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Jeng-Dau Tsai,1,2 Cheng-Li Lin,3,4 Cheng-Chieh Lin,5–7 Fung-Chang Sung,3,4,7,* Ko-Huang Lue1,2,* 1Institute of Medicine, Chung Shan Medical University Hospital, 2Department of Pediatrics, Chung Shan Medical University and Hospital, 3Institute of Clinical and Medical Science, China Medical University, 4Management Office for Health Data, China Medical University Hospital, 5Department of Family Medicine, China Medical University School of Medicine, 6Division of Family Medicine, China Medical University Hospital, 7Department of Healthcare Administration, College of Health Science, Asia University, Taichung, Taiwan *These authors contributed equally to this work Background: Systemic lupus erythematosus (SLE) affects central and peripheral nervous systems, manifesting neuropsychiatric disorders that vary from subtle signs to life-threatening complications. This study compared the risk of epilepsy between a general population and patients with SLE.Methods: From the national insurance claims data of the Taiwan National Health Research Institutes, we identified 32,301 patients with newly diagnosed SLE from 1997–2010 and, for comparison, 129,204 randomly selected people without SLE; the frequencies of both groups were matched by sex, age, and diagnosis date. The incidence of epilepsy was estimated for both cohorts by the end of 2010. Results: The incidence of epilepsy was 2.86-fold higher in the SLE cohort than in the non-SLE cohort (9.10 per 10,000 person-years versus 3.18 per 10,000 person-years), with a Cox method estimated adjusted hazard ratio (aHR) of 2.33 (95% confidence interval [CI] =1.89–2.88) for the SLE cohort. The incidence increased with age in the non-SLE cohort, while it decreased with the increase of age in the SLE cohort. Compared with the non-SLE cohort, the age-specific aHR of epilepsy for the SLE cohort decreased from 8.05 (95% CI =4.30–15.0) for those aged ≤20 years to 0.90 (95% CI =0.57–1.42) for those aged 60 years and above (P=0.01). Comorbidities that had a significant association with epilepsy included infarction (aHR =7.62), intracerebral hemorrhage (aHR =5.75), aseptic meningoencephalitis (aHR =5.35), and psychiatric disorder (aHR =3.31).Conclusion: Patients with SLE are at higher risk of epilepsy than the general population, especially younger SLE patients. Neurologic comorbidities and psychiatric disorders increase the epilepsy risk further. Keywords: epilepsy, incidence, lupus, health insurance data, cohort study

Objective: 6-[(18)F]Fluoro-L: -DOPA (FDOPA) is a radiopharmaceutical valuable for assessing the presynaptic dopaminergic function when used with positron emission tomography (PET). More specifically, the striatal-to-occipital ratio (SOR) of FDOPA uptake images has been extensively used as a quantitative parameter in these PET studies. Our aim was to develop an easy, automated method capable of performing objective analysis of SOR in FDOPA PET images of Parkinson's disease (PD) patients. Methods: Brain images from FDOPA PET studies of 21 patients with PD and 6 healthy subjects were included in our automated striatal analyses. Images of each individual were spatially normalized into an FDOPA template. Subsequently, the image slice with the highest level of basal ganglia activity was chosen among the series of normalized images. Also, the immediate preceding and following slices of the chosen image were then selected. Finally, the summation of these three images was used to quantify and calculate the SOR values. The results obtained by automated analysis were compared with manual analysis by a trained and experienced image processing technologist. Results: The SOR values obtained from the automated analysis had a good agreement and high correlation with manual analysis. The differences in caudate, putamen, and striatum were -0.023, -0.029, and -0.025, respectively; correlation coefficients 0.961, 0.957, and 0.972, respectively. Conclusions: We have successfully developed a method for automated striatal uptake analysis of FDOPA PET images. There was no significant difference between the SOR values obtained from this method and using manual analysis. Yet it is an unbiased time-saving and cost-effective program and easy to implement on a personal computer. [ABSTRACT FROM AUTHOR]

Objective: To investigate the prognostic value of 18 F-FDG PET-based intensity, volumetric features, and deep learning (DL) across different generations of PET scanners in patients with epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma receiving tyrosine kinase inhibitor (TKI) treatment., Methods: We retrospectively analyzed the pre-treatment 18 F-FDG PET of 217 patients with advanced-stage lung adenocarcinoma and actionable EGFR mutations who received TKI as first-line treatment. Patients were separated into analog (n = 166) and digital (n = 51) PET cohorts. 18 F-FDG PET-derived intensity, volumetric features, ResNet-50 DL of the primary tumor, and clinical variables were used to predict progression-free survival (PFS). Independent prognosticators were used to develop prediction model. Model was developed and validated in the analog and digital PET cohorts, respectively., Results: In the analog PET cohort, female sex, stage IVB status, exon 19 deletion, SUV max , metabolic tumor volume, and positive DL prediction independently predicted PFS. The model devised from these six prognosticators significantly predicted PFS in the analog (HR = 1.319, p < 0.001) and digital PET cohorts (HR = 1.284, p = 0.001). Our model provided incremental prognostic value to staging status (c-indices = 0.738 vs. 0.558 and 0.662 vs. 0.598 in the analog and digital PET cohorts, respectively). Our model also demonstrated a significant prognostic value for overall survival (HR = 1.198, p < 0.001, c-index = 0.708 and HR = 1.256, p = 0.021, c-index = 0.664 in the analog and digital PET cohorts, respectively)., Conclusions: Combining 18 F-FDG PET-based intensity, volumetric features, and DL with clinical variables may improve the survival stratification in patients with advanced EGFR-mutated lung adenocarcinoma receiving TKI treatment. Implementing the prediction model across different generations of PET scanners may be feasible and facilitate tailored therapeutic strategies for these patients., (© 2024. The Author(s), under exclusive licence to The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Fine particulate matter (PM 2.5 ) is a common major air pollutant associated with decreased lung function, induced allergic airway inflammation closely correlated with chronic lung diseases. Angiopoietin-like protein 4 (ANGPTL4) is a cytokine with multiple functions, participating in processes such as inflammation, angiogenesis, and metastasis. Curcumin is an active compound found in turmeric plants and possesses various pharmacological effects, including antioxidant, anti-inflammatory, anticancer, and immunomodulatory properties. The aim of this study was twofold: firstly, to investigate the involvement of ANGPTL4 in lung inflammation and carcinogenesis under PM 2.5 exposure, and secondly, to explore the impact of curcumin on ANGPTL4 expression and its potential in lung cancer chemoprevention. We used protein array to detect several proinflammatory cytokines and then used qPCR to confirm by increasing the concentration of PM 2.5 to enhance the expressions of CXCL1, CXCL5; IL-1α, IL-1β, MIP-3α and inflammation- or fibrosis-associated proteins. Curcumin inhibits PM 2.5 - induced ANGPTL4 and the IκB-α (inhibitor of NFκB)-dependent inflammatory pathway. Silencing ANGPTL4 by shRNA restore IκB-α and MIP-3α expression. In conclusion, the increased expression of ANGPTL4 after treatment with PM 2.5 in lung cells may be one of the mechanisms by which PM 2.5 exposure contributes to lung inflammation progression. Our results provide evidence that curcumin in anti-inflammation therapeutics could serve as a beneficial chemopreventive agent., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jiunn-Liang Ko reports financial support was provided by National Science and Technology Council, Taiwan. Ko-Huang Lue reports financial support was provided by Chung Shan Medical University Hospital. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: The impact of asthma on the severity of rhinitis when children with allergic rhinitis (AR) are exposed to air pollutants has not been studied., Methods: Children with AR (65 with asthma, 208 without asthma), aged 6-13 years, were recruited from a hospital in Taichung, Taiwan, between 2007 and 2011. Correlations between Pediatric-Rhinoconjunctivitis-Quality-of-Life score, nasal peak expiratory flow, and air pollutants were compared. With the same age, research time, and form the same city, children with AR (660 with asthma, 3174 without asthma) were selected from a database. Correlations between clinical visit times for AR and air pollutants were compared., Results: In male children with AR and asthma, both clinical and database studies revealed a correlation between higher rhinitis discomfort (quality-of-life score), higher visit times for AR, and higher PM 10 , PM 2.5, NO 2, NMHC concentrations. Correlations between higher nasal inflammation/obstruction (lower expiratory flow) and higher air pollutant concentrations were observed in male children with AR and asthma., Conclusion: In children with AR, comorbid asthma was associated with increased rhinitis severity when they were exposed to air pollutants, and the association was only noted in males. Increased nasal obstruction/inflammation from exposure to air pollutants may be the mechanisms underlying this association., Impact Statement: The influence of asthma on the severity of rhinitis when children with allergic rhinitis (AR) are exposed to air pollutants has not been studied. In children with AR, the correlation between higher rhinitis discomfort, higher number of clinical visits for AR, and higher PM 10 , PM 2.5, NO 2, NMHC concentrations were only noted in those who also had asthma. The correlation was only noted in male. Comorbid asthma was associated with higher rhinitis severity when children with AR are exposed to air pollutants The association was only noted in male., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Allergic asthma, a chronic disease characterized by airway inflammation, poses a significant public health concern. It is well-established that house dust mites (HDMs) are common inducers of allergic responses in individuals, particularly children. In central Taiwan, our research team observed that over 80% of allergic children exhibited sensitization to various HDMs species. This investigation aims to bridge the gap between these observations and a better understanding of the early fundamental mechanisms for preventing allergic diseases. Specifically, our study delves into the impact of crude extracts of HDMs on human epithelial BEAS-2B cells. Our findings, based on RNA sequencing (RNA-seq) analysis, shed light on how three major Dermatophagoides HDMs allergens activate a common Toll-like receptor signaling pathway in human epithelial cells within a 4-h treatment. During this process, the nuclear transcription factor NF-κB translocated into the cell nucleus within 30 min of allergen stimulation, triggering the expression of pro-inflammatory genes such as IL-6 and IL-8 over 4 h. Additionally, when the cells were treated with specific Dermatophagoides microceras (Der m) allergens, it resulted in the upregulation of genes that regulate type 1 diabetes mellitus (T1DM) signaling pathways. This led to the mediation of IL-12A inflammation. Furthermore, there was an increase in gene sets associated with cilia function and the microtubule cytoskeleton in human epithelial cells after treatment with a combination of Der m allergens and Dexamethasone. Additionally, OMICs analysis was conducted to examine the effects of HDMs allergenic stimulation on human epidermal cells. We aimed to improve our understanding of the molecular mechanisms within cells and identify potential targets and natural products in the treatment of asthma caused by HDMs allergens., (© 2023 Wiley Periodicals LLC.)

Purpose: 18 F-FDG PET quantitative features are susceptible to respiratory motion. However, studies using clinical patient data to explore the impact of respiratory motion on 18 F-FDG PET radiomic features are limited. In this study, we investigated the impact of respiratory motion on radiomics stability with clinical 18 F-FDG PET images using a data-driven gating (DDG) algorithm on the digital PET scanner., Materials and Methods: A total of 101 patients who underwent oncological 18 F-FDG PET scans were retrospectively included. A DDG algorithm combined with a motion compensation technique was used to extract the PET images with respiratory motion correction. 18 F-FDG-avid lesions from the thorax to the upper abdomen were analyzed on the non-DDG and DDG PET images. The lesions were segmented with a 40% threshold of the maximum standardized uptake. A total of 725 radiomic features were computed from the segmented lesions, including first-order, shape, texture, and wavelet features. The intraclass correlation coefficient (ICC) and coefficient of variation (COV) were calculated to evaluate feature stability. An ICC above 0.9 and a COV below 5% were considered high stability., Results: In total, 168 lesions with and without respiratory motion correction were analyzed. Our results indicated that most 18 F-FDG PET radiomic features are sensitive to respiratory motion. Overall, only 27 out of 725 (3.72%) radiomic features were identified as highly stable, including one from the first-order features (entropy), one from the shape features (sphericity), four from the gray-level co-occurrence matrix features (normalized and unnormalized inverse difference moment, joint entropy, and sum entropy), one from the gray-level run-length matrix features (run entropy), and 20 from the wavelet filter-based features., Conclusion: Respiratory motion has a significant impact on 18 F-FDG PET radiomics stability. The highly stable features identified in our study may serve as potential candidates for further applications, such as machine learning modeling., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Objective: The performance of 18 F-FDG PET-based radiomics and deep learning in detecting pathological regional nodal metastasis (pN+) in resectable lung adenocarcinoma varies, and their use across different generations of PET machines has not been thoroughly investigated. We compared handcrafted radiomics and deep learning using different PET scanners to predict pN+ in resectable lung adenocarcinoma., Methods: We retrospectively analyzed pretreatment 18 F-FDG PET from 148 lung adenocarcinoma patients who underwent curative surgery. Patients were separated into analog (n = 131) and digital (n = 17) PET cohorts. Handcrafted radiomics and a ResNet-50 deep-learning model of the primary tumor were used to predict pN+ status. Models were trained in the analog PET cohort, and the digital PET cohort was used for cross-scanner validation., Results: In the analog PET cohort, entropy, a handcrafted radiomics, independently predicted pN+. However, the areas under the receiver-operating-characteristic curves (AUCs) and accuracy for entropy were only 0.676 and 62.6%, respectively. The ResNet-50 model demonstrated a better AUC and accuracy of 0.929 and 94.7%, respectively. In the digital PET validation cohort, the ResNet-50 model also demonstrated better AUC (0.871 versus 0.697) and accuracy (88.2% versus 64.7%) than entropy. The ResNet-50 model achieved comparable specificity to visual interpretation but with superior sensitivity (83.3% versus 66.7%) in the digital PET cohort., Conclusion: Applying deep learning across different generations of PET scanners may be feasible and better predict pN+ than handcrafted radiomics. Deep learning may complement visual interpretation and facilitate tailored therapeutic strategies for resectable lung adenocarcinoma., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Kimura disease (KD) is a rare chronic inflammatory disorder involving the Th2 pathway. Although medical treatment with steroids or other immunosuppressants is available, they may cause developmental issues in the pediatric population. Surgical intervention has also been suggested; however, it is associated with high recurrence rates., Case Presentation: A 14-year-old boy presented with left retroauricular lymph node enlargement at the age of 5 years. At the age of 7 years, he was diagnosed with nephrotic syndrome which subsided after steroid treatment for approximately 6 years. The retroauricular lymph node was surgically excised, and KD was confirmed. However, recurrent enlargement of the left retroauricular and neck lymph nodes occurred after 2 years. Persistently high IgE levels and fluctuating eosinophil counts were observed following steroid treatment. Dupilumab was prescribed because of the difficulty in tapering the steroid dosage. A loading dose of 600 mg was administered, followed by a maintenance dose of 300 mg every 2 weeks. The IgE level decreased after 3 months, and a low eosinophil count was maintained after steroid discontinuation. Follow-up computed tomography revealed a decrease in the size of the lymph nodes with no side effects such as conjunctivitis., Conclusion: Traditional treatments have raised developmental concerns in the pediatric population and are associated with high recurrence rates. Dupilumab targets the Th2 pathway and provides effective results, with few adverse effects. Dupilumab may be a therapeutic option for KD and other diseases involving the Th2 pathway., (© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Background/aim: Postoperative adverse events are associated with poor clinical outcomes and survival in patients with non-small-cell lung cancer (NSCLC) treated with curative operation. However, comprehensive evaluation of the clinical characteristics associated with postoperative adverse events and survival outcomes is lacking., Patients and Methods: A retrospective study that evaluated patients with NSCLC who underwent curative surgery between 2008 and 2019 was conducted in a medical center. The baseline characteristics, five-item modified frailty index, sarcopenia, inflammatory biomarkers, surgical approach, postoperative adverse events, and survival were statistically analyzed., Results: Patients with a history of smoking and preoperative sarcopenia were at a higher risk of developing postoperative pulmonary complications. Smoking, frailty, and traditional open thoracotomy (OT) were associated with infections, and sarcopenia was identified as a risk factor for major complications. Advanced tumor stage, high neutrophil-to-lymphocyte ratio, OT, major complications, and infections were identified as risk factors for overall and disease-free survival., Conclusion: Pre-treatment sarcopenia was found to be a predictor of major complications. Infections and major complications were associated with survival outcomes in patients with NSCLC., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The association between air pollution, allergic rhinitis (AR), and obesity has not been studied. From 2007 to 2011, 52 obese and 152 non-obese children (7-17 years old) with AR were recruited. Pediatric-Rhinoconjunctivitis-Quality-of-Life Questionnaire (PRQLQ) and nasal peak expiratory flow (NPEF) were tested. Association between the scores and rates of the two tests and mean air pollutant concentrations within 7 days before the tests were compared. When exposed to higher concentrations of CO, PM 10 , and PM 2.5 , the rates of worse nasal discomfort were 39.4%, 44.4% and 39.3% in obese children; and 18.0%, 21.9% and 19.7% in non-obese children, respectively. Compare to non-obese children, the rates in obese children were higher for CO (odds ratio (OR) 3.54, 95% confidence interval (CI) 1.15 ~ 10.92); PM 10 (OR 3.26, 95% CI 1.01 ~ 10.57) and PM2.5 (OR 3.30; 95% CI 1.03 ~ 10.54). In obese children, correlations between higher concentrations of CO, PM 10 , PM 2.5 and higher nasal discomfort (higher PRQLQ); and correlations between higher concentrations of CO, PM 10 , PM 2.5 , NMHC (non-methane hydrocarbon) and higher nasal mucosa inflammation (lower NPEF) were noted. Obesity negatively affected AR severity when AR children experienced higher concentrations of CO, PM 10 , and PM 2.5 . Increased nasal inflammation induced by air pollutants might be the underlying mechanism., (© 2023. The Author(s).)

Background/aim: Infection is a common cause of morbidity and mortality in patients treated for diffuse large B-cell lymphoma (DLBCL). However, there is limited information on the impact and risk factors for infection among patients receiving rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone (R-CHOP)., Patients and Methods: A retrospective study evaluating patients with DLBCL receiving R-CHOP and R-COP between 2004 and 2021 was conducted at a medical center. Hospital patients' records for the five-item modified frailty index (mFI-5), sarcopenia, blood-based inflammatory markers, and clinical outcomes were statistically analyzed., Results: Patients with frailty, sarcopenia, and high neutrophil-to-lymphocyte ratio (NLR) were associated with a higher risk of infections. The revised International Prognostic Index poor-risk group, high NLR, infections, and treatment modality were risk factors for shorter progression-free and overall survival., Conclusion: Pre-treatment high NLR was a predictor of infection and survival outcome in DLBCL patients., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Radiogenomic heterogeneity features in 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET) have become popular in non-small cell lung cancer (NSCLC) research. However, the reliabilities of genomic heterogeneity features and of PET-based glycolytic features in different image matrix sizes have yet to be thoroughly tested. We conducted a prospective study with 46 NSCLC patients to assess the intra-class correlation coefficient (ICC) of different genomic heterogeneity features. We also tested the ICC of PET-based heterogeneity features from different image matrix sizes. The association of radiogenomic features with clinical data was also examined. The entropy-based genomic heterogeneity feature (ICC = 0.736) is more reliable than the median-based feature (ICC = -0.416). The PET-based glycolytic entropy was insensitive to image matrix size change (ICC = 0.958) and remained reliable in tumors with a metabolic volume of <10 mL (ICC = 0.894). The glycolytic entropy is also significantly associated with advanced cancer stages ( p = 0.011). We conclude that the entropy-based radiogenomic features are reliable and may serve as ideal biomarkers for research and further clinical use for NSCLC.

Objective: We investigated whether glycolytic heterogeneity correlated with histopathology, and further stratified the survival outcomes pertaining to resectable lung adenocarcinoma., Methods: We retrospectively analyzed the 18 F-fluorodeoxyglucose positron emission tomography-derived entropy and histopathology from 128 patients who had undergone curative surgery for lung adenocarcinoma. Disease-free survival (DFS) and overall survival (OS) were analyzed using univariate and multivariate Cox regression models. Independent predictors were used to construct survival prediction models., Results: Entropy significantly correlated with histopathology, including tumor grades, lympho-vascular invasion, and visceral pleural invasion. Furthermore, entropy was an independent predictor of unfavorable DFS (p = 0.031) and OS (p = 0.004), while pathological nodal metastasis independently predicted DFS (p = 0.009). Our entropy-based models outperformed the traditional staging system (c-index = 0.694 versus 0.636, p = 0.010 for DFS; c-index = 0.704 versus 0.630, p = 0.233 for OS). The models provided further survival stratification in subgroups comprising different tumor grades (DFS: HR = 2.065, 1.315, and 1.408 for grade 1-3, p = 0.004, 0.001, and 0.039, respectively; OS: HR = 25.557, 6.484, and 2.570, for grade 1-3, p = 0.006, < 0.001, and = 0.224, respectively)., Conclusion: The glycolytic heterogeneity portrayed by entropy is associated with aggressive histopathological characteristics. The proposed entropy-based models may provide more sophisticated survival stratification in addition to histopathology and may enable personalized treatment strategies for resectable lung cancer., (© 2022. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Objective: To investigate whether combining primary tumor and metastatic nodal glycolytic heterogeneity on 18 F-fluorodeoxyglucose PET ( 18 F-FDG PET) improves prognostic prediction in nonsmall cell lung cancer (NSCLC) with locoregional disease., Methods: We retrospectively analyzed 18 F-FDG PET-derived features from 94 patients who had undergone curative treatments for regional nodal metastatic NSCLC. Overall survival (OS) and progression-free survival (PFS) were analyzed using univariate and multivariate Cox regression models. We used the independent prognosticators to construct models to predict survival., Results: Combined entropy (entropy derived from the combination of the primary tumor and metastatic nodes) and age independently predicted OS (both P = 0.008) and PFS ( P = 0.007 and 0.050, respectively). At the same time, the Eastern Cooperative Oncology Group status was another independent risk factor for unfavorable OS ( P = 0.026). Our combined entropy-based models outperformed the traditional staging system (c-index = 0.725 vs. 0.540, P < 0.001 for OS; c-index = 0.638 vs. 0.511, P = 0.003 for PFS) and still showed prognostic value in subgroups according to sex, histopathology, and different initial curative treatment strategies., Conclusion: Combined primary tumor-nodal glycolytic heterogeneity independently predicted survival outcomes. In combination with clinical risk factors, our models provide better survival predictions and may enable tailored treatment strategies for NSCLC with locoregional disease., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The total metabolic tumor volume (TMTV) measured from fluorine-18 fluorodeoxyglucose (18F-FDG) PET can be useful for determining the prognosis of patients with lymphoma. Stratifying patients into high- and low-TMTV risk groups requires a cutoff point, which is determined through the dichotomization method. This study investigated whether different TMTV dichotomization methods influenced survival prediction in patients with lymphoma., Methods: We retrospectively enrolled 129 patients with lymphoma who had undergone baseline 18F-FDG PET. TMTV was calculated using a fixed standardized uptake value threshold of 4.0. A total of six methods were employed to determine the optimal TMTV cutoff point using receiver-operating characteristic curve analyses, X-Tile bioinformatics software, and the Cutoff Finder web application. The prognostic performance of each method in survival prediction was examined., Results: The median (interquartile range) TMTV was 123 cm3 (21-335 cm3). The optimal TMTV cutoff values for predicting progression-free survival (PFS) and overall survival (OS) were in the range of 144-748 cm3. The cutoff points were used to dichotomize patients into two groups with distinct prognoses. All TMTV dichotomizations were significantly predictive of PFS and OS. The survival curves showed significant differences between the high- and low-TMTV groups. The C-indices of the survival models did not significantly differ in any of the dichotomizations., Conclusion: The prognostic significance of TMTV was maintained regardless of the methodological aspects of dichotomization. However, the optimal TMTV cutoff point varied according to the chosen dichotomization method. Care should be taken when establishing an optimal TMTV cutoff point for clinical use., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest.

Background: Asthma is a complex multifactorial chronic airway inflammatory disease with diverse phenotypes and levels of severity and is associated with significant health and economic burden. In a certain population of asthma patients, the symptoms cannot be well controlled with steroid. There has been long standing interest in the use of probiotics for treating allergic diseases. The purpose of this study is to investigate whether the combination of Lactobacillus rhamnosus GG (LGG) with prednisolone could reduce the dosage of glucocorticoid in controlling airway inflammation in a murine model for allergic asthma., Material and Methods: We used Der p 2-sensitized asthma model in female BALB/c mice. The animals were treated with 75 μl or 50 μl oral prednisolone or combination treatment of these two doses of oral prednisolone with LGG. Airway hyperresponsiveness, serum specific IgE/IgG1/IgG2a, infiltrating inflammatory cells in lung and cytokines were assessed., Results: Compared to 75 μl prednisolone, a lower dose of prednisolone with 50 μl was less satisfactory in suppressing airway hyperresponsives, serum IgE and IgG1, Th2 cytokines and inflammatory cytokines such as IL-6, IL-8 and IL-17 as well as infiltrating inflammatory cells. However, combination of 50 μl prednisolone and LGG decreased airway resistance and serum IgE and IgG1, inhibited the production of IL-4, IL-5, IL-6, IL-8, IL-13 and IL-17, upregulated serum IgG2a and enhanced Th1 immune response., Conclusions: LGG may reduce the dosage of prednisolone and thus may be beneficial in the treatment of asthma., Competing Interests: Declaration of competing interest The study had no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

House dust mites (HDMs) are one of the most important allergy-causing agents of asthma. In central Taiwan, the prevalence of sensitization to Dermatophagoides microceras ( Der m ), a particular mite species of HDMs, is approximately 80% and is related to the IgE crossing reactivity of Dermatophagoides pteronyssinus ( Der p ) and Dermatophagoides farinae ( Der f ). Integrated OMICs examination was used to identify and characterize the specific group 1 mite-allergic component ( Der m 1 ). De novo draft genomic assembly and comparative genome analysis predicted that the full-length Der m 1 allergen gene is 321 amino acids in silico. Proteomics verified this result, and its recombinant protein production implicated the cysteine protease and α chain of fibrinogen proteolytic activity. In the sensitized mice, pathophysiological features and increased neutrophils accumulation were evident in the lung tissues and BALF with the combination of Der m 1 and 2 inhalation, respectively. Principal component analysis (PCA) of mice cytokines revealed that the cytokine profiles of the allergen-sensitized mice model with combined Der m 1 and 2 were similar to those with Der m 2 alone but differed from those with Der m 1 alone. Regarding the possible sensitizing roles of Der m 1 in the cells, the fibrinogen cleavage products (FCPs) derived from combined Der m 1 and Der m 2 induced the expression of pro-inflammatory cytokines IL-6 and IL-8 in human bronchial epithelium cells. Der m 1 biologically functions as a cysteine protease and contributes to the α chain of fibrinogen digestion in vitro. The combination of Der m 1 and 2 could induce similar cytokines expression patterns to Der m 2 in mice, and the FCPs derived from Der m 1 has a synergistic effect with Der m 2 to induce the expression of pro-inflammatory cytokines in human bronchial epithelium cells.

Objective: The diagnostic performance of 18 F-FDG PET for detecting regional lymph node metastasis in resectable lung cancer is variable, and its sensitivity for adenocarcinoma is even lower. We aimed to evaluate the value of 18 F-FDG PET-derived features in predicting pathological lymph node metastasis in patients with lung adenocarcinoma., Methods: We retrospectively analyzed pretreatment 18 F-FDG PET-derived features of 126 lung adenocarcinoma patients who underwent curative surgery. A logistic regression model was used to analyze the association between study variables and pathological regional lymph node status obtained from the curative surgery. Furthermore, Cox regression analysis was used to test the effect of the study variables on survival outcomes, including disease-free survival (DFS) and overall survival (OS)., Results: The primary tumor entropy (OR = 1.7, p = 0.014) and visual interpretation of regional nodes via 18 F-FDG PET (OR = 2.5, p = 0.026) independently predicted pathological regional lymph node metastasis. The areas under the receiver-operating-characteristic curves were 0.631, 0.671, and 0.711 for visual interpretation, primary tumor entropy, and their combination, respectively. Based on visual interpretation, a primary tumor entropy ≥ 3.0 improved the positive predictive value of positive visual interpretation from 51.2% to 63.0%, whereas an entropy < 3.0 improved the negative predictive value of negative visual interpretation from 75.3% to 82.6%. In cases with positive visual interpretation and low entropy, or negative visual interpretation and high entropy, the nodal metastasis rates were approximately 30%. In the survival analyses, the primary tumor entropy was also independently associated with DFS (HR = 2.7, p = 0.001) and OS (HR = 4.8, p = 0.001)., Conclusions: Our preliminary results show that the primary tumor entropy may improve 18 F-FDG PET visual interpretation in predicting pathological nodal metastasis in lung adenocarcinoma, and may also show a survival prognostic value. This versatile biomarker may facilitate tailored therapeutic strategies for patients with resectable lung adenocarcinoma., (© 2021. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Sarcopenia negatively affects oncologic outcomes. However, studies have yet to reveal whether it is associated with postoperative complications and survival among patients with oral cavity squamous cell carcinoma (OSCC). This study retrospectively enrolled 592 patients undergoing primary OSCC surgery with available computed tomography (CT) images of their third cervical vertebrae (C3) within 30 days before surgery between January 2011 and December 2020. Preoperative sarcopenia, nutritional and frailty status, tumor characteristics, comorbidities, and inflammatory markers were assessed. The outcome variables included 30-day complications based on the Buzby and Dindo classification, reoperation, 5- and 8-year overall survival, and disease-free survival. A total of 318 (53.7%) had sarcopenia; of these patients, 217 (68.2%) presented with postoperative complications, and 48 (15.1%) underwent reoperations. Sarcopenia and higher systemic immune-inflammatory index were independently associated with local to systemic 30-day complications. Sarcopenia, advanced-stage disease, and extracapsular spread were correlated with 5- and 8-year survival. The presence of sarcopenia is associated with the 30-day complications and short- and long-term survival of patients who had OSCC and underwent surgery.

Background: Allergic asthma, a chronic airway inflammatory disease, is a critical public health problem. Indoor house dust mites (HDMs) could cause allergic asthma. The prevalence of sensitization to Dermatophagoides microceras ( Der m ) was approximately 80% and is related to the immunoglobulin E crossing-reactivity of mites belonging to the same genus, Dermatophagoides pteronyssinus ( Der p ) and Dermatophagoides farina ( Der f ). However, studies on Der m are scant., Methods: We used integrated OMICs approaches to identify and characterize the group 2 mite allergen-like protein in Der m ( Der m 2 ). We established a Der m 2 -induced allergic asthma mouse model and treated the mice with a fungal immunomodulatory protein (FIP- fve ) isolated from Flammulina veluptipes to evaluate the allergenicity of Der m 2 and the immunomodulatory effects of FIP- fve ., Results: By performing de novo draft genome assembly and comparative genome analysis, we identified the putative 144-amino acid Der m 2 in silico and further confirmed its existence through liquid chromatography-tandem mass spectrometry. Der m 2 is a lipopolysaccharides (LPS)-binding protein. Thus, we examined the LPS-binding activity of recombinant Der m 2 by performing molecular docking analysis, co-immunoprecipitation (Co-IP), and a pull-down assay. Der m 2 elicited the production of pro-inflammatory cytokines, interleukin (IL)-6, and IL-8 in BEAS-2B cells, a human bronchial epithelial cell line, and induced airway hyperresponsiveness in mice. Furthermore, in mice sensitized with Der m 2 , the administration of FIP- fve in either the earlier stage or the late stage, FIP- fve alleviated allergic asthma by moderating airway inflammation and remodeling., Conclusions: Der m 2 induced inflammatory responses in cell and mouse models. FIP- fve alleviated inflammation in Der m 2 -induced asthma in mice by exerting an immunomodulatory effect., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hu, Wu, Wu, Yu, Ko, Lue and Liu.)

Tyrosine kinase inhibitors (TKIs) are the first-line treatment for patients with advanced epidermal growth factor receptor ( EGFR )-mutated lung adenocarcinoma. Over half of patients failed to achieve prolonged survival benefits from TKI therapy. Awareness of a reliable prognostic tool may provide a valuable direction for tailoring individual treatments. We explored the prognostic power of the combination of systemic inflammation markers and tumor glycolytic heterogeneity to stratify patients in this clinical setting. One hundred and five patients with advanced EGFR -mutated lung adenocarcinoma treated with TKIs were retrospectively analyzed. Hematological variables as inflammation-induced biomarkers were collected, including the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation index (SII). First-order entropy, as a marker of heterogeneity within the primary lung tumor, was obtained by analyzing 18 F-fluorodeoxyglucose positron emission tomography images. In a univariate Cox regression analysis, sex, smoking status, NLR, LMR, PLR, SII, and entropy were associated with progression-free survival (PFS) and overall survival (OS). After adjusting for confounders in the multivariate analysis, smoking status, SII, and entropy, remained independent prognostic factors for PFS and OS. Integrating SII and entropy with smoking status represented a valuable prognostic scoring tool for improving the risk stratification of patients. The integrative model achieved a Harrell's C-index of 0.687 and 0.721 in predicting PFS and OS, respectively, outperforming the traditional TNM staging system (0.527 for PFS and 0.539 for OS, both p < 0.001). This risk-scoring model may be clinically helpful in tailoring treatment strategies for patients with advanced EGFR -mutated lung adenocarcinoma.

This study aims to analyze whether bronchiolitis in children younger than one-year-old contributes to subsequent asthma. Medical data were retrieved from the National Health Insurance Research Database of Taiwan. Participants were divided into study (N = 65,559) and control (N = 49,656) groups, depending on whether they had early bronchiolitis. Incidences of asthma, potential comorbidities, and associated medical conditions were compared. The incidence of childhood asthma was significantly higher in the study group (aHR = 1.127, 95% CI: 1.063-1.195). Children with bronchiolitis hospitalization displayed higher asthma risk in the period between two and four years of age. The risk diminished as the children grew up. No relevant synergistic effects were found between bronchiolitis and atopic dermatitis. In conclusion, bronchiolitis before one year of age exhibits predictive value for development of preschool asthma, especially in children with bronchiolitis hospitalizations.

In this study, we aimed to evaluate the prognostic impact of sarcopenia, five-item modified frailty index (mFI-5), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR) in patients with oral cavity squamous cell carcinoma (OSCC) treated with adjuvant chemoradiotherapy (CRT) and their survival outcomes. We retrospectively enrolled 175 patients with OSCC undergoing adjuvant CRT between 2011 and 2018, who were divided into groups with ( n = 112) and without ( n = 63) sarcopenia. Logistic regression analysis and Cox proportional hazards models were used to determine prognostic factors for CRT-related toxicity, three-year overall survival (OS), and disease-free survival (DFS). Sarcopenia and high PLR were independently associated with CRT-induced anemia (CIA); advanced tumor stage was related to poor three-year OS. CRT and survival did not differ by mFI-5 and NLR. Our results indicate that sarcopenia and high PLR are significant predictors of adjuvant CRT, increasing toxicity outcomes and indicating worse short-term OS. Accurately identifying sarcopenia and high PLR in patients with OSCC is critical to help better select candidates for adjuvant CRT to improve their outcomes.

Troponin I is a biomarker for cardiac injury in children. The role of troponin I in neonatal Hypoxic-Ischemic encephalopathy (HIE) may have valuable clinical implications. Troponin I levels were measured within 6 h of birth to determine their relationship to HIE stage, short-term cardiac functional outcomes, and neurodevelopmental outcomes at 1 year. Seventy-three patients were divided into two groups: mild HIE and moderate to severe HIE. Troponin I levels within 6 h of birth were obtained in 61 patients, and were significantly higher in patients with moderate to severe HIE than in patients with mild HIE (Mann-Whitney U test, U = 146, p = 0.001). A troponin I cut-off level of ≥60 pg/mL predicted moderate to severe HIE with a specificity of 81.1% and a negative prediction rate of 76.9%. A troponin I cut-off level of ≥180 pg/mL was significantly (χ 2 (1, n = 61) = 33.1, p = 0.001, odds ratio 96.8) related with hypotension during first admission and significantly (χ 2 (1, n = 61) = 5.3, p = 0.021, odds ratio 4.53) related with abnormal neurodevelopmental outcomes at 1 year. Early troponin I level may be a useful biomarker for predicting moderate to severe HIE, and initialization of hypothermia therapy.

We investigated whether the combination of primary tumor and nodal 18 F-FDG PET parameters predict survival outcomes in patients with nodal metastatic non-small cell lung cancer (NSCLC) without distant metastasis. We retrospectively extracted pre-treatment 18 F-FDG PET parameters from 89 nodal-positive NSCLC patients (stage IIB-IIIC). The Cox proportional hazard model was used to identify independent prognosticators of overall survival (OS) and progression-free survival (PFS). We devised survival stratification models based on the independent prognosticators and compared the model to the American Joint Committee on Cancer (AJCC) staging system using Harrell's concordance index (c-index). Our results demonstrated that total TLG (the combination of primary tumor and nodal total lesion glycolysis) and age were independent risk factors for unfavorable OS ( p < 0.001 and p = 0.001) and PFS (both p < 0.001), while the Eastern Cooperative Oncology Group scale independently predicted poor OS ( p = 0.022). Our models based on the independent prognosticators outperformed the AJCC staging system (c-index = 0.732 versus 0.544 for OS and c-index = 0.672 versus 0.521 for PFS, both p < 0.001). Our results indicate that incorporating total TLG with clinical factors may refine risk stratification in nodal metastatic NSCLC patients and may facilitate tailored therapeutic strategies in this patient group.

Background: Asthma animal models provide valuable information about the pathogenesis and the treatment of asthma. An ovalbumin (OVA)/complete Freund's adjuvant (CFA)-sensitized model was developed to induce neutrophil-dominant asthma and to investigate whether fungal immunomodulatory peptide-fve (FIP-fve) could improve asthma features in the OVA/CFA-sensitized model., Methods: We used female BALB/c mice and sensitized them intraperitoneally with OVA/CFA on days 1, 2, and 3. On days 14, 17, 21, 24, and 27, they were challenged with intranasal OVA. The airway hyper-responsiveness (AHR) was detected by BUXCO, inflammatory cells were stained with Liu's stain, the cytokines were detected using ELISA, and the airway inflammation was analyzed with hematoxylin and eosin stain., Results: According to the results, OVA/CFA sensitization could induce AHR, high levels of IgE, and inflammatory cells especially neutrophils infiltration in the lung and airway inflammation. IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-17, IL-25, IL-33, and transforming growth factor-β (TGF-β) increased in the OVA/CFA-sensitized mice. OVA/CFA-sensitized mice treated with FIP-fve not only increased IL-12 and IFN-γ but also decreased IL-4, IL-5, IL-6, IL-8, IL-13, IL-17, IL-25, IL-33, and TGF-β in the bronchoalveolar lavage fluid. Moreover, FIP-fve significantly decreased neutrophil infiltration in the lung., Conclusion: The OVA/CFA model induced neutrophilic asthma successfully, and FIP-fve improved neutrophil-dominant asthma., (© 2021 S. Karger AG, Basel.)

This study investigates whether baseline 18 F-FDG PET radiomic features can predict survival outcomes in patients with diffuse large B-cell lymphoma (DLBCL). We retrospectively enrolled 83 patients diagnosed with DLBCL who underwent 18 F-FDG PET scans before treatment. The patients were divided into the training cohort ( n = 58) and the validation cohort ( n = 25). Eighty radiomic features were extracted from the PET images for each patient. Least absolute shrinkage and selection operator regression were used to reduce the dimensionality within radiomic features. Cox proportional hazards model was used to determine the prognostic factors for progression-free survival (PFS) and overall survival (OS). A prognostic stratification model was built in the training cohort and validated in the validation cohort using Kaplan-Meier survival analysis. In the training cohort, run length non-uniformity (RLN), extracted from a gray level run length matrix (GLRLM), was independently associated with PFS (hazard ratio (HR) = 15.7, p = 0.007) and OS (HR = 8.64, p = 0.040). The International Prognostic Index was an independent prognostic factor for OS (HR = 2.63, p = 0.049). A prognostic stratification model was devised based on both risk factors, which allowed identification of three risk groups for PFS and OS in the training ( p < 0.001 and p < 0.001) and validation ( p < 0.001 and p = 0.020) cohorts. Our results indicate that the baseline 18 F-FDG PET radiomic feature, RLN GLRLM , is an independent prognostic factor for survival outcomes. Furthermore, we propose a prognostic stratification model that may enable tailored therapeutic strategies for patients with DLBCL.

Background: To investigate the survival prognostic value of the radiomic features of 18F-FDG PET in patients who had EGFR (epidermal growth factor receptor) mutated lung adenocarcinoma and received targeted TKI (tyrosine kinase inhibitor) treatment., Methods: Fifty-one patients with stage III-IV lung adenocarcinoma and actionable EGFR mutation who received first-line TKI were retrospectively analyzed. All patients underwent pretreatment 18F-FDG PET/CT, and we calculated the PET-derived radiomic features. Cox proportional hazard model was used to examine the association between the radiomic features and the survival outcomes, including progression-free survival (PFS) and overall survival (OS). A score model was established according to the independent prognostic predictors and we compared this model to the TNM staging system using Harrell's concordance index (c-index)., Results: Forty-eight patients (94.1%) experienced disease progression and 41 patients (80.4%) died. Primary tumor SUV entropy > 5.36, and presence of pleural effusion were independently associated with worse OS (both p < 0.001) and PFS (p = 0.001, and 0.003, respectively). We used these two survival predictors to devise a scoring system (score 0-2). Patients with a score of 1 or 2 had a worse survival than those with a score of 0 (HR for OS: 3.6, p = 0.006 for score 1, and HR: 21.8, p < 0.001 for score 2; HR for PFS: 2.2, p = 0.027 for score 1 and HR: 8.8, p < 0.001 for score 2). Our scoring system surpassed the TNM staging system (c-index = 0.691 versus 0.574, p = 0.013 for OS, and c-index = 0.649 versus 0.517, p = 0.004 for PFS)., Conclusions: In this preliminary study, combining PET radiomics with clinical risk factors may improve survival stratification in stage III-IV lung adenocarcinoma with actionable EFGR mutation. Our proposed scoring system may assist with optimization of individualized treatment strategies in these patients., Competing Interests: The authors have declared that no competing interests exist.

Background: Taiwan's colleges and universities are struggling to maintain their student enrollment rates owing to the declining fertility rate. Focusing on students in higher education programs, this study aims to analyze online behavioral patterns for university departmental websites and accordingly, suggests response strategies to increase the rate of enrollment., Methods: We use Google Analytics to examine the websites of two departments in a medical university between February 1 and July 30, 2018. We study website patterns during the study periods for three college admission routes: STARS program, personal applications, and admission through examination and placement., Results: Most website visitors during the three visiting date ranges for the two departments are 18-24 years. The visitor groups are mainly freshmen at the university and their parents. The homepage and Subject Credits, Course Planning, Teacher Lineup, and Certificate of Subjects were the most visited webpages. The overall number of daily page views varied by academic event., Conclusions: University departments should enhance the presentation of featured courses on their webpage or distinguish course characteristics from those of competing departments in the curriculum to ensure clear market segmentation. In addition, departments should consider examining online data to identify suitable high schools that can be visited to attract potential students and to improve students' willingness to choose their university.

Background: Asthma is a consequence of complex gene-environment interactions. Exploring the heterogeneity of asthma in different stages is contributing to our understanding of its pathogenesis and the development of new therapeutic strategies, especially in severe cases., Objective: This study aimed to further understand the relationship between manifestations of acute and chronic asthma and various endotypes, and explore the severity of lung inflammation, cell types, cytokine/chemokine differences, and the effects of FIP-fve., Materials and Methods: Acute and chronic OVA-sensitization mouse asthma models, based on our previously published method, were used and FIP-fve was used to evaluate the effect on these two models. BALF cytokines/chemokines were detected according to the manufacturer's protocol., Results: Seventeen cytokine/chemokine secretions were higher in the chronic stage than in the acute stage. Whether in acute stage or chronic stage, the FIP-fve treatment groups had reduced airway hyperresponsiveness, infiltration of airway inflammatory cells, secretion of cytokines, chemokines by Th2 cells, and TNF-α, IL-8, IL-17, CXCL-1, CXCL-10, CCL-17, and CCL-22, and it was also found that the Treg cell cytokine IL-10 had increased significantly. PCA (Principal Component Analysis) was also used to compare statistics and laboratory data to find the important biomarkers in different stages and after treatment with FIP-fve., Conclusions: There are many different immune responses in the different stages of the asthma process. Drug treatment at the appropriate times might help reduce the worsening of asthma., (Copyright © 2020. Published by Elsevier B.V.)

Objective: Noting that the usefulness of cases diagnosed in administrative registers is dependent on diagnostic validity, in this study, we aim to elucidate the correlation between Tourette syndrome and allergy in children and adolescents, specifically with regard to incidence of asthma, allergic rhinitis, allergic conjunctivitis, and atopic dermatitis., Methods: Based on a set of inclusion and exclusion criteria, we intend to enroll 200 children and adolescents aged 18 years and younger, accompanied by their parents, for a duration of 2 years. We will administer an anonymous questionnaire in a case-control study. We will use the chi-squared test to evaluate differences between cases and controls., Results: According to the European Review for Medical and Pharmacological Sciences, the proportion of allergic diseases expected in patients with Tourette syndrome is 53.1% (17/32) and 22.9% (8/35) in the controls. Setting the type 1 error to 0.05 and the power to 0.8, we will ensure a 1:2 case-to-control ratio., Conclusions: This study protocol describes our analysis of anonymous questionnaire responses. Comorbidity rates, environmental factors, and genetic factors for various allergens, allergies, and other neuropsychiatric disorders will be studied.

Background: Sensitization to allergen has long been known to be relate to childhood allergic diseases. Polysensitised children have more severe atopic diseases, whereas allergic rhinitis or asthma children with cosensitized to food and inhalant allergens were under-researched., Objective: To realize the association between sensitization to food allergens and pediatric allergic rhinitis and asthma in Taiwan., Methods: We included 138 participants with sensitized to allergen as assessed by serum-specific IgE. 87 of 138 participants had allergic rhinitis and 51 participants had asthma. All participants underwent a physical examination and measurement of serum total and specific IgE values. Besides, nasal peak expiratory flow rate (nPEFR) that was performed by the participants with allergic rhinitis and were requested to complete the Pediatric Rhinoconjunctivitis Quality of Life Questionnaires (PRQLQ). Lung function test and asthma control test (ACT)/child asthma control test (C-ACT) were performed by the participants with asthma., Results: 39 of 87 allergic rhinitis participants with sensitized to food and inhalant allergens (AR food group), 48 of 87 allergic rhinitis participants with sensitized to inhalant allergen alone (AR inhalant group). The AR food group had significantly lower nPEFR values and higher total IgE values (p < 0.05) compared with the AR inhalant group. The AR food group had higher PRQLQ scores than the AR inhalant group. 24 of 51 asthma participants with sensitized to food and inhalant allergens (Asthma food group), 27 of 51 asthma participants with sensitized to inhalant allergen alone (Asthma inhalant group). The Asthma food group had significantly higher total IgE values (p < 0.05) compared with the Asthma inhalant group. The Asthma food group had lower lung function test values and asthma control test (ACT) scores than the other group., Conclusions: Children with cosensitized to food and inhalant allergens have more severe clinical symptoms and abnormal laboratory findings. Sensitization to food allergen was more related to pediatric allergic rhinitis than asthma. We may need larger, longer and extended studies to confirm these findings., (Copyright © 2019. Published by Elsevier B.V.)

Objectives: Currently, neck ultrasound is the preferred preoperative imaging in patients with secondary/tertiary hyperparathyroidism, and the use of Tc-99m sestamibi scan is limited in these patients. We conducted this study to compare the diagnostic utilities of F-18 fluorocholine PET/CT, Tc-99m sestamibi scintigraphy, and neck ultrasound for localizing hyperfunctioning parathyroid glands in secondary/tertiary hyperparathyroidism., Methods: We prospectively enrolled 30 dialysis patients with a diagnosis of secondary/tertiary hyperparathyroidism; of these, 27 participants underwent all three imaging modalities, including dual-phase F-18 fluorocholine PET/CT (PET acquired 5 and 60 min after tracer injection), dual-phase Tc-99 m sestamibi SPECT/CT, and neck ultrasound. All patients underwent parathyroidectomy after imaging. We compared the lesion-based sensitivity, specificity, and accuracy of the three image tools using histopathology as the reference., Results: A total of 27 patients (107 lesions) underwent all three imaging modalities and entered the final analysis. The lesion-based sensitivities of F-18 fluorocholine PET/CT, Tc-99m sestamibi, and ultrasound were 86%, 55%, and 62%, respectively (both p < 0.001, when comparing F-18 fluorocholine PET/CT to Tc-99 m sestamibi scan and to ultrasound). F-18 fluorocholine PET/CT, Tc-99m sestamibi, and ultrasound had similar specificities of 93%, 80%, and 87%, respectively. The accuracy of F-18 fluorocholine PET/CT (87%) was significantly higher than that of Tc-99m sestamibi (59%) and ultrasound (65%) (both p < 0.001). F-18 fluorocholine PET/CT identified more hyperplastic glands than ultrasound in 52% (14/27) patients. The sensitivity of F-18 fluorocholine PET/CT reached 95% for hyperplastic parathyroid masses as low as 200 mg., Conclusions: F-18 fluorocholine PET/CT shows superior accuracy over the conventional imaging modalities in patients with secondary or tertiary hyperparathyroidism. The combination of F-18 fluorocholine PET/CT and neck ultrasound may enable better surgical planning in these patients., Registration Identification Number: NCT04316845.

Rationale and Objectives: Radiomic analysis of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) images enables the extraction of quantitative information of intratumour heterogeneity. This study investigated whether the baseline 18 F-FDG PET/CT radiomics can predict treatment response and survival outcomes in patients with Hodgkin lymphoma (HL)., Materials and Methods: Thirty-five patients diagnosed with HL who underwent 18 F-FDG PET/CT scans before and during chemotherapy were retrospectively enrolled in this investigation. For each patient, we extracted 709 radiomic features from pretreatment PET/CT images. Clinical variables (age, gender, B symptoms, bulky tumor, and disease stage) and radiomic signatures (intensity, texture, and wavelet) were analyzed according to response to therapy, progression-free survival (PFS), and overall survival (OS). Receiver operating characteristic curve, logistic regression, and Cox proportional hazards model were used to examine potential predictive and prognostic factors., Results: High-intensity run emphasis (HIR) of PET and run-length nonuniformity (RLNU) of CT extracted from gray-level run-length matrix (GLRM) in high-frequency wavelets were independent predictive factors for the treatment response (odds ratio [OR] = 36.4, p = 0.014; OR = 30.4, p = 0.020). Intensity nonuniformity (INU) of PET and wavelet short run emphasis (SRE) of CT from GLRM and Ann Arbor stage were independently related to PFS (hazard ratio [HR] = 9.29, p = 0.023; HR = 18.40, p = 0.012; HR = 7.46, p = 0.049). Zone-size nonuniformity (ZSNU) of PET from gray-level size zone matrix (GLSZM) was independently associated with OS (HR = 41.02, p = 0.001). Based on these factors, a prognostic stratification model was devised for the risk stratification of patients. The proposed model allowed the identification of four risk groups for PFS and OS (p < 0.001 and p < 0.001)., Conclusion: HIR &#95; GLRM PET and RLNU &#95; GLRM CT in high-frequency wavelets serve as independent predictive factors for treatment response. ZSNU &#95; GLSZM PET , INU &#95; GLRM PET , and wavelet SRE &#95; GLRM CT serve as independent prognostic factors for survival outcomes. The present study proposes a prognostic stratification model that may be clinically beneficial in guiding risk-adapted treatment strategies for patients with HL., (Copyright © 2019 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Enterovirus-D68 (EV-D68) has been endemic in Taiwan for some years with a small number of positive cases. Detailed information about respiratory presentation is lacking. This study characterized the clinical course in children admitted to the medical center and regional hospital in Taichung during 2015., Methods: Retrospective chart review of patients with confirmed EV-D68 infection admitted to the medical center and regional hospital in Taichung with respiratory symptoms in the second half of 2015. Past medical history, clinical presentation, management, and course in hospital were collected and analyzed. Simple demographic data and clinical symptoms were also collected from patients confirmed with EV-D68 infection who visited clinics in Taichung., Results: Six children were included. Two patients had a prior history of asthma or recurrent dyspnea, and one had other preexisting medical comorbidities. One child was admitted to the pediatric intensive care unit. All the patients were cured. Cough, rhinorrhea, tachypnea and fever were the most common clinical symptoms among inpatients, while influenza-like illness (ILI) was prevalent in outpatients., Conclusion: EV-D68 infection resulted in respiratory presentations of asthma-like illness in the hospitalized pediatric population. Patients with a prior history of asthma or recurrent dyspnea appear to be more severely affected., (Copyright © 2019. Published by Elsevier B.V.)

Background/aim: This study aimed to evaluate the association of sarcopenia and Clinical Outcomes with esophageal cancer under neoadjuvant chemoradiotherapy (CRT)., Patients and Methods: A retrospective study assessing patients with esophageal cancer who underwent CRT between 2001 and 2014 was conducted in the medical center. Hospital patients' records on sarcopenia and treatment outcomes were statistically analyzed., Results: The sarcopenia group had significantly lower body mass index than the non-sarcopenia group. CRT-related severe adverse events with mucositis, fever, and neutropenic fever were greater in the sarcopenia group. Overall survival and disease-free survival were significantly better in the non-sarcopenia group. Sarcopenic patients who received nutritional support with enteral access had less severe mucositis. There was no difference in mortality of sarcopenia patients with nutritional support via enteral access or without. Moreover, sarcopenia and advanced tumor stage were independent factors for mortality outcome., Conclusion: Sarcopenia before CRT may be associated with increased toxicities and worse overall survival/ disease-free survival in esophageal cancer patients., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Asthma is a heterogeneous inflammatory disorder of the airway. A Th2 response usually contributes to high levels of allergen-specific IgE and eosinophilic airway inflammation. Several findings have demonstrated that neutrophils, not eosinophils, are the major inflammatory cells in chronic asthma patients with steroid-resistance. Lactobacillus rhammosus GG (LGG) exhibits anti-inflammatory properties on OVA-induced acute airway inflammation., Objective: We hypothesized that orally administrated LGG should reduce airway remodeling in chronic experimental models., Methods: Female Balb/c mice were sensitized with OVA. LGG was used to investigate whether oral administrations of LGG inhibited OVA-induced airway inflammation in a chronic asthma model and the different intervention times between LGG pre-treatment and post-treatment groups. BALF was analyzed with Liu's stain and ELISA assay. Lung histopathology was assayed with HE, IHC and Masson's trichrome staining. Lung tissues were assayed with PCR (T-bet, GATA3, RORrt and Foxp3). Many cytokines were detected in the serum and BALF., Results: LGG significantly decreased the number of infiltrating inflammatory cells. We also found that the oral LGG group suppressed not only Th2 cytokine, but also IL-17, TNF-α and HMGB1 in the BALF levels. However, GATA3 and RORrt decreased significantly in the RNA level in the LGG groups, but the T-bet and Foxp3 increased in the RNA level., Conclusions: LGG not only had anti-inflammatory effects on OVA-induced airway inflammation, but also improved airway remodeling and collagen expression in the chronic asthma mouse model. Moreover, LGG might be an additional or supplementary therapy for allergic airway diseases., (Copyright © 2019. Published by Elsevier B.V.)

Purpose: This study investigated whether a radiomic analysis of pretreatment F-FDG PET can predict prognosis in patients with Hodgkin lymphoma (HL)., Methods: Forty-two patients who were diagnosed as having HL and underwent pretreatment F-FDG PET scans were retrospectively enrolled. For each patient, we extracted 450 radiomic features from PET images. The prognostic significance of the clinical and radiomic features was assessed in relation to progression-free survival (PFS) and overall survival (OS). Receiver operating characteristic curve, Cox proportional hazards regression, and Kaplan-Meier analyses were performed to examine the potential independent predictors and to evaluate the predictive value., Results: Intensity nonuniformity extracted from a gray-level run-length matrix and the Ann Arbor stage were independently associated with PFS (hazard ratio [HR] = 22.8, P < 0.001; HR = 7.6, P = 0.024) and OS (HR = 14.5, P = 0.012; HR = 8.5, P = 0.048), respectively. In addition, SUV kurtosis was an independent prognosticator for PFS (HR = 6.6, P = 0.026). We devised a prognostic scoring system based on these 3 risk predictors. The proposed scoring system further improved the risk stratification of the current staging classification (P < 0.001)., Conclusions: The radiomic feature intensity nonuniformity is an independent prognostic predictor of PFS and OS in patients with HL. We devised a prognostic scoring system, which may be more beneficial for patient risk stratification in guiding therapy compared with the current Ann Arbor staging system.

Background: The association between asthma (AS), allergic rhinitis (AR) and oral diseases remains inconclusive in adults. AS and AR often coexist. However, studies that investigate AS, AR together and their association with oral diseases are scarce., Methods: Data from 22,898 men and 28,541 women, aged 21 to 25 years, were collected from a national database in Taiwan. Five common oral diseases: dental caries, periodontitis, pulpitis, gingivitis, and stomatitis/aphthae were studied. Differences in the incidence of the five oral diseases in AR vs. non-AR, and AS vs. non-AS groups were compared. The incidence of the five oral diseases in men/ women, urban/country citizen, and high/low income groups was studied. The frequencies of clinical visits and impact of topical steroid use between the groups were also studied. The confounding factors included sex, socioeconomic status, urbanization, dentofacial anomalies, disease of salivary flow, diabetes mellitus, and esophageal reflux., Results: The incidence and the frequencies of clinical visits for all five oral diseases were higher in those with AR than in the non-AR group after adjusting for confounding factors and AS. Similar observation was made for the AS group, without adjusting for AR. However, if AR was included for adjustment, no relationship was found between AS and oral diseases. In the AR group, those with higher incomes, and country residents had a high risk of developing oral disease. Intranasal steroids, rather than inhaled steroids, were also associated with oral diseases., Conclusion: AR, rather than AS, may be associated with oral diseases in young adults., Competing Interests: The authors declare there are no competing interests., (©2019 Ho et al.)

Objectives: To investigate the role of the traditional and radiomic parameters of 18 F-FDG PET for predicting the outcomes of patients with esophageal squamous cell carcinoma (SqCC)., Methods: Forty-four patients with primary esophageal SqCC who underwent neoadjuvant chemoradiotherapy (CCRT) followed by esophagectomy (tri-modality treatment) were retrospectively analyzed. All patients underwent 18 F-FDG PET/CT before and after neoadjuvant CCRT. The radiomic features were calculated using the pre-treatment PET scan. Pre-treatment radiomic features and changes in the PET-derived traditional parameters after neoadjuvant CCRT were analyzed according to the pathological response to esophagectomy, disease-free survival (DFS), and overall survival (OS). We further developed a scoring system based on the independent survival prognosticators and compared our model to the traditional TNM staging system and surgical pathology., Results: A pre-treatment primary tumor histogram entropy ≥ 3.69 predicts an unfavorable response to neoadjuvant CCRT (OR = 19.25, p = 0.009). An SUVmax reduction ratio ≤ 0.76, a pre-treatment primary tumor code similarity ≤ 0.0235, and incomplete pathological remission were independently associated with poor OS (p = 0.019, 0.033, and 0.038, respectively) and DFS (p = 0.049, 0.021, and 0.009, respectively). The three survival prognosticators were used to construct a scoring system (score 0-1, 2, and 3). Patients with a score of 2 or 3 had a significantly worse survival outcome than those with a score of 0-1 (HRs for OS: 3.58 for score 2, and 15.19 for score 3, p < 0.001; HRs for DFS: 1.39 for score 2 and 6.04 for score 3, p = 0.001).This survival prediction model was superior to the traditional TNM staging system (p < 0.001 versus p = 0.061 for OS, and p = 0.001 versus p = 0.027 for DFS) and the model based on surgical pathology (p < 0.001 versus p = 0.049 for OS, and p = 0.001 versus p = 0.022 for DFS)., Conclusions: The 18 F-FDG PET-derived radiomic parameter is useful for predicting the surgical pathological response in patients with esophageal SqCC treated with the tri-modality method. Using a combination of traditional and radiomic PET parameters with clinical profiles enables better stratification of patients into subgroups with various survival rates.

Antibiotics during infancy, delivery, and breastfeeding affect the intestinal microbiota in early life and is associated with allergic disease. Gastroenteritis (GE) during infancy also affects intestinal microbiota in early life, however, its relationship to allergic disease has not been investigated.Data of 45,499 males and 49,430 females, from birth to 5 years of age, were collected from a national database in Taiwan. Subjects were categorized into early GE (GE within 0-6 months) and non-early GE group (no GE within 0-6 months). The rates of asthma (AS), allergic rhinitis (AR), and atopic dermatitis (AD) over 5 years were evaluated and compared between the groups. In patients with AS, AR, and AD, the number of clinical visits and drug prescriptions for the allergic disease was also evaluated to assess the effect of early GE on allergic disease.After adjusting for the effect of GE in later life and other factors, the rates of AS [OR (odds ratio) 1.54, 95% confidence interval (CI) 1.48-1.60], AR [OR 1.49, 95% CI 1.45-1.54], and AD [OR 1.40, 95% CI 1.33-1.47] were higher in the early GE group than in the non-early GE group. The magnitude of the increase was higher in females than in males. In those with AS, AR, and AD, the number of clinical visits and drug prescriptions was not different between the early GE and non-early GE groups. In children with early GE, good control of GE in the following years lowered the rate of allergic disease.Early-life GE was associated with increased rates of AS, AR, and AD in later life and this was trend more prominent in females.

Steroid-insensitive asthma-related airway inflammation is associated with the expression of epidermal growth factor receptor (EGFR) tyrosine kinase in asthmatic bronchial epithelium. Proinflammatory cytokines IL-6 and IL-8 are related to steroid-insensitive asthma. It is currently unknown how EGFR-tyrosine kinase inhibitors (EGFR-TKIs) affects house dust mite (HDM)-induced asthma in terms of inflammatory cytokines related to steroid-resistant asthma and further signaling pathway. Cytokine expressions and EGFR signaling pathway were performed by ELISA, reverse transcriptase PCR, real-time PCR, and Western blot in cell-line models. AMP-activated protein kinase (AMPK) pathway-related inhibitors were applied to confirm the association between EGFR-TKI and AMPK pathway. HDM induced IL-6 and IL-8 in a dose-dependent manner. Both Erlotinib (Tarceva) and Osimertinib (AZD-9291) reduced the levels of HDM-stimulated IL-6 and IL-8 levels in BEAS-2B cells. AZD-9291 was more effective than Erlotinib in inhibiting phospho-EGFR, and downstream phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and phopho-signal transducer and activator of transcription 3 (p-STAT3) pathway signaling. In addition, AMPK pathway-related inhibitor, Calcium-/calmodulin-dependent protein kinase kinase β (CaMKKβ) inhibitor, down-regulated IL-8, but EGFR-TKI had no effect on AMPK pathway. Our findings highlight EGFR-TKIs, Tarceva, and AZD-9291, attenuate HDM-induced inflammatory IL-6 and IL-8 cytokines via EGFR signaling axis pathway, but not AMPK signaling pathway., (© 2019 Wiley Periodicals, Inc.)