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AIM: To investigate the efficacy of synthetic magnetic resonance imaging (MRI) in distinguishing high-grade gliomas (HGGs) from solitary brain metastases (SBMs) in peritumoural oedema. MATERIALS AND METHODS: Thirty-five patients with HGGs and 25 patients with SBMs were recruited and scanned using synthetic MRI using a 3 T scanner. Two radiologists measured synthetic MRI-derived relaxation values independently (T1, T2, proton density [PD]) in the peritumoural oedema, which was used to generate quantitative metrics before (T1native, T2native, and PDnative) and after (T1post, T2post, and PDpost) contrast agent injection. Student's t-test or the Mann-Whitney U-test was performed to detect statistically significant differences in the aforementioned metrics in peritumoural oedema between HGGs and SBMs. The receiver operating characteristic (ROC) curves were plotted to evaluate the efficacy of each metric in distinguishing the two groups, and the areas under the curves (AUCs) were compared pairwise by performing the Delong test. RESULTS: The mean T1native, T2native, and T1post values in the peritumoural oedema of HGGs were significantly lower compared with SBMs (all p<0.05). The T1post value had a higher AUC (0.843) in differentiating HGGs and SBMs than all other individual metrics (all p<0.05). The combined T1native, T2native, and T1post model had the best distinguishing performance with an AUC, sensitivity, and specificity of 0.987, 94.3%, and 100%, respectively. CONCLUSIONS: Synthetic MRI may be a potential supplement to the preoperative diagnosis of HGGs and SBMs in clinical practice, as the synthetic MRI-derived tri-parametric model in the peritumoural oedema showed significantly improved diagnostic performance in distinguishing HGGs from SBMs.
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Neoplasias Encefálicas , Glioma , Humanos , Glioma/diagnóstico por imagem , Glioma/patologia , Neoplasias Encefálicas/patologia , Imageamento por Ressonância Magnética/métodos , Curva ROC , Edema/diagnóstico por imagem , PrótonsRESUMO
INTRODUCTION: Atopic dermatitis (AD) is a chronic relapsing pruritic inflammatory skin disease that commonly occurs among children as well as adults. AD patients were reported to have high prevalence of ocular manifestations, which may be due to the disease nature or drug complications. This study aimed to determine the prevalence of ocular manifestations in patients with AD. MATERIALS AND METHODS: Eighty patients who fulfilled the UK Working Party's Diagnostic Criteria for Atopic Dermatitis were included in the cross-sectional study. A standardized case report form was formulated to collect the demographic data and disease profile of the participants. AD severity was evaluated using the EASI and SCORAD score. All patients underwent a complete ophthalmological evaluation. RESULTS: The prevalence of ocular manifestations among the patients with AD was 48.8%. Fifty-four (67.5%) patients had facial dermatitis and 37 (46.2%) showed periorbital signs. The mean AD disease duration was 10.99 ± 11.20 years. Majority of the patients had mild to moderate AD. The most frequent ocular manifestation was allergic conjunctivitis (18.75%) followed by cataract (8.75%) and ocular hypertension (8.75%). Among the patients with ocular manifestations, 27 (69.2%) patients regularly applied topical corticosteroids on the face. The use of systemic corticosteroids was seen in 19 (42.2%) patients. Prolonged AD duration was significantly associated with the development of ocular manifestations. CONCLUSIONS: Nearly half of the patients with AD were complicated with ocular disease regardless of the AD severity, facial dermatitis and presence of periorbital signs. Long disease duration is associated with ocular manifestations, especially steroid related complications.
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Dermatite Atópica , Adulto , Criança , Estudos Transversais , Dermatite Atópica/complicações , Dermatite Atópica/epidemiologia , Humanos , Malásia/epidemiologia , Prevalência , Índice de Gravidade de Doença , Centros de Atenção TerciáriaRESUMO
OBJECTIVE: To determine the Dermatology Life Quality Index (DLQI) among the subtypes of leprosy and to examine correlation with deformity and lepra reactions. METHODS: This was a cross-sectional study done at Dermatology Outpatient Clinic, Queen Elizabeth Hospital and two health clinics in Kota Kinabalu between 1st April 2019 and 30th November 2019. A standardised case report form was formulated to collect the demographic data and disease profile of the leprosy patients. The quality of life (QoL) was assessed using Dermatology Life Quality Index (DLQI) questionnaire. RESULTS: A total of 54 patients were included with a male to female ratio of 2.4:1 (38 males and 16 females). The mean DLQI score was 8.31±6.15. The difference between the mean DLQI scores among the leprosy subtypes was not significant. The most affected domain was symptoms and feeling followed by daily activities and leisure. Twenty-one patients (38.9%) had facial deformity and they were found to have significantly higher DLQI score. WHO grade 1 and 2 disability were observed in 37 patients (68.5%) with higher DLQI score compared to those without any disability. More than half of patients with MB leprosy (52.2%) developed lepra reactions but the difference of mean DLQI scores were not significant. CONCLUSIONS: Leprosy-related disabilities may predispose patients to develop psychosocial problems which may have negative impact on QoL. Thus, periodic assessment of QoL should be incorporated into the management of leprosy patients.
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Hanseníase , Qualidade de Vida , Estudos Transversais , Feminino , Humanos , Hanseníase/epidemiologia , Malásia , Masculino , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
Large thermal gradients in the melt pool from rapid heating followed by rapid cooling in metal additive manufacturing generate large thermoelectric currents. Applying an external magnetic field to the process introduces fluid flow through thermoelectric magnetohydrodynamics. Convective transport of heat and mass can then modify the melt pool dynamics and alter microstructural evolution. As a novel technique, this shows great promise in controlling the process to improve quality and mitigate defect formation. However, there is very little knowledge within the scientific community on the fundamental principles of this physical phenomenon to support practical implementation. To address this multi-physics problem that couples the key phenomena of melting/solidification, electromagnetism, hydrodynamics, heat and mass transport, the lattice Boltzmann method for fluid dynamics was combined with a purpose-built code addressing solidification modelling and electromagnetics. The theoretical study presented here investigates the hydrodynamic mechanisms introduced by the magnetic field. The resulting steady-state solutions of modified melt pool shapes and thermal fields are then used to predict the microstructure evolution using a cellular automata-based grain growth model. The results clearly demonstrate that the hydrodynamic mechanisms and, therefore, microstructure characteristics are strongly dependent on magnetic field orientation. This article is part of the theme issue 'Patterns in soft and biological matters'.
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Objective: To explore the effect and mechanism of bamboo leaf flavonoids on depression in type 2 diabetic rats. Methods: The streptozotocin (STZ) was used to induce the depression model of type 2 diabetic rats. Eight weeks old male Sprague-Dawley (SD) rats were randomly divided into 5 groups: the normal control group (n=8), the model group (n=9), the bamboo leaf flavonoid group (n=9), the solvent control group (n=9) and the bamboo leaf flavonoid normal control group (n=8). Rats of the bamboo leaf flavonoid group and the bamboo leaf flavonoid normal control group were treated with intragastric administration of bamboo leaf flavonoids (200 mg·kg(-1)·d(-1)) for 12 weeks. Tail suspension test (TST) and forced swimming test (FST) were used to measure the level of depression. Nissl staining was used to detect the survival amount of hippocampus neurons. The levels of interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA). The expression levels of receptor of advanced glycation endproducts (RAGE), phosphorylated signal protein P38 (p-P38), cleaved caspase-3 and the nuclear factor-κB (NF-κB) were detected by Western blotting. Results: Compared with the normal control group, the TST and FST immobility time of the model group rats increased [(206±13) s vs (101±9) s, (192±24) s vs (98±8) s, both P<0.01]. Furthermore, the injury of hippocampal neurons was more severe, and the boundary was unclear. The nissl bodies were scarce or disappeared, and nuclear pyknosis was observed. The levels of hippocampal CA3 IL-1ß and IL-6 elevated [(31.78±4.12) pg/ml vs (9.26±3.52) pg/ml, (49.15±3.47) pg/ml vs (19.63±2.18) pg/ml, both P<0.01]. The Western blotting showed that the expressions of RAGE, p-P38, cleaved caspase-3 enhanced and NF-κB nuclear translocation increased (all P<0.05). After bamboo leaf flavonoids treatment (for 12 weeks), compared with the model group, the immobility time of TST and FST reduced in the bamboo leaf flavonoid group [(152±11) s vs (206±13) s, (110±19) s vs (192±24) s, P<0.01], and hippocampal neuronal injury alleviated. In addition, the concentrations of IL-1ß and IL-6 decreased [(21.79±3.95) pg/ml vs (31.78±4.12) pg/ml, (34.68±4.28) pg/ml vs (49.15±3.47) pg/ml, both P<0.01] and the expressions of RAGE, p-P38, nuclear NF-κB, cleaved caspase-3 up-regulated in the bamboo leaf flavonoid group. Conclusion: Bamboo leaf flavonoids can effectively improve depression in diabetic rats through decreasing hippocampal neuronal injury and the release of inflammatory factors, and inhibiting RAGE/P38/NF-κB signaling pathway.
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Diabetes Mellitus Tipo 2 , Animais , Depressão , Diabetes Mellitus Experimental , Flavonoides , Masculino , NF-kappa B , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfaRESUMO
Perioperative fluid management impacts outcomes and plays a pivotal role in enhanced recovery pathways (ERPs). There have been major advances in understanding the effects of fluid therapy and administration during the perioperative period. Improving fluid management during this period leads to a decrease in complications, decrease in length of stay (LOS), and enhanced patient outcomes. It is important to consider preoperative and postoperative fluid management to be just as critical as intraoperative management given multiple associated benefits to the patients. Preoperative hydration with (complex) carbohydrate drinks up until 2 h before surgery is safe and should be encouraged, as this helps improve metabolism, decrease insulin resistance, reduce anxiety, and reduce nausea and vomiting. During the intraoperative period, the goals of fluid management are to maintain euvolemia using an individualized plan for fluid and haemodynamic management, matching the needs for monitoring with patient and surgical risk through goal-directed therapy (GDT). By combining the use of fluids and inotropes, GDT uses measurements and indicators of cardiac output and stroke volume to improve blood flow intraoperatively, and ultimately reduce LOS and complications. In the postoperative period, an early transition to oral hydration helps to enhance the conditions for healing and recovery from surgery. I.V. fluid therapy should be kept at a minimum, and urine output should not be the driving force for fluid administration. The optimization of perioperative fluid management is critical to ERPs as it helps improve pulmonary function, tissue oxygenation, gastrointestinal motility, and wound healing.
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Hidratação/tendências , Assistência Perioperatória/tendências , Hidratação/métodos , Objetivos , Humanos , Assistência Perioperatória/métodos , Período Perioperatório , Recuperação de Função Fisiológica , Volume SistólicoRESUMO
BACKGROUND: Maximising patient comfort during and after surgery is a primary concern of anaesthetists and other perioperative clinicians, but objective measures of what constitutes patient comfort in the perioperative period remain poorly defined. The Standardised Endpoints in Perioperative Medicine initiative was established to derive a set of standardised endpoints for use in perioperative clinical trials. METHODS: We undertook a systematic review to identify measures of patient comfort used in the anaesthetic, surgical, and other perioperative literature. A multi-round Delphi consensus process that included up to 89 clinician researchers was then used to refine a recommended list of outcome measures. RESULTS: We identified 122 studies in a literature search, which were the basis for a preliminary list of 24 outcome measures and their definitions. The response rates for Delphi Rounds 1, 2, and 3 were 100% (n=22), 90% (n=79), and 100% (n=13), respectively. A final list of six defined endpoints was identified: pain intensity (at rest and during movement) at 24 h postoperatively, nausea and vomiting (0-6 h, 6-24 h, and overall), one of two quality-of-recovery (QoR) scales (QoR score or QoR-15), time to gastrointestinal recovery, time to mobilisation, and sleep quality. CONCLUSIONS: As standardised outcomes will support benchmarking and pooling (meta-analysis) of trials, one or more of these recommended endpoints should be considered for inclusion in clinical trials assessing patient comfort and pain after surgery.
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Conforto do Paciente/métodos , Assistência Perioperatória/métodos , Consenso , Técnica Delphi , Humanos , Guias de Prática Clínica como Assunto , Projetos de PesquisaRESUMO
Enhanced recovery programmes (ERPs) are increasingly used to improve post-surgical recovery. However, compliance to various components of ERPs-a key determinant of success-remains sub-optimal. Emerging technologies have the potential to help patients and caregivers to improve compliance with ERPs.Preoperative physical condition, a major determinant of postoperative outcome, could be optimized with the use of text messages (SMS) or digital applications (Apps) designed to facilitate smoking cessation, modify physical activity, and better manage hypertension and diabetes. Several non-invasive haemodynamic monitoring techniques and decision support tools are now available to individualize perioperative fluid management, a key component of ERPs. Objective nociceptive assessment may help to rationalize the use of pain medications, including opioids. Wearable sensors designed to monitor cardio-respiratory function may help in the early detection of clinical deterioration during the postoperative recovery and to address 'failure to rescue'. Activity trackers may be useful to monitor early mobilization, another major element of ERPs. Finally, electronic checklists have been developed to ensure that none of the above-mentioned ERP elements is omitted during the surgical journey.By optimizing compliance to the multiple components of ERPs, digital innovations, non-invasive techniques and wearable sensors have the potential to magnify the clinical and economic benefits of ERPs. Among the growing number of technical innovations, studies are needed to clarify which tools and solutions have real clinical value and are cost-effective.
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Deambulação Precoce/métodos , Recuperação de Função Fisiológica , Lista de Checagem , Técnicas de Apoio para a Decisão , Hidratação , Hemodinâmica , Humanos , Monitorização Fisiológica , Medição da Dor , Complicações Pós-Operatórias/prevenção & controle , Smartphone , Envio de Mensagens de TextoRESUMO
BACKGROUND: The present interdisciplinary consensus review proposes clinical considerations and recommendations for anaesthetic practice in patients undergoing gastrointestinal surgery with an Enhanced Recovery after Surgery (ERAS) programme. METHODS: Studies were selected with particular attention being paid to meta-analyses, randomized controlled trials and large prospective cohort studies. For each item of the perioperative treatment pathway, available English-language literature was examined and reviewed. The group reached a consensus recommendation after critical appraisal of the literature. RESULTS: This consensus statement demonstrates that anaesthesiologists control several preoperative, intraoperative and postoperative ERAS elements. Further research is needed to verify the strength of these recommendations. CONCLUSIONS: Based on the evidence available for each element of perioperative care pathways, the Enhanced Recovery After Surgery (ERAS®) Society presents a comprehensive consensus review, clinical considerations and recommendations for anaesthesia care in patients undergoing gastrointestinal surgery within an ERAS programme. This unified protocol facilitates involvement of anaesthesiologists in the implementation of the ERAS programmes and allows for comparison between centres and it eventually might facilitate the design of multi-institutional prospective and adequately powered randomized trials.
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Anestesia , Consenso , Procedimentos Cirúrgicos do Sistema Digestório , Injúria Renal Aguda/etiologia , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Humanos , Complicações Intraoperatórias/prevenção & controle , Monitorização Fisiológica , Náusea e Vômito Pós-Operatórios/prevenção & controle , Recuperação de Função FisiológicaRESUMO
'Enhanced recovery after surgery' protocols implement a series of peri-operative interventions intended to improve recovery after major operations, one aspect of which is fluid management. The pre-operative goal is to prepare a hydrated, euvolaemic patient by avoiding routine mechanical bowel preparation and by encouraging patients to drink clear liquids up to two hours before induction of anaesthesia. The intra-operative goal is to achieve a 'zero' fluid balance at the end of uncomplicated surgery: goal-directed fluid therapy is recommended for poorly prepared or sick patients or those undergoing more complex surgery. The postoperative goal is eating and drinking without intravenous fluid infusions. Postoperative oliguria should be expected and accepted, as urine output does not indicate overall fluid status.
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Hidratação/métodos , Assistência Perioperatória/métodos , Complicações Pós-Operatórias/prevenção & controle , Humanos , Equilíbrio HidroeletrolíticoRESUMO
There are few data regarding postoperative hyperglycaemia in non-diabetic compared with diabetic patients following postoperative nausea and vomiting prophylaxis with dexamethasone. Eighty-five non-diabetic patients and patients with type-2 diabetes were randomly allocated to receive intravenous dexamethasone (8 mg) or ondansetron (4 mg). Blood glucose levels were measured at baseline and then 2, 4 and 24 h following induction of anaesthesia. In non-diabetic patients, the mean (SD) maximum blood glucose was higher in those who received dexamethasone compared with ondansetron (9.1 (2.2) mmol.l(-1) vs. 7.8 (1.4) mmol.l(-1) , p = 0.04). In diabetic patients, the mean (SD) maximum blood glucose was also higher in those who received dexamethasone compared with ondansetron (14.0 (2.5) mmol.l(-1) vs. 10.7 (2.4) mmol.l(-1) , p < 0.01). Multivariate analysis demonstrated that dexamethasone administration was a significant predictor of maximum postoperative blood glucose increase (p < 0.01) after adjusting for potential confounders. There was no interaction between baseline blood glucose level, or presence or absence of diabetes, and dexamethasone administration. We conclude that dexamethasone increases postoperative blood glucose levels in both non-diabetics and diabetics.
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Antieméticos/farmacologia , Glicemia/efeitos dos fármacos , Dexametasona/farmacologia , Diabetes Mellitus Tipo 2/sangue , Náusea e Vômito Pós-Operatórios/tratamento farmacológico , Adulto , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ondansetron , Estudos ProspectivosRESUMO
BACKGROUND: The present article has been written to convey concepts of anaesthetic care within the context of an Enhanced Recovery After Surgery (ERAS) programme, thus aligning the practice of anaesthesia with the care delivered by the surgical team before, during and after surgery. METHODS: The physiological principles supporting the implementation of the ERAS programmes in patients undergoing major abdominal procedures are reviewed using an updated literature search and discussed by a multidisciplinary group composed of anaesthesiologists and surgeons with the aim to improve perioperative care. RESULTS: The pathophysiology of some key perioperative elements disturbing the homoeostatic mechanisms such as insulin resistance, ileus and pain is here discussed. CONCLUSIONS: Evidence-based strategies aimed at controlling the disruption of homoeostasis need to be evaluated in the context of ERAS programmes. Anaesthesiologists could, therefore, play a crucial role in facilitating the recovery process.
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Procedimentos Cirúrgicos do Sistema Digestório , Assistência Perioperatória , Cuidados Pós-Operatórios , Recuperação de Função Fisiológica , Anestesia Epidural , Anestesiologia , Transtornos Cognitivos/etiologia , Homeostase , Humanos , Resistência à Insulina , Dor Pós-Operatória/prevenção & controle , Papel do Médico , Estresse Fisiológico , Equilíbrio HidroeletrolíticoRESUMO
UNLABELLED: Acquired multidrug resistance (MDR) is the main mechanism of chemotherapeutic drugs resistance. Nevertheless, the mechanisms of MDR are complex and still not very clear. Recently, including our previous study, several studies have revealed that macroautophagy (here referred to as autophagy) induced by anti-cancer drugs in breast cancer cells may facilitate the development of resistance to epirubicin (EPI), paclitaxel (PTX), tamoxifen or herceptin. Whereas there are a few studies on the relationship between autophagy and MDR, especially the studies designed directly employing induced resistant breast cancer cells. Based on previous study, we explored the relationship between autophagy and MDR. The results showed that induced EPI-resistant MCF-7er and SK-BR-3er cells were simultaneously resistant to PTX and vinorelbine (NVB), which demonstrated that the cells obtained MDR phenotype. Furthermore, PTX and NVB could also induce autophagy in MCF-7er and SK-BR-3er cells, and the induced autophagy protected the cells from apoptosis, which facilitated the development of resistance to PTX and NVB. Thus, autophagy promoted the development of MDR in breast cancer cells through inhibition of apoptosis. In addition, we found that P-glycoprotein (Pgp) was overexpressed in MCF-7er and SK-Br-3er cells. And we preliminarily investigated the relationship between autophagy and P-glycoprotein (Pgp). The results showed that the expression of the protein did not obviously change despite the inhibition of autophagy. Therefore, the role of Pgp in the development of MDR might be independent of autophahy. Also this finding implies that autophagy might be a target to overcome MDR in breast cancer cells, and clinical use autophagy inhibitors might be one of the important strategies for overcoming MDR in breast cancer therapy. KEYWORDS: Autophagy, apoptosis, multidrug resistance, breast cancer, chemotherapy.
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BACKGROUND: Despite many clinical trials and investigative efforts to determine appropriate therapeutic intervention(s) for shock, this topic remains controversial. The use of i.v. fluid has represented the cornerstone for the treatment of hypoperfusion for two centuries. METHODS: As a part of International Acute Dialysis Quality Initiative XII Fluids Workgroup meeting, we sought to incorporate recent advances in our understanding of vascular biology into a more comprehensive yet accessible approach to the patient with hypoperfusion. In this workgroup, we attempted to develop a framework that incorporates key aspects of the vasculature into a diagnostic approach. RESULTS: The four main components of our proposal involve the assessment of the blood flow (BF), vascular content (vC), the vascular barrier (vB), and vascular tone (vT). Any significant perturbation in any of these domains can lead to hypoperfusion at both the macro- and micro-circulatory level. We have termed the BF, vC, vB, and vT diagnostic approach the vascular component (VC) approach. CONCLUSIONS: The VC approach to hypoperfusion has potential advantages to the current diagnostic system. This approach also has the distinct advantage that it can be used to assess the systemic, regional, and micro-vasculature, thereby harmonizing the approach to clinical vascular diagnostics across these levels. The VC approach will need to be tested prospectively to determine if this system can in fact improve outcomes in patients who suffer from hypoperfusion.
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Vasos Sanguíneos/fisiopatologia , Hidratação/métodos , Hidratação/normas , Hemodinâmica/fisiologia , Técnica Delphi , Diálise , Humanos , Microcirculação , Perfusão , Fluxo Sanguíneo Regional/fisiologia , Sepse/terapiaRESUMO
Under recognition combined with suboptimal management of right ventricular (RV) dysfunction and failure is associated with significant perioperative morbidity and mortality. The contemporary perioperative team must be prepared with an approach for early recognition and prompt treatment. In this review, a consensus-proposed scoring system is described to provide a pragmatic approach for expeditious decision-making for these complex patients with a vulnerable RV. Importantly, this proposed scoring system incorporates the context of the planned surgical intervention. Further, as the operating room (OR) represents a unique environment where patients are susceptible to numerous insults, a practical approach to anesthetic management and monitoring both in the OR and in the intensive care unit is detailed. Lastly, an escalating approach to the management of RV failure and options for mechanical circulatory support is provided.
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BACKGROUND: The analgesic efficacy and adverse effects of a single perioperative dose of dexamethasone are unclear. We performed a systematic review to evaluate the impact of a single i.v. dose of dexamethasone on postoperative pain and explore adverse events associated with this treatment. METHODS: MEDLINE, EMBASE, CINAHL, and the Cochrane Register were searched for randomized, controlled studies that compared dexamethasone vs placebo or an antiemetic in adult patients undergoing general anaesthesia and reported pain outcomes. RESULTS: Forty-five studies involving 5796 patients receiving dexamethasone 1.25-20 mg were included. Patients receiving dexamethasone had lower pain scores at 2 h {mean difference (MD) -0.49 [95% confidence interval (CI): -0.83, -0.15]} and 24 h [MD -0.48 (95% CI: -0.62, -0.35)] after surgery. Dexamethasone-treated patients used less opioids at 2 h [MD -0.87 mg morphine equivalents (95% CI: -1.40 to -0.33)] and 24 h [MD -2.33 mg morphine equivalents (95% CI: -4.39, -0.26)], required less rescue analgesia for intolerable pain [relative risk 0.80 (95% CI: 0.69, 0.93)], had longer time to first dose of analgesic [MD 12.06 min (95% CI: 0.80, 23.32)], and shorter stays in the post-anaesthesia care unit [MD -5.32 min (95% CI: -10.49 to -0.15)]. There was no dose-response with regard to the opioid-sparing effect. There was no increase in infection or delayed wound healing with dexamethasone, but blood glucose levels were higher at 24 h [MD 0.39 mmol litre(-1) (95% CI: 0.04, 0.74)]. CONCLUSIONS: A single i.v. perioperative dose of dexamethasone had small but statistically significant analgesic benefits.
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Anti-Inflamatórios/uso terapêutico , Dexametasona/uso terapêutico , Dor Pós-Operatória/prevenção & controle , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Período de Recuperação da Anestesia , Anestesia Geral , Anti-Inflamatórios/efeitos adversos , Intervalos de Confiança , Dexametasona/efeitos adversos , Determinação de Ponto Final , Feminino , Humanos , Masculino , Medição da Dor , Dor Pós-Operatória/epidemiologia , Risco , Resultado do TratamentoRESUMO
BACKGROUND: Postoperative nausea and vomiting (PONV) remain significant clinical problems for patients, especially nausea. The D2-antagonist droperidol was popular for prophylaxis until safety concerns limited its use. In early testing, APD421 (amisulpride for i.v. injection), a D2/D3-antagonist, has shown promising antiemetic efficacy at very low doses. We conducted a randomized, double-blind, dose-finding study to investigate APD421 in PONV prophylaxis. METHODS: Adult surgical patients with ≥2 Apfel risk factors for PONV undergoing surgery expected to last ≥1 h and receiving standard inhalation anaesthesia were randomized to receive placebo or one of three doses of APD421 (1, 5, or 20 mg) as a single i.v. administration at anaesthesia induction. The primary endpoint was PONV (vomiting/retching or antiemetic rescue) in the 24 h period after surgery. RESULTS: Two hundred and fifteen patients received study drug, 92% female and 60% with ≥3 risk factors. Groups were well balanced for baseline characteristics and risk factors. The PONV incidence was 37/54 [69%; 90% confidence interval (CI), 57-79%] in the placebo group; 28/58 (48%; 90% CI, 37-60%) with 1 mg APD421 (P=0.048); 20/50 (40%; 90% CI, 28-53%) with 5 mg (P=0.006); and 30/53 (57%; 90% CI, 44-68%) with 20 mg (P>0.1). APD421 at 5 mg also significantly improved vomiting, rescue medication use, and nausea rates. The safety profile of APD421 was similar to that of placebo at all doses, with no significant central nervous system (CNS) or cardiac side-effects. CONCLUSIONS: APD421 given i.v. before surgery is safe and effective at reducing PONV in moderate/high-risk adult surgical patients. The optimal dose tested was 5 mg.
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Antieméticos/uso terapêutico , Antagonistas de Dopamina/uso terapêutico , Náusea e Vômito Pós-Operatórios/prevenção & controle , Sulpirida/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Amissulprida , Anestesia por Inalação/métodos , Antieméticos/administração & dosagem , Antieméticos/efeitos adversos , Antagonistas de Dopamina/administração & dosagem , Antagonistas de Dopamina/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Medicação Pré-Anestésica/métodos , Sulpirida/administração & dosagem , Sulpirida/efeitos adversos , Sulpirida/uso terapêutico , Resultado do Tratamento , Adulto JovemRESUMO
The aim of this study was to explore the changes in gene and protein expressions of tyrosine hydroxylase (TH) and growth-associated protein 43 (GAP43) in aging atrial fibrillation patients of Xinjiang Uygur and Han nationality, and the significance of the changes. Real-time polymerase chain reaction and Western blot analysis were used to detect gene and protein expressions of TH and GAP43 in atrial tissues of 54 patients with valvular heart disease. mRNA and protein expressions of GAP43 and TH were significantly different between the sinus rhythm and atrial fibrillation groups (P < 0.05). Protein expressions of GAP43 and TH of both nationalities differed significantly between the sinus rhythm group and the atrial fibrillation group (P < 0.05), whereas there was no statistical difference between the two nationalities within each group (P > 0.05). Protein expressions of GAP43 and TH differed significantly among different age groups of different nationalities in the sinus rhythm and atrial fibrillation groups (P < 0.05); only protein expression of GAP43 differed significantly in different age groups in the atrial fibrillation group (P < 0.05). The changes of mRNA and protein expressions of TH and GAP43 played a vital role in the process of maintaining the atrial fibrillation. Therefore, increased expression of TH and GAP43 might be a molecular mechanism for left atrial myoelectricity remodeling of aging atrial fibrillation patients, which might be potential therapeutic targets of atrial fibrillation.