Longitudinal plasma phosphorylated-tau217 and other related biomarkers in a non-demented Alzheimer's risk-enhanced sample.

INTRODUCTION: Understanding longitudinal change in key plasma biomarkers will aid in detecting presymptomatic Alzheimer's disease (AD). METHODS: Serial plasma samples from 424 Wisconsin Registry for Alzheimer's Prevention participants were analyzed for phosphorylated-tau217 (p-tau217; ALZpath) and other AD biomarkers, to study longitudinal trajectories in relation to disease, health factors, and cognitive decline. Of the participants, 18.6% with known amyloid status were amyloid positive (A+); 97.2% were cognitively unimpaired (CU). RESULTS: In the CU, amyloid-negative (A-) subset, plasma p-tau217 levels increased modestly with age but were unaffected by body mass index and kidney function. In the whole sample, average p-tau217 change rates were higher in those who were A+ (e.g., simple slopes(se) for A+ and A- at age 60 were 0.232(0.028) and 0.038(0.013))). High baseline p-tau217 levels predicted faster preclinical cognitive decline. DISCUSSION: p-tau217 stands out among markers for its strong association with disease and cognitive decline, indicating its potential for early AD detection and monitoring progression. HIGHLIGHTS: Phosphorylated-tau217 (p-tau217) trajectories were significantly different in people who were known to be amyloid positive. Subtle age-related trajectories were seen for all the plasma markers in amyloid-negative cognitively unimpaired. Kidney function and body mass index were not associated with plasma p-tau217 trajectories. Higher plasma p-tau217 was associated with faster preclinical cognitive decline.

Serum neopterin and orexin-A levels in different stages of diabetic retinopathy.

CLINICAL RELEVANCE: Retinopathy is one of the most common microvascular complications of diabetes mellitus and is the leading cause of vision loss in the working middle-aged population. BACKGROUND: This study aimed to investigate the value of neopterin and orexin-A levels in patients with diabetes mellitus with different stages of diabetic retinopathy and without diabetic retinopathy and to compare those findings with results from healthy individuals without diabetes mellitus. METHODS: In total, 65 patients with type 2 diabetes mellitus and 22 healthy individuals without diabetes mellitus were enrolled in this prospective study. The participants were separated into four subgroups. The first subgroup included 25 patients without diabetic retinopathy, the second subgroup included 20 patients non-proliferative diabetic retinopathy, the third subgroup included 20 patients with proliferative diabetic retinopathy, and the fourth subgroup included 22 healthy individuals without diabetes mellitus as controls. Serum neopterin and orexin-A levels were analysed and compared among the groups. RESULTS: The age and gender of the participants between the four subgroups were not statistically significantly different (p > 0.05). The mean neopterin levels were significantly higher in patients included in the diabetes mellitus subgroups compared with the controls (p < 0.001). Neopterin levels significantly increased as diabetic retinopathy progressed within the diabetes mellitus subgroups. Mean orexin-A levels were significantly lower in the diabetes mellitus subgroups compared with the controls (p < 0.001); however, orexin-A levels were not significantly different within the diabetes mellitus subgroups (p > 0.05). CONCLUSION: Patients with diabetes mellitus have higher serum neopterin and lower serum orexin-A levels compared with healthy individuals without diabetes mellitus. Moreover, serum neopterin levels increase with progression of diabetic retinopathy.

A Comprehensive Head-to-Head Comparison of Key Plasma Phosphorylated Tau 217 Biomarker Tests.

Plasma phosphorylated-tau 217 (p-tau217) is currently the most promising biomarkers for reliable detection of Alzheimer's disease (AD) pathology. Various p-tau217 assays have been developed, but their relative performance is unclear. We compared key plasma p-tau217 tests using cross-sectional and longitudinal measures of amyloid-ß (Aß)-PET, tau-PET, and cognition as outcomes, and benchmarked them against cerebrospinal fluid (CSF) biomarker tests. Samples from 998 individuals (mean[range] age 68.5[20.0-92.5], 53% female) from the Swedish BioFINDER-2 cohort were analyzed. Plasma p-tau217 was measured with mass spectrometry (MS) assays (the ratio between phosphorylated and non-phosphorylated [%p-tau217WashU]and ptau217WashU) as well as with immunoassays (p-tau217Lilly, p-tau217Janssen, p-tau217ALZpath). CSF biomarkers included p-tau217Lilly, and the FDA-approved p-tau181/Aß42Elecsys and p-tau181Elecsys. All plasma p-tau217 tests exhibited high ability to detect abnormal Aß-PET (AUC range: 0.91-0.96) and tau-PET (AUC range: 0.94-0.97). Plasma %p-tau217WashU had the highest performance, with significantly higher AUCs than all the immunoassays (P diff<0.007). For detecting Aß-PET status, %p-tau217WashU had an accuracy of 0.93 (immunoassays: 0.83-0.88), sensitivity of 91% (immunoassays: 84-87%), and a specificity of 94% (immunoassays: 85-89%). Among immunoassays, p-tau217Lilly and plasma p-tau217ALZpath had higher AUCs than plasma p-tau217Janssen for Aß-PET status (P diff<0.006), and p-tau217Lilly outperformed plasma p-tau217ALZpath for tau-PET status (P diff=0.025). Plasma %p-tau217WashU exhibited higher associations with all PET load outcomes compared to immunoassays; baseline Aß-PET load (R2: 0.72; immunoassays: 0.47-0.58; Pdiff<0.001), baseline tau-PET load (R2: 0.51; immunoassays: 0.38-0.45; Pdiff<0.001), longitudinal Aß-PET load (R2: 0.53; immunoassays: 0.31-0.38; Pdiff<0.001) and longitudinal tau-PET load (R2: 0.50; immunoassays: 0.35-0.43; Pdiff<0.014). Among immunoassays, plasma p-tau217Lilly was more strongly associated with Aß-PET load than plasma p-tau217Janssen (P diff<0.020) and with tau-PET load than both plasma p-tau217Janssen and plasma p-tau217ALZpath (all P diff<0.010). Plasma %p-tau217 also correlated more strongly with baseline cognition (Mini-Mental State Examination[MMSE]) than all immunoassays (R2 %p-tau217WashU: 0.33; immunoassays: 0.27-0.30; P diff<0.024). The main results were replicated in an external cohort from Washington University in St Louis (n =219). Finally, p-tau217Nulisa showed similar performance to other immunoassays in subsets of both cohorts. In summary, both MS- and immunoassay-based p-tau217 tests generally perform well in identifying Aß-PET, tau-PET, and cognitive abnormalities, but %p-tau217WashU performed significantly better than all the examined immunoassays. Plasma %p-tau217 may be considered as a stand-alone confirmatory test for AD pathology, while some immunoassays might be better suited as triage tests where positive results are confirmed with a second test.

The Role of Thrombocyte/Lymphocyte Ratio and Aspartate Transaminase/Alanine Transaminase (De Ritis) Ratio in Prediction of Recurrence and Progression in Non-muscle Invasive Bladder Cancer.

AIM: The purpose of the study was to determine the predictive value of platelet-to-lymphocyte ratio (PLR) and Aspartate transaminase (AST)/alanine transaminase (ALT) ratio (De Ritis ratio) for recurrence and progression in non-muscle-invasive bladder cancer (NMIBC). METHODS: A total of 231 patients who underwent transurethral tumor resection between 2016 and 2022 were retrospectively analyzed. Preoperative test results, including AST, ALT, platelet, and lymphocyte counts, were used to calculate the PLR and De Ritis ratio. Univariate and multivariate analyses were performed to identify the predictive factors associated with recurrence and progression. RESULTS: Based on the ROC curve, 1.19 and 1.21 were identified as the optimal cut-off values of the De Ritis ratio for recurrence and progression, respectively. Furthermore, PLR cut-off values for recurrence and progression were 114 and 118, respectively. There is a significant difference in recurrence-free survival (RFS) and progression-free survival (PFS) between the groups of patients with high and low De Ritis ratios (p = 0.028 and p = 0.021, respectively). In multivariate analysis, De Ritis ratio ≥ 1.19 and European Organization for Research and Treatment of Cancer (EORTC) high recurrence risk were determined to be significant predictors of tumor recurrence. Multivariate analysis also determined that T1 pathological stage, high tumor grade, European Organization for Research and Treatment of Cancer (EORTC) high progression risk, and De Ritis ratio ≥ 1.21 were risk factors for tumor progression. CONCLUSION: In our study, the preoperative De Ritis ratio represented an independent predictive factor for recurrence and progression in non-muscle invasive bladder cancer. The use of this biomarker in combination with other diagnostic/predictive tools might help urologists improve the clinical decision-making process in the future.

Comparison of two plasma p-tau217 assays to detect and monitor Alzheimer's pathology.

BACKGROUND: Blood-based biomarkers of Alzheimer's disease (AD) have become increasingly important as scalable tools for diagnosis and determining clinical trial eligibility. P-tau217 is the most promising due to its excellent sensitivity and specificity for AD-related pathological changes. METHODS: We compared the performance of two commercially available plasma p-tau217 assays (ALZpath p-tau217 and Janssen p-tau217+) in 294 individuals cross-sectionally. Correlations with amyloid PET and tau PET were assessed, and Receiver Operating Characteristic (ROC) analyses evaluated both p-tau217 assays for identifying AD pathology. FINDINGS: Both plasma p-tau217 assays were strongly associated with amyloid and tau PET. Furthermore, both plasma p-tau217 assays identified individuals with AD vs other neurodegenerative diseases (ALZpath AUC = 0.95; Janssen AUC = 0.96). Additionally, plasma p-tau217 concentrations rose with AD severity and their annual changes correlated with tau PET annual change. INTERPRETATION: Both p-tau217 assays had excellent diagnostic performance for AD. Our study supports the future clinical use of commercially-available assays for p-tau217. FUNDING: This research is supported by the Weston Brain Institute, Canadian Institutes of Health Research (CIHR), Canadian Consortium on Neurodegeneration in Aging, the Alzheimer's Association, Brain Canada Foundation, the Fonds de Recherche du Québec - Santé and the Colin J. Adair Charitable Foundation.

Effectiveness of osteopathic manipulative applications on hypothalamic-pituitary-adrenal (HPA) axis in youth with major depressive disorder: a randomized double-blind, placebo-controlled trial.

CONTEXT: Osteopathic treatments regulate the neurovegetative system through joint mobilizations and manipulations, and myofascial and craniosacral techniques. Despite the growing body of research, the precise impact of osteopathic medicine on the autonomic nervous system (ANS) is not yet fully elucidated. As to Kuchera's techniques, the stimulation of the sympathetic trunk and prevertebral ganglia contributed to harmonization of the sympathetic activity. However, potential relationships between the harmonization of the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis largely remain uncertain and warrant further exploration. OBJECTIVES: This study was designed to evaluate the effectiveness of the osteopathic sympathetic harmonization (OSH) on the SNS and the HPA axis in youth with major depressive disorder (MDD). METHODS: The study included 39 youths aged 15-21 years and diagnosed with MDD. The participants were randomly assigned into either the OSH or the placebo group. Stimulation was performed on the sympathetic truncus and prevertebral ganglia in the OSH group. The stimulation of the placebo group was performed with a lighter touch and a shorter duration in similar areas. Each participant completed the Beck Depression Inventory (BDI) and the State and Trait Anxiety Inventory (SAI and TAI) before the application. Blood pressure (BP) and pulse measurements were made, and saliva samples were taken before, immediately after, and 20 min after application. RESULTS: The baseline BDI (p=0.617) and TAI (p=0.322) scores were similar in both groups. Although the SAI scores decreased in both groups postintervention, no statistically significant difference was found between the two groups. Subjects who received OSH had a decrease in α-amylase level (p=0.028) and an increase in cortisol level (p=0.009) 20 min after the procedure. CONCLUSIONS: Following OSH application in depressed youth, SNS activity may decrease, whereas HPA axis activity may increase. Future studies may examine the therapeutic efficacy of repeated OSH applications in depressed individuals.

Does Second Trimester Maternal Serum Zonulin Level Predict Gestational Diabetes Mellitus?

Zonulin, a protein that regulates intestinal permeability, has attracted attention as a potential biomarker for GDM. Therefore, this study aims to investigate whether there are differences in zonulin levels between the GDM group and control groups, especially between those receiving different treatments (diet and insulin). Based on this idea, we included 90 patients with a gestational age between 24 and 28 weeks in our study. While GDM was not detected in 33 of these patients, as a result of OGTT, 57 patients were diagnosed with GDM and these patients were followed throughout their pregnancy. Gestational diabetes was diagnosed by an OGTT performed between 24 and 28 weeks of gestation according to American Diabetes Association (ADA) standards. During follow-up, GDM patients were divided into two groups according to whether they required insulin treatment. Plasma zonulin levels were determined using enzyme-linked immunosorbent assay (ELISA) techniques. The GDM group had significantly higher plasma zonulin levels than the control group (p < 0.005). According to our research, zonulin may be a non-invasive biomarker involved in the etiology of GDM. Large-scale research on this topic is still needed.

Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology.

Importance: Phosphorylated tau (p-tau) is a specific blood biomarker for Alzheimer disease (AD) pathology, with p-tau217 considered to have the most utility. However, availability of p-tau217 tests for research and clinical use has been limited. Expanding access to this highly accurate AD biomarker is crucial for wider evaluation and implementation of AD blood tests. Objective: To determine the utility of a novel and commercially available immunoassay for plasma p-tau217 to detect AD pathology and evaluate reference ranges for abnormal amyloid ß (Aß) and longitudinal change across 3 selected cohorts. Design, Setting, and Participants: This cohort study examined data from 3 single-center observational cohorts: cross-sectional and longitudinal data from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort (visits October 2017-August 2021) and Wisconsin Registry for Alzheimer's Prevention (WRAP) cohort (visits February 2007-November 2020) and cross-sectional data from the Sant Pau Initiative on Neurodegeneration (SPIN) cohort (baseline visits March 2009-November 2021). Participants included individuals with and without cognitive impairment grouped by amyloid and tau (AT) status using PET or CSF biomarkers. Data were analyzed from February to June 2023. Exposures: Magnetic resonance imaging, Aß positron emission tomography (PET), tau PET, cerebrospinal fluid (CSF) biomarkers (Aß42/40 and p-tau immunoassays), and plasma p-tau217 (ALZpath pTau217 assay). Main Outcomes and Measures: Accuracy of plasma p-tau217 in detecting abnormal amyloid and tau pathology, longitudinal p-tau217 change according to baseline pathology status. Results: The study included 786 participants (mean [SD] age, 66.3 [9.7] years; 504 females [64.1%] and 282 males [35.9%]). High accuracy was observed in identifying elevated Aß (area under the curve [AUC], 0.92-0.96; 95% CI, 0.89-0.99) and tau pathology (AUC, 0.93-0.97; 95% CI, 0.84-0.99) across all cohorts. These accuracies were comparable with CSF biomarkers in determining abnormal PET signal. The detection of abnormal Aß pathology using a 3-range reference yielded reproducible results and reduced confirmatory testing by approximately 80%. Longitudinally, plasma p-tau217 values showed an annual increase only in Aß-positive individuals, with the highest increase observed in those with tau positivity. Conclusions and Relevance: This study found that a commercially available plasma p-tau217 immunoassay accurately identified biological AD, comparable with results using CSF biomarkers, with reproducible cut-offs across cohorts. It detected longitudinal changes, including at the preclinical stage.

Blood-based biomarkers in Alzheimer's disease - moving towards a new era of diagnostics.

Alzheimer's disease (AD), a primary cause of dementia globally, is traditionally diagnosed via cerebrospinal fluid (CSF) measures and positron emission tomography (PET). The invasiveness, cost, and limited accessibility of these methods have led to exploring blood-based biomarkers as a promising alternative for AD diagnosis and monitoring. Recent advancements in sensitive immunoassays have identified potential blood-based biomarkers, such as Aß42/Aß40 ratios and phosphorylated tau (p-tau) species. This paper briefly evaluates the clinical utility and reliability of these biomarkers across various AD stages, highlighting challenges like refining plasma Aß42/Aß40 assays and enhancing the precision of p-tau, particularly p-tau181, p-tau217, and p-tau231. The discussion also covers other plasma biomarkers like neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and synaptic biomarkers, assessing their significance in AD diagnostics. The need for ongoing research and development of robust assays to match the performance of CSF and PET biomarkers is underscored. In summary, blood-based biomarkers are increasingly crucial in AD diagnosis, follow-up, prognostication, treatment response evaluation, and population screening, particularly in primary care settings. These developments are set to revolutionize AD diagnostics, offering earlier and more accessible detection and management options.

Predictive value of Prognostic Nutritional Index (PNI) for the severity of vasculogenic erectile dysfunction.

PURPOSE: Our aim was to investigate the association of prognostic nutritional index (PNI) score with erectile dysfunction (ED), therefore, we prospectively evaluated the relationship between penile doppler ultrasonography (PDU) findings, PNI and Sexual Health Inventory for Men (SHIM) scores in patients with ED. METHODS: A total of 414 patients' characteristics, laboratory findings, SHIM and PNI scores were recorded. The PNI is calculated using the formula: 10 × serum albumin + 0.005 × total lymphocyte count. PDU was performed in patients with a SHIM score of 17 and below, while patients with a SHIM score ≥ 18 were recruited for the control group. Correlation analysis was performed to evaluate the relationship between PNI, SHIM scores and PDU parameters. The predictive value of variables for severe ED was assessed with regression analysis. RESULTS: A significant difference was demonstrated between the ED subgroups and control group for total cholesterol (p = 0.04), serum albumin (p = 0.03), total lymphocyte count (p = 0.02), BDI score (p < 0.001), and PNI score (p = 0.03). A strong positive correlation between PNI score and PSV (rho = 0.73; p = 0.001), a moderate negative correlation between PNI score and EDV (rho = - 0.54; p = 0.02), and a moderate positive correlation between PNI and SHIM scores (rho = 0.61; p = 0.02) were demonstrated. PNI score ≤ 40 (OR: 3.49; p = 0.01), age (OR: 2.15; p = 0.03) and total cholesterol (OR: 2.03; p = 0.04) were determined as significant predictors of severe ED in multivariate analysis. CONCLUSION: Our results demonstrated that PNI score is significantly lower in patients with severe and moderate ED. It has been also revealed that the PNI score is an independent predictive factor for severe ED.

Diagnostic accuracy of the plasma ALZpath pTau217 immunoassay to identify Alzheimer's disease pathology.

Importance: Phosphorylated tau (pTau) is a specific blood biomarker for Alzheimer's disease (AD) pathology, with pTau217 considered to have the most utility. However, availability of pTau217 tests for research and clinical use has been limited. Expanding access to this highly accurate AD biomarker is crucial for wider evaluation and implementation of AD blood tests. Objective: To determine the utility of a novel and commercially available Single molecule array (Simoa) for plasma pTau217 (ALZpath) to detect AD pathology. To evaluate references ranges for abnormal Aß across three selected cohorts. Design Setting Participants: Three single-centre observational cohorts were involved in the study: Translational Biomarkers in Aging and Dementia (TRIAD), Wisconsin Registry for Alzheimer's Prevention (WRAP), and Sant Pau Initiative on Neurodegeneration (SPIN). MRI, Aß-PET, and tau-PET data were available for TRIAD and WRAP, while CSF biomarkers were additionally measured in a subset of TRIAD and SPIN. Plasma measurements of pTau181, pTau217 (ALZpath), pTau231, Aß42/40, GFAP, and NfL, were available for all cohorts. Longitudinal blood biomarker data spanning 3 years for TRIAD and 8 years for WRAP were included. Exposures: MRI, Aß-PET, tau-PET, CSF biomarkers (Aß42/40 and pTau immunoassays) and plasma pTau217 (ALZpath Simoa). Main Outcomes and Measures: The accuracy of plasma pTau217 for detecting abnormal amyloid and tau pathology. Longitudinal pTau217 change according to baseline pathology status. Results: The study included 786 participants (mean [SD] age, 66.3 [9.7] years; 504 females [64.1%]) were included in the study. High accuracy was observed in identifying elevated Aß (AUC, 0.92-0.96; 95%CI 0.89-0.99) and tau pathology (AUC, 0.93-0.97; 95%CI 0.84-0.99) across all cohorts. These accuracies were significantly higher than other plasma biomarker combinations and comparable to CSF biomarkers. The detection of abnormal Aß pathology using binary or three-range references yielded reproducible results. Longitudinally, plasma pTau217 showed an annual increase only in Aß-positive individuals, with the highest increase observed in those with tau-positivity. Conclusions and Relevance: The ALZpath plasma pTau217 Simoa assay accurately identifies biological AD, comparable to CSF biomarkers, with reproducible cut-offs across cohorts. It detects longitudinal changes, including at the preclinical stage, and is the first widely available, accessible, and scalable blood test for pTau217 detection.

Controlling nutritional status score in predicting International Society of Urological Pathology score upgrading and biochemical recurrence after radical prostatectomy.

AIM: The aim of our study was to assess the predictive value of controlling nutritional status (CONUT) score for the prognosis of prostate cancer. METHODS: A total of 257 patients' characteristics, prostate-specific antigen (PSA) values, biopsy, and pathological specimen features were all recorded. The CONUT score was calculated for each patient from three blood parameters: total lymphocyte count (TLC), serum albumin, and cholesterol concentrations. Spearman's correlation coefficient was used to assess the correlation between the total CONUT score and the variables including age, body mass index, prostate volume, PSA, biopsy and pathological specimen features, and PSA-recurrence free survival (PSA-RFS) time. The Kaplan-Meier method and log-rank test were used for PSA-RFS analysis. Regression analyses were performed to assess the association between clinicopathological factors, the International Society of Urological Pathology (ISUP) upgrading, and biochemical recurrence (BCR). RESULTS: Statistically significant differences were determined in pathologic ISUP grade, and total tumor volume between low and high CONUT score groups. Additionally, the high CONUT score group had a significantly higher BCR rate and lower PSA-RFS when compared with the low CONUT score group. A strong positive correlation between total CONUT score and pathologic ISUP grade and a moderate negative correlation between total CONUT score and PSA-RFS was determined. In multivariate analysis, a total CONUT score ≥2 had a statistically significant association with ISUP upgrading (odds ratio [OR] = 3.05) and BCR (3.52). CONCLUSION: Preoperative CONUT score is an independent predictive factor for ISUP score upgrading and BCR in patients who undergo radical prostatectomy.

Neurofilament light chain as neuronal injury marker - what is needed to facilitate implementation in clinical laboratory practice?

Neurobiomarkers have attracted significant attention over the last ten years. One promising biomarker is the neurofilament light chain protein (NfL). Since the introduction of ultrasensitive assays, NfL has been developed into a widely used axonal damage marker of relevance to the diagnosis, prognostication, follow-up, and treatment monitoring of a range of neurological disorders, including multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease. The marker is increasingly used clinically, as well as in clinical trials. Even if we have validated precise, sensitive, and specific assays for NfL quantification in both cerebrospinal fluid and blood, there are analytical, as well as pre- and post-analytical aspects of the total NfL testing process, including biomarker interpretation, to consider. Although the biomarker is already in use in specialised clinical laboratory settings, a more general use requires some further work. In this review, we provide brief basic information and opinions on NfL as a biomarker of axonal injury in neurological diseases and pinpoint additional work needed to facilitate biomarker implementation in clinical practice.

Predictive value of Controlling Nutritional Status score and Prognostic Nutritional Index for systemic inflammatory response syndrome/sepsis after percutaneous nephrolithotomy.

PURPOSE: Our aim was to investigate the predictive value of Controlling Nutritional Status (CONUT) score and Prognostic Nutritional Index (PNI) for systemic inflammatory response syndrome (SIRS)/sepsis after percutaneous nephrolithotomy (PNL). METHODS: Demographic and clinical data of 422 patients who underwent PNL were evaluated. The CONUT score was calculated from lymphocyte count, serum albumin, and cholesterol, while the PNI was calculated using lymphocyte count and serum albumin. Spearman's correlation coefficient was used to evaluate the relationship between nutritional scores and systemic inflammation markers. Logistic regression analysis was performed to determine the risk factors for SIRS/sepsis development after PNL. RESULTS: Patients with SIRS/sepsis had a significantly higher preoperative CONUT score and lower PNI compared with the SIRS/sepsis (-) group. A positive significant correlation between CONUT score and CRP (rho = 0.75), CONUT score and procalcitonin (rho = 0.36), and CONUT score and WBC (rho = 0.23) were determined. Additionally, a negative significant correlation was shown between PNI and procalcitonin (rho = - 0.30) and PNI and CRP (rho = - 0.64). The ROC curve analysis showed that the cut-off values for the CONUT score and PNI were 4 (AUC = 0.827) and 42 (AUC = 0.734), respectively. Age, stone size, history of pyelonephritis, residual stone, presence of infection stone, CONUT score ≥ 4, and PNI ≤ 42 were found to be independent predictors for postoperative SIRS/sepsis in multivariate analysis. CONCLUSION: Our results demonstrated that preoperative CONUT score and PNI are potential predictive factors for SIRS/sepsis development after PNL. Therefore, patients with CONUT score ≥ 4 and PNI ≤ 42 are suggested to be closely monitoring due to the risk of post-PNL SIRS/sepsis.

The evaluation of serum bisphenol A in patients with preeclampsia.

AIMS: High bisphenol A (BPA) concentration may compromise normal placental development. The aim of this study was to determine maternal serum BPA concentrations in pregnant women with complicated preeclampsia (PE) and normal pregnant women, to compare BPA concentrations, and to examine pregnancy outcomes. METHODS: This prospective case-control study was conducted between March 2021 and October 2021. Serum BPA levels of preeclamptic pregnancy and normal pregnancy were statistically evaluated. In addition, the PE group was divided into three subgroups according to the course of pregnancy. Group 1: patients with non-severe PE who delivered at 37 weeks or later, Group 2: patients with severe PE who delivered at less than 34 weeks, Group 3: patients with severe PE who delivered between 34 and 37 weeks. The association between BPA levels and pregnancy outcome was investigated. RESULTS: Forty-six cases in the PE group were compared with 46 cases of normal pregnancies. The median BPA level was 19.46 ng/mL in the PE group and 16.36 ng/mL in the control group. The median BPA levels in the PE group were significantly higher than those in the control group (p = 0.007). Serum BPA levels were significantly lower in women who delivered at 37 weeks or later than in women who delivered at less than 34 weeks due to severe PE (p ≤ 0.018). CONCLUSION: Our study highlights the association between elevated maternal serum levels of BPA and PE. Moreover, knowledge of BPA levels in women with PE may provide information about the prognosis of pregnancy.

Assessing the commutability of candidate reference materials for the harmonization of neurofilament light measurements in blood.

OBJECTIVES: Neurofilament light chain (NfL) concentration in blood is a biomarker of neuro-axonal injury in the nervous system and there now exist several assays with high enough sensitivity to measure NfL in serum and plasma. There is a need for harmonization with the goal of creating a certified reference material (CRM) for NfL and an early step in such an effort is to determine the best matrix for the CRM. This is done in a commutability study and here the results of the first one for NfL in blood is presented. METHODS: Forty paired individual serum and plasma samples were analyzed for NfL on four different analytical platforms. Neat and differently spiked serum and plasma were evaluated for their suitability as a CRM using the difference in bias approach. RESULTS: The correlation between the different platforms with regards to measured NfL concentrations were very high (Spearman's ρ≥0.96). Samples spiked with cerebrospinal fluid (CSF) showed higher commutability compared to samples spiked with recombinant human NfL protein and serum seems to be a better choice than plasma as the matrix for a CRM. CONCLUSIONS: The results from this first commutability study on NfL in serum/plasma showed that it is feasible to create a CRM for NfL in blood and that spiking should be done using CSF rather than with recombinant human NfL protein.

The use of natural killer cell activity and PPD test in the prediction of results in intravesical BCG treatment of patients with nonmuscle-invasive bladder cancer.

PURPOSE: To predict the efficacy of intravesical BCG therapy in patients with nonmuscle-invasive bladder tumors (NIBC) by using components of the cellular immune response such as the tuberculin skin test (PPD) and natural killer (NK) activity measurement. METHODS: Ninety-nine patients who were started on intravesical BCG therapy for NIBC were evaluated prospectively. Patients who were included in the intermediate, high, and very high-risk groups according to the EAU NMIBC Scoring System and who had never received intravesical BCG therapy previously were included. The clinical and demographic characteristics of the patients (age, gender, EAU NMBIC risk group, EORTC progression and recurrence scores, CUETO progression and recurrence scores, presence and types of comorbidity) were recorded. NK activity was measured and the PPD test was applied 3 days before the start of intravesical BCG therapy. The results of PPD were measured in millimeters 72 h after the test. RESULTS: PPD values measured before BCG treatment, as an independent variable, were found to be significantly lower in patients with recurrence. A significant correlation was detected between NK activity results obtained before BCG treatment and recurrence after treatment, when the cutoff was 200-500 pg/dl. There was no significant relationship between the time to recurrence and PPD and NKA measurements. CONCLUSION: We conclude that the results of PPD test and NK activity measurement performed before starting intravesical BCG therapy in NIBC may be a marker that can be used to predict the risk of recurrence under treatment.

Serum ciliary neurotrophic factor levels in children with attention deficit hyperactivity disorder.

Purpose/aim of the study: The study aimed to highlight the possible role of ciliary neurotrophic factor (CNTF) in the pathophysiology of attention deficit hyperactivity disorder (ADHD) and determine whether CNTF can be used as a biomarker for ADHD.Materials and methods: Patients with a diagnosis of ADHD and neurotypical subjects aged 6-12 years were recruited prospectively. The study applied Conners' Teacher Rating Scale (CTRS) to determine the patients' ADHD predominance and severity. Serum CNTF levels were measured with an enzyme-linked immunosorbent assay (ELISA) kit.Results: A total of 43 ADHD patients and 33 healthy controls were included in the study. A significant difference was found between the serum CNTF levels of the ADHD patients (22.17 pg/ml) and the controls (22.80 pg/ml). Correlations between the CNTF levels and CTRS scores were not significant.Conclusions: The study identified an alteration of serum CNTF levels in ADHD patients and thus asserted a link between CNTF and ADHD pathophysiology; children with ADHD had significantly lower serum CNTF levels compared to the neurotypical controls. Further research is needed to understand the mechanisms of CNTF.

Maternal plasma levels of vitamin D in postterm pregnancy.

This study was conducted to examine the levels of vitamin D in postterm pregnancy. The study consisted of two groups: Group 1: women with postterm pregnancy in whom labour has not started (n = 40). Group 2: pregnant women with spontaneous labour between 37 and 41 weeks of gestation (n = 40). Demographic characteristics of individuals, age, body mass index, gravida, parity, living child, number of abortions and birth characteristics were recorded. Prepartum and postpartum haemoglobin (Hb) and haematocrit (Hct) values ​​and vitamin D levels of pregnant women were measured. We found no significant differences in vitamin D levels, smoking, mode of delivery, induction of labour, methods of cervical ripening and maternal and perinatal complications between the groups (p > .05). D vitamin in the model had a statistically significant effect on prepartum Hb (p < .05). Vitamin D levels seem not to be associated with postterm pregnancy. Vitamin D had a statistically significant effect on prepartum Hb.IMPACT STATEMENTWhat is already known on this subject? The aetiology of post term pregnancy is not clearly known, factors such as foetal anencephaly, foetal sex, placental sulfatase deficiency, genetic factors, and high pre-pregnancy body mass index play a role.What do the results of this study add? Vitamin D levels seem not to be associated with postterm pregnancy. Vitamin D had a statistically significant effect on prepartum Hb.What are the implications of these findings for clinical practice and/or further research? Further studies are needed to clarify the relationship between vitamin D levels and postterm pregnancy.

Evaluation of cerebrospinal fluid neurofilament light chain levels in multiple sclerosis and non-demyelinating diseases of the central nervous system: clinical and biochemical perspective.

The neurofilament light chain (NfL) is a promising biomarker in the diagnosis, prognosis, and treatment response evaluation of neurological diseases. The aims of this study were to compare the cerebrospinal fluid (CSF) NfL levels in multiple sclerosis (MS) and certain non-demyelinating diseases of the central nervous system (NDCNS); to determine the relationship between clinical and radiological features and CSF NfL levels in patients with MS; and to compare the enzyme-linked immunosorbent assay (ELISA) and single molecule array (SIMOA) methods for NfL measurement using paired CSF and serum samples. We retrospectively analyzed the clinical data and performed NfL measurements in CSF and serum samples of newly diagnosed and treatment-naive patients with CNS diseases evaluated between 1 January 2019 and 1 January 2020. Eligible patients were divided into three groups: MS (n=23), differential diagnosis of MS (n=19), and NDCNS (n=42). First, we compared the CSF NfL levels among the three groups using the previously validated CSF ELISA assay. Next, we evaluated the relationship between CSF NfL levels and the clinical and radiological findings in MS group. Finally, we compared CSF and serum samples from patients of the MS groups (paired serum and CSF samples, n=19) using two different methods (ELISA and SIMOA). The CSF NfL level was the highest in the NDCNS group (1169.64 [535.92-5120.11] pg/mL, p=0.025). There was a strong positive correlation between the number of T2 lesions and CSF NfL level (r=0.786, p<0.001) in the MS group. There was excellent consistency between ELISA and SIMOA for CSF samples, but not for serum samples. Our results indicated that CSF NfL levels may also be used in the management of NDCNS and that SIMOA is the most reliable method for serum NfL determination.