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Influx of activated neutrophils into the lungs is the histopathologic hallmark of acute lung injury (ALI) after intestinal ischemia/reperfusion (I/R). Neutrophils can release DNA and granular proteins to form cytotoxic neutrophil extracellular traps (NETs), which promotes bystander tissue injury. However, whether NETs are responsible for the remote ALI after intestinal I/R and the mechanisms underlying the dissemination of harmful gut-derived mediators to the lungs are unknown. In the C57BL/6J mouse intestinal I/R model, DNase I-mediated degradation and protein arginine deiminase 4 (PAD4) inhibitor-mediated inhibition of NET treatments reduced NET formation, tissue inflammation, and pathological injury in the lung. High-mobility group protein B1 (HMGB1) blocking prevented NET formation and protected against tissue inflammation, as well as reduced cell apoptosis and improved survival rate. Moreover, recombinant human HMGB1 administration further drives NETs and concurrent tissue toxic injury, which in turn can be reversed by neutrophil deletion via anti-Ly6G Ab i.p. injection. Furthermore, global MyD88 deficiency regulated NET formation and alleviated the development of ALI induced by intestinal I/R. Thus, HMGB1 released from necroptotic enterocytes caused ALI after intestinal I/R by inducing NET formation. Targeting NETosis and the HMGB1 pathway might extend effective therapeutic strategies to minimize intestinal I/R-induced ALI.
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Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Armadilhas Extracelulares/genética , Proteína HMGB1/genética , Neutrófilos/imunologia , Neutrófilos/metabolismo , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Apoptose/genética , Biomarcadores , Modelos Animais de Doenças , Suscetibilidade a Doenças , Proteína HMGB1/metabolismo , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/deficiência , Traumatismo por Reperfusão/patologiaRESUMO
BACKGROUND: Myocardial injury after noncardiac surgery (MINS) is one of the most common complications associated with postoperative adverse cardiovascular outcomes and mortality. However, MINS often fails to be timely diagnosed due to the absence of clinical symptoms and limited diagnostic methods. The metabolomic analysis might be an efficient way to discover new biomarkers of MINS. Characterizing the metabolomic features of MINS patients may provide new insight into the diagnosis of MINS. METHODS: In this study, serum samples from 20 matched patients with or without MINS (n = 10 per group) were subjected to untargeted metabolomics analysis to investigate comprehensive metabolic information. Differential metabolites were identified, and the enriched metabolic pathway was determined based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. RESULTS: A comprehensive analysis revealed 124 distinct metabolites, predominantly encompassing lipids, amino acids and other compounds. The observed modifications in metabolic pathways in patients with or without MINS showed significant clustering in cholesterol metabolism, aldosterone synthesis and secretion, primary bile acid biosynthesis, as well as cysteine and methionine metabolism. Four specific metabolites (taurocholic acid, L-pyroglutamic acid, taurochenodeoxycholic acid, and pyridoxamine) exhibited promising potential as biomarkers for prognosticating MINS. CONCLUSIONS: This study contributes valuable insights into the metabolomic features of MINS and the discovery of potential biomarkers which may help the early diagnosis of MINS. The identified metabolites and altered pathways offer valuable insights into the molecular underpinnings of MINS, paving the way for improved diagnostic approaches and potential intervention strategies.
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Traumatismos Cardíacos , Complicações Pós-Operatórias , Humanos , Complicações Pós-Operatórias/diagnóstico , Metabolômica , Biomarcadores , CoraçãoRESUMO
BACKGROUND: Although mid-thoracic epidural analgesia benefits patients undergoing major surgery, technical difficulties often discourage its use. Improvements in technology are warranted to improve the success rate on first pass and patient comfort. The previously reported ultrasound-assisted technique using a generic needle insertion site failed to demonstrate superiority over conventional landmark techniques. A stratified needle insertion site based on sonoanatomic features may improve the technique. METHODS: Patients who presented for elective abdominal or thoracic surgery requesting thoracic epidural analgesia for postoperative pain control were included in this observational study. A modified ultrasound-assisted technique using a stratified needle insertion site based on ultrasound images was adopted. The number of needle passes, needle skin punctures, procedure time, overall success rate, and incidence of procedure complications were recorded. RESULTS: One hundred and twenty-eight subjects were included. The first-pass success and overall success rates were 75% (96/128) and 98% (126/128), respectively. In 95% (122/128) of patients, only one needle skin puncture was needed to access the epidural space. The median [IQR] time needed from needle insertion to access the epidural space was 59 [47-122] seconds. No complications were observed during the procedure. CONCLUSIONS: This modified ultrasound-assisted mid-thoracic epidural technique has the potential to improve success rates and reduce the needling time. The data shown in our study may be a feasible basis for a prospective study comparing our ultrasound-assisted epidural placements to conventional landmark-based techniques.
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Anestesia Epidural , Ultrassonografia de Intervenção , Humanos , Estudos Prospectivos , Ultrassonografia de Intervenção/métodos , Anestesia Epidural/métodos , Ultrassonografia , Espaço Epidural/diagnóstico por imagemRESUMO
BACKGROUND: Although sugammadex is well known for its use in reducing the incidence of residual neuromuscular blockade, this has not always been translated to improved clinical measures of postoperative respiratory muscle strength. Expiratory muscles play an important role in airway clearance and inspiratory muscle capacity augmentation, yet they have not been well studied. Therefore, we tested the hypothesis on whether sugammadex could enhance expiratory muscle strength recovery more completely than neostigmine in the immediate postextubation period. METHODS: Adult patients having microlaryngeal surgery under total intravenous anesthesia were randomized to receive sugammadex or neostigmine. The thickening fraction of internal oblique abdominal muscle (TF IO ) and diaphragm excursion, respectively, reflecting expiratory and inspiratory muscle strength, were measured via ultrasonography at 3 time points: before induction (baseline), train-of-four ratio (TOFR) recovery to 0.9, and 30 minutes after postanesthesia care unit (PACU) arrival. The primary outcome was the change in TF IO from baseline to TOFR ≥0.9. The postoperative changes of diaphragm excursion from baseline, incidences of TF IO and diaphragm excursion returning to baseline levels, and the time from TOFR 0.9 to 0.95 and 1 were also measured. RESULTS: Among 58 patients, a significant difference in the change in TF IO from baseline to TOFR ≥0.9 between the sugammadex and neostigmine groups was observed: mean ± standard deviation, 9% ± 6% vs 16% ± 9%; difference in means: -6% (95% confidence interval [CI], -10 to -2); and adjusted P =.005 (adjusting for imbalanced variables between 2 groups). Sugammadex resulted in smaller changes in diaphragm excursion from baseline to TOFR ≥0.9 compared with neostigmine: difference in means: -0.83 cm (99.4% CI, -1.39 to -0.28 cm; Bonferroni-corrected P < .001). After 30 minutes in the postanesthesia care unit (PACU),33% of patients reversed with sugammadex versus 14% of those receiving neostigmine reached baseline TF IO levels (99.4% CI, -14 to 52; Bonferroni-corrected P > .999). The incidences of TF IO and diaphragm excursion returning to baseline were relatively low (<40%) in both groups despite TOFR reaching 1. The median time from TOFR of 0.9 to 0.95 and to 1 among patients receiving sugammadex was 7 and 10× faster than those receiving neostigmine (0.3 vs 2 minutes, Bonferroni-corrected P = .003; 0.5 vs 5.3 minutes, Bonferroni-corrected P < .001, respectively). CONCLUSIONS: Sugammadex provides a more complete recovery of expiratory muscle strength than neostigmine at TOFR ≥0.9. Our data suggest that the respiratory muscle strength might still be impaired despite TOFR reaching 1.
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Neostigmina , Bloqueio Neuromuscular , Adulto , Humanos , Neostigmina/uso terapêutico , Sugammadex , Inibidores da Colinesterase/uso terapêutico , Bloqueio Neuromuscular/efeitos adversos , Bloqueio Neuromuscular/métodos , Músculos Respiratórios , Ultrassonografia , Período de Recuperação da AnestesiaRESUMO
BACKGROUND: The use of ultrasound has been reported to be beneficial in challenging neuraxial procedures. The angled probe is responsible for the main limitations of previous ultrasound-assisted techniques. We developed a novel technique for challenging lumbar puncture, aiming to locate the needle entry point which allowed for a horizontal and perpendicular needle trajectory and thereby addressed the drawbacks of earlier ultrasound-assisted techniques. CASE PRESENTATION: Patient 1 was an adult patient with severe scoliosis who underwent a series of intrathecal injections of nusinersen. The preprocedural ultrasound scan revealed a cephalad probe's angulation (relative to the edge of the bed) in the paramedian sagittal oblique view, and then the probe was rotated 90° into a transverse plane and we noted that a rocking maneuver was required to obtain normalized views. Then the shoulders were moved forward to eliminate the need for cephalad angulation of the probe. The degree of rocking was translated to a lateral offset from the midline of the spine through an imaginary lumbar puncture's triangle model, and a needle entry point was marked. The spinal needle was advanced through this marking-point without craniocaudal and lateromedial angulation, and first-pass success was achieved in all eight lumbar punctures. Patient 2 was an elderly patient with ankylosing spondylitis who underwent spinal anesthesia for transurethral resection of the prostate. The patient was positioned anteriorly obliquely to create a vertebral rotation that eliminated medial angulation in the paramedian approach. The procedure succeeded on the first pass. CONCLUSIONS: This ultrasound-assisted paramedian approach with a horizontal and perpendicular needle trajectory may be a promising technique that can help circumvent challenging anatomy. Larger case series and prospective studies are warranted to define its superiority to alternative approaches of lumbar puncture for patients with difficulties.
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Raquianestesia , Ressecção Transuretral da Próstata , Masculino , Adulto , Humanos , Idoso , Punção Espinal/métodos , Ultrassonografia de Intervenção/métodos , Coluna Vertebral , Ultrassonografia , Raquianestesia/métodosRESUMO
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrotic lung disease with high mortality and morbidity. ASPN (asporin), a member of the small leucine-rich proteoglycan family, plays crucial roles in tissue injury and regeneration. However, the precise pathophysiological role of ASPN and its molecular mechanisms in IPF remain unknown. We sought to investigate the role of ASPN during the development of pulmonary fibrosis and the therapeutic potential of targeting ASPN-related signaling pathways. In our study, three microarray datasets were downloaded from the Gene Expression Omnibus database, and differentially expressed genes were screened out by bioinformatic analysis. Hub genes were selected from the protein-protein interaction network. ASPN was examined in lung tissues from pulmonary fibrosis mouse models, and the role of ASPN in transforming growth factor (TGF)-ß/Smad signaling was determined by transfection with ASPN shRNA vectors in vitro. Biotinylation assays were conducted to measure plasma membrane TFG-ß receptor I (TßRI) and TßRI recycling after ASPN knockdown. The results showed ASPN expression was increased in the lungs of pulmonary fibrosis mouse models, and ASPN was primarily localized in α-SMA+ myofibroblasts. In vitro experiments proved that ASPN knockdown inhibited TGF-ß/Smad signaling and myofibroblast differentiation by regulating the stability of TßRI. Further molecular mechanisms revealed that ASPN knockdown inhibited TGF-ß/Smad signaling by suppressing recycling of TßRI to the cell surface in a Rab11-dependent manner and facilitated lysosome-mediated degradation of TßRI. In conclusion, our findings provide important evidence for the use of ASPN as a novel pharmacological target for treating pulmonary fibrosis.
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Proteínas da Matriz Extracelular/metabolismo , Pulmão/patologia , Miofibroblastos/patologia , Fibrose Pulmonar/patologia , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Animais , Antibióticos Antineoplásicos/toxicidade , Bleomicina/toxicidade , Estudos de Casos e Controles , Modelos Animais de Doenças , Proteínas da Matriz Extracelular/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Miofibroblastos/metabolismo , Mapas de Interação de Proteínas , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I/genética , Transdução de Sinais , Fator de Crescimento Transformador beta/genética , Proteínas rab de Ligação ao GTP/genéticaRESUMO
Background: Hypotension is a risk factor for postoperative complications, but evidence from randomized trials does not support that a higher blood pressure target always leads to optimized outcomes. The heterogeneity of underlying hemodynamics during hypotension may contribute to these contradictory results. Exploring the subtypes of hypotension can enable optimal management of intraoperative hypotension. Methods: This is a prospective, observational pilot study. Patients who were ≥ 45 years old and scheduled to undergo moderate-to-high-risk noncardiac surgery were enrolled in this study. The primary objective of this pilot study was to investigate the frequency and distribution of perioperative hypotension and its subtypes (hypotension with or without cardiac output reduction). The exposure of hypotension and its subtypes in patients with and without myocardial or acute kidney injury were also explored. Results: Sixty patients were included in the analysis. 83% (50/60) of the patients experienced perioperative hypotension. The median duration of hypotension for each patient was 8.0 [interquartile range, 3.1-23.3] minutes. Reduced cardiac output was present during 77% of the hypotension duration. Patients suffering from postoperative myocardial or acute kidney injury displayed longer duration and more extensive exposure in all hypotension subtypes. However, the percentage of different hypotension subtypes did not differ in patients with or without postoperative myocardial or acute kidney injury. Conclusion: Perioperative hypotension was frequently accompanied by cardiac output reduction in moderate-to-high-risk noncardiac surgical patients. However, due to the pilot nature of this study, the relationship between hypotension subtypes and postoperative myocardial or acute kidney injury still needs further exploration. Clinical trial registration: https://www.chictr.org.cn/showprojEN.html?proj=134260, CTR2200055929.
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BACKGROUND: Lumbar puncture is challenging for patients with scoliosis. Previous ultrasound-assisted techniques for lumbar puncture used the angle of the probe as the needle trajectory; however, reproducing the angle is difficult and increases the number of needle manipulations. In response, we developed a technique that eliminated both the craniocaudal and lateromedial angulation of the needle trajectory to overall improve this technique. We assessed the feasibility and safety of this method in patients with scoliosis and identify factors related to difficult lumbar puncture. METHODS: Patients with spinal muscular atrophy and scoliosis who were referred to the anesthesia department for intrathecal nusinersen administrations were included. With a novel approach that utilized patient position and geometry, lumbar puncture was performed under ultrasound guidance. Success rates, performance times and adverse events were recorded. Clinical-demographic and spinal radiographic data pertaining to difficult procedures were analyzed. RESULTS: Success was achieved in all 260 (100%) lumbar punctures for 44 patients, with first pass and first attempt success rates of 70% (183/260) and 87% (226/260), respectively. Adverse events were infrequent and benign. Higher BMI, greater skin dural sac depth and smaller interlaminar size might be associated with greater difficulty in lumbar puncture. CONCLUSIONS: The novel ultrasound-assisted horizontal and perpendicular interlaminar needle trajectory approach is an effective and safe method for lumbar puncture in patients with spinal deformities. This method can be reliably performed at the bedside and avoids other more typical and complex imaging such as computed tomography guided procedure.
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Injeções Espinhais , Atrofia Muscular Espinal , Oligonucleotídeos , Escoliose , Humanos , Escoliose/tratamento farmacológico , Escoliose/diagnóstico por imagem , Atrofia Muscular Espinal/tratamento farmacológico , Atrofia Muscular Espinal/diagnóstico por imagem , Feminino , Masculino , Injeções Espinhais/métodos , Oligonucleotídeos/administração & dosagem , Oligonucleotídeos/uso terapêutico , Criança , Adolescente , Punção Espinal/métodos , Adulto , Adulto Jovem , Pré-EscolarRESUMO
BACKGROUND: Remote ischemic preconditioning (RIPC) may confer the cytoprotection in critical organs. The authors hypothesized that limb RIPC would reduce intestinal and pulmonary injury in patients undergoing open infrarenal abdominal aortic aneurysm repair. METHODS: In this single-center, prospective, double-blinded, randomized, parallel-controlled trial, 62 patients undergoing elective open infrarenal abdominal aortic aneurysm repair were randomly assigned in a 1:1 ratio by computerized block randomization to receive limb RIPC or conventional abdominal aortic aneurysm repair (control). Three cycles of 5-min ischemia/5-min reperfusion induced by a blood pressure cuff placed on the left upper arm served as RIPC stimulus. The primary endpoint was arterial-alveolar oxygen tension ratio. The secondary endpoints mainly included the intestinal injury markers (serum intestinal fatty acid-binding protein, endotoxin levels, and diamine oxidase activity), the markers of oxidative stress and systemic inflammatory response, and the scores of the severity of intestinal and pulmonary injury. RESULTS: In limb RIPC group, a/A ratio was significantly higher than that in control group at 8, 12, and 24 h after cross-clamp release (66 ± 4 vs. 45 ± 4, P = 0.003; 60 ± 6 vs. 37 ± 4, P = 0.002; and 60 ± 5 vs. 47 ± 6, P = 0.039, respectively). All biomarkers reflecting intestinal injury increased over time, and there was significant differences between limb RIPC and control group (P < 0.001). The severity of intestinal and pulmonary injury was decreased by limb RIPC (P = 0.014 and P = 0.001, respectively). CONCLUSIONS: Limb RIPC attenuates intestinal and pulmonary injury in patients undergoing elective open infrarenal abdominal aortic aneurysm repair without any potential risk.
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Aneurisma da Aorta Abdominal/cirurgia , Procedimentos Cirúrgicos Eletivos/métodos , Intestinos/irrigação sanguínea , Precondicionamento Isquêmico/métodos , Pulmão/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Idoso , Amina Oxidase (contendo Cobre)/sangue , Aorta Abdominal/cirurgia , Braço , Biomarcadores/sangue , China , Método Duplo-Cego , Endotoxinas/sangue , Proteínas de Ligação a Ácido Graxo/sangue , Feminino , Humanos , Enteropatias/sangue , Enteropatias/prevenção & controle , Pneumopatias/sangue , Pneumopatias/prevenção & controle , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Estudos Prospectivos , Síndrome de Resposta Inflamatória Sistêmica/sangueRESUMO
BACKGROUND: Diagnostic error (DE) is a common problem in clinical practice, particularly in the emergency department (ED) setting. Among ED patients presenting with cardiovascular or cerebrovascular/neurological symptoms, a delay in diagnosis or failure to hospitalise may be most impactful in terms of adverse outcomes. Minorities and other vulnerable populations may be at higher risk of DE. We aimed to systematically review studies reporting the frequency and causes of DE in under-resourced patients presenting to the ED with cardiovascular or cerebrovascular/neurological symptoms. METHODS: We searched EBM Reviews, Embase, Medline, Scopus and Web of Science from 2000 through 14 August 2022. Data were abstracted by two independent reviewers using a standardised form. The risk of bias (ROB) was assessed using the Newcastle-Ottawa Scale, and the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Of the 7342 studies screened, we included 20 studies evaluating 7436,737 patients. Most studies were conducted in the USA, and one study was multicountry. 11 studies evaluated DE in patients with cerebrovascular/neurological symptoms, 8 studies with cardiovascular symptoms and 1 study examined both types of symptoms. 13 studies investigated missed diagnoses and 7 studies explored delayed diagnoses. There was significant clinical and methodological variability, including heterogeneity of DE definitions and predictor variable definitions as well as methods of DE assessment, study design and reporting.Among the studies evaluating cardiovascular symptoms, black race was significantly associated with higher odds of DE in 4/6 studies evaluating missed acute myocardial infarction (AMI)/acute coronary syndrome (ACS) diagnosis compared with white race (OR from 1.18 (1.12-1.24) to 4.5 (1.8-11.8)). The association between other analysed factors (ethnicity, insurance and limited English proficiency) and DE in this domain varied from study to study and was inconclusive.Among the studies evaluating DE in patients with cerebrovascular/neurological symptoms, no consistent association was found indicating higher or lower odds of DE. Although some studies showed significant differences, these were not consistently in the same direction.The overall ROB was low for most included studies; however, the certainty of evidence was very low, mostly due to serious inconsistency in definitions and measurement approaches across studies. CONCLUSIONS: This systematic review demonstrated consistent increased odds of missed AMI/ACS diagnosis among black patients presenting to the ED compared with white patients in most studies. No consistent associations between demographic groups and DE related to cerebrovascular/neurological diagnoses were identified. More standardised approaches to study design, measurement of DE and outcomes assessment are needed to understand this problem among vulnerable populations. TRIAL REGISTRATION NUMBER: The study protocol was registered in the International Prospective Register of Systematic Reviews PROSPERO 2020 CRD42020178885 and is available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020178885.
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Serviço Hospitalar de Emergência , Populações Vulneráveis , Humanos , Erros de Diagnóstico , Revisões Sistemáticas como AssuntoRESUMO
Dectin-1 (gene Clec7a), a receptor for ß-glucans, plays important roles in the host defense against fungi and immune homeostasis of the intestine. Although this molecule is also suggested to be involved in the regulation of tumorigenesis, the role in intestinal tumor development remains to be elucidated. In this study, we find that azoxymethane-dextran-sodium-sulfate-induced and ApcMin-induced intestinal tumorigenesis are suppressed in Clec7a-/- mice independently from commensal microbiota. Dectin-1 is preferentially expressed on myeloid-derived suppressor cells (MDSCs). In the Clec7a-/- mouse colon, the proportion of MDSCs and MDSC-derived prostaglandin E2 (PGE2) levels are reduced, while the expression of IL-22 binding protein (IL-22BP; gene Il22ra2) is upregulated. Dectin-1 signaling induces PGE2-synthesizing enzymes and PGE2 suppresses Il22ra2 expression in vitro and in vivo. Administration of short chain ß-glucan laminarin, an antagonist of Dectin-1, suppresses the development of mouse colorectal tumors. Furthermore, in patients with colorectal cancer (CRC), the expression of CLEC7A is also observed in MDSCs and correlated with the death rate and tumor severity. Dectin-1 signaling upregulates PGE2-synthesizing enzyme expression and PGE2 suppresses IL22RA2 expression in human CRC-infiltrating cells. These observations indicate a role of the Dectin-1-PGE2-IL-22BP axis in regulating intestinal tumorigenesis, suggesting Dectin-1 as a potential target for CRC therapy.
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Neoplasias Colorretais , Lectinas Tipo C , Células Supressoras Mieloides , Animais , Humanos , Camundongos , Carcinogênese/genética , Transformação Celular Neoplásica/genética , Neoplasias Colorretais/patologia , Dinoprostona/metabolismo , Lectinas Tipo C/genética , Células Supressoras Mieloides/metabolismo , Interleucina 22RESUMO
OBJECTIVES: This study aimed to explore clinicians' perceptions of the occurrence of and factors associated with diagnostic errors in patients evaluated during a rapid response team (RRT) activation or unplanned admission to the intensive care unit (ICU). METHODS: A multicenter prospective survey study was conducted among multiprofessional clinicians involved in the care of patients with RRT activations and/or unplanned ICU admissions (UIAs) at 2 academic hospitals and 1 community-based hospital between April 2019 and March 2020. A study investigator screened eligible patients every day. Within 24 hours of the event, a research coordinator administered the survey to clinicians, who were asked the following: whether diagnostic errors contributed to the reason for RRT/UIA, whether any new diagnosis was made after RRT/UIA, if there were any failures to communicate the diagnosis, and if involvement of specialists earlier would have benefited that patient. Patient clinical data were extracted from the electronic health record. RESULTS: A total of 1815 patients experienced RRT activations, and 1024 patients experienced UIA. Clinicians reported that 18.2% (95/522) of patients experienced diagnostic errors, 8.0% (42/522) experienced a failure of communication, and 16.7% (87/522) may have benefitted from earlier involvement of specialists. Compared with academic settings, clinicians in the community hospital were less likely to report diagnostic errors (7.0% versus 22.8%, P = 0.002). CONCLUSIONS: Clinicians report a high rate of diagnostic errors in patients they evaluate during RRT or UIAs.
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Equipe de Respostas Rápidas de Hospitais , Erros de Diagnóstico , Humanos , Unidades de Terapia Intensiva , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: Despite the use of quantitative neuromuscular monitoring together with the administration of reversal drugs (neostigmine or sugammadex), the incidence of residual neuromuscular blockade defined as a train-of-four ratio (TOFr) <0.9 remains high. Even TOFr >0.9 cannot ensure adequate recovery of neuromuscular function when T1 height is not recovered completely. Thus, a mathematical correction of TOFr needs to be applied because the return of a normal TOFr can precede the return of a normal T1 twitch height. On the other hand, different muscles have different sensitivities to neuromuscular blockade agents; thus, complete recovery of one specific muscle group does not represent complete recovery of all other muscles. Therefore, our study aims to assess the muscle strength recovery of respiratory-related muscle groups by ultrasound and evaluate global strength using handgrip dynamometry in the early postoperative period when TOFr=0.9 and corrected TOFr (cTOFr)=0.9 with comparison of neostigmine versus sugammadex as reversal drugs. METHODS AND ANALYSIS: This study will be a prospective, single-blinded, randomised controlled trial involving 60 patients with American Society of Anesthesiologists physical status I-II and aged between 18 and 65 years, who will undergo microlaryngeal surgery. We will assess geniohyoid muscle, parasternal intercostal muscle, diaphragm, abdominal wall muscle and handgrip strength at four time points: before anaesthesia, TOFr=0.9, cTOFr=0.9 and 30 min after admission to the post anaesthesia care unit. Our primary objective will be to compare the effects of neostigmine and sugammadex on the recovery of muscle strength of different muscle groups in the early postoperative period when TOFr=0.9 and cTOFr=0.9. The secondary objective will be to observe the difference of muscle strength between the time points of TOFr=0.9 and cTOFr=0.9 to find out the clinical significance of cTOFr >0.9. ETHICS AND DISSEMINATION: The protocol was reviewed and approved by the Ethics Committee of The First Affiliated Hospital, Sun Yat-sen University. The findings will be disseminated to the public through peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: ChiCTR2000033832.
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Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , Preparações Farmacêuticas , Adolescente , Adulto , Idoso , Período de Recuperação da Anestesia , Inibidores da Colinesterase , Força da Mão , Humanos , Pessoa de Meia-Idade , Força Muscular , Neostigmina , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Rocurônio , Sugammadex , Ultrassonografia , Adulto JovemRESUMO
OBJECTIVES: Diagnostic error and delay is a prevalent and impactful problem. This study was part of a mixed-methods approach to understand the organizational, clinician, and patient factors contributing to diagnostic error and delay among acutely ill patients within a health system, as well as recommendations for the development of tailored, targeted, feasible, and effective interventions. METHODS: We did a multisite qualitative study using focus group methodology to explore the perspectives of key clinician stakeholders. We used a conceptual framework that characterized diagnostic error and delay as occurring within 1 of 3 stages of the patient's diagnostic journey-critical information gathering, synthesis of key information, and decision making and communication. We developed our moderator guide based on the sociotechnical frameworks previously described by Holden and Singh for understanding noncognitive factors that lead to diagnostic error and delay. Deidentified focus group transcripts were coded in triplicate and to consensus over a series of meetings. A final coded data set was then uploaded into NVivo software. The data were then analyzed to generate overarching themes and categories. RESULTS: We recruited a total of 64 participants across 4 sites from emergency departments, hospital floor, and intensive care unit settings into 11 focus groups. Clinicians perceive that diverse organizational, communication and coordination, individual clinician, and patient factors interact to impede the process of making timely and accurate diagnoses. CONCLUSIONS: This study highlights the complex sociotechnical system within which individual clinicians operate and the contributions of systems, processes, and institutional factors to diagnostic error and delay.
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Comunicação , Consenso , Erros de Diagnóstico , Grupos Focais , Humanos , Pesquisa Qualitativa , Estados UnidosRESUMO
A growing number of studies on coronavirus disease 2019 (COVID-19) are becoming available, but a synthesis of available data focusing on the critically ill population has not been conducted. We performed a scoping review to synthesize clinical characteristics, treatment, and clinical outcomes among critically ill patients with COVID-19. Between January 1, 2020, and May 15, 2020, we identified high-quality clinical studies describing critically ill patients with a sample size of greater than 20 patients by performing daily searches of the World Health Organization and LitCovid databases on COVID-19. Two reviewers independently reviewed all abstracts (2785 unique articles), full text (218 articles), and abstracted data (92 studies). The 92 studies included 61 from Asia, 16 from Europe, 10 from North and South America, and 5 multinational studies. Notable similarities among critically ill populations across all regions included a higher proportion of older males infected and with severe illness, high frequency of comorbidities (hypertension, diabetes, and cardiovascular disease), abnormal chest imaging findings, and death secondary to respiratory failure. Differences in regions included newly identified complications (eg, pulmonary embolism) and epidemiological risk factors (eg, obesity), less chest computed tomography performed, and increased use of invasive mechanical ventilation (70% to 100% vs 15% to 47% of intensive care unit patients) in Europe and the United States compared with Asia. Future research directions should include proof-of-mechanism studies to better understand organ injuries and large-scale collaborative clinical studies to evaluate the efficacy and safety of antivirals, antibiotics, interleukin 6 receptor blockers, and interferon. The current established predictive models require further verification in other regions outside China.
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COVID-19/terapia , Cuidados Críticos/métodos , Estado Terminal/terapia , Humanos , SARS-CoV-2RESUMO
Background: Recent observational studies have reported a negative association between physical activity and chronic back pain (CBP), but the causality of the association remains unknown. We introduce bidirectional Mendelian randomization (MR) to assess potential causal inference between physical activity and CBP. Materials and Methods: This two-sample MR used independent genetic variants associated with physical activity and CBP as genetic instruments from large genome-wide association studies (GWASs). The effects of both directions (physical activity to CBP and CBP to physical activity) were examined. Inverse variance-weighted meta-analysis and alternate methods (weighted median and MR-Egger) were used to combine the MR estimates of the genetic instruments. Multiple sensitivity analyses were conducted to examine the robustness of the results. Results: The MR set parallel GWAS cohorts, among which, those involved in the primary analysis were comprised of 337,234 participants for physical activity and 158,025 participants (29,531 cases) for CBP. No evidence of a causal relationship was found in the direction of physical activity to CBP [odds ratio (OR), 0.98; 95% CI, 0.85-1.13; p = 0.81]. In contrast, a negative causal relationship in the direction of CBP to physical activity was detected (ß = -0.07; 95% CI, -0.12 to -0.01; p = 0.02), implying a reduction in moderate-vigorous physical activity (approximately 146 MET-minutes/week) for participants with CBP relative to controls. Conclusion: The negative relationship between physical activity and CBP is probably derived from the reduced physical activity of patients experiencing CBP rather than the protective effect of physical activity on CBP.
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BACKGROUND: Although diagnostic error (DE) is a significant problem, it remains challenging for clinicians to identify it reliably and to recognize its contribution to the clinical trajectory of their patients. The purpose of this work was to evaluate the reliability of real-time electronic health record (EHR) reviews using a search strategy for the identification of DE as a contributor to the rapid response team (RRT) activation. OBJECTIVES: Early and accurate recognition of critical illness is of paramount importance. The objective of this study was to test the feasibility and reliability of prospective, real-time EHR reviews as a means of identification of DE. METHODS: We conducted this prospective observational study in June 2019 and included consecutive adult patients experiencing their first RRT activation. An EHR search strategy and a standard operating procedure were refined based on the literature and expert clinician inputs. Two physician-investigators independently reviewed eligible patient EHRs for the evidence of DE within 24 hours after RRT activation. In cases of disagreement, a secondary review of the EHR using a taxonomy approach was applied. The reviewers categorized patient experience of DE as Yes/No/Uncertain. RESULTS: We reviewed 112 patient records. DE was identified in 15% of cases by both reviewers. Kappa agreement with the initial review was 0.23 and with the secondary review 0.65. No evidence of DE was detected in 60% of patients. In 25% of cases, the reviewers could not determine whether DE was present or absent. CONCLUSION: EHR review is of limited value in the real-time identification of DE in hospitalized patients. Alternative approaches are needed for research and quality improvement efforts in this field.
Assuntos
Erros de Diagnóstico/prevenção & controle , Registros Eletrônicos de Saúde , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , RiscoRESUMO
BACKGROUND: Identifying the nerve block region is important for the less experienced operators who are not skilled in ultrasound technology. Therefore, we constructed and shared a dataset of ultrasonic images to explore a method to identify the femoral nerve block region. METHODS: Ultrasound images of femoral nerve block were retrospectively collected and marked to establish the dataset. The U-net framework was used for training data and output segmentation of region of interest. The performance of the model was evaluated by Intersection over Union and accuracy. Then the predicted masks were highlighted on the original image to give an intuitive evaluation. Finally, cross validation was used for the whole data to test the robust of the results. RESULTS: We selected 562 ultrasound images as the whole dataset. The training set intersection over union (IoU) was 0.713, the development set IoU is 0.633 and the test set IoU is 0.638. For the single image, the median and upper/lower quartiles of IoU were 0.722 (0.647-0.789), 0.653 (0.586-0.703), 0.644 (0.555-0.735) for the training set, development set and test set respectively. The segmentation accuracy of the test set was 83.9%. For 10-fold cross validation, the median and quartiles of the 10-iteration sum IoUs was 0.656 (0.628-0.672); for accuracy, they were 88.4% (82.1-90.7%). CONCLUSIONS: We provided a dataset and trained a model for femoral-nerve region segmentation with U-net, obtaining a satisfactory performance. This technique may have potential clinical application.
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Previous studies have proved that activation of aldehyde dehydrogenase two (ALDH2) can attenuate oxidative stress through clearance of cytotoxic aldehydes, and can protect against cardiac, cerebral, and lung ischemia/reperfusion (I/R) injuries. In this study, we investigated the effects of the ALDH2 activator Alda-1 on hepatic I/R injury. Partial warm ischemia was performed in the left and middle hepatic lobes of Sprague-Dawley rats for 1 h, followed by 6 h of reperfusion. Rats received either Alda-1 or vehicle by intravenous injection 30 min before ischemia. Blood and tissue samples of the rats were collected after 6-h reperfusion. Histological injury, proinflammatory cytokines, reactive oxygen species (ROS), cellular apoptosis, ALDH2 expression and activity, 4-hydroxy-trans-2-nonenal (4-HNE) and malondialdehyde (MDA) were measured. BRL-3A hepatocytes were subjected to hypoxia/reoxygenation (H/R). Cell viability, ROS, and mitochondrial membrane potential were determined. Pretreatment with Alda-1 significantly alleviated I/R-induced elevations of alanine aminotransferase and aspartate amino transferase, and significantly blunted the pathological injury of the liver. Moreover, Alda-1 significantly inhibited ROS and proinflammatory cytokines production, 4-HNE and MDA accumulation, and apoptosis. Increased ALDH2 activity was found after Alda-1 administration. No significant changes in ALDH2 expression were observed after I/R. ROS was also higher in H/R cells than in control cells, which was aggravated upon treatment with 4-HNE, and reduced by Alda-1 treatment. Cell viability and mitochondrial membrane potential were inhibited in H/R cells, which was attenuated upon Alda-1 treatment. Activation of ALDH2 by Alda-1 attenuates hepatic I/R injury via clearance of cytotoxic aldehydes.
Assuntos
Aldeído-Desidrogenase Mitocondrial/genética , Antioxidantes/farmacologia , Benzamidas/farmacologia , Benzodioxóis/farmacologia , Ativadores de Enzimas/farmacologia , Fígado/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Alanina Transaminase/genética , Alanina Transaminase/metabolismo , Aldeído-Desidrogenase Mitocondrial/metabolismo , Aldeídos/metabolismo , Animais , Apoptose/efeitos dos fármacos , Aspartato Aminotransferases/genética , Aspartato Aminotransferases/metabolismo , Linhagem Celular , Expressão Gênica , Hepatócitos/efeitos dos fármacos , Hepatócitos/enzimologia , Hepatócitos/patologia , Injeções Intravenosas , Fígado/enzimologia , Fígado/patologia , Masculino , Malondialdeído/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/patologiaRESUMO
BACKGROUND: Neuropathic pain is one of the common complications after spinal cord injury (SCI), affecting individuals' quality of life. The molecular mechanism for neuropathic pain after SCI is still unclear. We aimed to discover potential genes and microRNAs (miRNAs) related to neuropathic pain by the bioinformatics method. METHODS: Microarray data of GSE69901 were obtained from Gene Expression Omnibus (GEO) database. Peripheral blood samples from individuals with or without neuropathic pain after SCI were collected. Twelve samples from individuals with neuropathic pain and 13 samples from individuals without pain as controls were included in the downloaded microarray. Differentially expressed genes (DEGs) between the neuropathic pain group and the control group were detected using the GEO2R online tool. Functional enrichment analysis of DEGs was performed using the DAVID database. Protein-protein interaction network was constructed from the STRING database. MiRNAs targeting these DEGs were obtained from the miRNet database. A merged miRNA-DEG network was constructed and analyzed with Cytoscape software. RESULTS: In total, 1134 DEGs were identified between individuals with or without neuropathic pain (case and control), and 454 biological processes were enriched. We identified 4 targeted miRNAs, including mir-204-5p, mir-519d-3p, mir-20b-5p, mir-6838-5p, which may be potential biomarkers for SCI patients. CONCLUSION: Protein modification and regulation of the biological process of the central nervous system may be a risk factor in SCI. Certain genes and miRNAs may be potential biomarkers for the prediction of and potential targets for the prevention and treatment of neuropathic pain after SCI.