Choosing Wisely in pediatric anesthesia: An interpretation from the German Scientific Working Group of Paediatric Anaesthesia (WAKKA)

Pediatric Anesthesia, EarlyView.


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Whole-genome RNAi screen identifies methylation-related genes influencing lipid metabolism in Caenorhabditis elegans

Publication date: Available online 30 May 2018
Source:Journal of Genetics and Genomics
Author(s): Xiaotong Zhu, Yangli Liu, Hong Zhang, Pingsheng Liu
Lipid droplets (LDs) are highly conserved multifunctional cellular organelles and aberrant lipid storage in LDs can lead to many metabolic diseases. However, the molecular mechanisms governing lipid dynamic changes remain elusive, and the high-throughput screen of genes influencing LD morphology was limited by lacking specific LD marker proteins in the powerful genetic tool Caenorhabditis elegans. In this study, we established a new method to conduct whole-genome RNAi screen using LD resident protein DHS-3 as a LD marker, and identified 78 genes involved in significant LD morphologic changes. Among them, mthf-1, as well as a series of methylation-related genes, was found dramatically influencing lipid metabolism. SREBP-1 and SCD1 homologs in C. elegans were involved in the lipid metabolic change of mthf-1(RNAi) worms, and the regulation of ATGL-1 also contributed to it by decreasing triacylglycerol (TAG) hydrolysis. Overall, this study not only identified important genes involved in LD dynamics, but also provided a new tool for LD study using C. elegans, with implications for the study of lipid metabolic diseases.



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CORL Expression in the Drosophila Central Nervous System Is Regulated by Stage Specific Interactions of Intertwined Activators and Repressors

CORL proteins (SKOR in mice and Fussel in humans) are a subfamily of central nervous system (CNS) specific proteins related to Sno/Ski oncogenes. Their developmental and homeostatic roles are largely unknown. We previously showed that Drosophila CORL (dCORL; fussel in Flybase) functions between the Activin receptor Baboon and Ecdysone Receptor-B1 (EcR-B1) activation in mushroom body neurons of third instar larval brains. To better understand dCORL regulation and function we generated a series of reporter genes. We examined the embryonic and larval CNS and found that dCORL is regulated by stage specific interactions between intertwined activators and repressors spanning numerous reporters. The reporter AH.lacZ, which contains sequences 7-11kb upstream of dCORL exon1, reflects dCORL brain expression at all stages. Surprisingly, AH.lacZ is not present in EcR-B1 expressing mushroom body neurons. In larvae AH.lacZ is coexpressed with Elav and the transcription factor Drifter as well as in dILP2 insulin producing cells of the pars intercerebralis. The presence of dCORL in insulin producing cells suggests that dCORL functions non-autonomously in the regulation of EcR-B1 mushroom body activation via the modulation of insulin signaling. Overall, the high level of sequence conservation seen in all CORL/SKOR/Fussel family members and their common CNS-specificity suggest that similarly complex regulation and a potential function in insulin signaling are associated with SKOR/Fussel proteins in mammals.

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Bayesian Networks Predict Neuronal Transdifferentiation

We employ the language of Bayesian networks to systematically construct gene-regulation topologies from deep-sequencing single-nucleus RNA-Seq data for human neurons. From the perspective of the cell-state potential landscape, we identify attractors that correspond closely to different neuron subtypes. Attractors are also recovered for cell states from an independent data set confirming our models accurate description of global genetic regulations across differing cell types of the neocortex (not included in the training data). Our model recovers experimentally confirmed genetic regulations and community analysis reveals genetic associations in common pathways. Via a comprehensive scan of all theoretical three-gene perturbations of gene knockout and overexpression, we discover novel neuronal trans-differrentiation recipes (including perturbations of SATB2, GAD1, POU6F2 and ADARB2) for excitatory projection neuron and inhibitory interneuron subtypes.

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A Collection of Transgenic Medaka Strains for Efficient Site-Directed Transgenesis Mediated by phiC31 Integrase

Genetic analysis is facilitated by the efficient production of transgenic strains expressing a DNA of interest as a single copy at a designated chromosomal location. However, technical progress toward this goal in medaka fish (Oryzias latipes), a vertebrate model organism, has been slow. It is well known that phiC31 integrase enables efficient site-directed transgenesis by catalyzing the recombination of an attP DNA motif in a host genome with an attB motif in a targeting vector. This system was pioneered in medaka using the Sleeping Beauty transposon system, and the attP site was established at three chromosomal locations. However, this number appeared insufficient with regard to genetic linkage between the attP-landing site and a genetically modified locus of interest. Here, to establish a collection of transgenic strains of medaka, we introduced an attP motif into the medaka genome using the Ac/Ds maize transposon system and established 12 independent transgenic strains harboring a single copy of the attP motif in at least 11 of the 24 medaka chromosomes. We designed an attB-targeting vector that was integrated efficiently and precisely into the attP-landing site, and with which the DNA of interest was efficiently transmitted to germline cells. Extraneous sequences in the integrants derived from the bacterial backbone of the attB-targeting vector as well as a transgenic fluorescence marker present in the attP-landing site were removable through flippase-mediated recombination. Further, an advanced targeting vector with a heart-specific recombination marker served as a useful tool for easily screening phiC31 integrase-mediated recombinant G₀ embryos, leading to the efficient establishment of transgenic strains. Thus, our resources advance genetic research in medaka.

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Upregulation of dNTP Levels After Telomerase Inactivation Influences Telomerase-Independent Telomere Maintenance Pathway Choice in Saccharomyces cerevisiae

In 10-15% of cancers, telomere length is maintained by a telomerase-independent, recombination-mediated pathway called alternative lengthening of telomeres (ALT). ALT mechanisms were first seen, and have been best studied, in telomerase-null Saccharomyces cerevisiae cells called "survivors". There are two main types of survivors. Type I survivors amplify Y' subtelomeric elements while type II survivors, similar to the majority of human ALT cells, amplify the terminal telomeric repeats. Both types of survivors require Rad52, a key homologous recombination protein, and Pol32, a non-essential subunit of DNA polymerase . A number of additional proteins have been reported to be important for either type I or type II survivor formation, but it is still unclear how these two pathways maintain telomeres. In this study, we performed a genome-wide screen to identify novel genes that are important for the formation of type II ALT-like survivors. We identified 23 genes that disrupt type II survivor formation when deleted. 17 of these genes had not been previously reported to do so. Several of these genes (DUN1, CCR4, and MOT2) are known to be involved in the regulation of dNTP levels. We find that dNTP levels are elevated early after telomerase inactivation and that this increase favors the formation of type II survivors.

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The Antitumor Mechanism of Paeonol on CXCL4/CXCR3-B Signals in Breast Cancer Through Induction of Tumor Cell Apoptosis

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.


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Bile acids and FXR in functional gastrointestinal disorders

Functional Gastrointestinal Disorders (FGIDs), such as Irritable Bowel Syndrome (IBS) and Chronic Constipation (CC), are commonly diagnosed conditions in clinical practice which create a substantial global burden. Since the Farnesoid X Receptor (FXR) and bile acids (BAs) are responsible for maintaining homeostasis in the GI tract, any disturbances in the expression of FXR or the composition of BAs may contribute to the development of the GI symptoms. Alterations in the mechanism of action of FXR directly affect the BAs pool and account for increased intestinal permeability and changes in abundance and diversity of gut microbiota leading to intestinal dysmotility.

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Long-term Follow-up in Adults with Coeliac Disease: Predictors and Effect on Health Outcomes

Guidelines recommend regular follow-up in coeliac disease, but effect of this on long-term outcomes remains unclear.

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Meta-analysis comparing the efficacy and adverse events of biologics and thiopurines for Crohn's Disease after surgery for ulcerative colitis

Long-term inflammatory complications of IPAA include Crohn's Disease (CD) or "CD-like" (CDL) condition. We performed a meta-analysis to evaluate the efficacy of anti-tumor necrosis factor (anti-TNF) with or without immunomodulator (IM) therapy in this group of patients.

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Antibiotic Resistance in Czech Urban Wastewater Treatment Plants: Microbial and Molecular Genetic Characterization

Microbial Drug Resistance, Ahead of Print.


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Impact of Franseen needle on rapid onsite evaluation and histological examination following endoscopic ultrasonography-guided tissue acquisition in patients with splenic malignant lymphoma

Publication date: Available online 30 May 2018
Source:Arab Journal of Gastroenterology
Author(s): Tesshin Ban, Hiroshi Kawakami, Yoshimasa Kubota, Yuichiro Sato
Rapid onsite evaluation (ROSE) following endoscopic ultrasonography (EUS)-guided fine-needle aspiration contributes to the establishment of a diagnosis for various organs. Newly designed three-plane symmetric needles for EUS-guided fine-needle biopsy (EUS-FNB), such as the Franseen needle, have been developed to enable histological core tissue acquisition. However, EUS-guided tissue acquisition for hypervascular splenic lesions remains challenging. Tissue acquisition in cases of splenic malignant lymphoma by using a conventional needle with multiple strokes and suction may result in indeterminate ROSE due to blood contamination and tiny fragments of lymphoma tissue, whereas EUS-FNB by using the Franseen needle with a minimal number of strokes with suction demonstrates qualified specimens for the ROSE as well as histological examination. For splenic malignant lymphomas, EUS-FNB by using the Franseen needle with a limited number of strokes may facilitate qualified specimen acquisition.



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The Cost Effectiveness of Minimally Invasive Spine Surgery in the Treatment of Adult Degenerative Scoliosis: A Comparison of Trans-psoas and Open Techniques

: Surgical treatment improves quality of life in patients with adult degenerative scoliosis (ADS). However, open ADS surgeries are complex, large magnitude operations associated with a high rate of complications. The lateral trans-psoas interbody fusion technique is a less invasive alternative to open ADS surgery, but less invasive techniques tend to be more expensive. The objective of this study was to evaluate the cost-effectiveness of the trans-psoas technique for patients with ADS over a 12-month time horizon from a public payer perspective.

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The impact of prophylactic intraoperative vancomycin powder on microbial profile, antibiotic regimen, length of stay, and reoperation rate in elective spine surgery

: There is growing concern that the microbial profile of surgical site infection (SSI) in the setting of prophylactic vancomycin powder may favor more resistant and uncommon organisms.

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Elevated Glycohemoglobin HbA1c is Associated with Low Back Pain in Non-Overweight Diabetics

Low back pain (LBP) is a common complaint in clinical practice of multifactorial origin. Although obesity has been thought to contribute to LBP primarily by altering the distribution of mechanical loads on the spine, the additional contribution of obesity-related conditions such as diabetes mellitus (DM) to LBP has not been thoroughly examined.

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3D-Printed Poly(ɛ-caprolactone)/Graphene Scaffolds Activated with P1-Latex Protein for Bone Regeneration

3D Printing and Additive Manufacturing, Ahead of Print.


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Ketamine Anesthesia Does Not Improve Depression Scores in Electroconvulsive Therapy: A Randomized Clinical Trial

Background: Although interest in ketamine use during electroconvulsive therapy (ECT) has increased, studies have been equivocal with regard to its efficacy. The aims of this clinical trial were to evaluate ketamine's antidepressive effects in ECT as a primary anesthetic, determine ketamine's tolerability when compared with standard anesthesia, and determine if plasma brain-derived neurotrophic factor (BDNF) is necessary for treatment response. Materials and Methods: Adults meeting criteria for treatment-resistant depression undergoing index course ECT received either methohexital (1 to 2 mg/kg) or ketamine (1 to 2 mg/kg) anesthesia in this dual-arm double-blinded randomized clinical trial (NCT02752724). The primary outcome of this study is change in depression questionnaire scores before and after ECT. Seizure data, depression severity using self-reported and clinician-assessed questionnaires, cognitive scoring, and plasma BDNF concentrations were obtained before and after completion of ECT. Results: There were no differences in seizure lengths, hemodynamics, or seizure stimuli between the ketamine (n=23;138 ECTs) and methohexital (n=27;159 ECTs) groups. Depression scores improved similarly after ECT in both groups. In the methohexital group, 15% of patients failed to achieve adequate seizures and were switched to ketamine and 26% were converted to bilateral ECT stimulus, whereas all ketamine patients achieved adequate seizures and only 4% required bilateral stimulus. Plasma BDNF increased after ECT only in the ketamine group. Conclusions: Our data show that ketamine does not significantly improve depression when compared with methohexital as a single induction agent for ECT, increases serum BDNF and does not increase rates of post-ECT agitation. Ketamine use in ECT may have some benefits for some patients that are not captured through standard depression assessment questionnaires alone. This work was supported in part by a Pilot Project Award #850 from the United States Department of Veterans Affairs. The content does not represent the views of the United States Department of Veterans Affairs or the United States Government. The sponsor had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The authors have no conflicts of interest to disclose. Address correspondence to: Charles William Carspecken, MD, MSc, MBA, Department of Anesthesiology and Critical Care, University of Pennsylvania, Hospital of the University of Pennsylvania, 3620 Hamilton Walk, Philadelphia, PA 19104 (e-mail: charles.carspecken@uphs.upenn.edu). Received March 2, 2018 Accepted April 23, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved

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Efficacy of Malignant Hyperthermia Association of the United States–Recommended Methods of Preparation for Malignant Hyperthermia-Susceptible Patients Using Dräger Zeus Anesthesia Workstations and Associated Costs

BACKGROUND: The objective of this study was to assess the efficacy and cost of Malignant Hyperthermia Association of the United States–recommended methods for preparing Dräger Zeus anesthesia workstations (AWSs) for the malignant hyperthermia-susceptible patient. METHODS: We studied washout profiles of sevoflurane, isoflurane, and desflurane in 3 Zeus AWS following 3 preparation methods. AWS was primed with 1.2 minimum alveolar concentration anesthetic for 2 hours using 2 L/min fresh gas flow, 500 mL tidal volume, and 12/min respiratory rate. Two phases of washout were performed: high flow (10 L/min) until anesthetic concentration was

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What Does a Red Meat Allergy Have to Do With Anesthesia? Perioperative Management of Alpha-Gal Syndrome

Over the past decade, there has been a growing awareness of a new allergic syndrome known as alpha-gal allergy or alpha-gal syndrome, commonly recognized as a red meat allergy. We performed a review of the literature to identify articles that provide both background on this syndrome in general and any reports of reactions to medications or medical devices related to alpha-gal syndrome. Alpha-gal syndrome results from IgE to the oligosaccharide galactose-α-1,3-galactose, expressed in the meat and tissues of noncatarrhine mammals. It is triggered by the bite of the lone star tick and has been implicated in immediate-onset hypersensitivity to the monoclonal antibody cetuximab and delayed-onset hypersensitivity reactions after the consumption of red meat. There is growing recognition of allergic reactions in these patients to other drugs and medical devices that contain alpha-gal. Many of these reactions result from inactive substances that are part of the manufacturing or preparation process such as gelatin or stearic acid. This allergy may be documented in a variety of ways or informally reported by the patient, requiring vigilance on the part of the anesthesiologist to detect this syndrome, given its serious implications. This allergy presents a number of unique challenges to the anesthesiologist, including proper identification of a patient with alpha-gal syndrome and selection of anesthetic and adjunctive medications that will not trigger this allergy. Accepted for publication April 16, 2018. Funding: Institutional and/or departmental. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to W. Jonathan Dunkman, MD, Department of Anesthesiology, Duke University Medical Center, Box 3094, Durham, NC 27710. Address e-mail to william.dunkman@duke.edu. © 2018 International Anesthesia Research Society

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Automated Assessment of Existing Patient’s Revised Cardiac Risk Index Using Algorithmic Software

BACKGROUND: Previous work in the field of medical informatics has shown that rules-based algorithms can be created to identify patients with various medical conditions; however, these techniques have not been compared to actual clinician notes nor has the ability to predict complications been tested. We hypothesize that a rules-based algorithm can successfully identify patients with the diseases in the Revised Cardiac Risk Index (RCRI). METHODS: Patients undergoing surgery at the University of California, Los Angeles Health System between April 1, 2013 and July 1, 2016 and who had at least 2 previous office visits were included. For each disease in the RCRI except renal failure—congestive heart failure, ischemic heart disease, cerebrovascular disease, and diabetes mellitus—diagnosis algorithms were created based on diagnostic and standard clinical treatment criteria. For each disease state, the prevalence of the disease as determined by the algorithm, International Classification of Disease (ICD) code, and anesthesiologist's preoperative note were determined. Additionally, 400 American Society of Anesthesiologists classes III and IV cases were randomly chosen for manual review by an anesthesiologist. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve were determined using the manual review as a gold standard. Last, the ability of the RCRI as calculated by each of the methods to predict in-hospital mortality was determined, and the time necessary to run the algorithms was calculated. RESULTS: A total of 64,151 patients met inclusion criteria for the study. In general, the incidence of definite or likely disease determined by the algorithms was higher than that detected by the anesthesiologist. Additionally, in all disease states, the prevalence of disease was always lowest for the ICD codes, followed by the preoperative note, followed by the algorithms. In the subset of patients for whom the records were manually reviewed, the algorithms were generally the most sensitive and the ICD codes the most specific. When computing the modified RCRI using each of the methods, the modified RCRI from the algorithms predicted in-hospital mortality with an area under the receiver operating characteristic curve of 0.70 (0.67–0.73), which compared to 0.70 (0.67–0.72) for ICD codes and 0.64 (0.61–0.67) for the preoperative note. On average, the algorithms took 12.64 ± 1.20 minutes to run on 1.4 million patients. CONCLUSIONS: Rules-based algorithms for disease in the RCRI can be created that perform with a similar discriminative ability as compared to physician notes and ICD codes but with significantly increased economies of scale. Accepted for publication March 5, 2018. Funding: None. Conflicts of Interest: See Disclosures at the end of the article. I. S. Hofer and A. Mahajan are working with counsel to patent the algorithms for the diseases described in this article. Reprints will not be available from the authors. Address correspondence to Ira S. Hofer, MD, Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine at University of California, Los Angeles, 757 Westwood Plaza, Los Angeles, CA 90095. Address e-mail to ihofer@mednet.ucla.edu. © 2018 International Anesthesia Research Society

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Pain Medicine Board Review

No abstract available

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Assessing the Association Between Blood Loss and Postoperative Hemoglobin After Cesarean Delivery: A Prospective Study of 4 Blood Loss Measurement Modalities

BACKGROUND: Visual estimation and gravimetric methods are commonly used to quantify the volume of blood loss during cesarean delivery (CD). However, the correlation between blood loss and post-CD hemoglobin (Hb) is poorly studied, and it is unclear whether the correlation varies according to how blood loss is measured. METHODS: After obtaining Institutional Review Board approval, we performed a prospective study of 61 women undergoing CD to assess the relations between post-CD Hb and blood loss measured using 4 modalities: gravimetric blood loss measurement (gBL), visual blood loss estimation by a blinded obstetrician (oBL) and anesthesiologist (aBL), and the Triton System (tBL). Hb was measured preoperatively and within 10 minutes after CD. gBL was quantified as blood volume in a suction canister in addition to the weight of blood-soaked sponges. tBL was measured with the Triton System by photographing blood-soaked sponges and suction canister contents. To assess the relation between blood loss and post-CD Hb, we performed correlation analyses and compared the magnitude of the correlations across the 4 measurement modalities using William t test. A Bonferroni correction was set to identify a statistically significant correlation (P

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Intraoperative Methadone in Same-Day Ambulatory Surgery: A Randomized, Double-Blinded, Dose-Finding Pilot Study

BACKGROUND: Approximately 50 million US patients undergo ambulatory surgery annually. Postoperative opioid overprescribing is problematic, yet many patients report inadequate pain relief. In major inpatient surgery, intraoperative single-dose methadone produces better analgesia and reduces opioid use compared with conventional repeated dosing of short-duration opioids. This investigation tested the hypothesis that in same-day ambulatory surgery, intraoperative methadone, compared with short-duration opioids, reduces opioid consumption and pain, and determined an effective intraoperative induction dose of methadone for same-day ambulatory surgery. METHODS: A double-blind, dose-escalation protocol randomized 60 patients (2:1) to intraoperative single-dose intravenous methadone (initially 0.1 then 0.15 mg/kg ideal body weight) or conventional as-needed dosing of short-duration opioids (eg, fentanyl, hydromorphone; controls). Intraoperative and postoperative opioid consumption, pain, and opioid side effects were assessed before discharge. Patient home diaries recorded pain, opioid use, and opioid side effects daily for 30 days postoperatively. Primary outcome was in-hospital (intraoperative and postoperative) opioid use. Secondary outcomes were 30 days opioid consumption, pain intensity, and opioid side effects. RESULTS: Median (interquartile range) methadone doses were 6 (5–6) and 9 (8–9) mg in the 0.1 and 0.15 mg/kg methadone groups, respectively. Total opioid consumption (morphine equivalents) in the postanesthesia care unit was significantly less compared with controls (9.3 mg, 1.3–11.0) in subjects receiving 0.15 mg/kg methadone (0.1 mg, 0.1–3.3; P

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Phentolamine Reverses Epinephrine-Enhanced Skin Antinociception of Dibucaine in Rats

BACKGROUND: The objective of the experiment was to assess the antinociceptive effect of dibucaine, bupivacaine, and epinephrine. To assess the mechanism of action of the interaction between dibucaine and epinephrine, phentolamine, a nonselective α-adrenergic antagonist, was added to the mixture. METHODS: We assessed sensory blockade with these drugs by injecting 0.6 mL of drug-in-saline in the dorsal thoracolumbar area of rats; pinprick of the "wheal" formed by the injectate was the area targeted for stimulation to elicit a cutaneous trunci muscle reflex. The sensory block of dibucaine was compared with that of bupivacaine or epinephrine. Drug–drug interactions were analyzed by isobologram. Phentolamine was added to investigate the antinociceptive effect of dibucaine coinjected with epinephrine. RESULTS: We demonstrated that dibucaine, epinephrine, and bupivacaine produced dose-dependent skin antinociception. On the median effective dose (ED50) basis, the potency was higher for epinephrine (mean, 0.011 [95% confidence interval {CI}, 0.007–0.015] μmol) than for dibucaine (mean, 0.493 [95% CI, 0.435–0.560] μmol) (P

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Mixing Studies in Patients With Prolonged Activated Partial Thromboplastin Time or Prothrombin Time

BACKGROUND: Patients presenting for surgery may have isolated or combined prolonged activated partial thromboplastin time (aPTT) and/or prothrombin time (PT). In patients not receiving anticoagulants or with no identifiable cause for abnormal clot formation, a mixing study is performed. The index of circulating anticoagulant (ICA) has been used to predict the presence of an inhibitor, usually a lupus anticoagulant. METHODS: We retrospectively reviewed the results of mixing studies performed at Northwestern Memorial Hospital, between January 1, 2010 and February 29, 2012. We determined the number of samples that normalized or remained prolonged, the clotting factors associated with prolonged test results, and the presence of coagulation inhibitors. We calculated the ICA in the samples with prolonged aPTT and PT to determine its ability to predict a lupus anticoagulant. The primary comparison of interest was the diagnostic utility of the ICA at cutoff values of 11% for predicting the presence of lupus anticoagulant. RESULTS: There were 269 mixing studies performed: 131 samples with prolonged aPTT; 95 with prolonged PT; and 43 with both prolonged aPTT and prolonged PT. Of the samples with a prolonged aPTT, 55 of 131 (42%) normalized, 36 of 131 (27%) partially corrected, and 40 of 131 (31%) remained prolonged. Thirty-three of 95 samples (35%) with prolonged PT normalized, while 62 of 95 (65%) remained prolonged. Eight of 43 (19%) mixing studies of patients with prolonged PT and aPTT normalized; the aPTT normalized, but the PT remained prolonged in 17 of 43 (39%); the PT normalized, but the aPTT remained prolonged in 7 of 43 (16%); and both tests remained prolonged in 11 of 43 (26%) samples. Prolongations in the aPTT were primarily associated with low activities of CF XII, while the majority of the prolongations in PT were secondary to low activities in CF VII. Combined prolongations were secondary to deficiencies in both the intrinsic and extrinsic as well as the common pathways. An ICA >11% had 100% (95% CI, 59%–100%) sensitivity, 53% (95% CI, 35%–70%) specificity, and 77% (95% CI, 62%–92%) accuracy in predicting the presence of lupus anticoagulant in patients with prolonged aPTT. CONCLUSIONS: Normalization of the aPTT and PT in a mixing study was associated with low clotting factor activity. The ICA may be helpful in predicting the presence of a lupus anticoagulant. As anesthesiologists take ownership of the perioperative surgical home, we need to understand the clinical implications of the results of mixing studies. Accepted for publication April 12, 2018. Funding: Departmental. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Honorio T. Benzon, MD, Northwestern University Feinberg School of Medicine, 251 E Huron, Feinberg Pavilion, 5–704, Chicago, IL 60611. Address e-mail to h-benzon@northwestern.edu. © 2018 International Anesthesia Research Society

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Opening the Black Box: Understanding the Science Behind Big Data and Predictive Analytics

Big data, smart data, predictive analytics, and other similar terms are ubiquitous in the lay and scientific literature. However, despite the frequency of usage, these terms are often poorly understood, and evidence of their disruption to clinical care is hard to find. This article aims to address these issues by first defining and elucidating the term big data, exploring the ways in which modern medical data, both inside and outside the electronic medical record, meet the established definitions of big data. We then define the term smart data and discuss the transformations necessary to make big data into smart data. Finally, we examine the ways in which this transition from big to smart data will affect what we do in research, retrospective work, and ultimately patient care. Accepted for publication March 22, 2018. Funding: None. Conflicts of Interest: See Disclosures at the end of the article. Reprints will not be available from the authors. Address correspondence to Ira S. Hofer, MD, Department of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA 90095. Address e-mail to ihofer@mednet.ucla.edu. © 2018 International Anesthesia Research Society

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Reversing Cholinergic Bronchoconstriction by Common Inotropic Agents: A Randomized Experimental Trial on Isolated Perfused Rat Lungs

BACKGROUND: The ability of inotropic agents to alter airway reactivity and lung tissue mechanics has not been compared in a well-controlled experimental model. Therefore, we compared the potential to alter lung tissue viscoelasticity and bronchodilator effects of commonly used inotropic agents in an isolated perfused rat lung model. METHODS: After achieving steady state lung perfusion, sustained bronchoconstriction was induced by acetylcholine (ACh). Isolated rat lungs were then randomly allocated to 6 groups treated with either saline vehicle (n = 8) or incremental concentrations of inotropes (adrenaline, n = 8; dopamine, n = 7; dobutamine, n = 7; milrinone, n = 8; or levosimendan, n = 6) added to the whole-blood perfusate. Airway resistance (Raw), lung tissue damping (G), and elastance were measured under baseline conditions, during steady-state ACh-induced constriction and for each inotrope dose. RESULTS: No change in Raw was observed after addition of the saline vehicle. Raw was significantly lower after addition of dopamine (maximum difference [95% CI] of 29 [12–46]% relative to the saline control, P = .004), levosimendan (58 [39–77]%, P

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The Effect of Labor Epidural Analgesia on Breastfeeding Outcomes: A Prospective Observational Cohort Study in a Mixed-Parity Cohort

BACKGROUND: The effect of labor epidural analgesia (LEA) on successful breastfeeding has been evaluated in several studies with divergent results. We hypothesized that LEA would not influence breastfeeding status 6 weeks postpartum in women who intended to breastfeed in an environment that encourages breastfeeding. METHODS: In this prospective observational cohort study, a total of 1204 women intending to breastfeed, delivering vaginally with or without LEA, were included; breastfeeding was recorded at 3 days and 6 weeks postpartum. Primary outcome was breastfeeding at 6 weeks, and the χ2 test was used for comparisons between women delivering with and without LEA, according to parity status and previous breastfeeding experience. Total epidural fentanyl dose and oxytocin use (yes/no) were recorded. A multivariable logistic regression was performed to assess factors affecting breastfeeding at 6 weeks. RESULTS: The overall breastfeeding rate at 6 weeks was 76.9%; it was significantly lower among women delivering with LEA (74.0%) compared with women delivering without LEA (83.4%; P

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Readiness for Discharge After Foot and Ankle Surgery Using Peripheral Nerve Blocks: A Randomized Controlled Trial Comparing Spinal and General Anesthesia as Supplements to Nerve Blocks

BACKGROUND: Neuraxial anesthesia is often viewed as superior to general anesthesia but may delay discharge. Comparisons do not typically use multimodal analgesics and nerve blockade. Combining nerve blockade with general anesthesia may reduce pain, opioid consumption, and nausea. We hypothesized that general anesthesia (with nerve blocks) would lead to earlier readiness for discharge, compared to spinal anesthesia (with nerve blocks). METHODS: All patients underwent ambulatory foot and ankle surgery, with a predicted case duration of 1–3 hours. All patients received popliteal and adductor canal nerve blocks using bupivacaine and dexamethasone. No intraoperative opioids were administered. All patients received ondansetron, dexamethasone, ketamine, and ketorolac. Patients, data collectors, and the data analyst were not informed of group assignment. Patients were randomized to spinal or general anesthesia with concealed allocation. Spinal anesthesia was performed with mepivacaine and accompanied with propofol sedation. After general anesthesia was induced with propofol, a laryngeal mask airway was inserted, followed by sevoflurane and propofol. Time until ready for discharge, the primary outcome, was compared between groups after adjusting for age and surgery time using multivariable unconditional quantile regression. Secondary outcomes compared at multiple timepoints were adjusted for multiple comparisons using the Holm–Bonferroni step-down procedure. RESULTS: General anesthesia patients were ready for discharge at a median of 39 minutes earlier (95% confidence interval, 2–75; P = .038) versus spinal anesthesia patients. Patients in both groups met readiness criteria for discharge substantially before actual discharge. Pain scores at rest were higher among general anesthesia patients 1 hour after leaving the operating room (adjusted difference in means, 2.1 [95% confidence interval, 1.0–3.2]; P

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In Response

No abstract available

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Opioid Use Disorders: Perioperative Management of a Special Population

Opioid-related overdose deaths have reached epidemic levels within the last decade. The efforts to prevent, identify, and treat opioid use disorders (OUDs) mostly focus on the outpatient setting. Despite their frequent overrepresentation, less is known about the inpatient management of patients with OUDs. Specifically, the perioperative phase is a very vulnerable time for patients with OUDs, and little has been studied on the optimal management of acute pain in these patients. The preoperative evaluation should aim to identify those with OUDs and assess factors that may interfere with OUD treatment and pain management. Efforts should be made to provide education and assistance to patients and their support systems. For those who are actively struggling with opioid use, the perioperative phase can be an opportunity for engagement and to initiate treatment. Buprenorphine, methadone, and naltrexone medication treatment for OUD and opioid tolerance complicate perioperative pain management. A multidisciplinary team approach is crucial to provide clinically balanced pain relief without jeopardizing the patient's recovery. This article reviews the existing literature on the perioperative management of patients with OUDs and provides clinical suggestions for the optimal care of this patient population. Accepted for publication March 22, 2018. Funding:None. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Emine Nalan Ward, MD, Department of Psychiatry, Massachusetts General Hospital, 16 Blossom St, Boston, MA 02114. Address e-mail to enward@partners.org. © 2018 International Anesthesia Research Society

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The Use of Hydroxyethyl Starch 130/0.4 in Surgery Patients

No abstract available

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Brain neurotransmitter transporter/receptor genomics and efavirenz central nervous system adverse events

Objective We characterized associations between central nervous system (CNS) adverse events and brain neurotransmitter transporter/receptor genomics among participants randomized to efavirenz-containing regimens in AIDS Clinical Trials Group studies in the USA. Participants and methods Four clinical trials randomly assigned treatment-naive participants to efavirenz-containing regimens. Genome-wide genotype and PrediXcan were used to infer gene expression levels in tissues including 10 brain regions. Multivariable regression models stratified by race/ethnicity were adjusted for CYP2B6/CYP2A6 genotypes that predict plasma efavirenz exposure, age, and sex. Combined analyses also adjusted for genetic ancestry. Results Analyses included 167 cases with grade 2 or greater efavirenz-consistent CNS adverse events within 48 weeks of study entry, and 653 efavirenz-tolerant controls. CYP2B6/CYP2A6 genotype level was independently associated with CNS adverse events (odds ratio: 1.07; P=0.044). Predicted expression of six genes postulated to mediate efavirenz CNS side effects (SLC6A2, SLC6A3, PGR, HTR2A, HTR2B, HTR6) were not associated with CNS adverse events after correcting for multiple testing, the lowest P value being for PGR in hippocampus (P=0.012), nor were polymorphisms in these genes or AR and HTR2C, the lowest P value being for rs12393326 in HTR2C (P=6.7×10−4). As a positive control, baseline plasma bilirubin concentration was associated with predicted liver UGT1A1 expression level (P=1.9×10−27). Conclusion Efavirenz-related CNS adverse events were not associated with predicted neurotransmitter transporter/receptor gene expression levels in brain or with polymorphisms in these genes. Variable susceptibility to efavirenz-related CNS adverse events may not be explained by brain neurotransmitter transporter/receptor genomics. Correspondence to David W. Haas, MD, Vanderbilt Health, One Hundred Oaks, 719 Thompson Lane, Suite 47183, Nashville, TN 37204, USA Tel: +1 615 936 8594; fax: +1 615 936 2644; e-mail: david.haas@vanderbilt.edu Received December 11, 2017 Accepted May 10, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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A comparison of the incidence of supraventricular arrhythmias between thoracic paravertebral and intercostal nerve blocks in patients undergoing thoracoscopic surgery: A randomised trial

BACKGROUND Postoperative supraventricular arrhythmias are common in patients after thoracoscopic lobectomy. Inadequate pain control has long been recognised as a significant risk factor for arrhythmias. The performance of ultrasound-guided (USG) thoracic paravertebral block (PVB) is increasing as an ideal technique for postoperative analgesia. OBJECTIVE We conducted this study to evaluate whether a single-shot USG thoracic PVB would result in fewer postoperative supraventricular tachycardias (SVT) than intercostal nerve blocks (ICNBs) after thoracoscopic pulmonary resection. DESIGN A randomised controlled study. SETTING A single university hospital. PATIENTS Sixty-eight patients undergoing thoracoscopic lobectomy were randomised into two equal groups of 34. INTERVENTIONS For postoperative pain control, all patients received a total of 0.3 ml kg−1 of a mixture containing 0.5% ropivacaine and 1/200 000 epinephrine after placement of needles for either a single thoracic PVB or two individual ICNBs, both guided by ultrasound. Data were obtained during the first 48 postoperative hours. MAIN OUTCOME MEASURES The primary outcome was the incidence of SVT after thoracoscopic pulmonary resection. RESULTS During the first 48 postoperative hours, the incidences of SVT and atrial fibrillation were lower in the USG thoracic PVB group (14.7 vs. 46.9%, P = 0.004 and 3.0 vs. 18.8%, P = 0.037, respectively). The requirement for β-receptor blockade was more frequent in the ICNBs group than in the PVB group (5.9 vs. 25%, P = 0.033). CONCLUSION After placement of the needle using ultrasound guidance, a single-shot thoracic PVB is a well tolerated and effective technique to reduce the incidences of postoperative SVT and atrial fibrillation in patients undergoing thoracoscopic pulmonary resection. TRIAL REGISTRATION https://ift.tt/2LGPFWU, registration number: ChiCTR-IOR-17010952. Correspondence to Ying Cao, MD, PhD, School of Pharmacological Science, Southern Medical University, Guangzhou 510515, China Tel: +86 20 36591230; fax: +86 20 36591350; e-mail: yingcao1986@163.com © 2018 European Society of Anaesthesiology

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Safety of moderate-to-deep sedation performed by sedation practitioners: A national prospective observational study

BACKGROUND In the Netherlands, a significant proportion of moderate-to-deep sedation is performed by sedation practitioners under the indirect supervision of an anaesthesiologist but there are limited safety data available. OBJECTIVE To estimate the rate of sedation-related adverse events and patient relevant outcomes (PRO). DESIGN This was a prospective national observational study. Data were collected with a modified adverse event reporting tool from the International Sedation Task Force of the World Society of Intravenous Anaesthesia. SETTING A total of 24 hospitals in the Netherlands where moderate-to-deep sedation was performed by sedation practitioners from the 1 February 2015 to 1 March 2016. PATIENTS Consecutive adults undergoing moderate-to-deep sedation for gastrointestinal, pulmonary and cardiac procedures. INTERVENTION Observation: Analysis included descriptive statistics and a multivariate logistic regression model for an association between adverse events and PRO. MAIN OUTCOME MEASURES The primary outcome was the rate of unfavourable PRO (admission to ICU, permanent neurological deficit, pulmonary aspiration or death). Secondary outcome was the rate of moderate-to-good PRO (unplanned hospital admission or escalation of care). Composite outcome was the sum of all primary and secondary outcomes. RESULTS A total of 11 869 patients with a median age of 64 years [interquartile range 51 to 72] were included. ASA physical score distribution was: first, 19.1%; second, 57.6%; third, 21.6%; fourth, 1.2%. Minimal adverse events occurred in 1517 (12.8%), minor adverse events in 113 (1.0%) and major adverse events in 80 instances (0.7%). Primary outcome: Five (0.04%) unfavourable PRO were observed; four patients needing admission to the intensive care unit; and one died. Secondary outcome: 12 (0.1%) moderate-to-good PRO were observed. Moderate and major adverse events were associated with the composite outcome [3.7 (95% confidence interval 1.1 to 11.9) and 40.6 (95% confidence interval 11.0 to 150.4)], but not minimal or minor adverse events. CONCLUSION Moderate-to-deep sedation performed by trained sedation practitioners has a very low rate of unfavourable outcome. Correspondence to Benedikt Preckel, Department of Anaesthesia, Academic Medical Centre, Meibergdreef 9, 1105 AZ, 1100 DD Amsterdam, The Netherlands Tel: +00 31 205669111; fax: +00 31 206979441; e-mail: b.preckel@amc.nl © 2018 European Society of Anaesthesiology

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Challenges of bringing a new sedative to market!

Purpose of review The current review examines the success and failures of the development of new hypnotic compounds for the human market. One of the important aspects is that one of the key present agents, propofol, is considered by many anaesthesiologists as 'the ideal'. However, all drugs have adverse or side-effects. Recent findings The last 30 years since the introduction of propofol has seen many new compounds evaluated; but as at the present time, only three agents may achieve a pivotal position in the market – fospropofol (a sedative agent which may have a role in endoscopic surgery); remimazolam (a short-acting benzodiazepine) whose development is also being focused on the sedation rather than anaesthesia market; and the pregnane steroid, alfaxalone (an anaesthetic agent first introduced in 1972, but withdrawn in 1984 because of adverse allergic reactions to the solvent, Cremophor EL) now solvented in a cyclodextrin. Summary Studies of these three agents thus far have shown that none of them has any major adverse side-effects; all have properties which warrant further clinical evaluation. Correspondence to John W. Sear, 6 Whites Forge, Abingdon, Appleton OXON OX13 5LG, UK. E-mail: john.sear@gtc.ox.ac.uk Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Recent advances in respiratory monitory in nonoperating room anesthesia

Purpose of review Sedation for nonoperating room procedures is experiencing a considerable increase in demand. Respiratory compromise is one of the most common adverse events seen in sedation. Capnography is a modality that has been widely adopted in this area, but may not be well suited to the special demands of nonoperating room sedation. This review is an assessment of new technologies that may improve outcomes beyond those achievable with capnography. Recent findings New devices for detecting the onset of apnea and for assessing respiratory depression have emerged which have advantages over conventional capnography for detecting apnea without excessive false positive and false negative rates. In addition, monitors that assess respiratory drive have become available, and these may prove useful in regulating depth of sedation. Summary No single monitor is ideal for all settings. During brief endoscopic sedation, detection of apnea is paramount, while during longer procedures, avoiding excessive respiratory depression is more critical. The clinician must choose the appropriate monitor based on an understanding of the challenges of the particular environment. Correspondence to Jeff E. Mandel, Assistant Professor of Anesthesiology & Critical Care, Perelman School of Medicine at the University of Pennsylvania, 7003 Dulles Building, 3400 Spruce Street, Philadelphia, PA 190103, USA. E-mail: mandelj@uphs.upenn.edu Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Epigenetics of pain mediators

Purpose of review The field of epigenetics continues its influential rise as a means to better understand an organism's unique developmental identity over a lifespan. Whereas a genome is constant and unchanging, an epigenome is dynamic and alterable. Epigenetic changes are in response to innumerable internal and external influences including environmental changes such as diet, exercise, disease, toxins, and stress. Epigenetics is of particular interest in the medical research community both for the potential to cause disease and as a target for therapeutic interventions. This article provides a succinct explanation of the potential for epigenetics to influence the understanding of pain as well as a review of relevant research on the topic. Recent findings Studies on epigenetics and pain remain largely preclinical and investigate the theoretical ability of epigenetics to alter the nociceptive pathways both in the periphery and centrally. Significant evidence now exists for the ability of epigenetics to modify broadly categorized pain types, including inflammatory, neuropathic, visceral, and cancer related. Summary Both patients and providers recognize that novel medications for the treatment of both acute and chronic pain conditions are sorely needed. The understanding of epigenetics and its influence on nociception remains in relative infancy but early evidence is strong for potential therapeutic benefits to treat these conditions. Correspondence to Daniel W. Odell, MD, Division of Pain Medicine, Department of Anesthesiology, University of Utah and Supportive Oncology and Survivorship, Huntsman Cancer Hospital, 30 N 1900 E Room 3C444, Salt Lake City, UT 84132-2501, USA. Tel: +1 801 581 6393; fax: +1 801 581 4367; e-mail: daniel.odell@hsc.utah.edu Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Calculations of consciousness: electroencephalography analyses to determine anesthetic depth

Purpose of review Electroencephalography (EEG) was introduced into anesthesia practice in the 1990s as a tool to titrate anesthetic depth. However, limitations in current analysis techniques have called into question whether these techniques improve standard of care, or instead call for improved, more ubiquitously applicable measures to assess anesthetic transitions and depth. This review highlights emerging analytical approaches and techniques from neuroscience research that have the potential to better capture anesthetic transitions to provide better measurements of anesthetic depth. Recent findings Since the introduction of electroencephalography, neuroscientists, engineers, mathematicians, and clinicians have all been developing new ways of analyzing continuous electrical signals. Collaborations between these fields have proliferated several analytical techniques that demonstrate how anesthetics affect brain dynamics and conscious transitions. Here, we review techniques in the following categories: network science, integration and information, nonlinear dynamics, and artificial intelligence. Summary Up-and-coming techniques have the potential to better clinically define and characterize altered consciousness time points. Such new techniques used alongside traditional measures have the potential to improve depth of anesthesia measurements and enhance an understanding of how the brain is affected by anesthetic agents. However, new measures will be needed to be tested for robustness in real-world environments and on diverse experimental protocols. Correspondence to Sarah L. Eagleman, PhD, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Grant Building, 300 Pasteur Dr, S288, Palo Alto, CA 94305–5117, USA. Tel: +650 725 5851; fax: +650 725 8544; e-mail: seagle@stanford.edu Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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How The West Was Won

No abstract available

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Who were the Nataruk people? Mandibular morphology among late Pleistocene and early Holocene fisher-forager populations of West Turkana (Kenya)

Publication date: Available online 29 May 2018
Source:Journal of Human Evolution
Author(s): Aurélien Mounier, Maria Correia, Frances Rivera, Federica Crivellaro, Ronika Power, Joe Jeffery, Alex Wilshaw, Robert A. Foley, Marta Mirazón Lahr
Africa is the birthplace of the species Homo sapiens, and Africans today are genetically more diverse than other populations of the world. However, the processes that underpinned the evolution of African populations remain largely obscure. Only a handful of late Pleistocene African fossils (∼50-12 Ka) are known, while the more numerous sites with human fossils of early Holocene age are patchily distributed. In particular, late Pleistocene and early Holocene human diversity in Eastern Africa remains little studied, precluding any analysis of the potential factors that shaped human diversity in the region, and more broadly throughout the continent. These periods include the Last Glacial Maximum (LGM), a moment of extreme aridity in Africa that caused the fragmentation of population ranges and localised extinctions, as well as the 'African Humid Period', a moment of abrupt climate change and enhanced connectivity throughout Africa. East Africa, with its range of environments, may have acted as a refugium during the LGM, and may have played a critical biogeographic role during the heterogene`ous environmental recovery that followed. This environmental context raises a number of questions about the relationships among early Holocene African populations, and about the role played by East Africa in shaping late hunter-gatherer biological diversity. Here, we describe eight mandibles from Nataruk, an early Holocene site (∼10 Ka) in West Turkana, offering the opportunity of exploring population diversity in Africa at the height of the 'African Humid Period'. We use 3D geometric morphometric techniques to analyze the phenotypic variation of a large mandibular sample. Our results show that (i) the Nataruk mandibles are most similar to other African hunter-fisher-gatherer populations, especially to the fossils from Lothagam, another West Turkana locality, and to other early Holocene fossils from the Central Rift Valley (Kenya); and (ii) a phylogenetic connection may have existed between these Eastern African populations and some Nile Valley and Maghrebian groups, who lived at a time when a Green Sahara may have allowed substantial contact, and potential gene flow, across a vast expanse of Northern and Eastern Africa.



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