Real-World Survival Outcomes Based on EGFR Mutation Status in Chinese Patients With Lung Adenocarcinoma After Complete Resection: Results From the ICAN Study.

INTRODUCTION: The adjuvant treatment of patients with resected lung adenocarcinoma (LUAD) remains unstandardized. We analyzed the survival outcomes of these patients based on EGFR mutation status and adjuvant chemotherapy treatment. METHODS: This noninterventional real-world study (ICAN) enrolled Chinese patients with resected stages I to III LUAD from April 8, 2010, to December 31, 2010. Tumor EGFR mutation status and 3-year disease-free survival (DFS) were determined. The extension phase provided long-term follow-up with overall survival (OS) as the primary end point. Secondary end points included DFS and prognostic factors of survival. Survival outcomes based on adjuvant chemotherapy treatment, EGFR mutation status, and postoperative stage were analyzed post hoc. RESULTS: Among 568 patients in the ICAN cohort, 472 continued to the extension phase and remained eligible. The 3-year DFS rate was 58.8%. In the extension cohort, 260 patients (55.1%) had EGFR-mutant disease and 207 (43.9%) received adjuvant chemotherapy. At a median follow-up of 109.0 (95% confidence interval [CI]: 106.6-111.4) months, median OS and DFS were 103.3 (95% CI: 101.7-104.9) and 67.4 (95% CI: 49.7-85.2) months, respectively. The 5-year OS and DFS rates were 68.9% (95% CI: 64.3-73.6) and 52.9% (95% CI: 48.2-57.7), respectively. EGFR wild-type disease was a significant independent predictor of worse OS (HR = 1.24, 95% CI: 1.07-1.44, p= 0.004) based on the Cox regression analysis of common factors. Post hoc subgroup analysis revealed that survival outcomes were not significantly different with adjuvant chemotherapy regardless of EGFR mutation status across all postoperative stages. CONCLUSIONS: EGFR mutations are common in operable LUAD, and recurrence and mortality after resection were considerable. Adjuvant chemotherapy did not improve survival outcomes, regardless of EGFR mutation status and postoperative stage.

The Clinicopathological Characteristics of Alpha-Fetoprotein-Producing Adenocarcinoma of the Gastrointestinal Tract-A Single-Center Retrospective Study.

Alpha-fetoprotein (AFP)-producing adenocarcinoma from the gastrointestinal tract (APA-GI) is a rare type of highly malignant tumor with a poor prognosis. It may originate from any site along the GI tract with similar clinicopathological characteristics. As limited research had ever described the characteristics of APA-GI, the present article intends to systemically investigate the clinicopathological characteristics of APA-GI from a single center's retrospective study to deepen the understanding of the disease. A total of 177 patients pathologically diagnosed with APA-GI between 2010 and 2017 at the Second Affiliated Hospital of Zhejiang University, School of Medicine, were included. Also, clinical data of 419 gastric cancers and 609 colorectal cancers from The Cancer Genome Atlas database were also extracted. Clinical information of patients from Second Affiliated Hospital of Zhejiang University, School of Medicine, was collected, and a median follow-up of 14.5 months was performed to investigate clinical characteristics of APA-GI. For the pathological characteristics of APA-GI, hematoxylin-eosin sections were reviewed, and immunohistochemistry of AFP was performed. The results showed that the primary tumor could develop through the whole GI tract, including the esophagus (0.6%), stomach (83.1%), duodenum (1.1%), ileum (0.6%), appendix (0.6%), colon (5.1%), and rectum (7.9%). Hepatoid adenocarcinoma is the main pathological feature of APA-GI. AFP expression level in tumor tissue was not strictly associated with serum AFP or hepatoid differentiation. The prognosis of APA-GI was worse than that of common adenocarcinoma of the GI tract and liver metastasis, and high AFP levels suggest poor prognosis in patients with APA-GI. Therefore, the present study was the first research to systemically explore the clinicopathological characteristics of APA-GI. APA-GI occurs through the whole GI tract with a significantly worse prognosis than common adenocarcinoma of GI. APA-GI should be regarded as one kind of disease for its similar clinicopathological characteristics within patients.

Fabrication of flexible composite drug films via foldable linkages using electrohydrodynamic printing.

The simple method to manufacture a flexible multi-drug with hydrophilic and hydrophobic molecules-loaded composite membrane via three dimensional (3D) electrohydrodynamic (EHD) printing has been demonstrated in this study. The composite membrane consists of two different drug-loaded sections: cellulose acetate-ibuprofen (CA-IBU) and cellulose acetate-paracetamol (CA-Para), respectively, with an intermediate polycaprolactone (PCL) folding component. The composite membranes can be folded and housed in commercial capsules to aid swallowing. By changing the number of PCL layers in the intermediate layers, it is possible to control and modify the mechanical and unfolding properties of the composite membrane. IBU and Para are loaded into the CA polymeric matrix in their amorphous states, with the matrices exhibiting Higuchi and first order release kinetics, respectively. The combination of IBU and Para can potentially be used as analgesic for patients. Magnetic nanoparticles as a functional material can be incorporated into the PCL matrix for wide targeting and traceable applications. The composite membrane here possesses good biocompatibility and flexibility; enabling extensive application prospects in drug combination therapy and personalized medicine.

Motor Progression in Early-Stage Parkinson's Disease: A Clinical Prediction Model and the Role of Cerebrospinal Fluid Biomarkers.

Background: The substantial heterogeneity of clinical symptoms and lack of reliable progression markers in Parkinson's disease (PD) present a major challenge in predicting accurate progression and prognoses. Increasing evidence indicates that each component of the neurovascular unit (NVU) and blood-brain barrier (BBB) disruption may take part in many neurodegenerative diseases. Since some portions of CSF are eliminated along the neurovascular unit and across the BBB, disturbing the pathways may result in changes of these substances. Methods: Four hundred seventy-four participants from the Parkinson's Progression Markers Initiative (PPMI) study (NCT01141023) were included in the study. Thirty-six initial features, including general information, brief clinical characteristics and the current year's classical scale scores, were used to build five regression models to predict PD motor progression represented by the coming year's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III score after redundancy removal and recursive feature elimination (RFE)-based feature selection. Then, a threshold range was added to the predicted value for more convenient model application. Finally, we evaluated the CSF and blood biomarkers' influence on the disease progression model. Results: Eight hundred forty-nine cases were included in the study. The adjusted R2 values of three different categories of regression model, linear, Bayesian and ensemble, all reached 0.75. Models of the same category shared similar feature combinations. The common features selected among the categories were the MDS-UPDRS Part III score, Montreal Cognitive Assessment (MOCA) and Rapid Eye Movement Sleep Behavior Disorder Questionnaire (RBDSQ) score. It can be seen more intuitively that the model can achieve certain prediction effect through threshold range. Biomarkers had no significant impact on the progression model within the data in the study. Conclusions: By using machine learning and routinely gathered assessments from the current year, we developed multiple dynamic models to predict the following year's motor progression in the early stage of PD. These methods will allow clinicians to tailor medical management to the individual and identify at-risk patients for future clinical trials examining disease-modifying therapies.

Dual-optimized adaptive Kalman filtering algorithm based on BP neural network and variance compensation for laser absorption spectroscopy.

A dual-optimized adaptive Kalman filtering (DO-AKF) algorithm based on back propagation (BP) neural network and variance compensation was developed for high-sensitivity trace gas detection in laser spectroscopy. The BP neural network was used to optimize the Kalman filter (KF) parameters. Variance compensation was introduced to track the state of the system and to eliminate the variations in the parameters of dynamic systems. The proposed DO-AKF algorithm showed the best performance compared with the traditional multi-signal average, extended KF, unscented KF, KF optimized by BP neural network (BP-KF) and KF optimized by variance compensation (VC-KF). The optimized DO-AKF algorithm was applied to a QCL-based gas sensor system for an exhaled CO analysis. The experimental results revealed a sensitivity enhancement factor of 23. The proposed algorithm can be widely used in the fields of environmental pollutant monitoring, industrial process control, and breath gas diagnosis.

Fast-track multidisciplinary treatment versus conventional treatment for colorectal cancer: a multicenter, open-label randomized controlled study.

BACKGROUND: Laparoscopic surgery, fast-track perioperative treatment and XELOX chemotherapy are effective strategies for shortening the duration of hospital stay for cancer patients. This trial aimed to clarify the safety and efficacy of the fast-track multidisciplinary treatment (FTMDT) model compared to conventional surgery combined with chemotherapy in Chinese colorectal cancer patients. METHODS: This trial was a prospective randomized controlled study with a 2 × 2 balanced factorial design and was conducted at six hospitals. Patients in group 1 (FTMDT) received fast-track perioperative treatment and XELOX adjuvant chemotherapy. Patients in group 2 (conventional treatment) received conventional perioperative treatment and mFOLFOX6 adjuvant chemotherapy. Subgroups 1a and 2a had laparoscopic surgery and subgroups 1b and 2b had open surgery. The primary endpoint was total length of hospital stay during treatment. RESULTS: A total of 374 patients were randomly assigned to the four subgroups, and 342 patients were finally analyzed, including 87 patients in subgroup 1a, 85 in subgroup 1b, 86 in subgroup 2a, and 84 in subgroup 2b. The total hospital stay of group 1 was shorter than that of group 2 [13 days, (IQR, 11-17 days) vs. 23.5 days (IQR, 15-42 days), P = 0.0001]. Compared to group 2, group 1 had lower surgical costs, fewer in-hospital complications and faster recovery (all P < 0.05). Subgroup 1a showed faster surgical recovery than that of subgroup 1b (all P < 0.05). There was no difference in 5-year overall survival between groups 1 and 2 [87.1% (95% CI, 80.7-91.5%) vs. 87.1% (95% CI, 80.8-91.4%), P = 0.7420]. CONCLUSIONS: The FTMDT model, which integrates laparoscopic surgery, fast-track treatment, and XELOX chemotherapy, was the superior model for enhancing the recovery of Chinese patients with colorectal cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01080547 , registered on March 4, 2010.

Porous Yolk-Shell Particle Engineering via Nonsolvent-Assisted Trineedle Coaxial Electrospraying for Burn-Related Wound Healing.

Yolk-shell particles (YSPs) have attracted increasing attention from various research fields because of their low density, large surface area, and excellent loading capacity. However, the fabrication of polymer-based porous YSPs remains a great challenge. In this work, multifunctional polycaprolactone YSPs were produced using trineedle coaxial electrospraying with a simple nonsolvent process. TiO2-Ag nanoparticles and Ganoderma lucidum polysaccharides (GLPs) were encapsulated into the outer shell of the YSPs as the major antibacterial and antioxidant components, whereas iron oxide (Fe3O4) nanoparticles were incorporated into the inner core to act as a photothermal agent. The morphology and structure, chemical composition, biocompatibility, antioxidant, and antibacterial effects of the fabricated YSPs, photothermal effects, and the release profile of the encapsulated GLP were studied in vitro. Furthermore, the in vivo wound healing effects of the YSPs and the laser-assisted therapy were explored based on a burn wound model on c57 mice.

Fabrication of patterned three-dimensional micron scaled core-sheath architectures for drug patches.

Recent advances in selective integration of micro and nano-scaled features towards material design have paved way to enhance desirable properties or functions of biomaterials. For drug delivery applications these include improved active component encapsulation, controlled drug release and managed interaction with the intended host environment. Electrohydrodynamic (EHD) direct-printing technique is a one-step on demand fiber deposition method which enables precise micron-scaled topographic and structural enhancement during material fabrication. In this study, core-sheath composite fibers comprising polycaprolactone, polyvinyl pyrrolidone and the drug tetracycline hydrochloride were prepared using the coaxial format of EHD direct-printing. Once positioned and aligned; multi-stacked fibers gave rise to patches. Coaxial fiber (diameter range ~13-25 µm) optimization (deposition and integrity) involved parameter-structure (e.g. collector speed, flow rate, working distance and applied voltage) impact analysis. Water contact angle measurements, tensile testing and Fourier transform infrared spectroscopy were used to analyze core-sheath integrated patches. In-vitro drug release studies clearly elude to the impact of core-shell and patterned architectures; demonstrating their viability and the forming method as emerging tools for advanced drug delivery system design and fabrication.

Dual rotation centrifugal electrospinning: a novel approach to engineer multi-directional and layered fiber composite matrices.

In this study, a dual rotation centrifugal electrospinning system (DRCES) is designed, developed, and used to prepare medicated fabrics. Through simultaneous rotation of both spinneret and collector, multi-directional blended fiber matrices (PVP and TPU) were deposited directly on the rotating collector. To detail the process, key stages of the centrifugal electrospinning process are elaborated, and the influence of gas infusion and collector rotation speed on resulting fiber morphologies was explored. Multi-directional fibrous structures show in vitro biocompatibility (fibroblast). Regulation of drug release rate was achieved using polymer composition and filament alignment. This study demonstrates a rapid fabrication method (~ 50 g/h) to engineer layered fibrous structures using DRCES, which provides a foundation for preparing complex drug matrices (single and multi-directional) for tailored active component release.

Pharmacological effects of natural Ganoderma and its extracts on neurological diseases: A comprehensive review.

Ganoderma, has been used for clinical applications for thousands of years as a highly-nutritious and significantly-effective medicinal herb. The active components and efficacy of Ganoderma are constantly being explored and supplemented every year. In recent years, more and more literature has reported the pharmacological effects of Ganoderma on anti-tumor, liver protection and immunity enhancement, especially on neuroprotection. Numerous research works on the neuroprotective effects of Ganoderma have been documented (e.g., modulation of neurogenesis, amelioration of Alzheimer's disease, therapeutic effect on epilepsy, the protective effect on neural cells in stroke injury, etc.) thus it has drawn increasing attention. However, an integrated and comprehensive review of recent research findings has not been detailed in any great depth. Therefore, the purpose of this review is to summarize and elucidate recent progress of neuroprotective effects of natural Ganoderma and its extracts.

Synthesis and Evaluation of Herbal Chitosan from Ganoderma Lucidum Spore Powder for Biomedical Applications.

Chitosan is an extremely valuable biopolymer and is usually obtained as a byproduct from the shells of crustaceans. In the current work, chitosan is obtained from an herbal source (Ganoderma lucidum spore powder (GLSP)) for the first time. To show this, both standard (thermochemical deacetylation, (TCD)) and emerging (ultrasound-assisted deacetylation (USAD)) methods of chitosan preparation were used. The obtained chitosan was characterized by elemental analysis, XRD (X-ray diffraction), FT-IR (Fourier transform infrared spectroscopy) and thermogravimetric measurements. The process resulted in chitosan possessing comparable values of DD, [η] and [Formula: see text] to the commercial product. Chitosan obtained via both processes (TCD and USAD) displayed excellent biocompatibility; although the USAD prepared biopolymer exhibited significantly improved fibroblast (L929 cell) viability and enhanced antibacterial zones for both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The findings of new herbal chitosan mark key developments of natural biomaterials; marking a potential shift from conventional sea-based organisms.

A small molecule fibrokinase inhibitor in a model of fibropolycystic hepatorenal disease.

AIM: To evaluate the novel platelet-derived growth factor receptor and vascular endothelial growth factor receptor dual kinase inhibitor ANG3070 in a polycystic kidney disease-congenital hepatic fibrosis model. METHODS: At 6 wk of age, PCK rats were randomized to vehicle or ANG3070 for 4 wk. At 10 wk, 24 h urine and left kidneys were collected and rats were continued on treatment for 4 wk. At 14 wk, 24 h urine was collected, rats were sacrificed, and liver and right kidneys were collected for histological evaluation. For Western blot studies, PCK rats were treated with vehicle or ANG3070 for 7 d and sacrificed approximately 30 min after the last treatments. RESULTS: Compared to the wild-type cohort, the PCK kidney (Vehicle cohort) exhibited a marked increase in kidney and liver mass, hepato-renal cystic volume, hepato-renal fibrosis and hepato-renal injury biomarkers. Intervention with ANG3070 in PCK rats decreased kidney weight, reduced renal cystic volume and reduced total kidney hydroxyproline, indicating significantly reduced rental interstitial fibrosis compared to the PCK-Vehicle cohort. ANG3070 treatment also mitigated several markers of kidney injury, including urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, cystatin C and interleukin-18 levels. In addition, this treatment attenuated key indices of renal dysfunction, including proteinuria, albuminuria and serum blood urea nitrogen and creatinine, and significantly improved renal function compared to the PCK-Vehicle cohort. ANG3070 treatment also significantly decreased liver enlargement, hepatic lesions, and liver fibrosis, and mitigated liver dysfunction compared to the PCK-Vehicle cohort. CONCLUSION: These results suggest that ANG3070 has the potential to slow disease, and may serve as a bridge toward hepato-renal transplantation in patients with fibropolycystic disease.

Targeting oxidative stress using tri-needle electrospray engineered Ganoderma lucidum polysaccharide-loaded porous yolk-shell particles.

Chronic lung diseases (e.g. chronic obstructive pulmonary disease and asthma) are associated with oxidative stress and common treatments include various types of inhalation therapies. In this work Ganoderma lucidum polysaccharide (GLP), a naturally occurring antioxidant is loaded into porous Poly (ε-caprolactone) (PCL) particles using a single step tri-needle coaxial electrospray process (Tri-needle CES); with a view to develop therapies to combat oxidative stress. Based on the core-shell structure of porous yolk shell particles (YSPs), GLP-loaded YSPs displayed a bi-phasic release pattern. In vitro cell studies indicate GLP-loaded porous YSPs display good biocompatibility and positive attributes towards H2O2-induced oxidative stress in MRC-5 cells and dramatically attenuate intracellular reactive oxygen species (ROS) levels as well as significantly increase cell viability. In vivo inhalation studies indicate that GLP-loaded porous YSPs can be delivered to deep lung tissue and remain deposited for over 48 h and are subsequently removed by natural clearance mechanisms. Based on current findings GLP-loaded porous YSPs are suitable for pulmonary delivery and display good inhalation therapy potential to treat chronic lung diseases.

POPCORN: A web service for individual PrognOsis prediction based on multi-center clinical data CollabORatioN without patient-level data sharing.

BACKGROUND AND OBJECTIVE: Clinical prognosis prediction plays an important role in clinical research and practice. The construction of prediction models based on electronic health record data has recently become a research focus. Due to the lack of external validation, prediction models based on single-center, hospital-specific datasets may not perform well with datasets from other medical institutions. Therefore, research investigating prognosis prediction model construction based on a collaborative analysis of multi-center electronic health record data could increase the number and coverage of patients used for model training, enrich patient prognostic features and ultimately improve the accuracy and generalization of prognosis prediction. MATERIALS AND METHODS: A web service for individual prognosis prediction based on multi-center clinical data collaboration without patient-level data sharing (POPCORN) was proposed. POPCORN focuses on solving key issues in multi-center collaborative research based on electronic health record systems; these issues include the standardization of clinical data expression, the preservation of patient privacy during model training and the effect of case mix variance on the prediction model construction and application. POPCORN is based on a multivariable meta-analysis and a Bayesian framework and can construct suitable prediction models for multiple clinical scenarios that can effectively adapt to complex clinical application environments. RESULTS: POPCORN was validated using a joint, multi-center collaborative research network between China and the United States with patients diagnosed with colorectal cancer. The performance of the models based on POPCORN was comparable to that of the standard prognosis prediction model; however, POPCORN did not expose raw patient data. The prediction models had similar AUC, but the BMA model had the lowest ECI across all prediction models, indicating that this model had better calibration performance than the other models, especially for patients in Chinese hospitals. CONCLUSIONS: The POPCORN system can build prediction models that perform well in complex clinical application scenarios and can provide effective decision support for individual patient prognostic predictions.

Three-Dimensional Electrohydrodynamic Printing and Spinning of Flexible Composite Structures for Oral Multidrug Forms.

A simple method to rapidly customize and to also mass produce oral dosage forms is arguably a current bottleneck in the development of modern personalized medicine. Specifically, delayed-release mechanisms with well-controlled dosage profiles for combinations of traditional Chinese herbal extracts and Western medications are not well established. Herein, we demonstrate a novel multidrug-loaded membrane sandwich with structures infused with ibuprofen (IBU) and Ganoderma lucidum polysaccharide (GLP) using three-dimensional electrohydrodynamic printing and electrospinning techniques. The resulting flexible membrane consists of microscaled, multilayered cellulose acetate (CA) membranes loaded with IBU in the shape of either concentric squares or circles, as the top and bottom layers of a sandwich structure. In between the CA-IBU layers are randomly electrospun polyvinyl pyrrolidone (PVP) layers loaded with GLP. The complete fibrous membrane sandwich can be folded and embedded into a 0-size capsule to achieve oral compliance. Simulated in vitro testing of gastric and intestinal fluids demonstrated a triphasic release profile. There was an immediate release of GLP after gastric juices dissolved the capsule shell and the PVP, followed by the short-term release of 60% of the IBU within an hour afterward, and the remaining IBU was released in a sustained manner following a Fickian diffusion profile. In summary, this multidrug (both hydrophilic and/or hydrophobic) oral system with precision-designed structures should enable personalized therapeutic dosing.

Intradialytic blood pressure pattern recognition based on density peak clustering.

End-stage renal disease (ESRD) is the final stage of chronic kidney disease (CKD) and requires hemodialysis (HD) for survival. Intradialytic blood pressure (IBP) measurements are necessary to ensure patient safety during HD treatments and have critical clinical and prognostic significance. Studies on IBP measurements, especially IBP patterns, are limited. All related studies have been based on a priori knowledge and artificially classified IBP patterns. Therefore, the results were influenced by subjective concepts. In this study, we proposed a new approach to identify IBP patterns to classify ESRD patients. We used the dynamic time warping (DTW) algorithm to measure the similarity between two series of IBP data. Five blood pressure (BP) patterns were identified by applying the density peak clustering algorithm (DPCA) to the IBP data. To illustrate the association between BP patterns and prognosis, we constructed three random survival forest (RSF) models with different covariates. Model accuracy was improved 3.7-6.3% by the inclusion of BP patterns. The results suggest that BP patterns have critical clinical and prognostic significance regarding the risk of cerebrovascular events. We can also apply this clustering approach to other time series data from electronic health records (EHRs). This work is generalizable to analyses of dense EHR data.

The role of multislice computed tomography of the costal cartilage in adult age estimation.

To establish population-specific age estimation models in adults from costal cartilage for contemporary Chinese by using three-dimensional volume-rendering technique. Five hundred and twelve individuals (254 females and 258 males) with documented ages between 20 and 85 years were retrospectively included. Their clinical CT examinations (1 mm slice thickness) were used to develop the sex-specific age prediction model. A validation sample comprising 26 female and 24 male individuals was then used to test the predictive accuracy of the established models. Simple linear regression (SLR), multiple linear regression (MLR), gradient boosting regression (GBR), support vector machine (SVM), and decision tree regression (DTR) were utilized to build the age diagnosis models from calibration samples. By comparison, the decision tree regression was the relatively more accurate age prediction model for male, with mean absolute error = 5.31 years, least absolute error = 0.10 years, correct percentage within 5 years = 54%, and the correct percentage within 10 years = 88%. The stepwise multiple linear regression equations was the relatively more accurate one for female, with mean absolute error = 6.72 years, least absolute error = 0.68 years, correct percentage within 5 years = 42%, and correct percentage within 10 years = 77%. Our results indicated that the present established age estimation model can be applied as an additional guidance for age estimation in adults.

Anti-steatotic and anti-fibrotic effects of the KCa3.1 channel inhibitor, Senicapoc, in non-alcoholic liver disease.

AIM: To evaluate a calcium activated potassium channel (KCa3.1) inhibitor attenuates liver disease in models of non-alcoholic fatty liver disease (NAFLD). METHODS: We have performed a series of in vitro and in vivo studies using the KCa3.1 channel inhibitor, Senicapoc. Efficacy studies of Senicapoc were conducted in toxin-, thioacetamide (TAA) and high fat diet (HFD)-induced models of liver fibrosis in rats. Efficacy and pharmacodynamic effects of Senicapoc was determined through biomarkers of apoptosis, inflammation, steatosis and fibrosis. RESULTS: Upregulation of KCa3.1 expression was recorded in TAA-induced and high fat diet-induced liver disease. Treatment with Senicapoc decreased palmitic acid-driven HepG2 cell death. (P < 0.05 vs control) supporting the finding that Senicapoc reduces lipid-driven apoptosis in HepG2 cell cultures. In animals fed a HFD for 6 wk, co-treatment with Senicapoc, (1) reduced non-alcoholic fatty liver disease (NAFLD) activity score (NAS) (0-8 scale), (2) decreased steatosis and (3) decreased hepatic lipid content (Oil Red O, P < 0.05 vs vehicle). Randomization of TAA animals and HFD fed animals to Senicapoc was associated with a decrease in liver fibrosis as evidenced by hydroxyproline and Masson's trichrome staining (P < 0.05 vs vehicle). These results demonstrated that Senicapoc mitigates both steatosis and fibrosis in liver fibrosis models. CONCLUSION: These data suggest that Senicapoc interrupts more than one node in progressive fatty liver disease by its anti-steatotic and anti-fibrotic activities, serving as a double-edged therapeutic sword.

An ontology-based approach to patient follow-up assessment for continuous and personalized chronic disease management.

OBJECTIVE: Chronic diseases are complex and persistent clinical conditions that require close collaboration among patients and health care providers in the implementation of long-term and integrated care programs. However, current solutions focus partially on intensive interventions at hospitals rather than on continuous and personalized chronic disease management. This study aims to fill this gap by providing computerized clinical decision support during follow-up assessments of chronically ill patients at home. METHODS: We proposed an ontology-based framework to integrate patient data, medical domain knowledge, and patient assessment criteria for chronic disease patient follow-up assessments. A clinical decision support system was developed to implement this framework for automatic selection and adaptation of standard assessment protocols to suit patient personal conditions. We evaluated our method in the case study of type 2 diabetic patient follow-up assessments. RESULTS: The proposed framework was instantiated using real data from 115,477 follow-up assessment records of 36,162 type 2 diabetic patients. Standard evaluation criteria were automatically selected and adapted to the particularities of each patient. Assessment results were generated as a general typing of patient overall condition and detailed scoring for each criterion, providing important indicators to the case manager about possible inappropriate judgments, in addition to raising patient awareness of their disease control outcomes. Using historical data as the gold standard, our system achieved a rate of accuracy of 99.93% and completeness of 95.00%. CONCLUSIONS: This study contributes to improving the accessibility, efficiency and quality of current patient follow-up services. It also provides a generic approach to knowledge sharing and reuse for patient-centered chronic disease management.

Time-dependent and nonlinear effects of prognostic factors in nonmetastatic colorectal cancer.

The survival risk following curative surgery for nonmetastatic colorectal cancer (CRC) may be over- or underestimated due to a lack of attention to nonlinear effects and violation of the proportional hazards assumption. In this paper, we aimed to detect and interpret the shape of time-dependent and nonlinear effects to improve the predictive performance of models of prognoses in nonmetastatic CRC patients. Data for nonmetastatic CRC patients diagnosed between 2004 and 2012 were obtained from the Surveillance Epidemiology End Results registry. Time-dependent and nonlinear effects were tested and plotted. A nonlinear model that used random survival forests was implemented. The estimated 5-year cancer-specific death rate was 17.95% (95% CI, 17.70-18.20%). Tumor invasion depth, lymph node status, age at diagnosis, tumor grade, histology and tumor site were significantly associated with cancer-specific death. Nonlinear and time-dependent effects on survival were detected. Positive lymph node number had a larger effect per unit of measurement at low values than at high values, whereas age at diagnosis showed the opposite pattern. Moreover, nonproportional hazards were detected for all covariates, indicating that the contributions of these risks to survival outcomes decreased over time. The nonlinear model predicted prognoses more accurately (C-index: 0.7934, 0.7933-0.7934) than did the Fine and Gray model (C-index: 0.7550, 0.7510-0.7583). The three-dimensional cumulative incidence curves derived from nonlinear model were used to identify the change points of the risk trends. It would be useful to implement these findings in treatment plans and follow-up surveillance in nonmetastatic CRC patients.