Association between type 2 inflammatory diseases and neurodevelopmental disorders in low-birth-weight children and adolescents

BackgroundEvidence of the association of certain neurodevelopmental disorder with specific type 2 inflammatory (T2) disease has been found. However, the association of various neurodevelopmental disorders with T2 diseases as a whole remains unclear in low-birth-weight (LBW) infants.ObjectiveTo evaluate the association of type 2 inflammatory (T2) diseases with intellectual disability (ID), autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and learning disability (LD) in LBW children and adolescents.MethodsThe study sample was derived from 2005 to 2018 National Health Interview Survey sample child files. LBW children and adolescents aged 3–17 were included. History of T2 diseases (including asthma and atopic dermatitis) and four neurodevelopmental disorders were reported by adults in families. The relationship between T2 diseases and the risk of four neurodevelopmental disorders was investigated through multiple-weighted logistic regression. Age, sex, race/ethnicity, region, highest education in family and ratio of family income to the poverty threshold were adjusted as covariates for model estimation. Subgroup analyses were conducted by age stratification (3–11 and 12–17 years), sex (male and female), and race (white and non-white).Results11,260 LBW children aged 3–17 years [mean age (SE), 9.73 (0.05) years] were included, in which 3,191 children had T2 diseases. History of T2 diseases was associated with an increased risk of neurodevelopmental disorders, with an OR of 1.35 (95% CI, 0.99–1.84) for ID, 1.47 (95% CI, 1.05–2.05) for ASD, 1.81 (95% CI, 1.51–2.16) for ADHD, and 1.74 (95% CI, 1.49–2.04) for LD following the adjustment of all the covariates. The correlations between T2 disorders and each of the four neurodevelopmental disorders were significantly different by sex and race (all P for interaction < 0.001), and no differences were found in age stratification (all P for interaction > 0.05).ConclusionIn a nationally representative sample of children, we found a significant association of T2 diseases with ASD, ADHD, and LD, even after adjusting for demographic baseline. We also found that the association of T2 disease with neurodevelopmental disorders differed between sex and race. Further investigation is needed to evaluate causal relationships and elucidate their potential mechanisms

Comparison of Nasopharyngeal MR, 18 F-FDG PET/CT, and 18 F-FDG PET/MR for Local Detection of Natural Killer/T-Cell Lymphoma, Nasal Type.

Objectives The present study aims to compare the diagnostic efficacy of MR, 18F-FDG PET/CT, and 18F-FDG PET/MR for the local detection of early-stage extranodal natural killer/T-cell lymphoma, nasal type (ENKTL). Patients and Methods Thirty-six patients with histologically proven early-stage ENKTL were enrolled from a phase 2 study (Cohort A). Eight nasopharyngeal anatomical regions from each patient were imaged using 18F-FDG PET/CT and MR. A further nine patients were prospectively enrolled from a multicenter, phase 3 study; these patients underwent 18F-FDG PET/CT and PET/MR after a single 18F-FDG injection (Cohort B). Region-based sensitivity and specificity were calculated. The standardized uptake values (SUV) obtained from PET/CT and PET/MR were compared, and the relationship between the SUV and apparent diffusion coefficients (ADC) of PET/MR were analyzed. Results In Cohort A, of the 288 anatomic regions, 86 demonstrated lymphoma involvement. All lesions were detected by 18F-FDG PET/CT, while only 70 were detected by MR. 18F-FDG PET/CT exhibited a higher sensitivity than MR (100% vs. 81.4%, χ2 = 17.641, P < 0.001) for local detection of malignancies. The specificity of 18F-FDG PET/CT and MR were 98.5 and 97.5%, respectively (χ2 = 0.510, P = 0.475). The accuracy of 18F-FDG PET/CT was 99.0% and the accuracy of MR was 92.7% (χ2 = 14.087, P < 0.001). In Cohort B, 72 anatomical regions were analyzed. PET/CT and PET/MR have a sensitivity of 100% and a specificity of 92.5%. The two methods were consistent (κ = 0.833, P < 0.001). There was a significant correlation between PET/MR SUVmax and PET/CT SUVmax (r = 0.711, P < 0.001), and SUVmean (r = 0.685, P < 0.001). No correlation was observed between the SUV and the ADC. Conclusion In early-stage ENKTL, nasopharyngeal MR showed a lower sensitivity and a similar specificity when compared with 18F-FDG PET/CT. PET/MR showed similar performance compared with PET/CT

Lifestyle Behaviors and Cardiometabolic Diseases by Race and Ethnicity and Social Risk Factors Among US Young Adults, 2011 to 2018

Background Cardiometabolic health has been worsening among young adults, but the prevalence of lifestyle risk factors and cardiometabolic diseases is unclear. Methods and Results Adults aged 18 to 44 years were included from the National Health and Nutrition Examination Survey, 2011 to 2018. Age‐standardized prevalence of lifestyle risk factors and cardiometabolic diseases was estimated overall and by demographic and social risk factors. A set of multivariable logistic regressions was sequentially performed by adjusting for age, sex, social risk factors, and lifestyle factors to determine whether racial and ethnic disparities in the prevalence of cardiometabolic diseases may be attributable to differences in social risk factors and lifestyle factors. Appropriate weights were used to ensure national representativeness of the estimates. A total of 10 405 participants were analyzed (median age, 30.3 years; 50.8% women; 32.3% non‐Hispanic White). The prevalence of lifestyle risk factors ranged from 16.3% for excessive drinking to 49.3% for poor diet quality. The prevalence of cardiometabolic diseases ranged from 4.3% for diabetes to 37.3% for dyslipidemia. The prevalence of having ≥2 lifestyle risk factors was 45.2% and having ≥2 cardiometabolic diseases was 22.0%. Racial and ethnic disparities in many cardiometabolic diseases persisted but were attenuated after adjusting for social risk factors and lifestyle factors. Conclusions The prevalence of lifestyle risk factors and cardiometabolic diseases was high among US young adults and varied by race and ethnicity and social risk factors. Racial and ethnic disparities in the prevalence of cardiometabolic diseases were not fully explained by differences in social risk factors and lifestyle factors

Age‐specific differences in hypertension combination management and associated factors influencing treatment choice

Abstract The current hypertension guideline emphasizes combination therapy, especially single‐pill combination therapy (SPC). However, few studies compared the prevalence and factors associated with initial therapy choice across heterogeneous age groups in a current population. First, the authors consecutively identified 964 treatment naïve hypertensive patients in a large academic hospital from 01/31/2019 to 01/31/2020. All patients were grouped into (1) young aged, age < 55; (2) middle‐aged, 55≤age < 65; and (3) older aged, age ≥65. The multivariable regression model examined the factors associated with the combination therapy by age group. Overall, 80 (8.3%) were young, 191 (19.8%) were middle, and 693 (71.9%) were older aged. Compared with older age, younger patients were more likely to be male, highly educated, regularly exercised, have metabolic syndrome, and less likely to have cardiovascular‐related comorbidities, with a lower systolic but higher diastolic pressure. Only one in five patients used SPC, and the prevalence decreased with age. Besides hypertension grade, young patients without catheterization or echo test were less likely to receive multiple therapies, while older patients who were male with lower weight and lower risk levels were less likely to receive multiple therapies. In conclusion, combination therapy, especially SPC, was underused in the targeted hypertensive population. Our contemporary population study showed that young patients (<55) without a history of catheterization or echo examination and male older‐aged (≥65) patients with low‐risk classification were the population most likely to be neglected. Such information can help triage medical care resources in improving SPC use

Data_Sheet_1_Association between type 2 inflammatory diseases and neurodevelopmental disorders in low-birth-weight children and adolescents.docx

BackgroundEvidence of the association of certain neurodevelopmental disorder with specific type 2 inflammatory (T2) disease has been found. However, the association of various neurodevelopmental disorders with T2 diseases as a whole remains unclear in low-birth-weight (LBW) infants.ObjectiveTo evaluate the association of type 2 inflammatory (T2) diseases with intellectual disability (ID), autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and learning disability (LD) in LBW children and adolescents.MethodsThe study sample was derived from 2005 to 2018 National Health Interview Survey sample child files. LBW children and adolescents aged 3–17 were included. History of T2 diseases (including asthma and atopic dermatitis) and four neurodevelopmental disorders were reported by adults in families. The relationship between T2 diseases and the risk of four neurodevelopmental disorders was investigated through multiple-weighted logistic regression. Age, sex, race/ethnicity, region, highest education in family and ratio of family income to the poverty threshold were adjusted as covariates for model estimation. Subgroup analyses were conducted by age stratification (3–11 and 12–17 years), sex (male and female), and race (white and non-white).Results11,260 LBW children aged 3–17 years [mean age (SE), 9.73 (0.05) years] were included, in which 3,191 children had T2 diseases. History of T2 diseases was associated with an increased risk of neurodevelopmental disorders, with an OR of 1.35 (95% CI, 0.99–1.84) for ID, 1.47 (95% CI, 1.05–2.05) for ASD, 1.81 (95% CI, 1.51–2.16) for ADHD, and 1.74 (95% CI, 1.49–2.04) for LD following the adjustment of all the covariates. The correlations between T2 disorders and each of the four neurodevelopmental disorders were significantly different by sex and race (all P for interaction 0.05).ConclusionIn a nationally representative sample of children, we found a significant association of T2 diseases with ASD, ADHD, and LD, even after adjusting for demographic baseline. We also found that the association of T2 disease with neurodevelopmental disorders differed between sex and race. Further investigation is needed to evaluate causal relationships and elucidate their potential mechanisms.</p

Pharmacogenomic study on anti-VEGF medicine in treatment of macular Neovascular diseases: a study protocol for a prospective observational study

Abstract Background Macular neovascular diseases can cause severe vision loss. A newly approved anti—VEGF drug Conbercept has shown good efficacy and safety in rigorous random controlled trials (RCT), however, it cannot fully reflect the clinical application of Conbercept in real world clinical practice. Moreover, anti-VEGF drugs are expensive and often require multiple treatments, and some patients have poor or even no response to the drugs,this resulted enormous waste of medical resources. Therefore, how to find out those patients who have good response, and how to develop individualized therapeutic regimen in real world need to be urgently investigated in the aspect of pharmacogenomics and pharmacometabolomics. Methods This study is a multicenter, prospective, observational study of Conbecept treating macular neovascular diseases in China. Patients suffered from age-related macular degeneration, polypoidal choroidal vasculopathy, and pathological myopia who already planned to receive Conbercept treatment will be recruited. We aimed to enroll more than 5000 patients from 43 ophthalmic centers in China. Patients’ clinical data and blood samples will be collected during the one-year follow-up period. Finally, the safety and efficacy of Conbercept, and the potential predictors of patients’ response to Conbercept will be investigated by pharmacogenomics and pharmacometabolomics analysis. Discussion This study will provide important data of Conbercept in treating macular neovascular diseases in real world. Besides, finding the predictor of patients’ response will help doctor make more precise individualized therapeutic regimens. Trial registration ClinicalTrials.gov, NCT03128463. Registered on 9 March 2017

Contemporary update of overall prognosis and nomogram to predict individualized survival for Chinese patients with eyelid sebaceous carcinomaResearch in context

Background: The prognosis of Chinese patients with eyelid sebaceous carcinoma (SC) has not been updated for >3 decades. The prognostic predictors are multifactorial, and there is no validated prognostic model for eyelid SC. Methods: This study included 238 consecutive patients with eyelid SC. All eligible patients were followed up for metastasis and mortality. The predictors of tumor-related survival were explored by Cox analyses. A prognostic nomogram was developed and validated using bootstrap resampling. The predictive accuracy and discriminative ability were compared between the nomogram and the Tumor, Node, Metastasis (TNM) staging system. Findings: After a median follow-up period of 55.5 months, 27 (11.3%) patients died of metastatic SC, with a median survival time of 48.0 months. The 5-year and 10-year tumor-related survival rates were 88.1% and 77.9%, respectively. Orbital involvement (HR: 3.11, p = .022), the greatest tumor basal diameter (HR: 1.06, p = .003), the presence of pagetoid spread (HR: 2.90, p = .017), and having lymph node metastasis at initial diagnosis (HR: 13.66, p < .001) were independent risk factors for tumor-related death. A nomogram integrating these 4 factors was developed with a C-index of 0.887, which is significantly better than that of the TNM staging system (p = .002). The risk groups stratified by nomogram scores (p < .001 (low vs intermediate risk); p = .001 (intermediate vs high risk)) displayed better discrimination ability than TNM staging (T1 vs T2: p = .358; T2 vs T3: p = .171; T3 vs T4: p < .001) in patients at an early stage. Interpretation: The prognosis of Chinese patients with eyelid SC has improved over the last 3 decades, and it is comparable to that of patients from other countries. This nomogram provides more accurate individualized estimates of survival for eyelid SC patients and may guide clinicians in their therapeutic decisions. Keywords: Eyelid sebaceous carcinoma, Nomogram, Tumor-related surviva

Development and validation of a simple-to-use clinical nomogram for predicting obstructive sleep apnea

Abstract Background The high cost and low availability of polysomnography (PSG) limits the timely diagnosis of OSA. Herein, we developed and validated a simple-to-use nomogram for predicting OSA. Methods We collected and analyzed the cross-sectional data of 4162 participants with suspected OSA, seen at our sleep center between 2007 and 2016. Demographic, biochemical and anthropometric data, as well as sleep parameters were obtained. A least absolute shrinkage and selection operator (LASSO) regression model was used to reduce data dimensionality, select factors, and construct the nomogram. The performance of the nomogram was assessed using calibration and discrimination. Internal validation was also performed. Results The LASSO regression analysis identified age, sex, body mass index, neck circumference, waist circumference, glucose, insulin, and apolipoprotein B as significant predictive factors of OSA. Our nomogram model showed good discrimination and calibration in terms of predicting OSA, and had a C-index value of 0.839 according to the internal validation. Discrimination and calibration in the validation group was also good (C-index = 0.820). The nomogram identified individuals at risk for OSA with an area under the curve (AUC) of 0.84 [95% confidence interval (CI), 0.83–0.86]. Conclusions Our simple-to-use nomogram is not intended to replace standard PSG, but will help physicians better make decisions on PSG arrangement for the patients referred to sleep center

Strategies for remote enantiocontrol in chiral gold(iii) complexes applied to catalytic enantioselective γ,δ-Diels-Alder reactions.

The use of chiral square planar gold(iii) complexes to access enantioenriched products has rarely been applied in asymmetric catalysis. In this context, we report a mechanistic and synthetic investigation into the use of N-heterocyclic (NHC) gold(iii) complexes in γ,δ-Diels-Alder reactions of 2,4-dienals with cyclopentadiene. The optimal catalyst bearing a unique 2-chloro-1-naphthyl substituent allowed efficient synthesis of functionally rich carbocycles in good yields, diastereo- and enantioselectivities. Transition state and multivariate linear regression (MLR) analysis of both catalyst and substrate trends using molecular descriptors derived from designer parameter acquisition platforms, reveals attractive non-covalent interactions (NCIs) to be key selectivity determinates. These analyses demonstrate that a putative π-π interaction between the substrate proximal double bond and the catalyst aromatic group is an essential feature for high enantioselectivity

Prognostic nomogram incorporating inflammatory cytokines for overall survival in patients with aggressive non-Hodgkin's lymphomaResearch in context

Background: This study aimed to investigate the association of pre-treatment inflammatory status with survival time and to develop a prognostic nomogram incorporating inflammatory cytokines in non-Hodgkin's lymphoma. Methods: A total of 228 patients with diffuse large B-cell lymphoma (DLBCL) received R-CHOP-based regimens from a prospective randomized study (NCT01852435) were included as a training cohort. Other cohorts of 886 lymphoma patients were served as validation cohorts. Lymphocyte-monocyte ratio (LMR), serum levels of soluble interleukin s(IL)-2R, IL-6, IL-8, IL-10 and tumor necrosis factor-α (TNF-α), were assessed before treatment. Least absolute shrinkage and selection operator (LASSO) regression were used to select variables for nomogram of overall survival (OS). The predictive accuracy of the nomogram was determined by concordance index (C-index). Findings: The nomogram included lactate dehydrogenase (LDH), sIL-2R, TNF-α and decreased LMR. The C-index of the nomogram for OS prediction were range from 0.61 to 0.86 for training cohort of DLBCL and validation cohorts of DLBCL, PTCL, NKTCL and ASCT, which were superior to the predictive power of International Prognostic Index (IPI, 0.67 to 0.84) or NCCN-IPI (0.59 to 0.78), but not in those of indolent lymphoma like FL and MALT. Interpretations: The nomogram incorporating inflammatory cytokines provides a useful tool for risk stratification in aggressive non-Hodgkin's lymphomas. Fund: National Natural Science Foundation of China, the Shanghai Commission of Science and Technology, Multicenter Clinical Research Project by Shanghai Jiao Tong University School of Medicine, Clinical Research Plan of SHDC, and Chang Jiang Scholars Program. Keywords: Non-Hodgkin's lymphoma, Lymphocyte-monocyte ratio, Interleukin-2 receptor, Tumor necrosis factor-α, Prognosi