years. A single lesion was seen in 52% of cases with multiple lesions in the remaining cases. Lesions measured between 0.3 and 10cm and exhibited a predilection for photo-exposed areas, chiefly on the head, neck and upper limbs. In most cases, an annular erythematous edge was seen together with a light centre, and slow centrifugal spread. The diagnosis was made by a clinician in only 5.5% of cases. These granulomas were chiefly in the superficial and mid dermis and only rarely deep, and contained numerous giant cells with a constant contingent of lymphocytes, but plasma cells were also seen in half of the cases. Orcein staining revealed marked decrease or total disappearance of elastic tissue within the granulomatous area together with elastophagocytosis in practically all images. More rarely, there was evidence of necrobiosis, palisading granuloma, vascular involvement or orcein-stained asteroid bodies. There were no notable clinical or histological differences between the cases initially classed as AEGCG or AG.DiscussionAEGCG is a separate entity from annular granuloma that must be assimilated with O'Brien actinic granuloma. The central role of elastic fibres seems clear, but that of ultraviolet radiation remains more controversial. The term annular elastolytic giant cell granuloma seems more appropriate since it is more descriptive and carries no physiopathological implications. There appears to be a significant association with sarcoidosis and with diabetes in a minority of cases, thus warranting screening for these diseases.



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Germline genetic variants in men with prostate cancer and one or more additional cancers

BACKGROUND

Prostate cancer has a significant heritable component, and rare deleterious germline variants in certain genes can increase the risk of the disease. The aim of the current study was to describe the prevalence of pathogenic germline variants in cancer-predisposing genes in men with prostate cancer and at least 1 additional primary cancer.

METHODS

Using a multigene panel, the authors sequenced germline DNA from 102 men with prostate cancer and at least 1 additional primary cancer who also met ≥1 of the following criteria: 1) age ≤55 years at the time of diagnosis of the first malignancy; 2) rare tumor type or atypical presentation of a common tumor; and/or 3) ≥3 primary malignancies. Cancer family history and clinicopathologic data were independently reviewed by a clinical genetic counselor to determine whether the patient met established criteria for testing for a hereditary cancer syndrome.

RESULTS

Sequencing identified approximately 3500 variants. Nine protein-truncating deleterious mutations were found across 6 genes, including BRCA2, ataxia telangiectasia mutated (ATM), mutL homolog 1 (MLH1), BRCA1 interacting protein C-terminal helicase 1 (BRIP1), partner and localizer of BRCA2 (PALB2), and fibroblast growth factor receptor 3 (FGFR3). Likely pathogenic missense variants were identified in checkpoint kinase 2 (CHEK2) and homeobox protein Hox-B13 (HOXB13). In total, 11 of 102 patients (10.8%) were found to have pathogenic or likely pathogenic mutations in cancer-predisposing genes. The majority of these men (64%) did not meet current clinical criteria for germline testing.

CONCLUSIONS

Men with prostate cancer and at least 1 additional primary cancer are enriched for harboring a germline deleterious mutation in a cancer-predisposing gene that may impact cancer prognosis and treatment, but the majority do not meet current criteria for clinical genetic testing. Cancer 2017. © 2017 American Cancer Society.



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Efficacy of tyrosine kinase inhibitors in EGFR -mutant lung cancer women in a real-world setting: the WORLD07 database

Abstract

Background

The WORLD07 project is a female specific database to assess the characteristics of women with lung cancer.

Methods

WORLD07 database sets up in 2007, and prospectively stores clinical characteristics, treatment, outcome, and follow-up of lung cancer women. All women with epidermal growth factor receptor (EGFR) mutation non-small cell lung cancer (NSCLC) were selected for this analysis.

Results

From October 2007 to December 2012, a total of 1775 NSCLC women were recruited. EGFR mutation was identified in 34.4% of patients. Upfront EGFR tyrosine kinase inhibitor (TKI) reported a response rate of 60%, a median progression-free survival of 11.7 months, and median overall survival of 23.0 months. EGFR TKI, EGFR-mutation type, and smoking status did not impact in the outcome of treated women.

Conclusion

Prevalence of EGFR mutation in women with NSCLC is higher than overall population with NSCLC. Efficacy of EGFR TKI in this real-world setting is similar to that previously reported.



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School Gender Composition, Laddish School Culture and the Ethnic Prejudice of Flemish Pupils.



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Les Raisons du livre: du statut de l’œuvre écrite à la figuration du symbole (XIIe – XVIIe siècles). Études réunies par GÉRARD GROS

Spencer-Hall, A; (2016) Les Raisons du livre: du statut de l'œuvre écrite à la figuration du symbole (XIIe – XVIIe siècles). Études réunies par GÉRARD GROS. [Review]. French Studies , 70 (3) pp. 436-437. 10.1093/fs/knw138 .

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Design out of complexity: A mathematical theory of design as an universal property of organization

Zamenopoulos, T; (2008) Design out of complexity: A mathematical theory of design as an universal property of organization. Doctoral thesis, UCL (University College London). Green open access

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Reducing systematic review workload using text mining: opportunities and pitfalls

Stansfield, CM; O'Mara-Eves, A; Thomas, J; (2015) Reducing systematic review workload using text mining: opportunities and pitfalls. Journal of the European Association for Health Information and Libraries , 11 (3) pp. 8-10. Green open access

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Development of a multi-location motion displacement test for detection of early glaucoma

Verdon-Roe, GM; (2006) Development of a multi-location motion displacement test for detection of early glaucoma. Doctoral thesis, UCL (University College London). Green open access

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Cost-Effectiveness Analysis Of Regorafenib In Gastrointestinal Stromal Tumours In England Using Crossover Adjustment Methods

Pitcher, A; Grabbi, E; Madin-Warburton, M; Vadgama, S; (2016) Cost-Effectiveness Analysis Of Regorafenib In Gastrointestinal Stromal Tumours In England Using Crossover Adjustment Methods. Presented at: ISPOR 19th Annual European Congress, Vienna, Austria.

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Surface Reactions of Ethanol over UO2(100) Thin Film

Senanayake, SD; Mudiyanselage, K; Burrell, AK; Sadowski, JT; Idriss, H; (2015) Surface Reactions of Ethanol over UO2(100) Thin Film. Journal of Physical Chemistry C , 119 (44) pp. 24895-24901. 10.1021/acs.jpcc.5b08577 .

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Granulome annulaire élastolytique à cellules géantes : étude anatomoclinique

Publication date: Available online 27 June 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): F. Margerin, B. Cribier
IntroductionLe rare granulome annulaire élastolytique à cellules géantes (GAECG), décrit en 1979, est très proche du granulome actinique (GA) de O'Brien, décrit en 1975. Depuis, de nombreux cas ont été publiés sous l'un ou l'autre nom. Nous avons effectué une étude anatomoclinique monocentrique afin d'en préciser les caractéristiques et de déterminer s'il existait une différence entre GAECG et GA.Matériel et méthodesLes cas classés GAECG ou GA au laboratoire de dermatopathologie de Strasbourg ont été inclus et analysés avec les colorations hématoxyline-éosine, orcéine et bleu alcian. Le diagnostic était retenu lorsqu'il existait un granulome riche en cellules géantes multinucléées et une diminution ou une disparition du tissu élastique. Les renseignements cliniques ont été collectés à partir des demandes d'analyse et des dossiers cliniques.RésultatsNous avons retenu 73 cas : 12 classés GAECG et 61 GA. L'âge moyen était de 60,5 ans et le sex-ratio de 0,55. La durée d'évolution variait de 8jours à 17 ans. Il s'agissait d'une lésion unique dans 52 % des cas et de lésions multiples dans les autres cas. Leur taille variait de 0,3 à 10cm. Elles siégeaient avec prédilection dans les zones photo-exposées, majoritairement la tête, le cou et les membres supérieurs. Il s'agissait le plus souvent de lésions à bordure érythémateuse annulaire et à centre clair, de croissance centrifuge lente. Le diagnostic n'avait été proposé que dans 5,5 % des cas par le clinicien. Ces granulomes étaient de siège dermique superficiel et moyen, rarement profond, comportaient de nombreuses cellules géantes avec un contingent lymphocytaire constant, mais aussi plasmocytaire dans la moitié des cas. La coloration à l'orcéine montrait une diminution nette ou une disparition totale du tissu élastique au sein de la zone granulomateuse et presque toujours des images d'élastophagocytose. De manière plus rare, des images de nécrobiose, d'organisation palissadique de granulome, d'atteinte vasculaire ou encore de corps astéroïdes orcéinophiles étaient observées. Il n'y avait pas de différence clinique ou histologique notable entre les cas initialement classés comme GAECG ou GA.DiscussionLe GAECG est une entité unique distincte du granulome annulaire, qui doit être assimilée au granulome actinique d'O'Brien. Le rôle central des fibres élastiques semble clair mais celui des ultraviolets est plus débattu. Le terme de granulome annulaire élastolytique à cellules géantes apparaît plus approprié car plus descriptif et sans implication physiopathologique. Le lien avec une sarcoïdose ou un diabète semble significatif dans une minorité de cas, justifiant leur dépistage.BackgroundAnnular elastolytic giant cell granuloma (AEGCG), a rare entity first described in 1979, is very similar to O'Brien actinic granuloma (AG), first described in 1975. Since then, many cases have been published under one or other of the two names. We performed a single-centre histopathology study to identify the distinguishing features and determine whether there was any objective difference between AEGCG and AG.Patients and methodsCases classed as AEGCG or AG at the dermatopathology laboratory in Strasbourg were included and analysed using haematoxylin-eosin, orcein and Alcian blue staining. The diagnosis was made in the event of granuloma rich in multi-nucleated giant cells and reduction or disappearance of elastic tissue. Clinical data were collected from the analysis requests and clinical files.ResultsWe identified 73 cases: 12 classed as AEGCG and 61 classed as AG. Mean age was 60.5 years with a sex ratio of 0.55. The duration of the disease ranged from 8 days to 17 years. A single lesion was seen in 52% of cases with multiple lesions in the remaining cases. Lesions measured between 0.3 and 10cm and exhibited a predilection for photo-exposed areas, chiefly on the head, neck and upper limbs. In most cases, an annular erythematous edge was seen together with a light centre, and slow centrifugal spread. The diagnosis was made by a clinician in only 5.5% of cases. These granulomas were chiefly in the superficial and mid dermis and only rarely deep, and contained numerous giant cells with a constant contingent of lymphocytes, but plasma cells were also seen in half of the cases. Orcein staining revealed marked decrease or total disappearance of elastic tissue within the granulomatous area together with elastophagocytosis in practically all images. More rarely, there was evidence of necrobiosis, palisading granuloma, vascular involvement or orcein-stained asteroid bodies. There were no notable clinical or histological differences between the cases initially classed as AEGCG or AG.DiscussionAEGCG is a separate entity from annular granuloma that must be assimilated with O'Brien actinic granuloma. The central role of elastic fibres seems clear, but that of ultraviolet radiation remains more controversial. The term annular elastolytic giant cell granuloma seems more appropriate since it is more descriptive and carries no physiopathological implications. There appears to be a significant association with sarcoidosis and with diabetes in a minority of cases, thus warranting screening for these diseases.



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Translation of clinical problems in osteoarthritis into pathophysiological research goals



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Analysis and modelling of recurrent solar flares observed with Hinode/EIS on March 9, 2012

Polito, V; Del Zanna, G; Valori, G; Pariat, E; Mason, HE; Dudk, J; Janvier, M; (2017) Analysis and modelling of recurrent solar flares observed with Hinode/EIS on March 9, 2012. Astronomy & Astrophysics , 601 , Article A39. 10.1051/0004-6361/201629703 . Green open access

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