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1.
Cell Prolif ; : e12936, 2020 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-33103338

RESUMO

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.

2.
J Clin Sleep Med ; 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33112227

RESUMO

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 different ethnic groups undergoing surgery. METHODS: This was a multicentre prospective cohort study involving patients with cardiovascular risk factors undergoing major non-cardiac surgery. Patients underwent home sleep apnea testing. All patients completed the STOP-Bang questionnaire. The predictive parameters of STOP-Bang scores were calculated against apnea-hypopnea index (AHI). RESULTS: 1,205 patients from four ethnic groups (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, diagnostic parameters were presented using BMI threshold of 27.5 kg/m² with the area under curve (AUC) to predict moderate-to-severe OSA were 0.709 (0.665-0.753) and 0.722 (0.635-0.808) respectively. For the Malay and Caucasian, diagnostic parameters were presented using BMI threshold of 35 kg/m² with the AUC for predicting moderate-to-severe OSA were 0.645 (0.572-0.720) and 0.657 (0.578-0.736) respectively. Balancing the sensitivity and specificity, the optimal STOP-Bang threshold for the Chinese, Indian, Malay and Caucasian 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, and 35 kg/m² for Malay and Caucasian. The optimal STOP-Bang threshold for the Chinese, Indian, Malay and Caucasian is 4 or greater. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov, title: Postoperative Vascular Events in Unrecognised Obstructive Sleep Apnea, identifier: NCT01494181, URL: https://clinicaltrials.gov/ct2/show/study/NCT01494181.

3.
Lancet ; 396(10252): 666-667, 2020 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-32891207

Assuntos
Anestesia
4.
BMC Infect Dis ; 20(1): 652, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894059

RESUMO

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 ).


Assuntos
Registros Eletrônicos de Saúde , Monitoramento Epidemiológico , Carga Global da Doença/métodos , Sepse/diagnóstico , Sepse/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Confiabilidade dos Dados , Estudos de Viabilidade , Feminino , Hong Kong/epidemiologia , Hospitalização , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Sepse/mortalidade , Centros de Atenção Terciária
5.
Eur J Anaesthesiol ; 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32833858

RESUMO

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.

6.
Front Genet ; 11: 853, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32849832

RESUMO

MiR-430 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 miR-430 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 miR-430 mutants. We further found that a reciprocal regulatory loop exists between miR-430 and maternally provided transcripts: the maternally provided transcripts (Nanog, Dicer1, Dgcr8, and AGOs) are required for miR-430 biogenesis and function, whereas miR-430 is required for the clearance of these maternally provided transcripts. These data provide the first genetic evidence that miR-430 is required for maternal-zygotic transition and subsequent establishment of embryonic body plan.

7.
Environ Sci Pollut Res Int ; 27(25): 31699-31705, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32500497

RESUMO

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/m3, 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.


Assuntos
Poluição do Ar , RNA Longo não Codificante , Animais , Criança , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Exposição Materna , Gravidez , RNA Mensageiro , Ratos
8.
J Leukoc Biol ; 108(5): 1575-1592, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32573822

RESUMO

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.

9.
Environ Sci Pollut Res Int ; 27(26): 32467-32473, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32556990

RESUMO

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.


Assuntos
Neoplasias Ósseas , Neoplasias Pulmonares/genética , Osteossarcoma , RNA Longo não Codificante , Regulação Neoplásica da Expressão Gênica , Humanos
10.
J Bone Joint Surg Am ; 102(10): 880-888, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32118652

RESUMO

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.

11.
Anesthesiology ; 132(4): 692-701, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32022771

RESUMO

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.


Assuntos
Analgésicos/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Aspirina/administração & dosagem , Clonidina/administração & dosagem , Assistência Perioperatória/métodos , Complicações Pós-Operatórias/diagnóstico , Idoso , Analgésicos/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Clonidina/efeitos adversos , Feminino , Seguimentos , Humanos , Internacionalidade , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/prevenção & controle , Assistência Perioperatória/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Fatores de Tempo
12.
Crit Care ; 24(1): 47, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-32041659

RESUMO

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.


Assuntos
Peptídeos Catiônicos Antimicrobianos , Mucosa Intestinal , Sepse , Animais , Peptídeos Catiônicos Antimicrobianos/fisiologia , Mucosa Intestinal/metabolismo , Macrófagos , Masculino , Camundongos , Camundongos Knockout , Neutrófilos , Sepse/fisiopatologia , Vitamina D/análogos & derivados , Vitamina D/farmacologia
13.
Semin Cell Dev Biol ; 101: 41-50, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31408699

RESUMO

Autophagy is a conserved intracellular degradation process enclosing the bulk of cytosolic components for lysosomal degradation to maintain cellular homeostasis. Accumulating evidences showed that a specialized form of autophagy, known as xenophagy, could serve as an innate immune response to defend against pathogens invading inside the host cells. Correspondingly, infectious pathogens have developed a variety of strategies to disarm xenophagy, leading to a prolonged and persistent intracellular colonization. In this review, we first summarize the current knowledge about the general mechanisms of intracellular bacterial infections and xenophagy. We then focus on the ongoing battle between these two processes.

14.
J Neurosurg Anesthesiol ; 32(1): 41-47, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30531556

RESUMO

BACKGROUND: The effect of choice of anesthesia on clinical outcome for endovascular treatment (EVT) in patients with acute ischemic stroke (AIS) remains unclear. METHODS: We conducted a pilot trial of 43 patients with acute anterior circulation ischemic stroke having EVT. Patients were randomly allocated to receive general anesthesia or conscious sedation. We documented the rate of recruitment and rate of conversion from conscious sedation to general anesthesia. In addition, we recorded the change in National Institute of Health stroke scale (NIHSS) on day 7, the rate of successful reperfusion and measured neurological function by certified researchers using modified Rankin Score (mRS 0 to 2) at 90 days. RESULTS: The recruitment rate was 31.4% and majority of patients were excluded because of delay in hospital presentation and posterior circulation stroke. The rate of conversion from conscious sedation to general anesthesia was 18.2%. This was primarily related to excessive sedation and uncontrolled movement. Change in NIHSS score, rate of successful reperfusion and functional recovery were similar between groups. CONCLUSIONS: It was feasible to randomize AIS patients receiving either general anesthesia or conscious sedation for EVT.


Assuntos
Anestesia Geral/métodos , Anestesia/métodos , Isquemia Encefálica/cirurgia , Sedação Consciente/métodos , Procedimentos Endovasculares/métodos , Acidente Vascular Cerebral/cirurgia , Idoso , Anestesia/efeitos adversos , Anestesia Geral/efeitos adversos , Sedação Consciente/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Recuperação de Função Fisiológica , Reperfusão , Resultado do Tratamento
15.
Anesthesiology ; 132(1): 121-130, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31651439

RESUMO

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.


Assuntos
Doenças Transmissíveis/epidemiologia , Cardiopatias/epidemiologia , Nefropatias/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Período Pré-Operatório , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Idoso , Doenças Transmissíveis/sangue , Comorbidade , Feminino , Cardiopatias/sangue , Humanos , Nefropatias/sangue , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Vitamina D/análogos & derivados , Vitamina D/sangue
16.
Cell Prolif ; 53(2): e12736, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31828859

RESUMO

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.


Assuntos
RNA não Traduzido/genética , Escoliose/genética , Animais , Humanos
17.
Ann Intern Med ; 172(2): 96-104, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31869834

RESUMO

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.


Assuntos
Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Complicações Pós-Operatórias/sangue , Procedimentos Cirúrgicos Operatórios , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Período Pré-Operatório , Estudos Prospectivos , Troponina T/sangue
18.
Anesth Analg ; 130(5): 1278-1291, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31764163

RESUMO

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.


Assuntos
Eletroencefalografia/normas , Monitorização Neurofisiológica Intraoperatória/normas , Assistência Perioperatória/normas , Qualidade da Assistência à Saúde/normas , Recuperação de Função Fisiológica , Sociedades Médicas/normas , Anestesia Geral/métodos , Anestesia Geral/normas , Consenso , Eletroencefalografia/métodos , Humanos , Monitorização Neurofisiológica Intraoperatória/métodos , Assistência Perioperatória/métodos , Resultado do Tratamento , Estados Unidos
19.
Eur Heart J ; 41(5): 645-651, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31237939

RESUMO

AIMS: To determine the 1-year risk of stroke and other adverse outcomes in patients with a new diagnosis of perioperative atrial fibrillation (POAF) after non-cardiac surgery. METHODS AND RESULTS: The PeriOperative ISchemic Evaluation (POISE)-1 trial evaluated the effects of metoprolol vs. placebo in 8351 patients, and POISE-2 compared the effect of aspirin vs. placebo, and clonidine vs. placebo in 10 010 patients. These trials included patients with, or at risk of, cardiovascular disease who were undergoing non-cardiac surgery. For the purpose of this study, we combined the POISE datasets, excluding 244 patients who were in atrial fibrillation (AF) at the time of randomization. Perioperative atrial fibrillation was defined as new AF that occurred within 30 days after surgery. Our primary outcome was the incidence of stroke at 1 year of follow-up; secondary outcomes were mortality and myocardial infarction (MI). We compared outcomes among patients with and without POAF using multivariable adjusted Cox proportional hazards models. Among 18 117 patients (mean age 69 years, 57.4% male), 404 had POAF (2.2%). The stroke incidence 1 year after surgery was 5.58 vs. 1.54 per 100 patient-years in patients with and without POAF, adjusted hazard ratio (aHR) 3.43, 95% confidence interval (CI) 2.00-5.90; P < 0.001. Patients with POAF also had an increased risk of death (incidence 31.37 vs. 9.34; aHR 2.51, 95% CI 2.01-3.14; P < 0.001) and MI (incidence 26.20 vs. 8.23; aHR 5.10, 95% CI 3.91-6.64; P < 0.001). CONCLUSION: Patients with POAF have a significantly increased risk of stroke, MI, and death at 1 year. Intervention studies are needed to evaluate risk reduction strategies in this high-risk population.

20.
Heart Asia ; 11(2): e011155, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31565074

RESUMO

Objectives: This meta-analysis and systematic review seeks to compare both characteristic parameters and procedural outcomes of atrial fibrillation (AF) catheter ablation in patients under general anaesthesia (GA)/deep sedation and mild/moderate sedation. Background: Catheter ablation has become a widely applied intervention for treating symptomatic AF and arrhythmias that are refractory to medical therapy. It can be conducted through from mild sedation to GA. Methods: PubMed and Embase were searched up to July 2018 for randomised controlled trials, cohort and observational studies that assessed the outcomes of catheter ablation under GA/deep sedation or mild/moderate sedation. Nine studies were included in this meta-analysis after screening with the inclusion and exclusion criteria. Heterogeneity between studies and publication bias was evaluated by I2 index and Egger's regression, respectively. Results: Our meta-analysis found catheter AF ablation with GA/deep sedation to be associated with reduced risk of recurrence (RR: 0.79, 95% CI 0.56 to 1.13, p=0.20) and complications (RR: 0.95, 95% CI 0.64 to 1.42, p=0.82), though statistically insignificant. In terms of procedural parameters, there was no significant difference between the two groups for both procedural time (SMD: -0.13, 95% CI -0.90 to 0.63, p=0.74) and fluoroscopy time (SMD: -0.41, 95% CI -1.40 to 0.58, p=0.41). Univariate meta-regression did not reveal any covariates as a moderating factor for complication and recurrence risk. Conclusion: Apart from an increased likelihood of procedural success, ablation by GA/deep sedation was found to be non-significantly different from the mild/moderate sedation approach in both procedural parameters and outcome measures.

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