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Background: Few studies have evaluated the comparative efficacy of biologics for asthma. This network meta-analysis aimed to compare the efficacy of biologics. Methods: This study included randomized controlled trials (RCTs) evaluating the efficacy of a biologic compared to a placebo or another biologic in patients with inadequately controlled asthma despite high-intensity treatment, published by January 6, 2022. Two researchers independently searched the PubMed, Embase, Web of Science, and Scopus and assessed the risk of bias using the Cochrane tool. The outcomes of interest were the annual asthma exacerbation rate (AER), forced expiratory volume per second before bronchodilator use (preBD FEV1), the asthma control questionnaire (ACQ), and asthma quality of life questionnaire (AQLQ) results. A frequentist network meta-analysis was conducted, and a random effects model was used to draw pooled incidence rate ratio or standardized mean differences. Results: Twenty-three RCTs with 8376 participants were retrieved. All biologics included in this study were associated with significantly better effects than placebo in AER, preBD FEV1, and ACQ outcomes. Although there were no significant differences between the biologics in the overall study population, patients with eosinophil levels ≥300 cells/µL or eosinophilic asthma showed that dupilumab and tezepelumab were significantly better than anti-IL-5 biologics in improving preBD FEV1. Additionally, in patients with eosinophil levels ≥300 cells/µL, benralizumab, unlike reslizumab, performed significantly better than placebo in improving ACQ and AQLQ outcomes. Conclusion: The comparative effects of biologics can be considered with phenotypes and biomarkers to help clinicians select an appropriate treatment for inadequately controlled asthma.
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BACKGROUND: Barrier films or dressings were reported to be effective in preventing radiation dermatitis (RD) in breast cancer patients, but their comparative efficacy is unknown. METHODS: A systematic literature search was performed on Embase, MEDLINE and Cochrane CENTRAL Registry of Clinical Trials from inception to October 20, 2023. Randomised controlled trials (RCTs) comparing barrier films or dressings to the standard of care (SOC) or other interventions were included. We estimated summary odds ratios and mean differences using network meta-analysis with random effects. This study was registered with PROSPERO (ID: CRD42023475021). RESULTS: Fourteen RCTs met inclusion criteria. Six interventions were analysed: 3M™ Moisturizing Double Barrier Cream (MDBC), 3M™ No Sting Barrier Film (BF), Hydrofilm® (HF), Mepitel® Film (MF), Silver Leaf Nylon Dressing and StrataXRT®. HF, MF and StrataXRT® reduced the incidence of moist desquamation compared to SOC (HF: OR = 0.08; p = 0.02; MF: OR = 0.31 p < 0.01; StrataXRT®: OR = 0.22, p = 0.04). The ranking of agents from most to least effective in preventing moist desquamation according to P-scores was HF (92.5%), MF (78.5%), StrataXRT® (70.1%), BF (46.4%), Silver Leaf Nylon Dressing (24.9%), MDBC (22.9%) and SOC (14.7%). Only four RCTs on HF and MF included patient-reported outcome (PRO) assessments that allowed pooling for analysis. HF and MF were more effective in reducing pain, itchiness and burning sensation compared to SOC (p < 0.01 for all symptoms). CONCLUSION: HF and MF were effective in preventing RD in breast cancer. Future RCTs should compare these interventions to effective cream preparations, such as topical corticosteroids.
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A single exposure to stress can induce functional changes in neurons, potentially leading to acute stress disorder or post-traumatic stress disorder. In this study, we used in vivo wide-field optical mapping to simultaneously measure neural calcium signals and hemodynamic responses over the whole cortical area. We found that cortical mapping to whisker stimuli was altered under acute stress conditions. In particular, callosal projections in the anterior cortex (primary/secondary motor, somatosensory forelimb cortex) relative to barrel field (S1BF) of somatosensory cortex were weakened. On the contrary, the projections in posterior cortex relative to S1BF were mostly unchanged or were only occasionally strengthened. In addition, changes in intra-cortical connection were opposite to those in inter-cortical connection. Thus, the S1BF connections to the anterior cortex were strengthened while those to the posterior cortex were weakened. This suggests that the well-known barrel cortex projection route was enhanced. In summary, our in vivo wide-field optical mapping study indicates that a single acute stress can impact whole-brain networks, affecting both neural and hemodynamic responses.
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This paper presents the first scanning electron microscopy (SEM)-based DNA imaging in biological samples. This novel approach incorporates a metal-free electro-stain reagent, formulated by combining DNA-binding proteins and synthetic polymers to enhance the visibility of 2-nm-thick DNA under SEM. Notably, DNA molecules stain with proteins and polymers appear as dark lines under SEM. The resulting DNA images exhibit a thickness of 15.0±4.0 nm. As SEM is the primary platform, it integrates seamlessly with various chemically functionalized large surfaces with the aid of microfluidic devices. The approach allows high-resolution imaging of various DNA structures including linear, circular, single-stranded DNA and RNA, originating from nuclear and mitochondrial genomes. Furthermore, quantum dots are successfully visualized as bright labels that are sequence-specifically incorporated into DNA molecules, which highlights the potential for SEM-based optical DNA mapping. In conclusion, DNA imaging using SEM with the novel electro-stain offers electron microscopic resolution with the ease of optical microscopy.
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Proteínas de Unión al ADN , ADN , Microscopía Electrónica de Rastreo , Polímeros , Microscopía Electrónica de Rastreo/métodos , ADN/química , ADN/metabolismo , Polímeros/química , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/ultraestructura , Proteínas de Unión al ADN/química , Puntos Cuánticos/químicaRESUMEN
Accurate quantification of neurofilament lights (NfLs), a prognostic blood biomarker, is highly required to predict neurodegeneration in the presymptomatic stages of Alzheimer's disease. Here, we report self-oxygen-enriching coral structures with triphase interfaces for the label-free photocathodic detection of NfLs in blood plasma with femtomolar sensitivities and high reliability. In conventional photocathodic immunoassays, the poor solubility and sluggish diffusion rate of the dissolved oxygen serving as electron acceptors have necessitated the incorporation of additional electron acceptors or aeration procedures. To address the challenge, we designed the coral-like copper bismuth oxides (CBO) with robust solid-liquid-air contact boundaries that enrich the interfacial oxygen levels without an external aeration source. By optimally assembling the perfluorododecyltrichlorosilane (FTCS) and platinum (Pt) co-catalysts into the silver-doped CBO (Ag:CBO), the stable solid-liquid-air contact boundaries were formed within the sensor interfaces, which allowed for the abundant supply of air phase oxygen through an air pocket connected to the atmosphere. The Pt/FTCS-Ag:CBO exhibited the stable background signals independent of the dissolved oxygen fluctuations and amplified photocurrent signals by 1.76-fold, which were attributed to the elevated interfacial oxygen levels and 11.15 times-lowered mass transport resistance. Under the illumination of white light-emitting diode, the oxygen-enriching photocathodic sensor composed of Pt/FTCS-Ag:CBO conjugated with NfLs-specific antibodies precisely quantified the NfLs in plasma with a low coefficient of variation (≤2.97%), a high degree of recovery (>97.0%), and a limit of detection of 40.38 fg/mL, which was 140 times lower than the typical photocathodic sensor with diphase interfaces.
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Enfermedad de Alzheimer , Técnicas Biosensibles , Bismuto , Oxígeno , Platino (Metal) , Humanos , Técnicas Biosensibles/métodos , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/diagnóstico , Bismuto/química , Platino (Metal)/química , Oxígeno/química , Oxígeno/sangre , Cobre/química , Límite de Detección , Biomarcadores/sangre , Plata/química , Técnicas Electroquímicas/métodos , Inmunoensayo/métodos , Proteínas de Neurofilamentos/sangre , Proteínas de Neurofilamentos/química , Proteínas de Neurofilamentos/análisis , AnimalesRESUMEN
Unlike classical systems based on the use of morphological data, modern phylogenetic analyses use genetic information to construct phylogenetic trees. Ongoing research in the field of phylogenetics is evaluating the accuracy of phylogenetic estimation results and the reliability of phylogenetic trees to explain evolutionary relationships. Recently, the probability of stochastic errors in large-scale phylogenetic datasets has decreased, while the probability of systematic errors has increased. Therefore, before constructing a phylogenetic tree, it is necessary to assess the causes of systematic bias to improve the accuracy of phylogenetic estimates. We performed analyses of three datasets (Terebelliformia, Daphniid, and Glires clades) using bioinformatics software to assess systematic error and improve phylogenetic tree accuracy. Then, we proposed a combination of systematic biases capable of discerning the most suitable gene markers within a series of taxa and generating conflicting phylogenetic topologies. Our findings will help improve the reliability of phylogenetic software to estimate phylogenies more accurately by exploiting systematic bias.
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Filogenia , Programas Informáticos , Biología Computacional/métodos , Animales , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND AND AIMS: Despite accumulating evidence on the potential of glucose-lowering agents (GLAs) to prevent cardiovascular events, the comparative effects of GLAs on vascular function remain unclear. This study utilized validated indicators such as flow-mediated dilation (FMD; positive value favors) and pulse wave velocity (PWV; negative value favors) to uncover the comparative effects of GLAs on vascular function. METHODS: Randomized controlled trials (RCTs) comparing the effects of GLAs on FMD or PWV with placebo or other GLAs in patients with type 2 diabetes (T2DM) were searched through PubMed and Embase. The frequentist method of network meta-analysis (NMA) was conducted using a random effects model, and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. RESULTS: The NMA included 38 RCTs with 2,065 patients. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium glucose cotransporter-2 inhibitors (SGLT-2Is) had significantly more positive effects on FMD improvement and PWV reduction than placebo. Thiazolidinedione (TZD) treatment resulted in significantly improved FMD compared to other GLAs as well as placebo (SMD: 1.14; 95% CI: 0.84 to 1.43). Both pioglitazone and rosiglitazone were discovered to have considerably more favorable effects on improving FMD and reducing PWV compared to placebo and other GLAs, as a result of the analysis incorporating each drug in the TZD class. The sensitivity analysis results corroborated the main findings. CONCLUSIONS: This NMA showed more favorable effects of GLP-1RAs and SGLT-2Is than placebo in improving both arterial stiffness and endothelial function in patients with T2DM. In addition, TZDs showed superior effects in improving endothelial function as compared with the other GLAs and placebo.
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Diabetes Mellitus Tipo 2 , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Rigidez Vascular , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Glucosa , Hipoglucemiantes/uso terapéutico , Metaanálisis en Red , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: This study aimed to determine whether self-regulation acts as a mediating factor in the relationship between obesity-related stress and weight control behavior, targeting Korean female college students. Obesity-related stress and weight control behaviors are important factors affecting an individual's health and well-being, and self-control, a psychological trait, can play a pivotal role in regulating how individuals respond to stress and engage in weight management behaviors. METHODS: This study employed a descriptive correlational design. A total of 109 female college students with overweight and obesity participated in the study. We used a self-report questionnaire to measure obesity-related stress, self-control, and degree of weight control behavior. Data were analyzed using descriptive statistics, Pearson's correlation coefficient analysis, and bootstrapping using Hayes' PROCESS macro for mediation. RESULTS: Significant relationships between obesity-related stress and weight control behavior (r = 0.25, p < 0.001), obesity-related stress and self-control (r = -0.36, p < 0.001), and weight control behavior and self-control (r = 0.26, p < 0.001) were observed. Self-control showed an indirect mediating effect on the relationship between obesity-related stress and weight control behavior (Β = 0.37, p = 0.001). CONCLUSIONS: Through the research results, it was confirmed that self-control is a factor that has a mediating effect in the relationship between obesity-related stress and weight control behavior among female college students with overweight and obesity. These results underscore the importance of addressing self-control strategies in interventions aimed at promoting healthy weight management among female college students with overweight or obesity.
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In order to flower in the appropriate season, plants monitor light and temperature changes and alter downstream pathways that regulate florigen genes such as Arabidopsis (Arabidopsis thaliana) FLOWERING LOCUS T (FT). In Arabidopsis, FT messenger RNA levels peak in the morning and evening under natural long-day conditions (LDs). However, the regulatory mechanisms governing morning FT induction remain poorly understood. The morning FT peak is absent in typical laboratory LDs characterized by high red:far-red light (R:FR) ratios and constant temperatures. Here, we demonstrate that ZEITLUPE (ZTL) interacts with the FT repressors TARGET OF EATs (TOEs), thereby repressing morning FT expression in natural environments. Under LDs with simulated sunlight (R:FR = 1.0) and daily temperature cycles, which are natural LD-mimicking environmental conditions, FT transcript levels in the ztl mutant were high specifically in the morning, a pattern that was mirrored in the toe1 toe2 double mutant. Low night-to-morning temperatures increased the inhibitory effect of ZTL on morning FT expression by increasing ZTL protein levels early in the morning. Far-red light counteracted ZTL activity by decreasing its abundance (possibly via phytochrome A (phyA)) while increasing GIGANTEA (GI) levels and negatively affecting the formation of the ZTL-GI complex in the morning. Therefore, the phyA-mediated high-irradiance response and GI play pivotal roles in morning FT induction. Our findings suggest that the delicate balance between low temperature-mediated ZTL activity and the far-red light-mediated functions of phyA and GI offers plants flexibility in fine-tuning their flowering time by controlling FT expression in the morning.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Temperatura , Luz Roja , Factores de Transcripción/metabolismo , Flores/fisiología , Fitocromo A/metabolismo , Regulación de la Expresión Génica de las Plantas , Luz , MutaciónRESUMEN
The growing interest in the self-similarity effect of avatars in virtual reality (VR) has spurred the creation of realistic avatars that closely mirror their users. However, despite extensive research on the self-similarity effect in single-user VR environments, our understanding of its impact in social VR settings remains underdeveloped. This shortfall exists despite the unique socio-psychological phenomena arising from the illusion of embodiment that could potentially alter these effects. To fill this gap, this paper provides an in-depth empirical investigation of how avatars' self-similarity influences social VR experiences. Our research uncovers several notable findings: 1) A high level of avatar self-similarity boosts users' sense of embodiment and social presence but has minimal effects on the overall presence and even slightly hinders immersion. These results are driven by increased self-awareness. 2) Among various factors that contribute to the self-similarity of avatars, voice stands out as a significant influencer of social VR experiences, surpassing other representational factors. 3) The impact of avatar self-similarity shows negligible differences between male and female users. Based on these findings, we discuss the pros and cons of incorporating self-similarity into social VR avatars. Our study serves as a foundation for further research in this field.
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BACKGROUND AND AIMS: In biliary epithelial cells, two bile acid receptors, sphingosine 1-phosphate receptor 2 (S1PR2) and Takeda G protein-coupled receptor 5 (TGR5) have been reported to trigger cell proliferation, as well as neoplastic cell invasiveness. In this study, we aimed to investigate the clinical significance of S1PR2/ TGR5 expression in extrahepatic cholangiocarcinoma (CCA) patients. METHODS: Patients who underwent surgical resection of extrahepatic CCA at Korea University Guro Hospital between 2002 and 2018 were included. Data on immunohistochemical staining and H-score of S1PR2 and TGR5 were evaluated using digital image analysis. RESULTS: A total of 115 cases of invasive CCA were analyzed. The H-score of S1PR2 showed a decrease in invasive CCA (p=0.052) but that of TGR5 showed a significant increase (p=0.02). Overall survival and disease-free survival were significantly lower in the low S1PR2 expression group (p<0.05) than in the control group; however, TGR5 expression was not significant (p=0.096). In multivariate analysis, low S1PR2 was only significant for poor prognosis. CONCLUSION: Low S1PR2 level was the only independent poor prognostic factor in patients with resected extrahepatic CCA.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Receptores de Esfingosina-1-Fosfato , Relevancia Clínica , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/patología , Colangiocarcinoma/patología , Receptores Acoplados a Proteínas G/metabolismo , Conductos Biliares Intrahepáticos/patologíaRESUMEN
AIMS: This study aimed to investigate the subsequent risk of type 2 diabetes mellitus (T2D) in adults newly diagnosed with atopic dermatitis (AD). METHODS: This propensity score-matching cohort study used data from the National Health Insurance Service-National Sample Cohort (NHIS-NSC) 2.0 database in South Korea from 2002 to 2015. The adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a Cox proportional hazards model, for the new onset of T2D (ICD-10 code, E11) in AD patients compared to the matched controls. Subgroup and sensitivity analyses were also conducted. RESULTS: Each of the 36,692 individuals in the AD group and matched control group was included in the analysis. The risk of T2D in the AD group was significantly higher than that of the matched controls in the adjusted model (adjusted HR 1.44; 95% CI 1.27-1.63, P <.001). The results of subgroup analysis by sex, age, and body mass index were consistent with the results of the primary analysis. Sensitivity analyses using different T2D and/or AD definitions also showed consistent results. CONCLUSIONS: The significant risk of subsequent T2D in adult AD patients suggested the necessity for efforts to prevent T2D in AD patients.
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Dermatitis Atópica , Diabetes Mellitus Tipo 2 , Humanos , Adulto , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Estudios de Cohortes , Factores de Riesgo , Dermatitis Atópica/epidemiología , Índice de Masa CorporalRESUMEN
OBJECTIVE: Famotidine, an H2 receptor antagonist (H2RA), is mainly prescribed to alleviate the early symptoms of gastritis. Our aim was to explore the possibilities of low-dose esomeprazole as a treatment of gastritis as well as the pharmacodynamic (PD) properties of esomeprazole and famotidine. MATERIALS AND METHODS: A randomized, multiple-dose, 6-sequence, 3-period crossover study was conducted with a 7-day washout between periods. For each period, the subjects were administered one dose of esomeprazole 10 mg or famotidine 20 mg or esomeprazole 20 mg each day. To evaluate the PDs, the 24-hour gastric pH was recorded after single and multiple doses. The mean percentage of time during which the gastric pH was above 4 was evaluated for PD assessment. To confirm the pharmacokinetic (PK) characteristics of esomeprazole, blood was collected for up to 24 hours after multiple doses. RESULTS: 26 subjects completed the study. Following the multiple doses of esomeprazole 10 mg, esomeprazole 20 mg, and famotidine 20 mg, the mean percentages of time during which the gastric pH was above 4 over the course of 24 hour were 35.77 ± 19.56%, 53.75 ± 20.55%, and 24.48 ± 17.36%, respectively. After multiple doses, the time of peak plasma concentration at steady state (tmax,ss) was 1.00 and 1.25 hours for 10 and 20 mg of esomeprazole, respectively. The geometric mean ratio and its 90% confidence interval of area under the plasma drug concentration-time curve in steady state (AUCT,ss) and maximum concentration of drug in plasma in steady state (Cmax,ss) for esomeprazole 10 mg compared to 20 mg were 0.3654 (0.3381 - 0.3948) and 0.5066 (0.4601 - 0.5579), respectively. CONCLUSION: The PD parameters of esomeprazole 10 mg were comparable to those of famotidine after multiple doses. These findings provide support for further evaluating the use of 10 mg of esomeprazole as a treatment option for gastritis.
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Esomeprazol , Gastritis , Humanos , Esomeprazol/farmacocinética , Famotidina/farmacología , Voluntarios Sanos , Estudios Cruzados , Gastritis/diagnóstico , Gastritis/tratamiento farmacológicoRESUMEN
Compared to pelubiprofen, a cyclooxygenase-2-selective inhibitor, pelubiprofen tromethamine has been reported to exhibit improved solubility and absorption. Pelubiprofen tromethamine combines the anti-inflammatory effect of pelubiprofen with the gastric protective function of tromethamine salt, making it a relatively safe class of non-steroidal anti-inflammatory drugs with low levels of gastrointestinal side effects in addition to its original analgesic, anti-inflammatory, and antipyretic effects. This study assessed the pharmacokinetic and pharmacodynamic characteristics of pelubiprofen and pelubiprofen tromethamine in healthy subjects. Two independent clinical trials were performed in healthy subjects using a randomized, open-label, oral, single-dose, two-sequence, four-period, crossover design. In Study I and Study II, subjects received 25 mg of pelubiprofen tromethamine and 30 mg of pelubiprofen tromethamine, respectively, with 30 mg of pelubiprofen being the reference. Study I fell within the bioequivalence study criteria. A trend of increased absorption and exposure for 30 mg of pelubiprofen tromethamine vs. the reference in Study II was observed. The maximum cyclooxygenase-2 inhibitory effect of 25 mg of pelubiprofen tromethamine was approximately 98% compared to the reference, showing no significant pharmacodynamic variation. It is thus predicted that 25 mg of pelubiprofen tromethamine would show no clinically significant discrepancies in clinical analgesic and antipyretic effects from 30 mg of pelubiprofen.
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PURPOSE: Despite increasing evidence for the potential association between atopic dermatitis (AD) and cardiovascular diseases (CVDs), results have still remained controversial. Therefore, this study investigated the association between AD and subsequent CVDs in adults newly diagnosed with AD. METHODS: Datasets from the National Health Insurance Service-National Sample Cohort in South Korea from 2002 to 2015 were analyzed. The primary outcome was new-onset CVD, which included angina pectoris, myocardial infarction, stroke, or any revascularization procedure. The crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated in the AD group compared with the matched control group using the Cox proportional hazards regression models. RESULTS: A total of 40,512 individuals with AD were matched with 40,512 control subjects without AD. The overall incidence of CVDs was 2,235 (5.5%) and 1,640 (4.1%) in the AD and matched control groups, respectively. In the adjusted model, AD was associated with an increased risk of CVDs (HR, 1.42; 95% CI, 1.33-1.52), angina pectoris (adjusted HR, 1.49; 95% CI, 1.36-1.63), myocardial infarction (adjusted HR, 1.40; 95% CI, 1.15-1.70), ischemic stroke (adjusted HR, 1.34; 95% CI, 1.20-1.49), and hemorrhagic stroke (adjusted HR, 1.26; 95% CI, 1.05-1.52). Most of the subgroup and sensitivity analysis results were consistent with those of the main analysis. CONCLUSIONS: The current study found that adult patients newly diagnosed with AD were at significantly increased risk for subsequent CVDs, suggesting the need to consider early prevention strategies for CVDs targeting patients with AD.
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BACKGROUND: Standard of care for adjuvant treatment of stage III endometrial cancer includes chemotherapy and radiation. In addition to stage, tumor molecular profiles may predict treatment outcomes, and prospective clinical trials are ongoing. However, tumor molecular testing is costly and time-consuming. Our objective was to evaluate the cost-effectiveness of tumor molecular testing in stage III endometrial cancer. METHODS: A Markov decision model compared two strategies for stage III endometrial cancer: Tumor Molecular Testing (TMT) versus No TMT. TMT included sequential POLE next generation sequencing, mismatch repair immunohistochemistry (IHC), and p53 IHC. POLE-mutated patients were assigned to adjuvant radiation therapy; all others including controls were assigned to adjuvant chemoradiation. First recurrences were treated with 6 cycles of carboplatin and paclitaxel. Second recurrences were treated with pembrolizumab alone for mismatch repair deficient patients and both pembrolizumab and lenvatinib for other patients. Sensitivity analyses were performed to test model robustness. RESULTS: Compared to No TMT, TMT was cost saving with equivalent effectiveness. On one-way sensitivity analysis, TMT remained cost saving over all parameter ranges. TMT was also favored on probabilistic sensitivity analysis in 80% of iterations at a willingness-to-pay threshold of $100,000/quality adjusted life-year (QALY) gained. However, when TMT was compared to mismatch repair IHC alone, TMT cost $182,798/QALY gained. CONCLUSIONS: In this model of patients with stage III endometrial cancer, TMT was cost saving compared to No TMT. However, when compared to mismatch repair IHC alone, TMT was economically unfavorable.
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Análisis de Costo-Efectividad , Neoplasias Endometriales , Femenino , Humanos , Estudios Prospectivos , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/genética , Carboplatino , Resultado del Tratamiento , Análisis Costo-Beneficio , Años de Vida Ajustados por Calidad de VidaRESUMEN
BACKGROUND/AIMS: Previous studies have revealed that glucagon-like peptide-1 receptor agonist (GLP-1RA) and thiazolidinedione (TZD) can improve nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH). However, comprehensive research comparing the effects of GLP-1RA and TZD is limited. Thus, this study aimed to compare the effects of GLP-1RA and TZD on NAFLD or NASH through a network meta-analysis. METHODS: The PubMed, Embase, Web of Science, and Scopus databases were searched for randomized controlled trials (RCTs) that explored the efficacy of GLP-1RAs or TZDs in adult patients with NAFLD or NASH. The outcomes were liver biopsy-based (NAFLD activity score [NAS], fibrosis stage, and NASH resolution), noninvasive technique-based (liver fat content on proton magnetic resonance spectroscopy [1H-MRS] and controlled attenuation parameter [CAP]), biological, and anthropometric indicators. A random effects model was used to calculate the mean difference (MD) and relative risk with 95% confidence interval (CI). RESULTS: Twenty-five RCTs with 2,237 overweight or obese patients were included. GLP-1RA was significantly superior in reducing liver fat content evaluated using 1H-MRS (MD -2.42, 95% CI -3.84 to -1.00), body mass index (MD -1.60, 95% CI -2.41 to -0.80), and waist circumference (MD -4.89, 95% CI -8.17 to -1.61) than TZD. In liver biopsy-based evaluation and liver fat content assessment using CAP, GLP-1RA tended to surpass TZD, albeit not significantly. Sensitivity analysis showed consistent results with the main results. CONCLUSION: Compared with TZD, GLP-1RA had better effects on liver fat content, body mass index, and waist circumference in overweight or obese patients with NAFLD or NASH.
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Enfermedad del Hígado Graso no Alcohólico , Tiazolidinedionas , Adulto , Humanos , Receptor del Péptido 1 Similar al Glucagón , Metaanálisis en Red , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/patología , Obesidad/complicaciones , Sobrepeso , Tiazolidinedionas/uso terapéuticoRESUMEN
BACKGROUND: As atopic dermatitis (AD) has been found to be related to various comorbidities as well as substantial patient burden, questions of a possible relationship between AD and nonallergic diseases beyond allergic diseases have also been raised. OBJECTIVE: The aim of this nationwide matched cohort study was to evaluate whether AD would increase the development of gastroesophageal reflux disease (GERD). METHODS: Patients diagnosed with AD were identified from the National Health Insurance Service-National Sample Cohort (NHIS-NSC) 2.0 database in South Korea from 2002 to 2015. Finally, 9,164 adults with AD (≥20 years old) and age, sex, household income, region of residence, disability, and baseline year-matched 9,164 controls were included in the analysis. Hazard ratio (HR) with 95% confidence interval (CI) for the development of GERD was estimated using a Cox proportional hazard regression model. RESULTS: Overall, 12.3% of the patients in the AD group developed GERD, whereas 10.4% of the individuals in the control group developed GERD. The results of the adjusted model revealed that patients with AD had a significantly increased risk of developing GERD (adjusted HR, 1.15; 95% CI, 1.06-1.26) compared with the matched controls. Increased risk of developing GERD was consistent in subgroup analyses by sex or age groups under 60 years old as well as all the sensitivity analyses performed. CONCLUSIONS: This study suggested that appropriate management should be considered in adults with AD to prevent GERD, because AD was found to be associated with an increased risk of subsequent GERD.
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Dermatitis Atópica , Reflujo Gastroesofágico , Adulto , Humanos , Persona de Mediana Edad , Adulto Joven , Factores de Riesgo , Dermatitis Atópica/complicaciones , Dermatitis Atópica/epidemiología , Estudios de Cohortes , Reflujo Gastroesofágico/complicaciones , Reflujo Gastroesofágico/epidemiología , ComorbilidadRESUMEN
BACKGROUND: Actinic keratosis (AK) is considered as precursor lesion of invasive squamous cell carcinoma. Molecular studies on AK are limited because of too small size of the biopsy specimen to obtain enough DNA or RNA. METHODS: Twenty biopsy cases of AK, followed by second same-sited biopsies, were included. Ten cases were diagnosed with total regression (regression group), while the other 10 were diagnosed with invasive carcinoma (progression group) in the follow-up biopsies. Using digital spatial profiling (DSP) technology, whole-gene expression analysis defined by specific regions of interest was performed for all 20 cases. After the clinicopathological features were assessed, separate and integrated analyses of these features and gene expression patterns were performed using machine-learning technology. All analyses were performed on both lesion keratinocytes (KT) and infiltrated stromal lymphocytes (LC). RESULTS: Among the 18,667 genes assessed, 33 and 72 differentially expressed genes (DEGs) between the regression and progression groups were found in KT and LC respectively. The primary genes distinguishing the two groups were KRT10 for KT and CARD18 for LC. Clinicopathological features were weaker in risk stratification of AK progression than the gene expression patterns. Pathways associated with various cancers were upregulated in the progression group of KT, whereas the nucleotide-binding oligomerization domain (NOD)-like receptor signalling pathway was upregulated in the progression of LC. CONCLUSION: Gene expression patterns were effective for risk stratification of AK progression, and their distinguishing power was higher than that of clinicopathological features.
Asunto(s)
Carcinoma de Células Escamosas , Queratosis Actínica , Neoplasias Cutáneas , Humanos , Queratosis Actínica/genética , Queratosis Actínica/patología , Neoplasias Cutáneas/patología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Expresión Génica , Medición de RiesgoRESUMEN
PURPOSE: To examine associations between ductal carcinoma in situ (DCIS) patients' characteristics, treating locations and DCIS treatments received and to pilot assessing quality-of-life (QoL) values among DCIS patients with diverse backgrounds. METHODS: We performed a retrospective tumor registry review of all patients diagnosed and treated with DCIS from 2018 to 2019 in the UPMC-integrated network throughout central and western Pennsylvania. Demographics, clinical information, and administered treatments were compiled from tumor registry records. We categorized contextual factors such as different hospital setting (academic vs. community), socioeconomic status based on the neighborhood deprivation index (NDI) as well as age and race. QoL survey was administered to DCIS patients with diverse backgrounds via QoL questionnaire breast cancer module 23 and qualitative assessment questions. RESULTS: A total of 912 patients were reviewed. There were no treatment differences noted for age, race, or NDI. Mastectomy rate was higher in academic sites than community sites (29 vs. 20.4%; p = 0.0045), while hormone therapy (HT) utilization rate was higher in community sites (74 vs. 62%; p = 0.0012). QoL survey response rate was 32%. Only HT side effects negatively affected in QoL scores and there was no significant difference in QoL domains and decision-making process between races, age, NDI, treatment groups, and treatment locations. CONCLUSION: Our integrated health network did not show chronically noted disparities arising from social determinates of health for DCIS treatments by implementing clinical pathways and system-wide peer review. Also, we demonstrated feasibility in collecting QoL for DCIS women with diverse backgrounds and different socioeconomic statuses.