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1.
Neurology ; 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35017312

RESUMO

BACKGROUND AND OBJECTIVES: Although the recent approval of selumetinib is expected to transform the management of children with Neurofibromatosis type 1 (NF1), particularly those with symptomatic and inoperable PN, no systematic review has summarized their efficacy and safety based on the latest studies. This study was conducted to systematically evaluate the efficacy and safety of selumetinib in children with NF1 METHODS: Original articles reporting the efficacy and safety of selumetinib in patients with NF1 were identified in PubMed and EMBASE up to January 28, 2021. The pooled objective response rates (ORRs) and disease control rates (DCRs) were calculated using the DerSimonian-Laird method based on random-effects modeling. The pooled proportion of adverse events (AEs) was also calculated. The quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation system. RESULTS: Five studies involving 126 patients were included in our analysis. The studies had a very low to moderate quality of the evidence. The pooled ORR was 73.8% (95% CI: 57.3-85.5%), and the DCR was 92.5% (95% CI: 66.5-98.7%). The two most common AEs were diarrhea, which had a pooled rate of 63.8% (95% CI, 52.9-73.4%) and an increase in creatine kinase levels, which had a pooled rate of 63.3% (95% CI, 35.6-84.3%). DISCUSSION: Our results indicate that selumetinib is an effective and safe treatment for pediatric patients with symptomatic, inoperable plexiform neurofibromas. Further larger-scale randomized controlled studies are needed to confirm the long-term outcome of patients treated with this drug.

2.
J Korean Med Sci ; 37(1): e3, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34981679

RESUMO

BACKGROUND: We aimed to examine the delay in antiviral initiation in rapid antigen test (RAT) false-negative children with influenza virus infection and to explore the clinical outcomes. We additionally conducted a medical cost-benefit analysis. METHODS: This single-center, retrospective study included children (aged < 10 years) with influenza-like illness (ILI), hospitalized after presenting to the emergency department during three influenza seasons (2016-2019). RAT-false-negativity was defined as RAT-negative and polymerase chain reaction-positive cases. The turnaround time to antiviral treatment (TAT) was from the time when RAT was prescribed to the time when the antiviral was administered. The medical cost analysis by scenarios was also performed. RESULTS: A total of 1,430 patients were included, 7.5% were RAT-positive (n = 107) and 2.4% were RAT-false-negative (n = 20). The median TAT of RAT-false-negative patients was 52.8 hours, significantly longer than that of 4 hours in RAT-positive patients (19.2-100.1, P < 0.001). In the multivariable analysis, TAT of ≥ 24 hours was associated with a risk of severe influenza infection and the need for mechanical ventilation (odds ratio [OR], 6.8, P = 0.009 and OR, 16.2, P = 0.033, respectively). The medical cost varied from $11.7-187.3/ILI patient. CONCLUSION: Antiviral initiation was delayed in RAT-false-negative patients. Our findings support the guideline that children with influenza, suspected of having severe or progressive infection, should be treated immediately.

3.
J Med Internet Res ; 24(1): e34415, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34982041

RESUMO

BACKGROUND: Detection and quantification of intra-abdominal free fluid (ie, ascites) on computed tomography (CT) images are essential processes for finding emergent or urgent conditions in patients. In an emergency department, automatic detection and quantification of ascites will be beneficial. OBJECTIVE: We aimed to develop an artificial intelligence (AI) algorithm for the automatic detection and quantification of ascites simultaneously using a single deep learning model (DLM). METHODS: We developed 2D DLMs based on deep residual U-Net, U-Net, bidirectional U-Net, and recurrent residual U-Net (R2U-Net) algorithms to segment areas of ascites on abdominopelvic CT images. Based on segmentation results, the DLMs detected ascites by classifying CT images into ascites images and nonascites images. The AI algorithms were trained using 6337 CT images from 160 subjects (80 with ascites and 80 without ascites) and tested using 1635 CT images from 40 subjects (20 with ascites and 20 without ascites). The performance of the AI algorithms was evaluated for diagnostic accuracy of ascites detection and for segmentation accuracy of ascites areas. Of these DLMs, we proposed an AI algorithm with the best performance. RESULTS: The segmentation accuracy was the highest for the deep residual U-Net model with a mean intersection over union (mIoU) value of 0.87, followed by U-Net, bidirectional U-Net, and R2U-Net models (mIoU values of 0.80, 0.77, and 0.67, respectively). The detection accuracy was the highest for the deep residual U-Net model (0.96), followed by U-Net, bidirectional U-Net, and R2U-Net models (0.90, 0.88, and 0.82, respectively). The deep residual U-Net model also achieved high sensitivity (0.96) and high specificity (0.96). CONCLUSIONS: We propose a deep residual U-Net-based AI algorithm for automatic detection and quantification of ascites on abdominopelvic CT scans, which provides excellent performance.

4.
Sci Rep ; 11(1): 23534, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34876644

RESUMO

The aim of the study is to develop artificial intelligence (AI) algorithm based on a deep learning model to predict mortality using abbreviate injury score (AIS). The performance of the conventional anatomic injury severity score (ISS) system in predicting in-hospital mortality is still limited. AIS data of 42,933 patients registered in the Korean trauma data bank from four Korean regional trauma centers were enrolled. After excluding patients who were younger than 19 years old and those who died within six hours from arrival, we included 37,762 patients, of which 36,493 (96.6%) survived and 1269 (3.4%) deceased. To enhance the AI model performance, we reduced the AIS codes to 46 input values by organizing them according to the organ location (Region-46). The total AIS and six categories of the anatomic region in the ISS system (Region-6) were used to compare the input features. The AI models were compared with the conventional ISS and new ISS (NISS) systems. We evaluated the performance pertaining to the 12 combinations of the features and models. The highest accuracy (85.05%) corresponded to Region-46 with DNN, followed by that of Region-6 with DNN (83.62%), AIS with DNN (81.27%), ISS-16 (80.50%), NISS-16 (79.18%), NISS-25 (77.09%), and ISS-25 (70.82%). The highest AUROC (0.9084) corresponded to Region-46 with DNN, followed by that of Region-6 with DNN (0.9013), AIS with DNN (0.8819), ISS (0.8709), and NISS (0.8681). The proposed deep learning scheme with feature combination exhibited high accuracy metrics such as the balanced accuracy and AUROC than the conventional ISS and NISS systems. We expect that our trial would be a cornerstone of more complex combination model.

5.
Medicine (Baltimore) ; 100(44): e27626, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34871226

RESUMO

ABSTRACT: Asthma is a heterogeneous disease characterized by chronic airway inflammation with a genetic predisposition. Butyrophilin-like 2 (BTNL2) is a member of the immunoglobulin superfamily that plays an important role in regulating T cell activation and immune homeostasis. Here, we aimed to investigate the association of the genetic variants of BTNL2 with childhood asthma and asthma-related traits by utilizing extreme asthma phenotypes and employing a genome-wide association study. Our study included 243 children with well-defined moderate to severe atopic asthma and 134 healthy children with no history of allergic diseases and allergic sensitization. DNA from these subjects was genotyped using AxiomTM Genome-Wide Array Plates. Although no single nucleotide polymorphisms (SNPs) reached a genome-wide threshold of significance, 3 SNPs, rs3817971, rs41355746, and rs41441651, at BTNL2 were significantly associated with moderate to severe atopic asthma after performing Bonferroni correction. These SNPs were also associated with the risk of allergic sensitization toward house dust mites and the presence and degree of bronchial hyperresponsiveness. Thus, we identified that BTNL2 was associated with atopic moderate to severe persistent asthma in Korean children, and this may play an important role in disease development and susceptibility.

6.
Sci Rep ; 11(1): 23496, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34873215

RESUMO

Air pollution may influence prenatal maternal stress, but research evidence is scarce. Using data from a prospective cohort study conducted on pregnant women (n = 2153), we explored the association between air pollution and perceived stress, which was assessed using the 14-item Perceived Stress Scale (PSS), among pregnant women. Average exposures to particulate matter with an aerodynamic diameter of < 2.5 µm (PM2.5) or < 10 µm (PM10), nitrogen dioxide (NO2), and ozone (O3) for each trimester and the entire pregnancy were estimated at maternal residential addresses using land-use regression models. Linear regression models were applied to estimate associations between PSS scores and exposures to each air pollutant. After adjustment for potential confounders, interquartile-range (IQR) increases in whole pregnancy exposures to PM2.5, PM10, and O3 in the third trimester were associated with 0.37 (95% confidence interval [CI] 0.01, 0.74), 0.54 (95% CI 0.11, 0.97), and 0.30 (95% CI 0.07, 0.54) point increases in prenatal PSS scores, respectively. Furthermore, these associations were more evident in women with child-bearing age and a lower level of education. Also, the association between PSS scores and PM10 was stronger in the spring. Our findings support the relationship between air pollution and prenatal maternal stress.

7.
Nutr Res Pract ; 15(6): 732-746, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34858551

RESUMO

BACKGROUND/OBJECTIVES: This study examined the differences in psychosocial factors and eating behaviors by the stages of change (SOC) in nutrition management among elementary and middle school athletes. SUBJECTS/METHODS: Subjects were young athletes recruited from the athletic clubs of 10 organizations. Subjects responded to a survey questionnaire, and data on 167 athletes were analyzed. Subjects were grouped into the pre-action or action stage in nutrition management. The χ2 test, t-test, analysis of covariance, and correlation analysis were used in data analysis. RESULTS: Athletes in the action stage (62.3%) compared to the pre-action stage, showed a higher self-efficacy (P < 0.01), and felt more confidence in performing specific eating behaviors (P < 0.05 to P < 0.01). Those in the action stage had more favorable beliefs regarding nutrition (P < 0.001) and agreed less strongly on the specific misconceptions/disadvantages of nutrition (P < 0.01) than those in the pre-action stage. Eating behaviors (P < 0.001) and subscales of the eating behaviors (P < 0.05 to P < 0.01) also differed significantly by the SOC group. Place of eating dinner (P < 0.05) and the person who prepares dinner (P < 0.05) showed significant differences by the SOC group. The relationship of self-efficacy, beliefs regarding nutrition, and eating behaviors to the SOC differed by sports type. Beliefs for football athletes, self-efficacy, and beliefs for baseball athletes were correlated significantly with the SOC, whereas all 3 variables were related to the SOC for handball and other athletes. CONCLUSIONS: This study showed differences in psychosocial factors and eating behaviors between the pre-action and action stages. Nutrition education should include strategies to help young athletes modify their beliefs, mainly misconceptions/disadvantages of nutrition, increase self-efficacy, and adopt specific and desirable eating behaviors. Nutrition education might employ different strategies considering the sports type that student-athletes participate.

8.
Dig Liver Dis ; 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34903501

RESUMO

BACKGROUND AND AIMS: The accurate differential diagnosis between autoimmune pancreatitis (AIP) and pancreatic ductal adenocarcinoma (PDAC) is clinically important. We aimed to determine significant MRI features for differentiating AIP from PDAC, including assessment of diffusion-weighted imaging (DWI). METHODS: We performed a systematic search using three databases. The pooled diagnostic odds ratio was calculated using a bivariate random effects model to determine significant MRI features for differentiating AIP from PDAC. The pooled sensitivity and specificity were calculated. The qualitative systematic review for DWI assessment was performed. RESULTS: Of nine studies (775 patients), multiple main pancreatic duct (MPD) strictures, absence of upstream marked MPD dilatation, peripancreatic rim, and duct penetration sign were significant MRI features for differentiating AIP from PDAC. Absence of MPD dilatation had the highest pooled sensitivity (87%, 95% CI=68-96%), whereas peripancreatic rim had the highest pooled specificity (100%, 95% CI=88-100%). Of 12 studies evaluating DWI, seven reported statistically significant differences in apparent diffusion coefficient (ADC) values between AIP and PDAC; however, four reported lower ADC values in AIP than in PDAC, but three reported the opposite result. CONCLUSION: The four significant MRI features can be useful to differentiate AIP from PDAC, but DWI assessment might be limited.

9.
Children (Basel) ; 8(12)2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34943306

RESUMO

Heiner syndrome is a rare cause of pulmonary hemosiderosis in children that is triggered by cow's milk allergy. Herein, we describe our experience with three recent cases of Heiner syndrome with diverse clinical courses. We recommend that clinicians should consider the possibility of Heiner syndrome in children who exhibit characteristics of idiopathic pulmonary hemosiderosis.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34843802

RESUMO

BACKGROUND: The pathophysiology of childhood food allergy (FA) and its natural history are poorly understood. Clarification of the underlying mechanism may aid in identifying novel biomarkers and strategies for clinical intervention in children with FA. OBJECTIVE: This study aimed to identify metabolites associated with the development and resolution of FA. METHODS: The metabolomic profiles of 20 children with FA and 20 healthy controls were assessed using liquid chromatography-mass spectrometry. Comparative analysis was performed to identify metabolites associated with FA and FA resolution. For subjects with FA, serum samples were collected at the time of diagnosis and after resolution to identify the changes in metabolite levels. The selected metabolites were then quantified in a quantification cohort to validate the results. Finally, genome-wide association analysis of the metabolite levels was performed. RESULTS: The study demonstrated a significantly higher level of sphingolipid metabolites and a lower level of acylcarnitine metabolites in children with FA than those in healthy controls. At diagnosis, subjects with resolving FA had a significantly high level of omega-3 metabolites and a low level of platelet-activating factors (PAF) compared to persistent FA. However, the level of omega-3 metabolites decreased in children with resolving FA but increased in children with persistent FA during the same time. The quantification data of omega-3 derived resolvins, PAF, and PAF acetylhydrolase activity further supported these results. CONCLUSION: The lipid metabolite profile is closely related to childhood FA and FA resolution. This study suggests potential predictive biomarkers and provides insight into mechanisms underlying childhood FA.

11.
Diabetes Metab Res Rev ; : e3513, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34799961

RESUMO

AIM: To examine the association between type 2 diabetes and the amount and quality of trunk muscle as assessed by computed tomography (CT) scan. MATERIALS AND METHODS: A total of 20,986 subjects (13,007 men and 7979 women) who underwent abdominal CT scan as part of a routine health check-up were included. The total abdominal muscle area (TAMA) measured at the third lumbar vertebrae was classified into skeletal muscle area (SMA), and intermuscular adipose tissue area. SMA was divided into good quality muscles (normal attenuation muscle area [NAMA]) and poor quality muscles (low attenuation muscle area). NAMA/TAMA index was calculated. RESULTS: Subjects with type 2 diabetes had higher values of TAMA and SMA but significantly lower values of NAMA and NAMA/TAMA index. Compared with those in the lowest quartile of NAMA/TAMA index, subjects in the highest quartile had metabolically favourable laboratory findings, a lower prevalence of type 2 diabetes (Q1 vs. Q4: 19.3% vs. 9.5% in men, 12.3% vs. 3.0% in women) and inverse association with type 2 diabetes (odds ratio for Q2, Q3, and Q4: 0.87, 0.78, and 0.75 in men; 0.82, 0.70, and 0.68 in women) after multivariable adjustment. CONCLUSIONS: The amount of good quality muscle on CT scan was associated with a lower prevalence of type 2 diabetes.

12.
Mod Pathol ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34764434

RESUMO

Overexpression of the BCL2 protein has been reported as a poor prognostic factor for diffuse large B-cell lymphoma (DLBCL). However, there are currently no standardized criteria for evaluating BCL2 protein expression. We aimed to evaluate the prognostic value of BCL2 expression determined by immunohistochemistry (IHC), incorporating both the staining intensity and proportion, in patients with de novo DLBCL who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as first-line treatment. We defined tumors with BCL2 expression in nearly all tumor cells with a uniformly strong intensity by IHC as BCL2 super-expressor. The BCL2 super-expressors (n = 35) showed significantly worse event-free survival (EFS; HR, 1.903; 95% CI, 1.159-3.126, P = 0.011) and overall survival (OS; HR, 2.467; 95% CI, 1.474-4.127, P = 0.001) compared with the non-BCL2 super-expressors (n = 234) independent of the international prognostic index (IPI), cell of origin (COO), and double expressor status in the training set (n = 269). The adverse prognostic impact of BCL2 super-expression was confirmed in the validation set (n = 195). When the survival outcomes were evaluated in the entire cohort (n = 464), BCL2 super-expressor group was significantly associated with inferior EFS and OS regardless of IPI, COO, MYC expression, and stages. BCL2 super-expressors had genetic aberrations enriched in the NOTCH and TP53 signaling pathways. This study suggests that the BCL2 super-expressor characterizes a distinct subset of DLBCL with a poor prognosis and warrants further investigation as a target population for BCL-2 inhibitors.

13.
Psychiatry Investig ; 18(11): 1137-1143, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34732031

RESUMO

OBJECTIVE: There are growing interests on suicide risk screening in clinical settings and classifying high-risk groups of suicide with suicidal ideation is crucial for a more effective suicide preventive intervention. Previous statistical techniques were limited because they tried to predict suicide risk using a simple algorithm. Machine learning differs from the traditional statistical techniques in that it generates the most optimal algorithm from various predictors. METHODS: We aim to analyze the Personality Assessment Inventory (PAI) profiles of child and adolescent patients who received outpatient psychiatric care using machine learning techniques, such as logistic regression (LR), random forest (RF), artificial neural network (ANN), support vector machine (SVM), and extreme gradient boosting (XGB), to develop and validate a classification model for individuals with high suicide risk. RESULTS: We developed prediction models using seven relevant features calculated by Boruta algorithm and subsequently tested all models using the testing dataset. The area under the ROC curve of these models were above 0.9 and the RF model exhibited the best performance. CONCLUSION: Suicide must be assessed based on multiple aspects, and although Personality Assessment Inventory for Adolescent assess an array of domains, further research is needed for predicting high suicide risk groups.

14.
Sci Rep ; 11(1): 21656, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34737340

RESUMO

As sarcopenia research has been gaining emphasis, the need for quantification of abdominal muscle on computed tomography (CT) is increasing. Thus, a fully automated system to select L3 slice and segment muscle in an end-to-end manner is demanded. We aimed to develop a deep learning model (DLM) to select the L3 slice with consideration of anatomic variations and to segment cross-sectional areas (CSAs) of abdominal muscle and fat. Our DLM, named L3SEG-net, was composed of a YOLOv3-based algorithm for selecting the L3 slice and a fully convolutional network (FCN)-based algorithm for segmentation. The YOLOv3-based algorithm was developed via supervised learning using a training dataset (n = 922), and the FCN-based algorithm was transferred from prior work. Our L3SEG-net was validated with internal (n = 496) and external validation (n = 586) datasets. Ground truth L3 level CT slice and anatomic variation were identified by a board-certified radiologist. L3 slice selection accuracy was evaluated by the distance difference between ground truths and DLM-derived results. Technical success for L3 slice selection was defined when the distance difference was < 10 mm. Overall segmentation accuracy was evaluated by CSA error and DSC value. The influence of anatomic variations on DLM performance was evaluated. In the internal and external validation datasets, the accuracy of automatic L3 slice selection was high, with mean distance differences of 3.7 ± 8.4 mm and 4.1 ± 8.3 mm, respectively, and with technical success rates of 93.1% and 92.3%, respectively. However, in the subgroup analysis of anatomic variations, the L3 slice selection accuracy decreased, with distance differences of 12.4 ± 15.4 mm and 12.1 ± 14.6 mm, respectively, and with technical success rates of 67.2% and 67.9%, respectively. The overall segmentation accuracy of abdominal muscle areas was excellent regardless of anatomic variation, with CSA errors of 1.38-3.10 cm2. A fully automatic system was developed for the selection of an exact axial CT slice at the L3 vertebral level and the segmentation of abdominal muscle areas.

15.
Lancet Oncol ; 22(11): 1560-1572, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34656226

RESUMO

BACKGROUND: The prognosis of patients with advanced biliary tract cancer who have progressed on gemcitabine plus cisplatin is dismal. We aimed to investigate the efficacy and safety of second-line liposomal irinotecan plus fluorouracil and leucovorin in patients with metastatic biliary tract cancer that has progressed on gemcitabine plus cisplatin. METHODS: This multicentre, open-label, randomised, phase 2b (NIFTY) study was done at five academic institutions in South Korea and included patients aged 19 years or older with histologically or cytologically confirmed metastatic biliary tract cancer that had progressed on first-line gemcitabine plus cisplatin and an Eastern Cooperative Oncology Group performance status of 0 or 1. By use of an interactive web-based response system integrated with an electronic data capture system, patients were randomly assigned (1:1) using permuted blocks (block size 4) to receive either intravenous liposomal irinotecan (70 mg/m2 for 90 min) plus intravenous leucovorin (400 mg/m2 for 30 min) and intravenous fluorouracil (2400 mg/m2 for 46 h) every 2 weeks or leucovorin and fluorouracil only every 2 weeks, and were stratified by primary tumour site, previous surgery with curative intent, and participating centre. Study treatment was continued until the patient had disease progression or unacceptable toxicities, or withdrew consent. The primary endpoint was blinded independent central review (BICR)-assessed progression-free survival. The primary endpoint and safety were assessed in the full analysis set and the safety analysis set, respectively, both of which comprised all randomly assigned patients who received at least one dose of the study treatment. This trial is registered with ClinicalTrials.gov, NCT03524508, and enrolment is complete. FINDINGS: Between Sept 5, 2018, and Feb 18, 2020, 193 patients were screened for eligibility, of whom 174 (88 in the liposomal irinotecan plus fluorouracil and leucovorin group and 86 in the fluorouracil plus leucovorin group) were enrolled and included in the full analysis and safety analysis sets. At a median follow-up of 11·8 months (IQR 7·7-18·7), the median BICR-assessed progression-free survival was significantly longer in the liposomal irinotecan plus fluorouracil and leucovorin group (7·1 months, 95% CI 3·6-8·8) than in the fluorouracil and leucovorin group (1·4 months, 1·2-1·5; hazard ratio 0·56, 95% CI 0·39-0·81; p=0·0019). The most common grade 3-4 adverse events were neutropenia (21 [24%] of 88 in the liposomal irinotecan plus fluorouracil and leucovorin group vs one [1%] of 86 in the fluorouracil and leucovorin group) and fatigue or asthenia (11 [13%] vs three [3%]). Serious adverse events occurred in 37 (42%) patients receiving liposomal irinotecan plus fluorouracil and leucovorin and 21 (24%) patients receiving fluorouracil and leucovorin. There were no treatment-related deaths. INTERPRETATION: Adding liposomal irinotecan to fluorouracil and leucovorin significantly improved BICR-assessed progression-free survival in patients with advanced biliary tract cancer. Liposomal irinotecan plus fluorouracil and leucovorin could be considered a standard-of-care second-line therapy for advanced biliary tract cancer. FUNDING: Servier and HK inno. N TRANSLATION: For the Korean translation of the abstract see Supplementary Materials section.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , Fluoruracila/uso terapêutico , Irinotecano/uso terapêutico , Leucovorina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Biliar/mortalidade , Neoplasias do Sistema Biliar/patologia , Cisplatino/uso terapêutico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Intervalo Livre de Progressão , República da Coreia , Taxa de Sobrevida , Inibidores da Topoisomerase I/uso terapêutico
16.
Clin Transl Allergy ; 11(8): e12069, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34667591

RESUMO

Background: The upper-airway microbiota may be associated with the pathogenesis of asthma and useful for predicting acute exacerbation. However, the relationship between the lower-airway microbiota and acute exacerbation in children with asthma is not well understood. We evaluated the characteristics of the airway microbiome using induced sputum from children with asthma exacerbation and compared the microbiota-related differences of inflammatory cytokines with those in children with asthma. Methods: We analysed the microbiome using induced sputum during acute exacerbation of asthma in children. We identified microbial candidates that were prominent in children with asthma exacerbation and compared them with those in children with stable asthma using various analytical methods. The microbial candidates were analysed to determine their association with inflammatory cytokines. We also developed a predictive functional profile using PICRUSt. Results: A total of 95 children with allergic sensitisation including 22 with asthma exacerbation, 67 with stable asthma, and 6 controls were evaluated. We selected 26 microbial candidates whose abundances were significantly increased, decreased, or correlated during acute exacerbation in children with asthma. Among the microbial candidates, Campylobacter, Capnocytophaga, Haemophilus, and Porphyromonas were associated with inflammatory cytokines including macrophage inflammatory protein (MIP)-1ß, programmed death-ligand 1, and granzyme B. Both Campylobacter and MIP-1ß levels were correlated with sputum eosinophils. Increased lipopolysaccharide biosynthesis and decreased glycan degradation were observed in children with asthma exacerbation. Conclusion: Gram-negative microbes in the lower airway were related to acute exacerbation in children with asthma. These microbes and associated cytokines may play a role in exacerbating asthma in children.

17.
Clin Transl Allergy ; 11(8): e12070, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34691390

RESUMO

Background: The prevalence of atopic dermatitis (AD) is increasing worldwide. Prenatal particulate matter with an aerodynamic diameter <2.5 µm (PM2.5) and maternal anxiety during pregnancy has been suggested as a potential causes of AD. This study investigated the effects of prenatal PM2.5 and maternal anxiety on AD and identified the critical period of PM2.5 exposure for AD in infants. Methods: This study included 802 children from the COCOA birth cohort study with follow-up data at 1 year of age. PM2.5 was estimated by land-use regression models and prenatal anxiety was measured with a questionnaire. AD was diagnosed by doctor at 1 year of age. Logistic regression analysis and Bayesian distributed lag interaction models were applied. Results: Higher PM2.5 during the first trimester of pregnancy, higher prenatal maternal anxiety, and male gender were associated with AD at 1 year of age (adjusted odds ratio [aOR] and 95% confidence interval [CI]: 1.86 [1.08-3.19], 1.58 [1.01-2.47], and 1.54 [1.01-2.36], respectively). Higher PM2.5 during the first trimester and higher maternal anxiety during pregnancy showed an additive effect on the risk of AD (aOR: 3.13; 95% CI: 1.56-6.28). Among boys exposed to higher maternal anxiety during pregnancy, gestational weeks 5-8 were the critical period of PM2.5 exposure for the development of AD. Conclusions: Higher PM2.5 exposure during gestational weeks 5-8 increased the probability of AD in infancy, especially in boys with higher maternal anxiety. Avoiding PM2.5 exposure and maternal anxiety from the first trimester may prevent infant AD.

18.
AJR Am J Roentgenol ; 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34704461

RESUMO

Background: Traditional approaches for evaluating multiple myeloma (MM) treatment response have low sensitivity for residual disease. Recent studies highlight utility of whole-body MRI or FDG PET/CT in evaluating treatment response, with increasing emphasis on DWI. Objective: This systematic review was conducted to assess the diagnostic accuracy of whole-body MRI and FDG PET/CT for treatment response assessment in MM. Evidence Acquisition: Studies using whole-body MRI or FDG PET/CT to evaluate MM treatment response were identified through search of PubMed and EMBASE databases through June 30, 2021. Pooled sensitivity and specificity for detecting response were calculated by bivariate modeling. Diagnostic performance of whole-body MRI and FDG PET/CT were compared. Subgroup analyses assessed studies comparing both modalities and studies in which whole-body MRI included DWI. Evidence Synthesis: Twelve studies comprising 373 patients were included: six evaluated both modalities, four evaluated whole-body MRI only, and two evaluated FDG PET/CT only; of studies with MRI, five used DWI. Pooled sensitivity and specificity were 87% (95% CI, 75%-93%) and 57% (95% CI, 37%-76%) for whole-body MRI, versus 64% (95% CI, 45%-79%) and 82% (95% CI, 75%-88%) for FDG PET/CT (sensitivity: p = .29; specificity: p = .01). For studies directly comparing the modalities, pooled sensitivity and specificity were 90% (95% CI, 80%-100%) and 56% (95% CI, 44%-68%) for whole-body MRI, versus 66% (95% CI, 47%-85%) and 81% (95% CI, 72%-90%) for FDG PET/CT (sensitivity: p = .18; specificity: p < .001). Sensitivity and specificity were 93% (95% CI, 75%-98%) and 57% (95% CI, 21%-87%) for DWI, versus 74% (95% CI, 60%-85%) and 56% (95% CI, 38%-73%) for whole-body MRI without DWI (sensitivity: p = .27; specificity: p = .99). AUC was 0.84 for whole-body MRI, 0.83 for FDG PET/CT, and 0.92 for DWI. Conclusion: FDG PET/CT had significantly higher specificity, whereas whole-body MRI had higher sensitivity (though non-significant). DWI may contribute to the high sensitivity of whole-body MRI. Clinical Impact: This meta-analysis suggests potential complementary roles of whole-body MRI and FDG PET/CT in MM treatment response assessment. Future studies should explore their combination through PET/MRI.

19.
PLoS One ; 16(10): e0259208, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34705883

RESUMO

BACKGROUND: Children with complex chronic multisystemic diseases frequently require care from multiple pediatric subspecialists. The aerodigestive program is a multidisciplinary program that diagnoses and treats pediatric patients with complex multi-systematic problems affecting airway, breathing, feeding, swallowing, or growth. The aim of this study is to present the protocol of the aerodigestive program of a children's hospital. METHODS AND DESIGN: This study is a prospective study to evaluate and compare the overall improvement of patients' objective and subjective conditions before and after the AeroDigestive Team (ADT) program. Among children from 1 month to 18 years of age, patients with complex problems of the airway, breathing, feeding, swallowing, or growth meeting at least two parameters of the inclusion criteria were enrolled. The overall process included referral based on the inclusion criteria, enrollment of ADT program with informed consents, interview and questionnaire for assessing patients' medical condition, prescheduling appointment, multi-specialists' evaluation, monthly team meetings, wrap-up discussion with the patients and family, therapeutic intervention, and follow-up at 6 months with the assessment of outcome measures. The outcome was evaluated objectively and subjectively. The objective outcome measure was divided into surgical or medical intervention, assessment of changes in medical condition, and follow-up study. Both caregiver interviews and questionnaires using a scoring system were used as subjective outcome measures before and after the ADT program. Children were scheduled to be followed-up at 6 months after the interventions or ADT meeting. DISCUSSION: The aerodigestive program is expected to provide comprehensive and multidisciplinary management of children with complex airway and digestive tract disorders.


Assuntos
Gastroenteropatias/terapia , Equipe de Assistência ao Paciente/normas , Guias de Prática Clínica como Assunto , Doenças Respiratórias/terapia , Adolescente , Criança , Pré-Escolar , Gerenciamento Clínico , Feminino , Gastroenteropatias/complicações , Humanos , Lactente , Comunicação Interdisciplinar , Masculino , Equipe de Assistência ao Paciente/organização & administração , Assistência Centrada no Paciente/organização & administração , Assistência Centrada no Paciente/normas , Doenças Respiratórias/complicações
20.
BMC Cancer ; 21(1): 1164, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34715813

RESUMO

BACKGROUND: The incidence of hepatocellular carcinoma (HCC) has been increasing among the elderly populations. Trans-arterial chemoembolization (TACE), a widely used first-line non-curative therapy for HCCs is an issue in geriatrics. We investigated the prognosis of elderly HCC patients treated with TACE and determined the factors that affect the overall survival. METHODS: We included 266 patients who were older than 65 years and had received TACE as initial treatment for HCC. We analyzed the skeletal muscle index (SMI) and visceral-to-subcutaneous fat ratio (VSR) around the third lumbar vertebrae using computed tomography scans. Muscle depletion with visceral adiposity (MDVA) was defined by falling below the median SMI and above the median VSR value sex-specifically. We evaluated the overall survival in association with MDVA and other clinical factors. RESULTS: The mean age was 69.9 ± 4.5 years, and 70.3% of the patients were men. According to the Barcelona Clinic Liver Cancer (BCLC) staging system, 29, 136, and 101 patients were classified as BCLC 0, A, and B stages, respectively, and 79 (29.7%) had MDVA. During the median follow-up of 4.1 years, patients with MDVA had a shorter life expectancy than those without MDVA (P = 0.007) even though MDVA group had a higher objective response rate after the first TACE (82.3% vs. 75.9%, P = 0.035). Multivariate analysis revealed that MDVA (Hazard ratio [HR] 1.515) age (HR 1.057), liver function (HR 1.078), tumor size (HR 1.083), serum albumin level (HR 0.523), platelet count (HR 0.996), tumor stage (stage A, HR 1.711; stage B, HR 2.003), and treatment response after the first TACE treatment (HR 0.680) were associated with overall survival. CONCLUSIONS: MDVA is a critical prognostic factor for predicting survival in the elderly patients with HCC who have undergone TACE.

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