Ferric carboxymaltose versus standard-of-care oral iron to treat second-trimester anaemia in Malawian pregnant women: a randomised controlled trial.

BACKGROUND: Anaemia affects 46% of pregnancies in Africa; oral iron is recommended by WHO but uptake and adherence are suboptimal. We tested a single dose of a modern intravenous iron formulation, ferric carboxymaltose, for anaemia treatment in Malawian pregnant women. METHODS: In this open-label, individually randomised controlled trial, we enrolled women with a singleton pregnancy of 13-26 weeks' gestation in primary care and outpatient settings across two regions in southern Malawi. Women were eligible if they had capillary haemoglobin of less than 10·0 g/dL and negative malaria rapid diagnostic test. Participants were randomised by sealed envelope 1:1. Assessors for efficacy outcomes (laboratory parameters and birthweight) were masked to intervention; participants and study nurses were not masked. Participants were given ferric carboxymaltose up to 1000 mg (given once at enrolment in an outpatient primary care setting), or standard of care (60 mg elemental iron twice daily for 90 days), along with intermittent preventive malaria treatment. The primary maternal outcome was anaemia at 36 weeks' gestation. The primary neonatal outcome was birthweight. Analyses were performed in the intention-to-treat population for mothers and liveborn neonates, according to their randomisation group. Safety outcomes included incidence of adverse events during infusion and all adverse events from randomisation to 4 weeks' post partum. The trial is registered with ANZCTR, ACTRN12618001268235. The trial has completed follow-up. FINDINGS: Between Nov 12, 2018, and March 2, 2021, 21 258 women were screened, and 862 randomly assigned to ferric carboxymaltose (n=430) or standard of care (n=432). Ferric carboxymaltose did not reduce anaemia prevalence at 36 weeks' gestation compared with standard of care (179 [52%] of 341 in the ferric carboxymaltose group vs 189 [57%] of 333 in the standard of care group; prevalence ratio [PR] 0·92, 95% CI 0·81 to 1·06; p=0·27). Anaemia prevalence was numerically lower in mothers randomly assigned to ferric carboxymaltose compared with standard of care at all timepoints, although significance was only observed at 4 weeks' post-treatment (PR 0·91 [0·85 to 0·97]). Birthweight did not differ between groups (mean difference -3·1 g [-75·0 to 68·9, p=0·93). There were no infusion-related serious adverse events or differences in adverse events by any organ class (including malaria; ≥1 adverse event: ferric carboxymaltose 183 [43%] of 430 vs standard of care 170 [39%] of 432; risk ratio 1·08 [0·92 to 1·27]; p=0·34). INTERPRETATION: In this malaria-endemic sub-Saharan African setting, treatment of anaemic pregnant women with ferric carboxymaltose was safe but did not reduce anaemia prevalence at 36 weeks' gestation or increase birthweight. FUNDING: Bill & Melinda Gates Foundation (INV-010612).

Should we depend on reference intervals from manufacturer package inserts? Comparing TSH and FT4 reference intervals from four manufacturers with results from modern indirect methods and the direct method.

OBJECTIVES: Correct interpretation of thyroid function tests relies on correct reference intervals (RIs) for thyroid-stimulating hormone (TSH) and free thyroxine (FT4). ISO15189 mandates periodic verification of RIs, but laboratories struggle with cost-effective approaches. We investigated whether indirect methods (utilizing historical laboratory data) could replace the direct approach (utilizing healthy reference individuals) and compared results with manufacturer-provided RIs for TSH and FT4. METHODS: We collected historical data (2008-2022) from 13 Dutch laboratories to re-establish RIs by employing indirect methods, TMC (for TSH) and refineR (for FT4). Laboratories used common automated platforms (Roche, Abbott, Beckman or Siemens). Indirect RIs (IRIs) were determined per laboratory per year and clustered per manufacturer (>1.000.000 data points per manufacturer). Direct RIs (DRIs) were established in 125 healthy individuals per platform. RESULTS: TSH IRIs remained robust over the years for all manufacturers. FT4 IRIs proved robust for three manufacturers (Roche, Beckman and Siemens), but the IRI upper reference limit (URL) of Abbott showed a decrease of 2 pmol/L from 2015. Comparison of the IRIs and DRIs for TSH and FT4 showed close agreement using adequate age-stratification. Manufacturer-provided RIs, notably Abbott, Roche and Beckman exhibited inappropriate URLs (overall difference of 0.5-1.0 µIU/mL) for TSH. For FT4, the URLs provided by Roche, Abbott and Siemens were overestimated by 1.5-3.5 pmol/L. CONCLUSIONS: These results underscore the importance of RI verification as manufacturer-provided RIs are often incorrect and RIs may not be robust. Indirect methods offer cost-effective alternatives for laboratory-specific or platform-specific verification of RIs.

Albumin determined by bromocresol green leads to erroneous results in routine evaluation of patients with chronic kidney disease.

OBJECTIVES: Measurement of plasma albumin is pivotal for clinical decision-making in patients with chronic kidney disease (CKD). Routinely used methods as bromocresol green (BCG) and bromocresol purple (BCP) can suffer from aselectivity, but the impact of aselectivity on the accuracy of plasma albumin results of CKD-patients is still unknown. Therefore, we evaluated the performance of BCG-, BCP- and JCTLM-endorsed immunological methods in patients with various stages of CKD. METHODS: We evaluated the performance of commonly used albumin methods in patients with CKD stages G1 through G5, the latter divided in two groups based on whether they received hemodialysis treatment. In total, 163 patient plasma samples were measured at 14 laboratories, on six different BCG and BCP-platforms, and four different immunological platforms. The results were compared with an ERM-DA-470k-corrected nephelometric assay. The implications on outcome is evaluated by the proportion of patient results <38 g/L for the diagnosis of protein energy wasting. RESULTS: Albumin results determined with BCP- and immunological methods showed the best agreement with the target value (92.7 and 86.2 %, respectively vs. 66.7 % for BCG, namely due to overestimation). The relative agreement of each method with the target value was platform-dependent, with larger variability in agreement between platforms noted for BCG and immunological methods (3.2-4.6 and 2.6-5.3 %) as opposed to BCP (0.7-1.5 %). The stage of CKD had similar effects on the variability in agreement for the three method-groups (0.6-1.8 % vs. 0.7-1.5 % vs. 0.4-1.6 %). The differences between methods cause discrepancies in clinical decision-making, as structurally fewer patients were diagnosed with protein energy wasting upon using BCG-based albumin results. CONCLUSIONS: Our study shows that BCP is fit for the intended use to measure plasma albumin levels in CKD patients from all stages, including patients on hemodialysis. In contrast, most BCG-based platforms falsely overestimate the plasma albumin concentration.

Toll-interacting protein may affect doxorubicin resistance in hepatocellular carcinoma cell lines.

BACKGROUND: Liver cancer is the third leading cause of cancer-related deaths worldwide, and hepatocellular carcinoma (HCC) is the most common type of liver cancer. Transarterial interventions are among the chemotherapeutic approaches used in hardly operable regions prior to transplantation, and in electrochemotherapy, where doxorubicin is used. However, the efficacy of treatment is affected by resistance mechanisms. Previously, we showed that overexpression of the CUE5 gene results in doxorubicin resistance in Saccharomyces cerevisiae (S. cerevisiae). In this study, the effect of Toll-interacting protein (TOLLIP), the human ortholog of CUE5, on doxorubicin resistance was evaluated in HCC cells to identify its possible role in increasing the efficacy of transarterial interventions. METHODS AND RESULTS: The NIH Gene Expression Omnibus (GEO) and Oncomine datasets were analyzed for HCC cell lines with relatively low and high TOLLIP expression, and SNU449 and Hep3B cell lines were chosen, respectively. TOLLIP expression was increased by plasmid transfection and decreased by TOLLIP-siRNA in both cell lines and evaluated by RT-PCR and ELISA. Cell proliferation and viability were examined using xCELLigence and MTT assays after doxorubicin treatment, and growth inhibitory 50 (GI 50) concentrations were evaluated. Doxorubicin GI 50 concentrations decreased approximately 2-folds in both cell lines upon silencing TOLLIP after 48 h of drug treatment. CONCLUSIONS: Our results showed for the first time that silencing TOLLIP in hepatocellular carcinoma cells may help sensitize these cells to doxorubicin and increase the efficacy of chemotherapeutic regimens where doxorubicin is used.

The incidence and prevalence of medical device-related pressure injuries in pediatric patients: Systematic review and meta-analysis.

PROBLEM: To determine the pooled incidence and prevalence rate of medical device-related pressure injuries(MDRPIs) using the Braden QD scale, medical devices that frequently cause MDRPIs, and anatomical locations that are vulnerable to them. ELIGIBILITY CRITERIA: Using the Braden QD scale, being published in English between 01/01/2018-and 01/03/2023. METHODS: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations and registered in the International Prospective Register of Systematic Reviews database (No: CRD42021276501). SAMPLE: A total of 7 studies with 25,742 pediatric patients were included. RESULTS: The pooled prevalence and cumulative incidence of hospital-acquired pressure injuries(HAPIs) were 7.8% (95% CI: 5.2-11.4%) and 3.9% (95% CI: 0.5-24.6%) respectively, and the incidence rate was 8.2/1000 person-days (95% CI: 2.4-14.2/1000 person-days). The pooled prevalence and cumulative incidence of MDRPIs were 7% (95% CI: 5.5-8.8%) and 5% (95% CI: 3.2-7.8%) respectively, and the incidence rate was 6.7/1000 person-days (95% CI, 0.11-13.4/1000 person-days). The most affected anatomical locations were the face (29.1%), ankle/foot (20.1%), and head (15.7%). Medical devices that frequently caused MDRPIs were external monitoring devices (24.5%), respiratory devices (22.8%), and supportive/securing devices (14.9%). CONCLUSIONS: According to the current systematic review and meta-analyses, the incidence and prevalence of HAPIs and MDRPIs are moderate to high. IMPLICATIONS: The findings suggested that healthcare providers should pay more attention to reducing HAPIs and MDRPIs and future studies should be conducted to understand their characteristics and risk factors.

Effect of virtual reality on pain during burn dressing in children: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Burn dressing, a necessary and regular procedure for burn management, causes significant pain and distress for children. Recent technological advancements in VR have opened up new possibilities for pain management in children undergoing burn dressing. However, there is limited evidence regarding their efficacy in burn dressing specifically. This study aims to synthesize and analyze the effect of VR on pain during burn dressing in children. METHODS: In this review, we investigated studies from PubMed, Web of Science, Cochrane, MEDLINE, CINAHL, Scopus and Google Scholar databases that met inclusion criteria. We also assessed the studies' methodological quality with the Cochrane and JBI checklists. This study was performed based on the Guidelines of Systematic Reporting of Examination presented in the PRISMA checklist. The search protocol has been registered at the PROSPERO International Prospective Register of Systematic Reviews. RESULTS: A total of six published studies including 241 pediatric patients were included in this review. The meta-analysis results showed a significant effect of VR intervention on the pain levels of children (Hedge's g = -1199, Q = 31,106, I2 = 83,926%, p < 0.001). CONCLUSION: Findings from this study show that VR is a promising and effective intervention for reducing pain scores in children undergoing dressing changes for burn injuries. IMPLACATION TO PRACTICE: Our meta-analysis suggest that the significant potential of integrating VR into clinical practice, presenting a non-pharmacological intervention to reduce pain during dressing changes in pediatric burn patients. Implementing VR in healthcare settings can lead to improved pain management and better patient outcomes for pediatric population.

Personal Protective Equipment-Related Problems Experienced by Healthcare Workers, Solutions, and Recommendations: A Qualitative Study.

OBJECTIVE: To understand the problems experienced by healthcare workers (HCWs) who used personal protective equipment (PPE) on their face during the COVID-19 pandemic, their interventions to prevent these problems, and their recommendations for improving the quality of PPE. METHODS: This descriptive and qualitative study included HCWs (N = 29) from health institutions at different levels in Turkey. Researchers collected data using a semistructured data collection form (13 items) and in-depth individual interviews. Data were analyzed with descriptive statistics and qualitative inductive content analysis. RESULTS: Of the 29 participants, 15 (51.7%) were women, and 18 (62.1%) were nurses. Participants' answers regarding problems related to PPE use were grouped into four main categories, answers regarding the prevention of these problems were grouped into three main categories, and answers regarding improving the quality of PPE were grouped into three main categories. Skin concerns were the most commonly reported problems related to PPE, and interventions to prevent these problems primarily related to skin protection and care. Recommendations to improve the quality of PPE focused on using materials for masks and face shields that reduce pressure and friction; participants also suggested that face shields be produced in sterile and disposable packages. CONCLUSIONS: This research indicates that HCWs need support and they are able to create individual solutions for the problems with PPE that they experience. Skin-friendly PPE that ensures the safety and comfort of HCWs should be produced, and hospitals should develop policies for institutional use to prevent PPE injury.

Testosterone analysis in castrated prostate cancer patients: suitability of the castration cut-off and analytical accuracy of the present-day clinical immunoassays.

OBJECTIVES: Testosterone testing is relevant for evaluating castration adequacy and diagnosis of castration-resistant prostate cancer (PCa). However, the recommended testosterone cut-off of 1.7 nmol/L (50 ng/dL) to define adequate castration is based on consensus and not validated for the automated immunoassays (AIA) used in today's medical laboratories. Furthermore, appropriate population intervals have not been determined by a state-of-the-art assay. We investigated the analytical suitability of this cut-off and the accuracy of the present-day AIAs for testosterone analysis in castrated PCa patients. METHODS: Leftover serum from 120 PCa patients castrated with luteinizing hormone-releasing hormone agonists was analysed for testosterone by five methods: Architect i2000 (Abbott), Access (Beckman), Cobas 6000 (Roche), Atellica (Siemens), LC-MS/MS. For all assays, the castration 95th, 97.5th and 99th percentile upper limits were determined. Furthermore, Passing-Bablok regression, mean bias and Spearman's correlation coefficients were compared to the LC-MS/MS method and total error based on biological variation. RESULTS: All castration upper limits, ranging from 0.472 nmol/L (LC-MS/MS) to 1.25 nmol/L (Access) (95% percentile), were significantly lower than the current castration cut-off (1.7 nmol/L). Slopes of Passing-Bablok regressions comparing the AIA with the LC-MS/MS method ranged from 1.4 (Cobas and Atellica) to 3.8 (Access). The Architect showed the highest correlation with LC-MS/MS (ρ=0.58). All AIA failed to meet the desirable total error criterion. CONCLUSIONS: These results suggest that a lower general testosterone castration cut-off may be more appropriate in evaluating the adequacy of castration in PCa and that present-day AIA lack analytical accuracy to quantify testosterone levels in castrated PCa.

Evaluation of carbohydrate-deficient transferrin measurements on the V8 capillary electrophoresis system and comparison with the IFCC approved HPLC reference method and N-Latex immunonephelometric assay.

OBJECTIVES: Carbohydrate-deficient transferrin (CDT) measurements are commonly used for the identification and follow-up of individuals suspected of chronic alcohol abuse. This study describes the analytical characteristics of the CDT assay on the Helena Biosciences V8 electrophoresis analyzer and compares its diagnostic performance to the International Federation of Clinical Chemistry and Laboratory Medicine approved high performance liquid chromatography (HPLC) method and the N-Latex CDT immunonephelometric assay. METHODS: The analytical performance of the V8 assay, including the linearity and the imprecision, was studied at two separate locations. Method comparison analysis was performed by studying the correlation, bias and agreement between the V8, HPLC and the N-Latex assays in 231 patient samples. RESULTS: The total imprecision ranged between 5.1 and 24.3% and was ≤13.1% for samples with concentrations above the clinical cut-off value (≥1.62%). The method comparisons revealed excellent correlations with r2≥0.97 for all comparisons. Measurements on the V8 showed a bias of -0.83 (-22.24%) and -0.40 (-12.26%) with the HPLC and N-Latex assays, respectively. The assays showed excellent agreements (Kappa scores ≥ 0.8) in classifying subjects with elevated CDT values. Receiver operating characteristic (ROC)-curve analysis, using the HPLC classification as reference, revealed areas under the ROC-curves of 0.981 (95% CI, 0.97-0.99) and 0.996 (0.99-1.00) for the N-Latex and V8 assays, respectively. CONCLUSIONS: CDT measurements on the V8 assay are highly correlated with both the HPLC and the N-Latex assay and show excellent agreement in classifying subjects with elevated CDT values. Overall, the V8 CDT analysis is a robust, reliable and effective method to measure CDT concentrations in serum samples.

Analysis of Three Mutations in Italian Strains of SARS-CoV-2: Implications for Pathogenesis.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped virus initially detected in Wuhan in December 2019, responsible for coronavirus disease 2019 (COVID-19), a respiratory syndrome currently affecting >220 countries around the world, with >80 million cases registered and >1.8 million deaths. OBJECTIVE: As several vaccines are still being developed and 2 have been approved, it is particularly important to perform evolutionary surveillance to identify mutations potentially affecting vaccine efficacy. METHODS: DynaMut server has been used to evaluate the impact of the mutation found on SARS-CoV-2 isolates available on GISAID. RESULTS: In this article, we analyze whole genomes sequenced from Italian patients, and we report the characterization of 3 mutations, one of which presents in the spike protein. CONCLUSION: The mutations analyzed in this article can be useful to evaluate the evolution of SARS-CoV-2.

Evaluation of the Atellica® UAS 800: a new member of the automated urine sediment analyzer family.

BACKGROUND: In 2017 the Atellica® UAS 800 urine sediment analyzer was introduced by Siemens Healthineers. We investigated its applicability in the standardization and automation of the laboratory urinalysis workflow, including the prediction of urine culture outcome and glomerular pathology. METHODS: We evaluated the performance characteristics of the Atellica® UAS 800 and its correlation with the iQ200 (Beckman Coulter). In addition, we studied the agreement between Atellica® UAS 800 and CLINITEK Novus® and determined the predictive value of bacteria and leukocyte counts for urine culture outcome. Furthermore, we investigated the ability of Atellica® UAS 800 to identify pathological casts and dysmorphic erythrocytes in comparison to manual microscopy. RESULTS: Erythrocyte and leukocyte analyses indicated high intra- and inter-run precisions and good correlations with the iQ200. We found that the Atellica® UAS 800 detects bacteria with higher sensitivity than the iQ200. The Atellica® UAS 800 and CLINITEK Novus® showed a high degree of conformity. We determined seven combinations of clinical cut-off values of bacteria and leukocytes for predicting urine culture outcome with sensitivity, specificity, and negative predictive values of 95%, 52%, and 93%, respectively. Using the Atellica® UAS 800, hyaline casts, erythrocyte casts, leukocyte casts, and dysmorphic erythrocytes were correctly recognized in 76%, 22%, 2%, and 39% of the samples, respectively. CONCLUSIONS: The Atellica® UAS 800 is a robust, fast, and user-friendly analyzer, which accurately quantifies erythrocytes, leukocytes, bacteria and squamous epithelial cells, and may be utilized for predicting positive urine cultures. The detection of clinically important pathological casts and dysmorphic erythrocytes proved insufficient.

[Analysis of Nucleotide Changes in RT-PCR Primer/Probe Binding Regions in SARS-CoV-2 Isolates Reported from Turkey]. / Türkiye'den Bildirilen Sars-CoV-2 Izolatlarinda RT-PCR Primer/Prob Baglanma Bölgelerindeki Nükleotit Degisimlerinin Analizi.

The SARS-CoV-2 virus, which caused the COVID-19 epidemic, caused more than 55 million cases and nearly 1.5 million deaths worldwide. For the microbiological diagnosis of the disease, the most valid method is detecting the presence of the viral genome by real-time reverse transcription polymerase chain reaction (rRT-PCR). However, due to the nature of the RNA viruses, frequent mutations may affect the sensitivity of the analyses made on the genetic material of the virus, such as PCR. In this study, we aimed to investigate the mutations in the primer-probe binding regions of the rRT-PCR panels used in COVID-19 diagnosis. SARS-CoV-2 whole genome sequence data (n= 194) isolated from COVID-19 cases in Turkey and uploaded on GISAID database from the centers in Istanbul (n= 78), Ankara (n= 58), Kars (n= 47), Bursa (n= 2), Adiyaman (n= 2), Erciyes (n= 1) and Kocaeli (n= 1) between March 17-September 14, 2020 were analyzed. In order to determine the nucleotide changes, SARS-CoV-2 sequences from Turkey were compared to the reference genome sequence (NC_045512.1) present in "GenBank" website. The constructed data set was aligned using the MAFFT program and was checked manually if the sequences were in the same frame by using the AliView program. Primer-probe binding sites of the thirteen SARS-CoV-2 rRT-PCR panels from seven different institutes (US CDC, China CDC, Charite CDC, Pasteur, HKU, Thailand, NIID) that are being used in COVID-19 diagnosis were evaluated in terms of nucleotide changes within the corresponding regions compared to the reference genome. Sequence diversities in the viral genomes were determined via positional nucleotide numerical calculator and entropy calculator modules and nucleotide and entropy changes in primer-probe binding regions for each rRT-PCR panel were examined. Among thirteen different primer-probe panels, nucleotide changes in the target regions of the seven primer-probe panels were determined. When viral sequences with nucleotide changes in the primer-probe binding regions were examined, the most common changes were observed in the "China CDC" N-forward primer and "US CDC" N3-forward primer binding regions. It is important that the kits to be used as diagnostic tests are designed specific to the regions with less nucleotide changes. Nucleotide changes may not be critical for DNA amplification for most PCR panels, but should be carefully monitored as they may affect the sensitivity of the assay. If the risk of alteration of the designed region is high, the primer - probe binding sites should be checked frequently and updated when necessary.

Evidence for mutations in SARS-CoV-2 Italian isolates potentially affecting virus transmission.

Italy is the first western country suffering heavy severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and disease impact after coronavirus disease-2019 pandemia started in China. Even though the presence of mutations on spike glycoprotein and nucleocapsid in Italian isolates has been reported, the potential impact of these mutations on viral transmission has not been evaluated. We have compared SARS-CoV-2 genome sequences from Italian patients with virus sequences from Chinese patients. We focussed upon three nonsynonymous mutations of genes coding for S(one) and N (two) viral proteins present in Italian isolates and absent in Chinese ones, using various bioinformatics tools. Amino acid analysis and changes in three-dimensional protein structure suggests the mutations reduce protein stability and, particularly for S1 mutation, the enhanced torsional ability of the molecule could favor virus binding to cell receptor(s). This theoretical interpretation awaits experimental and clinical confirmation.

Current state of the morphological assessment of urinary erythrocytes in The Netherlands: a nation-wide questionnaire.

Background The morphological assessment of urinary erythrocytes (uRBC) is a convenient screening tool for the differentiation of nephrological (dysmorphic) and urological (isomorphic) causes of hematuria. Considering the morphological heterogeneity, this analysis is often perceived as difficult. There is no clear (inter)national consensus and there is a lack of external quality assessment programs. To gain insight into the heterogeneity within and between laboratories, we scrutinized the current state of this analysis in Dutch medical laboratories. Methods The laboratories, affiliated with the Dutch Foundation for Quality Assessment in Medical Laboratories, were invited to participate in a web-based survey, consisting of two questionnaires. The first one provided information about the institution and laboratory organization, and the second explored the variability in the morphological analysis of uRBC on the basis of categorization of 160 uRBC images. Statistical analysis was premised on binomial significance testing and principal component analysis. Results Nearly one third of the Dutch medical laboratories (65/191) with 167 staff members participated in the survey. Most of these laboratories (83%) were an integral part of secondary care. The statistical analysis of the evaluations of the participants in comparison to the consensus (three experts from two different medical laboratories) suggested a great degree of heterogeneity in the agreement. Nearly half of the participants consciously disagreed with the consensus, whereas one fifth demonstrated a random relationship with it. Conclusions In Dutch medical laboratories, results from morphological analysis of uRBC are heterogeneous, which point out the necessity for standardization and harmonization.

Detection of hip osteoarthritis by using plain pelvic radiographs with deep learning methods.

OBJECTIVE: The incidence of osteoarthritis is gradually increasing in public due to aging and increase in obesity. Various imaging methods are used in the diagnosis of hip osteoarthritis, and plain pelvic radiography is the first preferred imaging method in the diagnosis of hip osteoarthritis. In this study, we aimed to develop a computer-aided diagnosis method that will help physicians for the diagnosis of hip osteoarthritis by interpreting plain pelvic radiographs. MATERIALS AND METHODS: In this retrospective study, convolutional neural networks were used and transfer learning was applied with the pre-trained VGG-16 network. Our dataset consisted of 221 normal hip radiographs and 213 hip radiographs with osteoarthritis. In this study, the training of the network was performed using a total of 426 hip osteoarthritis images and a total of 442 normal pelvic images obtained by flipping the raw data set. RESULTS: Training results were evaluated with performance metrics such as accuracy, sensitivity, specificity, and precision calculated by using the confusion matrix. We achieved accuracy, sensitivity, specificity and precision results at 90.2%, 97.6%, 83.0%, and 84.7% respectively. CONCLUSION: We achieved promising results with this computer-aided diagnosis method that we tried to develop using convolutional neural networks based on transfer learning. This method can help clinicians for the diagnosis of hip osteoarthritis while interpreting plain pelvic radiographs, also provides assistance for a second objective interpretation. It may also reduce the need for advanced imaging methods in the diagnosis of hip osteoarthritis.

MicroRNA-17, MicroRNA-19b, MicroRNA-146a, MicroRNA-302d Expressions in Hepatoblastoma and Clinical Importance.

Hepatoblastoma (HB) is the most common liver malignancy in children. The prognosis changes according to the histologic subtypes of HB. In the present study, we aimed to characterize the expression level of selected microRNAs (miRNAs) in HB as well as in histologic subtypes, and to consider the association with the prognosis. A total of 22 HB tumor samples, subtyped as fetal (n=16) and embryonal (n=6), and 10 nontumorous surrounding liver samples were evaluated in this study. Expressions of miR-17, miR-146a, miR-302d, and miR-19b were analyzed in 22 HB tumor samples and 10 nontumorous surrounding liver samples by quantitative real-time polymerase chain reaction. Lower miRNA-17 expression levels were obtained in tumor samples in comparison with nontumorous surrounding liver samples (P=0.028). Lower miRNA-17 expression was significant for predicting prognosis in HB patients (area under receiver-operator characteristic curve=0.875, P=0.044). A higher-level of miR-19b was found in embryonal samples (P=0.008). Overall and event-free survival was not found to correlate with miRNA expression levels (P>0.05). This research finds miRNA-17 and miRNA-19b expression levels can provide important data on diagnosis and prognosis in HB showing different clinical behaviors.

Biological and genetic evaluation of IL-23/IL-17 pathway in ankylosing spondylitis patients.

Ankylosing spondylitis is the most common form of the chronic inflammatory disease group known as spondyloarthritides. Recent discoveries of the CD4+ Th17 cells and IL-23/IL-17 axis have changed the paradigms in many autoimmune diseases. In this study, we aimed to evaluate the importance of IL-23/IL-17 pathway and IL-23 receptor polymorphism in the pathogenesis of ankylosing spondylitis. Blood samples for this study were obtained from 109 ankylosing spondylitis patients and 40 healthy control subjects. Serum levels of TNF-α, IL-6, IL-17, and IL-23 were measured by the ELISA method. The IL-23R gene polymorphisms rs11209026 (Arg381Gln) and rs4131362 (Val362Ile) were performed by the Sanger Sequence method. IL-6 levels were higher in the active and inactive ankylosing spondylitis groups than in the control group. However, levels of IL-17 and IL-23 were lower in the patient group. The frequency of IL-23R gene rs11209026 and rs4131362 polymorphism were 3.7% and 8.3% in the patient, respectively. As a result, dysregulation of the IL-23 / IL-17 pathway, which is caused by reduced levels of IL-17 and IL-23 in systemic circulation in patients with ankylosing spondylitis, may contribute to the pathogenesis of the disease by systemically producing chronic autoimmune inflammation.

Influence of point-of-care C-reactive protein testing on antibiotic prescription habits in primary care in the Netherlands.

Background: Bacterial resistance to antibiotics represents a serious global challenge that is associated with high morbidity and mortality. One of the most important causes of this threat is antibiotic overuse. The Dutch College of General Practitioners (DCGP) recommends the use of point-of-care (POC) testing for C-reactive protein (CRP) in two guidelines ('Acute Cough' and 'Diverticulitis') to achieve a more sensible prescription pattern of antibiotics. Objective: To evaluate the use of POC-CRP testing in light of the DCGP guidelines and the effect of CRP measurements on antibiotic prescription policy in primary care. Methods: In a prospective observational study, which included 1756 patients, general practitioners (GPs) were asked to complete a questionnaire after every POC-CRP testing, stating the indication for performing the test, the CRP result and their decision whether or not to prescribe antibiotics. Indications were verified against the DCGP guidelines and categorized. Antibiotic prescription was evaluated in relation to CRP concentrations. Results and Conclusion: Indications to perform POC-CRP test and the prescription pattern of antibiotics based on CRP value varied considerably between GPs. Differences in antibiotic prescription rate were most obvious in patients who presented with CRP values between 20 and 100 mg/l, and could in part be explained by the indication for performing POC-CRP test and patient age. Most GPs followed the DCGP guidelines and used low CRP values to underpin their decision to refrain from antibiotic prescription. Peer-based reflection on differences in POC-CRP usage and antibiotic prescription rate amongst GPs may further nourish a more critical approach to prescription of antibiotics.

The potential contribution of yellow cassava to dietary nutrient adequacy of primary-school children in Eastern Kenya; the use of linear programming.

OBJECTIVE: Introduction of biofortified cassava as school lunch can increase vitamin A intake, but may increase risk of other deficiencies due to poor nutrient profile of cassava. We assessed the potential effect of introducing a yellow cassava-based school lunch combined with additional food-based recommendations (FBR) on vitamin A and overall nutrient adequacy using Optifood (linear programming tool). DESIGN: Cross-sectional study to assess dietary intakes (24 h recall) and derive model parameters (list of foods consumed, median serving sizes, food and food (sub)group frequency distributions, food cost). Three scenarios were modelled, namely daily diet including: (i) no school lunch; (ii) standard 5d school lunch with maize/beans; and (iii) 5d school lunch with yellow cassava. Each scenario and scenario 3 with additional FBR were assessed on overall nutrient adequacy using recommended nutrient intakes (RNI). SETTING: Eastern Kenya. SUBJECTS: Primary-school children (n 150) aged 7-9 years. RESULTS: Best food pattern of yellow cassava-based lunch scenario achieved 100 % RNI for six nutrients compared with no lunch (three nutrients) or standard lunch (five nutrients) scenario. FBR with yellow cassava and including small dried fish improved nutrient adequacy, but could not ensure adequate intake of fat (52 % of average requirement), riboflavin (50 % RNI), folate (59 % RNI) and vitamin A (49 % RNI). CONCLUSIONS: Introduction of yellow cassava-based school lunch complemented with FBR potentially improved vitamin A adequacy, but alternative interventions are needed to ensure dietary adequacy. Optifood is useful to assess potential contribution of a biofortified crop to nutrient adequacy and to develop additional FBR to address remaining nutrient gaps.