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BACKGROUND: The benefit of adding Zolbetuximab to the treatment in patients with Claudin-18 isoform 2 (CLDN18.2)-positive, human epidermal growth factor receptor 2-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GC/GEJ) is not yet fully elucidated. METHODS: We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) that investigated Zolbetuximab plus chemotherapy versus chemotherapy alone for GC or GEJ adenocarcinoma. We computed hazard-ratios (HRs) or odds-ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). RESULTS: Three studies and 1,233 patients were included. Comparing with Zolbetuximab plus chemotherapy versus chemotherapy alone, progression-free survival (PFS) rate (HR 0.64; 95% CI 0.49-0.84; p < 0.01) and overall survival (OS) rate (HR 0.72; 95% CI 0.62-0.83; p < 0.01) were significant in favor of the Zolbetuximab group. Regarding effectiveness, the Objective Response Rate (ORR) was (OR 1.15; 95% CI 0.87-1.53; p = 0.34). CONCLUSIONS: In this comprehensive systematic review and meta-analysis of RCTs, the incorporation of Zolbetuximab alongside chemotherapy offers a promising prospect for reshaping the established treatment paradigms for patients diagnosed with advanced CLDN18.2-positive GC/GEJ cancer.
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Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Gástricas/patologia , Anticorpos Monoclonais/efeitos adversos , Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Junção Esofagogástrica/patologia , ClaudinasRESUMO
This systematic review and meta-analysis investigated the efficacy and safety of fezolinetant for the treatment of moderate-to-severe vasomotor symptoms (VMS) associated with menopause. PubMed, Cochrane Library, Embase and Web of Science were searched for randomized controlled trials (RCTs) published from inception to June 2023, comparing fezolinetant to placebo in postmenopausal women suffering from moderate-to-severe VMS. The mean difference and risk ratio were calculated for continuous and binary outcomes, respectively. R software was used for the statistical analysis, and RoB-2 (Cochrane) to assess the risk of bias. We performed subgroup analysis based on different dosing regimens. Five RCTs comprising 3302 patients were included. Compared with placebo, at 12-week follow-up, fezolinetant significantly reduced the daily frequency of moderate-to-severe VMS (weighted mean difference [WMD] - 2.36; 95% confidence interval [CI] - 2.92, -1.81) and daily severity of moderate-to-severe VMS (WMD -0.22; 95% CI -0.31, -0.13). Also, fezolinetant significantly improved the quality of life (WMD -0.42; 95% CI -0.58, -0.26) and sleep disturbance (WMD -1.10; 95% CI -1.96, -0.24). There were no significant differences between groups in adverse events. These findings support the efficacy and safety of fezolinetant for the treatment of VMS related to menopause.
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Fogachos , Menopausa , Humanos , Feminino , Fogachos/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Pessoa de Meia-Idade , Resultado do Tratamento , Sistema Vasomotor/efeitos dos fármacos , Qualidade de VidaRESUMO
Geopropolis resins are produced by stingless bees (Meliponinae), developed from the collection of resinous materials, waxes and exudates, from the flora of the region where stingless bees are present, in addition to the addition of clay or earth in its composition. Several biological activities are attributed to Ethanol Extracts of Geopropolis (EEGP). The bioactive properties are associated with the complex chemical composition that the samples have. This work aims to evaluate the biological activities of the EEGP, in order to contribute with a natural therapeutic alternative, to face infections, mainly those caused by resistant strains of Staphylococcus aureus. The EEGP MIC tests showed antibacterial activity against two strains of S. aureus, both at concentrations of 550â µg/mL. The MBC performed with the inhibition values showed that the EEGP has bacteriostatic activity in both strains. Biofilm inhibition rates exhibited an average value greater than 65 % at the highest concentration. The EEGP antioxidant potential test showed good antioxidant activity (IC50) of 11.05±1.55â µg/mL. In the cytotoxicity test against HaCat cells, after 24â hours, EEGP induced cell viability at the three tested concentrations (550â µg/mL: 81.68±3.79 %; 1100â µg/mL: 67.10±3.76 %; 2200â µg/mL: 67.40±1.86 %). In view of the above, the safe use of EEGP from the brazilian northeast could be proven by the cytotoxicity test, and its use as an antioxidant and antibacterial agent has proven to be effective, as an alternative in combating oxidative stress and microorganisms such as S.â aureus, which, through the spread and ongoing evolution of drug resistance, generates an active search for effective solutions.
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Antibacterianos , Biofilmes , Testes de Sensibilidade Microbiana , Staphylococcus aureus , Staphylococcus aureus/efeitos dos fármacos , Animais , Abelhas , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Humanos , Biofilmes/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Própole/química , Própole/farmacologia , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Relação Dose-Resposta a DrogaRESUMO
OBJECTIVES: To provide an update on the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on stroke in patients with type 2 diabetes (T2D). METHODS: PubMed, Embase, and Cochrane Library were systematically searched for randomized controlled trials (RCTs) comparing SGLT2 inhibitors versus placebo or other therapies in patients with T2D and reporting stroke endpoint. We computed the risk ratios (RRs) to binary endpoints, with 95â¯% confidence intervals (CIs). RESULTS: A total of 71 RCTs and 105,914 patients were included, of whom 62,488 (59â¯%) were randomized to the SGLT2 inhibitors group. The follow-up ranged from 12 weeks to 4.2 years. There were no significant differences between groups in all types of stroke (RR 0.96; 95â¯% CI 0.89-1.04), ischemic stroke (RR 0.89; 95â¯% CI 0.76-1.04), and transient ischemic attack (RR 0.96; 95â¯% CI 0.79-1.16). Patients on SGLT2 inhibitors experienced lower rates of hemorrhagic stroke (RR 0.62; 95â¯% CI 0.39-0.98). In the subgroup analysis of the type of drug, sotagliflozin significantly reduced all types of stroke (RR 0.74; 95â¯% CI 0.56-0.97). CONCLUSION: In this meta-analysis of 71 RCTs comprising 105,914 patients with T2D, SGLT2 inhibitors were not associated with a reduced risk of stroke and transient ischemic attack compared to placebo or other therapies; however, there was a trend toward reduced risk of hemorrhagic stroke. Among all SGLT2 inhibitors, sotagliflozin significantly reduced the risk of stroke.
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Diabetes Mellitus Tipo 2 , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores do Transportador 2 de Sódio-Glicose , Acidente Vascular Cerebral , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Resultado do Tratamento , Fatores de Risco , Medição de Risco , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Acidente Vascular Cerebral Hemorrágico/diagnóstico , Fatores de Tempo , AVC Isquêmico/diagnóstico , AVC Isquêmico/tratamento farmacológico , Transportador 2 de Glucose-SódioRESUMO
Syagrus coronata, a native palm tree in the Caatinga domain, produces fixed oil (ScFO) used therapeutically and dietary by Northeast Brazilian communities. This study evaluated its anti-inflammatory potential of CFA-induced arthritis and its effect on behavioral parameters. In the acute model, ScFO at 25, 50, and 100 mg/kg showed edematogenic effects similar to indomethacin at 4 mg/kg (p > 0.05). In the arthritis model, 100 mg/kg ScFO treatment was comparable to indomethacin (4 mg/kg) (p > 0.05). TNF-α and IL-1ß levels were significantly reduced in ScFO-treated groups at 25, 50, and 100 mg/kg, and the indomethacin group (4 mg/kg) versus the positive control (p > 0.05). Radiographs showed severe soft-tissue swelling and bone deformities in the control group, while the 100 mg/kg ScFO group had few alterations, similar to the indomethacin group. Histopathological analysis revealed intense lymphocytic infiltration in the control group, mild diffuse lymphocytic infiltration in the indomethacin group, and mild lymphoplasmacytic infiltration with focal polymorphonuclear infiltrates in the 100 mg/kg ScFO group. Behavioral analysis showed improved exploratory stimuli in ScFO and indomethacin-treated mice compared to the positive control (p > 0.05). ScFO demonstrated anti-inflammatory effects in both acute and chronic arthritis models, reducing edema and pro-inflammatory cytokines, and improved exploratory behavior due to its analgesic properties.
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During the transition period, dairy cows are often exposed to negative energy balance (NEB), leading to lipid mobilization from adipose tissue into nonesterified fatty acids (NEFA), a common indicator of heightened illness risk. This study aimed to use blood near-infrared (NIR) spectra data to classify NEB into high or low categories, based on early-lactation cow NEFA thresholds. We collected a total of 186 plasma samples from 100 Holstein cows. The samples were categorized into critical thresholds, based on previous literature, of ≥0.60 and ≥0.70 mEq/L for identifying high NEB. Spectral data were preprocessed before the development of the predictive modes, which included the implementation of multiplicative scatter correction, standard normal variate (SNV), and first and second derivatives. The classification was performed using partial least square discriminant analyses (PLS-DA), and predictive performance was assessed using leave-one-out cross-validation. Predictive quality for each class was evaluated through specificity, precision, sensitivity, and F1 score. The study showed promising results, with the SNV technique achieving higher F1 scores. The model found 72.7% specificity, 78.9% precision, 80.8% sensitivity, and 79.8% F1 score to classify animals with NEFA levels of ≥0.60 mEq/L, and 82.1% specificity, 78.7% precision, 80.8% sensitivity, and 79.7% F1 score to classify animals with NEFA levels ≥0.70 mEq/L. These results indicate that NIR spectroscopy could serve as a tool for detecting cows under severe NEB, also showing potential for broader application across the entire transition period, as the spectral signal carried relevant information regarding cow metabolism. Furthermore, the combination of predictors derived from plasma spectra and other cow-level information can lead to more accurate disease alerts, given their relationship with the NEB.
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PURPOSE: To present a method for analyzing breathing modes with infrared thermography. METHODS: This exploratory cross-sectional study used 38 thermal images of inspiration and expiration with nasal breathing and simulated mouth breathing in four nasal breathers without respiratory complaints. Three different data selection forms (line, rectangle, and ellipse) were used to extract the minimum, mean, and maximum temperatures of the regions of interest (nose and mouth) using the FLIR Tools® software. RESULTS: Among the three selection forms, there was greater temperature variability obtained with the line, revealing limitations in this measurement. There were no differences between the rectangle and ellipse values, showing that both selection forms present similar temperature extraction results. The comparison results between nose and mouth temperatures during inspiration and expiration indicated a statistically significant difference between all measurements, except for mean inspiration temperatures with the rectangle and ellipse. The breathing mode can be distinguished in both inspiration and expiration when using mean mouth temperatures with the rectangle and ellipse. CONCLUSION: Breathing modes should be assessed based on mean mouth temperatures during inspiration, using the ellipse.
OBJETIVO: Apresentar um método de análise do modo respiratório por meio da termografia infravermelha. MÉTODO: Estudo transversal exploratório de 38 imagens térmicas que representavam o momento da inspiração e da expiração durante a respiração nasal e durante a simulação da respiração oral de quatro voluntárias respiradoras nasais sem queixas respiratórias. Para a extração da temperatura das regiões de interesse (nariz e boca) foram utilizadas três formas de seleção distintas de dados (linha, retângulo e elipse) e três medidas de temperatura (mínima, média e máxima) por meio do software FLIR Tools®. RESULTADOS: Dentre as três formas de seleção houve maior variabilidade nas medidas obtidas pela linha, revelando limitações nessa medida. Não houve diferenças entre as medidas do retângulo e elipse, mostrando que ambas as formas de seleção apresentam resultados semelhantes para a extração das temperaturas. Na comparação entre as temperaturas do nariz e da boca na inspiração e expiração, os resultados indicaram que houve diferença com relevância estatística em todas as medidas realizadas, exceto para as medidas de temperatura média da inspiração, usando o retângulo e a elipse. Percebe-se diferenciação do modo respiratório tanto na inspiração quanto na expiração quando utilizada a temperatura média da boca com o retângulo e a elipse. CONCLUSÃO: Sugere-se para avaliação do modo respiratório a avaliação da boca, por meio da elipse, com análise da temperatura média durante a inspiração.
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Respiração , Termografia , Humanos , Projetos Piloto , Estudos Transversais , Nariz , Respiração BucalRESUMO
PRCIS: Selective laser trabeculoplasty (SLT) and medical therapy groups displayed comparable intraocular pressure (IOP) at most follow-ups. SLT was associated with significantly decreased rates of glaucoma surgeries, antiglaucomatous medications, and ocular adverse effects. PURPOSE: To evaluate the efficacy and safety of selective laser trabeculoplasty (SLT) compared to medical therapy in the treatment of open-angle glaucoma (OAG) or ocular hypertension (OHT). METHODS: A systematic search was performed in PubMed, Embase, Cochrane Library and Web of Science databases. Randomized controlled trials (RCTs) comparing SLT with medical therapy were included. We computed mean differences (MDs) or standardized mean differences (STDs) for continuous endpoints and risk ratios (RRs) for binary endpoints, with 95% confidence intervals (CIs). Heterogeneity was assessed with I2 statistics. Software R, version 4.2.1, was used for statistical analyses. Subgroup analyses were performed on treatment-naive patients and on the class of drugs in the medical therapy group. RESULTS: Fourteen RCTs comprising 1,706 patients were included, of whom 936 were submitted to SLT. Medical therapy was associated with a significantly improved IOP at 1 month and a higher proportion of patients achieving ≥20% IOP reduction. There were no significant differences between groups in IOP at 2, 3, 6, and 12 months, IOP fluctuation, rate of eyes at target IOP, visual field, and quality of life. The SLT group exhibited significantly decreased rates of glaucoma surgeries, antiglaucoma medications, and ocular adverse effects. CONCLUSION: SLT demonstrated comparable efficacy to medical therapy in IOP control at most follow-ups, along with favorable impacts on critical treatment-related factors. Our findings support SLT as a safe and effective treatment for OAG or OHT.
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The aim of this study was to assess the efficacy and safety of hybrid closed-loop (HCL) systems for insulin delivery in children and adolescents with type 1 diabetes (T1D). We searched Embase, PubMed, and Cochrane Library for randomized controlled trials (RCTs) published until March 2023 comparing the HCL therapy with control therapies for children and adolescents with T1D. We computed weighted mean differences (WMDs) for continuous outcomes and risk ratios (RRs) with 95% confidence intervals (CIs) for binary endpoints. Four RCTs and 501 patients were included, of whom 323 were randomized to HCL therapy. Compared with control therapies, HCL significantly improved the period during which glucose level was 70-180 mg/dL (WMD 10.89%, 95% CI 8.22-13.56%) and the number of participants with glycated hemoglobin (HbA1c) level < 7% (RR 2.61, 95% CI 1.29-5.28). Also, HCL significantly reduced the time during which glucoselevel was > 180 mg/dL (WMD-10.46%, 95% CI-13.99 to-6.93%) and the mean levels of glucose (WMD-16.67 mg/dL, 95% CI-22.25 to-11.09 mg/dL) and HbA1c (WMD-0.50%, 95% CI-0.68 to-0.31). There were no significant differences between therapies regarding time during which glucose level was < 70 mg/dL or <54 mg/dL or number of episodes of ketoacidosis, hyperglycemia, and hypoglycemia. In this meta-analysis, HCL compared with control therapies was associated with improved time in range and HbA1c control in children and adolescents with T1D and a similar profile of side effects. These findings support the efficacy of HCL in the treatment of T1D in this population.
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Diabetes Mellitus Tipo 1 , Hiperglicemia , Criança , Adolescente , Humanos , Insulina , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hemoglobinas Glicadas , Glucose , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Furosemide is the most used diuretic for volume overload symptoms in patients with heart failure (HF). Recent data suggested that torsemide may be superior to furosemide in this setting. However, whether this translates into better clinical outcomes in this population remains unclear. To assess whether torsemide is superior to furosemide in the setting of HF. We performed a systematic review and meta-analysis of RCTs comparing the efficacy of torsemide versus furosemide in patients with HF. PubMed, Embase, and Web of Science were searched for eligible trials. Outcomes of interest were all-cause hospitalizations, hospitalizations for HF (HHF), hospitalizations for all cardiovascular causes, all-cause mortality, and NYHA class improvement. Echocardiographic parameters were also assessed. We applied a random-effects model to calculate risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) and a 0.05 level of significance. 12 RCTs were included, comprising 4,115 patients. Torsemide significantly reduced HHF (RR 0.60; 95% CI, 0.43-0.83; p=0.002; I2=0%), hospitalization for cardiovascular causes (RR 0.72; 95% CI, 0.60-0.88; p=0.0009; I2=0%), and improved LVEF (MD 4.51%; 95% CI, 2.94 to 6.07; p<0.0001; I2=0%) compared with furosemide. There was no significant difference in all-cause hospitalizations (RR 0.93; 95% CI, 0.86-1.00; p=0.04; I2=0%), all-cause mortality (RR 0.98; 95% CI, 0.87-1.10; p=0.73; I2=0%), NYHA class improvement (RR 1.25; 95% CI, 0.92-1.68; p=0.15; I2=0%), or NYHA class change (MD -0.04; 95% CI, -0.24 to 0.16; p=0.70; I2=15%) between groups. Torsemide significantly reduced hospitalizations for HF and cardiovascular causes, also improving LVEF.
A furosemida é o diurético mais utilizado para o tratamento de sintomas de sobrecarga de volume em pacientes com insuficiência cardíaca. Dados recentes sugerem que a torsemida pode ser superior à furosemida neste contexto. No entanto, ainda não é claro se isso se traduz em melhores resultados clínicos nesta população. Avaliar se a torsemida é superior à furosemida no contexto da insuficiência cardíaca. Realizamos uma revisão sistemática e metanálise de estudos clínicos randomizados (ECRs) comparando a eficácia da torsemida em comparação com a furosemida em pacientes com insuficiência cardíaca. PubMed, Embase e Web of Science foram as bases de dados pesquisadas em busca de estudos elegíveis. Os desfechos de interesse foram internações por todas as causas, internações por insuficiência cardíaca (IIC), internações por todas as causas cardiovasculares, mortalidade por todas as causas, e melhoria de classe da NYHA. Parâmetros ecocardiográficos também foram avaliados. Foi aplicado um modelo de efeitos aleatórios para calcular as razões de risco (RR) e as diferenças médias (DM) com intervalos de confiança (IC) de 95% e nível de significância de 0,05. Foram incluídos 12 ECRs, envolvendo 4.115 pacientes. A torsemida reduziu significativamente a IIC (RR de 0,60; IC de 95%, 0,43-0,83; p=0,002; I2=0%), internação por causas cardiovasculares (RR de 0,72; IC de 95%, 0,60-0,88; p=0,0009; I2=0%), e melhora da fração de ejeção do ventrículo esquerdo (FEVE) (DM de 4,51%; IC de 95%, 2,94 a 6,07; p<0,0001; I2=0%) em comparação com a furosemida. Não houve diferença significativa no número de internações por todas as causas (RR de 0,93; IC de 95%, 0,86-1,00; p=0,04; I2=0%), mortalidade por todas as causas (RR de 0,98; IC de 95%, 0,87-1,10; p=0,73; I2=0%), melhora da classe NYHA (RR de 1,25; IC de 95%, 0,92-1,68; p=0,15; I2=0%), ou mudança de classe NYHA (DM de -0,04; IC de 95%, -0,24 a 0,16; p=0,70; I2=15%) entre os grupos. A torsemida reduziu significativamente as internações por insuficiência cardíaca e causas cardiovasculares, melhorando também a FEVE.
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Furosemida , Insuficiência Cardíaca , Hospitalização , Ensaios Clínicos Controlados Aleatórios como Assunto , Torasemida , Humanos , Furosemida/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Torasemida/uso terapêutico , Hospitalização/estatística & dados numéricos , Resultado do Tratamento , Diuréticos/uso terapêuticoRESUMO
Background: Patients with heart failure have high rehospitalisation rates and poor cardiovascular outcomes. Home-based monitoring (HBM) has emerged with promising results in different settings. However, its long-term effects on patients recently admitted for acute decompensated heart failure (ADHF) remain uncertain. Methods: We systematically searched PubMed, Embase, and Cochrane Library for randomised controlled trials (RCTs) comparing HBM with usual care (UC) that were published between database inception and June 24, 2023. We included studies with patients admitted for ADHF in the previous 6 months and with a minimum follow-up of 6 months. We excluded studies with patients hospitalised for reasons other than ADHF and studies with disproportional education interventions between arms. Statistical analyses were performed using R software version 4.3.2. We pooled risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) for categorical and continuous outcomes, respectively. Cochrane Collaboration's tool for assessing risk of bias in RCTs (RoB 2) was used to assess study quality. Publication bias was assessed via funnel plots and Egger's test, and heterogeneity was assessed through I2 statistics and sensitivity analysis. The protocol for this systematic review and meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO, CRD42023465359). Findings: We included 16 RCTs comprising 4629 patients, of whom 2393 (51.7%) were randomised to HBM and 3150 (68%) were men. Follow-up ranged from six to fifteen months. As compared with UC, HBM significantly reduced all-cause mortality (RR 0.75; 95% CI 0.61, 0.91; p = 0.005), all-cause hospitalisations (RR 0.82; 95% CI 0.70, 0.97; p = 0.018), cardiovascular (CV) mortality (RR 0.53; 95% CI 0.36, 0.79; p = 0.002), hospitalisations for heart failure (RR 0.75; 95% CI 0.62, 0.91; p = 0.004), and CV hospitalisations (RR 0.72; 95% CI 0.55, 0.95; p = 0.018). There were no significant differences in length of hospital stay (MD 0.97 days; 95% CI -0.90, 2.84; p = 0.308). Interpretation: In patients recently admitted with ADHF, HBM significantly reduces long-term all-cause mortality and hospitalisations, CV mortality and hospitalisations, and hospitalisations for heart failure, as compared with UC. This supports the implementation of HBM as a standard practice to optimise patient outcomes following admissions for ADHF. However, future studies are warranted to evaluate the efficacy and safety of implementing HBM in the real-world setting. Funding: None.
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Introduction: There is an emerging body of evidence that vitamin C consumption can modulate microbiota abundance and can also impact DNA methylation in the host, and this could be a link between diet, microbiota, and immune response. The objective of this study was to evaluate common CpG sites associated with both vitamin C and microbiota phyla abundance. Methods: Six healthy women participated in this cohort study. They were divided into two groups, according to the amount of vitamin C they ingested. Ingestion was evaluated using the 24-h recall method. The Illumina 450 k BeadChip was used to evaluate DNA methylation. Singular value decomposition analyses were used to evaluate the principal components of this dataset. Associations were evaluated using the differentially methylated position function from the Champ package for R Studio. Results and discussion: The group with higher vitamin C (HVC) ingestion also had a higher relative abundance of Actinobacteria. There was a positive correlation between those variables (r = 0.84, p = 0.01). The HVC group also had higher granulocytes, and regarding DNA methylation, there were 207 CpG sites commonly related to vitamin C ingestion and the relative abundance of Actinobacteria. From these sites, there were 13 sites hypomethylated and 103 hypermethylated. The hypomethylated targets involved the respective processes: immune function, glucose homeostasis, and general cellular metabolism. The hypermethylated sites were also enriched in immune function-related processes, and interestingly, more immune responses against pathogens were detected. These findings contribute to understanding the interaction between nutrients, microbiota, DNA methylation, and the immune response.
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This study investigated the effect of the serine protease on metabolizable energy and amino acids' digestibility of different soybean meal for broilers. A total of 684 broilers chickens form 14 to 23 d age were distributed with nineteen treatments, six replicates, and six birds per replicate. Nine samples of soybean meal from different regions in Brazil were used, with some samples supplemented with the protease enzyme and others without addition. Apparent and corrected-for-nitrogen-balance metabolizable energy were evaluated, as well as the coefficients of amino acid digestibility. All collected data were submitted to ANOVA at a significance level of 5% and Tukey's test was applied. The results showed that the addition of the protease enzyme significantly increased the values of AME and AMEn in all soybean meal samples. The soybean meal of different origins has significant variations in AME and AMEn. The addition of the protease improved the digestibility of essential amino acids compared to soybean meal without enzyme addition. These results indicate that supplementation with serine protease can improve the metabolizable energy and amino acid digestibility of soybean meal from different regions in the diet of broilers, potentially being an effective strategy to enhance nutrient utilization and animal performance.
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BACKGROUND: The optimal treatment of atrial fibrillation (AF) in patients with heart failure with reduced ejection fraction (HFrEF) remains unsettled. OBJECTIVE: The purpose of this study was to assess the efficacy of catheter ablation (CA) and medical therapy compared to medical therapy alone in patients with AF and HFrEF. METHODS: We performed a systematic review of randomized controlled trials (RCTs) comparing CA with guideline-directed medical therapy for AF in patients with HFrEF (left ventricular ejection fraction [LVEF] ≤ 40%). We systematically searched PubMed, Embase, and Cochrane for eligible trials. A random effects model was used to calculate the risk ratios (RRs) and mean differences (MDs), with 95% confidence intervals (CIs). RESULTS: Six RCTs comprising 1055 patients were included, of whom 530 (50.2%) were randomized to CA. Compared with medical therapy, CA was associated with a significant reduction in heart failure (HF) hospitalization (RR 0.57; 95% CI 0.45-0.72; P < .01), cardiovascular mortality (RR 0.46; 95% CI 0.31-0.70; P < .01), all-cause mortality (RR 0.53; 95% CI 0.36-0.78; P < .01), and AF burden (MD -29.8%; 95% CI -43.73% to -15.90%; P < .01). Also, there was a significant improvement in LVEF (MD 3.8%; 95% CI 1.6%-6.0%; P < .01) and quality of life (Minnesota Living with Heart Failure Questionnaire; MD -4.92 points; 95% CI -8.61 to -1.22 points; P < .01) in the ablation group. CONCLUSION: In this meta-analysis of RCTs of patients with AF and HFrEF, CA was associated with a reduction in HF hospitalization, cardiovascular mortality, and all-cause mortality as well as a significant improvement in LVEF and quality of life.
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PURPOSE: Patients with atrial fibrillation (AF) and end-stage renal disease on chronic hemodialysis are at risk for thromboembolic and bleeding events. We aimed to perform a meta-analysis to evaluate the safety and efficacy of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) in this population. METHODS: We systematically searched PubMed, Excerpta Medica Database (EMBASE) and Cochrane Library for randomized controlled trials (RCTs) comparing DOACs with VKAs in patients with AF on chronic hemodialysis from inception to February 2023 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Outcomes were reported using risk ratios (RRs) with 95% confidence intervals (CIs). Statistical analyses were performed using R version 4.2.2. RESULTS: We selected three RCTs including 341 patients, of whom 176 (51.6%) were randomized to DOACs. Follow-up ranged from 174 days to 3.38 years. There was no significant difference between groups in terms of cardiovascular mortality (RR 1.34; 95% CI 0.69-2.60; p = 0.39), all-cause mortality (RR 0.96; 95% CI 0.72-1.27; p = 0.77), ischemic/uncertain type of stroke or transient ischemic attack (RR 0.50; 95% CI 0.19-1.35; p = 0.17), or major or life-threatening bleeding (RR 0.70; 95% CI 0.39-1.25; p = 0.22). CONCLUSION: In this meta-analysis of three RCTs, no significant difference was observed between DOACs and VKAs in cardiovascular mortality, all-cause mortality, ischemic/uncertain type of stroke or transient ischemic attack, or major or life-threatening bleeding in patients with AF on chronic hemodialysis.
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Anticoagulantes , Fibrilação Atrial , Ensaios Clínicos Controlados Aleatórios como Assunto , Diálise Renal , Vitamina K , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Vitamina K/antagonistas & inibidores , Administração Oral , Anticoagulantes/uso terapêutico , Falência Renal Crônica/terapia , Falência Renal Crônica/complicaçõesRESUMO
BACKGROUND: Vitamin K antagonists (VKAs) are the recommended first-line treatment for left ventricular thrombus (LVT); however, direct oral anticoagulants (DOACs) have been considered an alternative therapy. OBJECTIVES: To evaluate the efficacy and safety of DOACs compared with VKAs therapy in patients with LVT. METHODS: PubMed, Embase, and Cochrane were systematically searched for randomized clinical trials or cohort studies that compared DOACs versus VKAs for LVT. Risk ratios (RRs) were computed for binary endpoints, with 95% confidence intervals (95% CIs). Statistical significance was defined as p value < 0.05. RESULTS: A total of 4 randomized clinical trials and 29 cohort studies were included, with 4,450 patients assigned to either DOACs or VKAs. There was no significant difference between groups for stroke or systemic embolic (SSE) events (RR 0.84; 95% CI 0.65 to 1.07; p = 0.157), stroke (RR 0.73; 95% CI 0.48 to 1.11; p = 0.140), systemic embolic (SE) events (RR 0.69; 95% CI 0.40 to 1.17; p = 0.166), thrombus resolution (RR 1.05; 95% CI 0.99 to 1.11; p = 0.077), any bleeding (RR 0.78; 95% CI 0.60 to 1.00; p = 0.054), clinically relevant bleeding (RR 0.69; 95% CI 0.46 to 1.03; p = 0.066), minor bleeding (RR 0.73; 95% CI 0.43 to 1.23; p = 0.234), major bleeding (RR 0.87; 95% CI 0.42 to 1.80; p = 0.705), and all-cause mortality (RR 1.05; 95% CI 0.79 to 1.39; p = 0.752). Compared with VKAs, rivaroxaban significantly reduced SSE events (RR 0.35; 95% CI 0.16 to 0.91; p = 0.029) and SE events (RR 0.39; 95% CI 0.16 to 0.95; p = 0.037). CONCLUSIONS: DOACs had a similar rate of thromboembolic and hemorrhagic events, as well as thrombus resolution, compared to VKAs in the treatment of LVTs. Rivaroxaban therapy had a significant reduction in thromboembolic events, compared to VKAs.
Assuntos
Anticoagulantes , Ventrículos do Coração , Trombose , Vitamina K , Humanos , Vitamina K/antagonistas & inibidores , Anticoagulantes/uso terapêutico , Trombose/tratamento farmacológico , Ventrículos do Coração/efeitos dos fármacos , Administração Oral , Hemorragia/induzido quimicamente , Cardiopatias/tratamento farmacológico , Resultado do Tratamento , Acidente Vascular Cerebral/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Neoadjuvant pembrolizumab plus chemotherapy (P + CT) has emerged as a standard of care for stage II-III triple-negative breast cancer (TNBC). However, the best anthracycline-cyclophosphamide (AC) schedule remains to be determined. While the KEYNOTE-522 regimen employs AC every 3 weeks (q3w AC), previous studies have shown overall survival benefits of dose-dense regimens for early-stage breast cancer. The Neo-Real study (GBECAM-0123) is a real-world data effort evaluating patients with TNBC treated with neoadjuvant P + CT in ten cancer centers since July 2020. The objective of this analysis was to evaluate the effectiveness and safety of dose-dense AC (ddAC) versus q3w AC. Among 333 patients included until November 2023, 311 completed neoadjuvant therapy and 279 underwent surgery with pathology reports available; ddAC was used in 58.2% and q3w AC in 41.8% of the cases. Most patients (69.1%) had stage II TNBC. A pCR was observed in 65.4% with ddAC and 58.7% with q3w AC (P = 0.260), while RCB 0-1 occurred in 82.4% and 73.5%, respectively (P = 0.115). Patients with stage III disease had a numerically higher pCR with ddAC (59% vs 40%, P = 0.155), while pCR rates were similar regardless of AC regimen in stage II disease (66.6% vs 64.5%; P = 0.760). While no significant disparities in drug discontinuation was noted, ddAC showed a trend towards higher rates of grade ≥3 AE (40.5% vs. 30.7%, P = 0.092). The Neo-Real study could not rule out a difference between ddAC and q3w AC during neoadjuvant P + CT. The observation of a potentially higher pCR with ddAC in stage III disease warrants further investigation.
RESUMO
Endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS) are surgical methods for treating obstructive hydrocephalus. However, there is still disagreement regarding the most effective technique, in terms of both operative success and postoperative complications. Therefore, we performed a systematic review and meta-analysis to compare the efficacy and safety of these two methods in patients with obstructive hydrocephalus. We performed a systematic search of the PubMed, Scopus, and Cochrane Library databases. Randomized clinical trials (RCTs) comparing ETV and VPS in pediatric or adult patients with obstructive hydrocephalus were included. The outcomes included were operative success, postoperative cerebrospinal fluid leak, postoperative infection, postoperative or intraoperative bleeding, blockage rate, and mortality. The risk ratio (RR) was calculated with a 95% confidence interval (CI). Heterogeneity was evaluated with I 2 statistics. We used a fixed-effects model for outcomes with I 2 < 25% and DerSimonian and Laird random-effects model for other conditions. The Cochrane collaboration tool for assessing the risk of bias in randomized trials was used for risk-of-bias assessment. R, version 4.2.1, was used for statistical analyses. Of the 2,353 identified studies, 5 RCTs were included, involving 310 patients with obstructive hydrocephalus, of which 163 underwent ETV. There was a significant difference in favor of ETV for postoperative infection (risk ratio [RR]: 0.11; 95% confidence interval [CI]: 0.04-0.33; p < 0.0001; I 2 = 0%) and blockage rate (RR: 0.15; 95% CI: 0.03-0.75; p = 0.02; I 2 = 53%). Meanwhile, there was no significant difference between groups for the postoperative or intraoperative bleeding (RR: 0.44; 95% CI: 0.17-1.15; p = 0.09; I 2 = 0%), postoperative cerebrospinal fluid leak (RR: 0.65; 95% CI: 0.22-1.92; p = 0.44; I 2 = 18%), operative success (RR: 1.18; 95% CI: 0.77-1.82; p = 0.44; I 2 = 84%), and mortality (RR: 0.19; 95% CI: 0.03-1.09; p = 0.06; I 2 = 0%). Three RCTs had some concerns about the risk of bias and one RCT had a high risk of bias due to the process of randomization and selection of reported results. Thus, this meta-analysis of RCTs evaluating ETV compared with VPS demonstrated that although there is no superiority of ETV in terms of operative success, the incidence of complications was significantly higher in patients who underwent VPS. Our results suggest that the use of ETV provides greater benefits for the treatment of obstructive hydrocephalus. However, more RCTs are needed to corroborate the superiority of ETV.
RESUMO
RESUMO Objetivo Apresentar um método de análise do modo respiratório por meio da termografia infravermelha. Método Estudo transversal exploratório de 38 imagens térmicas que representavam o momento da inspiração e da expiração durante a respiração nasal e durante a simulação da respiração oral de quatro voluntárias respiradoras nasais sem queixas respiratórias. Para a extração da temperatura das regiões de interesse (nariz e boca) foram utilizadas três formas de seleção distintas de dados (linha, retângulo e elipse) e três medidas de temperatura (mínima, média e máxima) por meio do software FLIR Tools®. Resultados Dentre as três formas de seleção houve maior variabilidade nas medidas obtidas pela linha, revelando limitações nessa medida. Não houve diferenças entre as medidas do retângulo e elipse, mostrando que ambas as formas de seleção apresentam resultados semelhantes para a extração das temperaturas. Na comparação entre as temperaturas do nariz e da boca na inspiração e expiração, os resultados indicaram que houve diferença com relevância estatística em todas as medidas realizadas, exceto para as medidas de temperatura média da inspiração, usando o retângulo e a elipse. Percebe-se diferenciação do modo respiratório tanto na inspiração quanto na expiração quando utilizada a temperatura média da boca com o retângulo e a elipse. Conclusão Sugere-se para avaliação do modo respiratório a avaliação da boca, por meio da elipse, com análise da temperatura média durante a inspiração.
ABSTRACT Purpose To present a method for analyzing breathing modes with infrared thermography. Methods This exploratory cross-sectional study used 38 thermal images of inspiration and expiration with nasal breathing and simulated mouth breathing in four nasal breathers without respiratory complaints. Three different data selection forms (line, rectangle, and ellipse) were used to extract the minimum, mean, and maximum temperatures of the regions of interest (nose and mouth) using the FLIR Tools® software. Results Among the three selection forms, there was greater temperature variability obtained with the line, revealing limitations in this measurement. There were no differences between the rectangle and ellipse values, showing that both selection forms present similar temperature extraction results. The comparison results between nose and mouth temperatures during inspiration and expiration indicated a statistically significant difference between all measurements, except for mean inspiration temperatures with the rectangle and ellipse. The breathing mode can be distinguished in both inspiration and expiration when using mean mouth temperatures with the rectangle and ellipse. Conclusion Breathing modes should be assessed based on mean mouth temperatures during inspiration, using the ellipse.