Non-invasive fibrosis markers for assessment of liver fibrosis in chronic hepatitis delta.

Assessment of liver fibrosis by non-invasive means is clinically important. Studies in chronic hepatitis delta (CHD) are scarce. We evaluated the performance of eight serum fibrosis markers [fibrosis-4 score (FIB-4), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), age-platelet index (API), AST-to platelet-ratio-index (APRI), Goteborg University Cirrhosis Index (GUCI), Lok index, cirrhosis discriminant score (CDS) and Hui score] in CHD and chronic hepatitis B (CHB). Liver stiffness was assessed by transient elastography (TE) in CHD. The ability of fibrosis markers to detect significant fibrosis and cirrhosis were evaluated in 202 CHB and 108 CHD patients using published and new cut-offs through receiver operating characteristics (ROC) analysis. The latter was also applied to obtain cut-offs for TE. APRI, Fib-4, API and Hui score were assessed for significant fibrosis, and APRI, GUCI, Lok index, CDS and AAR for cirrhosis determination. Fibrosis markers displayed weak performance in CHB for significant fibrosis with area under ROC (AUROC) curves between 0.62 and 0.71. They did slightly better for CHD. TE displayed an AUROC of 0.92 and performed better than serum fibrosis markers (p < 0.05 for fibrosis markers). For cirrhosis determination, CDS and Lok Index displayed an AUROC of 088 and 0.89 in CHB and GUCI, Lok index and APRI displayed AUROCs around 0.90 in CHD. TE displayed the best AUROC (0.95). Hence TE is superior to serum fibrosis markers for diagnosing significant liver fibrosis and cirrhosis. GUCI, Lok index and APRI displayed a reasonable performance in CHD, which needs further confirmation.

Evaluation of the Performance of Vasoactive Ventilation Renal Score in Predicting the Duration of Mechanical Ventilation and Intensive Care Hospitalization After Pediatric Cardiac Surgery.

Various methods have been used to evaluate the predictivity of some markers during the recovery process after cardiac surgery in children. The aim herein was to evaluate the vasoactive ventilation renal (VVR) score in predicting the clinical outcomes of children who underwent congenital cardiac surgery within the early period in the pediatric intensive care unit (PICU). Patients who underwent congenital heart surgery (CHS) between November 2016 and March 2020 were enrolled and evaluated prospectively. The VVR score was calculated as follows: vasoactive inotrope score (VIS) + ventilation index + (change in serum creatinine level based on the baseline value × 10). The relationship between the duration of mechanical ventilation and the length of stay (LOS) in the PICU was evaluated via receiver operating characteristic (ROC) curve analysis and the cut-off values were calculated. At all of the time points identified in the study, the VVR score had a higher area under the ROC curve (AUC) when compared to the VIS and serum lactate levels, and the 48-h VVR score had the highest AUC (AUC 0.851, 95% confidence interval (CI) 0.761-0.942/LOS in the PICU; AUC 0.946, 95% CI 0.885-1.000/duration of mechanical ventilation). The 48-h VVR score for the LOS in the PICU was 6.7 (sensitivity 70%, specificity 92%) and that for the duration of mechanical ventilation was 9.1 (sensitivity 87%, specificity 97%). As a result, in our study, it was found that the VVR score is a new and effective predictor of the duration of mechanical ventilation and LOS in the PICU in postoperative CHS patients.

Validity and reliability of the Turkish version of three screening tools (PYMS, STAMP, and STRONG-kids) in hospitalized children.

BACKGROUND: There are different malnutrition screening tools developed in the English language, but limited data available on the validity of their versions translated into other languages. The aim of this study is to construct a Turkish version of PYMS, STRONG-kids, and STAMP and to determine their validity and reliability in a pediatric population. METHODS: The present study was conducted at two stages. First, the process of translating PYMS, STRONG-kids, and STAMP into the Turkish language was performed. In the second stage, the validity and reliability were evaluated in the new version of the tools. The anthropometric assessment was used as the reference standard in evaluating the validity of criteria. The reliability was observed through inter-rater and intra-rater agreement. RESULTS: 202 children in total were involved in the present study, 42 of whom took part in the reliability phase. The inter-rater agreement between one dietitian and one nurse was kappa (κ) = 0.955 (95% CI 0.904-1.000) for PYMS, 0.901 (95% CI 0.828-0.974) for STRONG-kids, and 0.963 (95% CI 0.912-1.000) for STAMP (almost perfect agreement). Sensitivity of the PYMS, STRONG-kids, and STAMP were 96.8%, 87.1%, and 77.4%, respectively. Specificity of the PYMS, STRONG-kids, and STAMP was found to be 65.0%, 30%, and 60.0%, respectively. CONCLUSION: The inter-rater and intra-rater reliability of the three tools were determined to be good. While PYMS was found to be more sensitive in detecting the malnutrition risk when compared to the other tools, STRONG-kids had the lowest specificity according to the agreement between tool results and anthropometric assessment.

Outcomes of renal replacement therapy in boys with prune belly syndrome: findings from the ESPN/ERA-EDTA Registry.

BACKGROUND: As outcome data for prune belly syndrome (PBS) complicated by end-stage renal disease are scarce, we analyzed characteristics and outcomes of children with PBS using the European Society for Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry data. METHODS: Data were available for 88 male PBS patients aged <20 years who started renal replacement therapy (RRT) between 1990 and 2013 in 35 European countries. Patient characteristics, survival, and transplantation outcomes were compared with those of male patients requiring RRT due to congenital obstructive uropathy (COU) and renal hypoplasia or dysplasia (RHD). RESULTS: Median age at onset of RRT in PBS was lower [7.0; interquartile range (IQR) 0.9-12.2 years] than in COU (9.6; IQR: 3.0-14.1 years) and RHD (9.4; IQR: 2.7-14.2 years). Unadjusted 10-year patient survival was 85% for PBS, 94% for COU, and 91% for RHD. After adjustment for country, period, and age, PBS mortality was similar to that of RHD but higher compared with COU [hazard ratio (HR) 1.96, 95% confidence interval (CI) 1.03-3.74]. Seventy-four PBS patients (84%) received a first kidney transplant after a median time on dialysis of 8.4 (IQR 0.0-21.1) months. Outcomes with respect to time on dialysis before transplantation, chance of receiving a first transplant within 2 years after commencing RRT, and death-censored, adjusted risk of graft loss were similar for all groups. CONCLUSIONS: This study in the largest cohort of male patients with PBS receiving RRT to date demonstrates that outcomes are comparable with other congenital anomalies of the kidney and urinary tract, except for a slightly higher mortality risk compared with patients with COU.

Evaluating Left-Censored Data Through Substitution, Parametric, Semi-parametric, and Nonparametric Methods: A Simulation Study.

In this study, an attempt was made to determine the degrees of bias in particular sampling sizes and methods. The aim of the study was to determine deviations from the median, the mean, and the standard deviation (SD) in different sample sizes and at different censoring rates for log-normal, exponential, and Weibull distributions in the case of full and censored data sampling. Thus, the concept of "censoring" and censoring types was handled in the first place. Then substitution, parametric (MLE), nonparametric (KM), and semi-parametric (ROS) methods were introduced for the evaluation of left-censored observations. Within the scope of the present study, the data were produced uncensored based on the different parameters of each distribution. Then the datasets were left-censored at the ratios of 5, 25, 45, and 65 %. The censored data were estimated through substitution (LOD and LOD/[Formula: see text]), parametric (MLE), semi-parametric (ROS), and nonparametric (KM) methods. In addition, evaluation was made by increasing the sample size from 20 to 300 by tens. Performance comparison was made between the uncensored dataset and the censored dataset on the basis of deviations from the median, the mean, and the SD. The results of simulation studies show that LOD/[Formula: see text] and ROS methods give better results than other methods in deviation from the mean in different sample sizes and at different censoring rates, while ROS gives better results than other methods in deviation from the median in almost all sample sizes and at almost all censoring rates.

Prognostic Importance of Bone Marrow Uptake on Baseline 18F-FDG Positron Emission Tomography in Diffuse Large B Cell Lymphoma.

AIM: To define the role of 18F-flourodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in the detection of bone marrow (BM) involvement in patients with diffuse large B cell lymphoma (DLBCL). MATERIALS AND METHODS: Fifty-four (mean age: 55.5 ± 18.3 years, 20 female and 34 male) DLBCL patients who underwent pretreatment 18F-FDG PET/CT were included to the study. Focal or diffuse BM 18F-FDG uptake that is higher than mediastinal blood pool uptake was accepted as positive. After staging of disease by CT and 18F-FDG PET/CT, all the patients received R-CHOP treatment after diagnostic blinded bone marrow biopsy (BMB). Presence of positive BM uptake in 18F-FDG PET/CT and histopathological examination results of BMBs were analyzed by Chi-square test. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of 18F-FDG PET/CT in the detection of BM involvement were calculated. Prognostic importance of the presence of BM 18F-FDG uptake was analyzed by Kaplan-Meier analysis. RESULTS: BM 18F-FDG uptake was detected in 8 patients. Histopathological examination of BMB revealed BM involvement in 6 out of 8 patients. BMB was negative in all patients who have no 18F-FDG uptake in the evaluation of PET/CT images. Sensitivity, specificity, accuracy, PPV, and NPV of 18F-FDG PET/CT in the detection of BM involvement were calculated as 100%, 96%, 96%, 75%, and 100%, respectively. In the Kaplan-Meier analysis, we found that presence of pretreatment 18F-FDG uptake in BM has a prognostic importance. Whereas mean time to progression (TTP) in patients with BM uptake was 32.25 ± 10.9 months and mean TTP in those without was 51.69 ± 3.6 months (p = 0.013). CONCLUSIONS: BM uptake in pretreatment 18F-FDG PET/CT is an important prognostic factor in DLBCL patients. Moreover, in consideration of high NPV, 18F-FDG PET/CT could eliminate unnecessary BMB in FDG-negative patients.

Optimization of gene expression microarray protocol for formalin-fixed paraffin-embedded tissues.

Formalin-fixed paraffin-embedded (FFPE) tissue is a widely available clinical specimen for retrospective studies. The possibility of long-term clinical follow-up of FFPE samples makes them a valuable source to evaluate links between molecular and clinical information. Working with FFPE samples in the molecular research area, especially using high-throughput molecular techniques such as microarray gene expression profiling, has come into prominence. Because of the harmful effects of formalin fixation process such as degradation of nucleic acids, cross-linking with proteins, and chemical modifications on DNA and RNA, there are some limitations in gene expression profiling studies using FFPE samples. To date many studies have been conducted to evaluate gene expression profiling using microarrays (Thomas et al., Thomas et al. (2013) [1]; Scicchitano et al., Scicchitano et al. (2006) [2]; Frank et al., Frank et al. (2007) [3]; Fedorowicz et al., Fedorowicz et al. (2009) [4]). However, there is still no generally accepted, efficient and standardized procedure for microarray analysis of FFPE samples. This paper describes the microarray data presented in our recently accepted to be published article showing a standard protocol from deparaffinization of FFPE tissue sections and RNA extraction to microarray gene expression analysis. Here we represent our data in detail, deposited in the gene expression omnibus (GEO) database with the accession number GSE73883. Four combinations of two different cRNA/cDNA preparation and labeling protocols with two different array platforms (Affymetrix Human Genome U133 Plus 2.0 and U133_X3P) were evaluated to determine which combination gives the best percentage of present call. The study presents a dataset for comparative analysis which has a potential in terms of providing a robust protocol for gene expression profiling with FFPE tissue samples.

The Interaction of Nepafenac and Prostaglandin Analogs in Primary Open-angle Glaucoma Patients.

PURPOSE: To investigate the effect of nepafenac on intraocular pressure (IOP) in primary open-angle glaucoma (POAG) patients treated with prostaglandin (PG) analogs. MATERIALS AND METHODS: This prospective clinical study included 35 patients who had been receiving latanoprost (n=12), travoprost (n=12), or bimatoprost (n=11) for POAG. Nepafenac 0.1% and placebo drops were administered to the right and left eyes of patients, respectively, 3 times a day for 7 days. IOP measurements were taken at 9:00 AM, 12:00 PM, and 4:00 PM at baseline and all consecutive visits. The visits were scheduled on days 1 and 7 during treatment and 1 and 7 days after discontinuation of the treatment. RESULTS: The mean age of the patients was 60.28±7.51 years (range, 48 to 75 y). The baseline IOP was similar in the nepafenac and placebo groups (15.33±1.45 vs. 15.41±1.41, respectively, P>0.05). The decrease in the mean IOP was significant in the nepafenac group compared with the placebo group throughout the treatment period (P<0.001). After the discontinuation of nepafenac treatment, the mean IOP became similar with the placebo group from the first day (P>0.05). The change in mean IOP was not significant between the PG subgroups during treatment and discontinuation periods (P=0.712). CONCLUSIONS: Nepafenac potentiates the IOP-lowering effects of 3 different PG analogs in POAG patients.

Foetal biometry in polyhydramnios: Does femur length fall behind?

We aimed to identify the growth patterns in polyhydramnios, and therefore evaluated 108 singleton pregnancies complicated with polyhydramnios according to the changes in biparietal diameter (BPD), abdominal circumference (AC) and femur length (FL) percentiles. The pregnancy outcomes according to the growth features were analysed. In the study population, BPD and AC percentiles exhibited a significant increase (p = 0.023 and 0.05, respectively), although FL percentiles showed a significant decrease (p = 0.006) according to the changes in third trimester relative to second trimester. In the overgrown group (n = 52), the FL/BPD ratio was lower (p < 0.001), with more foetuses with FL/BPD ratios below 71 (p = 0.05). In conclusion, there was a significant increase in BPD and AC percentiles and a decrease in FL percentiles in third trimester relative to second trimester in foetuses with polyhydramnios. However, we observed a shorter FL and a lower FL/BPD ratio without associated skeletal dysplasia in overgrown foetuses.

Repeatability and reproducibility of a new optical biometer in normal and keratoconic eyes.

PURPOSE: To evaluate the repeatability and reproducibility of measurements obtained by a new optical biometer (Nidek AL-Scan) in normal eyes and keratoconic eyes. SETTING: Department of Ophthalmology, Turgut Özal University, Medical School, Ankara, Turkey. DESIGN: Evaluation of diagnostic technology. METHODS: To assess the repeatability and reproducibility of the optical biometer, 2 independent examiners performed 3 consecutive measurements. The following parameters were evaluated: central corneal thickness (CCT), anterior chamber depth, axial length (AL), corneal dioptric power in the flattest meridian (flat keratometry [K]) and in the steepest meridian (steep K), and white-to-white (WTW) distance. Repeatability was assessed using the within-subject standard deviation (S(w)), repeatability, and precision. Reproducibility was evaluated using the 95% limits of agreement proposed by Bland and Altman. RESULTS: Thirty healthy subjects and 27 patients with keratoconus were evaluated. Both examiners achieved high repeatability for all parameters in each group except for the steep K measurement in keratoconic eyes performed by examiner 2 (S(w) = 3.341). The WTW in normal eyes and the CCT and steep K in keratoconic eyes showed less repeatability. In both groups, the smallest range of agreement was in AL measurements whereas the largest was in CCT measurements. In keratoconic eyes, the range of agreement for steep K was also greater (3.766). CONCLUSIONS: The precision of the measurements obtained by the new optical biometer was high. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Transient intrauterine fluid accumulation not due to hydrosalpinx or any identifiable pelvic pathology is not detrimental to IVF outcome.

PURPOSE: This study is to assess whether transient intrauterine fluid accumulation (IUFA) first noted during controlled ovarian hyperstimulation that does not persist on the day of embryo transfer not due to any identifiable pelvic pathology has any detrimental effect on in vitro fertilization (IVF) outcome. METHODS: From a database of 16,900 cycles, 144 patients with transient "physiological" IUFA were recruited. Four hundred fifty-one consecutive patients who had male factor infertility served as the control group. The amount of IUFA classified as largest dimension in the antero-posterior (AP) plane; ≤2, 3-5 or >5 mm. RESULTS: The mean female age, the mean number of embryos transferred and endometrial thickness on the day of hCG administration were comparable among the study and control groups. Similarly, clinical pregnancy, ongoing pregnancy and implantation rates were comparable among the study and control groups. Female age was noted to be the only significant independent predictor of ongoing pregnancy. The AP dimension of IUFA did not have any impact on pregnancy and implantation rates. CONCLUSIONS: Transient IUFA not due to hydrosalpinx or any identifiable pelvic pathology has no detrimental effect on IVF pregnancy rates. Hence, cycle cancellation should be avoided in such cycles.

Familial Mediterranean fever in siblings.

OBJECTIVE: Genetic and environmental factors have been implicated in disease severity and development of amyloidosis in familial Mediterranean fever (FMF). We investigated similarities in clinical characteristics, disease severity, and treatment response within siblings with FMF. METHODS: The study group consisted of 2 or more siblings who were followed in our center with the diagnosis of FMF. Siblings were evaluated for demographic data, clinical and laboratory disease features, genetic analysis of MEFV mutations, and disease severity score. The intraclass correlation coefficient (ICC), which can be interpreted as the expected correlation between 2 siblings, was used to reflect within-family similarity. RESULTS: The study included 67 pediatric patients from 31 different families. When we investigated the similarity of siblings after adjusting for genetic effects, we found very low ICC with p > 0.05 in the majority of clinical features, disease severity, and colchicine dosages. However, age at disease onset, age at onset of therapy, attack-free acute-phase reactant levels, and presence of amyloidosis were found to be similar within siblings (relatively high ICC with p < 0.05). CONCLUSION: Siblings with FMF had different clinical findings and disease severity. They had similar amyloidogenic potential, proven by both similar presence of amyloid and increased levels of acute-phase reactants between attacks. Our findings strongly support that genetic factors may be more dominant in the development of amyloidosis.