Lipemia impact on HBA1C measurements in patients with and without hemoglobin variant: a rational laboratory use evaluation.

This study aims to compare the HbA1c test results obtained by widely used methods using samples with various lipemia levels and Hb variants, and to determine whether it is possible to correct the lipemia effect in the identical samples. Out of the laboratory information system (LIS), 48 patients with various HbA1c results were identified including patients with and without Hb variants. After the baseline measurements, all samples were spiked with intralipid solution and treated by a subsequent 0.9% saline replacement procedure. HbA1c values were measured four times sequentially with enzymatic and capillary electrophoresis (CE) methods for each sample, and the measurements were categorized as follows: Baseline; Spiked, 5g/L; Spiked, 20g/L; Post-saline replacement. Sequential HbA1c measurements using the CE method did not show a significant difference, but samples containing 20 g/L triglycerides and samples treated with 0.9% saline replacement showed a significant difference when compared to baseline measurements in both patients with and without Hb variants using the enzymatic method (p < 0.001). The correlation between the two methods was strong at baseline measurements (r = 0.977), declined with lipemia (r = 0.968 and r = 0.737 for 5 g/L and 20 g/L triglycerides, respectively), and then increased with 0.9% saline replacement (r = 0.962) in patients without Hb variants. This study revealed that the enzymatic method, but not CE was susceptible to lipemia interference both in patients with and without Hb variants. Lipemia interference could be partially eliminated with 0.9% saline replacement, but enzymatic measurements were still somewhat affected.

Investigation of the effects of pneumatic tube transport system on routine biochemistry, hematology, and coagulation tests in Ankara City Hospital.

OBJECTIVES: Academics are far from a consensus regarding the effects of pneumatic tube system (PTS) delivery on sample integrity and laboratory test results. As for the reasons for conflicting opinions, each PTS is uniquely designed, sample tubes and patient characteristics differ among studies. This study aims to validate the PTS utilized in Ankara City Hospital for routine chemistry, coagulation, and hematology tests by comparing samples delivered via PTS and porter. METHODS: The study comprises 50 healthy volunteers. Blood samples were drawn into three biochemistry, two coagulation, and two hemogram tubes from each participant. Each of the duplicate samples was transferred to the emergency laboratory via Swiss log PTS (aka PTS-immediately) or by a porter. The last of the biochemistry tubes were delivered via the PTS, upon completion of coagulation of the blood (aka PTS-after). The results of the analysis in these groups were compared with multiple statistical analyses. RESULTS: The study did not reveal any correlation between the PTS and serum hemolysis index. There were statistically significant differences in several biochemistry tests. However, none of them reached the clinical significance threshold. Basophil and large unidentified cell (LUC) tests had poor correlations (r=0.47 and r=0.60; respectively) and reached clinical significance threshold (the average percentages of bias, 10.2%, and 15.4%, respectively). The remainder of the hematology and coagulation parameters did not reach clinical significance level either. CONCLUSIONS: The modern PTS validated in this study is safe for sample transportation for routine chemistry, coagulation, and hematology tests frequently requested in healthy individuals except for basophil and LUC.

Antibody response with SARS-CoV-2 inactivated vaccine (CoronaVac) in Turkish geriatric population.

BACKGROUND: Sars-CoV-2 infection influences older individuals at the forefront, and there is still limited data on the COVID-19 vaccine response in the geriatric population. This study aimed to assess antibody response after vaccination with SARS-CoV-2 inactivated vaccine and examine possible factors affecting this response in a geriatric population. METHODS: individuals who have been on at least the 28th day after the second dose of the COVID-19 vaccine were included. Comprehensive geriatric assessment tools and the Clinical Frailty Scale were performed. SARS-CoV-2 spike-specific IgG antibodies were detected and, levels ≥1 U/ml were defined as seropositive, <1 U/ml were defined as seronegative. RESULTS: a total of 497 patients were included and divided into three groups according to the days past after the second dose of the vaccine (Group 1: 28-59 days, Group 2: 60-89 days and Group 3: 90 days and more). Groups included 188, 148 and 171 patients, respectively. Seropositivity rate in each group was 80.9,73.2 and 57.3%, respectively. In Groups 1 and 2, Charlson Comorbidity Index score was higher in the seronegative group (P = 0.023 and P = 0.011, respectively). In Group 3, the prevalence of frailty was significantly higher in the seronegative group (P = 0.002). CONCLUSION: to the best of our knowledge, this is the first study assessing the antibody response after vaccination with Sars-CoV 2 inactivated vaccine in the Turkish geriatric population. Moreover, this is the first study revealing the relationship between antibody response and frailty. Larger studies are needed to confirm the antibody response duration and the association between frailty and COVID-19 vaccine response.

Comparison of three different HbA1c measurement methods - the Atellica®CH930, Capillary 3 Tera, and BioRad Variant Turbo II.

AIM: HbA1c measurement is very useful for the follow-up and detection of glycemic disorder, since it is easier and faster test and is independent of the patient's fasting status. In this study, we aimed to perform the comparative evaluation of 3 different methods for HbA1c measurement including capillary electrophoresis, immunoturbidimetric assay and high-performance liquid chromatography-HPLC. MATERIALS AND METHODS: This study comprised 134 leftover whole blood samples obtained from the subjects submitted for routine HbA1c testing. All blood samples were collected in EDTA-containing vacutainer tubes. The HbA1c levels were measured simultaneously using three different methods. Bias estimation, method agreement and concordance between the pairwise methods comparisons were evaluated by Bland-Altman plot and Passing-Bablok regression test. RESULTS: HbA1c levels ranged from 3.8% to 13.4% and measured by three different methods to make the comparison. The median values of samples based on immunoturbidimetric method (6.05%, IQR = 1.80) were higher than capillary electrophoresis method (5.90%, IQR = 1.80) and HPLC (5.85%, IQR = 1.80) method. The study group was classified into three subgroups based on the HbA1c levels measured with the HPLC method: Group 1 (n = 57) was composed of subjects with HbA1c levels less than 5.7%, Group 2 (n = 35) had HbA1c levels between 5.7% and 6.4%, Group 3 (n = 42) had HbA1c levels equal and more than 6.5%. CONCLUSION: To our knowledge, there is no study evaluating the HbA1c measurement on the Atellica® CH 930 Analyzer. We compared the Atellica®CH930 Analyzer with both HPLC and capillary electrophoresis. The Atellica®CH930 Analyzer showed acceptable performance and a strong correlation with both mentioned methods.

Progranulin and tumor necrosis factor-alpha in lean polycystic ovary syndrome patients.

OBJECTIVE: In this study, levels of progranulin (PGRN) and tumor necrosis factor-alpha (TNF-α) were measured to detect the presence of inflammation in lean polycystic ovary (PCOS) patients. METHODS: 40 lean PCOS patients were assessed by Rotterdam criteria. Forty healthy women with regular menstrual cycles and without biochemical and clinical hyperandrogenism were involved in our study. Blood samples were taken from the patient and control groups for the measurement of progranulin (PGRN), tumor necrosis factor-alpha (TNF-α), lipid parameters, glucose, insulin, and other hormones. RESULTS: Serum PGRN and TNF-α levels were significantly higher in patients with lean PCOS, compared with the control group (p = .037, p = .041). PGRN levels were positively correlated with TNF-α levels in lean PCOS patients. CONCLUSION: PGRN is known as a ligand for the TNF-α receptor. PGRN level increase in lean PCOS patients may be due to inhibiting the inflammatory effects of TNF-α. To observe the PGRN and TNF-α connection in obesity, further study is needed in obese PCOS patients and obese control groups.

Aqueous humor IL-8, IL-10, and VEGF levels in Fuchs' uveitis syndrome and Behçet's uveitis.

PURPOSE: This study investigated the levels of interleukin (IL)-8, IL-10, and vascular endothelial growth factor (VEGF) in the aqueous humor (AqH) of patients with Behçet's uveitis (BU) and Fuchs' uveitis syndrome (FUS) during an inactive period and compared these levels with those in the AqH of noninflammatory healthy control subjects. METHODS: This prospective and case-control study included 33 patients (16 patients with BU and 17 patients with FUS) and 35 control subjects. IL-8, IL-10, and VEGF levels in the AqH were quantified by performing sandwich enzyme-linked immunosorbent assay. Kruskal-Wallis test was used to compare the cytokine levels in the different groups, and statistical significance was set at p < 0.05. RESULTS: IL-8 levels were significantly higher in the AqH of patients with BU and FUS than in the AqH of control subjects (p < 0.001 and p < 0.001, respectively). IL-10 levels were significantly lower in the AqH of patients with BU than in the AqH of patients with FUS and of control subjects (p = 0.001 and p < 0.001, respectively). Although VEGF levels were higher in the AqH of patients with FUS than in the AqH of patients with BU and of control subjects, the difference was significant only between patients with FUS and control subjects (p < 0.001). CONCLUSIONS: We observed a significant decrease in IL-10 levels in the AqH of patients with BU and a significant increase in VEGF levels in the AqH of patients with FUS compared to controls. IL-8 and VEGF levels showed no significant difference among uveitis patients.

Higher Serum Endocan Level Is Associated with Alzheimer Disease.

BACKGROUND: The novel molecule endocan, which is released by endothelium and is regulated by proangiogenic and proinflammatory cytokines, may have a role in the pathophysiology of Alzheimer disease (AD). The aim of this study was to evaluate the relationship between serum endocan levels and AD. METHODS: A total of 134 patients (47 AD, 42 amnestic mild cognitive impairment [aMCI], and 45 control patients) 65 years of age and older were recruited in this study. Cognitive status of the patients was evaluated by performing the Montreal Cognitive Assessment (MOCA) and the Mini-Mental State Examination (MMSE). Serum endocan levels were measured with an enzyme-linked immunosorbent assay kit. RESULTS: Median serum endocan level was significantly higher in AD patients (380.1 ng/mL) than in both aMCI patients (247.7 ng/mL) and controls (277.6 ng/mL; p < 0.01). Serum endocan level had a weak but significant correlation with MMSE and MOCA scores (r = -0.219 and r = -0.232; p = 0.012 and p = 0.01, respectively). Serum endocan level was detected as a factor independently associated with AD. The cutoff serum level of endocan predicting AD was >288.94 ng/mL in receiver operating characteristic curve analysis (area under the curve 0.71, 95% CI 66.7-90.9, sensitivity 80.9%, specificity 59.8%; p < 0.01). CONCLUSION: Higher serum endocan levels may be associated with the pathogenesis of AD.

Gestation specific reference intervals for thyroid function tests in pregnancy.

BACKGROUND: Thyroid function tests are frequently assessed during pregnancy to evaluate thyroid dysfunction or to monitor pre-existing thyroid disease. However, using non-pregnant reference intervals can lead to misclassification. International guidelines recommended that institutions should calculate their own pregnancy-specific reference intervals for free thyroxine (FT4), free triiodothyronine (FT3) and thyroid-stimulating hormone (TSH). The objective of this study is to establish gestation-specific reference intervals (GRIs) for thyroid function tests in pregnant Turkish women and to compare these with the age-matched non-pregnant women. METHODS: Serum samples were collected from 220 non-pregnant women (age: 18-48), and 2460 pregnant women (age: 18-45) with 945 (39%) in the first trimester, 1120 (45%) in the second trimester, and 395 (16%) in the third trimester. TSH, FT4 and FT3 were measured using the Abbott Architect i2000SR analyzer. RESULTS: GRIs of TSH, FT4 and FT3 for first trimester pregnancies were 0.49-2.33 mIU/L, 10.30-18.11 pmol/L and 3.80-5.81 pmol/L, respectively. GRIs for second trimester pregnancies were 0.51-3.44 mIU/L, 10.30-18.15 pmol/L and 3.69-5.90 pmol/L. GRIs for third trimester pregnancies were 0.58-4.31 mIU/L, 10.30-17.89 pmol/L and 3.67-5.81 pmol/L. GRIs for TSH, FT4 and FT3 were different from non-pregnant normal reference intervals. CONCLUSIONS: TSH levels showed an increasing trend from the first trimester to the third trimester, whereas both FT4 and FT3 levels were uniform throughout gestation. GRIs may help in the diagnosis and appropriate management of thyroid dysfunction during pregnancy which will prevent both maternal and fetal complications.

Tamoxifen citrate: a glimmer of hope for silicosis.

BACKGROUND: Inhalation of crystalline silica nanoparticles causes pulmonary damage resulting in progressive lung fibrosis. Currently, there is no effective treatment for silicosis. Tamoxifen citrate is a selective estrogen receptor modulator, which is one of the adjuvant treatment choices for breast cancer. It is also known with its inhibitory effect on the production of transforming growth factor-beta (TGF-ß) and studied for the anti-fibrotic effect in some fibrotic diseases. The aim of the study was to determine the effect of tamoxifen citrate on the prevention of pulmonary fibrosis and the treatment of silicosis. METHODS: A total of 100 adult female Wistar Albino rats (200-250 g) were used in this study. The rats were divided into five groups including 20 rats in each. Rats were exposed to silica for 84 d in all groups. In group 1, rats were sacrificed on the day 84 without receiving treatment. In group 2, rats received 1 mg/kg tamoxifen (tmx1 + 1), from the first day of the study for the whole 114 d of the study. In group 3, (tmx10 + 10) rats were given 10 mg/kg tamoxifen from the first day of the study for the whole 114 d of the study. In group 4 (tmx1), rats were started 1 mg/kg of tamoxifen on day 84 and were given until day 114. In group 5 (tmx10), rats were fed with 10 mg/kg tamoxifen starting from day 84 to day 114. All rats except group 1 were sacrificed on 114 day of the study. Lung inflammation and fibrosis scores, serum TGF ß levels, lung smooth muscle antigen and tissue transforming growth factor ß (t-TGF-ß) antibody staining levels, and number of silicotic rats were compared between groups. RESULTS: Silicosis was caused successfully in all rats in group 1. There were six silicotic rats in group 3 and it was the lowest number of all groups. Plasma TGF-ß levels and fibrosis score were significantly lower in all groups when compared with the control group. Tamoxifen could have preventive or treating effects in silicosis and found that lung fibrosis score was significantly lower in rats treated with tamoxifen. CONCLUSIONS: Tamoxifen treatment after and/or before induction of silicosis decreased lung fibrosis score with blood TGF-ß levels. We hope that this study may introduce a new indication as prophylactic use of tamoxifen in high-risk groups for silicosis and for treatment of silicosis.

Acoustic Radiation Force Impulse (ARFI) for Fibrosis Staging in Patients with Autoimmune Hepatitis.

BACKGROUND/AIMS: The performance of non-invasive fibrosis markers has not been well studied in autoimmune hepatitis (AIH). Acoustic radiation force impulse imaging (ARFI) is a non-invasive radiological method for assessment of liver fibrosis. The aim of this study was to evaluate the accuracy of ARFI for fibrosis staging in patients with AIH. METHODOLOGY: AIH patients who undergone for control liver biopsy after at least two years of biochemical remission period were also assessed by ARFI. Liver fibrosis was staged according to the METAVIR scoring system. RESULTS: A total of 15 patients (13 women and 2 men) with mean age of 40.9 (18-59 years) were included in the study. Repeat liver biopsy was performed a mean of 4.9 (3-9 years) after AIH diagnosis. Nine patients had significant fibrosis scores (F ≥ 2) while, remain 6 patients had mild or no fibrosis. The mean (±SD) shear wave velocities for patients with fibrosis stage II-IV was significantly higher than those with fibrosis stage 0-I (2.28 ± 0.68 m/s and 1.20 ± 0.24, respectively, p = 0.002). CONCLUSIONS: ARFI is able to differentiate significant from non significant liver fibrosis in patients with AIH. Our study suggests that this non-invasive method can be used for monitoring fibrosis progression in AIH.

Concordance and generalization of an AI algorithm with real-world clinical data in the pre-omicron and omicron era.

All viruses, including SARS-CoV-2, the virus responsible for COVID-19, continue to evolve, which can lead to new variants. The objective of this study is to assess the agreement between real-world clinical data and an algorithm that utilizes laboratory markers and age to predict the progression of disease severity in COVID-19 patients during the pre-Omicron and Omicron variant periods. The study evaluated the performance of a deep learning (DL) algorithm in predicting disease severity scores for COVID-19 patients using data from the USA, Spain, and Turkey (Ankara City Hospital (ACH) data set). The algorithm was developed and validated using pre-Omicron era data and was tested on both pre-Omicron and Omicron-era data. The predictions were compared to the actual clinical outcomes using a multidisciplinary approach. The concordance index values for all datasets ranged from 0.71 to 0.81. In the ACH cohort, a negative predictive value (NPV) of 0.78 or higher was observed for severe patients in both the pre-Omicron and Omicron eras, which is consistent with the algorithm's performance in the development cohort.

Memory T cell responses in seronegative older adults following SARS-CoV-2 vaccination.

Generating memory T cell responses besides humoral immune responses is essential when it comes to the efficacy of a vaccine. In this study, the presence of memory T cell responses after aluminum-adjuvanted inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac) in seronegative and seropositive elderly individuals were examined. CD4+ and CD8+ memory T cell proliferation and IFN-γ production capacities were evaluated. Additionally, clinical frailty scale (CFS) and FRAIL scales of the individuals were scored. CD4+ memory T cell responses more prominent than CD8+ memory T cells. In seronegative individuals, 80% of them had memory CD4+ and IFN-γ, whereas 50% of them had memory CD4+ and all of them had IFN-γ responses. Additionally, 40% of seronegative patients and 50% of seropositive patients had memory CD8+ responses. To sum up, humoral immune responses are not associated with memory T cell responses, and in seronegative individuals, memory T cell responses can be detected.

Effect of montelukast and MK-886 on hepatic ischemia-reperfusion injury in rats.

BACKGROUND: Hepatic ischemia-reperfusion injury (I/R) may occur in transplantation, trauma, and elective hepatic resections. Leukotrienes have been shown to play a major role in hepatic I/R injury. Five-lipoxygenase enzyme is an important enzyme in the production of leukotrienes from arachidonic acid. MK-886 is an inhibitor of 5-lipoxygenase, and montelukast is a cysteinyl leukotriene receptor antagonist. The aim of this study was to investigate whether MK-886 and montelukast are effective in preventing hepatic I/R injury. MATERIALS AND METHODS: Rats were divided into five groups consisting of seven rats in each: (1) Control I/R, (2) Control-montelukast, (3) Control-MK-886, (4) I/R+montelukast, and (5) I/R+MK-886. Thirty min of total hepatic vascular occlusion and then 60 min reperfusion were performed to animals in groups 1, 4, and 5. In groups 2 and 4, montelukast, and in groups 3 and 5, MK-886 was applied intraperitoneally before and during the surgical procedures. RESULTS: Apoptosis in the liver and intestine decreased significantly in the I/R+montelukast and I/R+MK-886 groups compared with the I/R group. Tissue malondialdehyde levels and glutathione consumptions also decreased significantly in the I/R+montelukast and I/R+MK-886 groups compared with the I/R group. The difference in serum alanine aminotransferase and aspartate aminotransferase levels between the groups did not reach significance. CONCLUSIONS: Montelukast and MK-886 were found to be effective in prevention of liver and intestine injury by reducing apoptosis and oxidative stress in a hepatic I/R model. Anti-inflammatory properties and inhibition of lipid peroxidation by montelukast and MK-886 could be protective for these organs in I/R injury.

TKI-Related Platelet Dysfunction Does Not Correlate With Bleeding in Patients With Chronic Phase-Chronic Myeloid Leukemia With Complete Hematological Response.

Bleeding has been reported in patients with chronic myeloid leukemia (CML) using tyrosine kinase inhibitors (TKIs). In this study, we aimed to evaluate platelet functions and associated bleeding symptoms in patients with CML using TKIs. A standardized questionnaire that was developed for inherited bleeding disorders (ISTH/SSC Bleeding Assessment Tool) was used to score bleeding symptoms in 68 chronic phase patients with CML receiving imatinib (n = 47), dasatinib (n = 15), or nilotinib (n = 6). Light transmission aggregometry was used for platelet function testing. None of the patients had major bleeding (score > 3). Minor bleeding was observed in 25.6% and 20% of the patients in imatinib and dasatinib treatment groups. Impaired/decreased platelet aggregation was observed in 29.8% of imatinib treatment group, 50% of nilotinib group, and 40% of dasatinib group. A secondary aggregation abnormality compatible with the release defect was observed in 26% of patients with CML; 25.5%, 33.3%, and 16.7% of patients receiving imatinib, dasatinib, and nilotinib, respectively. No correlation was found between bleeding symptoms and the impaired platelet function. We can conclude that TKIs may impair in vitro platelet aggregation but this impairment is not associated with bleeding diathesis.

Prenatal bisphenol a and phthalate exposure are risk factors for male reproductive system development and cord blood sex hormone levels.

Bisphenol A (BPA) and phthalates can adversely affect the fetal development. However, observational studies on the effects of these chemicals on fetal male reproductive system are still limited. A hundred of umbilical cord blood samples were analyzed for the levels of BPA, di-2-ethylhexyl phthalate (DEHP), mono-2-ethylhexyl phthalate (MEHP), and sex hormones. After birth, male newborns underwent physical examination that included measurements of anogenital distance, stretched penile length (SPL), and penile width. BPA, DEHP and MEHP levels were detectable in ≈99% of cord blood samples. In covariate-adjusted models, cord blood BPA levels were inversely associated with SPL of newborns and positively associated with cord blood estradiol levels. In addition, there was a significant inverse relationship between cord blood DEHP levels and anogenital distance index of newborn males. Our results suggest that in utero BPA and DEHP exposure exerted adverse effects on fetal male reproductive development and cord blood estradiol levels.

Clock gene PERIOD3 polymorphism is associated with susceptibility to Graves' disease but not to Hashimoto's thyroiditis.

Circadian disruption has been linked with immune-related morbidities including autoimmune diseases. PERIOD3 (PER3) clock gene is a key player in the mammalian circadian system. This study evaluated the possible association of PER3 rs2797685 (G/A) polymorphism and susceptibility of autoimmune thyroid diseases (AITD) and assessed if this SNP contributes to disease characteristics and serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). The PER3 rs2797685 (G/A) polymorphism was assessed in 125 patients with AITD [Graves' disease (GD), 69; Hashimoto's thyroiditis (HT), 56] and 115 unrelated healthy controls. Subjects carrying at least one variant allele of PER3 rs2797685 (GA+AA) had increased risk for GD (OR 1.9, 95% CI 1-3.61, p= .05). There were no differences in the frequencies of genotypes and alleles of the PER3 rs2797685 polymorphism between HT patients and control subjects. No association was observed between genotypes of the studied SNP and any of the disease characteristics in GD and HT patients. The GA+AA genotype of PER3 rs2797685 was associated with lower levels of IL-6 in patients with Graves' disease. There were no differences between genotypes of the studied SNP regarding TNF-α levels in GD, HT or control groups. In conclusion, this study provides the first evidence for a genetic association between GD and the PER3 gene, highlighting the possible relevance of polymorphisms in clock genes in the etiopathogenesis of AITD. However, functional studies to identify the underlying molecular mechanisms of this association are needed to translate these findings to clinical applications.

A statistical approach to evaluate the performance of cardiac biomarkers in predicting death due to acute myocardial infarction: time-dependent ROC curve

Background/aim: Myoglobin, cardiac troponin T, B-type natriuretic peptide (BNP), and creatine kinase isoenzyme MB (CK-MB) are frequently used biomarkers for evaluating risk of patients admitted to an emergency department with chest pain. Recently, time- dependent receiver operating characteristic (ROC) analysis has been used to evaluate the predictive power of biomarkers where disease status can change over time. We aimed to determine the best set of biomarkers that estimate cardiac death during follow-up time. We also obtained optimal cut-off values of these biomarkers, which differentiates between patients with and without risk of death. A web tool was developed to estimate time intervals in risk. Materials and methods: A total of 410 patients admitted to the emergency department with chest pain and shortness of breath were included. Cox regression analysis was used to determine an optimal set of biomarkers that can be used for estimating cardiac death and to combine the significant biomarkers. Time-dependent ROC analysis was performed for evaluating performances of significant biomarkers and a combined biomarker during 240 h. The bootstrap method was used to compare statistical significance and the Youden index was used to determine optimal cut-off values. Results : Myoglobin and BNP were significant by multivariate Cox regression analysis. Areas under the time-dependent ROC curves of myoglobin and BNP were about 0.80 during 240 h, and that of the combined biomarker (myoglobin + BNP) increased to 0.90 during the first 180 h. Conclusion: Although myoglobin is not clinically specific to a cardiac event, in our study both myoglobin and BNP were found to be statistically significant for estimating cardiac death. Using this combined biomarker may increase the power of prediction. Our web tool can be useful for evaluating the risk status of new patients and helping clinicians in making decisions.

Urine nerve growth factor (NGF) level, bladder nerve staining and symptom/problem scores in patients with interstitial cystitis.

BACKGROUND: Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a challenging disease, affecting thousands of people all around the world, especially women. Although there have been numerous theories regarding IC/BPS etiology, the physiopathology of the disease still remains unclear and there is a lack of certain treatment. OBJECTIVES: The aim of the study was to assess the role of nerve fibers and nerve growth factor (NGF) in the etiopathogenesis of IC/BPS symptoms by demonstrating if there is a correlation between urine NGF levels, amount of peripheral nerves in bladder mucosa and symptom severity. MATERIAL AND METHODS: A prospective clinical study was conducted with 15 IC/BPS patients and 18 controls. Urine NGF levels were measured by enzyme-linked immunosorbent assay (ELISA). Bladder punch biopsies were obtained from 15 IC/BPS patients and 9 controls. Immunohistochemistry was performed for S-100 to highlight peripheral nerve twigs in bladder mucosa. The O'Leary-Sant Interstitial Cystitis Symptom and Problem Index (OSICSPI) was used to assess symptom severity and effects of the disease on the patients' life. RESULTS: NGF normalized to urine creatinine (NGF/Cr) levels in IC/BPS patients were significantly higher than in controls, 0.34 ±0.22 and 0.09 ±0.08 pg/mL: mg/dL, respectively (p < 0.001). The mean symptom score in IC patients was 12.27 ±2.4 (median: 12) and the mean problem score was 10.9 ±2.3 (median: 12). The mean mucosal nerve (S-100 stained) area in the IC/BPS group was significantly higher than in the controls, 2.53 ±1.90 vs 1.0 ±0.70, respectively (p = 0.018). In correlation analyses, the NGF/Cr level in IC/BPS patients was found significantly correlated with the O'Leary-Sant IC Symptom and Problem Index scores independently (p = 0.001 and p = 0.028, respectively). CONCLUSIONS: NGF seems to be a promising biomarker in IC/BPS. It may help clinicians in diagnoses and patient follow-up. Thus, unnecessary, expensive and invasive tests, interventions and treatments might be avoided.

Metal Ion Release During Growth-Friendly Instrumentation for Early-Onset Scoliosis: A Preliminary Study.

BACKGROUND: Metal ions released from spinal instruments can cause localized debris and distribute systemically to settle on distant organs. Children with early-onset deformities live with metallic implants for a substantial amount of time. No research focused on metal distribution in growth-friendly instrumentations. The aim of this study was to compare age-matched growing rod (GR) and magnetically controlled growing rod (MCGR) groups to noninstrumented controls. METHODS: The study was designed as a multicenter, prospective, cross-sectional case series. GR and MCGR applications of three institutions were included. A total of 52 children were enrolled. Blood samples were collected between December 2014 and February 2015. Biochemical serum analyses were performed to trace and quantify titanium, vanadium, aluminum, and boron. The GR group included 15 children. Mean age was 10.7 (range 6-15). MCGR group included 22 children. Mean age was 8.5 (range 2-13). Fifteen age-matched nonoperated children formed the control group. The mean age was 10.4 (range 5-15). One-way analysis of variance, Kruskal-Wallis, and Mann-Whitney U tests were used for comparisons. RESULTS: The mean serum titanium level in control, GR, and MCGR groups were 2.8 ± 1.4, 7.3 ± 4.3, and 10.2 ± 6.8 µg/L, respectively. GR and MCGR group titanium levels were higher than controls' (p = .008 and p < .001). The mean serum vanadium level in control, GR, and MCGR groups were 0.2 ± 0.0, 0.2 ± 0.0, and 0.5 ± 0.5 µg/L, respectively. MCGR group vanadium level was higher than control (p < .001) and GR groups (p = .004). Mean serum levels in control, GR, and MCGR groups were, respectively, 5.4 ± 4.1, 8.1 ± 7.4, and 7.8 ± 5.1 µg/L for aluminum and 86.7 ± 2.7, 86.9 ± 2.5, and 85.0 ± 6.6 µg/L for boron. The distribution of aluminum and boron were similar across groups (p = .675 and p = .396). CONCLUSIONS: Both GR and MCGR applications significantly release titanium and possibly aluminum. MCGR further releases vanadium. MCGR possibly releases more titanium than traditional GR. Time-dependent alterations of serum ion levels, structural properties of the MCGR device, and exposure caused by magnetic distraction processes warrant investigation.

Triple test with tumor markers CYFRA 21.1, HE4, and ProGRP might contribute to diagnosis and subtyping of lung cancer.

BACKGROUND AND AIM: Early diagnosis and histological subtyping are important issues in the management of patients with lung cancer (LC). The aim of this study is to investigate the diagnostic value of a panel of serum tumor markers in newly diagnosed patients with LC. METHODS: Venous blood samples were collected from 99 patients with LC (42 adenocarcinoma, 35 squamous, and 22 small cell carcinoma) and 30 patients with benign lung disease. Progastrin releasing peptide (ProGRP), squamous cell carcinoma antigen (SCCAg), cytokeratin 19-fragments (CYFRA 21.1), human epididymis protein 4 (HE4), Chromogranin A (CgA) and neuron specific enolase (NSE) levels were measured. The diagnostic value of the biomarkers was assessed with ROC curve analyses; the area under the curve (AUC) was calculated. RESULTS: Serum CYFRA 21.1, ProGRP, SCCAg, NSE levels were significantly higher in LC patients. While ProGRP levels were higher (p = 0.009) in SCLC; CYFRA 21.1 and SCCAg levels were higher in NSCLC (p = 0.019 and p = 0.001, respectively). The sensitivity and specificity of tumor markers were 72%, 83% for CYFRA 21.1; 70%, 57% for HE4; 18%, 93% for ProGRP; 43%, 77% for SCCAg; 54%, 53% for CgA; 73%, 50% for NSE. CYFRA 21.1 (p < 0.001, r = 0.394), HE4 (p = 0.014, r = 0.279) and CgA (p = 0.023, r = 0.259) levels were positively correlated with tumor stage in NSCLC. CgA levels were significantly higher in extensive stage SCLC (p = 0.004). CYFRA 21.1 had the highest diagnostic value for LC (AUC = 0.865). When it is combined with HE4, diagnostic value increased (AUC = 0.899). ProGRP had the highest diagnostic value (AUC = 0.875, p < 0.001) for discriminating SCLC from NSCLC. CONCLUSION: A panel of three tumor markers CYFRA 21.1, HE4 and ProGRP may play a role for discriminating LC from benign lung disease and subtyping as SCLC.