Evaluation of the Risk Prediction Models in Predicting Kidney Outcomes in Antiglomerular Basement Membrane Disease.

Introduction: A previous study showed that the renal risk score (RRS) was transferrable to antiglomerular basement membrane (anti-GBM) disease and proposed a risk stratification according to the need of renal replacement therapy (RRT) and the percentage of normal glomeruli (N). Herein, we analyzed the risk factors associated with kidney outcomes in patients with biopsy-proven anti-GBM disease and evaluated these 2 prognosis systems. Methods: A total of 120 patients with biopsy-proven anti-GBM disease with complete clinicopathologic and outcome data were analyzed. Results: The median time to kidney biopsy was 41 days (interquartile range [IQR]: 22-63 days). RRT and N were the only independent predictors of end-stage kidney disease (ESKD). Patients with N ≥10% were more likely to achieve ESKD-free outcomes, even in the subcohort of patients who underwent posttreatment biopsies (P < 0.001). N and serum creatinine at presentation (cut-off values 750 µmol/l and 1300 µmol/l) were 2 independent factors for predicting kidney recovery. The RRS and the risk stratification tool exhibited predictive value for ESKD and could be transferred to patients with kidney biopsy following treatment (Harrell's C statistic [C] = 0.738 and C = 0.817, respectively). However, a cross-over of outcomes among groups was observed in the risk stratification tool in long-term follow-up, when patients with RRT and N ≥10% achieved better kidney outcomes than those without RRT but N <10%. Conclusion: Normal glomeruli percentage, even posttreatment, was a strong indicator for kidney outcomes, especially on long-term prognosis. Serum creatinine is a predictor for kidney recovery, independent of biopsy findings. The risk stratification tool for kidney survival was transferrable to patients with anti-GBM disease with biopsy following treatment in our cohort; however, this needs further validations for long-term outcomes.

Clinical and pathological characteristics of DKD patients with early-onset type 2 diabetes.

AIMS: In diabetic kidney disease (DKD) patients, early-onset T2DM effects on renal disease severity and outcomes remain uncertain. Herein, we aim to investigate the clinicopathological characteristics and renal outcomes in DKD patients with early-onset T2DM. METHODS: 489 patients with T2DM and DKD were retrospectively recruited and classified as having early (age at onset of T2DM < 40 years) and late (age at onset of T2DM ≥ 40 years) T2DM onset, analyzing the clinical and histopathological data. The predictive value of early-onset T2DM to renal outcomes in DKD patients was analyzed by Cox's regression. RESULTS: Among 489 DKD patients, 142 and 347 were classified as early and late T2DM onset, respectively. Early-onset T2DM patients exhibited worse glycaemic control (7.36 % ± 1.80 % vs. 6.86 % ± 1.57 %, P = 0.007) and more severe proteinuria (3.69 [1.55 to 7.03] vs. 1.81 [0.50 to 4.33] g/24 h, P < 0.001). Those with early-onset T2DM presented more severe glomerular lesions. In univariable Cox regression, early-onset T2DM showed a significant correlation with renal composite endpoint (HR [95%CI]: 0.56 [0.43 to 0.73], P < 0.001). However, after adjusting for potential confounders, early-onset T2DM was not independently correlated with renal composite endpoint (HR [95%CI]: 0.74 [0.46 to 1.21], P = 0.232). CONCLUSIONS: In DKD patients with early-onset T2DM, renal clinicopathological manifestations were severe. Age at onset in T2DM was significantly correlated with eGFR slope (r = 0.211, P < 0.001).

Adhesive hydrogels in osteoarthritis: from design to application.

Osteoarthritis (OA) is the most common type of degenerative joint disease which affects 7% of the global population and more than 500 million people worldwide. One research frontier is the development of hydrogels for OA treatment, which operate either as functional scaffolds of tissue engineering or as delivery vehicles of functional additives. Both approaches address the big challenge: establishing stable integration of such delivery systems or implants. Adhesive hydrogels provide possible solutions to this challenge. However, few studies have described the current advances in using adhesive hydrogel for OA treatment. This review summarizes the commonly used hydrogels with their adhesion mechanisms and components. Additionally, recognizing that OA is a complex disease involving different biological mechanisms, the bioactive therapeutic strategies are also presented. By presenting the adhesive hydrogels in an interdisciplinary way, including both the fields of chemistry and biology, this review will attempt to provide a comprehensive insight for designing novel bioadhesive systems for OA therapy.

Multi-Scalar Data Integration Links Glomerular Angiopoietin-Tie Signaling Pathway Activation With Progression of Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD). Prognostic biomarkers reflective of underlying molecular mechanisms are critically needed for effective management of DKD. A three-marker panel was derived from a proteomics analysis of plasma samples by an unbiased machine learning approach from participants (N = 58) in the Clinical Phenotyping and Resource Biobank study. In combination with standard clinical parameters, this panel improved prediction of the composite outcome of ESKD or a 40% decline in glomerular filtration rate. The panel was validated in an independent group (N = 68), who also had kidney transcriptomic profiles. One marker, plasma angiopoietin 2 (ANGPT2), was significantly associated with outcomes in cohorts from the Cardiovascular Health Study (N = 3,183) and the Chinese Cohort Study of Chronic Kidney Disease (N = 210). Glomerular transcriptional angiopoietin/Tie (ANG-TIE) pathway scores, derived from the expression of 154 ANG-TIE signaling mediators, correlated positively with plasma ANGPT2 levels and kidney outcomes. Higher receptor expression in glomeruli and higher ANG-TIE pathway scores in endothelial cells corroborated potential functional effects in the kidney from elevated plasma ANGPT2 levels. Our work suggests that ANGPT2 is a promising prognostic endothelial biomarker with likely functional impact on glomerular pathogenesis in DKD.

Comparation of predictive value of CAT and change in CAT in the short term for future exacerbation of chronic obstructive pulmonary disease.

PURPOSE: Our study aimed to compare the predictive value of the COPD Assessment Test (CAT) score at baseline and short-term change in CAT for future exacerbations in chronic obstructive pulmonary disease (COPD) patients. METHODS: This was a multicentre prospective study. Patients with COPD were recruited into the study and followed up for one year. CAT score and exacerbation in the previous year were collected at baseline. Change in CAT was defined as CAT score changing between baseline and the 6-month follow-up. Exacerbation was recorded during the one-year follow-up from 0th to 12th month. RESULT: A total of 536 patients were enrolled for final analysis. The mean baseline CAT score was 14.5 ± 6.6 and the median (IQR) change in CAT was -2 (8). On Cox regression analysis, baseline CAT score, change in CAT and history of exacerbation were independent risk factors for exacerbation in the one-year follow-up. Compared with the r value of correlation between baseline CAT score and frequency of exacerbations during the one-year follow-up (r = 0.286, p < .001), that correlation between the change in CAT and frequency of exacerbations during follow-up was higher (r = 0.421, p < .001). The receiver operating characteristic (ROC) curves showed that change in CAT had a better predictive capacity for future exacerbation than baseline CAT (0.789 versus 0.609, p = .001). The ROC showed that change in CAT also had a better predictive capacity for future exacerbation than exacerbation in the previous year (0.789 versus 0.689, p = .011). CONCLUSION: The correlation between baseline CAT score and future exacerbation was weak, however, the correlation between change in CAT and future exacerbation was moderate. Change in CAT in the short term had a better predictive value for future exacerbations of COPD than baseline CAT and exacerbation in the previous year.

The Characteristics of Airflow Limitation and Future Exacerbations in Different GOLD Groups of COPD Patients.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 separated pulmonary function from combined assessment. We aimed to analyze the characteristics of airflow limitation and future exacerbations in different GOLD groups of chronic obstructive pulmonary disease (COPD) patients. METHODS: For this prospective observational study, stable COPD outpatients were enrolled and divided into Groups A, B, C and D based on GOLD 2017, and followed-up for 18 months. Data on demographics, pulmonary function, COPD assessment test (CAT), Clinical COPD Questionnaire (CCQ), modified Medical Research Council (mMRC), exacerbations, mortality and treatments were collected. A post-bronchodilator ratio of forced expiratory volume in one second to forced vital capacity <0.70 confirms the presence of airflow limitation. RESULTS: A total of 993 subjects were classified into Groups A (n = 170, 17.1%), B (n = 360, 36.3%), C (n = 122, 12.3%), and D (n = 341, 34.3%). There were significant differences in mMRC, CAT, CCQ, exacerbations and hospitalizations rates among the different groups (P < 0.001). Groups B and D had more severe airflow limitation than Groups A and C (P < 0.05). In the same groups with different severity of airflow limitation, the differences were mainly observed in body mass index, CAT, CCQ and treatment with long-acting muscarinic antagonist (LAMA) and LAMA + long-acting ß2-agonist + inhaled corticosteroid (P < 0.05). After 18 months of follow-up, the exacerbations and hospitalizations rates were significantly different among different groups (P < 0.05). However, in the same groups with different airflow limitation severity, the mortality rates and number of exacerbations, hospitalizations and frequent exacerbators showed no differences. CONCLUSION: In the GOLD groups, different severity of airflow limitation had no impact on future exacerbations and mortality rate. It implies that pulmonary function is not a good indicator for predicting exacerbation.

Modified and simplified clinically important deterioration: multidimensional indices of short-term disease trajectory to predict future exacerbations in patients with chronic obstructive pulmonary disease.

BACKGROUND AND AIMS: Various prediction indices based on the single time point observation have been proposed in chronic obstructive pulmonary disease (COPD), but little was known about disease trajectory as a predictor of future exacerbations. Our study explored the association between disease trajectory and future exacerbations, and validated the predictive value of the modified and simplified short-term clinically important deterioration (CID). METHODS: This study was a multicenter, prospective observational study. Patients with COPD were recruited into our study and followed up for 18 months. The modified CID (CID-C) was defined as a decrease of 100 mL in forced expiratory volume in 1 second (FEV1), or suffering exacerbations, or increase of 2 units in COPD Assessment Test (CAT) during the first 6 months follow-up. Simplified CID was defined when excluding CAT from the CID-C model. RESULTS: A total of 127 patients were enrolled in our final analysis. Compared with patients without exacerbations during the period of the 6th to the 18th month, patients with exacerbations were more likely to have frequent short-term exacerbations in the first 6 months (2.14 versus 0.21, p < 0.001). The short-term exacerbations were the best predictor for future exacerbations [odds ratio (OR): 13.25; 95% confidence interval: 5.62-34.67; p < 0.001], followed by the history of exacerbation before study entry, short-term changes in FEV1 and CAT. CID-C and Simplified CID were both significantly associated with exacerbations (OR: 7.14 and 9.74, both p < 0.001). The receiver operating characteristic curves showed that the Simplified CID had slightly better predictive capacity for future exacerbation than CID-C (0.754 versus 0.695, p = 0.02). CONCLUSION: Disease trajectory, including both the CID-C and the Simplified CID had significant predictive value for future exacerbations.The reviews of this paper are available via the supplemental material section.

Microarray Analysis of Long Non-Coding RNAs in Lung Tissues of Patients with COPD and HOXA-AS2 Promotes HPMECs Proliferation via Notch1.

Background and Objectives: Long non-coding RNAs (lncRNAs) play an important role in the pathogenesis of many diseases, including cancer, pulmonary fibrosis and chronic obstructive pulmonary disease (COPD). In this study, we intended to identify the differentially expressed lncRNAs and the role of HOXA cluster antisense RNA 2 (HOXA-AS2) in patients with COPD. Methods: We analyzed lncRNA profiles of three non-COPD and seven COPD patients' lungs via microarray and then validated the expression of the top differentially expressed lncRNAs by using real-time polymerase chain reaction (PCR). To identify the mechanism of HOXA-AS2 during COPD pathogenesis and endothelial cell proliferation, we knocked down and overexpressed HOXA-AS2 with siRNA and lentivirus transfection approach in human pulmonary microvascular endothelial cells (HPMECs). Results: Among 29,150 distinct lncRNA transcripts, 353 lncRNAs were significantly (≥2-fold change and P<0.05) upregulated and 552 were downregulated in COPD patients. The fold change of HOXA-AS2 is 9.32; real-time PCR confirmed that HOXA-AS2 was downregulated in COPD patients. In in vitro experiments, cigarette smoke extract (CSE) treatment reduced the expression of HOXA-AS2 and cell proliferation of HPMECs. Knocking down HOXA-AS2 inhibited HPMECs proliferation and the expression of Notch1 in HPMECs. Overexpressing Notch1 could partly rescue the inhibition of cell viability induced by the silence of HOXA-AS2. Conclusion: Our results demonstrated that differentially expressed lncRNAs may act as potential molecular biomarkers for the diagnosis of COPD, and HOXA-AS2 was involved in the pathogenesis of COPD by regulating HPMECs proliferation via Notch1, which may provide a new approach for COPD treatment.

Cost-effectiveness of afatinib, gefitinib, erlotinib and pemetrexed-based chemotherapy as first-line treatments for advanced non-small cell lung cancer in China.

PURPOSE: Tyrosine kinase inhibitors (TKI) of the epidermal growth factor receptor (EGFR) are becoming the standard treatments for Chinese patients with advanced non-small cell lung cancer (NSCLC) harboring an EGFR mutation. However, the economic impact is unclear yet in China. MATERIALS AND METHODS: A decision-analytic model was developed to simulate 1-month patient transitions in a 10-year time horizon from Chinese heath care system perspective. The health and economic outcomes of four first-line strategies (pemetrexed plus cisplatin [PC], gefitinib, erlotinib, and afatinib) among NSCLC patients harboring EGFR mutations were estimated and assessed via indirect comparisons. Costs in the Chinese setting were estimated by using local hospital data and literatures. A 5% annual discount rate was applied to both costs and outcomes. The primary outcome was the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed. RESULTS: Afatinib achieved additional 0.382, 0.216 and 0.174 quality-adjusted life-years (QALYs) with marginal $7930, $3680 and $2818 costs in comparison with PC, gefitinib and erlotinib, which resulted in the ICERs of $20,758, $17,693 and $16,197 per QALY gained, respectively. The hazard ratios (HR) of overall survival (OS) of afatinib against gefitinib, erlotinib and PC strategy had substantial influential parameters. CONCLUSIONS: First-line afatinib is cost-effective compared with gefitinib, erlotinib and PC treatment for Chinese patients with EGFR mutation-positive NSCLC.

Cost-effectiveness of afatinib and erlotinib as second-line treatments for advanced squamous cell carcinoma of the lung.

AIM: To investigate the cost-effectiveness of afatinib and erlotinib as second-line therapy for advanced squamous cell carcinoma of the lung. MATERIALS & METHODS: A decision-analytic model was developed for projecting the economic outcomes. Clinical parameters and utilities were from the LUX-Lung 8 trial. Costs were mainly estimated from the Chinese health system. The outcome was the incremental cost-effectiveness ratio. RESULTS: The afatinib strategy generated additional 0.154 quality-adjusted life-years compared with erlotinib, with incremental costs of ¥16,852. Relative to erlotinib, afatinib resulted in an incremental cost-effectiveness ratio of ¥109,429 per quality-adjusted life-year gained. The overall survival time of afatinib had a considerable impact on the model outcomes. CONCLUSION: Afatinib is a cost-effective treatment option compared with erlotinib in patients with squamous cell carcinoma.

Hyperglycemia and its association with clinical outcomes for patients in the pediatric intensive care unit after abdominal surgery.

PURPOSE: We investigated the incidence of hyperglycemia of patients in the pediatric intensive care unit (PICU) after receiving abdominal surgery and its association with clinical outcomes. METHODS: A retrospective review was performed from November 1, 2010 to November 1, 2011 on all PICU admissions after abdominal surgery. Maximum serum glucose concentrations (Gmax) in PICU, PICU length of stay, total hospital length of stay, deep and systemic infection, wound infection and mortality rates were recorded and analyzed. RESULTS: A total of 193 children met the inclusion criteria of our research. Maximum glucose levels ranged from 55.7 mg/dL to 415.9 mg/dL (median: 132 mg/dL). Hyperglycemia in PICU was prevalent, with 125 (64.8%) patients having Gmax >110 mg/dL during their PICU stay and 35 (18.8%) having Gmax >200 mg/dL. Average PICU length of stay and total hospital length of stay grew as the maximum glucose levels rose among the four plasma glycemic ranges. The highest serum glucose range patient group also had the highest wound infection rates (14.3% and 11.4%). CONCLUSIONS: Hyperglycemia was prevalent among patients after major abdominal surgery in PICU and was correlated with increased PICU length of stay, total hospital length of stay. Appropriate glycemic control may improve clinical outcomes for this group of patients.