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Background: To allow early diagnosis and monitoring of disease progression, there is a need for biomarkers in amyotrophic lateral sclerosis (ALS). Neurofilaments (NF) are emerging protein biomarkers in other neurological diseases, and are of possible use in ALS. Objective: The aim of this study is to evaluate the utility of NF levels as blood or cerebrospinal fluid (CSF) biomarker in patients with ALS. Methods: A systematic search of Pubmed, Embase and Scopus was performed. Methodological quality assessment was applied to refine the final search results. Meta-analysis of the data was performed. Results: Level of NF heavy chain and light chains were significantly elevated in the CSF of ALS patients compared to healthy controls/controls without parenchymal central nervous system (CNS) involvement and ALS mimic disease patients. NF light chain level in CSF was higher in ALS patients than in neurological patients with CNS involvement (SMD = 1.352, P = 0.01). NF light chain concentration in blood was higher in ALS patients than healthy controls/controls without CNS involvement (SMD = 1.448, P<0.0001). NF heavy chain levels in CSF were negatively correlated disease duration and ALSFRS-R ((r = -0.447, P<0.0001; r = -0.486, P<0.0001). NF light chain levels in CSF were negatively correlated with disease duration (r = -0.273, P = 0.011). Conclusion: NF heavy and light chain levels have potential use as a marker of neural degeneration in ALS, but are not specific for the disease, and are more likely to be used as measures of disease progression. [ABSTRACT FROM AUTHOR]

To eliminate and eradicate gambiense human African trypanosomiasis (HAT), maximizing the effectiveness of active case finding is of key importance. The progression of the epidemic is largely influenced by the planning of these operations. This paper introduces and analyzes five models for predicting HAT prevalence in a given village based on past observed prevalence levels and past screening activities in that village. Based on the quality of prevalence level predictions in 143 villages in Kwamouth (DRC), and based on the theoretical foundation underlying the models, we consider variants of the Logistic Model—a model inspired by the SIS epidemic model—to be most suitable for predicting HAT prevalence levels. Furthermore, we demonstrate the applicability of this model to predict the effects of planning policies for screening operations. Our analysis yields an analytical expression for the screening frequency required to reach eradication (zero prevalence) and a simple approach for determining the frequency required to reach elimination within a given time frame (one case per 10000). Furthermore, the model predictions suggest that annual screening is only expected to lead to eradication if at least half of the cases are detected during the screening rounds. This paper extends knowledge on control strategies for HAT and serves as a basis for further modeling and optimization studies. [ABSTRACT FROM AUTHOR]

Background: Neither environmental nor genetic factors are sufficient to predict the transdiagnostic expression of psychosis. Therefore, analysis of gene-environment interactions may be productive. Objective: A meta-analysis was performed using papers investigating the interaction between cannabis use and catechol-O-methyl transferase (COMT) polymorphism Val158Met (COMTVal158Met). Data sources: PubMed, Embase, PsychInfo. Study eligibility criteria: All observational studies assessing the interaction between COMTVal158Met and cannabis with any psychosis or psychotic symptoms measure as an outcome. Study appraisal and synthesis methods: A meta-analysis was performed using the Meta-analysis of Observational Studies in Epidemiology guidelines and forest plots were generated. Thirteen articles met the selection criteria: 7 clinical studies using a case-only design, 3 clinical studies with a dichotomous outcome, and 3 studies analysing a continuous outcome of psychotic symptoms below the threshold of psychotic disorder. The three study types were analysed separately. Validity of the included studies was assessed using "A Cochrane Risk of Bias Assessment Tool: for Non-Randomized Studies of Interventions". Results: For case-only studies, a significant interaction was found between cannabis use and COMTVal158Met, with an OR of 1.45 (95% Confidence Interval = 1.05–2.00; Met/Met as the risk genotype). However, there was no evidence for interaction in either the studies including dichotomous outcomes (B = -0.51, 95% Confidence Interval -1.72, 0.70) or the studies including continuous outcomes (B = -0.04 95% Confidence Interval -0.16–0.08). Limitation: A substantial part of the included studies used the case-only design, which has lower validity and tends to overestimate true effects. Conclusion: The interaction term between cannabis use and COMTVal158Met was only statistically significant in the case-only studies, but not in studies using other clinical or non-clinical psychosis outcomes. Future additional high quality studies might change current perspectives, yet currently evidence for the interaction remains unconvincing. [ABSTRACT FROM AUTHOR]

Background: Minimal hepatic encephalopathy (MHE) is clinically undetectable and the diagnosis requires psychometric tests. However, a lack of clarity exists as to whether the tests are in fact able to detect changes in cognition. Aim: To examine if the continuous reaction time test (CRT) can detect changes in cognition with anti-HE intervention in patients with cirrhosis and without clinically manifest hepatic encephalopathy (HE). Methods: Firstly, we conducted a reproducibility analysis and secondly measured change in CRT induced by anti-HE treatment in a randomized controlled pilot study: We stratified 44 patients with liver cirrhosis and without clinically manifest HE according to a normal (n = 22) or abnormal (n = 22) CRT. Each stratum was then block randomized to receive multimodal anti-HE intervention (lactulose+branched-chain amino acids+rifaximin) or triple placebos for 3 months in a double-blinded fashion. The CRT is a simple PC-based test and the test result, the CRT index (normal threshold > 1.9), describes the patient’s stability of alertness during the 10–minute test. Our study outcome was the change in CRT index in each group at study exit. The portosystemic encephalopathy (PSE) test, a paper-and-pencil test battery (normal threshold above -5), was used as a comparator test according to international guidelines. Results: The patients with an abnormal CRT index who were randomized to receive the active intervention normalized or improved their CRT index (mean change 0.92 ± 0.29, p = 0.01). Additionally, their PSE improved (change 3.85 ± 1.83, p = 0.03). There was no such effect in any of the other study groups. Conclusion: In this cohort of patients with liver cirrhosis and no manifest HE, the CRT identified a group in whom cognition improved with intensive anti-HE intervention. This finding infers that the CRT can detect a response to treatment and might help in selecting patients for treatment. [ABSTRACT FROM AUTHOR]

The recently proposed Parkinson’s Disease (PD) telediagnosis systems based on detecting dysphonia achieve very high classification rates in discriminating healthy subjects from PD patients. However, in these studies the data used to construct the classification model contain the speech recordings of both early and late PD patients with different severities of speech impairments resulting in unrealistic results. In a more realistic scenario, an early telediagnosis system is expected to be used in suspicious cases by healthy subjects or early PD patients with mild speech impairment. In this paper, considering the critical importance of early diagnosis in the treatment of the disease, we evaluate the ability of vocal features in early telediagnosis of Parkinson's Disease (PD) using machine learning techniques with a two-step approach. In the first step, using only patient data, we aim to determine the patient group with relatively greater severity of speech impairments using Unified Parkinson’s Disease Rating Scale (UPDRS) score as an index of disease progression. For this purpose, we use three supervised and two unsupervised learning techniques. In the second step, we exclude the samples of this group of patients from the dataset, create a new dataset consisting of the samples of PD patients having less severity of speech impairments and healthy subjects, and use three classifiers with various settings to address this binary classification problem. In this classification problem, the highest accuracy of 96.4% and Matthew’s Correlation Coefficient of 0.77 is obtained using support vector machines with third-degree polynomial kernel showing that vocal features can be used to build a decision support system for early telediagnosis of PD. [ABSTRACT FROM AUTHOR]

Purpose: Visual Stress (VS) is a condition in which words appear blurred, in motion, or otherwise distorted when reading. Some people diagnosed with VS find that viewing black text on white paper through coloured overlays or precision tinted lenses (PTLs) reduces symptoms attributed to VS. The aim of the present study is to determine whether the choice of colour of overlays or PTLs is influenced by a patient’s gender. Methods: Records of all patients attending a VS assessment in two optometry practices between 2009 and 2014 were reviewed retrospectively. Patients who reported a significant and consistent reduction in symptoms with either overlay and or PTL were included in the analysis. Overlays and PTLs were categorized as stereotypical male, female or neutral colours based on gender preferences as described in the literature. Chi-square analysis was carried out to determine whether gender (across all ages or within age groups) was associated with overlay or PTL colour choice. Results: 279 patients (133 males and 146 females, mean age 17 years) consistently showed a reduction in symptoms with an overlay and were included. Chi-square analysis revealed no significant association between the colour of overlay chosen and male or female gender (Chi-square 0.788, p = 0.674). 244 patients (120 males and 124 females, mean age 24.5 years) consistently showed a reduction in symptoms with PTLs and were included. Chi-square analysis revealed a significant association between stereotypical male/female/neutral colours of PTLs chosen and male/female gender (Chi-square 6.46, p = 0.040). More males preferred stereotypical male colour PTLs including blue and green while more females preferred stereotypical female colour PTLs including pink and purple. Conclusions: For some VS patients, the choice of PTL colour is influenced not only by the alleviation of symptoms but also by other non-visual factors such as gender. [ABSTRACT FROM AUTHOR]

Nowadays, drug abuse and addiction are serious public health problems in the USA. Methamphetamine (METH) is one of the most abused drugs and is known to cause brain damage after repeated exposure. In this paper, we conducted a neuroproteomic study to evaluate METH-induced brain protein dynamics, following a two-week chronic regimen of an escalating dose of METH exposure. Proteins were extracted from rat brain hippocampal and olfactory bulb tissues and subjected to liquid chromatography-mass spectrometry (LC-MS/MS) analysis. Both shotgun and targeted proteomic analysis were performed. Protein quantification was initially based on comparing the spectral counts between METH exposed animals and their control counterparts. Quantitative differences were further confirmed through multiple reaction monitoring (MRM) LC-MS/MS experiments. According to the quantitative results, the expression of 18 proteins (11 in the hippocampus and 7 in the olfactory bulb) underwent a significant alteration as a result of exposing rats to METH. 13 of these proteins were up-regulated after METH exposure while 5 were down-regulated. The altered proteins belonging to different structural and functional families were involved in processes such as cell death, inflammation, oxidation, and apoptosis. [ABSTRACT FROM AUTHOR]

Objectives: To determine the potential of intravoxel incoherent motion (IVIM) MR imaging for staging of hepatic fibrosis (HF). Methods: We searched PubMed and EMBASE from their inception to 31 July 2015 to select studies reporting IVIM MR imaging and HF staging. We defined F1-2 as non-advanced HF, F3-4 as advanced HF, F0 as normal liver, F1 as very early HF, and F2-4 as significant HF. Then we compared stage F0 with F1, F0-1 with F2-3, and F1-2 with F3-4 using IVIM-derived parameters (pseudo-diffusion coefficient D*, perfusion fraction f, and pure molecular diffusion parameter D). The effect estimate was expressed as a pooled weighted mean difference (WMD) with 95% confidence interval (CI), using the fixed-effects model. Results: Overall, we included six papers (406 patients) in this study. Significant differences in D* were observed between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 2.46, 95% CI 0.83–4.09, P = 0.006; WMD 13.10, 95% CI 9.53–16.67, P < 0.001; WMD 14.34, 95% CI 10.26–18.42, P < 0.001, respectively). Significant differences in f were also found between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 1.62, 95% CI 0.06–3.18, P = 0.027; WMD 5.63, 95% CI 2.74–8.52, P < 0.001; WMD 3.30, 95% CI 2.10–4.50, P < 0.001, respectively). However, D showed no differences between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 0.05, 95% CI -0.01─0.11, P = 0.105; WMD 0.04, 95% CI -0.01─0.10, P = 0.230; WMD 0.02, 95% CI -0.02─0.06, P = 0.378, respectively). Conclusions: IVIM MR imaging provides an effective method of staging HF and can distinguish early HF from normal liver, significant HF from normal liver or very early HF, and advanced HF from non-advanced HF. [ABSTRACT FROM AUTHOR]

Background: While iron deficiency (ID) is a frequent cause of anemia in hemodialysis patients, the clinical impact of ID without anemic level of hemoglobin remains unclear. As such, this study was designed to clarify the manifestations of ID itself in subjects on hemodialysis. Methods: Maintenance hemodialysis patients achieving target hemoglobin levels (≥ 10.0g/dL) under treatment in our clinic were stratified for comparison from three perspectives: ID (transferrin saturation [TSAT] < 20% or ferritin < 100ng/mL) vs non-ID, level of TSAT (< or ≥ 20%), and level of serum ferritin concentration (< or ≥ 100ng/mL). The severity of frequent symptoms was determined by a self-rating symptom score questionnaire, and the rate of those with severe manifestations was calculated for each symptom. Significant difference was examined between groups; univariate and adjusted multivariate odds ratios and 95% confidence intervals were obtained by logistic regression. Results: Among 154 subjects selected for analysis, the ratio of severe arthralgia and fatigue was significantly higher in the ID group (n = 94) compared to the non-ID group (n = 60), in both univariate and adjusted multivariate analyses. Moreover, in multivariate analysis, low TSAT was significantly associated with exacerbation of pain during vascular access puncture and intradialytic leg cramps, while low serum ferritin concentration was related to significant increase in severe arthralgia, fatigue, intradialytic headache and leg cramps. Conclusions: ID was identified as a risk factor regarding severity of several symptoms even without low hemoglobin level among chronic hemodialysis patients, and supplementation of iron was considered efficacious for improving critical symptoms affecting those undergoing maintenance dialysis. [ABSTRACT FROM AUTHOR]

Background: Diagnosis of fetal anomaly is a significant life event and social stigma can negatively impact on the well-being of women opting for an abortion. This study investigated the psychometric properties of a measure of stigma among women who had had an abortion after diagnosis of fetal anomaly in a German setting. Methods: The Individual Level Abortion Stigma (ILAS) scale was translated into German. Psychometric properties of the ILAS scale were examined among 130 women with a history of an abortion after diagnosis of fetal anomaly. Individual and situational factors associated with stigma in the context of an abortion after diagnosis of fetal anomaly were explored. Results: Factor analysis suggested a four-dimensional structure of the German version of the Individual Level Abortion Stigma scale (Cronbach’s α, .83–.91), corresponding to the subscales of the original scale. Test-retest reliability was acceptable for the worries about judgment subscale, the self-judgment subscale, and the community condemnation subscale, but less convincing for the isolation subscale. Associations between the subscales and measures of depression, self-esteem and secrecy were found in directions consistent with theory. Women who did not perceive their fetus to have a low survival chance and women whose fetus was at higher gestational age reported higher levels of stigma, whereas higher perceived partner support was associated with lower levels of stigma. Limitation: Generalizability of study results was limited, as participants were recruited from one clinic in Germany and the study had a response rate of 46.5%. Conclusions: The ILAS subscales are largely reliable and valid measures to assess stigma among women who have had an abortion after diagnosis of fetal anomaly. Suggestions for improving the assessment of stigma experienced in this population are outlined. The scales can be useful in research aiming at investigating psychological outcomes of abortion after diagnosis of fetal anomaly and improving care structures. [ABSTRACT FROM AUTHOR]

Introduction: Diffusion Tensor MRI (DT-MRI) is a promising tool for the evaluation of brachial plexus pathology. Therefore, we introduce and evaluate a fast DT-MRI protocol (8min33s scanning with 5–10 min postprocessing time) for the brachial plexus. Materials and methods: Thirty healthy volunteers within three age-groups (18–35, 36–55, and > 56) received DT-MRI of the brachial-plexus twice. Means of fractional-anisotropy (FA), mean-diffusivity (MD), axial-diffusivity (AD), and radial-diffusivity (RD) for the individual roots and trunks were evaluated. A stepwise forward approach was applied to test for correlations with age, sex, body-mass-index (BMI), bodysurface, height, and bodyweight. Within-subject, intra-rater, and inter-rater repeatability were assessed using Bland-Altman analysis, coefficient of variation (CV), intraclass-correlation (ICC), and minimal detectable difference (MDD). Results: No differences between sides and root levels were found. MD, AD, and RD correlated (P < 0.05) with bodyweight. Within-subject quantification proved repeatable with CVs for FA, MD, AD, and RD of 16%, 12%, 11%, and 14%, respectively. Discussion: The DT-MRI protocol was fast and repeatable. Found correlations should be considered in future studies of brachial plexus pathology. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study is to provide an updated systematic review to identify studies describing the prevalence of psychosis in order to explore methodological factors that could account for the variation in prevalence estimates. Methods: Studies with original data related to the prevalence of psychosis (published between 1990 and 2015) were identified via searching electronic databases and reviewing manual citations. Prevalence estimates were sorted according to prevalence type (point, 12-months and lifetime). The independent association between key methodological variables and the mean effect of prevalence was examined (prevalence type, case-finding setting, method of confirming diagnosis, international classification of diseases, diagnosis category, and study quality) by meta-analytical techniques and random-effects meta-regression. Results: Seventy-three primary studies were included, providing a total of 101 estimates of prevalence rates of psychosis. Across these studies, the pooled median point and 12-month prevalence for persons was 3.89 and 4.03 per 1000 respectively; and the median lifetime prevalence was 7.49 per 1000. The result of the random-effects meta-regression analysis revealed a significant effect for the prevalence type, with higher rates of lifetime prevalence than 12-month prevalence (p<0.001). Studies conducted in the general population presented higher prevalence rates than those carried out in populations attended in health/social services (p = 0.006). Compared to the diagnosis of schizophrenia only, prevalence rates were higher in the probable psychotic disorder (p = 0.022) and non-affective psychosis (p = 0.009). Finally, a higher study quality is associated with a lower estimated prevalence of psychotic disorders (p<0.001). Conclusions: This systematic review provides a comprehensive comparison of methodologies used in studies of the prevalence of psychosis, which can provide insightful information for future epidemiological studies in adopting the most relevant methodological approach. [ABSTRACT FROM AUTHOR]

Applying differentially expressed genes (DEGs) to identify feasible biomarkers in diseases can be a hard task when working with heterogeneous datasets. Expression data are strongly influenced by technology, sample preparation processes, and/or labeling methods. The proliferation of different microarray platforms for measuring gene expression increases the need to develop models able to compare their results, especially when different technologies can lead to signal values that vary greatly. Integrative meta-analysis can significantly improve the reliability and robustness of DEG detection. The objective of this work was to develop an integrative approach for identifying potential cancer biomarkers by integrating gene expression data from two different platforms. Pancreatic ductal adenocarcinoma (PDAC), where there is an urgent need to find new biomarkers due its late diagnosis, is an ideal candidate for testing this technology. Expression data from two different datasets, namely Affymetrix and Illumina (18 and 36 PDAC patients, respectively), as well as from 18 healthy controls, was used for this study. A meta-analysis based on an empirical Bayesian methodology (ComBat) was then proposed to integrate these datasets. DEGs were finally identified from the integrated data by using the statistical programming language R. After our integrative meta-analysis, 5 genes were commonly identified within the individual analyses of the independent datasets. Also, 28 novel genes that were not reported by the individual analyses (‘gained’ genes) were also discovered. Several of these gained genes have been already related to other gastroenterological tumors. The proposed integrative meta-analysis has revealed novel DEGs that may play an important role in PDAC and could be potential biomarkers for diagnosing the disease. [ABSTRACT FROM AUTHOR]

Background: Few studies have reported the diagnostic variability in patients with a possible usual interstitial pneumonia (UIP) pattern on high-resolution CT (HRCT) who underwent surgical lung biopsy (SLB), and the prognostic factors for these patients have not been fully evaluated. We retrospectively investigated the frequency of idiopathic pulmonary fibrosis (IPF) and prognostic factors in patients with possible UIP pattern on HRCT. Methods: Consecutive patients who had a possible UIP pattern on HRCT, underwent SLB, and had a diagnosis of IIPs before SLB were retrospectively recruited from 10 hospitals. Diagnoses were made based on multidisciplinary discussion using the criteria for current IPF guidelines and multidisciplinary classification for IIPs in each hospital. Results: 179 patients who underwent SLB were enrolled. The diagnoses were IPF in 91 patients (51%), unclassifiable IIPs in 47 (26%), idiopathic NSIP in 18 (10%), and chronic hypersensitivity pneumonia in 17 (9%). One-year FVC changes showed significant differences between IPF and non-IPF (-138.6 mL versus 18.2 mL, p = 0.014). Patients with IPF had a worse mortality than those with non-IPF (Logrank test, p = 0.025). Multivariable Cox regression analysis demonstrated that diagnoses of IPF (HR, 2.961; 95% CI, 1.183–7.410; p = 0.02), high modified MRC score (HR, 1.587; 95% CI, 1.003–2.510; p = 0.049), and low %FVC (HR, 0.972; 95% CI, 0.953–0.992; p = 0.005). Conclusions: About a half of patients with a possible UIP pattern on HRCT had diagnoses other than IPF, and patients with IPF had a worse mortality than those with an alternative diagnosis. We reaffirmed that multidisciplinary discussion is crucial in patients with possible UIP pattern on HRCT. [ABSTRACT FROM AUTHOR]

Glioma is the most common malignant intracranial tumour. Recently, several publications have suggested that miRNAs can be used as potential diagnostic biomarkers of glioma. Here we performed a meta-analysis to identify the diagnostic accuracy of differentially expressed circulating miRNAs in gliomas. Using PubMed, Medline and Cochrane databases, we searched for studies which evaluated a single or panel of miRNAs from circulating blood as potential biomarkers of glioma. Sixteen publications involving 23 studies of miRNAs from serum or plasma met our criteria and were included in this meta-analysis. The pooled diagnostic parameters were calculated by random effect models and overall diagnostic performance of altered miRNAs was illustrated by the summary receiver operator characteristic (SROC) curves. The pooled sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) from each study were calculated. The pooled PLR, NLR and Diagnostic Odds Ratio were 6.39 (95% CI, 4.61–8.87), 0.15 (95% CI, 0.11–0.21) and 41.91 (95% CI, 23.15–75.88), respectively. The pooled sensitivity, specificity and area under the curve (AUC) were 0.87 (95% CI, 0.82–0.91), 0.86 (95% CI, 0.82–0.90) and 0.93 (95% CI, 0.91–0.95), respectively. This meta-analysis demonstrated that circulating miRNAs are capable of distinguishing glioma from healthy controls. Circulating miRNAs are promising diagnostic biomarkers for glioma and can potentially be used as a non-invasive early detection. [ABSTRACT FROM AUTHOR]

Background: Advances in bronchoscopy and CT-guided lung biopsy have improved the evaluation of small pulmonary lesions (PLs), leading to an increase in preoperative histological diagnosis. We aimed to evaluate the efficacy and safety of transbronchial lung biopsy using radial endobronchial ultrasound and virtual bronchoscopic navigation (TBLB-rEBUS&VBN) and CT-guided transthoracic needle biopsy (CT-TNB) for tissue diagnosis of small PLs. Methods: A systematic search was performed in five electronic databases, including MEDLINE, EMBASE, Cochrane Library Central Register of Controlled Trials, Web of Science, and Scopus, for relevant studies in May 2016; the selected articles were assessed using meta-analysis. The articles were limited to those published after 2000 that studied small PLs ≤ 3 cm in diameter. Results: From 7345 records, 9 articles on the bronchoscopic (BR) approach and 15 articles on the percutaneous (PC) approach were selected. The pooled diagnostic yield was 75% (95% confidence interval [CI], 69–80) using the BR approach and 93% (95% CI, 90–96) using the PC approach. For PLs ≤ 2 cm, the PC approach (pooled diagnostic yield: 92%, 95% CI: 88–95) was superior to the BR approach (66%, 95% CI: 55–76). However, for PLs > 2 cm but ≤ 3 cm, the diagnostic yield using the BR approach was improved to 81% (95% CI, 75–85). Complications of pneumothorax and hemorrhage were rare with the BR approach but common with the PC approach. Conclusions: CT-TNB was superior to TBLB-rEBUS&VBN for the evaluation of small PLs. However, for lesions greater than 2 cm, the BR approach may be considered considering its diagnostic yield of over 80% and the low risk of procedure-related complications. [ABSTRACT FROM AUTHOR]

Background and objectives: ADPKD is erroneously perceived as a not rare condition, which is mainly due to the repeated citation of a mistaken interpretation of old epidemiological data, as reported in the Dalgaard's work (1957). Even if ADPKD is not a common condition, the correct prevalence of ADPKD in the general population is uncertain, with a wide range of estimations reported by different authors. In this work, we have performed a meta-analysis of available epidemiological data in the European literature. Furthermore we collected the diagnosis and clinical data of ADPKD in a province in the north of Italy (Modena). We describe the point and predicted prevalence of ADPKD, as well as the main clinical characteristics of ADPKD in this region. Methods: We looked at the epidemiological data according to specific parameters and criteria in the Pubmed, CINAHL, Scopus and Web of Science databases. Data were summarized using linear regression analysis. We collected patients’ diagnoses in the Province of Modena according to accepted clinical criteria and/or molecular analysis. Predicted prevalence has been calculated through a logistic regression prediction applied to the at-risk population. Results: The average prevalence of ADPKD, as obtained from 8 epidemiological studies of sufficient quality, is 2.7: 10,000 (CI95 = 0.73–4.67). The point prevalence of ADPKD in the province of Modena is 3.63: 10,000 (CI95 = 3.010–3.758). On the basis of the collected pedigrees and identification of the at-risk subjects, the predicted prevalence in the Province of Modena is 4.76: 10,000 (CI 95% = 4.109–4.918). Conclusion: As identified in our study, point prevalence is comparable with the majority of the studies of literature, while predicted prevalence (4.76: 10,000) generally appears higher than in the previous estimates of the literature, with a few exceptions. Thus, this could suggest that undiagnosed ADPKD subjects, as predicted by our approach, could be relevant and will most likely require more clinical attention. Nevertheless, our estimation, in addition to the averaged ones derived from literature, not exceeding the limit of 5:10,000 inhabitants, are compatible with the definition of rare disease adopted by the European Medicines Agency and Food and Drug Administration. [ABSTRACT FROM AUTHOR]

Predicting novel microRNA (miRNA)-disease associations is clinically significant due to miRNAs’ potential roles of diagnostic biomarkers and therapeutic targets for various human diseases. Previous studies have demonstrated the viability of utilizing different types of biological data to computationally infer new disease-related miRNAs. Yet researchers face the challenge of how to effectively integrate diverse datasets and make reliable predictions. In this study, we presented a computational model named Laplacian Regularized Sparse Subspace Learning for MiRNA-Disease Association prediction (LRSSLMDA), which projected miRNAs/diseases’ statistical feature profile and graph theoretical feature profile to a common subspace. It used Laplacian regularization to preserve the local structures of the training data and a L1-norm constraint to select important miRNA/disease features for prediction. The strength of dimensionality reduction enabled the model to be easily extended to much higher dimensional datasets than those exploited in this study. Experimental results showed that LRSSLMDA outperformed ten previous models: the AUC of 0.9178 in global leave-one-out cross validation (LOOCV) and the AUC of 0.8418 in local LOOCV indicated the model’s superior prediction accuracy; and the average AUC of 0.9181+/-0.0004 in 5-fold cross validation justified its accuracy and stability. In addition, three types of case studies further demonstrated its predictive power. Potential miRNAs related to Colon Neoplasms, Lymphoma, Kidney Neoplasms, Esophageal Neoplasms and Breast Neoplasms were predicted by LRSSLMDA. Respectively, 98%, 88%, 96%, 98% and 98% out of the top 50 predictions were validated by experimental evidences. Therefore, we conclude that LRSSLMDA would be a valuable computational tool for miRNA-disease association prediction. [ABSTRACT FROM AUTHOR]

Objective: Assessing risk of adverse outcomes among patients with chronic liver disease has been challenging due to non-linear disease progression. We previously developed accurate prediction models for fibrosis progression and clinical outcomes among patients with advanced chronic hepatitis C (CHC). The primary aim of this study was to validate fibrosis progression and clinical outcomes models among a heterogeneous patient cohort. Design: Adults with CHC with ≥3 years follow-up and without hepatic decompensation, hepatocellular carcinoma (HCC), liver transplant (LT), HBV or HIV co-infection at presentation were analyzed (N = 1007). Outcomes included: 1) fibrosis progression 2) hepatic decompensation 3) HCC and 4) LT-free survival. Predictors included longitudinal clinical and laboratory data. Machine learning methods were used to predict outcomes in 1 and 3 years. Results: The external cohort had a median age of 49.4 years (IQR 44.3–54.3); 61% were male, 80% white, and 79% had genotype 1. At presentation, 73% were treatment naïve and 31% had cirrhosis. Fibrosis progression occurred in 34% over a median of 4.9 years (IQR 3.2–7.6). Clinical outcomes occurred in 22% over a median of 4.4 years (IQR 3.2–7.6). Model performance for fibrosis progression was limited due to small sample size. The area under the receiver operating characteristic curve (AUROC) for 1 and 3-year risk of clinical outcomes was 0.78 (95% CI 0.73–0.83) and 0.76 (95% CI 0.69–0.81). Conclusion: Accurate assessments for risk of clinical outcomes can be obtained using routinely collected data across a heterogeneous cohort of patients with CHC. These methods can be applied to predict risk of progression in other chronic liver diseases. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluates the correlation between injuries to deep gray matter nuclei, as quantitated by lesions in these nuclei on MR T2 Fast Spin Echo (T2 FSE) images, with 6-month neurological outcome after severe traumatic brain injury (TBI). Materials and methods: Ninety-five patients (80 males, mean age = 36.7y) with severe TBI were prospectively enrolled. All patients underwent a MR scan within the 45 days after the trauma that included a T2 FSE acquisition. A 3D deformable atlas of the deep gray matter was registered to this sequence; deep gray matter lesions (DGML) were evaluated using a semi-quantitative classification scheme. The 6-month outcome was dichotomized into unfavorable (death, vegetative or minimally conscious state) or favorable (minimal or no neurologic deficit) outcome. Results: Sixty-six percent of the patients (63/95) had both satisfactory registration of the 3D atlas on T2 FSE and available clinical follow-up. Patients without DGML had an 89% chance (P = 0.0016) of favorable outcome while those with bilateral DGML had an 80% risk of unfavorable outcome (P = 0.00008). Multivariate analysis based on DGML accurately classified patients with unfavorable neurological outcome in 90.5% of the cases. Conclusion: Lesions in deep gray matter nuclei may predict long-term outcome after severe TBI with high sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Objectives: There has been renewed interest in lactate as a risk biomarker in sepsis and septic shock. However, the ability of the odds ratio (OR) and change in the area under the receiver operator characteristic curve (AUC-ROC) to assess biomarker added-value has been questioned. Design, setting and participants: A sepsis cohort was identified from the ICU database of an Australian tertiary referral hospital using APACHE III diagnostic codes. Demographic information, APACHE III scores, 24-hour post-admission patient lactate levels, and hospital mortality were accessed. Measurements and main results: Hospital mortality was modelled using a base predictive logistic regression model and sequential addition of admission lactate, lactate clearance ([lactateadmission—lactatefinal]/lactateadmission), and area under the lactate-time curve (LTC). Added-value was assessed using lactate index OR; AUC-ROC difference (base-model versus lactate index addition); net (mortality) reclassification index (NRI; range -2 to +2); and net benefit (NB), the number of true positives per patient adjusted for the number of false positives. The data set comprised 717 patients with mean(SD) age and APACHE III score 61.1(16.5) years and 68.3(28.2) respectively; 59.2% were male. Admission lactate was 2.3(2.5) mmol/l; with lactate of ≥ 4 mmol/L (37% hospital mortality) in 17% and patients with lactate < 4 mmol/L having 18% hospital mortality. The admission base-model had an AUC-ROC = 0.81 with admission lactate OR = 1.127 (95%CI: 1.038, 1.224), AUC-ROC difference of 0.0032 (-0.0037, 0.01615; P = 0.61), and NRI 0.240(0.030, 0.464). The over-time model had an AUC-ROC = 0.86 with (i) clearance OR = 0.771, 95%CI: 0.578, 1.030; P = 0.08; AUC-ROC difference 0.001 (-0.003, 0.014; P = 0.78), and NRI 0.109(-0.193, 0.425) and (ii) LTC OR = 0.997, 95%CI: 0.989, 1.005, P = 0.49; AUC-ROC difference 0.004 (-0.002, 0.004; P = 0.34), and NRI 0.111(-0.222, 0.403). NB was not incremented by any lactate index. Conclusions: Lactate added-value assessment is dependent upon the performance of the underlying predictive model and should incorporate risk reclassification and net benefit measures. [ABSTRACT FROM AUTHOR]

Objective: The adenoma detection rate (ADR) varies widely between physicians, possibly due to patient population differences, hampering direct ADR comparison. We developed and validated a prediction model for adenoma detection in an effort to determine if physicians’ ADRs should be adjusted for patient-related factors. Materials and methods: Screening and surveillance colonoscopy data from the cross-sectional multicenter cluster-randomized Endoscopic Quality Improvement Program-3 (EQUIP-3) study (NCT02325635) was used. The dataset was split into two cohorts based on center. A prediction model for detection of ≥1 adenoma was developed using multivariable logistic regression and subsequently internally (bootstrap resampling) and geographically validated. We compared predicted to observed ADRs. Results: The derivation (5 centers, 35 physicians, overall-ADR: 36%) and validation (4 centers, 31 physicians, overall-ADR: 40%) cohort included respectively 9934 and 10034 patients (both cohorts: 48% male, median age 60 years). Independent predictors for detection of ≥1 adenoma were: age (optimism-corrected odds ratio (OR): 1.02; 95%-confidence interval (CI): 1.02–1.03), male sex (OR: 1.73; 95%-CI: 1.60–1.88), body mass index (OR: 1.02; 95%-CI: 1.01–1.03), American Society of Anesthesiology physical status class (OR class II vs. I: 1.29; 95%-CI: 1.17–1.43, OR class ≥III vs. I: 1.57; 95%-CI: 1.32–1.86), surveillance versus screening (OR: 1.39; 95%-CI: 1.27–1.53), and Hispanic or Latino ethnicity (OR: 1.13; 95%-CI: 1.00–1.27). The model’s discriminative ability was modest (C-statistic in the derivation: 0.63 and validation cohort: 0.60). The observed ADR was considerably lower than predicted for 12/66 (18.2%) physicians and 2/9 (22.2%) centers, and considerably higher than predicted for 18/66 (27.3%) physicians and 4/9 (44.4%) centers. Conclusion: The substantial variation in ADRs could only partially be explained by patient-related factors. These data suggest that ADR variation could likely also be due to other factors, e.g. physician or technical issues. [ABSTRACT FROM AUTHOR]

Background: Exploring ways to improve the trajectory and symptoms of autism spectrum disorder is prevalent in research, but less is known about the natural prognosis of autism spectrum disorder and course of symptoms. The objective of this study was to examine the temporal stability of autism spectrum disorder and autism diagnosis, and the longitudinal trajectories of autism core symptom severity. We furthermore sought to identify possible predictors for change. Methods: We searched PubMed, PsycInfo, EMBASE, Web of Science, Cochrane Library up to October 2015 for prospective cohort studies addressing the autism spectrum disorder/autism diagnostic stability, and prospective studies of intervention effects. We included people of all ages with autism spectrum disorder/autism or at risk of having autism spectrum disorder, who were diagnosed and followed up for at least 12 months using the Autism Diagnostic Observation Schedule (ADOS). Both continuous ADOS scores and dichotomous diagnostic categories were pooled in random-effects meta-analysis and meta-regression. Results: Of 1443 abstracts screened, 44 were eligible of which 40 studies contained appropriate data for meta-analysis. A total of 5771 participants from 7 months of age to 16.5 years were included. Our analyses showed no change in ADOS scores across time as measured by Calibrated Severity Scores (mean difference [MD] = 0.05, 95% CI -0.26 to 0.36). We observed a minor but statistically significant change in ADOS total raw scores (MD = -1.51, 95% CI -2.70 to -0.32). There was no improvement in restricted and repetitive behaviours (standardised MD [SMD] = -0.04, 95% CI -0.19 to 0.11), but a minor improvement in social affect over time (SMD = -0.31, 95% CI -0.50 to -0.12). No changes were observed for meeting the autism spectrum disorder criteria over time (risk difference [RD] = -0.01, 95% CI -0.03 to 0.01), but a significant change for meeting autism criteria over time (RD = -0.18, 95% CI -0.29 to -0.07). On average, there was a high heterogeneity between studies (I2 range: 65.3% to 93.1%). Discussion: While 18% of participants shifted from autism to autism spectrum disorder diagnosis, the overall autism spectrum disorder prevalence was unchanged. Overall autism core symptoms were remarkably stable over time across childhood indicating that intervention studies should focus on other areas, such as quality of life and adaptive functioning. However, due to high heterogeneity between studies and a number of limitations in the studies, the results need to be interpreted with caution. [ABSTRACT FROM AUTHOR]

Objective: Obstructive sleep apnea (OSA) is associated with increased carotid intima-media thickness (IMT), an early marker of atherosclerosis. Continuous positive airway pressure (CPAP) is the first-line treatment for OSA. A meta-analysis was performed to determine whether CPAP therapy could decrease carotid IMT. Methods: The PubMed, Embase, Web of Science, and Cochrane library were searched before March, 2017. Weighted mean difference (WMD) was calculated to estimate the treatment effects of pre and post-CPAP therapy. Seven studies were examined and the meta-analysis was performed using STATA 12.0. Results: There was no change of carotid IMT before and after CPAP treatment in OSA patients (WMD = 0.052, 95% confidence interval (CI) = −0.002 to 0.105, z = 1.90, p = 0.057). Meanwhile, meta-analysis of the two RCTs showed that carotid IMT was not changed in CPAP group when compared with control group (WMD = 0.002 95% CI = −0.125 to 0.129, z = 0.03, p = 0.976). Subgroup analyses indicated that carotid IMT was significantly decreased after CPAP use in more severe OSA patients (AHI≥50) (WMD = 0.073, 95% CI = 0.022 to 0.124, z = 2.80, p = 0.005) and patients with therapeutic duration ≥6 months (WMD = 0.121, 95% CI = 0.019 to 0.223, z = 2.32, p = 0.021). Conclusions: CPAP had no impact on carotid IMT in OSA patients. However, carotid IMT was significantly decreased after CPAP treatment in more severe OSA patients and patients with longer CPAP usage. [ABSTRACT FROM AUTHOR]

Quantitative trait locus (QTL) analyses of intercross populations between widely used mouse inbred strains provide a powerful approach for uncovering genetic factors that influence susceptibility to atherosclerosis. Epistatic interactions are common in complex phenotypes and depend on genetic backgrounds. To dissect genetic architecture of atherosclerosis, we analyzed F2 progeny from a cross between apolipoprotein E-null mice on DBA/2J (DBA-apoE) and C57BL/6J (B6-apoE) genetic backgrounds and compared the results with those from two previous F2 crosses of apolipoprotein E-null mice on 129S6/SvEvTac (129-apoE) and DBA-apoE backgrounds, and B6-apoE and 129-apoE backgrounds. In these round-robin crosses, in which each parental strain was crossed with two others, large-effect QTLs are expected to be detectable at least in two crosses. On the other hand, observation of QTLs in one cross only may indicate epistasis and/or absence of statistical power. For atherosclerosis at the aortic arch, Aath4 on chromosome (Chr)2:66 cM follows the first pattern, with significant QTL peaks in (DBAx129)F2 and (B6xDBA)F2 mice but not in (B6x129)F2 mice. We conclude that genetic variants unique to DBA/2J at Aath4 confer susceptibility to atherosclerosis at the aortic arch. A similar pattern was observed for Aath5 on chr10:35 cM, verifying that the variants unique to DBA/2J at this locus protect against arch plaque development. However, multiple loci, including Aath1 (Chr1:49 cM), and Aath2 (Chr1:70 cM) follow the second type of pattern, showing significant peaks in only one of the three crosses (B6-apoE x 129-apoE). As for atherosclerosis at aortic root, the majority of QTLs, including Ath29 (Chr9:33 cM), Ath44 (Chr1:68 cM) and Ath45 (Chr2:83 cM), was also inconsistent, being significant in only one of the three crosses. Only the QTL on Chr7:37 cM was consistently suggestive in two of the three crosses. Thus QTL analysis of round-robin crosses revealed the genetic architecture of atherosclerosis. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to investigate the relationship between visual score of emphysema and homology-based emphysema quantification (HEQ) and evaluate whether visual score was accurately predicted by machine learning and HEQ. Materials and methods: A total of 115 anonymized computed tomography images from 39 patients were obtained from a public database. Emphysema quantification of these images was performed by measuring the percentage of low-attenuation lung area (LAA%). The following values related to HEQ were obtained: nb0 and nb1. LAA% and HEQ were calculated at various threshold levels ranging from −1000 HU to −700 HU. Spearman’s correlation coefficients between emphysema quantification and visual score were calculated at the various threshold levels. Visual score was predicted by machine learning and emphysema quantification (LAA% or HEQ). Random Forest was used as a machine learning algorithm, and accuracy of prediction was evaluated by leave-one-patient-out cross validation. The difference in the accuracy was assessed using McNemar’s test. Results: The correlation coefficients between emphysema quantification and visual score were as follows: LAA% (−950 HU), 0.567; LAA% (−910 HU), 0.654; LAA% (−875 HU), 0.704; nb0 (−950 HU), 0.552; nb0 (−910 HU), 0.629; nb0 (−875 HU), 0.473; nb1 (−950 HU), 0.149; nb1 (−910 HU), 0.519; and nb1 (−875 HU), 0.716. The accuracy of prediction was as follows: LAA%, 55.7% and HEQ, 66.1%. The difference in accuracy was statistically significant (p = 0.0290). Conclusion: LAA% and HEQ at −875 HU showed a stronger correlation with visual score than those at −910 or −950 HU. HEQ was more useful than LAA% for predicting visual score. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the utility of the Corneal Visualization Scheimpflug Technology instrument (CST) to assess the progression of visual field (VF) damage in primary open angle glaucoma patients. Method: A total of 75 eyes from 111 patients with primary open-angle glaucoma were investigated. All patients underwent at least nine VF measurements with the Humphrey Field Analyzer, CST measurements, axial length (AL), central corneal thickness (CCT) and intraocular pressure (IOP) with Goldmann applanation tonometry (GAT). Mean total deviation (mTD) progression rates of the eight VFs, excluding the first VF, were calculated and the association between progression rate and the other listed measurements was analyzed using linear regression, and the optimal to describe mTD progression rate was selected based on the second order bias corrected Akaike Information Criterion (AICc) index. Results: VF progression was described best in a model that included CST parameters as well as other ocular measurements. The optimal linear model to describe mTD progression rate was given by the equation: -8.9–0.068 x mean GAT + 0.68 x A1 time + 0.31 x A2 time -0.39 x A2 length– 1.26 x highest deformation amplitude. Conclusion: CST measurements are useful when assessing VF progression in glaucoma patients. In particular, careful consideration should be given to patients where: (i) an eye is observed to be applanated fast in the first and second applanations, (ii) the applanated area is wide in the second applanation and (iii) the indentation is deep at the maximum deformation, since these eyes appear to be at greater risk of VF progression. [ABSTRACT FROM AUTHOR]

Background: Post-stroke Depression, Obstructive sleep apnea (OSA) and Cognitive impairment (“DOC”) are associated with greater mortality, worse recovery and poorer quality of life. Best practice recommendations endorse routine screening for each condition; yet, all are under-assessed, diagnosed and treated. We seek to determine the feasibility and validity of an integrated tool (“DOC” screen) to identify stroke clinic patients at high-risk of depression, OSA, and cognitive impairment. Methods: All consecutive new referrals to a regional Stroke Prevention Clinic who were English-speaking and non-aphasic were eligible to be screened. Time for screen completion was logged. DOC screen results were compared to the neuropsychological battery and polysomnogram assessments using a modified receiver operator characteristic and area under the curve analysis. Data is reported to conform to STARD guidelines. Findings: 1503 people were screened over 2 years. 89% of eligible patients completed the screen in 5 minutes or less (mean 4.2 minutes), less than half the time it takes to complete the Montreal Cognitive Assessment (MoCA). 437 people consented to detailed testing. Of those, 421 completed the Structured Clinical Interview for Depression within 3 months of screening, 387 completed detailed neuropsychological testing within 3 months, and 88 had overnight polysomnograms. Screening scores combined with demographic variables (age, sex, education, body mass index), had excellent validity compared to gold standard diagnoses: DOC-Mood AUC 0.90; DOC-Apnea AUC 0.80; DOC-Cog AUC 0.81. DOC screen scores can reliably categorize patients in to low-, intermediate- or high-risk groups for further action and can do so with comparable accuracy to more time-consuming screens. Conclusions: Systematic screening of depression, obstructive sleep apnea, and cognitive impairment in 5 minutes or less is feasible and valid in a high volume stroke clinic using the DOC screen. The DOC screen may facilitate improved identification and treatment of these comorbidities to improve function in patients after stroke and in those with other neurological diseases that share these comorbid conditions (e.g. Alzheimer’s disease/mild cognitive impairment, Parkinson’s disease, Traumatic Brain Injury, multiple sclerosis). [ABSTRACT FROM AUTHOR]

Purpose: To investigate the altered intrinsic functional connectivity (iFC) of the primary visual cortex (V1) in primary angle-closure glaucoma (PACG) patients before and after surgery using resting-state functional MRI. Materials and Methods: Twenty-five preoperative PACG (pre-PACG) patients and 25 well-matched healthy controls (HCs) were included in this study, and 9 PACG patients were assessed again at least 3 months after treatment (post-PACG). We generated the iFC maps of the seed regions in the centers of the left and right V1 and conducted group comparisons. Then, the relationships between the altered iFC coefficients and clinical variables were investigated in the pre-PACG patients. Results: Compared with the HCs, the pre-PACG patients showed decreased iFC between the left V1 and right V2 (covering the cuneus, calcarine and lingual gyrus) and increased iFC between the left V1 and left temporal-parietal region, left frontal opercula-insula-basal ganglia region, right insula-basal ganglia region, and right inferior parietal lobule (P < 0.01, corrected). Compared with the pre-PACG patients, the post-PACG patients showed increased iFC between the left V1 and bilateral V2, and between the left V1 and left or right postcentral gyrus; in addition, they showed decreased iFC between the left V1 and the dorsal-attention and frontoparietal-control networks. In the pre-PACG patients, visual activity (VA) was positively correlated with increased iFC between the left V1 and the left temporal-parietal region or the right inferior parietal lobule. Similar patterns of alterations were observed in the right V1-iFC in both the pre- and post-PACG patients. Conclusions: The primary findings have demonstrated a gradual decrease in visual information integration in the left V1-V2 pathway and VA-related functional compensation in the pre-PACG patients, generating further evidence of functional restoration in post-PACG patients. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to perform a systematic review to assess the short-, middle- and long-term consequences of sarcopenia. Methods: Prospective studies assessing the consequences of sarcopenia were searched across different electronic databases (MEDLINE, EMBASE, EBM Reviews, Cochrane Database of Systematic Reviews, EBM Reviews ACP Journal Club, EBM Reviews DARE and AMED). Only studies that used the definition of the European Working Group on Sarcopenia in Older People to diagnose sarcopenia were included. Study selection and data extraction were performed by two independent reviewers. For outcomes reported by three or more studies, a meta-analysis was performed. The study results are expressed as odds ratios (OR) with 95% CI. Results: Of the 772 references identified through the database search, 17 were included in this systematic review. The number of participants in the included studies ranged from 99 to 6658, and the duration of follow-up varied from 3 months to 9.8 years. Eleven out of 12 studies assessed the impact of sarcopenia on mortality. The results showed a higher rate of mortality among sarcopenic subjects (pooled OR of 3.596 (95% CI 2.96–4.37)). The effect was higher in people aged 79 years or older compared with younger subjects (p = 0.02). Sarcopenia is also associated with functional decline (pooled OR of 6 studies 3.03 (95% CI 1.80–5.12)), a higher rate of falls (2/2 studies found a significant association) and a higher incidence of hospitalizations (1/1 study). The impact of sarcopenia on the incidence of fractures and the length of hospital stay was less clear (only 1/2 studies showed an association for both outcomes). Conclusion: Sarcopenia is associated with several harmful outcomes, making this geriatric syndrome a real public health burden. [ABSTRACT FROM AUTHOR]

Background and Purpose: Although bevacizumab (BV) has been approved as second-line therapy for recurrent glioblastoma (GB), the efficacy and safety of BV for patients with newly diagnosed GB remain unclear. Methodology/Principal Findings: We systematically searched electronic databases (PubMed, EMBASE, OVID, etc.) to identify related studies published from January 1966 and August 2016. Eight randomized controlled trials including a total of 2,185 patients with GB were included. We found that the median progression-free survival (PFS) was higher in the BV group than in the standard therapy (ST) group (pooled hazard ratio, 0.73; 95%CI, 0.62–0.86; P = 0.0001). Compared with ST, BV improved the PFS rate at 6 months (OR 3.33, 95% CI 2.73–4.06, p<0.00001) and 12 months (OR 2.10, 95% CI 1.74–2.54, p<0.00001). There were no significant differences in median overall survival between the BV and ST groups (OR, 1.01; 95%CI, 0.83–1.23; P = 0.95). The BV group had higher survival rates at 6 months (OR, 1.41; 95% CI, 1.09–1.84; P = 0.01) and 12 months (OR, 1.23; 95% CI, 1.02–1.48; P = 0.03), but a low survival rate at the 36-month follow-up (OR, 0.57; 95% CI, 0.32–0.98; P = 0.04). For the incidence of adverse events, three adverse outcomes were found to be significantly different between BV and ST groups, including hypertension (8.37% vs. 1.62%, p<0.000001), proteinuria (7.65% vs. 0%, p<0.001), and fatigue (14.54% vs. 9.01%, p = 0.05). Conclusions/Significance: Our study indicates that combination of BV with ST for newly diagnosed GB did not improve the median overall survival but result in longer median PFS, maintaining the quality of life and functional status. However, the long-term use of BV is associated with a higher incidence of adverse events and mortality. Study Registration: This research was registered at PROSPERO. (Registration Number: CRD42016038247). [ABSTRACT FROM AUTHOR]

The continuous development of resuscitation techniques and intensive care reduced the mortality rate induced by the initial shock in burn patients and, currently, infections (especially sepsis) are the main causes of mortality of these patients. The misuse of antimicrobial agents is strongly related to antimicrobial and adverse patient outcomes, development of microbial resistance and increased healthcare-related costs. To overcome these risks, antimicrobial stewardship is mandatory and biomarkers are useful to avoid unnecessary medical prescription, to monitor antimicrobial therapy and to support the decision of its stop. Among a large array of laboratory tests, procalcitonin (PCT) emerged as the leading biomarker to accurately and time-effectively indicate the presence of systemic infection. In the presence of systemic infection, PCT blood levels undergo a sudden and dramatic increase, following the course of the infection, and quickly subside after the control of the septic process. This work is a meta-analysis on PCT performance as a biomarker for sepsis. This meta–analysis showed that overall pooled area under the curve (AUC) is 0.83 (95% CI = 0.76 to 0.90); the estimated cut-off is 1.47 ng/mL. The overall sepsis effect in PCT levels is significant and strong (Cohen's d is 2.1 and 95% CI = 1.1 to 3.2). This meta–analysis showed PCT may be considered as a biomarker with a strong diagnostic ability to discriminate between the septic from the non-septic burn patients. Thus, this work encourages the determination of PCT levels in clinical practice for the management of these patients, in order to timely identify the susceptibility to sepsis and to initiate the antimicrobial therapy, improving the patients’ outcomes. [ABSTRACT FROM AUTHOR]

Lymphatic Filariasis and Onchocerciasis (river blindness) constitute pressing public health issues in tropical regions. Global elimination programs, involving mass drug administration (MDA), have been launched by the World Health Organisation. Although the drugs used are generally well tolerated, individuals who are highly co-infected with Loa loa are at risk of experiencing serious adverse events. Highly infected individuals are more likely to be found in communities with high prevalence. An understanding of the relationship between individual infection and population-level prevalence can therefore inform decisions on whether MDA can be safely administered in an endemic community. Based on Loa loa infection intensity data from individuals in Cameroon, the Republic of the Congo and the Democratic Republic of the Congo we develop a statistical model for the distribution of infection levels in communities. We then use this model to make predictive inferences regarding the proportion of individuals whose parasite count exceeds policy-relevant levels. In particular we show how to exploit the positive correlation between community-level prevalence and intensity of infection in order to predict the proportion of highly infected individuals in a community given only prevalence data from the community in question. The resulting prediction intervals are not substantially wider, and in some cases narrower, than the corresponding binomial confidence intervals obtained from data that include measurements of individual infection levels. Therefore the model developed here facilitates the estimation of the proportion of individuals highly infected with Loa loa using only estimated community level prevalence. It can be used to assess the risk of rolling out MDA in a specific community, or to guide policy decisions. [ABSTRACT FROM AUTHOR]

Background: Hallux abducto valgus (HAV) is one of the most common forefoot deformities in adulthood with a variable prevalence but has been reported as high as 48%. The study proposed that HAV development involves a skeletal parameter of the first metatarsal bone and proximal phalanx hallux (PPH) to determine if the length measurements of the metatarsal and PPH can be used to infer adult HAV. Methods: All consecutive patients over 21 years of age with HAV by roentgenographic evaluation were included in a cross-sectional study. The control group included patients without HAV. The study included 160 individuals. We identified and assessed the following radiographic measurements to evaluate HAV: the distances from the medial (LDM), central (LDC), and lateral (LDL) aspects of the base to the corresponding regions of the head of the PPH. The difference between the medial and lateral aspect of PPH was also calculated. Results: The reliability of the variables measured in 40 radiographic films show perfect reliability ranging from 0.941 to 1 with a small error ranging from 0.762 to 0. Also, there were no systematic errors between the two measurements for any variable (P > 0.05). The LDM PPH showed the highest reliability and lowest error. Conclusion: It is more suitable to measure the LDM PPH instead of the LDC PPH when calculating the hallux valgus angle based on our reliability results. When the differences of the medial and lateral PPH are greater, the risk for developing HAV increases. [ABSTRACT FROM AUTHOR]

Background and Aims: Liver stiffness (LS) and spleen stiffness (SS) are two most widely accessible non-invasive parameters for predicting esophageal varices (EV), but the reported accuracy of the two predictors have been inconsistent across studies. This meta-analysis aims to evaluate the diagnostic performance of LS and SS measurement for detecting EV in patients with chronic liver disease (CLD), and compare their accuracy. Methods: Pubmed/Medline, Embase, Cochrane Library and Ovid were searched for all studies assessing SS and LS simultaneously in EV diagnosis. A total of 16 studies including 1892 patients were included in this meta-analysis, and the pooled statistical parameters were calculated using the bivariate mixed effects models. Results: In detection of any EV, for LS measurement, the summary sensitivity was 0.83 (95% confidence interval [CI]: 0.78–0.87), and the specificity was 0.66 (95% CI: 0.60–0.72). While for SS measurement, the pooled sensitivity and specificity was 0.88 (95% CI: 0.83–0.92) and 0.78 (95% CI: 0.73–0.83). The summary receiver operating characteristic (SROC) curve values of LS and SS were 0.81 (95% CI: 0.77–0.84) and 0.88 (95% CI: 0.85–0.91) respectively, and the results had statistical significance (P<0.01). The diagnostic odds ratio (DOR) of SS (25.73) was significantly higher than that of LS (9.54), with the relative DOR value was 2.48 (95%CI: 1.10–5.60), P<0.05. Conclusions: Under current techniques, SS is significantly superior to LS for identifying the presence of EV in patients with CLD. SS measurement may help to select patients for endoscopic screening. [ABSTRACT FROM AUTHOR]

Background: Myopia subjects usually have long axial lengths and are predisposed to deep anterior chamber depths and open angles. Jiangning eye study is a randomized, population based study in Shanghai to determine whether myopia has an effect on the prevalence of occludable angles. Methods: A total of 2478 residents aged 50 years and over were randomly selected, and 2044 (82.5%) individuals of them participated in ophthalmic examinations between November 2012 and February 2013. Eye examinations included autorefraction, noncontact tonometry, measurement of axial length, anterior chamber depth, lens thickness and spectral domain optical coherence tomography. Results: The crude prevalences of iris trabecular meshwork contact in Jiangning Chinese individuals with myopia, emmetropia, and hyperopia are 1.25%, 6.44%, and 7.43%, respectively. There is also iris trabecular meshwork contact and shallow anterior chamber depth in myopia subjects even with long axial lengths. Conclusions: The prevalence of iris trabecular meshwork contact in myopia subjects is lower than their emmetropia or hyperopia counterparts. Axial length is an important factor associate with occludable angle. [ABSTRACT FROM AUTHOR]

Objectives: It has been shown that an increasing number of adults deliberately feign attention deficit hyperactivity disorder (ADHD), which demonstrates the need for new tests designed to detect feigned ADHD. Methods: An Embedded Figures Test (EFT) was developed for the detection of feigned ADHD in adulthood. EFT performance of 51 adults with ADHD was compared to the performance of 52 matched healthy individuals, as well as to 268 undergraduate students who were randomly allocated in a simulation design to one of four experimental conditions, i.e. a control group, a naïve simulation group, a symptom-coached simulation group or a test-coached simulation group. Furthermore, an independent sample of 11 adults with ADHD as well as a sample of 17 clinicians experienced in the work with adults with ADHD were assessed for further validation of the EFT. Results: The EFT was relatively easy to perform for both patients with ADHD and healthy comparisons as shown by low error rates and non-significant group differences. However, simulation groups differed from patients with ADHD by significant and large effects. An EFT index for the prediction of feigned ADHD was derived based on logistic regression coefficients. Receiver Operating Characteristics (ROC) demonstrated good classification accuracy of feigned ADHD relative to ADHD (AUC = 94.8%), i.e. high sensitivity (88%) and specificity (90%). Conclusions: This study supports the utility of the EFT for the detection of feigned adult ADHD. [ABSTRACT FROM AUTHOR]

The macrophage migration inhibitory factor (MIF) gene is located on human chromosome 22q11.2 and is linked to atopic phenotypes. Plasma MIF and log [total IgE] levels are significantly elevated in atopic dermatitis (AD) patients. The aim of this study was to evaluate the relationship between two MIF polymorphisms, −173 G to C and −794 CATT5–8, and total plasma IgE levels in AD patients in Korea. We performed PCR-RFLP analysis in 178 AD patients and 80 control subjects to determine whether MIF SNPs are associated with susceptibility to AD. Plasma total IgE and MIF levels were determined, and then logistic regression analyses were performed to determine the associations between a SNP or haplotype and plasma total IgE or MIF levels. The −173 G/C polymorphism, located in the MIF promoter, was significantly associated with AD; the odds ratios (ORs) for the CC homozygotes and GC heterozygotes were 9.3 and 2.5, respectively. The MIF C/5-CATT and the MIF C/7-CATT haplotypes were significantly associated with AD; the ORs for the MIF C/5-CATT and MIF C/7-CATT haplotypes were 9.7 and 4.5, respectively. Log [total IgE] levels were highly associated with the MIF −794 7-CATT polymorphism. Notably, the MIF C/7-CATT haplotype was associated with a decrease in plasma log [total IgE] levels in a gene dose-dependent manner. Although log [MIF] levels were not associated with the MIF polymorphisms, the frequencies of the MIF C/5-CATT haplotype-containing genotypes decreased in order of MIF levels. Our results demonstrate that MIF promoter polymorphisms in the −173 C allele and the MIF C/5-CATT and C/7-CATT haplotypes were significantly associated with an increased risk for AD. In particular, the −794 7-CATT locus and the MIF C/7-CATT haplotype were significantly associated with decreased total IgE levels in the plasma, suggesting that these polymorphisms might be a marker for intrinsic AD rather than extrinsic AD that shows high total IgE levels and presence of allergen-specific IgE. [ABSTRACT FROM AUTHOR]

Methods commonly used clinically to assess cardiac function in patients with heart failure include ejection fraction (EF), exercise treadmill testing (ETT), and symptom evaluation. Although these approaches are useful in evaluating patients with heart failure, there are at times substantial mismatches between individual assessments. For example, ETT results are often discordant with EF, and patients with minimal symptoms sometimes have surprisingly low EFs. To better define the relationship of these methods of assessment, we studied 56 patients with heart failure with reduced EF (HFrEF) who underwent measurement of ETT duration, EF by echocardiography, quantitative symptom evaluation, and LV peak dP/dt (rate of left ventricular pressure development and decline, measured invasively). Correlations were determined among these four tests in order to assess the relationship of EF, ETT, and symptoms against LV peak dP/dt. In addition, we sought to determine whether EF, ETT, and symptoms correlated with each other. Overall, correlations were poor. Only 15 of 63 total correlations (24%) were significant (p < 0.05). EF correlated most closely with LV peak -dP/dt. Linear regression analysis indicated that EF, ETT, and symptoms taken together predicted LV peak dP/dt better than any one measure alone. We conclude that clinical tests used to assess LV function in patients with HFrEF may not be as accurate or correlate as well as expected. All three clinical measures considered together may be the best representation of cardiac function in HFrEF patients currently available. [ABSTRACT FROM AUTHOR]

We previously developed a method for determining MYCN gene amplification status using cell-free DNA fragments released from cancer cells into the blood of patients with neuroblastoma (NB). Here, we analyzed the relationship between MYCN amplification (MNA) status and neuroblastoma prognosis. We screened serum samples from 151 patients with NB for MNA, using real-time quantitative PCR, and compared the results with MYCN status determined using paired tumor samples. We additionally investigated whether MNA status correlates with patient survival. When a cut-off value of 5 was used, serum-based MNA analysis was found to show good sensitivity (86%) and very high specificity (95%). The sensitivities for stage 1 and 2 might be acceptable, even though it is not as good as for stage 3 and 4 (67% for stage 1 and 2, 92% for stage 3, and 87% for stage 4). MNA status correlated with overall survival in our cohort of 82 patients, with survival data available (p < 0.01). The hazard ratio of MNA status was 4.98 in patients diagnosed at less than 18 months of age (95% confidence interval, 1.00–24.78), and 1.41 (95% confidence interval, 0.63–3.14) for those diagnosed at 18 months of age or older. Serum-based MNA analysis is rapid and non-invasive compared with tumor-based MNA analysis, and has potential to predict tumor MNA status. There is still a room to improve the sensitivity of the test for tumors of stages 1 and 2, nonetheless this assay might help to determine therapeutic strategies prior to tumor biopsy, especially for patients with a life-threatening condition, as well as for patients of less than 18 months of age whose risk-grouping and treatment allocation depends on their MNA status. [ABSTRACT FROM AUTHOR]

In a Perspective article, Sigrid Carlsson and Michael Kattan discuss Gnanapragasam and colleagues' accompanying research study on refining risk stratification in early prostate cancer. [ABSTRACT FROM AUTHOR]

Objective: Glutamate plays an important role in brain development, neuronal migration, differentiation, survival and synaptogenesis. Recent studies have explored the relationship between blood glutamate levels and autism spectrum disorder (ASD). However, the findings are inconsistent. We undertook the first systematic review with a meta-analysis of studies examining blood glutamate levels in ASD compared with controls. Methods: A literature search was conducted using PubMed, Embase, and the Cochrane Library for studies published before March 2016. A random-effects model was used to calculate the pooled standardized mean difference (SMD) of the outcomes. Subgroup analyses were used to explore the potential sources of heterogeneity, and the publication bias was estimated using Egger’s tests. Results: Twelve studies involving 880 participants and 446 incident cases were included in this meta-analysis. The meta-analysis provided evidence for higher blood glutamate levels in ASD [SMD = 0.99, 95% confidence interval (95% CI) = 0.58–1.40; P < 0.001] with high heterogeneity (I2 = 86%, P < 0.001) across studies. The subgroup analyses revealed higher glutamate levels in ASD compared with controls in plasma [SMD = 1.04, 95% CI = 0.58–1.50; P < 0.001] but not true in serum [SMD = 0.79, 95% CI = -0.41–1.99; P = 0.20]. Studies employing high performance liquid chromatography (HPLC) or liquid chromatography-tandem mass spectrometry (LC-MS) assays also revealed higher blood glutamate levels in ASD. A sensitivity analysis found that the results were stable, and there was no evidence of publication bias. Conclusions: Blood glutamate levels might be a potential biomarker of ASD. [ABSTRACT FROM AUTHOR]

Background: Recently, the all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) protocol has become a promising first-line therapeutic approach in patients with newly diagnosed acute promyelocytic leukemia (APL), but its benefits compared with standard ATRA plus chemotherapy regimen needs to be proven. Herein, we conducted a meta-analysis comparing the efficacy of ATRA plus ATO with ATRA plus chemotherapy for adult patients with newly diagnosed APL. Methods: We systematically searched biomedical electronic databases and conference proceedings through February 2016. Two reviewers independently assessed all studies for relevance and validity. Results: Overall, three studies were eligible for inclusion in this meta-analysis, which included a total of 585 patients, with 317 in ATRA plus ATO group and 268 in ATRA plus chemotherapy group. Compared with patients who received ATRA and chemotherapy, patients who received ATRA plus ATO had a significantly better event-free survival (hazard ratio [HR] = 0.38, 95% confidence interval [CI]: 0.22–0.67, p = 0.009), overall survival (HR = 0.44, 95% CI: 0.24–0.82, p = 0.009), complete remission rate (relative risk [RR] = 1.05; 95% CI: 1.01–1.10; p = 0.03). There were no significant differences in early mortality (RR = 0.48; 95% CI: 0.22–1.05; p = 0.07). Conclusion: Thus, this analysis indicated that ATRA plus ATO protocol may be preferred to standard ATRA plus chemotherapy protocol, particularly in low-to-intermediate risk APL patients. Further larger trials were needed to provide more evidence in high-risk APL patients. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the utility of preoperative multiparametric magnetic resonance imaging (MP-MRI) in predicting biochemical recurrence (BCR) following radical prostatectomy (RP). Materials/Methods: From March 2007 to January 2015, 421 consecutive patients with prostate cancer (PCa) underwent preoperative MP-MRI and RP. BCR-free survival rates were estimated using the Kaplan-Meier method. Cox proportional hazards models were used to identify clinical and imaging variables predictive of BCR. Logistic regression was performed to generate a nomogram to predict three-year BCR probability. Results: Of the total cohort, 370 patients met inclusion criteria with 39 (10.5%) patients experiencing BCR. On multivariate analysis, preoperative prostate-specific antigen (PSA) (p = 0.01), biopsy Gleason score (p = 0.0008), MP-MRI suspicion score (p = 0.03), and extracapsular extension on MP-MRI (p = 0.03) were significantly associated with time to BCR. A nomogram integrating these factors to predict BCR at three years after RP demonstrated a c-index of 0.84, outperforming the predictive value of Gleason score and PSA alone (c-index 0.74, p = 0.02). Conclusion: The addition of MP-MRI to standard clinical factors significantly improves prediction of BCR in a post-prostatectomy PCa cohort. This could serve as a valuable tool to support clinical decision-making in patients with moderate and high-risk cancers. [ABSTRACT FROM AUTHOR]

Background: Neurogenic bladder dysfunction represents one of the most common and devastating sequelae of traumatic spinal cord injury (SCI). As early prediction of bladder outcomes is essential to counsel patients and to plan neurourological management, we aimed to develop and validate a model to predict urinary continence and complete bladder emptying 1 y after traumatic SCI.Methods and Findings: Using multivariate logistic regression analysis from the data of 1,250 patients with traumatic SCI included in the European Multicenter Spinal Cord Injury study, we developed two prediction models of urinary continence and complete bladder emptying 1 y after traumatic SCI and performed an external validation in 111 patients. As predictors, we evaluated age, gender, and all variables of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) and of the Spinal Cord Independence Measure (SCIM). Urinary continence and complete bladder emptying 1 y after SCI were assessed through item 6 of SCIM. The full model relies on lower extremity motor score (LEMS), light-touch sensation in the S3 dermatome of ISNCSI, and SCIM subscale respiration and sphincter management: the area under the receiver operating characteristics curve (aROC) was 0.936 (95% confidence interval [CI]: 0.922-0.951). The simplified model is based on LEMS only: the aROC was 0.912 (95% CI: 0.895-0.930). External validation of the full and simplified models confirmed the excellent predictive power: the aROCs were 0.965 (95% CI: 0.934-0.996) and 0.972 (95% CI 0.943-0.999), respectively. This study is limited by the substantial number of patients with a missing 1-y outcome and by differences between derivation and validation cohort.Conclusions: Our study provides two simple and reliable models to predict urinary continence and complete bladder emptying 1 y after traumatic SCI. Early prediction of bladder function might optimize counselling and patient-tailored rehabilitative interventions and improve patient stratification in future clinical trials. [ABSTRACT FROM AUTHOR]

Background: Elevated homocysteine levels have been observed in previous studies of PCOS; however, the nature of the associations between high homocysteine levels and the biochemical characteristics of polycystic ovarian syndrome (PCOS)—such as obesity, insulin resistance (IR), and androgen levels—is still uncertain. Methods: A systematic search was conducted electronically up to December 28, 2015 using specific eligibility criteria. Standardized mean difference (SMD) and the corresponding 95% confidence intervals (95% CIs) were used as a measure of effect size. Results: A total of 34 studies (with 1,718 cases and 1,399 controls) of homocysteine levels in PCOS were pooled in this meta-analysis. Significantly lower homocysteine levels were found in controls than in PCOS patients (SMD = 0.895, 95% CI = 0.643–1.146, P<0.001; I2 = 90.4% and P<0.001 for heterogeneity), regardless of the degree of obesity, IR, or androgen levels. Homocysteine levels in non-IR PCOS patients were significantly lower than those of PCOS patients with IR (SMD = 0.69, 95% CI = 0.37–1.01, P<0.01; I2 = 0% and P = 0.50 for heterogeneity). However, metformin treatment did not appear to cause any significant change in the homocysteine levels of PCOS patients (SMD = –0.17, 95% CI = –1.10–0.75, P = 0.71; I2 = 92% and P<0.01 for heterogeneity). Conclusions: High homocysteine levels in women with PCOS are not related to degree of obesity, IR, or androgen levels. Metformin treatment cannot decrease the homocysteine levels in PCOS patients. [ABSTRACT FROM AUTHOR]

Triple therapy of chronic hepatitis C virus (HCV) infection with boceprevir (BOC) or telaprevir (TVR) leads to virologic failure in many patients which is often associated with the selection of resistance-associated variants (RAVs). These resistance profiles are of importance for the selection of potential rescue treatment options. In this study, we sequenced baseline NS3 RAVs population-based and investigated the sensitivity of NS3 phenotypes in an HCV replicon assay together with clinical factors for a prediction of treatment response in a cohort of 165 German and Swiss patients treated with a BOC or TVR-based triple therapy. Overall, the prevalence of baseline RAVs was low, although the frequency of RAVs was higher in patients with virologic failure compared to those who achieved a sustained virologic response (SVR) (7% versus 1%, P = 0.06). The occurrence of RAVs was associated with a resistant NS3 quasispecies phenotype (P<0.001), but the sensitivity of phenotypes was not associated with treatment outcome (P = 0.2). The majority of single viral and host predictors of SVR was only weakly associated with treatment response. In multivariate analyses, low AST levels, female sex and an IFNL4 CC genotype were independently associated with SVR. However, a combined analysis of negative predictors revealed a significantly lower overall number of negative predictors in patients with SVR in comparison to individuals with virologic failure (P<0.0001) and the presence of 2 or less negative predictors was indicative for SVR. These results demonstrate that most single baseline viral and host parameters have a weak influence on the response to triple therapy, whereas the overall number of negative predictors has a high predictive value for SVR. [ABSTRACT FROM AUTHOR]

Oral Tongue Squamous cell carcinoma (OTSCC), the most frequently affected oral cancer sub-site, is associated with a poor therapeutic outcome and survival despite aggressive multi- modality management. Till date, there are no established biomarkers to indicate prognosis and outcome in patients presenting with tongue cancer. There is an urgent need for reliable molecular prognostic factors to enable identification of patients with high risk of recurrence and treatment failure in OTSCC management. In the current study, we present the meta-analysis of OTSCC microarray based gene expression profiles, deriving a comprehensive molecular portrait of tongue cancer biology, showing the relevant genes and pathways which can be pursued further to derive novel, tailored therapeutics as well as for prognostication. We have studied 5 gene expression profiling data sets available on exclusively oral tongue subsite comprising of sample size; n = 190, consisting of 111 tumors and 79 normals. The meta- analysis results showed 2405 genes differentially regulated comparing OTSCC tumor and normal. The top up regulated genes were found to be involved in Extracellular matrix degradation (ECM) and Epithelial to mesenchymal transition (EMT) pathways. The top down regulated genes were found to be involved in detoxication pathways. We validated the results in clinical samples (n = 206), comprising of histologically normals (n = 10), prospective (n = 29) and retrospective (n = 167) OTSCC by evaluating MMP9 and E-cadherin gene expression by qPCR and immunohistochemistry. Consistent with meta-analysis results, MMP9 mRNA expression was significantly up regulated in OTSCC primary tumors compared to normals. MMP9 protein over expression was found to be a significant predictor of poor prognosis, disease recurrence and poor Disease Free Survival (DFS) in OTSCC patients. Analysis by univariate and multivariate Cox proportional hazard model showed patients with loss of E-cadherin expression in OTSCC tumors having a poorer DFS (HR = 1.566; P value = 0.045) and poorer Overall Survival (OS) (HR = 1.224; P value = 0.003) respectively. Combined over-expression of MMP9 and loss of E-cadherin membrane positivity in the invasive tumor front (ITF) of OTSCC had a significant association with poorer DFS (Log Rank = 16.040; P value = 0.001). These results suggest that along with known clinical indicators of prognosis like occult node positivity, assessment of MMP9 and E-cadherin expression at ITF can be useful to identify patients at high risk and requiring a more intensive treatment strategy for OTSCC. Meta-analysis study of gene expression profiles indicates that OTSCC is a disease of ECM degradation leading to activated EMT processes implying the aggressive nature of the disease. The triggers for these processes should be studied further. Newer clinical application with agents that can inhibit the mediators of ECM degradation may be a key to achieving clinical control of invasion and metastasis of OTSCC. [ABSTRACT FROM AUTHOR]

Renal-cell carcinoma (RCC) affects over 330,000 new patients every year, of whom 1/3 present with metastatic RCC (mRCC) at diagnosis. Most mRCC patients treated with a first-line agent relapse within 1 year and need second-line therapy. The present study aims to compare overall survival (OS) between nivolumab and cabozantinib from two recent pivotal studies comparing, respectively, each one of the two emerging treatments against everolimus in patients who relapse following first-line treatment. Comparison is traditionally carried out using the Bucher method, which assumes proportional hazard. Since OS curves intersected in one of the pivotal studies, models not assuming proportional hazards were also considered to refine the comparison. Four Bayesian parametric survival network meta-analysis models were implemented on overall survival (OS) data digitized from the Kaplan-Meier curves reported in the studies. Three models allowing hazard ratios (HR) to vary over time were assessed against a fixed-HR model. The Bucher method favored cabozantinib, with a fixed HR for OS vs. nivolumab of 1.09 (95% confidence interval: [0.77, 1.54]). However, all models with time-varying HR showed better fits than the fixed-HR model. The log-logistic model fitted the data best, exhibiting a HR for OS initially favoring cabozantinib, the trend inverting to favor nivolumab after month 5 (95% credible interval <1 from 10 months). The initial probability of cabozantinib conferring superior OS was 54%, falling to 41.5% by month 24. Numerical differences in study-adjusted OS estimates between the two treatments remained small. This study evidences that HR for OS of nivolumab vs. cabozantinib varies over time, favoring cabozantinib in the first months of treatment but nivolumab afterwards, a possible indication that patients with poor prognosis benefit more from cabozantinib in terms of survival, nivolumab benefiting patients with better prognosis. More evidence, including real-world observational data, is needed to compare effectiveness between cabozantinib and nivolumab. [ABSTRACT FROM AUTHOR]

Background and Aims: Low-quality bowel preparation reduces efficacy of colonoscopy. We aimed to summarize effects of bowel preparation on detection of adenomas, advanced adenomas and colorectal cancer. Methods: A systematic literature search was performed regarding detection of colonic lesions after normal and low-quality bowel preparation. Reported bowel preparation quality was transformed to the Aronchick scale with its qualities “excellent”, “good”, “fair”, “poor”, and “insufficient” or “optimal” (good/excellent), “suboptimal” (fair/poor/insufficient), “adequate” (good/excellent/fair) and “inadequate” (poor/insufficient). We identified two types of studies: i) Comparative studies, directly comparing lesion detection according to bowel preparation quality, and ii) repeat colonoscopy studies, reporting results of a second colonoscopy after previous low-quality preparation. Results: The detection of early adenomas was reduced with inadequate vs. adequate bowel preparation (Odds Ratio (OR) 0.53, CI: 0.46–0.62, p<0.001). The advanced adenomas were affected less in comparison (0.74, CI: 0.62–0.87, p<0.001). The large number of subjects considered in the present meta-analysis resulted in smaller confidence intervals compared to earlier studies. Classifying the bowel-preparation quality as suboptimal vs. optimal led to the same qualitative conclusion (OR: 0.81, CI: 0.74–0.89, p<0.001 for early adenomas, OR: 0.94, CI: 0.87–1.01, n.s. for advanced adenomas). Bowel preparation was equally important for right-sided/ flat/ serrated vs. other lesions in most observational studies but more relevant in some repeat colonoscopy studies; data regarding carcinoma detection were insufficient. Conclusion: Inadequate bowel preparation affects detection of early colonic lesions stronger than advanced lesions. [ABSTRACT FROM AUTHOR]