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Beta-amyloid pathology in human brain microvessel extracts from the parietal cortex: relation with cerebral amyloid angiopathy and Alzheimer’s disease

Abstract

Several pieces of evidence suggest that blood–brain barrier (BBB) dysfunction is implicated in the pathophysiology of Alzheimer's disease (AD), exemplified by the frequent occurrence of cerebral amyloid angiopathy (CAA) and the defective clearance of Aβ peptides. However, the specific role of brain microvascular cells in these anomalies remains elusive. In this study, we validated by Western, ELISA and immunofluorescence analyses a procedure to generate microvasculature-enriched fractions from frozen samples of human cerebral cortex. We then investigated Aβ and proteins involved in its clearance or production in microvessel extracts generated from the parietal cortex of 60 volunteers in the Religious Orders Study. Volunteers were categorized as AD (n = 38) or controls (n = 22) based on the ABC scoring method presented in the revised guidelines for the neuropathological diagnosis of AD. Higher ELISA-determined concentrations of vascular Aβ40 and Aβ42 were found in persons with a neuropathological diagnosis of AD, in apoE4 carriers and in participants with advanced parenchymal CAA, compared to respective age-matched controls. Vascular levels of two proteins involved in Aβ clearance, ABCB1 and neprilysin, were lower in persons with AD and positively correlated with cognitive function, while being inversely correlated to vascular Aβ40. In contrast, BACE1, a protein necessary for Aβ production, was increased in individuals with AD and in apoE4 carriers, negatively correlated to cognitive function and positively correlated to Aβ40 in microvessel extracts. The present report indicates that concentrating microvessels from frozen human brain samples facilitates the quantitative biochemical analysis of cerebrovascular dysfunction in CNS disorders. Data generated overall show that microvessels extracted from individuals with parenchymal CAA–AD contained more Aβ and BACE1 and less ABCB1 and neprilysin, evidencing a pattern of dysfunction in brain microvascular cells contributing to CAA and AD pathology and symptoms.

http://bit.ly/2RKc0Vh

Medical Education Texts

Objective Skills Clinical Examination: Every Day in the Field of Practice

https://www.amazon.co.uk/Objective-Skills-Clinical-Examination-Practice/dp/1980880417

Assessing Competence in Medicine and Other Health Professions

https://www.crcpress.com/Assessing-Competence-in-Medicine-and-Other-Health-Professions/Violato/p/book/9781498785082

Field dependence–independence differently affects retrospective time estimation and flicker-induced time dilation

Abstract

Field dependence–independence (FDI) is a stable dimension of individual functioning, transversal to different cognitive domains. While the role of some individual variables in time perception has received considerable attention, it is not clear whether and how FDI influences timing abilities. In this study, we tested the hypothesis that FDI differently affects timing performance depending on whether the task requires cognitive restructuring. Participants were assessed for FDI using the embedded figures test (EFT). They performed a prospective timing task, reproducing the duration of a flickering stimulus, and a retrospective timing task, estimating the duration of the task. We expected performance of field-dependent (FD) and field-independent (FI) individuals not to differ in the prospective task, since restructuring of task material is not needed to reproduce the stimulus duration. Conversely, we predicted that FI individuals should be more accurate than FD ones in the retrospective condition, involving restructuring skills. Results show that while both FD and FI individuals under-reproduced the stimulus duration in the prospective task, only FD participants significantly underestimated the duration of the timing task in the retrospective condition. These results suggest that differences across FD and FI individuals are apparent in timing only when the task requires high-level cognitive processing; conversely, these differences do not affect basic sensory processing.

http://bit.ly/2St6yKX

Kindlin is mechanosensitive: A force-induced conformational switch mediates crosstalk among integrins

Mechanical stresses directly regulate the function of several proteins of the integrin-mediated focal adhesion complex as they experience intra- and extra-cellular forces. Kindlin is a largely overlooked member of the focal adhesion complex whose roles in cellular mechanotransduction are only recently being identified. Recent crystallographic experiments have revealed that kindlins can form dimers that bind simultaneously to two integrins providing a mechanistic explanation of how kindlins may promote integrin activation and clustering.

http://bit.ly/2RLLRoW

Protection from EAE in DOCK8 mutant mice occurs despite increased Th17 cell frequencies in the periphery

Abstract

Mutation of Dedicator of cytokinesis 8 (DOCK8) has previously been reported to provide resistance to the Th17 cell dependant experimental autoimmune encephalomyelitis (EAE) in mice. Contrary to expectation, we observed an elevation of Th17 cells in two different DOCK8 mutant mouse strains in the steady state. This was specific for Th17 cells with no change in Th1 or Th2 cell populations. In vitro T helper cell differentiation assays revealed that the elevated Th17 cell population was not due to a T cell intrinsic differentiation bias. Challenging these mutant mice in the EAE model, we confirmed a resistance to this autoimmune disease with Th17 cells remaining elevated systemically while cellular infiltration in the central nervous system (CNS) was reduced. Infiltrating T cells lost the bias towards Th17 cells indicating a relative reduction of Th17 cells in the CNS and a Th17 cell specific migration disadvantage. Adoptive transfers of Th1 and Th17 cells in EAE‐affected mice further supported the Th17 cell‐specific migration defect, however, DOCK8‐deficient Th17 cells expressed normal Th17 cell‐specific CCR6 levels and migrated towards chemokine gradients in transwell assays. This study shows that resistance to EAE in DOCK8 mutant mice is achieved despite a systemic Th17 bias.

This article is protected by copyright. All rights reserved

http://bit.ly/2GdY3xo

In Response

No abstract available

http://bit.ly/2GsZ2cA

A Multivariable Model Predictive of Unplanned Postoperative Intubation in Infant Surgical Patients

BACKGROUND: Unplanned postoperative intubation is an important quality indicator, and is associated with significantly increased mortality in children. Infant patients are more likely than older pediatric patients to experience unplanned postoperative intubation, yet the literature provides few characterizations of this outcome in our youngest patients. The objective of this study was to identify risk factors for unplanned postoperative intubation and to develop a scoring system to predict this complication in infants undergoing major surgical procedures. METHODS: In this retrospective cohort study, The National Surgical Quality Improvement Program-Pediatric database was surveyed for all infants who underwent noncardiac surgery between January 1, 2012 and December 31, 2015 (derivation cohort, n = 56,962) and between January 1 and December 31, 2016 (validation cohort, n = 20,559). Demographic and perioperative clinical characteristics were examined in association with our primary outcome of unplanned postoperative intubation within 30 days of surgery. Risk factors were analyzed in the derivation cohort (2012–2015 data) using multivariable logistic regression with stepwise selection. Parameters from the final model were used to create a scoring system for predicting unplanned postoperative intubation. Data from the validation cohort were utilized to assess the performance of the scoring system using the area under the receiver operating characteristic curve. RESULTS: In the derivation cohort, 2.2% of the infants experienced unplanned postoperative intubation within 30 days of surgery. Of the 14 risk factors identified in multivariable analysis, 10 (age, prematurity, American Society of Anesthesiologists physical status, inpatient status, operative time >120 minutes, cardiac disease, malignancy, hematologic disorder, oxygen supplementation, and nutritional support) were included in the final multivariable logistic regression model to create the risk score. The area under the receiver operating characteristic curve of the final model was 0.86 (95% CI, 0.85–0.87) for the derivation cohort and 0.83 (95% CI, 0.82–0.85) for the validation cohort. CONCLUSIONS: About 1 in 50 infants undergoing major surgical procedures experiences unplanned postoperative intubation. Our scoring system based on routinely collected perioperative assessment data can predict risk in infants with good accuracy. Further investigation should assess the clinical utility of the scoring system for risk stratification and improvement in perioperative care quality and patient outcomes. Accepted for publication December 20, 2018. Funding: L.D.E. is supported by an institutional training grant from the National Institutes of Health, T32GM008464-26. M.K. is supported by the National Center for Advancing Translational Sciences, National Institutes of Health through Grant Number KL2TR001874. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. 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://bit.ly/KegmMq). Reprints will not be available from the authors. Address correspondence to Lisa D. Eisler, MD, Department of Anesthesiology, Columbia University Medical Center, 622 W 168th St, PH 5, Suite 505C, New York, NY 10032. Address e-mail to LDL2113@cumc.columbia.edu. © 2019 International Anesthesia Research Society

http://bit.ly/2Sdi263

Cataract Surgery: When the Eyes Are Bigger Than the Stomach

No abstract available

http://bit.ly/2GuFpRw

Effectiveness of Magnesium in Preventing Shivering in Surgical Patients: A Systematic Review and Meta-analysis

BACKGROUND: Clinical trials regarding the antishivering effect of perioperative magnesium have produced inconsistent results. We conducted a systematic review and meta-analysis with Trial Sequential Analysis to evaluate the effect of perioperative magnesium on prevention of shivering. METHODS: We searched PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, and 2 registry sites for randomized clinical trials that compared the administration of magnesium to a placebo or no treatment in patients undergoing surgeries. The primary outcome of this meta-analysis was the incidence of shivering. The incidence of shivering was combined as a risk ratio with 95% CI using a random-effect model. The effect of the route of administration was evaluated in a subgroup analysis, and Trial Sequential Analysis with a risk of type 1 error of 5% and power of 90% was performed. The quality of each included trial was evaluated, and the quality of evidence was assessed using the Grading of Recommendation Assessment, Development, and Evaluation approach. We also assessed adverse events. RESULTS: Sixty-four trials and 4303 patients (2300 and 2003 patients in magnesium and control groups, respectively) were included. The overall incidence of shivering was 9.9% in the magnesium group and 23.0% in the control group (risk ratio, 0.42; 95% CI, 0.33–0.52). Subgroup analysis revealed that the incidence of shivering was lower with IV (risk ratio, 0.29; 95% CI, 0.29–0.54; Grading of Recommendation Assessment, Development, and Evaluation, moderate), epidural (risk ratio, 0.24; 95% CI, 0.13–0.43; Grading of Recommendation Assessment, Development, and Evaluation, low), and intrathecal administration (risk ratio, 0.64; 95% CI, 0.43–0.96; Grading of Recommendation Assessment, Development, and Evaluation, moderate). Only trials with low risk of bias were included for Trial Sequential Analysis. The Z-cumulative curve for IV magnesium crossed the Trial Sequential Analysis monitoring boundary for benefit even though only 34.9% of the target sample size had been reached. The Z-cumulative curve for epidural or intrathecal administration did not cross the Trial Sequential Analysis monitoring boundary for benefit. No increase in adverse events was reported. CONCLUSIONS: Perioperative IV administration of magnesium effectively reduced shivering and Trial Sequential Analysis suggested that no more trials are required to confirm that IV magnesium effectively reduces shivering. Accepted for publication December 12, 2018. Funding: This study was supported by funding from the Department of Anesthesiology, Yokohama City University, Yokohama, Japan. 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://bit.ly/KegmMq). Trial registry number: CRD42018083337 (PROSPERO). URL: http://bit.ly/2Gu1mjl. Reprints will not be available from the authors. Address correspondence to Hiromasa Kawakami, MD, Department of Anesthesiology, Yokohama City University Medical Center, Urafunecho 4-57 Minamiku Yokohama, Kanagawa 232-0024, Japan. Address e-mail to hiro.k210@gmail.com. © 2019 International Anesthesia Research Society

http://bit.ly/2Sc7hka

Perioperative Care for Adolescents Undergoing Major Surgery: A Biopsychosocial Conceptual Framework

No abstract available

http://bit.ly/2GqT9MU

American Society for Enhanced Recovery and Perioperative Quality Initiative-4 Joint Consensus Statement on Persistent Postoperative Opioid Use: Definition, Incidence, Risk Factors, and Health Care System Initiatives

Persistent postoperative opioid use is thought to contribute to the ongoing opioid epidemic in the United States. However, efforts to study and address the issue have been stymied by the lack of a standard definition, which has also hampered efforts to measure the incidence of and risk factors for persistent postoperative opioid use. The objective of this systematic review is to (1) determine a clinically relevant definition of persistent postoperative opioid use, and (2) characterize its incidence and risk factors for several common surgeries. Our approach leveraged a group of international experts from the Perioperative Quality Initiative-4, a consensus-building conference that included representation from anesthesiology, surgery, and nursing. A search of the medical literature yielded 46 articles addressing persistent postoperative opioid use in adults after arthroplasty, abdominopelvic surgery, spine surgery, thoracic surgery, mastectomy, and thoracic surgery. In opioid-naive patients, the overall incidence ranged from 2% to 6% based on moderate-level evidence. However, patients who use opioids preoperatively had an incidence of >30%. Preoperative opioid use, depression, factors associated with the diagnosis of substance use disorder, preoperative pain, and tobacco use were reported risk factors. In addition, while anxiety, sex, and psychotropic prescription are associated with persistent postoperative opioid use, these reports are based on lower level evidence. While few articles addressed the health policy or prescriber characteristics that influence persistent postoperative opioid use, efforts to modify prescriber behaviors and health system characteristics are likely to have success in reducing persistent postoperative opioid use. Accepted for publication October 16, 2018. The authors declare no conflicts of interest. Funding: The PeriOperative Quality Initiative (POQI)-4 consensus conference was supported by unrestricted educational grants from the American Society for Enhanced Recovery (ASER) and the POQI, which have received grants from Baxter, Bev MD, Cadence, Cheetah Medical, Edwards, Heron Pharmaceutical, Mallinckrodt, Medtronic, Merck, Pacira, and Trevena. 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://bit.ly/KegmMq). Please see Supplemental Digital Content, Appendix 1, http://bit.ly/2GxzQ4N, for a list of the POQI-4 Workgroup members. Reprints will not be available from the authors. Address correspondence to Michael L. Kent, MD, Department of Anesthesiology, Duke University Medical Center, 3094 #4, Durham, NC 27710. Address e-mail to Michael.kent@duke.edu. © 2019 International Anesthesia Research Society

http://bit.ly/2Sdhq0f

I Tweet, Therefore I Learn: An Analysis of Twitter Use Across Anesthesiology Conferences

BACKGROUND: Twitter in anesthesiology conferences promotes rapid science dissemination, global audience participation, and real-time updates of simultaneous sessions. We designed this study to determine if an association exists between conference attendance/registration and 4 defined Twitter metrics. METHODS: Using publicly available data through the Symplur Healthcare Hashtags Project and the Symplur Signals, we collected data on total tweets, impressions, retweets, and replies as 4 primary outcome metrics for all registered anesthesiology conferences occurring from May 1, 2016 to April 30, 2017. The number of Twitter participants, defined as users who contributed a tweet, retweet, or reply 3 days before through 3 days after the conference, was collected. We also collected influencer data as determined by mentions (number of times a user is referenced). Two authors independently verified the categories for influencers assigned by Symplur. Conference demographic data were obtained by e-mail inquiries. Associations between meeting attendees/registrants and Twitter metrics, between Twitter participants and the metrics, and between physician influencers and Twitter participants were tested using Spearman rho. RESULTS: Fourteen conferences with 63,180 tweets were included. With the American Society of Anesthesiologists annual meeting included, the correlations between meeting attendance/registration and total tweets (rs = 0.588; P = .074), impressions (rs = 0.527; P = .117), and retweets (rs = 0.539; P = .108) were not statistically significant; for replies, it was moderately positive (rs = 0.648; P = .043). Without the American Society of Anesthesiologists annual meeting, total tweets (rs = 0.433; P = .244), impressions (rs = 0.350; P = .356), retweets (rs = 0.367; P = .332), and replies (rs = 0.517; P = .154) were not statistically significant. Secondary outcomes include a highly positive correlation between Twitter participation and total tweets (rs = 0.855; P

http://bit.ly/2Gpo10p

Contemplating Our Maternity Care Crisis in the United States: Reflections of an Obstetrician Anesthesiologist

No abstract available

http://bit.ly/2GuFnJo

High-Flow Nasal Oxygen Improves Safe Apnea Time in Morbidly Obese Patients Undergoing General Anesthesia: A Randomized Controlled Trial

BACKGROUND: Morbidly obese patients undergoing general anesthesia are at risk of hypoxemia during anesthesia induction. High-flow nasal oxygenation use during anesthesia induction prolongs safe apnea time in nonobese surgical patients. The primary objective of our study was to compare safe apnea time, between patients given high-flow nasal oxygenation or conventional facemask oxygenation during anesthesia induction, in morbidly obese surgical patients. METHODS: Research ethics board approval was obtained. Elective surgical patients ≥18 years with body mass index ≥40 kg·m−2 were included. Patients with severe comorbidity, gastric reflux disease, known difficult airway, or nasal obstruction were excluded. After obtaining informed consent patients were randomized. In the intervention (high-flow nasal oxygenation) group, preoxygenation was provided by 100% nasal oxygen for 3 minutes at 40 L·minute−1; in the control group, preoxygenation was delivered using a facemask with 100% oxygen, targeting end-tidal O2 >85%. Anesthesia was induced with propofol, remifentanil, and rocuronium. Bag-mask ventilation was not performed. At 2 minutes after rocuronium, videolaryngoscopy was performed. If the laryngoscopy grade was I or II, laryngoscope was left in place and the study was continued; if grade III or IV was observed, the patient was excluded from the study. During the apnea period, high-flow nasal oxygenation patients received nasal oxygen at 60 L·minute−1; control group patients received no supplemental oxygen. The primary outcome, safe apnea time, was reached when oxygen saturation measured by pulse oximetry (SpO2) fell to 95% or maximum 6 minutes of apnea. The patient was then intubated. T tests and χ2 analyses were used to compare groups. P

http://bit.ly/2SjuqBh

Questions About the Study by Said Et Al

No abstract available

http://bit.ly/2GxzLy1

Effect of integrated urban and rural residents medical insurance on the utilisation of medical services by residents in China: a propensity score matching with difference-in-differences regression approach

Objectives

In this study, we aim to evaluate the effect of urban and rural resident medical insurance scheme (URRMI) on the utilisation of medical services by urban and rural residents in the four pilot provinces.

Setting and participants

The sample used in this study is 13 305 individuals, including 2620 in the treatment group and 10 685 in the control group, from the 2011 and 2015 surveys of China Health and Retirement Longitudinal Study.

Outcome measures

Propensity score matching and difference-in-differences regression approach (PSM-DID) is used in the study. First, we match the baseline data by using kernel matching. Then, the average treatment effect of the four outcome variables are analysed by using the DID model. Finally, the robustness of the PSM-DID estimation is tested by simple model and radius matching.

Results

Kernel matching have improved the overall balance after matching. The URRMI policy has significantly reduced the need-but-not outpatient care and significantly increased outpatient care cost and inpatient care cost for rural residents, with DID value of –0.271, 0.090 and 0.256, respectively. After robustness test, the DID competing results of four outcome variables are consistent.

Conclusions

URRMI has a limited effect on the utilisation of medical and health services by all residents, but the effect on rural residents is obvious. The government should establish a unified or income-matching payment standard to prevent, control the use of medical insurance funds and increase its efforts to implement URRMI integration in more regions to improve overall fundraising levels.

http://bit.ly/2Gfb223

The China Patient-centred Evaluative Assessment of Cardiac Events (PEACE) prospective heart failure study design

Introduction

China faces the prospect of a large growth in the prevalence of heart failure (HF). However, there is limited knowledge about outcomes in patients after HF hospitalisations, including patient-reported outcomes (PROs). This paper is to present the study goal, methodology and data collection of the China Patient-centred Evaluative Assessment of Cardiac Events Prospective Heart Failure Study (China PEACE 5p-HF Study).

Methods and analysis

The China PEACE 5p-HF Study, a prospective cohort study, will enrol 5000 patients with HF during 2016–2018 from 52 diverse hospitals throughout China and the follow-up period will be 12 months. Information on patients' medical history, in-hospital treatment and in-hospital outcomes are being abstracted from medical records. Details of patients' demographics, socioeconomic status, cardiovascular risk factors, access to healthcare services are being collected through comprehensive baseline interviews. Generic and disease-specific health status, depression, stress, anxiety and cognitive function are being administered using validated PRO instruments. Follow-up interviews will capture PROs and hospitalisation events at 1, 6 and 12 months follow-up. Standardised transthoracic echocardiograms and 6 min walk tests are being done in patients who enrolled in hospitals with these facilities at baseline and at 1 and 12 months after discharge. Collection of blood and urine samples are also being conducted at baseline, 1 and 12 months follow-up and stored for future analyses.

Ethics and dissemination

The National Center for Cardiovascular Diseases/Fuwai Hospital ethics committee approved this study, and all collaborating hospitals received approval from their local ethics committee. Written informed consent will be obtained from all patients. Findings will be disseminated in future peer-reviewed papers and will help to support improvements in the quality of care for HF nationwide.

Trial registration number

NCT02878811.

http://bit.ly/2HUfYuR

Core and optional infant and young child feeding indicators in Sub-Saharan Africa: a cross-sectional study

Objective

The objective of the study is to determine the status of infant and young child feeding (IYCF) in Sub-Saharan Africa (SSA) based on multiple indicators.

Design

Secondary data analysis of 32 Demographic and Health Surveys conducted in SSA since 2010.

Setting

Thirty-two countries in SSA.

Participants

151 575 infants and young children born in the preceding 2 years of the surveys.

Indicators determined

Eight core and six optional IYCF indicators.

Results

Majority (95.8%) of the children born in the preceding 24 months were ever breastfed, and 50.5% initiated breastfeeding within the first hour of birth. Among infants 0–5 months of age, 72.3% were predominantly breastfed and 41.0% were exclusively breastfed. Continued breastfeeding at 1 year (89.5%) was reasonably high, but only 53.7% continued breastfeeding at 2 years and 60.4% had age-appropriate breastfeeding. About two-thirds (69.3%) of infants 6–8 months of age received solid, semisolid or soft food over the previous day across the countries. Among children 6–23 months of age, 41.9% met the minimum recommended meal frequency, while smaller proportions satisfied the minimum dietary diversity (21.0%) and acceptable diet (9.8%). About one-third (37.6%) of children 6–23 months of age consumed iron-rich or iron-fortified food over the previous day. Among non-breastfed children, only 15.0% received the recommended two or more milk feedings. Thirteen per cent were fed with a bottle with a nipple in the previous day. Country-level estimates for most indicators showed remarkable variations. Yet the minimum dietary diversity and acceptable diet indicators were consistently low.

Conclusion

Most breastfeeding-related indicators, except exclusive and early initiation of breastfeeding, are in an acceptable level in SSA. However, complementary feeding indicators are generally low.

http://bit.ly/2GfaZmT

Mat Pilates and aquatic aerobic exercises for women with fibromyalgia: a protocol for a randomised controlled blind study

Introduction

Physical exercises have been recommended to improve the overall well-being of patients with fibromyalgia, with the main objective of repairing the effects of lack of physical conditioning and of improving the symptoms, especially pain and fatigue. Although widely recommended and widely known, few studies support the use of Pilates as an effective method in improving the symptoms of the disease, comparing it with other well-founded exercise modalities. This protocol was developed to describe the design of a randomised controlled study with a blind evaluator that evaluates the effectiveness of mat Pilates, comparing it with aquatic aerobic exercises, in improving pain in women with fibromyalgia.

Methods

Sixty women aged 18–60 years with a diagnosis of fibromyalgia, with a score of between 3 and 8 points on the Visual Analogue Scale for pain, and who sign the clear and informed consent form will be recruited according to the inclusion criteria. They will be randomised into one of the two intervention groups: (1) Pilates, to perform an exercise programme based on mat Pilates; and (2) aquatic exercise, to participate in a programme of aerobic exercises in the swimming pool. The protocol will correspond to 12 weeks of treatment, with both groups performing the exercises with supervision twice a week. The primary outcome will be pain (Visual Analogue Scale for pain). The secondary outcomes are to include impact related to the disease, functional capacity, sleep quality and overall quality of life. The evaluations will be performed at three points: at baseline and after 6 weeks and 12 weeks of treatment.

Ethics and dissemination

This protocol has been approved by the Ethics Committee of FACISA/UFRN (number: 2.116.314). Data collection will begin after approval by the ethics committee. There will be prior contact with the women, at which time all the information about the study and the objectives will be presented, as well as resolution no 466/2012 of the National Health Council of Brazil for the year 2012, which provides guidelines and regulatory standards for research involving human beings. Participants must sign the informed consent form before the study begins.

Trial registration number

NCT03149198.

http://bit.ly/2HXzNBy

Tramadol/dexketoprofen (TRAM/DKP) compared with tramadol/paracetamol in moderate to severe acute pain: results of a randomised, double-blind, placebo and active-controlled, parallel group trial in the impacted third molar extraction pain model (DAVID study)

Objectives

To compare efficacy/safety of oral tramadol 75 mg/dexketoprofen 25 mg (TRAM/DKP) and TRAM 75 mg/paracetamol 650 mg (TRAM/paracetamol) in moderate to severe pain following surgical removal of impacted lower third molar.

Design

Multicentre, randomised, double-blind, placebo-controlled, phase IIIb study.

Participants

Healthy adult patients scheduled for surgical extraction of at least one fully/partially impacted lower third molar requiring bone manipulation. 654 patients were randomised and 653 were eligible for analysis.

Interventions

Surgery was performed under local anaesthetic. No sedation was permitted. Patients rated pain intensity (PI) using an 11-Numerical Rating Scale (NRS) (0 no pain; 10 worst pain). Participants experiencing moderate/severe pain (≥4) within 4 hours of surgery were randomised (2:2:1 ratio) to a single oral dose of TRAM/DKP 75/25 mg, TRAM/paracetamol 75/650 mg or placebo.

Main outcome measures

Efficacy was based patients' electronic diaries. Analgesia and pain were recorded as follows: pain relief (PAR) on a 5-point Verbal Rating Scale (0='no relief', 1='a little (perceptible) relief', 2='some (meaningful) relief', 3='lot of relief', 4='complete relief') at the predefined postdose time points t15 min, t30 min, t1 hour, t1.5 hour, t2 hour, t4 hour, t6 hour and t8 hour and PI on the 11-point NRS at t0 and at the same predefined postdose time points. Onset of analgesia documented using double stopwatch method over a 2-hour period. Primary endpoint was total pain relief over 6 hours (TOTPAR6). Rescue medication was available during the treatment period.

Results

TRAM/DKP was superior to TRAM/paracetamol and placebo at the primary endpoint TOTPAR6 (p<0.0001). Mean (SD) TOTPAR6 in the TRAM/DKP group was 13 (6.97), while those in the active control and placebo groups were 9.1 (7.65) and 1.9 (3.89), respectively. Superiority of TRAM/DKP over active comparator and placebo was observed at all secondary endpoints. Incidence of adverse events was comparable between active groups.

Conclusions

TRAM/DKP (75/25 mg) is effective and superior to TRAM/paracetamol (75/650 mg) in relieving moderate to severe acute pain following surgical removal of impacted lower third molar, with a faster onset of action, greater and durable analgesia, together with a favourable safety profile.

Trial registration number

EudraCT 2015-004152-22 and NCT02777970.

http://bit.ly/2GfaTf1

Neuropsychiatric Genetics of African Populations-Psychosis (NeuroGAP-Psychosis): a case-control study protocol and GWAS in Ethiopia, Kenya, South Africa and Uganda

Introduction

Schizophrenia and bipolar disorder account for a large proportion of the global burden of disease. Despite their enormous impact, little is known about their pathophysiology. Given the high heritability of schizophrenia and bipolar disorder, unbiased genetic studies offer the opportunity to gain insight into their neurobiology. However, advances in understanding the genetic architecture of schizophrenia and bipolar disorder have been based almost exclusively on subjects of Northern European ancestry. The Neuropsychiatric Genetics of African Populations-Psychosis (NeuroGAP-Psychosis) project aims to expand our understanding of the causes of schizophrenia and bipolar disorder through large-scale sample collection and analyses in understudied African populations.

Methods and analysis

NeuroGAP-Psychosis is a case-control study of 34 000 participants recruited across multiple sites within Ethiopia, Kenya, South Africa and Uganda. Participants will include individuals who are at least 18 years old with a clinical diagnosis of schizophrenia or bipolar disorder ('psychosis') or those with no history of psychosis. Research assistants will collect phenotype data and saliva for DNA extraction. Data on mental disorders, history of physical health problems, substance use and history of past traumatic events will be collected from all participants.

DNA extraction will take place in-country, with genotyping performed at the Broad Institute. The primary analyses will include identifying major groups of participants with similar ancestry using the computation-efficient programme single nucleotide polymorphisms (SNP) weights. This will be followed by a GWAS within and across ancestry groups.

Ethics and dissemination

All participants will be assessed for capacity to consent using the University of California, San Diego Brief Assessment of Capacity to Consent. Those demonstrating capacity to consent will be required to provide informed consent. Ethical clearances to conduct this study have been obtained from all participating sites. Findings from this study will be disseminated in publications and shared with controlled access public databases, such as the database of Genotypes and Phenotypes, dbGaP.

http://bit.ly/2I6D1m2

Pharmacological interventions for prevention and management of delirium in intensive care patients: a systematic overview of reviews and meta-analyses

Objectives

We assessed the evidence from reviews and meta-analyses of randomised clinical trials on the effects of pharmacological prevention and management of delirium in intensive care unit (ICU) patients.

Methods

We searched for reviews in July 2017 in: Cochrane Library, MEDLINE, Embase, Science Citation Index, BIOSIS Previews, CINAHL and LILACS. We assessed whether reviews were systematic according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and assessed the methodological quality using ROBIS.

Outcome measures

Primary outcomes: all-cause mortality, serious adverse events, prevention of delirium and management of delirium. Secondary outcomes: quality of life; non-serious adverse events and cognitive function.

Results

We included 378 reviews: 369 narrative reviews, eight semisystematic reviews which failed on a maximum of two arbitrary PRISMA criteria and one systematic review fulfilling all 27 PRISMA criteria. For the prevention of delirium, we identified the one systematic review and eight semisystematic reviews all assessing the effects of alpha-2-agonists. None found evidence of a reduction of mortality (systematic review RR 0.99, 95% CI 0.79 to 1.24). The systematic review and three semisystematic reviews found no evidence of an effect for the prevention of delirium (systematic review RR 0.85, 0.63 to 1.14). Conversely, four semisystematic reviews found a beneficial effect. Serious adverse events, quality of life, non-serious adverse events and cognitive function were not assessed. We did not identify any systematic or semisystematic reviews addressing other pharmacological interventions for the prevention of delirium. For the management of manifest delirium, we did not identify any systematic or semisystematic review assessing any pharmacological agents.

Conclusion

Based on systematic reviews, the evidence for the use of pharmacological interventions for prevention or management of delirium is poor or sparse. A systematic review with low risk of bias assessing the effects of pharmacological prevention of delirium and management of manifest delirium in ICU patients is urgently needed.

PROSPERO registration number

CRD42016046628.

http://bit.ly/2GdXZho

Intramural oesophageal abscess: an unusual complication of tonsillitis

Tonsillitis is an extremely common condition, usually it is self-limiting, of viral origin, and managed conservatively in general practice. Rarely patients require inpatient management, usually when bacterial infection is present or when the cause is virulent organisms such as Epstein Barr virus. Complications can be divided into non-suppurative; sepsis, scarlet fever, rheumatic fever, glomerulonephritis and Lemierres disease, and suppurative; quinsy, parapharyngeal abscess and retropharyngeal abscess, respectively. Anecdotally, there is concern that modern medical practice that counsels vigilance against overuse of antibiotics, could lead to increased complications of tonsillitis. We report a case of an otherwise healthy man who presented with dysphagia, odynophagia and neck pain following a sore throat. Despite antibiotic treatment he developed an intramural oesophageal abscess, to our knowledge, an unreported complication of tonsillitis.

http://bit.ly/2GqF3em

Peripheral Blood Mononuclear Cells Demonstrate Mitochondrial Damage Clearance During Sepsis

Objectives: Metabolic derangements in sepsis stem from mitochondrial injury and contribute significantly to organ failure and mortality; however, little is known about mitochondrial recovery in human sepsis. We sought to test markers of mitochondrial injury and recovery (mitochondrial biogenesis) noninvasively in peripheral blood mononuclear cells from patients with sepsis and correlate serial measurements with clinical outcomes. Design: Prospective case-control study. Setting: Academic Medical Center and Veterans Affairs Hospital. Patients: Uninfected control patients (n = 20) and septic ICU patients (n = 37). Interventions: Blood samples were collected once from control patients and serially with clinical data on days 1, 3, and 5 from septic patients. Gene products for HMOX1, NRF1, PPARGC1A, and TFAM, and mitochondrial DNA ND1 and D-loop were measured by quantitative reverse transcriptase-polymerase chain reaction. Proinflammatory cytokines were measured in plasma and neutrophil lysates. Measurements and Main Results: Median (interquartile range) Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores were 21 (8) and 10 (4), respectively, and 90-day mortality was 19%. Transcript levels of all four genes in peripheral blood mononuclear cells were significantly reduced in septic patients on day 1 (p

http://bit.ly/2SwQ5oT

Circulating Secretoneurin Concentrations After Cardiac Surgery: Data From the FINNish Acute Kidney Injury Heart Study

Objectives: Secretoneurin is associated with cardiomyocyte Ca2+ handling and improves risk prediction in patients with acute myocardial dysfunction. Whether secretoneurin improves risk assessment on top of established cardiac biomarkers and European System for Cardiac Operative Risk Evaluation II in patients undergoing cardiac surgery is not known. Design: Prospective, observational, single-center sub-study of a multicenter study. Setting: Prospective observational study of survival in patients undergoing cardiac surgery. Patients: A total of 619 patients undergoing cardiac surgery. Interventions: Patients underwent either isolated coronary artery bypass graft surgery, single noncoronary artery bypass graft surgery, two procedures, or three or more procedures. Procedures other than coronary artery bypass graft were valve surgery, surgery on thoracic aorta, and other cardiac surgery. Measurements and Main Results: We measured preoperative and postoperative secretoneurin concentrations and adjusted for European System for Cardiac Operative Risk Evaluation II, N-terminal pro-B-type natriuretic peptide, and cardiac troponin T concentrations in multivariate analyses. During 961 days of follow-up, 59 patients died (9.5%). Secretoneurin concentrations were higher among nonsurvivors compared with survivors, both before (168 pmol/L [quartile 1–3, 147–206 pmol/L] vs 160 pmol/L [131–193 pmol/L]; p = 0.039) and after cardiac surgery (173 pmol/L [129–217 pmol/L] vs 143 pmol/L [111–173 pmol/L]; p

http://bit.ly/2GqFkOq

Targeting CD39 Toward Activated Platelets Reduces Systemic Inflammation and Improves Survival in Sepsis: A Preclinical Pilot Study

Objectives: Sepsis is associated with a systemic inflammatory reaction, which can result in a life-endangering organ dysfunction. Pro-inflammatory responses during sepsis are characterized by increased activation of leukocytes and platelets, formation of platelet-neutrophil aggregates, and cytokine production. Sequestration of platelet-neutrophil aggregates in the microvasculature contributes to tissue damage during sepsis. At present no effective therapeutic strategy to ameliorate these events is available. In this preclinical pilot study, a novel anti-inflammatory approach was evaluated, which targets nucleoside triphosphate hydrolase activity toward activated platelets via a recombinant fusion protein combining a single-chain antibody against activated glycoprotein IIb/IIIa and the extracellular domain of CD39 (targ-CD39). Design: Experimental animal study and cell culture study. Setting: University-based experimental laboratory. Subjects: Human dermal microvascular endothelial cells 1, human platelets and neutrophils, and C57BL/6NCrl mice. Interventions: Platelet-leukocyte-endothelium interactions were evaluated under inflammatory conditions in vitro and in a murine lipopolysaccharide-induced sepsis model in vivo. The outcome of polymicrobial sepsis was evaluated in a murine cecal ligation and puncture model. To evaluate the anti-inflammatory potential of activated platelet targeted nucleoside triphosphate hydrolase activity, we employed a potato apyrase in vitro and in vivo, as well as targ-CD39 and as a control, nontarg-CD39 in vivo. Measurements and Main Results: Under conditions of sepsis, agents with nucleoside triphosphate hydrolase activity decreased platelet-leukocyte-endothelium interaction, transcription of pro-inflammatory cytokines, microvascular platelet-neutrophil aggregate sequestration, activation marker expression on platelets and neutrophils contained in these aggregates, leukocyte extravasation, and organ damage. Targ-CD39 had the strongest effect on these variables and retained hemostasis in contrast to nontarg-CD39 and potato apyrase. Most importantly, targ-CD39 improved survival in the cecal ligation and puncture model to a stronger extent then nontarg-CD39 and potato apyrase. Conclusions: Targeting nucleoside triphosphate hydrolase activity (CD39) toward activated platelets is a promising new treatment concept to decrease systemic inflammation and mortality of sepsis. This innovative therapeutic approach warrants further development toward clinical application. Prof. Peter and Dr. Straub contributed equally and share senior authorship. 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://bit.ly/29S62lw). Supported, in part, by grants from the German Research Foundation (Deutsche Forschungsgemeinschaft [DFG], Bonn, Germany) to Dr. Straub (grant number STR-687/4-1); Prof. Rosenberger (grant number DFG-RO 3672/6-2); and Prof. Mirakaj (MI-1506/4-1) and the Interdisciplinary Center for Clinical Research (IZKF) program of the University of Tübingen, Germany (grant number IZKF-No. PK 2015-1-05; granted to Prof. Rosenberger and Mr. Glück); by a grant of the Dr. Karl Kuhn Foundation to Dr. Straub; and Dr. Xang was supported by a future leader fellowship of the National Heart Foundation of Australia). Mr. Glück received scholarship support for 1 year and travel support for visits at scientific meetings (German Anaesthesiology Congress and German Intensive Care and Emergency Medicine Congress) by the "IZKF—Promotionskolleg" University of Tübingen (Germany). Mr. Glück and Dr. Straub disclosed targ-CD39 as an experimental agent. Prof. Peter was supported by a principal research fellowship from the National Health and Medical Research Council of Australia. Dr. Straub's institution received funding from Deutsche Forschungsgemeinschaft (German Research Foundation) and Interdisciplinary Center for Clinical Research (IZKF) program of the University of Tübingen, Germany, and he received speaker honoraria from CSL Behring GmbH Munich, Germany and Schöchl Medical Education GmbH Mattsee, Austria. The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Andreas Straub, MD, Department of Anesthesiology and Intensive Care Medicine, Eberhard-Karls University Tübingen, Waldhörnlestr. 22, 72072 Tübingen, Germany. E-mail: andreas.straub@uni-tuebingen.de Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Central Venous Access Capability and Critical Care Telemedicine Decreases Inter-Hospital Transfer Among Severe Sepsis Patients: A Mixed Methods Design

Objectives: Severe sepsis is a complex, resource intensive, and potentially lethal condition and rural patients have worse outcomes than urban patients. Early identification and treatment are important to improving outcomes. The objective of this study was to identify hospital-specific factors associated with inter-hospital transfer. Design: Mixed method study integrating data from a telephone survey and retrospective cohort study of state administrative claims. Setting and Subjects: Survey of Iowa emergency department administrators between May 2017 and June 2017 and cohort of adults seen in Iowa emergency departments for severe sepsis and septic shock between January 2005 and December 2013. Interventions: None. Measurements and Main Results: Multivariable logistic regression was used to identify independent predictors of inter-hospital transfer. We included 114 institutions that provided data (response rate = 99%), and responses were linked to a total of 150,845 visits for severe sepsis/septic shock. In our adjusted model, having the capability to place central venous catheters or having a subscription to a tele-ICU service was independently associated with lower odds of inter-hospital transfer (adjusted odds ratio, 0.69; 95% CI, 0.54–0.86 and adjusted odds ratio, 0.69; 95% CI, 0.54–0.88, respectively). A facility's participation in a sepsis-specific quality improvement initiative was associated with 62% higher odds of transfer (adjusted odds ratio, 1.62; 95% CI, 1.10–2.39). Conclusions: The insertion of central venous catheters and access to a critical care physician during sepsis treatment are important capabilities in hospitals that transfer fewer sepsis patients. In the future, hospital-specific capabilities may be used to identify institutions as regional sepsis centers. This work was performed at the University of Iowa Carver College of Medicine, Iowa City, IA. Mr. Ilko and Drs. Ahmed and Mohr conceived the study, designed the data collection tool, and obtained research funding. Mr. Ilko undertook participant recruitment and data collection with data collection oversight and quality control from Dr. Ahmed. Ms. Vakkalanka and Dr. Harland were responsible for management of the datasets. Ms. Vakkalanka and Drs. Harland and Mohr provided statistical advice on study design and analyzed the data. Mr. Ilko, Ms. Vakkalanka, and Dr. Mohr drafted the article. Dr. Mohr takes responsibility for the article as a whole. All authors contributed substantially to its revision. 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://bit.ly/29S62lw). This was delivered as an oral presentation, in part, at the Medical Student Research Conference at the University of Iowa, Carver College of Medicine, Iowa City, IA, on September 14, 2017. It was delivered as a poster presentation at Society for Academic Emergency Medicine Great Plains Regional Meeting in Columbia, MO, on October 7, 2017. Dr. Mohr disclosed that this research was funded by the HL007485 from the National Heart, Lung, and Blood Institute (Short Term Training for Students in the Health Professions) and support from the Department of Emergency Medicine, University of Iowa Carver College of Medicine. Mr. Ilko, Ms. Vakkalanka, and Dr. Mohr received support for article research from the NIH. Dr. Ahmed received funding from UptoDate. Dr. Harland disclosed that she does not have any potential conflicts of interest. For information regarding this article, E-mail: nicholas-mohr@uiowa.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

http://bit.ly/2GvkgX9

The Effect of Mechanical Ventilation on Peripheral Perfusion Index and Its Association With the Prognosis of Critically Ill Patients

Objectives: This study aimed to explore the relationship between the variables of mechanical ventilation and circulatory perfusion and its association with ICU mortality during the first day of mechanical ventilation. Design: Retrospective cohort study. Setting: The Department of Critical Care Medicine, Peking Union Medical College Hospital. Patients: Patients who have undergone mechanical ventilation. Interventions: None. Measurements and Main Results: This study used the main clinical data obtained from the real-time bedside messaging systems of mechanically ventilated patients during their first day in the ICU from May 2013 to May 2016, including data on the variables of mechanical ventilation and circulatory perfusion. An analysis was then performed on the association of the above data with the patient's in-ICU mortality. There were 5,103 patients who received mechanical ventilation during this period, and of these, 309 patients died during their ICU treatment. Peak airway pressure, mean airway pressure, respiratory rate, heart rate, mean arterial pressure, FIO2, blood oxygen saturation, PO2, peripheral perfusion index, and lactate level were correlated with patient outcomes. A Cox logistic regression analysis suggested that mean airway pressure and perfusion index were the most independent risk and protective factors, respectively, for patient ICU mortality. The areas under the curve for a poor prognosis for mean airway pressure and perfusion index were 0.799 (95% CI, 0.77–0.829) and 0.759 (95% CI, 0.729–0.789), respectively. Further, mean airway pressure and perfusion index exhibited a causal interaction. The relative excess risk due to interaction was 2.061 (–0.691 to 4.814), the attributable proportion due to interaction was 0.210 (–0.027 to 0.447), and the synergy index was 1.306 (0.930–1.833). Conclusions: A higher mean airway pressure and lower perfusion index provided a worse prognosis in mechanically ventilated patients, and it appears that these two variables have a casual interaction. 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://bit.ly/29S62lw). Supported, in part, by Capital Characteristic Clinic Project of Beijing (No. Z181100001718209). The authors have not disclosed any potential conflicts of interest. For information regarding this article, E-mail: Yun Long: ly_icu@aliyun.com Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

http://bit.ly/2Sw4tOo

The Effect of Goal-Directed Therapy on Patient Morbidity and Mortality After Traumatic Brain Injury, Results From the Progesterone for the Treatment of Traumatic Brain Injury III Clinical Trial

Objectives: To estimate the impact of goal-directed therapy on outcome after traumatic brain injury, our team applied goal-directed therapy to standardize care in patients with moderate to severe traumatic brain injury, who were enrolled in a large multicenter clinical trial. Design: Planned secondary analysis of data from Progesterone for the Treatment of Traumatic Brain Injury III, a large, prospective, multicenter clinical trial. Setting: Forty-two trauma centers within the Neurologic Emergencies Treatment Trials network. Patients: Eight-hundred eighty-two patients were enrolled within 4 hours of injury after nonpenetrating traumatic brain injury characterized by Glasgow Coma Scale score of 4–12. Measurements and Main Results: Physiologic goals were defined a priori in order to standardize care across 42 sites participating in Progesterone for the Treatment of Traumatic Brain Injury III. Physiologic data collection occurred hourly; laboratory data were collected according to local ICU protocols and at a minimum of once per day. Physiologic transgressions were predefined as substantial deviations from the normal range of goal-directed therapy. Each hour where goal-directed therapy was not achieved was classified as a "transgression." Data were adjudicated electronically and via expert review. Six-month outcomes included mortality and the stratified dichotomy of the Glasgow Outcome Scale-Extended. For each variable, the association between outcome and either 1) the occurrence of a transgression or 2) the proportion of time spent in transgression was estimated via logistic regression model. Results: For the 882 patients enrolled in Progesterone for the Treatment of Traumatic Brain Injury III, mortality was 12.5%. Prolonged time spent in transgression was associated with increased mortality in the full cohort for hemoglobin less than 8 gm/dL (p = 0.0006), international normalized ratio greater than 1.4 (p

http://bit.ly/2SvfgbE

Arterial thrombosis as primary presentation of endogenous Cushings syndrome

Cushing's syndrome is known to present with a characteristic set of clinical manifestations and complications, well described in literature. However, hypercoagulability remains an under recognised entity in Cushing's syndrome. A 31-year-old woman from Southern India presented with history of fever, left upper quadrant pain and progressive breathing difficulty for 3 weeks. Clinical examination revealed discriminatory features of Cushing's syndrome. Laboratory investigations showed biochemical features of endogenous ACTH-dependent Cushing's syndrome. Imaging of the abdomen revealed splenic collection, left-sided empyema and extensive arterial thrombosis. Gadolinium enhanced dynamic MRI of the pituitary gland revealed no evidence of an adenoma while a Ga-68 DOTATATE positron emission tomography CT scan ruled out an ectopic Cushing's. A diagnosis of endogenous Cushing's syndrome causing a prothrombotic state with extensive arterial thrombosis was made. She was initiated on oral anticoagulation and oral ketoconazole for medical adrenal suppression. She subsequently underwent bilateral adrenalectomy and was well at follow-up.

http://bit.ly/2Gpjmvr

High tibial osteotomy in combination with arthroscopic abrasion arthroplasty and autologous adipose-derived mesenchymal stem cell therapy in the treatment of advanced knee osteoarthritis

Osteoarthritis is a progressive and debilitating condition. An increasing number of total knee replacements are being performed under the age of 65. Improved understanding of the action of mesenchymal stem cells (MSC) has seen renewed interest in their role in cartilage repair. A 43-year-old man presented with grade IV medial compartment knee osteoarthritis. The patient underwent high tibial osteotomy (HTO) and arthroscopic abrasion arthroplasty in combination with adipose-derived MSC therapy. The patient reported improvement in pain and function as measured by validated outcome scores. Repeat MRI including T2 mapping techniques showed hyaline-like cartilage regeneration. This case highlights the potential benefit of surgical interventions including HTO in combination with MSC therapy in early-onset severe osteoarthritis. This technique may considerably delay or prevent the need for total knee replacement in young patients. Further controlled trials are needed to confirm the reproducibility of this outcome.

http://bit.ly/2SDmwSy

Pneumomediastinum, ST elevation and urgent cardiac catheterisation: a crucial triad?

Pneumomediastinum (PNMD) entails the presence of air or other gas in the mediastinum and is also known as mediastinal emphysema. PNMD may cause a wide variety of signs and symptoms, as well as ECG abnormality, including ST segment changes. We present a 56-year-old man admitted to our hospital after a facial trauma. After undergoing tracheostomy, he complained of chest discomfort. A chest X-ray in the posteroanterior view showed PNMD, and an ECG was suggestive of inferior-lateral wall myocardial infarction. An urgent cardiac catheterisation identified a critical obstruction at the origin of the right coronary artery. Following a balloon angioplasty, chest discomfort continued; and the ECG ST segments did not show any dynamic change during the subsequent 72 hours. We urge clinicians to perform a comprehensive workup for every patient presenting with PNMD and ST segment changes, to prevent unnecessary invasive procedures.

http://bit.ly/2SvOzU9

Pins and needles in the groin: an incidental finding of retained needle fragments in an intravenous drug user

A female intravenous drug user was reviewed in A&E following a deliberate overdose. After claiming to have swallowed a razor blade, an abdominal radiograph was performed; this showed a linear metallic density projected over the right side of the pelvis, eventually identified as a needle fragment. Subsequent CT imaging revealed three additional needles situated within the groin. Duplex assessment also identified bilateral arteriovenous fistulae. The patient remained asymptomatic and was managed conservatively. She could recall several occasions when a needle had broken while injecting. This scenario was more likely if the needle had been used many times previously, causing it to become blunt and bent. There are cases reported of adverse patient outcomes secondary to broken needle fragments but awareness among medical professionals remains poor.

http://bit.ly/2GraZiU

The influence of GDF11 on brain fate and function

Abstract

Growth differentiation factor 11 (GDF11) is a transforming growth factor β (TGFβ) protein that regulates aspects of central nervous system (CNS) formation and health throughout the lifespan. During development, GDF11 influences CNS patterning and the genesis, differentiation, maturation, and activity of new cells, which may be primarily dependent on local production and action. In the aged brain, exogenous, peripherally delivered GDF11 may enhance neurogenesis and angiogenesis, as well as improve neuropathological outcomes. This is in contrast to a predominantly negative influence on neurogenesis in the developing CNS. Seemingly antithetical effects may correspond to the cell types and mechanisms activated by local versus circulating concentrations of GDF11. Yet undefined, distinct mechanisms of action in young and aged brains may also play a role, which could include differential receptor and binding partner interactions. Exogenously increasing circulating GDF11 concentrations may be a viable approach for improving deleterious aspects of brain aging and neuropathology. Caution is warranted, however, since GDF11 appears to negatively influence muscle health and body composition. Nevertheless, an expanding understanding of GDF11 biology suggests that it is an important regulator of CNS formation and fate, and its manipulation may improve aspects of brain health in older organisms.

http://bit.ly/2TzvCwV

Correction to: Habit in Peirce: a Review of Consensus on Peirce’s Concept of Habit

Please note that the original article with DOI number http://bit.ly/2RK49XL has been corrected. The copyright holder has changed as the article is no longer an open access article.

http://bit.ly/2WMRUxp

A Case of Mediastinal Leiomyosarcoma Demonstrated on FDG PET/CT Imaging

A 56-year-old man presented with persisting chest tightness over 1 month. A mediastinal mass was found by chest radiography. To further evaluate the mass, chest CT was performed and the malignancy was suspected. Staging FDG PET/CT demonstrated a hypermetabolic lesion located in the left middle mediastinum without extra-lesion involvement. The lesion pathologically confirmed mediastinal leiomyosarcoma after surgical resection.

http://bit.ly/2BoCd6e

Comparisons Between PET With 11C-Methyl-L-Methionine and Arterial Spin Labeling Perfusion Imaging in Recurrent Glioblastomas Treated With Bevacizumab

Purpose The aim of this study was to clarify whether arterial spin labeling (ASL) perfusion imaging can assess biological effects from bevacizumab (BEV) therapy as reliably as PET with 11C-methyl-L-methionine (11C-met-PET). Materials and Methods Twenty-four patients with recurrent glioblastoma were examined using both ASL and 11C-met-PET before and 4 and 8 weeks after starting BEV treatment. Tumor-to-normal brain (T/N) ratios, fluctuations in T/N ratio, and tumor volumes were compared between ASL and 11C-met-PET. Accuracy of predicting patient with long progression-free survival (PFS) was assessed for T/N ratios and fluctuations for ASL and 11C-met-PET in each phase and in each period using receiver operating characteristic curves. Between 2 groups of patients assigned by cutoff values from receiver operating characteristic curves, PFS was compared in each phase or in each period. Results T/N ratios, fluctuations in ratio, and tumor volumes correlated significantly between ASL and 11C-met-PET at all time points and all periods. Arterial spin labeling was eligible as a predictor for long PFS only in assessment of fluctuations in T/N ratio. However, the most accurate predictors for long PFS were T/N ratio from 11C-met-PET at 8 weeks and the fluctuation from baseline to 4 weeks in T/N ratio from 11C-met-PET. Conclusions Blood flows on ASL correlated with accumulations of 11C-met on PET in recurrent glioblastoma under BEV treatment. Although 11C-met-PET offered superior accuracy for predicting patients with long PFS from time points, ASL offered reliable prediction of long PFS, provided that fluctuations in T/N ratio between consecutive scans are assessed.

http://bit.ly/2TC2VQ3

18F-Fluciclovine PET/CT Detection of Recurrent Prostate Carcinoma in Patients With Serum PSA ≤ 1 ng/mL After Definitive Primary Treatment

Purpose The aims of this study were to report on our initial experience using 18F-fluciclovine PET/CT to detect recurrent prostate carcinoma in patients with low serum prostate-specific antigen (PSA) after definitive treatment of primary disease and to conduct a preliminary investigation for factors associated with positive scan findings. Patients and Methods In this retrospective study, 18F-fluciclovine PET/CT scans from 28 men with suspected recurrence of prostate carcinoma and PSA values of 1 ng/mL or less were examined to identify the site(s) of disease recurrence. Differences in detection rate for Gleason scores of 7 and greater than 7, T2 and T3 disease, negative and positive surgical margins, and negative and positive seminal vesicle invasion were compared using the Fisher exact test. Mean PSA and mean PSA doubling time of patients with positive scans and negative scans were compared using the independent 2-group t test. Results At least one site of disease recurrence was identified in 13 (46.4%) of 28 patients. Disease detection rate was significantly higher in patients with history of Gleason score greater than 7 (Fisher exact test, P = 0.004). Mean PSA and PSA doubling time were not significantly different between patients with positive and negative 18F-fluciclovine PET/CT scans (P = 0.29 and 0.70, respectively). Conclusions Detection of recurrent prostate cancer using 18F-fluciclovine PET/CT is possible in patients with low but rising PSA levels of 1 ng/mL or less. In such patients, local and nodal recurrences are more common than distant metastasis, and Gleason score greater than 7 is associated with positive scan results.

http://bit.ly/2BmLGek

Diagnostic Accuracy of 18F-FDG PET/CT in Patients With Biochemical Evidence of Recurrent, Residual, or Metastatic Medullary Thyroid Carcinoma

Objective Medullary thyroid carcinoma (MTC) is a rare malignancy. Location of residual, recurrent, or metastatic disease is crucial to treatment management and outcome. We aimed to evaluate the use of 18F-FDG PET/CT in localizing MTC foci in patients with biochemical relapse. Methods This is a retrospective cohort study. Review of 51 FDG PET/CT studies of 45 patients referred to restage MTC due to increased calcitonin (Ctn) and carcinoembryonic antigen (CEA) values at follow-up. FDG PET/CT diagnostic accuracy was determined through a patient-based analysis, using histology as criterion standard when available, or other imaging studies and clinical follow-up otherwise (mean, 4 years). Results There were 25 positive scans. Sensitivity, specificity, positive and negative predictive values, diagnostic accuracy, and positive likelihood ratio were 66.7%, 83.3%, 88.0%, 57.7%, 72.5%, and 4.0, respectively. Using a Ctn cutoff of 1000 pg/mL, sensitivity increased to 76.9%. There were significant differences of Ctn and CEA values between positive and negative FDG PET/CT (P

http://bit.ly/2TzoRez

Diffuse Bone Metastases in Pancreatic Neuroendocrine Tumor Shown on Octreoscan

A 32-year-old man with a pancreatic neuroendocrine tumor and known liver metastasis presented with diffuse back pain. Workup octreoscan showed newly developed diffuse bone metastases, in addition to the persistent liver metastases. The bone metastases were later confirmed on MRI spine images.

http://bit.ly/2BpTqwf

18F-FDG PET/CT for Prognostic Stratification of Patients With Extranodal Natural Killer/T-Cell Lymphoma

Purpose The prognostic value of PET/CT for extranodal natural killer/T-cell lymphoma (ENKTL) patients is controversial. We sought to investigate the use of pretreatment and interim PET/CT in this disease. Methods Sixty-five patients diagnosed with ENKTL who underwent pretreatment (n = 53) and/or interim PET/CT scans (after 2–4 cycles of chemotherapy and/or radiotherapy, n = 33) were retrospectively enrolled. Interim PET/CT images were interpreted according to the Deauville 5-point scale. PET/CT results were assessed for their predictive value of progression-free survival (PFS) and overall survival (OS). Kaplan-Meier estimates were generated to evaluate the predictive value of clinical parameters and PET/CT scans for prognosis evaluation. The Cox proportional hazards model was performed to assess the potential independent predictors for PFS and OS. Results Patients with a high score (4/5) according to the Deauville scale had heavier tumor burdens and tended to have elevated serum LDH and β2-microglobulin (β2-MG). In univariate analysis, the following parameters were predictive of PFS: age (≤60 vs > 60 years), stage (I/II vs III/IV), lesion location (nasal vs extranasal), LDH (normal vs elevated), β2-MG (normal vs elevated), SUVmax before treatment (≤8.3 vs > 8.3), and interim PET/CT results. For OS, the predictive factors were composed of stage, lesion location, LDH, β2-MG, and interim PET/CT results. However, in multivariate analysis, only interim PET/CT scan interpreted by the Deauville scale remained as an independent predictor for both PFS and OS. Conclusions Interim PET/CT scan displayed potential predictive value for ENKTL patients. Response assessment according to the Deauville 5-point scale may help to improve the accuracy of prediction. Patients with advanced stage (III/IV), elevated LDH or β2-MG, and a high Deauville score of 4 to 5 on the interim PET/CT scan were more likely to have reduced PFS and OS.

http://bit.ly/2TCmRlM

Diffuse Skeletal Hemangiomatosis Mimicking Metastastic Disease on 18F-FDG PET/CT

Diffuse skeletal hemangiomatosis is a rare vascular proliferation disorder involving multiple bones and may be confused with metastatic bone malignancy. We present a case of a 53-year-old man suffering back and proximal right femur pain underwent 18F-FDG PET/CT scan. Multiple hypermetabolic lesions of bone were concerning for metastatic carcinoma. Since no primary malignancy was found, open biopsy was performed and histologic examination led to a diagnosis of diffuse skeletal angiomatosis. This case highlighted the importance of including diffuse skeletal hemangiomatosis in the differential diagnosis of multiple hypermetabolic skeletal lesions on 18F-FDG PET/CT.

http://bit.ly/2BpqZyr

99mTc-HYNIC-TOC in the Evaluation of Recurrent Tumor-Induced Osteomalacia

Purpose Tumor-induced osteomalacia (TIO) is rare paraneoplastic disorder generally caused by small benign neoplasm. Somatostatin receptor imaging has emerged as imaging of the choice in the localization of the causative tumors in new patients with clinical diagnosis of TIO. An accurate localization of the causative tumor using somatostatin receptor imaging followed by successful surgical removal offers cure of the disease. In small percentage of the patients, however, there can be recurrent disease after the surgery. In this retrospective investigation, we tried to assess whether somatostatin receptor imaging using 99mTc-HYNIC-TOC (99mTc-hydrazinonicotinyl-Tyr3-octreotide) is also useful in patients with recurrent TIO after initial successful surgery. Methods The images of 99mTc-HYNIC-TOC images and clinical charts of total 18 patients with suspected recurrent TIO were retrospectively reviewed. The image findings were compared with the clinical chart, which include clinical follow-up and subsequent imaging and surgery. Results Among all 18 patients, 99mTc-HYNIC-TOC imaging results were negative in 5 of them. Among these 5 patients with negative imaging study, the causes of recurrent symptoms and hypophosphatemia in 3 patients were eventually found unrelated to TIO. 99mTc-HYNIC-TOC successfully identified either recurrent causative tumors in the same location (n = 10) or different causative tumor in other locations (n = 3) in 13 patients, which rendered a sensitivity of 86.7% (13 of 15). Conclusions The efficacy of 99mTc-HYNIC-TOC imaging in the evaluation of patients with potential recurrent TIO is compatible to that with new patients who never received surgical resection for the culprit tumors. It can play an important role in known TIO patients who were suspected to have recurrent disease.

http://bit.ly/2TzT9xV

Anaplastic Oligodendroglioma Found as an Incidental Photopenic Lesion on 18F-FP-CIT PET/CT Image

18F-FP-CIT PET is a useful modality for imaging dopamine transporters. It has excellent resolution compared with 123I-beta-CIT SPECT and is widely used clinically for the evaluation of Parkinson disease. In general, the main focus of 18F-FP-CIT PET imaging is the basal ganglia, and it is important to observe whether 18F-FP-CIT uptake is normal in the putamen and caudate nuclei. However, abnormal findings may be seen in other brain regions besides the basal ganglia. Here, we present a case of anaplastic oligodendroglioma, a high-grade tumor, which was found as an incidental photopenic lesion on 18F-FP-CIT PET/CT.

http://bit.ly/2BnLxY9

Hybrid 11C-MET PET/MRI Combined With “Machine Learning” in Glioma Diagnosis According to the Revised Glioma WHO Classification 2016

Purpose With the advent of the revised WHO classification from 2016, molecular features, including isocitrate dehydrogenase (IDH) mutation have become important in glioma subtyping. This pilot trial analyzed the potential for 11C-methionine (MET) PET/MRI in classifying glioma according to the revised WHO classification using a machine learning model. Methods Patients with newly diagnosed WHO grade II–IV glioma underwent preoperative MET-PET/MRI imaging. Patients were retrospectively divided into four groups: IDH wild-type glioblastoma (GBM), IDH wild-type grade II/III glioma (GII/III-IDHwt), IDH mutant grade II/III glioma with codeletion of 1p19q (GII/III-IDHmut1p19qcod) or without 1p19q-codeletion (GII/III-IDHmut1p19qnc). Within each group, the maximum tumor-to-brain-ratio (TBRmax) of MET-uptake was calculated. To gain generalizable implications from our data, we made use of a machine learning algorithm based on a development and validation subcohort. A support vector machine model was fit to the development subcohort and evaluated on the validation subcohort. Receiver operating characteristic (ROC) analysis served as metric to assess model performance. Results Of a total of 259 patients, 39 patients met the inclusion criteria. TBRmax was highest in the GBM cohort (TBRmax 3.83 ± 1.30) and significantly higher (P = 0.004) compared to GII/III-IDHmut1p19qnc group, where TBRmax was lowest (TBRmax 2.05 ± 0.94). ROC analysis showed poor AUC for glioma subtyping (AUC 0.62) and high AUC of 0.79 for predicting IDH status. In the GII/III-IDHmut1p19qcod group, TBR values were slightly higher than in the IDHmut1p19qnc group. Conclusions MET-PET/MRI imaging in pre-operatively classifying glioma entities appears useful for the assessment of IDH status. However, a larger trial is needed prior to translation into the clinical routine.

http://bit.ly/2TF4RYg

Diffuse Intense Intestinal FDG Activity in a Patient With Familial Adenomatous Polyposis

Familial adenomatous polyposis is a rare autosomal dominant intestinal syndrome with a high rate of malignant transformation. Here, we report a 20-year-old woman with a diagnosis of familial adenomatous polyposis by pathologic examination after colonoscopy biopsy, who underwent an 18F-FDG PET/CT to assess the extent of this disease. The images showed diffuse elevated FDG uptake along the entire colorectum. Additionally, focal enlarged lymph nodes with increased FDG uptake were noted. These findings promoted proctocolectomy and lymphadenectomy.

http://bit.ly/2BmOV5N

Quality and Safety in Health Care, Part XLV: Introduction to Burnout

Burnout not only is a serious problem for physicians, but it also adversely affects the quality and safety of health care for the patients they care for. A doctor with burnout may commit more errors, exhibit unprofessional behavior and a callous attitude to others, have diminished productivity, and cause other problems for the health care system. Furthermore, the percentage of doctors who experience at least 1 symptom of burnout is increasing.

http://bit.ly/2TCqfgr

SPECT/CT Findings in Scapular Notching After Reverse Shoulder Arthroplasty

Scapular notching (SN) is a unique complication in reverse shoulder arthroplasty, caused by repetitive impingement of the humeral polyethylene liner against the inferior scapular neck. It occurs in up to 96% of cases, with bone loss beneath the glenoid baseplate and polyethylene wear. SN can be associated with pain, decreased range of motion, and might result in glenoid implant failure. Modification of glenosphere design and humeral neck angle showed substantially less SN. SPECT/CT is a promising tool providing combined morphologic and metabolic information in symptomatic SN. We present SPECT/CT findings in 7 cases of symptomatic SN in reverse shoulder arthroplasty patients.

http://bit.ly/2BipSkf

Delayed Response (Partial Remission) 3 Years After Peptide Receptor Radionuclide Therapy in a Patient Participating in the NETTER-1 Trial

Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogues has been shown to be highly efficacious concerning progression-free survival and response rates in patients with advanced, progressive, well-differentiated, somatostatin-receptor–positive neuroendocrine neoplasm. We report here delayed response of a midgut neuroendocrine neoplasm patient, who had stable disease after 4 cycles of PRRT and over a long period of 5 restaging admissions with excellent quality of life (full working hours), persisting for 3 years of follow-up, and presented as further partial remission according to both Response Evaluation Criteria in Solid Tumors and EORTC criteria, respectively, 36 months after the last PRRT cycle.

http://bit.ly/2TyrxZW

Multiple Intravascular Papillary Endothelial Hyperplasia of Bone Mimicking Malignancy on 99mTc-MDP Bone Scan and 18F-FDG PET/CT

Multiple intravascular papillary endothelial hyperplasia involved with bone is rare. In this study, we present the case of a 53-year-old woman having occasional chest pains located in the middle of the sternum and the left chest wall. Multiple intravascular papillary endothelial hyperplasia lesions with high metabolism distributed in the sternum, left ribs, 12th thoracic vertebra, and left ilium on bone scintigraphy as well as PET/CT, which were easily misdiagnosed as bone malignant tumors. Increased awareness of this benign lesion and its high metabolic findings will improve preoperative diagnosis and avoid misinterpretation that may lead to an unnecessary invasive treatment.

http://bit.ly/2BmDsTA

Whole-Body Staging of Metastatic Atypical Meningioma Using 68Ga-DOTATATE PET/CT

A 43-year-old woman with suspected recurrence of atypical meningioma World Health Organization grade II presented extensive intracranial lesions with high 68Ga-DOTATATE uptake. Moreover, numerous 68Ga-DOTATATE–positive bone, lung, and liver lesions were seen. For final diagnosis, biopsies taken from a lung lesion revealed distant metastases of the atypical meningioma. This case underlines the high diagnostic power of 68Ga-DOTATATE PET/CT for the staging of meningioma even beyond cerebral or spinal lesions; in case of distant lesions in patients with known meningioma, differential diagnosis should also contain metastases despite their rare occurrence. Moreover, this case emphasizes radioligand therapy especially in metastatic meningioma.

http://bit.ly/2TCqeZV

Asymptomatic Isolated Vulvar Metastasis in Old Treated Case of Carcinoma Rectum—Diagnosis and Treatment Response Evaluation by 18F-FDG PET/CT Scan

We report a clinically asymptomatic, old treated case of carcinoma rectum, presenting with raised serum carcinoembryonic antigen level, referred for 18F-FDG PET/CT scan for restaging. Whole-body PET/CT scan revealed an isolated FDG-avid lesion in the left labia majora region, which on histopathology was found to be metastasis from carcinoma rectum. Subsequent 18F-FDG PET/CT done after 4 cycles of chemotherapy revealed favorable response to therapy. 18F-FDG PET/CT facilitates the detection of unusual site of metastasis and its subsequent response evaluation in the index case.

http://bit.ly/2BlSPvK

Hepatoblastoma Mimicking Hemangioma in Labeled Red Blood Cell Scintigraphy

Although 99mTc red blood cell (RBC) scintigraphy is a very specific method to differentiate a hemangioma from other hepatic masses, several cases of false-positive 99mTc RBC scintigraphy have been previously reported throughout the literature. We report an additional case that presented in a 15-month-old boy with hepatoblastoma showing increased labeled RBC activity mimicking hemangioma.

http://bit.ly/2TznZGN

The New Possibility of Lymphoscintigraphy to Guide a Clinical Treatment for Lymphedema in Patient With Breast Cancer

Objectives Lymphedema is a chronic disease that occurs frequently after breast cancer treatment. For the treatment of lymphedema, surgical approach such as vascularized lymph node transfer and super-microscopic lymphovenous anastomosis surgery is well established. Complex decongestive therapy (CDT) and sympathetic ganglion block (SGB) are two non-surgical therapeutic options. This study aimed to evaluate the effectiveness of lymphoscintigraphy in guiding the selection of the optimal non-surgical treatment in lymphedema. Methods A total of 81 lymphedema patients who underwent lymphoscintigraphy and were treated with CDT or SGB were retrospectively evaluated. The parameters for the lymphoscintigraphic findings included the extent of dermal backflow (small extent/large extent groups), the level of lymphatic flow (trunk flow pattern/upper arm-restricted pattern/forearm-restricted pattern groups), and the visualization of lymph nodes (visualized/non-visualized groups). The change in the circumferential difference between the two sides of the body at the upper arm and forearm was used as the clinical outcome variable. Paired comparison and group comparison analysis were conducted. Results Of 81 patients, 41 received CDT and 40 received SGB. There were no significant differences in demographic data between the CDT and SGB groups. Both CDT and SGB had a significant therapeutic effect. Upper arm edema was more significantly reduced after SGB than after CDT in the small extent group (P = 0.004), the forearm-restricted pattern group (P = 0.002), and the non-visualized group (P = 0.018). In the other groups, SGB and CDT showed comparable therapeutic effects without statistical differences. Conclusion SGB was found to have a better therapeutic effect in the lymphedema patients with specific lymphoscintigraphic findings compared with CDT. Lymphoscintigraphy may be helpful in selecting the appropriate approach to lymphedema treatment. Further well-designed prospective studies are warranted to validate the findings of this study.

http://bit.ly/2BnLwU5

Primary Common Iliac Artery Angiosarcoma With Multiple Bone Metastases Revealed by Dual-Time Point FDG PET/CT Imaging

Iliac artery angiosarcoma is rare, and bone metastasis as its presenting initial symptom is extremely rare. A 67-year-old man with a history of low back pain presented with multiple MRI-identified lumbar and sacrum lesions highly suggestive of bone metastasis. On subsequent PET/CT scan, in addition to multiple vertebrae and pelvis hypermetabolism, a lesion with intense focal uptake was discovered within the lumen of left common iliac artery. Dual-time point quantitative analysis revealed that the lesion-to-liver ratio of SUVmax was significantly increased in the delayed phase. Biopsy confirmed the lesion as a primary iliac artery angiosarcoma.

http://bit.ly/2TznSel

Treatment and Outcomes in Nutritional Optic Neuropathy

Abstract

Purpose of review

Nutritional optic neuropathy is a potential cause of severe visual loss; however, appropriate and timely management can result in excellent visual outcomes. The purpose of this review is to outline our current understanding of the treatment and outcomes for nutritional optic neuropathy.

Recent findings

Current understanding of nutritional optic neuropathy has been greatly aided by some well-reported and investigated epidemics of the condition, most notably the Cuban epidemic optic neuropathy of the early 1990s. More recently, there is an emerging literature surrounding nutritional deficiencies that can occur in patients who have undergone bariatric surgery. There also continues to be a stream of case reports in the literature that add to our understanding. Nutritional optic neuropathy has a great deal of overlap with toxic optic neuropathies and hereditary optic neuropathies and should not be thought of in isolation from these conditions.

Summary

The mainstay of treatment for nutritional optic neuropathy involves identifying and replacing deficient nutrients as well as identifying and eliminating contributory toxins. It is also important to identify contributory genetic factors and to consider the broader social, economic and societal factors which may contribute.

http://bit.ly/2SqyAXx

Laminin-511 Supplementation Enhances Stem Cell Localization with Suppression in the Decline of Cardiac Function in Acute Infarct Rats

Background. The extracellular matrix (ECM), in particular, basement membrane components such as laminins (LMs), is essential for stem cell differentiation and self-renewal. LM511 and LM221 are the main ECM components of the epicardium, where stem cells were abundant. Here, we examined whether LMs affected the regeneration process by modulating stem cell activities. Methods. In vitro, adhesive and proliferative activities of mesenchymal stem cells (MSCs) were evaluated on LM511 and LM221. To examine the effects of LMs in vivo, we established an acute myocardial infarction (MI) model by ligation of the proximal part of the left anterior descending artery at the height of the left atrial appendage and then placed atelocollagen sheets with or without LM511 and LM221 over the anterolateral surface of the left ventricular wall. Four or eight weeks later, cardiac function, histology, and cytokine expressions were analyzed. Results. MSCs showed greater proliferation and adhesive properties on LM511 than on LM221. In vivo, at four weeks, isolectin B4 (ILB4)-positive cells were significantly higher in the LM511-transplanted group than in the control group. Moreover, some ILB4-positive cells expressed both platelet-derived growth factor receptor α and CD90, suggesting that LM511 enhanced MSC recruitment and attachment at the implanted site. After eight weeks, these cells were more abundant than at 4 weeks. Transplantation with LM511-conjugated sheets increased the expression of cardioprotective and angiogenic factors. Conclusion. Transplantation with LM511-conjugated sheets enhanced MSC localization to the implantation site and modulated stem cells activities, leading to angiogenesis in acute MI rat models. Disclosures: The authors disclose no conflict of interest. Funding: This study was supported in part by the New Energy and Industrial Technology Development Organization. *Corresponding author: Professor Yoshiki Sawa, Chairman for Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Phone: +81-6-6879-3154, Fax: +81-6-6879-3163, E-mail: sawa-p@surg1.med.osaka-u.ac.jp Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

http://bit.ly/2Sgb6oD

Development of Predictive Models in Patients with Epiphora Using Lacrimal Scintigraphy and Machine Learning

Abstract

Purpose

We developed predictive models using different programming languages and different computing platforms for machine learning (ML) and deep learning (DL) that classify clinical diagnoses in patients with epiphora. We evaluated the diagnostic performance of these models.

Methods

Between January 2016 and September 2017, 250 patients with epiphora who underwent dacryocystography (DCG) and lacrimal scintigraphy (LS) were included in the study. We developed five different predictive models using ML tools, Python-based TensorFlow, R, and Microsoft Azure Machine Learning Studio (MAMLS). A total of 27 clinical characteristics and parameters including variables related to epiphora (VE) and variables related to dacryocystography (VDCG) were used as input data. Apart from this, we developed two predictive convolutional neural network (CNN) models for diagnosing LS images. We conducted this study using supervised learning.

Results

Among 500 eyes of 250 patients, 59 eyes had anatomical obstruction, 338 eyes had functional obstruction, and the remaining 103 eyes were normal. For the data set that excluded VE and VDCG, the test accuracies in Python-based TensorFlow, R, multiclass logistic regression in MAMLS, multiclass neural network in MAMLS, and nuclear medicine physician were 81.70%, 80.60%, 81.70%, 73.10%, and 80.60%, respectively. The test accuracies of CNN models in three-class classification diagnosis and binary classification diagnosis were 72.00% and 77.42%, respectively.

Conclusions

ML-based predictive models using different programming languages and different computing platforms were useful for classifying clinical diagnoses in patients with epiphora and were similar to a clinician's diagnostic ability.

http://bit.ly/2DXDX8m

Recommendations Updated for Tonsillectomy in Children

WEDNESDAY, Feb. 6, 2019 -- Recommendations have been updated for tonsillectomy in children; the revised clinical practice guideline was published in a supplement to the February issue of Otolaryngology-Head and Neck Surgery. Ron B. Mitchell, M.D.,...

http://bit.ly/2BourJA

EEG-Guided Anesthesia Does Not Cut Postop Delirium in Seniors

WEDNESDAY, Feb. 6, 2019 -- For older adults undergoing surgery, electroencephalogram (EEG)-guided anesthetic administration is not associated with a reduction in postoperative delirium, according to a study published in the Feb. 5 issue of the...

http://bit.ly/2TBUzb9

Patient Tested for Ebola at Philadelphia Hospital

WEDNESDAY, Feb. 6, 2019 -- Preliminary results from a patient being tested for Ebola suggest that the patient has another condition, say officials at the Hospital of the University of Pennsylvania in Philadelphia. "Proper protocols and precautions...

http://bit.ly/2BmuKES

FDA Approves Cablivi for Rare Blood-Clotting Disorder

WEDNESDAY, Feb. 6, 2019 -- Cablivi (caplacizumab-yhdp) injection has been approved by the U.S. Food and Drug Administration to treat adults with acquired thrombotic thrombocytopenic purpura (aTTP). "Patients with aTTP endure hours of treatment with...

http://bit.ly/2TAIRNX

Omadacycline Noninferior to Moxifloxacin for Pneumonia

WEDNESDAY, Feb. 6, 2019 -- Omadacycline is noninferior to moxifloxacin for community-acquired bacterial pneumonia and noninferior to linezolid for acute bacterial skin infections, according to two studies published in the Feb. 7 issue of the New...

http://bit.ly/2Bourcy

A double-blind, placebo-controlled, randomised, multicentre, proof-of-concept and dose-finding phase II clinical trial to investigate the safety, tolerability and efficacy of adrecizumab in patients with septic shock and elevated adrenomedullin concentration (AdrenOSS-2)

Introduction

Sepsis remains a major health problem with an increasing incidence, high morbidity and high mortality. Apart from treatment with antibiotics and organ support, no approved specific adjunct therapies currently exist. Adrenomedullin (ADM) is a vasoactive peptide. High plasma concentrations of ADM correlate with worse outcome in sepsis patients. Preclinical work with the non-neutralising ADM-binding antibody adrecizumab showed promising effects in animal models of septic shock, including improved vascular barrier function, reduced vasopressor demand and organ dysfunction and increased survival. Therapeutic use of adrecizumab may therefore improve outcome in critically ill patients with septic shock and high ADM plasma concentrations. Phase I studies in healthy volunteers did not reveal any safety concerns. In this biomarker-guided trial, the safety and efficacy of adrecizumab will be investigated in patients with septic shock.

Methods and analysis

We describe a phase II, randomised, double-blind, placebo-controlled, biomarker-guided, proof-of-concept and dose-finding clinical trial in patients with early septic shock and high concentration of circulating ADM. A total of 300 patients will be enrolled at approximately 30 sites within the European Union. Patients are randomised to receive active treatment (2 and 4 mg/kg adrecizumab) or placebo, in a 1:1:2 ratio. Patient selection is guided by clinical parameters, and biomarker-guided by measurement of circulating biologically active ADM concentration at admission. Primary endpoint is safety and tolerability of adrecizumab over a 90-day period. A key secondary endpoint is the Sepsis Severity Index over a 14-day period.

Ethics and dissemination

This study is approved by relevant institutional review boards/independent ethics committees and is conducted in accordance with the ethical principles of the Declaration of Helsinki, the European Medicines Agency guidelines of Good Clinical Practice and all other applicable regulations. Results of this study will be published in a peer-reviewed scientific journal.

Trial registration number

NCT03085758; Pre-results.

http://bit.ly/2DY4QJm

Feasibility of working with a wholesale supplier to co-design and test acceptability of an intervention to promote smaller portions: an uncontrolled before-and-after study in British Fish & Chip shops

Objectives

To explore the feasibility of working with a wholesale supplier to co-design and deliver, and to assess the acceptability of, an intervention to promote smaller portions in Fish & Chip shops.

Design

Uncontrolled before-and-after study.

Setting

Fish & Chip shops in northern England, 2016.

Participants

Owners (n=11), a manager and customers (n=46) of Fish & Chip shops; and intervention deliverers (n=3).

Intervention

Supplier-led, three-hour engagement event with shop owners and managers, highlighting the problem of excessive portion sizes and potential ways to reduce portion sizes; provision of box packaging to serve smaller portions; promotional posters and business incentives.

Data collection

In-store observations and sales data collected at baseline and postintervention. Exit survey with customers. Semistructured interviews with owners/managers and intervention deliverers postintervention.

Results

Twelve Fish & Chip shops were recruited. Observational data were collected from eight shops: at baseline, six shops did not promote the availability of smaller portion meals; at follow-up, all eight did and five displayed the promotional poster. Seven out of 12 shops provided sales data and all reported increased sales of smaller portion meals postintervention. Of 46 customers surveyed: 28% were unaware of the availability of smaller portion meals; 20% had bought smaller portion meals; and 46% of those who had not bought these meals were interested to try them in the future. Interviews revealed: owners/managers found the intervention acceptable but wanted a clearer definition of a smaller portion meal; the supplier valued the experience of intervention co-production and saw the intervention as being compatible with their responsibility to drive innovation.

Conclusions

The co-design of the intervention with a supplier was feasible. The partnership facilitated the delivery of an intervention that was acceptable to owners and customers. Sales of smaller meal packaging suggest that promotion of such meals is viable and may be sustainable.

http://bit.ly/2Gu9xw0

Cardiac complications and iron overload in beta thalassemia major patients—a systematic review and meta-analysis

Abstract

Despite the major improvement in therapeutic management of thalassemia major, iron overload is considered a challenging conundrum in these patients and heart disease still remains a major cause of morbidity and mortality in these patients. Therefore, this study aimed to investigate the prevalence of cardiac iron overload and cardiovascular complications in transfusion-dependent thalassemia patients in the worldwide. The following databases were searched: ISI/Web of Science, Embase, PubMed, Scopus, up to February 30, 2018. The quality of the studies was evaluated using the Joanna Briggs Institute Prevalence Critical Appraisal Tool. The random model based on Metaprop was used. One hundred forty-two studies were included. The total number of patients included was 26,893. The mean age of patients was 22.6 (SD = 1.7) years. Based on Metaprop, the overall prevalence of cardiac iron overload/myocardial sidoresis (T2* < 20 ms) and cardiac complications in thalassemia major patients in the worldwide was 25% (95% CI 22–28%) and 42% (95% CI 37–46%), respectively. The results of this study show that the prevalence of cardiac iron overload and cardiovascular complications in patients with thalassemia major is almost high. Therefore, iron chelation and careful monitoring of serum ferritin level will prevent the cardiac iron overload, and interval monitoring of patients with transfusion-dependent thalassemia (TDT) by echocardiography and electrocardiography will help with early detection of cardiovascular complications.

http://bit.ly/2DVJRXN

The role of ABCB1 polymorphism as a prognostic marker for primary central nervous system lymphoma

Abstract

To investigate the possible role of functional single nucleotide polymorphism (SNP) in circadian genes as prognostic markers of primary central nervous system lymphoma (PCNSL). We conducted a prospective study using data from Huashan Hospital 2006–2015 and followed up 91 PCNSL patients until June 30, 2016. The survival of patients with different prognostic factors was compared by log-rank test. Univariate and multivariate analyses were performed by Cox regression. During a long-term follow-up (6–110 months), overall survival (OS) was 32 months (95% CI, 13.3–91.1) and progression-free survival (PFS) was 23 months (95% CI, 9.0–41.0) for the entire cohort. Age (P = 0.046, P = 0.001) and performance status (PS) score (P = 0.013, P = 0.003) showed differences in OS and PFS. ABCB1 rs1045642 variant showed significant difference in PFS between patients with CC genotype and those with CT/TT genotypes (P = 0.020). In multivariate analysis, age (HR = 2.3; 95% CI, 1.2–4.2, P = 0.008), PS (HR = 2.4; 95% CI, 1.3–4.4, P = 0.007), and ABCB1 rs1045642 (HR = 1.9; 95% CI, 1.0–3.3, P = 0.036) were the independent risk factors for PFS. In our results, the most important prognostic factors associated with higher risk of progression were ABCB1 rs1045642 CC genotype, PS > 2, and older age.

http://bit.ly/2GsJZ2A