Letter to the Editor concerning “Can standard anterior Smith–Robinson supramanubrial approach be utilized for approach down to T2 or T3?” by Singhatanadgige W, Zebala LP, Luksanapruksa P, Riew KD [Eur Spine J (2017) 26:2357–2362]

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2ykCXFe

Histological Assessment of the Liver Explant in Transplanted HCV-Patients Achieving Sustained Virologic Response with Direct-Acting Antiviral Agents

Abstract

Aims

The use of direct-acting anti-viral agents (DAAs) has resulted in extremely high sustained virologic response (SVR) rates in patients being treated while on liver transplantation (LT) waiting lists. The aim of this study was to evaluate the histological findings of HCV patients who achieved SVR after receiving DAA treatment (SVR(+)) prior to LT and comparing them to HCV patients who had not achieved SVR (SVR(-)).

Methods and Results

Fifty-eight adult HCV patients who underwent LT at our institution from 2014-2016 were included in the study. Two pathologists, blinded to SVR status, simultaneously evaluated the histological sections. Assessment included the Histology Activity Index (HAI/modified Knodell score), fibrosis stage (Ishak score), and Laennec cirrhosis stage. The study group comprised of 25 SVR(+) patients (56% male, mean age=63.8), while the control group was composed of 33 SVR(-) patients (69% male, mean age=61.7). There was no significant difference in HAI between groups (p=0.414). Patients who achieved SVR also did not show less portal inflammation (p=0.787), interface hepatitis (p=0.999), confluent necrosis (p=0.627), or spotty necrosis (p=0.093) compared to the control group. There was a trend towards higher degree of inflammation in patients who achieved SVR shorter than 24 weeks (p=0.07). The degree of focal lytic necrosis/apoptosis and portal inflammation was more prominent in SVR(+) patients with shorter interval time.

Conclusions

Our study is the first to report the persistent inflammation in HCV patients who received DAAs prior to LT. This supports the notion that inflammation is immunologically driven and inflammation persists despite the absence of virus.

This article is protected by copyright. All rights reserved.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2o14dcf

Increased resting-state brain entropy in Alzheimer’s disease

Entropy analysis of resting-state functional MRI (R-fMRI) is a novel approach to characterize brain temporal dynamics and facilitates the identification of abnormal brain activity caused by several disease conditions. However, Alzheimer's disease (AD)-related brain entropy mapping based on R-fMRI has not been assessed. Here, we measured the sample entropy and voxel-wise connectivity of the network degree centrality (DC) of the intrinsic brain activity acquired by R-fMRI in 26 patients with AD and 26 healthy controls. Compared with the controls, AD patients showed increased entropy in the middle temporal gyrus and the precentral gyrus and also showed decreased DC in the precuneus. Moreover, the magnitude of the negative correlation between local brain activity (entropy) and network connectivity (DC) was increased in AD patients in comparison with healthy controls. These findings provide new evidence on AD-related brain entropy alterations. Correspondence to Shao-Wei Xue, PhD, Center for Cognition and Brain Disorders, Hangzhou Normal University, Hangzhou, China, Room 301, Shuyuan Building No. 19, Yuhangtang Road No. 2318, Hangzhou 311121, Zhejiang Province, China Tel: +86 152 5715 2036; fax: +86 571 2886 7717; e-mail: xuedrm@126.com Received October 16, 2017 Accepted November 2, 2017 © 2017 Wolters Kluwer Health | Lippincott Williams & Wilkins

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AScku4

Abnormalities of P300 before and after antidepressant treatment in depression: an ERP-sLORETA study

Despite a wide range of reports on depression-induced P300 changes, it is still debatable whether P300 can return to a pattern characteristic of healthy individuals following antidepressant treatment. Thus, the present study aims to compare P300 and its underlying neural activation in depressed patients before and after antidepressant treatment to explore the brain regions related to pathogenesis and to evaluate the prognosis after treatment. P300 was evoked by the oddball auditory paradigm and collected from 14 sex-matched, age-matched, and education level-matched patients and controls. P300 was also collected in the same patients after treatment. sLORETA was used to explore the source activation of P300 components. Depressed patients before and after antidepressant treatment tended to show lower P300 amplitudes compared with healthy controls, and their P300 amplitudes of F3 electrodes were correlated negatively to their scores on the 24-item Hamilton Depression Rating Scale, the Snaith-Hamilton Pleasure Scale, and the nine-item Patient Health Questionnaire. P300 amplitudes of P4 electrodes were correlated negatively with their scores on the Dysfunctional Attitude Scale. P300 source activation of depressed patients before antidepressant treatment was reduced in the left superior parietal lobule and the precuneus compared with healthy controls and depressed patients after treatment. No difference was found between healthy controls and depressed patients after treatment. The left superior parietal lobule and the precuneus might be therapeutic targets of depression. Correspondence to Gaohua Wang, MD, Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China Tel: +86 136 0716 7402; fax: +86 27 8807 2022; e-mail: wgh6402@163.com Received October 6, 2017 Accepted November 7, 2017 © 2017 Wolters Kluwer Health | Lippincott Williams & Wilkins

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2C0gBvc

Apport de la conception assistée par ordinateur (CAO) à la réalisation des implants thoraciques sur mesure pour correction des pectus excavatum. Expérience du CHU de Nantes

Publication date: Available online 12 December 2017
Source:Annales de Chirurgie Plastique Esthétique
Author(s): H. Tilliet Le Dentu, U. Lancien, O. Sellal, F. Duteille, P. Perrot
IntroductionLe pectus excavatum est la malformation congénitale thoracique la plus fréquente et constitue un motif de consultation courant en chirurgie plastique. Notre attitude consiste le plus souvent en un comblement de la dépression par une prothèse sur mesure en silicone. L'objectif de ce travail était d'évaluer les gains apportés par la conception assistée par ordinateur (CAO) dans la fabrication des implants en comparaison de la méthode classique de moulage plâtré.Patients et méthodeNous avons colligé l'ensemble des cas ayant bénéficié de la mise en place d'implants sur mesure en silicone au sein du service de chirurgie plastique du CHU de Nantes. Les critères de jugement étaient la qualité des résultats évaluée par le patient, et par l'équipe chirurgicale en aveugle sur photographies et par questionnaires standardisés. Les délais pré-opératoires, les durées d'interventions et d'hospitalisation, le nombre de reprises chirurgicales à visée cosmétique, les suites et complications postopératoires, étaient relevés.RésultatsEntre 1990 et 2016, 29 implants thoraciques en silicone ont été posés dans notre service. Avant 2012, les implants étaient conçus par moulage plâtré (n=13). Après cette date, les implants étaient conçus par CAO (n=16). Les patients jugeaient leurs résultats « bons » ou « excellents » dans 77 % et 86 % des cas respectivement dans les groupes Plâtre et CAO. Les notes attribuées par l'équipe chirurgicale aux reconstructions par implants CAO étaient meilleures que dans le groupe Plâtre : 8,17 versus 6,96 (p=0,001). Les implants CAO étaient significativement moins perceptibles que les implants du groupe Plâtre. La durée opératoire était réduite dans le groupe CAO : 60,2 versus 74,7minutes dans le groupe Plâtre (p=0,04), de même que la durée d'hospitalisation : 3,5 versus 5,3jours (p=0,01). Il n'y avait pas de différences significatives entre les deux groupes en termes de complications postopératoires.ConclusionLa prise en charge des pectus excavatum par pose d'un implant en silicone sur mesure constitue une méthode peu invasive et pourvoyeuse de bons résultats cosmétiques. La conception de ces implants est facilitée et améliorée qualitativement par la CAO.IntroductionPectus excavatum is the most common congenital chest malformation and is a common reason for consultation in plastic surgery. Our attitude is most often a filling of the depression with a custom-made silicone prosthesis. The objective of this work was to evaluate the interest of computer-aided design (CAD) of implants compared to the conventional plaster molds method.Patients and methodsWe have collected all the cases of custom-made silicone implants to treat funnel chests in our plastic surgery department. The quality of the results was evaluated by the patient, and in a blind manner by the surgical team using photographs and standardized surveys. The pre-operative delays, the operating time and length of hospital stays, the number of surgical recoveries, and the post-operative surgical outcomes were recorded.ResultsBetween 1990 and 2016, we designed 29 silicone thoracic implants in our department. Before 2012, implants were made from plaster chest molds (n=13). After this date, implants were designed by CAD (n=16). Patients rated their results as "good" or "excellent" in 77% and 86% of cases respectively in the plaster and CAD groups. The surgical team's ratings for CAD implant reconstructions were better than in the plaster group: 8.17 versus 6.96 (P=0.001). CAD implants were significantly less detectable than the plaster group implants. The operating time was reduced in the CAO group: 60.2 compared to 74.7minutes in the plaster group (P=0.04), as was the length of hospitalization: 3.5 versus 5.3 days (P=0.01). There were no significant differences between the two groups in terms of post-operative complications.ConclusionThe management of pectus excavatum by a custom-made silicone implant is a minimally invasive method that provides good cosmetic results. The design of these implants is facilitated and qualitatively improved by CAD.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2z6Tkcb

Prolonged Duration Local Anesthesia Using Liposomal Bupivacaine Combined With Liposomal Dexamethasone and Dexmedetomidine

BACKGROUND: The relatively short duration of effect of local anesthetics has been addressed by encapsulation in drug delivery systems. Codelivery with a single compound that produces an adjuvant effect on nerve block but without intrinsic local anesthetic properties can further prolong the nerve block effect. Here, we investigated whether codelivery of more than 1 encapsulated adjuvant compound can further enhance nerve blockade. METHODS: Liposomes loaded with bupivacaine (Bup), dexamethasone phosphate (DexP), or dexmedetomidine (DMED) were synthesized and its in vitro drug release profiles were determined. Animals (Sprague-Dawley rats) were injected with liposomal Bup (Lipo-Bup) and adjuvants at the sciatic nerve and underwent a modified hot plate test to assess the degree of nerve block. The duration of block was monitored and the tissue reaction was assessed. RESULTS: Coinjection of Lipo-Bup with liposomal DexP (Lipo-DexP) and liposomal DMED (Lipo-DMED) prolonged the duration of sciatic nerve block 2.9-fold compared to Lipo-Bup alone (95% confidence interval, 1.9- to 3.9-fold). The duration of the block using this combination was significantly increased to 16.2 ± 3.5 hours compared to Lipo-Bup with a single liposomal adjuvant (8.7 ± 2.4 hours with Lipo-DMED, P = .006 and 9.9 ± 5.9 hours with Lipo-DexP, P = .008). The coinjection of Lipo-Bup with liposomal adjuvants decreased tissue inflammation (P = .014) but did not have a significant effect on myotoxicity when compared to Lipo-Bup alone. Coinjection of Lipo-Bup with unencapsulated adjuvants prolonged the duration of nerve block as well (25.0 ± 6.3 hours; P

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nUy6KZ

Meeting Report for the 39th Annual Meeting and Workshops of the Society of Cardiovascular Anesthesiologists

No abstract available

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2C9Nfvc

Targeted Temperature Management After Cardiac Arrest: Systematic Review and Meta-analyses

BACKGROUND: Targeted temperature management (TTM) with therapeutic hypothermia is an integral component of postarrest care for survivors. However, recent randomized controlled trials (RCTs) have failed to demonstrate the benefit of TTM on clinical outcomes. We sought to determine if the pooled data from available RCTs support the use of prehospital and/or inhospital TTM after cardiac arrest. METHODS: A comprehensive search of SCOPUS, Elsevier's abstract and citation database of peer-reviewed literature, from 1966 to November 2016 was performed using predefined criteria. Therapeutic hypothermia was defined as any strategy that aimed to cool post.cardiac arrest survivors to a temperature ≤34°C. Normothermia was temperature of ≥36°C. We compared mortality and neurologic outcomes in patients by categorizing the studies into 2 groups: (1) hypothermia versus normothermia and (2) prehospital hypothermia versus in-hospital hypothermia using standard meta-analytic methods. A random effects modeling was utilized to estimate comparative risk ratios (RR) and 95% confidence intervals (CIs). RESULTS: The hypothermia and normothermia strategies were compared in 5 RCTs with 1389 patients, whereas prehospital hypothermia and in-hospital hypothermia were compared in 6 RCTs with 3393 patients. We observed no difference in mortality (RR, 0.88; 95% CI, 0.73– 1.05) or neurologic outcomes (RR, 1.26; 95% CI, 0.92–1.72) between the hypothermia and normothermia strategies. Similarly, no difference was observed in mortality (RR, 1.00; 95% CI, 0.97–1.03) or neurologic outcome (RR, 0.96; 95% CI, 0.85–1.08) between the prehospital hypothermia versus in-hospital hypothermia strategies. CONCLUSIONS: Our results suggest that TTM with therapeutic hypothermia may not improve mortality or neurologic outcomes in postarrest survivors. Using therapeutic hypothermia as a standard of care strategy of postarrest care in survivors may need to be reevaluated. Accepted for publication September 19, 2017. The authors Kalra and Arora contributed equally to preparation of this manuscript. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Funding: This study was supported in part by the Walter B. Frommeyer Investigative Fellowship awarded to P.A. N.S.B. was supported by National Institutes of Health grant 5T32HL094301-07. N.P. was supported by National Institutes of Health grant 1T32HL129948-01A1. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Navkaranbir S. Bajaj, MD, MPH, Division of Cardiovascular Medicine, Department of Radiology, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115. Address e-mail to bajaj.navkaran@gmail.com; Pankaj Arora, MD, FAHA, Division of Cardiovascular Disease, University of Alabama at Birmingham, 1670 University Blvd, Volker Hall B140, Birmingham, AL 35294. Address e-mail to parora@uabmc.edu. © 2017 International Anesthesia Research Society

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nVbLx0

Achieving Milestones as a Prerequisite for Proceeding With a Clinical Trial

BACKGROUND: Although the National Institutes of Health (NIH) invests $30 billion in research annually, many funded studies fail to generate results that can inform practice. The National Institutes of Health introduced a phased funding mechanism as one potential solution. Study-specific milestones are established for an initial pilot phase. We assess the utility of this phased approach through the ongoing Electroencephalography (EEG) Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) pragmatic clinical trial. The hypothesis of the trial is that EEG guidance of general anesthesia, through prevention of EEG suppression, can decrease postoperative delirium and its downstream negative sequelae. METHODS: In collaboration with study stakeholders, we identified critical milestones for the ENGAGES study, with themes common to many clinical trials. These themes include: regulatory tasks; enrollment targets; feasibility and impact of study intervention; primary outcome incidence; measurement reliability of primary outcome; and follow-up. Progress in achieving the milestones was assessed at regular intervals during the pilot phase by ENGAGES investigators, a National Institute on Aging program officer, and a nonpartisan research organization (Westat). RESULTS: Regulatory tasks, including institutional review board approval, infrastructure establishment, and trial registration, were completed on schedule. A total of 117 patients were randomized, exceeding the target by 51. The EEG-guided protocol was successfully implemented, and a relevant effect on anesthetic practice was demonstrated (decrease in median age–adjusted minimum alveolar anesthetic concentration from 0.93 to 0.78 [P

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2C9N9nk

Retrospective Review of Universal Preoperative Pregnancy Testing: Results and Perspectives

Unrecognized pregnancy in patients presenting for elective surgery is of particular concern due to the potential for significant complications. Accurate and inexpensive urine pregnancy tests are widely available in the developed world. As a result, universal preoperative pregnancy screening is commonly implemented. However, the utility of such routine testing is controversial. We retrospectively studied 8245 immediate presurgery pregnancy tests at Mayo Clinic Hospital, Phoenix, AZ, and found 11 positive tests of which 6 were false positives. We constructed a census-based approximation for unrecognized pregnancies, which shows significantly low pretest probability in this patient population. Taken together, the utility of immediate universal presurgical pregnancy testing is questionable. Accepted for publication October 30, 2017. Funding: None. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Reprints will not be available from the authors. from the authors., Address correspondence to Karl A. Poterack, MD, Mayo Clinic Hospital, 5777 E Mayo Blvd, Phoenix, AZ 85054. Address e-mail to poterack.karl@mayo.edu. © 2017 International Anesthesia Research Society

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nVbFp8

Error Grid Analysis for Arterial Pressure Method Comparison Studies

The measurement of arterial pressure (AP) is a key component of hemodynamic monitoring. A variety of different innovative AP monitoring technologies became recently available. The decision to use these technologies must be based on their measurement performance in validation studies. These studies are AP method comparison studies comparing a new method ("test method") with a reference method. In these studies, different comparative statistical tests are used including correlation analysis, Bland-Altman analysis, and trending analysis. These tests provide information about the statistical agreement without adequately providing information about the clinical relevance of differences between the measurement methods. To overcome this problem, we, in this study, propose an "error grid analysis" for AP method comparison studies that allows illustrating the clinical relevance of measurement differences. We constructed smoothed consensus error grids with calibrated risk zones derived from a survey among 25 specialists in anesthesiology and intensive care medicine. Differences between measurements of the test and the reference method are classified into 5 risk levels ranging from "no risk" to "dangerous risk"; the classification depends on both the differences between the measurements and on the measurements themselves. Based on worked examples and data from the Multiparameter Intelligent Monitoring in Intensive Care II database, we show that the proposed error grids give information about the clinical relevance of AP measurement differences that cannot be obtained from Bland-Altman analysis. Our approach also offers a framework on how to adapt the error grid analysis for different clinical settings and patient populations. Accepted for publication September 8, 2017. Funding: None. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Julia Y. Nicklas, MD, Department of Anesthesiology, Center of Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. Address e-mail to jnicklas.science@gmail.com. © 2017 International Anesthesia Research Society

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2C9b7Pv

In Response

No abstract available

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nVbAlk

Treatment of Chronic Pain With Various Buprenorphine Formulations: A Systematic Review of Clinical Studies

Clinical studies demonstrate that buprenorphine is a pharmacologic agent that can be used for the treatment of various types of painful conditions. This study investigated the efficacy of 5 different types of buprenorphine formulations in the chronic pain population. The literature was reviewed on PubMed/MEDLINE, EMBASE, Cochrane Database, clinicaltrials.gov, and PROSPERO that dated from inception until June 30, 2017. Using the population, intervention, comparator, and outcomes method, 25 randomized controlled trials were reviewed involving 5 buprenorphine formulations in patients with chronic pain: intravenous buprenorphine, sublingual buprenorphine, sublingual buprenorphine/naloxone, buccal buprenorphine, and transdermal buprenorphine, with comparators consisting of opioid analgesics or placebo. Of the 25 studies reviewed, a total of 14 studies demonstrated clinically significant benefit with buprenorphine in the management of chronic pain: 1 study out of 6 sublingual and intravenous buprenorphine, the only sublingual buprenorphine/naloxone study, 2 out of 3 studies of buccal buprenorphine, and 10 out of 15 studies for transdermal buprenorphine showed significant reduction in pain against a comparator. No serious adverse effects were reported in any of the studies. We conclude that a transdermal buprenorphine formulation is an effective analgesic in patients with chronic pain, while buccal buprenorphine is also a promising formulation based on the limited number of studies. Accepted for publication 24, 2017. Funding: None. Conflicts of Interest: See Disclosures at the end of the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). This systematic review discusses off-label use of pharmacologic agents. Reprints will not be available from the authors. Address correspondence to Neel Mehta, MD, Division of Pain Medicine, Weill Cornell Department of Anesthesiology, P300, New York Presbyterian Hospital, 525 E 68th St, New York, NY 10065. Address e-mail to nem9015@med.cornell.edu. © 2017 International Anesthesia Research Society

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2C9paob

Oxford Textbook of Anaesthesia, 1st Edition

No abstract available

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nUCM3r

Labor Analgesia as a Predictor for Reduced Postpartum Depression Scores: A Retrospective Observational Study

BACKGROUND: Using labor, epidural analgesia has been linked to a reduced risk of postpartum depression, but the role of labor pain relief in this association remains unclear. The goal of this study was to test the hypothesis that effective epidural analgesia during labor is associated with reduced postpartum depression symptomatology. METHODS: A single, institutional, retrospective, observational cohort design was chosen. The primary outcome was Edinburgh postnatal depression scale (EPDS) score, measured at the 6-week postpartum visit. Subjects included in the final analysis had (1) received labor epidural analgesia; (2) pain assessed during labor both before and during initiation of labor epidural analgesia by 0–10 numeric rating scores; and (3) depression risk assessed by the EPDS and documented at their 6-week postpartum visit. Simple and multiple linear regression was used to identify the best model for assessing the association between pain improvement, defined as percent improvement in pain (PIP), and depression, after adjusting for a history of anxiety or depression, other psychiatric history, abuse, trauma, mode of delivery, and other maternal or fetal comorbid diseases. RESULTS: Two hundred one patients were included in the final analysis. Women with higher improvements in pain were associated with lower EPDS scores (r = 0.025; P = .002). Variables known to be associated with depression (body mass index, anxiety and/or depression, third- and fourth-degree perineal lacerations, and anemia) were significantly correlated with EPDS score and included in the final model. After we adjusted for these covariates, PIP remained a significant predictor of EPDS score (r = 0.49; P = .008), accounting for 6.6% of the variability in postpartum depression scores. The full model including pain, body mass index, anxiety and/or depression, perineal lacerations, and anemia explained 24% of the variability in postpartum depression scores. CONCLUSIONS: Although the extent of labor pain relief by epidural analgesia predicts lower postpartum depression scores, the relative contribution of PIP to risk for postpartum depression symptoms may be less than other established risk factors for depression. These data support that the clinical significance of labor analgesia in the development of postpartum depression needs to be more clearly defined. Accepted for publication October 30, 2017. Funding: G.L. is supported in part by the National Institutes of Health, T32GM075770 and K12HD043441. The authors declare no conflicts of interest. Institutional Review Board: This study was approved by the University of Pittsburgh Institutional Review Board (PRO15060463), 3500 5th Ave, Hieber Building, Room 106, Pittsburgh, PA 15213. E-mail: askirb@pitt.edu. This study was presented as an abstract at the annual meeting of the Society for Obstetric Anesthesia and Perinatology (SOAP), May 18–22, 2016, Boston, MA, and at the annual meeting of the American Society of Anesthesiologists (ASA), October 26, 2016, Chicago, IL. Reprints will not be available from the authors. Address correspondence to Grace Lim, MD, MS, Department of Anesthesiology, Magee-Women's Hospital of the University of Pittsburgh Medical Center, 300 Halket St, Suite 3510, Pittsburgh, PA 15232. Address e-mail to limkg2@upmc.edu. © 2017 International Anesthesia Research Society

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2CbMsKg

A Retrospective Analysis of Clinical Research Misconduct Using FDA-Issued Warning Letters and Clinical Investigator Inspection List From 2010 to 2014

BACKGROUND: The US Food and Drug Administration (FDA) conducts inspections of clinical investigation sites as a component of clinical trial regulation. The FDA describes the results of these inspections in the Clinical Investigator Inspection List (CLIIL). More serious violations are followed up in FDA warning letters issued to investigators. The primary objective of the current study is to qualitatively and quantitatively describe the CLIIL data and contents of FDA-issued warning letters from 2010 to 2014. METHODS: We retrospectively analyzed the CLIIL and FDA warning letters. For the CLIIL, we quantified the frequency of each violation among other data points. We compared recent data (2010–2014) to the previous 5 years (2005–2009). To analyze FDA warning letters, we developed a coding system to quantify the frequency of violations found. RESULTS: We analyzed 3637 inspections in the CLIIL database and 60 warning letters. Overall, there was a decrease or no change in all violations in the CLIIL database. The largest violation code reported was "failure to follow investigational plan" in both the 2005–2009 and 2010–2014 timeframes. Coding of FDA warning letters shows that the most common violations reported were failing to maintain accurate case histories (10.82%), enrolling ineligible subjects (8.85%), and failing to perform required tests (8.52%). CONCLUSIONS: The overall decrease in violations is encouraging. But, the high proportion of violations related to failure to follow the investigational plan is concerning as the complexity of trials increases. We conclude that more detailed information is necessary to accurately evaluate these violations. The current study provides a model for creating more granular data of violations to better inform clinical investigators and improve clinical trials. Accepted for publication October 24, 2017. Funding: None. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Christopher A. Romano, BS, Department of Anesthesiology, Montefiore Medical Center, 111 E 210th St, Bronx, NY 10467. Address e-mail to caromano@mail.einstein.yu.edu. © 2017 International Anesthesia Research Society

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nXRvKW

The Clinical Utility of Noninvasive Pulse Co-oximetry Hemoglobin Measurements in Dark Skinned Critically Ill Patients

BACKGROUND: The primary objective of this study was to assess the clinical usefulness of a point-of-care device which measures hemoglobin noninvasively (SpHb) in a group of critically ill participants with dark skin pigmentation. METHODS: One hundred forty-six adult and pediatric participants from a multidisciplinary intensive care unit had intermittent readings of noninvasive hemoglobin measurements performed at a minimum of 4 hourly intervals. A total of 371 readings were analyzed. Concurrent blood samples were taken to assess hemoglobin levels using point-of-care blood gas analyzer, as well as sent to a central laboratory where hemoglobin was measured using the sodium lauryl sulfate method. Bland-Altman plots were constructed to assess the agreement between results from the 2 point-of-care devices with the reference standard (laboratory hemoglobin). RESULTS: SpHb exhibited significant bias when compared to laboratory hemoglobin, while blood gas hemoglobin did not. Mean bias for SpHb was +1.64 with limits of agreement of −1.03 to 4.31 compared to blood gas hemoglobin which showed a bias of 0.26 and limits of agreement of −0.84 to 1.37. The magnitude of the bias for SpHb increased with increasing mean hemoglobin levels. Of all the additional study variables assessed for effect on the bias, only Acute Physiology and Chronic Health Evaluation II score in adult patients (P

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2C99st8

In Response

No abstract available

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nXRoiu

The Impact of Prehospital Tranexamic Acid on Blood Coagulation in Trauma Patients

BACKGROUND: There is limited data on prehospital administration of tranexamic acid (TXA) in civilian trauma. The aim of this study was to evaluate changes in coagulation after severe trauma from on-scene to the hospital after TXA application in comparison to a previous study without TXA. METHODS: The study protocol was registered at ClinicalTrials.gov (NCT02354885). A prospective, multicenter, observational study investigating coagulation status in 70 trauma patients receiving TXA (1 g intravenously) on-scene versus a control group of 38 patients previously published without TXA. To account for potential differences in patient and trauma epidemiology, crystalloid and colloidal resuscitation fluid, 2 propensity score matched groups (n = 24 per group) were created. Measurements included ROTEM, standard coagulation tests and blood gas analyses on-scene and emergency department admission. Presented values are mean and [standard deviation], and difference in means and 95% confidence intervals. RESULTS: Patient epidemiology was not different between groups. Coagulation assays on-scene were comparable between the TXA and C. Prehospital hyperfibrinolysis was blunted in all 4 patients in the TXA group. Viscoelastic FIBTEM maximum clot firmness (MCF), representing functional fibrinogen levels, did not change from on-scene to the emergency department in the TXA group, whereas MCF decreased -3.7 [1.8] mm in the control group. Decrease of MCF was significantly reduced in the TXA group in EXTEM by 9.2 (7.2–11.2) mm (P

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2CbM9iA

Analysis of Inpatient Falls After Total Knee Arthroplasty in Patients With Continuous Femoral Nerve Block

Continuous femoral nerve block (cFNB) is thought to increase the risk of falls after total knee arthroplasty (TKA). Previous studies have failed to consider the timing of cFNB removal in relation to inpatient falls. We investigated all inpatient falls after TKA over a 3-year period using our institutional safety report database. Ninety-five falls were reported from a total of 3745 patients. The frequency of falls after TKA persisted at a similar rate despite removal of cFNB and likely regression of femoral nerve block. Other modifiable risk factors may play a more prominent role in falls risk after TKA. Accepted for publication October 24, 2017. Funding: This work was supported by Sunnybrook Health Sciences Centre, Department of Anesthesia, University of Toronto, Toronto, Ontario, Canada. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Stephen Choi, MD, FRCPC, Department of Anesthesia, Sunnybrook Health Sciences Centre, M3-200, 2075 Bayview Ave, Toronto, Ontario, Canada, M4N 3M5. Address e-mail to stephen.choi@sunnybrook.ca. © 2017 International Anesthesia Research Society

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2z6paG4

Response to Improving the Success Rate of Chest Compression-Only CPR by Untrained Bystanders in Adult Out-of-Hospital Cardiac Arrest: Maintaining Airway Patency May Be the Way Forward

No abstract available

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nVOL0W

The Anesthesia Workstation: Quo Vadis?

Ensuring adequate ventilation and oxygenation and delivering inhaled anesthetic agent to the patient remain core responsibilities of the anesthesia provider during general anesthesia. Because of the emphasis placed on physiology, pharmacology, clinical sciences, and administrative duties, the stellar anesthesia workstation technology may be underutilized by the anesthesia community. Target-controlled O2 and agent delivery and automated end-expired CO2 control have entered the clinical arena, with only cost, luddism, and administrative hurdles preventing their more widespread use. This narrative review will explain technological aspects of existing and recently introduced anesthesia workstations. Concepts rather than particular anesthesia machines will be addressed, but examples will mostly pertain to the more recently introduced workstations. The anesthesia workstation consists of a ventilator, a carrier gas and agent delivery system, a scavenging system, and monitors. Mainly, the circle breathing circuit configuration, ventilator, and carrier gas and agent delivery technology are discussed. Occasionally, technical details are provided to give the reader a taste of the modern technology. Accepted for publication October 23, 2017. Funding: None. Conflicts of Interest: See Disclosures at the end of the article. Both the authors contributed equally to this article. Reprints will not be available from the authors. Address correspondence to Jan F. A. Hendrickx, MD, PhD, Department of Anesthesiology, OLV Hospital, Moorselbaan 164, 9300, Aalst, Belgium. Address e-mail to jcnwahendrickx@yahoo.com. © 2017 International Anesthesia Research Society

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2z6eSpb

American College of Surgeons Children’s Surgery Verification Quality Improvement Program: What Anesthesiologists Need to Know Now

A task force of pediatric surgical specialists with the support of The American College of Surgeons recently launched a verification program for pediatric surgery, the Children's Surgery Verification quality improvement program, with the goal of improving pediatric surgical, procedural, and perioperative care. Included in this program are specific standards for the delivery of pediatric anesthesia care across a variety of practice settings. We review the background, available evidence, requirements for verification, and verification process and its implications for the practice of pediatric anesthesia across the country. In addition, we have included a special roundtable interview of 3 recently Children's Surgery Verification–verified program directors to provide an up-to-date real-world perspective of this children's surgery quality improvement program. Accepted for publication October 16, 2017. Funding: None. Conflicts of Interest: See Disclosures at the end of the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). The authors M. Brooks Peterson and C. S. Houck are equally contributing first authors. Reprints will not be available from the authors. Address correspondence to Melissa Brooks Peterson, MD, 13123 E, 16th Ave, Box 090, Aurora, CO 80045. Address e-mail to melissa.brooks@childrenscolorado.org. © 2017 International Anesthesia Research Society

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2z6Tdxs

Nerve Blockade and Chronic Opiate Use After Orthopedic Surgery

No abstract available

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nUZg4D

Bias in Before–After Studies: Narrative Overview for Anesthesiologists

Before–after study designs are effective research tools and in some cases, have changed practice. These designs, however, are inherently susceptible to bias (ie, systematic errors) that are sometimes subtle but can invalidate their conclusions. This overview provides examples of before–after studies relevant to anesthesiologists to illustrate potential sources of bias, including selection/assignment, history, regression to the mean, test–retest, maturation, observer, retrospective, Hawthorne, instrumentation, attrition, and reporting/publication bias. Mitigating strategies include using a control group, blinding, matching before and after cohorts, minimizing the time lag between cohorts, using prospective data collection with consistent measuring/reporting criteria, time series data collection, and/or alternative study designs, when possible. Improved reporting with enforcement of the Enhancing Quality and Transparency of Health Research (EQUATOR) checklists will serve to increase transparency and aid in interpretation. By highlighting the potential types of bias and strategies to improve transparency and mitigate flaws, this overview aims to better equip anesthesiologists in designing and/or critically appraising before–after studies. Accepted for publication October 13, 2017. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Glenio B. Mizubuti, MD, MSc, Department of Anesthesiology and Perioperative Medicine, Victory 2, Kingston General Hospital, Queen's University, 76 Stuart St, Kingston, Ontario K7L 2V7, Canada. Address e-mail to gleniomizubuti@hotmail.com. © 2017 International Anesthesia Research Society

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2z6ypG8

Classification of C2C12 cells at differentiation by convolutional neural network of deep learning using phase contrast images

Abstract

In the field of regenerative medicine, tremendous numbers of cells are necessary for tissue/organ regeneration. Today automatic cell-culturing system has been developed. The next step is constructing a non-invasive method to monitor the conditions of cells automatically. As an image analysis method, convolutional neural network (CNN), one of the deep learning method, is approaching human recognition level. We constructed and applied the CNN algorithm for automatic cellular differentiation recognition of myogenic C2C12 cell line. Phase-contrast images of cultured C2C12 are prepared as input dataset. In differentiation process from myoblasts to myotubes, cellular morphology changes from round shape to elongated tubular shape due to fusion of the cells. CNN abstract the features of the shape of the cells and classify the cells depending on the culturing days from when differentiation is induced. Changes in cellular shape depending on the number of days of culture (Day 0, Day 3, Day 6) are classified with 91.3% accuracy. Image analysis with CNN has a potential to realize regenerative medicine industry.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2APPcwv

Value of complex evoked auditory brainstem response in patients with post-stroke aphasia (prospective study)

Publication date: Available online 12 December 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): S. Mourad, M. Abd Al-Ghaffar, Mohamed Al-Amir Bassiony, G. Fawzi
ObjectiveTo evaluate the perception of complex ABR (C-ABR) in aphasic patients and to compare it before and 3 months after management of stroke.MethodologyA prospective study was conducted on 30 aphasic patients using C-ABR. The results were compared within 2 weeks post-stroke and 3 months after management. The results of aphasic patients were compared with normal subjects.ResultsThe seven C-ABR waves regarding the onset (wave V and A), offset (peak O), transition (peak C) and frequency following responses (peak D, E and F) were identified in all participants. There was a statistically significant difference in C-ABR latencies between control and study group in the waves D, E, F and O, this means that aphasic patients exhibited abnormal neural synchrony affecting the source elements (fundamental frequency) (waves D, E, F and O) however there was no effect on the filter elements (transients).ConclusionAphasic patients exhibited abnormal neural synchrony affecting the source elements (waves D, E, F and O) however there was no effect on the filter elements (transients).



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AyNq5Y

Melanotic neuroectodermal tumor of infancy (MNTI) of the head and neck: A French multicenter study

Publication date: Available online 12 December 2017
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Audrey Moreau, Louise Galmiche, Veronique Minard-Colin, Martin Rachwalski, Kahina Belhous, Daniel Orbach, Aline Joly, Arnaud Picard, Natacha Kadlub
ObjectivesMelanotic neuroectodermal tumor of infancy (MNTI) of the head and neck is a rare entity with uncertain clinical behavior. Radical surgical resection is the current recommended treatment, however this can cause severe aesthetic and functional sequelae. The aim of this study was to clinically characterize MNTIs and to stratify risk factors that may influence locoregional recurrence.MethodsA retrospective multicenter study, including 11 patients from eight centers with a confirmed diagnosis of MNTI, was conducted. Epidemiological, clinical, radiological, pathological, and immunohistochemical examinations were reviewed. A statistical analysis using a t-test was conducted to calculate parameters correlating with tumor recurrence.ResultsMNTIs mainly occurred in the maxilla, with a mean age at diagnosis of 3.18 months (range: 0–6 months). Primary surgery was performed on 10 patients, with a clear margin resection on two patients. Overall recurrence rate was 27% with a survival of 100% at time of follow-up. No statistical correlation between recurrence rate, age at diagnosis, localization, resection margins, and pathological and immunohistochemical characteristics could be established.ConclusionIn our study, locoregional tumor recurrence did not seem to correlate with resection margins, so a conservative surgical approach may need to be considered to avoid functional and aesthetic sequelae.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2iXioJR

Melanotic neuroectodermal tumor of infancy (MNTI) of the head and neck: A French multicenter study

Publication date: Available online 12 December 2017
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Audrey Moreau, Louise Galmiche, Veronique Minard-Colin, Martin Rachwalski, Kahina Belhous, Daniel Orbach, Aline Joly, Arnaud Picard, Natacha Kadlub
ObjectivesMelanotic neuroectodermal tumor of infancy (MNTI) of the head and neck is a rare entity with uncertain clinical behavior. Radical surgical resection is the current recommended treatment, however this can cause severe aesthetic and functional sequelae. The aim of this study was to clinically characterize MNTIs and to stratify risk factors that may influence locoregional recurrence.MethodsA retrospective multicenter study, including 11 patients from eight centers with a confirmed diagnosis of MNTI, was conducted. Epidemiological, clinical, radiological, pathological, and immunohistochemical examinations were reviewed. A statistical analysis using a t-test was conducted to calculate parameters correlating with tumor recurrence.ResultsMNTIs mainly occurred in the maxilla, with a mean age at diagnosis of 3.18 months (range: 0–6 months). Primary surgery was performed on 10 patients, with a clear margin resection on two patients. Overall recurrence rate was 27% with a survival of 100% at time of follow-up. No statistical correlation between recurrence rate, age at diagnosis, localization, resection margins, and pathological and immunohistochemical characteristics could be established.ConclusionIn our study, locoregional tumor recurrence did not seem to correlate with resection margins, so a conservative surgical approach may need to be considered to avoid functional and aesthetic sequelae.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2iXioJR

Pharmacokinetically-targeted dosed everolimus maintenance therapy in lymphoma patients

Abstract

Background

Everolimus, an mTOR inhibitor, is active in refractory lymphomas. However, toxicity with flat dosing limits its usage. Speculatively, pharmacokinetically-targeted dosing could improve tolerability. Therefore, we studied serum-trough dosing with rituximab as maintenance after high-dose cyclophosphamide (HDC) consolidation in lymphoma patients.

Patients/methods

After HDC, everolimus was dosed to serum trough levels (goal 3–15 ng/mL), with quarterly rituximab infusions for 1 year while maintaining < grade II non-hematologic and < grade III hematologic toxicities. Adult patients in first PR/CR with: mantle cell, transformed, double-hit, or high risk chronic lymphocytic leukemia or in second PR for any relapsed B cell lymphoma were eligible. Prophylaxis was given for encapsulated organisms, HSV and PCP. Serum IgG levels were maintained > 500 mg/dL.

Results

49 patients, median age: 59.0 years enrolled; MCL (26), CLL (10), transformed lymphoma (7), and other histologies (6). During the life of the study, the most frequent everolimus dosing has been 2.5 mg daily or 2.5 mg every other day; at these doses, serum levels are within the therapeutic range and non-hematologic toxicity is rare. At a median follow-up of 27.1 months, three patients remain on active therapy. Two patients withdrew secondary to potentially-attributable adverse events including a bacterial pneumonia and a viral pneumonia; this low rate of discontinuation compares well to other long-term everolimus trials. While a 58 and 76% EFS at 30 months for the entire cohort and MCL cohort, respectively, compares similarly to previously published HDC/rituximab data, longer follow-up is required.

Conclusions

Pharmacokinetically-targeted dosing appears to increase everolimus tolerability. This finding may be applicable to other patient populations.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AxuVyR

Synchronous Premaxillary Osteotomy with Primary Cheiloplasty for BCLP Patients with Protrusion of the Premaxillae

Background: In bilateral cleft lip and palate (BCLP) patients with protrusion and/or torsion of the premaxillae, it is difficult to achieve a good outcome. We have developed a series of procedures of premaxillary osteotomy with primary cheiloplasty for BCLP patients who did not respond well to presurgical orthodontics (PSO). Methods: A total of 27 BCLP patients with protrusion and/or torsion of the premaxillae underwent PSO. For 3 BCLP patients in whom the protruded premaxillae could not be returned to a good position, a primary premaxillary osteotomy and gingivoperiosteoplasty (GPP) with cheiloplasty were performed simultaneously. Subsequently, Furlow palatoplasty was performed by one and a half years of age. Maxillary growth was evaluated by dental occlusion at 4 years of age. Results: A premaxillary osteotomy and GPP with cheiloplasty were performed at 6 months. The patients' facial structures improved, their premaxillae were positioned more superiorly, and normal inclination of the incisors was achieved. They had edge-to-edge occlusions or cross bites at 4 years of age. Conclusions: As advantages, the patients' facial structures improved, and the alveolar bones were formed by GPP. As a disadvantage, premaxillary necrosis might occur because of poor blood circulation. It is important to secure the following 2 blood supplies: from the periosteum and soft-tissue of the anterior premaxillae and from the periosteum and mucosa of the nasal septum. Synchronous premaxillary osteotomy and GPP with primary cheiloplasty are appropriate when the premaxillae cannot be properly repositioned by PSO or PSO cannot be done.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2j17aYj

Craniofacial Reconstruction by a Cost-Efficient Template-Based Process Using 3D Printing

Summary: Craniofacial defects often result in aesthetic and functional deficits, which affect the patient's psyche and wellbeing. Patient-specific implants remain the optimal solution, but their use is limited or impractical due to their high costs. This article describes a fast and cost-efficient workflow of in-house manufactured patient-specific implants for craniofacial reconstruction and cranioplasty. As a proof of concept, we present a case of reconstruction of a craniofacial defect with involvement of the supraorbital rim. The following hybrid manufacturing process combines additive manufacturing with silicone molding and an intraoperative, manual fabrication process. A computer-aided design template is 3D printed from thermoplastics by a fused deposition modeling 3D printer and then silicone molded manually. After sterilization of the patient-specific mold, it is used intraoperatively to produce an implant from polymethylmethacrylate. Due to the combination of these 2 straightforward processes, the procedure can be kept very simple, and no advanced equipment is needed, resulting in minimal financial expenses. The whole fabrication of the mold is performed within approximately 2 hours depending on the template's size and volume. This reliable technique is easy to adopt and suitable for every health facility, especially those with limited financial resources in less privileged countries, enabling many more patients to profit from patient-specific treatment.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2iXquSB

Reliability of High-speed Videoendoscopic Ratings of Essential Voice Tremor and Adductor Spasmodic Dysphonia

Publication date: Available online 13 December 2017
Source:Journal of Voice
Author(s): Lindsey A. Parker, Melda Kunduk, Daniel S. Fink, Andrew McWhorter
ObjectivesThe main objectives of this study were to (1) examine intrarater and inter-rater reliabilities in perceptual ratings of vocal fold vibratory patterns and supraglottic characteristics for essential vocal tremor and adductor spasmodic dysphonia (AdSD) using high-speed videoendoscopy (HSV), and (2) to investigate the specificity of the parameters in differentiating these two voice disorders.MethodsHSV recordings of 34 cases diagnosed with essential vocal tremor, AdSD, or AdSD with vocal tremor were evaluated blindly by two voice speech pathologists. The two raters examined all HSV video segments twice across nine supraglottic and vocal fold vibratory characteristics for inter-rater and intrarater reliabilities. A separate consensus rating was then developed, with the results analyzed to explore differentiation.ResultsRaters demonstrated moderate intrarater reliability with mean Spearman's rho correlation coefficients of 0.68 (rater 1) and 0.73 (rater 2). Moderate inter-rater reliability for the two raters was seen across all parameters with a mean Cohen's kappa coefficient of 0.51. Raters showed higher intrarater and inter-rater reliabilities for supraglottic parameters. Only the presence of tremor differentiated between the two voice disorders in cases with a consistent diagnosis.ConclusionsThe high level of concomitance between vocal tremor and AdSD may affect subjective perceptual analysis of supraglottic and vocal fold vibratory patterns. Results indicate similar global involvement of supraglottic laryngeal structures for both vocal tremor and AdSD.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2ykTo4p

Extended Alar Contour Grafts in Rhinoplasty

The authors discuss the extended alar contour graft as another technique in the open approach to rhinoplasty.
Plastic and Reconstructive Surgery

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2BfAQbw

Thoracic surgeon and patient focus groups on decision-making in early-stage lung cancer surgery

Future Oncology, Ahead of Print.


from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Az1xZ5

A critical review on ramucirumab in the treatment of advanced urothelial cancer

Future Oncology, Ahead of Print.


from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2yk99Zy

Reliability of High-speed Videoendoscopic Ratings of Essential Voice Tremor and Adductor Spasmodic Dysphonia

Publication date: Available online 13 December 2017
Source:Journal of Voice
Author(s): Lindsey A. Parker, Melda Kunduk, Daniel S. Fink, Andrew McWhorter
ObjectivesThe main objectives of this study were to (1) examine intrarater and inter-rater reliabilities in perceptual ratings of vocal fold vibratory patterns and supraglottic characteristics for essential vocal tremor and adductor spasmodic dysphonia (AdSD) using high-speed videoendoscopy (HSV), and (2) to investigate the specificity of the parameters in differentiating these two voice disorders.MethodsHSV recordings of 34 cases diagnosed with essential vocal tremor, AdSD, or AdSD with vocal tremor were evaluated blindly by two voice speech pathologists. The two raters examined all HSV video segments twice across nine supraglottic and vocal fold vibratory characteristics for inter-rater and intrarater reliabilities. A separate consensus rating was then developed, with the results analyzed to explore differentiation.ResultsRaters demonstrated moderate intrarater reliability with mean Spearman's rho correlation coefficients of 0.68 (rater 1) and 0.73 (rater 2). Moderate inter-rater reliability for the two raters was seen across all parameters with a mean Cohen's kappa coefficient of 0.51. Raters showed higher intrarater and inter-rater reliabilities for supraglottic parameters. Only the presence of tremor differentiated between the two voice disorders in cases with a consistent diagnosis.ConclusionsThe high level of concomitance between vocal tremor and AdSD may affect subjective perceptual analysis of supraglottic and vocal fold vibratory patterns. Results indicate similar global involvement of supraglottic laryngeal structures for both vocal tremor and AdSD.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2ykTo4p

Fenestrated Thoracic Endovascular Aortic Repair Using Physician Modified Stent Grafts for Acute Type B Aortic Dissection with Unfavourable Landing Zone

Publication date: Available online 12 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Jiechang Zhu, Lujing Zhao, Xiangchen Dai, Yudong Luo, Hailun Fan, Zhou Feng, Yiwei Zhang, Fanguo Hu
ObjectivesThe aim was to evaluate the early results of fenestrated thoracic endovascular aortic repair (fTEVAR) using physician modified stent grafts (PMSGs) to revascularise aortic branches for acute type B aortic dissection (ABAD) with unfavourable proximal landing zone.MethodsTwenty consecutive patients who underwent fenestrated TEVAR using PMSGs between November 2015 and December 2016 were retrospectively reviewed. Pre-, intra-, and post-operative clinical data were recorded.ResultsThe median patient age was 53 years (range, 18–83 years), and 16 of the 20 (80%) patients were men. Indications were complicated ABAD with unfavourable proximal landing zones, including inadequate proximal landing zone (n = 4), retrograde dissection extending to the left subclavian artery (LSA) (n = 13), and retrograde haematoma involving the LSA (n = 3). Twenty PMSGs (Medtronic Valiant stent grafts, n = 4; Relay thoracic stent grafts, n = 10; Ankura thoracic stent grafts, n = 6) were deployed. One LSA fenestration was created in 19 patients, and one LSA fenestration combined with a left common carotid artery (LCCA) scallop was created in one patient. Branch stents consist of a covered stent for the LSA (n = 7), an uncovered stent for the LSA (n = 14), and an uncovered stent for the LCCA (n = 1). The median duration for stent graft modifications was 40 min (range 30–60 min). The mean interval between symptom onset and treatment was 5 ± 3 days (range, 1–10 days). The initial technical success rate was 90% (18 of 20). Partial coverage of the LCCA in one patient resolved after uncovered chimney stent implantation in the LCCA. Type III endoleak between the LSA covered stent and the PMSG occurred in this patient 1 week post fTEVAR and resolved after re-intervention with deployment of an Amplatzer occluder device across the site of the leak. A chimney stent was deployed to solve the misalignment of the LSA in another patient. The mean operation time was 101 ± 48 min, and fluoroscopy time was 24 ± 16 min. There were no in hospital deaths and no peri-operative neurological complications. The median length of stay was 9 ± 6 days (range, 5–26 days). One patient had a left brachial artery (LBA) pseudoaneurysm at the puncture site that required open repair. One patient presented renal deterioration post-operatively and recovered uneventfully after conservative therapy. All patients survived at a mean follow-up of 6.95 months (range, 2–14 months). During follow-up, no post-operative complications occurred and all target vessels remained patent. No fenestration related Type I or III endoleaks were observed.ConclusionsfTEVAR using PMSGs may be a viable alternative for patients who present with ABAD without healthy proximal landing zones and who are unable to wait for a custom made fenestrated device.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2ykIcoE

Endovascular Repair of Acute Thoraco-abdominal Aortic Aneurysms

Publication date: Available online 12 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Chiara Mascoli, Massimo Vezzosi, Andreas Koutsoumpelis, Mauro Iafrancesco, Aaron Ranasinghe, Paul Clift, Jorge Mascaro, Martin Claridge, Donald J. Adam
ObjectivesThe outcome of endovascular repair (EVAR) for acute TAAA is reported and the applicability of the t-Branch off the shelf (OTS) device is determined.MethodsInterrogation of a prospectively maintained database identified all patients who underwent EVAR for acute TAAA between September 2012 (when the first non-elective t-Branch case was performed) and November 2015. Early and medium-term outcomes were analysed. Survival and re-intervention-free survival were calculated by Kaplan–Meier analysis.ResultsA total of 39 patients (27 men; mean ± SD age, 72 ± 8 years) were treated for acute symptomatic (n = 29) or ruptured (n = 10) TAAA (20 anatomical extent I–III, 19 extent IV). Fourteen patients had mycotic aneurysms. The mean aneurysm diameter was 80 ± 20 mm. The mean ± SD follow-up was 21.4 ± 15.4 months. Surgeon modified fenestrated EVAR was used in 24 patients, chimney/periscope EVAR in two, and t-Branch in 13 (33%) patients. Aortic coverage was greater than 40 mm above the coeliac axis in all patients. A total of 127 target vessels (TVs) were preserved (mean 3.3 per patient) and two occluded within 30 days. The 30 day mortality was 26%. Four (10%) patients developed spinal cord ischaemia (SCI): two with paraplegia died within 30 days, and two with paraparesis recovered completely with blood pressure manipulation and cerebrospinal fluid drainage. Estimated overall survival (±SD) at 12 and 24 months was 71.8 ± 7.2% and 63.2 ± 7.9%, respectively. Estimated freedom from re-intervention at 12 and 24 months was 93 ± 4.8% and 85.3 ± 6.8%, respectively.ConclusionsEVAR for acute TAAA is associated with acceptable early and mid-term results in patients who have no other treatment options. Only one third of these patients were suitable for the t-Branch device, indicating that further advances in device design are required to treat the majority of acute TAAA patients with commercially available OTS technology.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AzuAvL

Re: “Catheter Foam Sclerotherapy of the Great Saphenous Vein, with Peri-saphenous Tumescence Infiltration and Saphenous Irrigation”—Is Modified Catheter Foam Sclerotherapy a Step Back in the Evolution of Endovenous Ablation for Varicose Veins?

Publication date: Available online 12 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Alok Tiwari, Tze Tec Chong, Tjun Y. Tang




from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2ykls8f

Aortofemoral Reconstruction for an Infected Graft Using Thrombosed Femoral Veins

Publication date: Available online 12 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Grigol Keshelava, Davit Kovziridze, Alexander Mkervalishvili
IntroductionTreatment of an infected aortic prosthesis is difficult and the ideal graft material is subject to debate.ReportA case of infected aortic prosthesis treated using bilateral thrombosed superficial femoral veins (SFVs) is presented. Bilateral reversed SFVs were cut longitudinally at both proximal ends about 3–4 cm and were sutured side by side. The operating time was 5 h. No sign of recurrent infection was observed when the patient suffered a myocardial infarction and died 6 months post-operatively.DiscussionThrombosed SFVs may be considered as a therapeutic option for infected aortic graft replacement.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AzR8MU

Perforator mapping reduces the operative time of DIEP flap breast reconstruction: a systematic review and meta-analysis of preoperative ultrasound, computed tomography and magnetic resonance angiography

Publication date: Available online 12 December 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Ryckie G. Wade, James Watford, Justin C.R. Wormald, Russell Bramhall, Andrea Figus
BackgroundPrior to DIEP flap breast reconstruction, mapping the perforators of the lower abdominal wall using ultrasound, computed tomography angiography (CTA) or magnetic resonance angiography (MRA) reduces the risk of flap failure. This review aimed to investigate the additional potential benefit of a reduction in operating time.MethodsWe systematically searched the literature for studies concerning adult women undergoing DIEP flap breast reconstruction, which directly compared the operating times and adverse outcomes for those with and without preoperative perforator mapping by ultrasound, CTA or MRA. Outcomes were extracted, data meta-analysed and the quality of the evidence appraised.ResultsFourteen articles were included. Preoperative perforator mapping by CTA or MRA significantly reduced operating time (mean reduction of 54 minutes [95% CI 3, 105], p=0.04), when directly compared to DIEP flap breast reconstruction with no perforator mapping. Further, perforator mapping by CTA was superior to ultrasound, as CTA saved more time in theatre (mean reduction of 58 minutes [95% CI 25, 91], p<0.001) and was associated with a lower risk of partial flap failure (RR 0.15 [95% CI 0.04, 0.6], p=0.007). All studies were at risk of methodological bias and the quality of the evidence was very low.ConclusionsThe quality of research regarding perforator mapping prior to DIEP flap breast reconstruction is poor and although preoperative angiography appears save operative time, reduce morbidity and confer cost savings, higher quality research is needed.RegistrationPROSPERO ID CRD42017065012



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AgwMUl

Cosmetic, minimally invasive, partial matricectomy of ingrown toenails with granulation tissue

Publication date: Available online 12 December 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Ning Zhang, Zheng Huang, Song-Hua Cao, Yang Wang, Yong Hu




from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2z5hEuT

Outcome predictors in elderly head and neck free flap reconstruction: a retrospective study and systematic review of the current evidence

Publication date: Available online 12 December 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Cindy Siaw-Lin Goh, Yee-Onn Kok, Cheryl Pei-Chyi Yong, Esther Wan-Xian Tan, Lee-Gan Goh, Khong-Yik Chew, Constance Ee-Hoon Teo, Terence Lin-Hon Goh
Free flap tissue transfer has become the gold standard for reconstruction of composite head and neck defects. We sought to investigate the efficacy and morbidity of these procedures in the elderly. We retrospectively reviewed 245 head and neck free flap procedures (234 patients). Patients were stratified by age group (≥ or <65 years). Univariate and multivariate analyses were used to evaluate the following primary outcomes – free flap survival, postoperative medical and surgical complications and 30-day mortality. We found that free flap success and surgical complication rates were similar between the two age groups. Overall flap success and perioperative mortality rates were 94.3% and 2.1% respectively. Medical complications were significantly more common in the elderly group (p<0.001) and this correlated with comorbidity (OR=2.81, p=0.044) and advanced tumour stage (OR=10.20, p=0.029). Age was not independently associated with poor outcomes in our cohort. We then performed a systematic review of similar case-control studies worldwide and compared their findings with our results. We conclude that advanced age does not preclude free flap success in head and neck reconstruction. Rather, the presence of comorbidity appears to predict the development of medical complications postoperatively. Elderly patients with low comorbidity scores may be offered free flap reconstruction with less reservation.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AfAk9F

Assessment of Bone Dimensions in the Anterior Maxilla: A Cone Beam Computed Tomography Study

Abstract

Purpose

To evaluate labial and palatal bone thickness at the maxillary anterior teeth as well as distance from cemento-enamel junction (CEJ) to bone crest using cone beam computed tomography (CBCT).

Materials and Methods

Measurements were obtained for maxillary anterior teeth of 120 subject CBCT volumes including thickness of labial and palatal plates of bone (coronal, middle, and apical thirds), and distance between CEJ and alveolar bone crest mid-labially, mesially, and distally.

Results

The mean value of bone thickness at coronal, middle, and apical thirds of the labial side for central incisor roots were respectively: 0.73, 0.69, 0.60 (mm), for lateral incisors: 0.70, 0.61, 0.49 (mm), and for canines: 0.74, 0.53, 040 (mm). The thickness of palatal bone was significantly larger. The mean distance between CEJ and mid-labial bone crest for all sites was 2.16 mm.

Conclusion

Labial bone thickness is thin in the vast majority of maxillary anterior teeth. Use of CBCT facilitates planning for immediate implant placement and is helpful in the decision-making process when further bone augmentation is needed.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nVERfE

The Effect of Surface Treatment on Shear Bond Strength between Y-TZP and Veneer Ceramic: A Systematic Review and Meta-Analysis

Abstract

Purpose

The objective of this systematic review with meta-analysis was to evaluate surface treatment in yttria-stabilized tetragonal zirconia polycrystal ceramic (Y-TZP) on the shear bond strength (SBS) values between Y-TZP (core ceramic) and veneer ceramic, compared to untreated specimens.

Materials and Methods

This review was registered at PROSPERO platform under the number CRD42016036493. The systematic review of the extracted publications was performed to compare the effect of surface treatment on SBS between Y-TZP ceramic and veneering ceramic. A comprehensive review of the literature from the earliest available dates through January 2017 was performed in the PubMed/Medline, Embase, Scopus, and Cochrane Library databases.

Results

A total of 15 studies were identified for the inclusion of data, with only in vitro studies. A random-effect model found statistically significant differences between untreated and treated surfaces of Y-TZP (p < 0.00001; MD: 2.84; 95% CI: 2.19 to 3.49). In another analysis, a random-effect model found statistically significant differences between the groups that only performed the associations of treatments and control group (p < 0.00001; MD: 3.19; 95% CI: 2.11 to 4.28).

Conclusions

Surface treatment in Y-TZP improved the values of SBS between the Y-TZP and veneer ceramic. The associations between two or more treatments also showed positive effect on the bond strength due the cumulative effect of the treatments.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2C8M6DV

Three-Dimensional Static Articulation Accuracy of Virtual Models – Part I: System Trueness and Precision

Abstract

Purpose

To evaluate the 3D static articulation accuracy of 3 model scanner-CAD systems (Ceramill Map400 [AG], inEos X5 [SIR], Scanner S600 Arti [ZKN]) using a coordinate measuring machine (CMM). Trueness and precision for each system will be reported in Part I.

Materials and Methods

The master model simulated a single crown opposing a 3-unit fixed dental prosthesis. Five mounted stone cast sets were prepared, and one set was randomly selected. Reference values were obtained by measuring interarch and interocclusal reference features with the CMM. The stone cast set was scanned 5 times consecutively and articulated virtually with each system (3 test groups, n = 5). STL files of the virtual models were measured with CMM software. dR_R, dR_C, and dR_L, represented interarch global distortions at right, central, and left sides, respectively, while dR_M, dX_M, dY_M, and dZ_M represented interocclusal global and linear distortions between preparations.

Results

For trueness values, mean interarch global distortions ranged from 13.1 to 40.3 μm for dR_R, –199.0 to –48.1 μm for dR_C, and –114.1 to –47.7 μm for dR_L. Mean percentage error of interarch distortion did not exceed 0.6%. Mean interocclusal distortions ranged from 16.0 to 117.0 μm for dR_M, -33.1 to 101.3 μm for dX_M, 32.9 to 49.9 μm for dY_M and –32.0 to 133.1 μm for dZ_M. ANOVA of trueness found statistically significant differences for dR_C, dR_L, dR_M, dX_M, and dZ_M. For precision values, absolute mean difference between the 10 superimposition combinations ranged from 25.3 to 91.0 μm for dR_R, 21.5 to 85.5 μm for dR_C, 24.8 to 70.0 μm for dR_L. Absolute mean difference ranged from 49.9 to 66.1 μm for dR_M, 20.7 to 92.1 μm for dX_M, 86.8 to 96.0 μm for dY_M, and 36.5 to 100.0 μm for dZ_M. ANOVA of precision of all test groups found statistically significant differences for dR_R, dR_C, dR_L, dX_M and dZ_M, and the SIR group was the least precise.

Conclusion

The overall interarch global distortion of all three model scanner-CAD systems was low and did not exceed 0.6%. Variations in scanner technology, virtual articulation algorithm, and use of physical articulators contributed to the differences in distortion observed among all three groups.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nWSSK0

Influence of Implant Position in Implant-Assisted Removable Partial Denture: A Three-Dimensional Finite Element Analysis

Abstract

Purpose

To determine the ideal position of a dental implant to assist a posterior extended partial removable dental prosthesis (PRDP), through stress values, displacement values, and deformation of periodontal ligament (PDL).

Materials and Methods

A finite element analysis of different implant positions was analyzed using a 3D mandible model from a human patient. Test models were created: model A (implant in second molar area), model B (implant in the first molar area), and model C (implant in premolar area). A control model without implant support was also created. Overall displacement values, von Mises stress distribution maps, and nonlinear deformations were evaluated.

Results

Some differences could be observed between test models. The introduction of an implant in the edentulous area, unlike a conventional removable partial denture without implant support, decreases stress values in the biological structures such as: mandible, tooth, soft tissue, and PDL. Placing the implant in the first molar area resulted in improved displacement values, and reduced maximum stress values at the peri-implant bone area, metal structure, and implant were observed.

Conclusions

Within the limitations of this study we can conclude that placing the implant in the position of the first molar improves biomechanical behavior of implant-assisted PRDPs.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2C8qLKQ

Influence of Particle and Air-Abrasion Moment on Y-TZP Surface Characterization and Bond Strength

Abstract

Purpose

To evaluate the influence of particle and air-abrasion on the surface characterization and shear bond strength (SBS) of a Y-TZP ceramic with a resin cement.

Materials and Methods

Y-TZP specimens were air-abraded with 50 μm alumina particles; 120 μm alumina particles; 30 μm silica-coated alumina particles (Rocatec Soft); 110 μm silica-coated alumina particles (Rocatec Plus). Air-abrasion was performed before (BS); after (AS); before and after (BAS) zirconia sintering. Surface characterization included roughness (n = 10), wettability (n = 10), morphology (n = 2), and elemental composition (n = 2). For SBS (n = 11), composite resin discs were bonded to the air-abraded and silane-treated zirconia surface, with the resin cement RelyX ARC. Failure mode was determined. Roughness, wettability, and SBS data were analyzed by two-way ANOVA with pairwise interaction and Tukey's test (α = 0.05).

Results

Air-abrasion performed with coarser particles at BS and BAS moments provided the highest roughness values, while the lowest roughness values were observed with particles combined with AS moment (p < 0.01). Rocatec Plus provided lower contact angle than the 120 μm alumina particles (p = 0.013), and BAS exhibited lower contact angle than BS (p = 0.002). The combinations 120 μm/BS and the silica-coated alumina particles/AS and /BAS showed the highest SBS (p < 0.05). The combination of each particle/BAS was statistically similar to the same particle/AS. Failure mode was 100% adhesive for all groups. The interaction particle size/air-abrasion moment determined the morphological pattern. Silicon was observed only in the Rocatec groups.

Conclusions

Roughness was influenced by the particle size and was higher when the zirconia was air-abraded in its green stage. The particle composition played an important role in the wettability and both studied air-abrasion moments provided similar wettability than the one in which air-abrasion is usually performed. The highest SBS values were observed in the three moments, by using certain particles for each moment.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nXCXLC

Issue Information

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AijO8P

MPO-ANCA associated vasculitis with mononeuritis multiplex following influenza vaccination

Although influenza vaccines are generally safe and effective, a variety of autoimmune phenomena have been reported after vaccination over the past years, such as Guillain–Barre syndrome, rheumatoid arthritis, ...

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2BYXJww

Polyploidy and nuclear phenotype characteristics of cardiomyocytes from diabetic adult and normoglycemic aged mice

Publication date: Available online 12 December 2017
Source:Acta Histochemica
Author(s): Isabela S. Silva, Flávia G. Ghiraldini, Giovana M.B. Veronezi, Maria Luiza S. Mello
The frequency of polyploid nuclei in the aging human heart is in sharp contrast with that in the human liver. An inverse pattern exists between the mouse heart and liver cells. Ploidy degrees in mouse hepatocytes under hyperglycemic conditions are elevated to higher levels than those in aged hepatocytes. In this study, image analysis cytometry was used to investigate the effect of diabetes and aging on Feulgen-DNA quantities, ploidy degrees, nuclear shapes and chromatin texture in mouse cardiomyocytes compared to previously reported data for mouse hepatocytes. Adult, non-obese diabetic (NOD) hyperglycemic and normoglycemic females and 56-week-old normoglycemic BALB/c females were used. A small percentage (∼7%) of the cardiomyocyte nuclei in severely hyperglycemic NOD adult mice possessed higher ploidy values than those in the 8-week-old normoglycemic mice. Surprisingly, the Feulgen-DNA values and the frequency of nuclei belonging to the 4C and 8C ploidy classes were even higher (∼6%) in normoglycemic NOD specimens than in age-matched hyperglycemic NOD specimens. Additionally, a pronounced elongated nuclear shape was observed especially in adult normoglycemic NOD mice. In conclusion, NOD mice, irrespective of their glycemic level, exhibit a moderate increase in ploidy degrees within cardiomyocyte nuclei during the adult lifetime. As expected, aging did not affect the Feulgen-DNA values and the ploidy degrees of cardiomyocytes in BALB/c mice. The differences in ploidy degrees and chromatin textures such as absorbance variability and entropy, between adult NOD and aged BALB/c mice are consistent with other reports, indicating dissimilarities in chromatin functions between diabetes and aging.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2z5Whtv

Confirmation of the immunoreactivity of monoclonal anti-human C-terminal EGFR antibodies in bronze Corydoras Corydoras aeneus (Callichthyidae Teleostei) by Western Blot method

Publication date: Available online 13 December 2017
Source:Acta Histochemica
Author(s): Jennifer Mytych, Leszek Satora, Katarzyna Kozioł
Bronze corydoras (Corydoras aeneus) uses the distal part of the intestine as accessory respiratory organ. Our previous study showed the presence of epidermal growth factor receptor (EGFR) cytoplasmic domain in the digestive tract of the bronze corydoras. In this study, using Western Blot method, we validated the results presented in the previous research. In detail, results of Western Blot analysis on digestive and respiratory part of bronze corydoras intestine homogenates confirmed the immunoreactivity of anti-cytoplasmic domain (C-terminal) human EGFR antibodies with protein band of approximately 180kDa (EGFR molecular weight). This indicates a high homology of EGFR domain between these species and the possibility of such antibody use in bronze corydoras. Statistically significantly higher EGFR expression was observed in the respiratory part of intestine when compared to the digestive part. This implies higher proliferation activity and angiogenesis of epithelium in this part of intestine, creating conditions for air respiration. Therefore, Corydoras aeneus may be considered as a model organism for the molecular studies of the mechanisms of epithelial proliferation initiation and inhibition depending on hypoxia and normoxia.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AgMGhI

The Changing Role of Sound-Symbolism for Small Versus Large Vocabularies

Abstract

Natural language contains many examples of sound-symbolism, where the form of the word carries information about its meaning. Such systematicity is more prevalent in the words children acquire first, but arbitrariness dominates during later vocabulary development. Furthermore, systematicity appears to promote learning category distinctions, which may become more important as the vocabulary grows. In this study, we tested the relative costs and benefits of sound-symbolism for word learning as vocabulary size varies. Participants learned form-meaning mappings for words which were either congruent or incongruent with regard to sound-symbolic relations. For the smaller vocabulary, sound-symbolism facilitated learning individual words, whereas for larger vocabularies sound-symbolism supported learning category distinctions. The changing properties of form-meaning mappings according to vocabulary size may reflect the different ways in which language is learned at different stages of development.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2z64LRC

Analysis of NRAS gain in 657 patients with melanoma and evaluation of its sensitivity to a MEK inhibitor

Publication date: January 2018
Source:European Journal of Cancer, Volume 89
Author(s): Junya Yan, Xiaowen Wu, Jiayi Yu, Huan Yu, Tianxiao Xu, Kevin M. Brown, Xue Bai, Jie Dai, Meng Ma, Huan Tang, Lu Si, Zhihong Chi, Xinan Sheng, Chuanliang Cui, Yan Kong, Jun Guo
BackgroundNeuroblastoma rat-sarcoma (NRAS) mutations have been described in Chinese patients with melanoma. However, the status and the clinical significance of NRAS gain have not been investigated on a large scale.MethodsA total of 657 melanoma samples were included in the study. NRAS copy number was examined using the QuantiGene Plex DNA assay. The sensitivities of cell lines and patient-derived xenograft (PDX) models containing NRAS gain to a MAP/ERK kinase (MEK) inhibitor (binimetinib) were also evaluated.ResultsThe overall incidence of NRAS gain was 14.0% (92 of 657). Incidence of NRAS gain in acral, mucosal, chronic sun-induced damage (CSD) and non-CSD melanomas was 12.2%, 15.8%, 9.5% and 19.4%, respectively. NRAS gain was mutually exclusive to NRAS mutations (P = 0.036). The median survival time for melanoma patients with NRAS gain was significantly shorter than that for patients with normal NRAS copy number (P = 0.006). For patients containing NRAS gain, the median survival time for higher copy number (>4 copies) was significantly shorter than those with lower copy number (2–4 copies; P = 0.002). The MEK inhibitor (binimetinib) inhibited the proliferation of melanoma cells and the tumour growth of PDX models with NRAS gain.ConclusionsNRAS gain is frequent in patients with melanoma and may predict a poor prognosis of melanoma. The melanoma cells and PDX models containing NRAS gain are sensitive to MEK inhibitor (binimetinib), indicating that NRAS gain might be a new therapeutic target for melanoma.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2z5lLqQ

No overdiagnosis in the Norwegian Breast Cancer Screening Program estimated by combining record linkage and questionnaire information in the Norwegian Women and Cancer study

Publication date: January 2018
Source:European Journal of Cancer, Volume 89
Author(s): Eiliv Lund, Aurelie Nakamura, Jean-Christophe Thalabard
BackgroundThe Norwegian Breast Cancer Screening Program (NBCSP) was implemented across the country in 2005 and has been criticised for potential 'overdiagnosis', i.e. a breast cancer diagnosis that otherwise would not have been detected or treated in a woman's lifetime. We aimed to estimate overdiagnosis in the NBCSP based on the Norwegian Women and Cancer (NOWAC) study using both questionnaire information and record linkage information from NBCSP.MethodFor 124,978 women aged 49–79 years from the NOWAC study, information on screened women could be cross-validated from the NBCSP database. Based on information from the NOWAC questionnaire, unscreened women were further divided into those who had mammograms taken only outside the NBCSP and those who had never had taken a mammogram. Breast cancers diagnosed in 2005–2013 were identified through linkage to the Cancer Registry of Norway; in situ or DCIS 417; invasive 2845; combined 3262. Cumulative incidence rates (CIRs) for ages 49–79 years of breast cancer were compared using the log-rank test.ResultsAfter exclusion of women with a family history of breast cancer, screened women had a CIR of 9.7% for combined breast cancer, non-significantly lower compared with unscreened women. Screened women had a 1.1% increased CIR or 13.0% increased relative risk of breast cancer diagnosis (significant) compared with women who had never had a mammogram, but for invasive breast cancer alone the difference was reduced to −0.2% (95% CI: −9.1; 8.8). Invasive breast cancers were significantly smaller (<2.5 cm) in screened versus unscreened women. There was a borderline significant decrease in lymph node positive cancer among screened (p = 0.06).ConclusionThe findings of no significant overdiagnosis combined with smaller tumours and less lymph node metastases suggest that the prevailing view of overdiagnosis in the NBCSP should be challenged.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2z6fhbw

Comparison of published and unpublished phase I clinical cancer trials: an analysis of the CliniclTrials.gov database

Summary

Introduction The role of phase I cancer trials is constantly evolving and they are increasingly being used in 'go/no' decisions in drug development. As a result, there is a growing need to ensure trials are published when completed. There are limited data on the publication rate and the factors associated with publication in phase I trials. Methods The ClinicalTrials.gov database was searched for completed adult phase I cancer trials with reported results. PubMed was searched for matching publications published prior to April 1, 2017. Logistic regression was used to identify factors associated with unpublished trials. Linear regression was used to explore factors associated with time lag from study database lock to publication for published trials. Results The study cohort included 319 trials. 95 (30%) trials had no matching publication. Thirty (9%) trials were not published in abstract form as well. On multivariable analysis, the most significant factor associated with unpublished trials was industry funding (odds ratio 3.3, 95% confidence interval 1.7-6.6, p=0.019). For published trials, time lag between database lock and publication was longer by 10.9 months (standard error 3.6, p<0.001) for industry funded trials compared with medical center funded trials. Conclusions Timely publishing of early cancer clinical trials results remains unsatisfactory. Industry funded phase I cancer trials were more likely to remain unpublished, and were associated with a longer time lag from database lock to publication. Policies that promote transparency and data sharing in clinical trial research might improve accountability among industry and investigators and improve timely results publication.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2ykout7

Correction to: FDG uptake in cervical lymph nodes in children without head and neck cancer

Abstract

The original version of this article unfortunately contained a mistake. Author name Alaa Bakkari was incorrect. The correct spelling is given above.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2BXuuu4

Single-staged implant placement using bone ring technique with and without membrane placement: An experimental study in the Beagle dog

Abstract

Aim

To evaluate the impact of a collagen membrane on bone remodeling and osseointegration of implants placed simultaneously with a bone ring technique.

Material and Methods

Standardized, vertical alveolar bone defects in the mandibles of six dogs were created. Tapered dental implants designed for two-stage subcrestal placement were inserted simultaneously with a bone ring technique. On one side of the mandible, the augmented sites were covered with a collagenous membrane. Implants with (M Group) and without membranes (NM Group) were left for an osseointegration period of 3 and 6 months, respectively. Block biopsies of the implants with surrounding bone were harvested and analyzed histologically.

Results

Implant exposure was a common finding (2/3) concomitantly with loss of healing caps. It appeared to be related to advanced bone loss around the implants. Exposure of implants was more frequent in M Group, however, without significant differences when compared to NM Group. The total bone area within the region of the bone ring was greater in the NM Group compared to the M Group. Moreover, in the region of the pristine bone of the M Group, the total bone was greater than at the corresponding NM Group sites at both observation periods. A nonparametric analysis of variance (ANOVA) revealed no significant effects of membrane placement or healing period on the total area of the bone. The total bone-to-implant contact (BIC) for the two groups was similar at each observation time point. However, BIC increased significantly at 6-month compared with 3-month observation period (p = .0088) in both groups.

Conclusions

In vertical bone augmentation applying the bone ring technique, the disruption of soft tissue was a frequent complication. Membrane placement yielded no significant advantage on the osseointegration (BIC) of implants or bone characteristics.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AhV4NN

Etiology of isolated pontine infarctions: a study based on high-resolution MRI and brain small vessel disease scores

In this retrospective study, we investigated the main pathogenesis of the two types of isolated pontine infarction: paramedian pontine infarcts (PPIs) and small deep pontine infarcts (SDPIs).

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nSSwnA

Autologous dendritic cells pulsed with allogeneic tumor cell lysate in mesothelioma: From mouse to human

Purpose: Mesothelioma has been regarded as a non-immunogenic tumor, which is also shown by the low response rates to treatments targeting the PD-1/PD-L1 axis.  Previously, we demonstrated that autologous tumor lysate-pulsed dendritic cell (DC) immunotherapy increased T-cell response towards malignant mesothelioma. However, the use of autologous tumor material hampers implementation in large clinical trials, which might be overcome by using allogeneic tumor cell lines as tumor antigen source.  The purpose of this study was to investigate if allogeneic lysate pulsed DC immunotherapy is effective in mice and safe in humans. Experimental Design: Firstly, in two murine mesothelioma models, mice were treated with autologous DCs pulsed with either autologous or allogeneic tumor lysate, or injected with PBS (negative control). Survival and tumor-directed T cell responses of these mice were monitored.  Results were taken forward in a first-in-human clinical trial, in which 9 patients were treated with 10, 25 or 50 million DC per vaccination. DC vaccination consisted of autologous monocyte-derived DC pulsed with tumor lysate from 5 mesothelioma cell lines. Results: In mice, allogeneic lysate-pulsed DC immunotherapy induced tumor-specific T cells and led to an increased survival, to a similar extent as DC immunotherapy with autologous tumor lysate. In the first-in-human clinical trial, no dose limiting toxicities were established and radiographic responses were observed. Median PFS was 8.8 months (95% CI 4.1-20.3) and median OS not reached (median follow up 22.8 months). Conclusions: DC immunotherapy with allogeneic tumor lysate is effective in mice and safe and feasible in humans.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2iUy00C

Clinical significance of PD-L1+ exosomes in plasma of Head and Neck Cancer patients

Purpose: The microenvironment of head and neck squamous cell carcinomas (HNSCCs) is highly immunosuppressive. HNSCCs expressing elevated levels of PD-L1 have especially poor outcome. Exosomes that carry PD-L1 and suppress T-cell functions have been isolated from plasma of patients with HNSCC. The potential contributions of PD-L1+ exosomes to immune suppression and disease activity are evaluated. Methods: Exosomes isolated from plasma of 40 HNSCC patients by size exclusion chromatography were captured on beads using anti-CD63 Abs, stained for PD-1 and PD-L1 and analyzed by flow cytometry. The percentages and mean fluorescence intensities (MFIs) of PD-L1+ and PD-1+ exosome/bead complexes were correlated with the patients' clinicopathological data. PD-L1high or PD-L1low exosomes were incubated with activated CD69+ human CD8+ T-cells ± PD-1 inhibitor. Changes in CD69 expression levels on T cells were measured. Patients' plasma was tested for soluble PD-L1 (sPD-L1) by ELISA. Results: Levels of PD-L1 carried by exosomes correlated with patients' disease activity, the UICC stage and the lymph node status (p= 0.0008-0.013). In contrast, plasma levels of sPD-L1 or exosome PD-1 levels did not correlate with any clinicopathological parameters. CD69 expression levels were inhibited (p<0.03) by co-incubation with PD-L1high but not by PD-L1low exosomes. Blocking of PD-L1+ exosome signaling to PD-1+ T cells attenuated immune suppression. Conclusions: PD-L1 levels on exosomes, but not levels of sPD-L1, associated correlate with disease progression in HNSCC patients. Circulating PD-L1+ exosomes emerge as useful metrics of disease and immune activity in HNSCC patients.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2Bgre01

Neddylation blockade diminishes hepatic metastasis by dampening cancer stem-like cells and angiogenesis in uveal melanoma

Purpose: Liver metastasis is the major and direct cause of death in patients with uveal melanoma (UM). There is no effective therapy for patients with metastatic UM. Improved treatments of hepatic metastatic patients with UM were urgently needed. Inspired by readily detectable key components in neddylation pathway in UM cells, we aimed at exploring whether neddylation pathway was a therapeutic target for liver metastatic UM. Experimental Design: Expression of key proteins in neddylation pathway in UM was detected by Western blotting, real-time quantitative RT-PCR (qRT-PCR), and immunohistochemical staining. Cellular proliferation, apoptosis, cell cycle, migration, and cancer stem-like cells (CSCs) properties were examined upon treatment with MLN4924, a potent and selective NAE inhibitor. Antitumor activity and frequency of CSCs were determined by using NOD-SCID mouse xenograft model. Liver metastasis was evaluated by use of a NOD-scid-IL2Rg–(NSI) mouse model. Results: NAE1 expression was readily detectable in UM. Inhibition of neddylation pathway by MLN4924 repressed the CSCs properties in UM [capacities of tumorsphere formation and serially-replating, aldehyde dehydrogenase positive (ALDH+) cells, and frequency of CSCs] through Slug protein degradation. MLN4924 treatment disturbed the paracrine secretion of NF-B-mediated VEGF-C and its dependent angiogenesis. The inhibitory effect of neddylation blockade on proliferation which was confirmed by xenografted UM tumor in NOD-SCID mice was involved in activation of ATM-Chk1-Cdc25C DNA damage response, and G2/M-phase arrest. Neddylation inhibition profoundly inhibited hepatic metastasis in UM. Conclusions: Our studies validate the neddylation pathway as a promising therapeutic target for the treatment of patients with hepatic metastasis of UM.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2iYf6Gk

Single-cell RNA-seq reveals a subpopulation of prostate cancer cells with enhanced cell cycle-related transcription and attenuated androgen response

Increasing evidence suggests the presence of minor cell subpopulations in prostate cancer that are androgen independent and poised for selection as dominant clones after androgen-deprivation therapy. In this study, we investigated this phenomenon by stratifying cell subpopulations based on transcriptome profiling of 144 single LNCaP prostate cancer cells treated or untreated with androgen after cell cycle synchronization. Model-based clustering of 397 differentially expressed genes identified eight potential subpopulations of LNCaP cells, revealing a previously unappreciable level of cellular heterogeneity to androgen stimulation. One subpopulation displayed stem-like features with a slower cell doubling rate, increased sphere formation capability, and resistance to G2/M arrest induced by a mitosis inhibitor. Advanced growth of this subpopulation was associated with enhanced expression of 10 cell cycle-related genes (CCNB2, DLGAP5, CENPF, CENPE, MKI67, PTTG1, CDC20, PLK1, HMMR, and CCNB1) and decreased dependence upon androgen receptor signaling. In silico analysis of RNA-seq data from The Cancer Genome Atlas (TCGA) further demonstrated that concordant upregulation of these genes was linked to recurrent prostate cancers. Analysis of receiver-operating characteristic curves implicates aberrant expression of these genes and could be useful for early identification of tumors that subsequently develop biochemical recurrence. Moreover, this single-cell approach provides a better understanding of how prostate cancer cells respond heterogeneously to androgen-deprivation therapies and reveals characteristics of subpopulations resistant to this treatment.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2yjQooU

Targeting CDK6 and BCL2 exploits the "MYB addiction" of Ph+ acute lymphoblastic leukemia

Philadelphia Chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is currently treated with BCR-ABL1 tyrosine kinase inhibitors (TKI) in combination with chemotherapy. However, most patients develop resistance to TKI through BCR-ABL1-dependent and -independent mechanisms. Newly developed TKI can target Ph+ ALL cells with BCR-ABL1-dependent resistance; however, overcoming BCR-ABL1-independent mechanisms of resistance remains challenging because transcription factors (TF), which are difficult to inhibit, are often involved. We show here that: i) the growth of Ph+ ALL cell lines and primary cells is highly dependent on MYB-mediated transcriptional upregulation of CDK6, cyclin D3, and BCL2 and ii) restoring their expression in MYB-silenced Ph+ ALL cells rescues their impaired proliferation and survival. Levels of MYB and CDK6 were highly correlated in adult Ph+ ALL (p=0.00008). Moreover, Ph+ ALL cells exhibited a specific requirement for CDK6 but not CDK4 expression, most likely because, in these cells, CDK6 was predominantly localized in the nucleus while CDK4 was almost exclusively cytoplasmic. Consistent with their essential role in Ph+ ALL, pharmacological inhibition of CDK6 and BCL2 markedly suppressed proliferation, colony formation, and survival of Ph+ ALL cells ex vivo and in mice. In summary, these findings provide a proof-of-principle, rational strategy to target the MYB "addiction" of Ph+ ALL.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2AA1YlO