Publications by authors named "Matthew T V Chan"

203 Publications

Deep learning approach for guiding three-dimensional computed tomography reconstruction of lower limbs for robotically-assisted total knee arthroplasty.

Int J Med Robot 2021 Jun 9:e2300. Epub 2021 Jun 9.

Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Robotic-assisted total knee arthroplasty (TKA) was performed to promote the accuracy of bone resection and mechanical alignment. Among these TKA system procedures, 3D reconstruction of CT data of lower limbs consumes significant manpower. Artificial intelligence (AI) algorithms applying deep learning has been proved efficient in automated identification and visual processing.

Methods: CT data of a total of 200 lower limbs scanning were used for AI-based 3D model construction and CT data of 20 lower limbs scanning were utilized for verification.

Results: we showed that the performance of an AI-guided 3D reconstruction of CT data of lower limbs for robotic-assisted TKA was similar to that of the operator-based approach. The time of 3D lower limb model construction using AI was 4.7 minutes. AI-based 3D models can be used for surgical planning.

Conclusion: AI was used for the first time to guide the 3D reconstruction of CT data of lower limbs for facilitating robotic-assisted TKA. Incorporation of AI in 3D model reconstruction before TKA might reduce the workload of radiologists. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/rcs.2300DOI Listing
June 2021

The international ENIGMA-II substudy on postoperative cognitive disorders (ISEP).

Sci Rep 2021 Jun 2;11(1):11631. Epub 2021 Jun 2.

Department of Anesthesiology and Perioperative Medicine, Alfred Hospital and Monash University, Melbourne, VIC, Australia.

There is a large controversy as to whether nitrous oxide (NO) added to the anaesthetic gas mixture is harmful or harmless for postoperative cognitive function recovery. We performed a nested study in the ENIGMA-II trial and compared postoperative neurocognitive recovery of patients randomly receiving NO (70%) or Air (70%) in 30% O during anesthesia. We included adults having non cardiac surgery. We compared recovery scores for episodic memory, decision making/processing speed and executive functions measured with the computerised Cambridge Neuropsychological Test Automated Battery (CANTAB). Assessments were performed at baseline, seven and ninety days. At first interim analysis, following recruitment of 140 participants, the trial was suspended. We found that the mean (95%CI) changes of scores for episodic memory were in the Pocock futility boundaries. Decision making/processing speed did not differ either between groups (P > 0.182). But for executive functions at seven days, the mean number (95% CI) of problems successfully solved and the number of correct box choices made was higher in the N2O group, P = 0.029. NO with the limitations of an interim analysis appears to have no harmful effect on cognitive functions (memory/processing speed). It may improve the early recovery process of executive functions. This preliminary finding warrants further investigations.
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http://dx.doi.org/10.1038/s41598-021-91014-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173006PMC
June 2021

Predictive performance of oximetry in detecting sleep apnea in surgical patients with cardiovascular risk factors.

PLoS One 2021 6;16(5):e0250777. Epub 2021 May 6.

Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.

Introduction: In adults with cardiovascular risk factors undergoing major noncardiac surgery, unrecognized obstructive sleep apnea (OSA) was associated with postoperative cardiovascular complications. There is a need for an easy and accessible home device in predicting sleep apnea. The objective of the study is to determine the predictive performance of the overnight pulse oximetry in predicting OSA in at-risk surgical patients.

Methods: This was a planned post-hoc analysis of multicenter prospective cohort study involving 1,218 at-risk surgical patients without prior diagnosis of sleep apnea. All patients underwent home sleep apnea testing (ApneaLink Plus, ResMed) simultaneously with pulse oximetry (PULSOX-300i, Konica Minolta Sensing, Inc). The predictive performance of the 4% oxygen desaturation index (ODI) versus apnea-hypopnea index (AHI) were determined.

Results: Of 1,218 patients, the mean age was 67.2 ± 9.2 years and body mass index (BMI) was 27.0 ± 5.3 kg/m2. The optimal cut-off for predicting moderate-to-severe and severe OSA was ODI ≥15 events/hour. For predicting moderate-to-severe OSA (AHI ≥15), the sensitivity and specificity of ODI ≥ 15 events per hour were 88.4% (95% confidence interval [CI], 85.7-90.6) and 95.4% (95% CI, 94.2-96.4). For severe OSA (AHI ≥30), the sensitivity and specificity were 97.2% (95% CI, 92.7-99.1) and 78.8% (95% CI, 78.2-79.0). The area under the curve (AUC) for moderate-to-severe and severe OSA was 0.983 (95% CI, 0.977-0.988) and 0.979 (95% CI, 0.97-0.909) respectively.

Discussion: ODI from oximetry is sensitive and specific in predicting moderate-to-severe or severe OSA in at-risk surgical population. It provides an easy, accurate, and accessible tool for at-risk surgical patients with suspected OSA.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250777PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101727PMC
May 2021

Dexamethasone and Surgical-Site Infection.

N Engl J Med 2021 05;384(18):1731-1741

From Royal Perth Hospital (T.B.C., P.C., K.M.H.), the University of Western Australia (T.B.C., E.O., K.M.H.), Murdoch University (K.M.H.), and Fiona Stanley Hospital (E.O.), Perth, and the Alfred Hospital (P.S.M., A.C.C., L.A.B.), Monash University (T.B.C., P.S.M., A.B.F., A.C.C., L.A.B., K.L., C.M.), the University of Melbourne (K.L., D.S.), and Royal Melbourne Hospital (K.L.), Melbourne, VIC - all in Australia; the Chinese University of Hong Kong, Hong Kong (M.T.V.C.); and Auckland City Hospital and the University of Auckland - both in Auckland, New Zealand (T.G.S.).

Background: The glucocorticoid dexamethasone prevents nausea and vomiting after surgery, but there is concern that it may increase the risk of surgical-site infection.

Methods: In this pragmatic, international, noninferiority trial, we randomly assigned 8880 adult patients who were undergoing nonurgent, noncardiac surgery of at least 2 hours' duration, with a skin incision length longer than 5 cm and a postoperative overnight hospital stay, to receive 8 mg of intravenous dexamethasone or matching placebo while under anesthesia. Randomization was stratified according to diabetes status and trial center. The primary outcome was surgical-site infection within 30 days after surgery. The prespecified noninferiority margin was 2.0 percentage points.

Results: A total of 8725 participants were included in the modified intention-to-treat population (4372 in the dexamethasone group and 4353 in the placebo group), of whom 13.2% (576 in the dexamethasone group and 572 in the placebo group) had diabetes mellitus. Of the 8678 patients included in the primary analysis, surgical-site infection occurred in 8.1% (354 of 4350 patients) assigned to dexamethasone and in 9.1% (394 of 4328) assigned to placebo (risk difference adjusted for diabetes status, -0.9 percentage points; 95.6% confidence interval [CI], -2.1 to 0.3; P<0.001 for noninferiority). The results for superficial, deep, and organ-space surgical-site infections and in patients with diabetes were similar to those of the primary analysis. Postoperative nausea and vomiting in the first 24 hours after surgery occurred in 42.2% of patients in the dexamethasone group and in 53.9% in the placebo group (risk ratio, 0.78; 95% CI, 0.75 to 0.82). Hyperglycemic events in patients without diabetes occurred in 22 of 3787 (0.6%) in the dexamethasone group and in 6 of 3776 (0.2%) in the placebo group.

Conclusions: Dexamethasone was noninferior to placebo with respect to the incidence of surgical-site infection within 30 days after nonurgent, noncardiac surgery. (Funded by the Australian National Health and Medical Research Council and others; PADDI Australian New Zealand Clinical Trials Registry number, ACTRN12614001226695.).
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http://dx.doi.org/10.1056/NEJMoa2028982DOI Listing
May 2021

Vulnerability to Postoperative Complications in Obstructive Sleep Apnea: Importance of Phenotypes.

Anesth Analg 2021 05;132(5):1328-1337

From the Adelaide Institute for Sleep Health, Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia.

Obstructive sleep apnea (OSA) is a common comorbidity in patients undergoing surgical procedures. Patients with OSA are at heightened risk of postoperative complications. Current treatments for OSA focus on alleviating upper airway collapse due to impaired upper airway anatomy. Although impaired upper airway anatomy is the primary cause of OSA, the pathogenesis of OSA is highly variable from person to person. In many patients, nonanatomical traits play a critical role in the development of OSA. There are 4 key traits or "phenotypes" that contribute to OSA pathogenesis. In addition to (1) impaired upper airway anatomy, nonanatomical contributors include: (2) impaired upper airway dilator muscle responsiveness; (3) low respiratory arousal threshold (waking up too easily to minor airway narrowing); and (4) unstable control of breathing (high loop gain). Each of these phenotypes respond differently to postoperative factors, such as opioid medications. An understanding of these phenotypes and their highly varied interactions with postoperative risk factors is key to providing safer personalized care for postoperative patients with OSA. Accordingly, this review describes the 4 OSA phenotypes, highlights how the impact on OSA severity from postoperative risk factors, such as opioids and other sedatives, is influenced by OSA phenotypes, and outlines how this knowledge can be applied to provide individualized care to minimize postoperative risk in surgical patients with OSA.
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http://dx.doi.org/10.1213/ANE.0000000000005390DOI Listing
May 2021

A new robotically assisted system for total knee arthroplasty: A sheep model study.

Int J Med Robot 2021 Apr 14:e2264. Epub 2021 Apr 14.

Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: We investigated the accuracy and safety of a new HURWA robotic-assisted total knee arthroplasty (TKA) system in a sheep model.

Methods: Ten male small-tailed Han sheep were used in this study. Sheep were imaged by computed tomography scan before and after bone resection and the cutting errors between actual bone preparation and preoperative planning of the femur and tibia in three dimensions were measured.

Results: The overall accuracies after surgery compared with that from preoperative surgical planning of the left and right femurs were 1.93 ± 1.02° and 1.93 ± 1.23°, respectively. Additionally, similarly high overall accuracies for the left and right tibia of 1.26 ± 1.04 and 1.68 ± 0.92°, respectively, were obtained. The gap distances of the distal cut, anterior chamfer, anterior cut, posterior chamfer and posterior cut on the medial side were 0.47 ± 0.35 mm, 0.41 ± 0.37 mm, 0.12 ± 0.26 mm, 0.41 ± 0.44 mm and 0.12 ± 0.23 mm, respectively. No intraoperative complications, such as intraoperative fracture, massive bleeding or death, occurred.

Conclusion: This new HURWA robotic-assisted TKA system is an accurate and safe tool for TKA surgery based on the sheep model.
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http://dx.doi.org/10.1002/rcs.2264DOI Listing
April 2021

Emergency Airway Management in Patients with COVID-19: A Prospective International Multicenter Cohort Study.

Anesthesiology 2021 Apr 13. Epub 2021 Apr 13.

Background: Tracheal intubation for patients with COVID-19 is required for invasive mechanical ventilation. The authors sought to describe practice for emergency intubation, estimate success rates and complications, and determine variation in practice and outcomes between high-income and low- and middle-income countries. The authors hypothesized that successful emergency airway management in patients with COVID-19 is associated with geographical and procedural factors.

Methods: The authors performed a prospective observational cohort study between March 23, 2020, and October 24, 2020, which included 4,476 episodes of emergency tracheal intubation performed by 1,722 clinicians from 607 institutions across 32 countries in patients with suspected or confirmed COVID-19 requiring mechanical ventilation. The authors investigated associations between intubation and operator characteristics, and the primary outcome of first-attempt success.

Results: Successful first-attempt tracheal intubation was achieved in 4,017/4,476 (89.7%) episodes, while 23 of 4,476 (0.5%) episodes required four or more attempts. Ten emergency surgical airways were reported-an approximate incidence of 1 in 450 (10 of 4,476). Failed intubation (defined as emergency surgical airway, four or more attempts, or a supraglottic airway as the final device) occurred in approximately 1 of 120 episodes (36 of 4,476). Successful first attempt was more likely during rapid sequence induction versus non-rapid sequence induction (adjusted odds ratio, 1.89 [95% CI, 1.49 to 2.39]; P < 0.001), when operators used powered air-purifying respirators versus nonpowered respirators (odds ratio, 1.60 [95% CI, 1.16 to 2.20]; P = 0.006), and when performed by operators with more COVID-19 intubations recorded (odds ratio, 1.03 for each additional previous intubation [95% CI, 1.01 to 1.06]; P = 0.015). Intubations performed in low- or middle-income countries were less likely to be successful at first attempt than in high-income countries (odds ratio, 0.57 [95% CI, 0.41 to 0.79]; P = 0.001).

Conclusions: The authors report rates of failed tracheal intubation and emergency surgical airway in patients with COVID-19 requiring emergency airway management, and identified factors associated with increased success. Risks of tracheal intubation failure and success should be considered when managing COVID-19.

Editor’s Perspective:
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http://dx.doi.org/10.1097/ALN.0000000000003791DOI Listing
April 2021

Multi-omic analysis suggests tumor suppressor genes evolved specific promoter features to optimize cancer resistance.

Brief Bioinform 2021 Mar 30. Epub 2021 Mar 30.

Chinese University of Hong Kong and a researcher at the CUHK-Shenzhen Research Institute, China.

Tumor suppressor genes (TSGs) exhibit distinct evolutionary features. We speculated that TSG promoters could have evolved specific features that facilitate their tumor-suppressing functions. We found that the promoter CpG dinucleotide frequencies of TSGs are significantly higher than that of non-cancer genes across vertebrate genomes, and positively correlated with gene expression across tissue types. The promoter CpG dinucleotide frequencies of all genes gradually increase with gene age, for which young TSGs have been subject to a stronger evolutionary pressure. Transcription-related features, namely chromatin accessibility, methylation and ZNF263-, SP1-, E2F4- and SP2-binding elements, are associated with gene expression. Moreover, higher promoter CpG dinucleotide frequencies and chromatin accessibility are positively associated with the ability of TSGs to resist downregulation during tumorigenesis. These results were successfully validated with independent datasets. In conclusion, TSGs evolved specific promoter features that optimized cancer resistance through achieving high expression in normal tissues and resistance to downregulation during tumorigenesis.
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http://dx.doi.org/10.1093/bib/bbab040DOI Listing
March 2021

Bioinformatic analyses hinted at augmented T helper 17 cell differentiation and cytokine response as the central mechanism of COVID-19-associated Guillain-Barré syndrome.

Cell Prolif 2021 May 10;54(5):e13024. Epub 2021 Mar 10.

CUHK-Shenzhen Research Institute, Shenzhen, China.

Objectives: Guillain-Barré syndrome (GBS) results from autoimmune attack on the peripheral nerves, causing sensory, motor and autonomic abnormalities. Emerging evidence suggests that there might be an association between COVID-19 and GBS. Nevertheless, the underlying pathophysiological mechanism remains unclear.

Materials And Methods: We performed bioinformatic analyses to delineate the potential genetic crosstalk between COVID-19 and GBS.

Results: COVID-19 and GBS were associated with a similar subset of immune/inflammation regulatory genes, including TNF, CSF2, IL2RA, IL1B, IL4, IL6 and IL10. Protein-protein interaction network analysis revealed that the combined gene set showed an increased connectivity as compared to COVID-19 or GBS alone, particularly the potentiated interactions with CD86, IL23A, IL27, ISG20, PTGS2, HLA-DRB1, HLA-DQB1 and ITGAM, and these genes are related to Th17 cell differentiation. Transcriptome analysis of peripheral blood mononuclear cells from patients with COVID-19 and GBS further demonstrated the activation of interleukin-17 signalling in both conditions.

Conclusions: Augmented Th17 cell differentiation and cytokine response was identified in both COVID-19 and GBS. PBMC transcriptome analysis also suggested the pivotal involvement of Th17 signalling pathway. In conclusion, our data suggested aberrant Th17 cell differentiation as a possible mechanism by which COVID-19 can increase the risk of GBS.
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http://dx.doi.org/10.1111/cpr.13024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088459PMC
May 2021

Association of Obstructive Sleep Apnea With Difficult Intubation: Prospective Multicenter Observational Cohort Study.

Anesth Analg 2021 Mar 10. Epub 2021 Mar 10.

Department of Anaesthesia and Intensive Care, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.

Background: Obstructive sleep apnea (OSA) has been found to be associated with difficult airway, although there is a paucity of prospective studies investigating thresholds of OSA severity with difficult airway outcomes. The aim of this study was to examine the association between OSA and difficult intubation or difficult mask ventilation. We also explored the utility of the Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index, Age, Neck circumference, and Gender (STOP-Bang) score for difficult airway prediction.

Methods: The Postoperative Vascular Complications in Unrecognized Obstructive Sleep Apnea (POSA) trial was an international prospective cohort study of surgical patients 45 years or older with one or more cardiac risk factor presenting for noncardiac surgery, with planned secondary analyses of difficult airway outcomes. Multivariable logistic regression analyses tested associations between OSA severity and predictors of difficult airway with difficult intubation or difficult mask ventilation. Overall, 869 patients without prior diagnosis of OSA were screened for OSA risk with the STOP-Bang tool, underwent preoperative sleep study, and had routine perioperative care, including general anesthesia with tracheal intubation. The primary outcome analyzed was difficult intubation, and the secondary outcome was difficult mask ventilation.

Results: Based on the sleep studies, 287 (33%), 324 (37%), 169 (20%), and 89 (10%) of the 869 patients had no, mild, moderate, and severe OSA, respectively. One hundred and seventy-two (20%) had a STOP-Bang score of 0-2 (low risk), 483 (55%) had a STOP-Bang score of 3-4 (intermediate risk), and 214 (25%) had a STOP-Bang score 5-8 (high risk). The incidence of difficult intubation was 6.7% (58 of 869), and difficult mask ventilation was 3.7% (32 of 869). Multivariable logistic regression demonstrated that moderate OSA (odds ratio [OR] = 3.26 [95% confidence interval {CI}, 1.37-8.38], adjusted P = .010) and severe OSA (OR = 4.05 [95% CI, 1.51-11.36], adjusted P = .006) but not mild OSA were independently associated with difficult intubation compared to patients without OSA. Relative to scores of 0-2, STOP-Bang scores of 3-4 and 5-8 were associated with increased odds of difficult intubation (OR = 3.01 [95% CI, 1.13-10.40, adjusted P = .046] and 4.38 [95% CI, 1.46-16.36, adjusted P = .014]), respectively. OSA was not associated with difficult mask ventilation, and only increasing neck circumference was found to be associated (adjusted P = .002).

Conclusions: Moderate and severe OSA were associated with difficult intubation, and increasing neck circumference was associated with difficult mask ventilation. A higher STOP-Bang score of 3 or more may be associated with difficult intubation versus STOP-Bang score of 0-2. Anesthesiologists should be vigilant for difficult intubation when managing patients suspected or diagnosed with OSA.
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http://dx.doi.org/10.1213/ANE.0000000000005479DOI Listing
March 2021

Miller Fisher syndrome associated with COVID-19: an up-to-date systematic review.

Environ Sci Pollut Res Int 2021 May 6;28(17):20939-20944. Epub 2021 Mar 6.

Department of Anaesthesia and Intensive Care and Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Hong Kong, China.

Recently, during the pandemic infection of the novel SARS-CoV-2, some cases of Miller Fisher syndrome (MFS) have been reported. We want to summarize the main features of patients with MFS and COVID-19. A PubMed search was performed on 8 October to identify references reporting cases with MFS associated with COVID-19 from the first report of COVID-19 to 8 October 2020 using the following keywords: "Miller Fisher syndrome" AND "COVID-19" OR "SARS-CoV-2". A systematic review from the first report of coronavirus disease 2019 (COVID-19) to 8 October 2020 revealed 7 cases with Miller Fisher syndrome (MFS) associated with COVID-19. The 7 cases came from 5 countries but most of these patients were from Europe (85.7%), especially Spain. There are 5 cases of MFS diagnosed after the laboratory confirmation of SARS-CoV-2 infection. The mean onset time of MFS-associated neurological symptoms was 14.75 days after the diagnosis of COVID-19. However, the two remaining cases presented initially with MFS-associated neurological symptoms followed by the diagnosis of COVID-19. The most common symptoms of COVID-19-associated MFS were perioral paresthesias (57.1%), ataxia (57.1%), blurred vision (42.9), ophthalmoplegia (42.9), and generalized areflexia (42.9). However, more cohort and case-control studies are required to establish the epidemiological linkage.
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http://dx.doi.org/10.1007/s11356-021-13233-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936860PMC
May 2021

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).

Autophagy 2021 Jan 8;17(1):1-382. Epub 2021 Feb 8.

University of Crete, School of Medicine, Laboratory of Clinical Microbiology and Microbial Pathogenesis, Voutes, Heraklion, Crete, Greece; Foundation for Research and Technology, Institute of Molecular Biology and Biotechnology (IMBB), Heraklion, Crete, Greece.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
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http://dx.doi.org/10.1080/15548627.2020.1797280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996087PMC
January 2021

Diagnostic performance of the STOP-Bang questionnaire as a screening tool for obstructive sleep apnea in different ethnic groups.

J Clin Sleep Med 2021 Mar;17(3):521-532

Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.

Study Objectives: The STOP-Bang questionnaire is a concise and easy screening tool for obstructive sleep apnea (OSA). Using modified body mass index (BMI), we assessed the diagnostic performance of the STOP-Bang questionnaire in predicting OSA in ethnically different groups of patients undergoing surgery.

Methods: This was a multicenter prospective cohort study involving patients with cardiovascular risk factors who were undergoing major noncardiac surgery. Patients underwent home sleep apnea testing. All patients completed the STOP-Bang questionnaire. The predictive parameters of STOP-Bang scores were calculated against the apnea-hypopnea index.

Results: From 4 ethnic groups 1,205 patients (666 Chinese, 161 Indian, 195 Malay, and 183 Caucasian) were included in the study. The mean BMI ranged from 25 ± 4 to 30 ± 6 kg/m² and mean age ranged from 64 ± 8 to 71 ± 10 years. For the Chinese and Indian patients, diagnostic parameters are presented using BMI threshold of 27.5 kg/m² with the area under curve to predict moderate-to-severe OSA being 0.709 (0.665-0.753) and 0.722 (0.635-0.808), respectively. For the Malay and Caucasian, diagnostic parameters are presented using BMI threshold of 35 kg/m² with the area under curve for predicting moderate-to-severe OSA being 0.645 (0.572-0.720) and 0.657 (0.578-0.736), respectively. Balancing the sensitivity and specificity, the optimal STOP-Bang thresholds for the Chinese, Indian, Malay, and Caucasian groups were determined to be 4 or greater.

Conclusions: For predicting moderate-to-severe OSA, we recommend BMI threshold of 27.5 kg/m² for Chinese and Indian patients and 35 kg/m² for Malay and Caucasian patients. The optimal STOP-Bang threshold for the Chinese, Indian, Malay and Caucasian groups is 4 or greater.

Clinical Trial Registration: Registry: ClinicalTrials.gov; Name: Postoperative Vascular Events in Unrecognized Obstructive Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/study/NCT01494181; Identifier: NCT01494181.
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http://dx.doi.org/10.5664/jcsm.8940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927338PMC
March 2021

An update on the roles of circular RNAs in osteosarcoma.

Cell Prolif 2021 Jan 25;54(1):e12936. Epub 2020 Oct 25.

Department of Anaesthesia and Intensive Care, Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Hong Kong City, Hong Kong.

Osteosarcoma is the most common primary bone malignancy and is a neoplasm thought to be derived from the bone-forming mesenchymal stem cells. Aberrant activation of oncogenes and inactivation of tumour suppressor genes by somatic mutations and epigenetic mechanisms play a pivotal pathogenic role in osteosarcoma. Aside from alterations in these protein-coding genes, it has now been realized that dysregulation of non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and the recently discovered circular RNAs (circRNAs), is crucial to the initiation and progression of osteosarcoma. CircRNAs are single-stranded RNAs that form covalently closed loops and function as an important regulatory element of the genome through multiple machineries. Recently, an increasing number of studies suggested that circRNAs also played critical roles in osteosarcoma. This review summarizes recent development and progression in circRNA transcriptome analysis and their functions in the modulation of osteosarcoma progression.
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http://dx.doi.org/10.1111/cpr.12936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791175PMC
January 2021

A surveillance method to identify patients with sepsis from electronic health records in Hong Kong: a single centre retrospective study.

BMC Infect Dis 2020 Sep 7;20(1):652. Epub 2020 Sep 7.

Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, Hong Kong, China.

Background: Currently there are only two population studies on sepsis incidence in Asia. The burden of sepsis in Hong Kong is unknown. We developed a sepsis surveillance method to estimate sepsis incidence from a population electronic health record (EHR) in Hong Kong using objective clinical data. The study objective was to assess our method's performance in identifying sepsis using a retrospective cohort. We compared its accuracy to administrative sepsis surveillance methods such as Angus' and Martin's methods.

Method: In this single centre retrospective study we applied our sepsis surveillance method on adult patients admitted to a tertiary hospital in Hong Kong. Two clinicians independently reviewed the clinical notes to determine which patients had sepsis. Performance was assessed by sensitivity, specificity, positive predictive value, negative predictive value and area under the curve (AUC) of Angus', Martin's and our surveillance methods using clinical review as "gold standard."

Results: Between January 1 and February 28, 2018, our sepsis surveillance method identified 1352 adult patients hospitalised with suspected infection. We found that 38.9% (95%CI 36.3-41.5) of these patients had sepsis. Using a 490 patient validation cohort, two clinicians had good agreement with weighted kappa of 0.75 (95% CI 0.69-0.81) before coming to consensus on diagnosis of uncomplicated infection or sepsis for all patients. Our method had sensitivity 0.93 (95%CI 0.89-0.96), specificity 0.86 (95%CI 0.82-0.90) and an AUC 0.90 (95%CI 0.87-0.92) when validated against clinician review. In contrast, Angus' and Martin's methods had AUCs 0.56 (95%CI 0.53-0.58) and 0.56 (95%CI 0.52-0.59), respectively.

Conclusions: A sepsis surveillance method based on objective data from a population EHR in Hong Kong was more accurate than administrative methods. It may be used to estimate sepsis population incidence and outcomes in Hong Kong.

Trial Registration: This study was retrospectively registered at clinicaltrials.gov on October 3, 2019 ( NCT04114214 ).
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http://dx.doi.org/10.1186/s12879-020-05330-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487694PMC
September 2020

Deep anaesthesia - Authors' reply.

Lancet 2020 09;396(10252):666-667

Department of Anaesthesia and Perioperative Medicine, Alfred Hospital, Melbourne, VIC, Australia; Department of Anaesthesia and Perioperative Medicine, Monash University, Melbourne, VIC, Australia.

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http://dx.doi.org/10.1016/S0140-6736(20)30898-9DOI Listing
September 2020

Genetic Deletion of Disrupts Maternal-Zygotic Transition and Embryonic Body Plan.

Front Genet 2020 4;11:853. Epub 2020 Aug 4.

School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.

is considered an important regulator during embryonic development, but genetic loss-of-function study is still lacking. Here we demonstrated that genetic deletion of the cluster resulted in developmental defects in cell movement, germ layer specification, axis patterning and organ progenitor formation in zebrafish. Transcriptome analysis indicated that the maternally provided transcripts were not properly degraded whereas the zygotic genome expressed genes were not fully activated in the mutants. We further found that a reciprocal regulatory loop exists between and maternally provided transcripts: the maternally provided transcripts (, , , and ) are required for biogenesis and function, whereas is required for the clearance of these maternally provided transcripts. These data provide the first genetic evidence that is required for maternal-zygotic transition and subsequent establishment of embryonic body plan.
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http://dx.doi.org/10.3389/fgene.2020.00853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417628PMC
August 2020

Perioperative ADministration of Dexamethasone And blood Glucose concentrations in patients undergoing elective non-cardiac surgery - the randomised controlled PADDAG trial.

Eur J Anaesthesiol 2020 Aug 21. Epub 2020 Aug 21.

From the Department of Anaesthesia and Pain Medicine, Royal Perth Hospital (TBC), School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia (TBC, EOL), Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria (TBC), Department of Anaesthesia and Pain Medicine, Fiona Stanley Hospital, Perth, Western Australia, Australia (EOL), Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, China (MAC), Department of Intensive Care Medicine, Royal Perth Hospital (KMH), Medical School, University of Western Australia (KMH) and School of Veterinary & Life Sciences, Murdoch University, Perth, Western Australia, Australia (KMH).

Background: The hyperglycaemic effect of dexamethasone in diabetic and nondiabetic patients in the peri-operative period is unknown.

Objective: To assess the effect of a single dose of intra-operative dexamethasone on peri-operative blood glucose.

Design: Multicentre, stratified, randomised trial.

Setting: University hospitals in Australia and Hong Kong.

Patients: A total of 302 adults scheduled for elective, noncardiac and nonobstetric surgical procedures under general anaesthesia, stratified by diabetes mellitus status, were randomised to receive placebo, 4 or 8 mg dexamethasone administered intravenously after induction of anaesthesia.

Main Outcome Measures: Maximum blood glucose within 24 h of surgery, and the interaction between glycated haemoglobin (HbA1c) and dexamethasone were the primary and secondary outcomes.

Results: The median [IQR] baseline blood glucose in the nondiabetes stratum in the placebo (n=81), 4 mg (n=81) and 8 mg dexamethasone (n=77) trial arms were respectively 5.3 [4.6 to 5.8], 5.0 [4.7 to 5.4] and 5.0 [4.2 to 5.9] mmol l. In the diabetes stratum these values were 6.6 [6.0 to 8.3]; (n=22), 6.1 [5.5 to 10.4]; (n=22) and 6.7 [5.6 to 8.3]; (n=19) mmol l. The median [IQR] maximum peri-operative blood glucose values in the nondiabetes stratum were 6.0 [5.3 to 6.8], 6.3 [5.5 to 7.3] and 6.3 [5.8 to 7.4] mmol l in the control, dexamethasone 4 mg and dexamethasone 8 mg arms, respectively. In the diabetes stratum these values were 10.3 [8.1 to 12.4], 12.6 [10.3 to 18.3] and 13.6 [11.2 to 0.1] mmol l. There was a significant interaction between pre-operative HbA1c value and 8 mg dexamethasone: every 1% increment in HbA1c produced a 4.0 mmol l elevation in maximal peri-operative glucose concentration.

Conclusion: Dexamethasone four or 8 mg did not induce greater hyperglycaemia compared with placebo for nondiabetic and well controlled diabetic patients. Maximal peri-operative blood glucose concentrations in patients with diabetes were related to baseline HbA1c values in a concentration-dependent fashion after 8 mg of dexamethasone.

Trial Registration: Australia and New Zealand Clinical Trials Registry (ACTRN12614001145695): URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367272.
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http://dx.doi.org/10.1097/EJA.0000000000001294DOI Listing
August 2020

Spinal microglia-neuron interactions in chronic pain.

J Leukoc Biol 2020 11 23;108(5):1575-1592. Epub 2020 Jun 23.

Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, Hong Kong SAR.

Current deficiency in our understanding of acute-to-chronic pain transition remains a hurdle for developing effective treatments against chronic pain. Whereas neurocentric mechanisms alone are insufficient to provide satisfactory explanation for such transition, neuro-immune crosstalk has attracted attention in recent pain research. In contrast to brain microglia, spinal microglia are activated immediately in various pain states. The fast-responsive enrichment and activation of spinal microglia among different pain conditions have highlighted the crucial role of neuroinflammation caused by microglia-neuron crosstalk in pain initiation. Recent studies have revealed spinal microglia-neuron interactions are also involved in chronic pain maintenance, albeit, with different anatomic distribution, cellular and molecular mechanisms, and biologic functions. Delineating the exact temporal discrepancies of spinal microglia distribution and functions along acute-to-chronic pain transition may provide additional mechanistic insights for drug development to prevent deterioration of acute pain into the chronic state. This narrative review summerizes the longitudinal alterations of spinal microglia-neuron interactions in the initiation of pain hypersensitivity, acute-to-chronic pain progression, and chronic pain maintenance, followed by an overview of current clinical translation of preclinical studies on spinal microglia. This review highlights the crucial role of the interaction between spinal microglia and neighboring neurons in the initiation and maintenance of pain hypersensitivity, in relation to the release of cytokines, chemokines, and neuroactive substances, as well as the modulation of synaptic plasticity. Further exploration of the uncharted functions of spinal microglia-neuron crosstalk may lead to the design of novel drugs for preventing acute-to-chronic pain transition.
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http://dx.doi.org/10.1002/JLB.3MR0520-695RDOI Listing
November 2020

LINC01133: an emerging tumor-associated long non-coding RNA in tumor and osteosarcoma.

Environ Sci Pollut Res Int 2020 Sep 19;27(26):32467-32473. Epub 2020 Jun 19.

Department of Anaesthesia and Intensive Care and Peter Hung Pain Research Institute, The University of Hong Kong, Pok Fu Lam, Hong Kong.

Emerging evidence suggested that long non-coding RNAs (lncRNAs) play pivotal roles in tumorigenesis. LINC01133 is a newly identified lncRNA first discovered as an oncogene in lung squamous cell carcinoma. Subsequent studies further demonstrated this lncRNA was deregulated in a wide spectrum of tumors, including colorectal, gastric, lung, and pancreatic ductal adenocarcinoma as well as osteosarcoma and hepatocellular carcinoma. Intriguingly, this lncRNA exerted oncogenic or tumor-suppressive action in a tissue-dependent manner. This review sought to summarize our current understanding concerning the deregulation of LINC01133 in human tumors in relation to its molecular mechanisms and cellular functions. The clinical utilization of LINC01133 as a potential prognostic biomarker and a treatment target is also discussed.
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http://dx.doi.org/10.1007/s11356-020-09631-1DOI Listing
September 2020

Embryonic gene expression altered by maternal exposure to air pollution in rats.

Environ Sci Pollut Res Int 2020 Sep 4;27(25):31699-31705. Epub 2020 Jun 4.

Department of Anaesthesia and Intensive Care and Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Hong Kong, Hong Kong.

Exposure to air pollution is known to increase the risks for cardiovascular, pulmonary and metabolic diseases. Growing evidences also indicated that air pollution exposure during pregnancy could negatively impact on early embryonic development and children's health. We performed RNA sequencing to identify deregulated mRNAs in air pollution-exposed rat embryos. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to analyse the potential cellular functions of deregulated mRNAs. Our analysis indicated that a total of 1678 mRNAs were differentially expressed on gestation day 9 upon in utero exposure to fine particulate matter of > 200 μg/m, among which 1098 mRNAs were downregulated and 580 mRNAs were upregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed gap junction, cell adhesion, axon guidance and the neurotrophin signalling pathway as key biological processes perturbed by air pollution exposure. Furthermore, reconstruction of the mRNA regulatory network highlighted the central roles of Tbx4, Bmp4, Sox10, Wnt9b, Bmp7 and Foxc2. These data suggested that embryonic mRNA deregulation may underlie the formation of air pollution-associated congenital defects.
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http://dx.doi.org/10.1007/s11356-020-09413-9DOI Listing
September 2020

Association Between Myocardial Injury and Cardiovascular Outcomes of Orthopaedic Surgery: A Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION) Substudy.

J Bone Joint Surg Am 2020 May;102(10):880-888

McMaster University, Hamilton, Ontario, Canada.

Background: Myocardial injury after noncardiac surgery (MINS) is common and of prognostic importance. Little is known about MINS in orthopaedic surgery. The diagnostic criterion for MINS was a level of ≥0.03 ng/mL on a non-high-sensitivity troponin T (TnT) assay due to myocardial ischemia.

Methods: We undertook an international, prospective study of 15,103 patients ≥45 years of age who had inpatient noncardiac surgery; 3,092 underwent orthopaedic surgery. Non-high-sensitivity TnT assays were performed on postoperative days 0, 1, 2, and 3. Among orthopaedic patients, we determined (1) the prognostic relevance of the MINS diagnostic criteria, (2) the 30-day mortality rate for those with and without MINS, and (3) the probable proportion of MINS cases that would go undetected without troponin monitoring because of a lack of an ischemic symptom.

Results: Three hundred and sixty-seven orthopaedic patients (11.9%) had MINS. MINS was associated independently with 30-day mortality including among those who had had orthopaedic surgery. Orthopaedic patients without and with MINS had a 30-day mortality rate of 1.0% and 9.8%, respectively (odds ratio [OR], 11.28; 95% confidence interval [CI], 6.72 to 18.92). The 30-day mortality rate was increased for patients with MINS who had an ischemic feature (i.e., symptoms, or evidence of ischemia on electrocardiography or imaging) (OR, 18.25; 95% CI, 10.06 to 33.10) and for those who did not have an ischemic feature (OR, 7.35; 95% CI, 3.37 to 16.01). The proportion of orthopaedic patients with MINS who were asymptomatic and in whom the myocardial injury would have probably gone undetected without TnT monitoring was 81.3% (95% CI, 76.3% to 85.4%).

Conclusions: One in 8 orthopaedic patients in our study had MINS, and MINS was associated with a higher mortality rate regardless of symptoms. Troponin levels should be measured after surgery in at-risk patients because most MINS cases (>80%) are asymptomatic and would go undetected without routine measurements.

Level Of Evidence: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.2106/JBJS.18.01305DOI Listing
May 2020

Cathelicidin preserves intestinal barrier function in polymicrobial sepsis.

Crit Care 2020 02 10;24(1):47. Epub 2020 Feb 10.

Department of Anaesthesia and Intensive Care and Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region, China.

Objectives: The intestinal epithelium compartmentalizes the sterile bloodstream and the commensal bacteria in the gut. Accumulating evidence suggests that this barrier is impaired in sepsis, aggravating systemic inflammation. Previous studies reported that cathelicidin is differentially expressed in various tissues in sepsis. However, its role in sepsis-induced intestinal barrier dysfunction has not been investigated.

Design: To examine the role of cathelicidin in polymicrobial sepsis, cathelicidin wild-(Cnlp) and knockout (Cnlp) mice underwent cecal-ligation and puncture (CLP) followed by the assessment of septic mortality and morbidity as well as histological, biochemical, immunological, and transcriptomic analyses in the ileal tissues. We also evaluated the prophylactic and therapeutic efficacies of vitamin D3 (an inducer of endogenous cathelicidin) in the CLP-induced murine polymicrobial sepsis model.

Results: The ileal expression of cathelicidin was increased by three-fold after CLP, peaking at 4 h. Knockout of Cnlp significantly increased 7-day mortality and was associated with a higher murine sepsis score. Alcian-blue staining revealed a reduced number of mucin-positive goblet cells, accompanied by reduced mucin expression. Increased number of apoptotic cells and cleavage of caspase-3 were observed. Cnlp deletion increased intestinal permeability to 4kD fluorescein-labeled dextran and reduced the expression of tight junction proteins claudin-1 and occludin. Notably, circulating bacterial DNA load increased more than two-fold. Transcriptome analysis revealed upregulation of cytokine/inflammatory pathway. Depletion of Cnlp induced more M1 macrophages and neutrophils compared with the wild-type mice after CLP. Mice pre-treated with cholecalciferol (an inactive form of vitamin D3) or treated with 1alpha, 25-dihydroxyvitamin D3 (an active form of VD3) had decreased 7-day mortality and significantly less severe symptoms. Intriguingly, the administration of cholecalciferol after CLP led to worsened 7-day mortality and the associated symptoms.

Conclusions: Endogenous cathelicidin promotes intestinal barrier integrity accompanied by modulating the infiltration of neutrophils and macrophages in polymicrobial sepsis. Our data suggested that 1alpha, 25-dihydroxyvitamin D3 but not cholecalciferol is a potential therapeutic agent for treating sepsis.
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http://dx.doi.org/10.1186/s13054-020-2754-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011568PMC
February 2020

One-year Results of a Factorial Randomized Trial of Aspirin versus Placebo and Clonidine versus Placebo in Patients Having Noncardiac Surgery.

Anesthesiology 2020 04;132(4):692-701

From the Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio (D.I.S., A.K., A.T.) Population Health Research Institute (D.I.S., D.C., S.Y., Y.L.M., A.L., K.B., S.P., P.J.D.) Department of Medicine (D.C., S.Y., G.G., P.J.D.) Department of Health Research Methods, Evidence, and Impact (D.C., S.Y., G.G., Y.L.M., A.L., P.J.D.) Faculty of Health Sciences, Department of Anesthesia (Y.L.M.) Department of Surgery (R.W., A.L.), McMaster University, Hamilton, Ontario, Canada Department of Anaesthesia and Pain Management, Royal Melbourne Hospital and Centre for Integrated Critical Care, University of Melbourne, Melbourne, Australia (K.L.) Public Health and Clinical Epidemiology-Iberoamerican Cochrane Centre, Barcelona, Spain (E.P.) University of Alberta and Mazankowski Alberta Heart Institute, Edmonton, Alberta, Canada (M.G.) Department of Research, Foundation for Pediatric Cardiology, Institute of Cardiology and Faculty of Health Sciences (Departamento de Investigaciones, Fundación Cardioinfantil-Instituto de Cardiología and Facultad de Ciencias de la Salud), Universidad Autónoma de Bucaramanga, Colombia (J.C.V.) University of Western Ontario, London, Ontario, Canada (M.M.) Department of Clinical Research, Narayana Hrudayalaya Limited, Bangalore, India (A.S.) University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa (B.M.B.) Department of Anaesthesia and Intensive Care, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark (C.S.M.) Department of Anesthesiology and Perioperative Medicine, Kingston Health Sciences Centre and Queen's University, Kingston, Canada (J.L.P., I.G.) St. John's Medical College and Research Institute, Bangalore, Karnataka, India (D.X.) Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong (M.T.V.C.) University of North Carolina School of Medicine, Chapel Hills, North Carolina (P.A.K.) NHS Grampian and the University of Aberdeen, Aberdeen, United Kingdom (P.F.) Knowledge and Evidence Unite (Unidad de Conocimiento y Evidencia), Universidad Peruana Cayetano Heredia, Lima, Peru (G.M.) Department of Anaesthesia, Intensive Care, and Pain Medicine, Medical University of Vienna, Vienna, Austria (E.F.) Shifa International Hospitals, Islamabad, Pakistan (M.A.) University of the Andes and Santa Maria Clinic (Universidad de Los Andes and Clinica Santa María), Santiago, Chile (D.T.) Department of Anesthesiology, University of Malaya, Kuala Lumpur, Malaysia (C.Y.W.) Biomedical Research Institute (IIB - Sant Pau), Barcelona, Spain (P.P.) Hospital Israelita Albert Einstein, São Paulo, Brazil (O.B.) Department of Surgery, University of Manitoba, Winnipeg, Manitoba, Canada (S.S.) Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy (G.L.).

Background: The authors previously reported that perioperative aspirin and/or clonidine does not prevent a composite of death or myocardial infarction 30 days after noncardiac surgery. Moreover, aspirin increased the risk of major bleeding and clonidine caused hypotension and bradycardia. Whether these complications produce harm at 1 yr remains unknown.

Methods: The authors randomized 10,010 patients with or at risk of atherosclerosis and scheduled for noncardiac surgery in a 1:1:1:1 ratio to clonidine/aspirin, clonidine/aspirin placebo, clonidine placebo/aspirin, or clonidine placebo/aspirin placebo. Patients started taking aspirin or placebo just before surgery; those not previously taking aspirin continued daily for 30 days, and those taking aspirin previously continued for 7 days. Patients were also randomly assigned to receive clonidine or placebo just before surgery, with the study drug continued for 72 h.

Results: Neither aspirin nor clonidine had a significant effect on the primary 1-yr outcome, a composite of death or nonfatal myocardial infarction, with a 1-yr hazard ratio for aspirin of 1.00 (95% CI, 0.89 to 1.12; P = 0.948; 586 patients [11.8%] vs. 589 patients [11.8%]) and a hazard ratio for clonidine of 1.07 (95% CI, 0.96 to 1.20; P = 0.218; 608 patients [12.1%] vs. 567 patients [11.3%]), with effect on death or nonfatal infarction. Reduction in death and nonfatal myocardial infarction from aspirin in patients who previously had percutaneous coronary intervention at 30 days persisted at 1 yr. Specifically, the hazard ratio was 0.58 (95% CI, 0.35 to 0.95) in those with previous percutaneous coronary intervention and 1.03 (95% CI, 0.91to 1.16) in those without (interaction P = 0.033). There was no significant effect of either drug on death, cardiovascular complications, cancer, or chronic incisional pain at 1 yr (all P > 0.1).

Conclusions: Neither perioperative aspirin nor clonidine have significant long-term effects after noncardiac surgery. Perioperative aspirin in patients with previous percutaneous coronary intervention showed persistent benefit at 1 yr, a plausible sub-group effect.
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http://dx.doi.org/10.1097/ALN.0000000000003158DOI Listing
April 2020

Preoperative N-Terminal Pro-B-Type Natriuretic Peptide and Cardiovascular Events After Noncardiac Surgery: A Cohort Study.

Ann Intern Med 2020 01 24;172(2):96-104. Epub 2019 Dec 24.

McMaster University and Population Health Research Institute, Hamilton, Ontario, Canada (F.K.B., M.M., G.P., M.W., R.W., A.L., S.Y., P.D.).

Background: Preliminary data suggest that preoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP) may improve risk prediction in patients undergoing noncardiac surgery.

Objective: To determine whether preoperative NT-proBNP has additional predictive value beyond a clinical risk score for the composite of vascular death and myocardial injury after noncardiac surgery (MINS) within 30 days after surgery.

Design: Prospective cohort study.

Setting: 16 hospitals in 9 countries.

Patients: 10 402 patients aged 45 years or older having inpatient noncardiac surgery.

Measurements: All patients had NT-proBNP levels measured before surgery and troponin T levels measured daily for up to 3 days after surgery.

Results: In multivariable analyses, compared with preoperative NT-proBNP values less than 100 pg/mL (the reference group), those of 100 to less than 200 pg/mL, 200 to less than 1500 pg/mL, and 1500 pg/mL or greater were associated with adjusted hazard ratios of 2.27 (95% CI, 1.90 to 2.70), 3.63 (CI, 3.13 to 4.21), and 5.82 (CI, 4.81 to 7.05) and corresponding incidences of the primary outcome of 12.3% (226 of 1843), 20.8% (542 of 2608), and 37.5% (223 of 595), respectively. Adding NT-proBNP thresholds to clinical stratification (that is, the Revised Cardiac Risk Index [RCRI]) resulted in a net absolute reclassification improvement of 258 per 1000 patients. Preoperative NT-proBNP values were also statistically significantly associated with 30-day all-cause mortality (less than 100 pg/mL [incidence, 0.3%], 100 to less than 200 pg/mL [incidence, 0.7%], 200 to less than 1500 pg/mL [incidence, 1.4%], and 1500 pg/mL or greater [incidence, 4.0%]).

Limitation: External validation of the identified NT-proBNP thresholds in other cohorts would reinforce our findings.

Conclusion: Preoperative NT-proBNP is strongly associated with vascular death and MINS within 30 days after noncardiac surgery and improves cardiac risk prediction in addition to the RCRI.

Primary Funding Source: Canadian Institutes of Health Research.
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http://dx.doi.org/10.7326/M19-2501DOI Listing
January 2020

Emerging roles of non-coding RNAs in scoliosis.

Cell Prolif 2020 Feb 12;53(2):e12736. Epub 2019 Dec 12.

Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong, Hong Kong.

Scoliosis, a complex three-dimensional deformity of the spine with the Cobb angle (a measure of the spinal lateral curvature) >10 degree, encompasses a spectrum of pathologies, including congenital, idiopathic, syndromic and neuromuscular aetiologies. The pathogenesis is multifactorial involving both environmental and genetic factors but the exact cellular and molecular mechanisms of disease development remain largely unknown. Emerging evidence showed that non-coding RNAs (ncRNAs), namely microRNAs, long ncRNAs and circular RNAs, are deregulated in many orthopaedic diseases, including scoliosis. Importantly, these deregulated ncRNAs functionally participate in the initiation and progression of scoliosis. Here, we review recent progress in ncRNA research on scoliosis.
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http://dx.doi.org/10.1111/cpr.12736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046479PMC
February 2020

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on the Role of Neuromonitoring in Perioperative Outcomes: Electroencephalography.

Anesth Analg 2020 05;130(5):1278-1291

Department of Anesthesiology, Stony Brook School of Medicine, Stony Brook, New York.

Electroencephalographic (EEG) monitoring to indicate brain state during anesthesia has become widely available. It remains unclear whether EEG-guided anesthesia influences perioperative outcomes. The sixth Perioperative Quality Initiative (POQI-6) brought together an international team of multidisciplinary experts from anesthesiology, biomedical engineering, neurology, and surgery to review the current literature and to develop consensus recommendations on the utility of EEG monitoring during anesthesia. We retrieved a total of 1023 articles addressing the use of EEG monitoring during anesthesia and conducted meta-analyses from 15 trials to determine the effect of EEG-guided anesthesia on the rate of unintentional awareness, postoperative delirium, neurocognitive disorder, and long-term mortality after surgery. After considering current evidence, the working group recommends that EEG monitoring should be considered as part of the vital organ monitors to guide anesthetic management. In addition, we encourage anesthesiologists to be knowledgeable in basic EEG interpretation, such as raw waveform, spectrogram, and processed indices, when using these devices. Current evidence suggests that EEG-guided anesthesia reduces the rate of awareness during total intravenous anesthesia and has similar efficacy in preventing awareness as compared with end-tidal anesthetic gas monitoring. There is, however, insufficient evidence to recommend the use of EEG monitoring for preventing postoperative delirium, neurocognitive disorder, or postoperative mortality.
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http://dx.doi.org/10.1213/ANE.0000000000004502DOI Listing
May 2020

Preoperative Vitamin D Concentration and Cardiac, Renal, and Infectious Morbidity after Noncardiac Surgery.

Anesthesiology 2020 01;132(1):121-130

From the Department of Outcomes Research (A.T., A.S.A., C.H., P.S., K.M., A.K., K.R., D.I.S.) Department of General Anesthesiology (A.T., K.M., A.K., K.R.) Anesthesiology Institute, and the Department of Quantitative Health Sciences (A.S.A.), Cleveland Clinic, Cleveland, Ohio the Department of Health Research Methods, Evidence, and Impact (P.J.D., E.D.) the Department of Medicine (A.P., M.T.), McMaster University, Hamilton, Canada the Population Health Research Institute, Hamilton, Canada (P.J.D., E.D.) Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom (R.P.) the Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China (M.T.V.C., W.K.K.W.) the Department of Surgery, University of Manitoba, Winnipeg, Canada (S.S.) the Department of Medicine, Western University, London, Canada (A.X.G.) the Department of Cardiology, Leeds General Infirmary, Leeds, United Kingdom (R.S.).

Background: Low 25-hydroxyvitamin D is associated with cardiovascular, renal, and infectious risks. Postsurgical patients are susceptible to similar complications, but whether vitamin D deficiency contributes to postoperative complications remains unclear. We tested whether low preoperative vitamin D is associated with cardiovascular events within 30 days after noncardiac surgery.

Methods: We evaluated a subset of patients enrolled in the biobank substudy of the Vascular events In noncardiac Surgery patIents cOhort evaluatioN (VISION) study, who were at least 45 yr with at least an overnight hospitalization. Blood was collected preoperatively, and 25-hydroxyvitamin D was measured in stored samples. The primary outcome was the composite of cardiovascular events (death, myocardial injury, nonfatal cardiac arrest, stroke, congestive heart failure) within 30 postoperative days. Secondary outcomes were kidney injury and infectious complications.

Results: A total of 3,851 participants were eligible for analysis. Preoperative 25-hydroxyvitamin D concentration was 70 ± 30 nmol/l, and 62% of patients were vitamin D deficient. Overall, 26 (0.7%) patients died, 41 (1.1%) had congestive heart failure or nonfatal cardiac arrest, 540 (14%) had myocardial injury, and 15 (0.4%) had strokes. Preoperative vitamin D concentration was not associated with the primary outcome (average relative effect odds ratio [95% CI]: 0.93 [0.85, 1.01] per 10 nmol/l increase in preoperative vitamin D, P = 0.095). However, it was associated with postoperative infection (average relative effect odds ratio [95% CI]: 0.94 [0.90, 0.98] per 10 nmol/l increase in preoperative vitamin D, P adjusted value = 0.005) and kidney function (estimated mean change in postoperative estimated glomerular filtration rate [95% CI]: 0.29 [0.11, 0.48] ml min 1.73 m per 10 nmol/l increase in preoperative vitamin D, P adjusted value = 0.004).

Conclusions: Preoperative vitamin D was not associated with a composite of postoperative 30-day cardiac outcomes. However, there was a significant association between vitamin D deficiency and a composite of infectious complications and decreased kidney function. While renal effects were not clinically meaningful, the effect of vitamin D supplementation on infectious complications requires further study.
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http://dx.doi.org/10.1097/ALN.0000000000003000DOI Listing
January 2020

Anaesthetic depth and complications after major surgery: an international, randomised controlled trial.

Lancet 2019 11 20;394(10212):1907-1914. Epub 2019 Oct 20.

Monash University, Melbourne, VIC, Australia; Royal Melbourne Hospital and University of Melbourne, Melbourne, VIC, Australia.

Background: An association between increasing anaesthetic depth and decreased postoperative survival has been shown in observational studies; however, evidence from randomised controlled trials is lacking. Our aim was to compare all-cause 1-year mortality in older patients having major surgery and randomly assigned to light or deep general anaesthesia.

Methods: In an international trial, we recruited patients from 73 centres in seven countries who were aged 60 years and older, with significant comorbidity, having surgery with expected duration of more than 2 h, and an anticipated hospital stay of at least 2 days. We randomly assigned patients who had increased risk of complications after major surgery to receive light general anaesthesia (bispectral index [BIS] target 50) or deep general anaesthesia (BIS target 35). Anaesthetists also nominated an appropriate range for mean arterial pressure for each patient during surgery. Patients were randomly assigned in permuted blocks by region immediately before surgery, with the patient and assessors masked to group allocation. The primary outcome was 1-year all-cause mortality. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12612000632897, and is closed to accrual.

Findings: Patients were enrolled between Dec 19, 2012, and Dec 12, 2017. Of the 18 026 patients screened as eligible, 6644 were enrolled, randomly assigned to treatment or control, and formed the intention-to-treat population (3316 in the BIS 50 group and 3328 in the BIS 35 group). The median BIS was 47·2 (IQR 43·7 to 50·5) in the BIS 50 group and 38·8 (36·3 to 42·4) in the BIS 35 group. Mean arterial pressure was 3·5 mm Hg (4%) higher (median 84·5 [IQR 78·0 to 91·3] and 81·0 [75·4 to 87·6], respectively) and volatile anaesthetic use was 0·26 minimum alveolar concentration (30%) lower (0·62 [0·52 to 0·73] and 0·88 [0·74 to 1·04], respectively) in the BIS 50 than the BIS 35 group. 1-year mortality was 6·5% (212 patients) in the BIS 50 group and 7·2% (238 patients) in the BIS 35 group (hazard ratio 0·88, 95% CI 0·73 to 1·07, absolute risk reduction 0·8%, 95% CI -0·5 to 2·0). Grade 3 adverse events occurred in 954 (29%) patients in the BIS 50 group and 909 (27%) patients in the BIS 35 group; and grade 4 adverse events in 265 (8%) and 259 (8%) patients, respectively. The most commonly reported adverse events were infections, vascular disorders, cardiac disorders, and neoplasms.

Interpretation: Among patients at increased risk of complications after major surgery, light general anaesthesia was not associated with lower 1-year mortality than deep general anaesthesia. Our trial defines a broad range of anaesthetic depth over which anaesthesia may be safely delivered when titrating volatile anaesthetic concentrations using a processed electroencephalographic monitor.

Funding: Health Research Council of New Zealand; National Health and Medical Research Council, Australia; Research Grant Council of Hong Kong; National Institute for Health and Research, UK; and National Institutes of Health, USA.
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http://dx.doi.org/10.1016/S0140-6736(19)32315-3DOI Listing
November 2019

Differentially expressed circular RNAs in air pollution-exposed rat embryos.

Environ Sci Pollut Res Int 2019 Nov 21;26(33):34421-34429. Epub 2019 Oct 21.

Department of Orthopedic Surgery, The General Hospital of Xingtai Mining Industry Bloc., Orthopaedic Hospital of Xingtai, Xingtai, Hebei, China.

Circular RNAs (circRNAs) are an important class of non-coding RNAs partly by acting as microRNA sponges. Growing evidence indicates that air pollution exposure during pregnancy could lead to congenital defects in the offspring. In this study, using circRNAs sequencing, we profiled differentially expressed circRNAs in rat embryos exposed to a high concentration (> 200 μg/m) of fine particulate matter (PM) in utero. Compared with the control embryos whose mothers were reared in clean air, 25 and 55 circRNAs were found to be downregulated and upregulated, respectively, in the air pollution-exposed group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of circRNA-coexpressed genes indicated that segmentation, brain development, and system development together with lysine degradation, Rap1 signaling pathway, and adrenergic signaling were deregulated by in utero air pollution exposure. We also identified the central role of three circRNAs, namely circ_015003, circ_030724, and circ_127215 in the circRNA-microRNA interaction network. These data suggested that circRNA deregulation might play a crucial role in the development of air pollution-associated congenital malformations.
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http://dx.doi.org/10.1007/s11356-019-06489-wDOI Listing
November 2019