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1.
World J Surg Oncol ; 19(1): 296, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635107

RESUMO

PURPOSE: To investigate the lymph node metastasis pattern and significance of dissection of the left gastric artery lymph nodes in radical en bloc esophagectomy for esophageal squamous carcinomas based on the lymphatic drainage pathway revealed by carbon nanoparticle labeling. MATERIALS AND METHODS: Patients who underwent en bloc esophagectomy endoscopically were retrospectively enrolled. Carbon nanoparticles were injected in the submucosa of upper thoracic esophagus to label the relevant draining lymph nodes. The clinical data, lymph nodes dissected, surgical technique, and complications were analyzed. RESULTS: En bloc esophagectomy was successful in all 179 patients. Metastases to the left gastric artery lymph nodes were positive in 42 patients (23.5%) but negative in 137 (76.5%). The left gastric lymph nodes were labeled, whereas no celiac lymph nodes were labeled by carbon nanoparticles. A total of 4652 lymph nodes were resected, with 26 lymph nodes per patient. Seventy-three patients had lymph node metastasis (73/179). Seventeen patients had metastasis to the recurrent laryngeal nerve lymph nodes (9.5%). The metastasis rate of the lower thoracic esophageal cancer to the left gastric artery lymph nodes was 37.0%, significantly greater than that at the middle (15.4%) or upper (6.7%) thoracic segment. The lymph node metastasis rate was significantly (P < 0.05) increased with the length of the cancerous lesion, infiltration depth, and poor differentiation. Univariate analysis revealed that the metastasis rate to the left gastric artery lymph nodes was significantly (P < 0.05) associated with paraesophageal lymph node metastasis, para-cardial lymph metastasis, and TNM classification. Multivariate analysis indicated that cancer location (odds ratio 8.32, 95% confidence interval 2.12-32.24) was significantly (P < 0.05) associated with metastasis to the left gastric artery lymph nodes, with the cancer at the middle and lower thoracic segments significantly more than in the upper thoracic segment. CONCLUSION: Certain patterns exist in lymph node metastasis of esophageal cancer, and in radical esophagectomy of esophageal cancers, dissection of the left gastric artery lymph nodes is necessary to prevent possible residual or metastasis of esophageal squamous carcinomas based on the lymphatic drainage pathway of esophageal carcinomas demonstrated by carbon nanoparticle labeling.


Assuntos
Neoplasias Esofágicas , Esofagectomia , Dissecação , Neoplasias Esofágicas/cirurgia , Artéria Gástrica , Humanos , Excisão de Linfonodo , Linfonodos/cirurgia , Metástase Linfática , Prognóstico , Estudos Retrospectivos
2.
J Clin Lab Anal ; : e24078, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34708891

RESUMO

OBJECTIVE: This study was carried out to explore the potential involvement of miR-125a-5p in the oncogenic effects of EphA2, TAZ, and TEAD2 and the activity of the Hippo signaling pathway in gastric cancer progression. METHODS: In vitro transfection of miR-125a-5p mimics or inhibitors, qRT-PCR, colony formation assays, and cell invasion assays were used to assess the effect of miR-125a-5p on the growth and invasion in gastric cancer (GC). Male nude mice bearing tumors derived from human GC cells were used for evaluating the effects of miR-125a-5p on tumor growth. Luciferase reporter assay, immunofluorescence, immunohistochemistry, qRT-PCR, and immunoblotting were performed to explore the role of miR-125a-5p in the epithelial-mesenchymal transition (EMT) and association among miR-125a-5p, EphA2, TAZ, and TEAD2 in GC cells. RESULTS: MiR-125a-5p enhanced GC cell viability and invasion in vitro, whereas inhibition of miR-125a-5p using a specific inhibitor and antagomir suppressed cancer cell invasion and tumor growth. Moreover, inhibition of miR-125a-5p reversed EMT in vitro. miR-125a-5p upregulated the expression of EphA2, TAZ, and TEAD2, promoted TAZ nuclear translocation, and induced changes in the activity of the Hippo pathway by enhancing the expression of TAZ target genes. Finally, miR-125a-5p was overexpressed in late-stage GCs, and positive correlations were observed with its targets EphA2, TAZ, and TEAD2. CONCLUSION: miR-125a-5p can promote GC growth and invasion by upregulating the expression of EphA2, TAZ, and TEAD2.

3.
Nat Microbiol ; 6(10): 1319-1333, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34556855

RESUMO

The fate of influenza A virus (IAV) infection in the host cell depends on the balance between cellular defence mechanisms and viral evasion strategies. To illuminate the landscape of IAV cellular restriction, we generated and integrated global genetic loss-of-function screens with transcriptomics and proteomics data. Our multi-omics analysis revealed a subset of both IFN-dependent and independent cellular defence mechanisms that inhibit IAV replication. Amongst these, the autophagy regulator TBC1 domain family member 5 (TBC1D5), which binds Rab7 to enable fusion of autophagosomes and lysosomes, was found to control IAV replication in vitro and in vivo and to promote lysosomal targeting of IAV M2 protein. Notably, IAV M2 was observed to abrogate TBC1D5-Rab7 binding through a physical interaction with TBC1D5 via its cytoplasmic tail. Our results provide evidence for the molecular mechanism utilised by IAV M2 protein to escape lysosomal degradation and traffic to the cell membrane, where it supports IAV budding and growth.


Assuntos
Autofagia , Evasão da Resposta Imune , Vírus da Influenza A/fisiologia , Antivirais/metabolismo , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Vírus da Influenza A/patogenicidade , Lisossomos/metabolismo , Ligação Proteica , Proteínas da Matriz Viral/metabolismo , Replicação Viral , Proteínas rab de Ligação ao GTP/metabolismo
5.
Respir Res ; 22(1): 201, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238280

RESUMO

BACKGROUND: The effect of inhaled corticosteroids (ICS) on risk of hyperglycemia in patients with chronic obstructive pulmonary disease (COPD) remains ambiguous. The aim of this study is to evaluate the association between ICS use and the incidence of hyperglycemia related adverse effects in COPD patients. METHODS: Medline/PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov were searched from inception to 25 May 2020. Randomized controlled trials (RCTs) of ICS versus control (non-ICS) treatment for COPD patients reporting on risk of hyperglycemia were included. The Mantel-Haenszel method with fixed-effects modeling was used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Seventeen RCTs with 43,430 subjects were included in the meta-analysis. Pooled results suggested that there was no statistically significant difference in the risk of hyperglycemia between the ICS group and the control group (RR 1.02, 95% CI 0.90-1.16, P = 0.76). In addition, no significant difference was noted in the effect on glucose level (RR 1.20, 95% CI 0.79-1.82, P = 0.40), risk of diabetes progression (RR 0.84, 95% CI 0.20-3.51, P = 0.81) and new onset diabetes mellitus (RR 1.0, 95% CI 0.88-1.15, P = 0.95) between the ICS group and the control group. These findings also were consistent across all subgroup analyses. CONCLUSIONS: Use of ICS does not have an effect on the blood glucose and is not associated with the risk of new onset diabetes mellitus and diabetes progression in patients with COPD. Further RCTs exploring the association between ICS use and risk of hyperglycemia in COPD patients are still needed to verify our results of this analysis.

6.
Front Neurol ; 12: 646990, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34234732

RESUMO

Up to one-third (12-35%) of patients with aneurysmal subarachnoid hemorrhage experience intracerebral hematoma. Ruptured middle cerebral artery (MCA) aneurysm with hematoma is usually accompanied by progressive cerebral swelling with poor outcomes; however, it can be successfully treated by coil embolization and minimally invasive puncture and drainage. From February 2012 to March 2019, six surgeries for ruptured MCA aneurysms with intrasylvian hematoma were performed at our clinic. All patients had intracranial hematomas of <30 ml and GCS scores >8. The patients were treated by coil embolization and minimally invasive puncture and drainage. The aneurysms in all patients were completely embolized and the hematomas were mostly removed by minimally invasive puncture. The Glasgow outcome scale (GOS) scores of all patients were more than 4 at discharge when they discharged. Coil embolization and minimally invasive puncture and drainage are viable treatments for ruptured MCA aneurysms with hematomas, especially if the patient is too old, in a complicated state to undergo craniotomy, is unwilling to undergo craniotomy, or is at a greater risk of bleeding 3 days after surgery.

7.
Food Chem ; 364: 130413, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34175629

RESUMO

Citrus peels have health-promoting effects and are a rich source of antioxidant substances. This study evaluated the compositions of phenolic compounds and antioxidant activities in the peels of 52 citrus varieties with consistent planting time and management. The highest levels of total phenols (72.95 ± 37.60 mg/g DW) and total flavonoids (71.43 ± 37.64 mg/g DW) were found in mandarin. The highest phenolic acid content (18.78 ± 0.38 mg/g DW), dominated by protocatechuic acid, was found in kumquat. The antioxidant potency composite index was 6.23-94.56, suggesting mandarin varieties HJ, TWPG, TTPG, AY28, BZH and TCJC had the highest antioxidant activity. Statistics analysis indicated phenolic compounds and antioxidant activity were positively correlated. Principal component analysis and hierarchical cluster analysis suggested a strong relationship between phenolic compound composition and genetic background. This study indicated significant differences in the biological properties of various types of citrus peels; which are valuable for future utilization and research of citrus peels.


Assuntos
Citrus , Antioxidantes , China , Flavonoides , Fenóis/análise , Extratos Vegetais/análise
8.
Pharm Biol ; 59(1): 629-638, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34062090

RESUMO

CONTEXT: Selenium-containing protein from selenium-enriched Spirulina platensis (Se-SP) (syn. Arthrospira platensis [Microcoleaceae]) showed novel antioxidant activity. However, the protective effect of Se-SP against oxygen glucose deprivation (OGD)-induced neural apoptosis has not been reported yet. OBJECTIVE: To verify whether Se-SP can inhibit OGD-induced neural apoptosis and explore the underlying mechanism. MATERIALS AND METHODS: Primary hippocampal neurons were separated from Sprague-Dawley (SD) rats. 95% N2 + 5% CO2 were employed to establish OGD model. Neurons were treated with 5 and 10 µg/mL Se-SP under OGD condition for 6 h. Neurons without treatment were the control group. Neural viability and apoptosis were detected by MTT, immunofluorescence and western blotting methods. RESULTS: Se-SP significantly improved neuronal viability (from 57.2% to 94.5%) and inhibited apoptosis in OGD-treated primary neurons (from 45.6% to 6.3%), followed by improved neuronal morphology and caspases activation. Se-SP co-treatment also effectively suppressed OGD-induced DNA damage by inhibiting ROS accumulation in neurons (from 225.6% to 106.3%). Additionally, mitochondrial dysfunction was also markedly improved by Se-SP co-treatment via balancing Bcl-2 family expression. Moreover, inhibition of mitochondrial permeability transition pore (MPTP) by CsA (an MPTP inhibitor) dramatically attenuated OGD-induced ROS generation (from 100% to 56.2%), oxidative damage, mitochondrial membrane potential (MPP) loss (from 7.5% to 44.3%), and eventually reversed the neuronal toxicity and apoptosis (from 57.4% to 79.6%). DISCUSSION AND CONCLUSIONS: Se-SP showed enhanced potential to inhibit OGD-induced neurotoxicity and apoptosis by inhibiting ROS-mediated oxidative damage through regulating MPTP opening, indicating that selenium-containing protein showed broad application in the chemoprevention and chemotherapy against human ischaemic brain injury.

9.
Psychiatry Res ; 302: 114019, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34058715

RESUMO

Although some studies have reported the potential efficacy of electroconvulsive therapy (ECT) in the treatment of acute mania, there is no consensus on the matter. Therefore, we performed a meta-analysis to determine the efficacy and safety of ECT combination with medication (ECT-combo) vs. medication alone (Med-alone) in the treatment of acute mania. Randomized controlled trials (RCTs) of ECT-combo versus Med-alone in acute mania were searched in Chinese databases and English databases from their inceptions up to February 2020. Twelve RCTs (including 863 patients, n=863) met our criteria and were included into meta-analysis. The pooled results found that ECT-combo outperformed Med-alone in reducing manic symptoms from baseline to endpoint with a standardized mean difference of -3.50 (95% CI: -4.57, -2.44, p<0.00001). The significant difference occurred after 3-5 treatments or after a 1-week treatment. ECT-combo had significantly increased memory impairment compared to Med-alone. Apart from increased memory impairment in ECT-combo group (SMD=8.33; 95% CI: 2.73 to 25.45, p= 0.0002), no other statistically significant differences in side effects or drop-out rates were found between groups. The results of this meta-analysis suggest that ECT-combo was significantly superior to Med-alone in efficacy and well-tolerated as Med-alone in the acute treatment of mania. However, larger studies with randomized, double-blind design, and standardized treatment regimens are still warranted due to the high heterogeneity of studies included in the present meta-analysis.


Assuntos
Eletroconvulsoterapia , Método Duplo-Cego , Humanos , Mania , Transtornos da Memória , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
11.
PeerJ Comput Sci ; 7: e504, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34013032

RESUMO

Sensors in Cyber-Physical Systems (CPS) are typically used to collect various aspects of the region of interest and transmit the data towards upstream nodes for further processing. However, data collection in CPS is often unreliable due to severe resource constraints (e.g., bandwidth and energy), environmental impacts (e.g., equipment faults and noises), and security concerns. Besides, detecting an event through the aggregation in CPS can be intricate and untrustworthy if the sensor's data is not validated during data acquisition, before transmission, and before aggregation. This paper introduces In-network Generalized Trustworthy Data Collection (IGTDC) framework for event detection in CPS. This framework facilitates reliable data for aggregation at the edge of CPS. The main idea of IGTDC is to enable a sensor's module to examine locally whether the event's acquired data is trustworthy before transmitting towards the upstream nodes. It further validates whether the received data can be trusted or not before data aggregation at the sink node. Additionally, IGTDC helps to identify faulty sensors. For reliable event detection, we use collaborative IoT tactics, gate-level modeling with Verilog User Defined Primitive (UDP), and Programmable Logic Device (PLD) to ensure that the event's acquired data is reliable before transmitting towards the upstream nodes. We employ Gray code in gate-level modeling. It helps to ensure that the received data is reliable. Gray code also helps to distinguish a faulty sensor. Through simulation and extensive performance analysis, we demonstrate that the collected data in the IGTDC framework is reliable and can be used in the majority of CPS applications.

12.
Harmful Algae ; 103: 102012, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33980451

RESUMO

Harmful algal blooms that can produce toxins are common in the Indian River Lagoon (IRL), which covers ~250 km of Florida's east coast. The current study assessed the dynamics of microcystins and saxitoxin in six segments of the IRL: Banana River Lagoon (BRL), Mosquito Lagoon (ML), Northern IRL (NIRL), Central IRL (CIRL), Southern IRL (SIRL), and the St. Lucie Estuary (SLE). Surface water samples (n = 40) collected during the 2018 wet and 2019 dry season were analyzed to determine associations between toxins and temperature, salinity, pH, oxygen saturation, concentrations of dissolved nutrients and chlorophyll-a, presence of biosynthetic genes for toxins, relative abundance of planktonic species, and composition of the microbial community. The potential toxicity of samples was assessed using multiple mammalian cell lines. Enzyme-Linked Immunosorbent Assays were used to determine concentrations of microcystins and saxitoxin. Overall, the microcystins concentration ranged between 0.01-85.70 µg/L, and saxitoxin concentrations ranged between 0.01-2.43 µg/L across the IRL. Microcystins concentrations were 65% below the limit of quantification (0.05 µg/L), and saxitoxin concentrations were 85% below the limit of detection (0.02 µg/L). Microcystins concentrations were higher in the SLE, while saxitoxin was elevated in the NIRL and BRL. Cytotoxicity related to the presence of microcystins was seen in the SLE during the wet season. No significant patterns between cytotoxicity and saxitoxin were identified. Dissolved nutrients were identified as the most highly related parameters, explaining 53% of microcystin and 47% of saxitoxin variability. Multivariate models suggested cyanobacteria, flagellates, ciliates, and diatoms as the subset of microorganisms whose abundances were maximally correlated with saxitoxin and microcystins concentrations. Lastly, biosynthetic genes for microcystins were detected in the SLE and for saxitoxin in the BRL and NIRL. These results highlight the synergistic roles environmental and biological parameters play in influencing the dynamics of toxin production by harmful algae in the IRL.


Assuntos
Microcistinas , Rios , Animais , Florida , Saxitoxina
13.
Aust N Z J Psychiatry ; : 4867421998804, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33726535

RESUMO

OBJECTIVES: Physical diseases are well-established risk factor for suicide, particularly among older adults. However, little is known about the underlying mechanism of the association. This study aimed to describe the prevalence of physical diseases and their influences on the elderly in rural China and to examine the underlying mechanisms of the relationship between physical diseases and suicide. METHODS: This matched case-control psychological autopsy study was conducted from June 2014 to September 2015. Consecutive suicide cases (242) among people aged 60 years or above were identified in three Chinese provinces. The suicide cases were 1:1 matched with living comparisons based on age, gender and residential area. Two informants for each participant were interviewed to collect data on their demographic characteristics, the severity index of physical diseases, depressive symptoms, feelings of hopelessness, mental disorders and social support. RESULTS: A significant difference was found between suicide cases and living comparisons regarding the prevalence of physical diseases (83.5% vs 66.5%, p < 0.001) and their severity (11.3 ± 6.2 vs 6.7 ± 5.3, p < 0.001). Independent risks of suicide included the following: not currently married (OR = 2.81, 95% CI = [1.04, 7.62]), mental disorders (OR = 7.18, 95% CI = [1.83, 28.13]), depressive symptoms (OR = 1.15, 95% CI = [1.05, 1.26]) and feelings of hopelessness (OR = 1.51, 95% CI = [1.20, 1.90]). The structural equation model indicated that the relationship between the severity index of physical diseases and suicide was mediated by depressive symptoms, feelings of hopelessness and mental disorders. CONCLUSION: The severity and number of physical diseases were found to be correlated with suicide among the elderly in rural China, after controlling for demographic characteristics. Physical diseases elevate one's suicide risk by increasing depressive symptoms, feelings of hopelessness and mental disorders. Efforts for suicide prevention should be integrated with strategies to treat physical diseases along with psychological interventions.

15.
Microbiol Resour Announc ; 10(8)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33632867

RESUMO

The genome sequence of the Forcepia sponge-derived bacterium Streptomyces sp. strain HB-N217 was determined, with approximately 8.25 Mbp and a G+C content of 72.1%. Thirty biosynthetic gene clusters that bear the capability to produce secondary metabolites were predicted. The results will aid marine natural product chemistry and sponge-microbe association studies.

16.
Biomed Res Int ; 2021: 6623426, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33506024

RESUMO

Design: A systematic document retrieval of studies published in the past 10 years reporting periprocedural stroke/mortality/MI after carotid endarterectomy (CEA) related to the time between CEA and qualifying neurological symptoms. The application database has "PubMed, EMbase and Cochrane databases." RevMan5.3 software provided by the Cochrane collaboration was used for meta-analysis. Results: A systematic literature search was conducted in databases. A total of 10 articles were included in this study. They were divided into early CEA and delayed CEA with operation within 48 h, 1 w, or 2 w after onset of neurological symptoms. Incidence of the postoperative stroke in patients undergoing delayed CEA (≥48 h) was significantly higher than patients with delayed CEA (<48 h) (OR = 2.14, 95% CI: 1.43-3.21, P = 0.0002). The postoperative mortality of patients after delayed CEA (≥48 h) was significantly higher than patients after early CEA (<48 h) (OR = 1.35, 95% CI: 1.06-1.71, P = 0.02). The risk of postoperative mortality of patients treated with delayed CEA (≥7 d) was significantly higher than patients after the early CEA group (<7 d) (OR = 1.69, 95% CI: 1.21-2.32, P = 0.001). Conclusion: Early CEA is safe and effective for a part of patients with symptomatic carotid stenosis, but a comprehensive preoperative evaluation of patients with carotid stenosis must be performed.


Assuntos
Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas , Complicações Pós-Operatórias , Acidente Vascular Cerebral , Endarterectomia das Carótidas/efeitos adversos , Endarterectomia das Carótidas/métodos , Endarterectomia das Carótidas/mortalidade , Endarterectomia das Carótidas/estatística & dados numéricos , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/mortalidade , Tempo para o Tratamento , Resultado do Tratamento
17.
Artigo em Inglês | MEDLINE | ID: mdl-33497343

RESUMO

Modeling, prediction, and recognition tasks depend on the proper representation of the objective curves and surfaces. Polynomial functions have been proved to be a powerful tool for representing curves and surfaces. Until now, various methods have been used for polynomial fitting. With a recent boom in neural networks, researchers have attempted to solve polynomial fitting by using this end-to-end model, which has a powerful fitting ability. However, the current neural network-based methods are poor in stability and slow in convergence speed. In this article, we develop a novel neural network-based method, called Encoder-X, for polynomial fitting, which can solve not only the explicit polynomial fitting but also the implicit polynomial fitting. The method regards polynomial coefficients as the feature value of raw data in a polynomial space expression and therefore polynomial fitting can be achieved by a special autoencoder. The entire model consists of an encoder defined by a neural network and a decoder defined by a polynomial mathematical expression. We input sampling points into an encoder to obtain polynomial coefficients and then input them into a decoder to output the predicted function value. The error between the predicted function value and the true function value can update parameters in the encoder. The results prove that this method is better than the compared methods in terms of stability, convergence, and accuracy. In addition, Encoder-X can be used for solving other mathematical modeling tasks.

18.
J Proteome Res ; 20(1): 950-959, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33105993

RESUMO

Drug addiction is a chronic relapsing brain disease. Alterations of glucose uptake and metabolism are found in the brain of drug addicts. Insulin mediates brain glucose metabolism and its abnormality could induce brain injury and cognitive impairment. Here, we established a rat model of phenobarbital addiction by 90 days of dose escalation and evaluated addiction-related symptoms. We also performed 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) to detect glucose uptake in the brain and proteomic analysis of the function of the differentially expressed (DE) proteins via bioinformatics in brain tissues by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) on days 60 and 90 of phenobarbital or 0.5% carboxymethyl cellulose sodium (CMC-Na) (vehicle) administration. The results showed that phenobarbital-addictive rats developed severe withdrawal symptoms after abstinence and glucose uptake was significantly increased in the brain. Proteomics analysis showed that numerous DE proteins were enriched after phenobarbital administration, among which CALM1, ARAF, and Cbl proteins (related to the insulin signaling pathway) were significantly downregulated on day 60 but not day 90. However, SLC27A3 and NF-κB1 proteins (related to insulin resistance) were significantly upregulated on day 90 (data are available via ProteomeXchange with identifier PXD021101). Our data indicate that the insulin signaling pathway and insulin resistance may play a role in the development of phenobarbital addiction and brain injury, so the findings may have important clinical implications.


Assuntos
Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Animais , Encéfalo/diagnóstico por imagem , Cromatografia Líquida , Glucose , Insulina , Fenobarbital/toxicidade , Proteômica , Ratos , Transdução de Sinais , Espectrometria de Massas em Tandem
19.
J Glob Antimicrob Resist ; 24: 136-147, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32889142

RESUMO

OBJECTIVES: This study aimed to compare the efficacy and safety of combination therapy with high-dose sulbactam or colistin with additional antibacterial agents for treating multidrug-resistant or extensively drug-resistant Acinetobacter baumannii (MDR-AB or XDR-AB) infections. METHODS: We systematically searched PubMed, Embase, Cochrane, and Web of Science (through March 30, 2020) for studies that examined high-dose sulbactam or colistin with additional antibacterial agents as therapy for patients with infections with MDR-AB and XDR-AB. Through a network meta-analysis (NMA), using both direct and indirect evidence, we determined risk ratios and 95% confidence intervals. Primary outcomes included clinical improvement, clinical cure, microbiological eradication, and mortality from any cause. Secondary outcomes included nephrotoxicity. RESULTS: The NMA included 18 studies and 1835 patients. We found that high-dose sulbactam (≥6 g per day), combined with another single antibacterial agent (levofloxacin or tigecycline), which were the highest ranking in clinical improvement and clinical cure. Still colistin-based combination in drug-resistant Acinetobacter baumannii therapy occupied the main position (the number of studies and patients) in most studies. Colistin combined with additional antibacterial agents was associated with a higher risk of nephrotoxicity. CONCLUSIONS: Therapeutic regimens including high-dose sulbactam in combination with additional antibacterial agents (including colistin) might be one of the promising options for the treatment of MDR-AB or XDR-AB infections and high-quality study will be needed to confirm clinical efficacy.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Preparações Farmacêuticas , Infecções por Acinetobacter/tratamento farmacológico , Antibacterianos/efeitos adversos , Colistina/farmacologia , Farmacorresistência Bacteriana Múltipla , Quimioterapia Combinada , Humanos , Testes de Sensibilidade Microbiana , Minociclina/farmacologia , Metanálise em Rede , Sulbactam/efeitos adversos
20.
Respir Care ; 66(2): 316-326, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33051255

RESUMO

BACKGROUND: Although systemic corticosteroids (SCS) have long been used to treat patients with COPD exacerbation, the recommended dose remains controversial. We aimed to perform a meta-analysis and an indirect treatment comparison to investigate the efficacy and safety of different doses of SCS in subjects with COPD exacerbation. METHODS: Studies were identified by searching different databases for randomized controlled trials that investigated the efficacy and safety of SCS with placebo in subjects with exacerbation of COPD. The different doses of SCS were assigned to low-dose (ie, initial dose ≤ 40 mg prednisone equivalent/d [PE/d]), medium-dose (initial dose = 40-100 mg PE/d, and high-dose (initial dose > 100 mg PE/d) groups. The indirect treatment comparison was performed between low-, medium-, and high-dose SCS groups. RESULTS: Twelve trials with 1,375 participates were included. Compared to placebo, the risk of treatment failure was lower in the low-dose SCS groups (risk ratio 0.61 [95% CI 0.43-0.88], P = .007) and high-dose SCS groups (risk ratio 0.64 [95% CI 0.48-0.85], P = .002); the FEV1 was significantly improved in low-dose (mean difference 0.09 [95% CI 0.06-0.12], P < .001), medium-dose (mean difference 0.23 [95% CI 0.02-0.44], P = .036), and high-dose SCS groups (mean difference 0.09, [95% CI 0.03-0.15], P < .001, respectively). Regarding safety, the incidence of hyperglycemia was higher in high-dose SCS groups versus placebo (risk ratio 2.52 [95% CI 1.13-5.62], P = .02). The indirect comparison between low-, medium-, and high-dose SCS found that the risk of treatment failure and changes in FEV1 were similar between these doses of SCS. CONCLUSIONS: This meta-analysis indicates that low-dose SCS (initial dose ≤ 40 mg PE/d) was sufficient and safer for treating subjects with COPD exacerbation, and it was noninferior to higher doses of SCS (initial dose > 40 mg PE/d) in improving FEV1 and reducing the risk of treatment failure. However, our findings need to be verified in head-to-head randomized controlled trials.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Corticosteroides/efeitos adversos , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Testes de Função Respiratória
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