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Olanzapine is a thienobenzodiazepine class antipsychotic that strongly antagonises the 5-HT2A serotonin receptor, but acute poisonings are reported rarely. Symptoms of an overdose include disorder of consciousness, hypersalivation, myosis, and coma. Serum concentration higher than 0.1 mg/L is toxic, while concentration above 1 mg/L can be fatal. Here we report key data about 61 patients admitted to the National Poison Control Centre in Belgrade, Serbia over olanzapine poisoning in 2017 and 2018. The ingested doses ranged from 35 to 1680 mg, and time from ingestion to determination from two to 24 hours. In 34 patients olanzapine serum concentrations were in the therapeutic range and in 27 in the toxic range. In five patients they were higher than fatal, but only one patient died. The most common symptoms of poisoning were depressed consciousness (fluctuating from somnolence to coma), tachycardia, hypersalivation, hypotension, myosis, and high creatine kinase. All patients but one recovered fully after nonspecific detoxification and symptomatic and supportive therapy., Olanzapin je antipsihotik koji pripada grupi tienobenzodiazepina. Kao i drugi atipični antipsihotici, olanzapin je jak antagonist 5-HT2A serotoninskih receptora. Akutna trovanja olanzapinom su rijetka. Simptomi predoziranja uključuju duboki ili fluktuirajući poremećaj stanja svijesti s hipersalivacijom i miozom, kao i komu i smrt u slučaju ingestije velikih doza. Koncentracije olanzapina u serumu veće od 0,1 mg/L smatraju se toksičnima, a letalnima veće od 1 mg/L. U radu su prikazana akutna trovanja olanzapinom zabilježena u Nacionalnom centru za kontrolu trovanja u Beogradu tijekom dvije godine. Koncentracije olanzapina u serumu pacijenata akutno otrovanih olanzapinom određene su pouzdanom metodom tekuće kromatografije s masenom spektrometrijom. Registriran je 61 pacijent s predoziranjem olanzapinom: u njih 34 koncentracije olanzapina bile su u terapijskom opsegu, a u njih 27 zabilježene su toksične koncentracije. Pet pacijenata imalo je koncentracije veće od letalnih, a zabilježen je i jedan smrtni ishod. Najčešći simptomi trovanja bili su hipotenzija, tahikardija i povećanje aktivnosti enzima kreatin kinaze. Nakon primjene nespecifičnog detoksikacijskog simptomatskog i potpornog liječenja svi pacijenti osim jednog su se potpuno oporavili.

Background:The optimal sampling points and thresholds for initial serum vancomycin (VCM) concentrations have not been determined in hemodialysis (HD) patients. To clarify this, multiple blood tests were performed, and the correlations between VCM concentrations at several sampling points and the area under the concentration-time curve for 24 hours (AUC24h) were analyzed., Methods:A single-center, prospective observational study was conducted. Patients with end-stage renal failure who received VCM treatment while undergoing chronic maintenance HD were enrolled in this study. HD was performed using a high-flux membrane as the dialyzer. After VCM administration, 7 points were sampled between the first and second HD. The AUC24h after the end of the first HD (AUC0-24) and that before the end of the second HD (AUC24-48) were calculated using the linear trapezoidal method. Correlation analysis and simple regression analysis between AUC24h and serum concentrations were performed at each sampling point., Results:Nine patients were evaluated. Strong correlations were found between AUC24-48 and serum concentrations at 24 hours after the initiation of VCM treatment following the first HD (C24h, R = 0.983 and P < 0.001), between AUC0-24 and C24h (R = 0.967 and P < 0.001), and between AUC24-48 and serum concentration just before the second HD (Cpre(HD2), R = 0.965 and P < 0.001). Regression equations with high coefficients of determination (R2 > 0.9) were obtained, and a C24h of ≥18.0 mg/L and a Cpre(HD2) of ≥16.5 mg/L were required to achieve an AUC24-48 value of ≥400 mg·h/L. In addition, a C24h of ≤23.3 mg/L was estimated to satisfy the AUC0-24 range of ≤600 mg·h/L., Conclusions:C24h and Cpre(HD2) are optimal sampling points for predicting VCM-AUC24h in HD patients.

We aimed to compare serum concentrations of sclerostin and DKK-1 in young (20-30 yrs, n = 25) and middle-aged (35-45 yrs, n = 25) premenopausal women and based on physical activity (PA) status. PA status was assessed by the International Physical Activity Questionnaire (low-moderate (≤ 2999 MET-min/week) and high (≥ 3000 MET-min/week). Serum sclerostin and DKK-1 levels were measured in fasting morning blood samples by ELISA. Areal bone mineral density (aBMD) was measured by DXA, and non-dominant tibia bone characteristics were assessed by pQCT. After adjusting for total body aBMD, middle-aged women had significantly (p0.001) higher (0.54 ± 0.01 ng/mL) serum sclerostin than young women (0.41 ± 0.01 ng/mL), and sclerostin was positively correlated with age (r

Background Separation gels are often used in collection tubes, but adsorption of drugs onto the gel may cause falsely low concentrations in therapeutic drug monitoring. In this study, the stability of apixaban, edoxaban, rivaroxaban, flecainide, amiodarone, and desethylamiodarone was assessed in tubes, with and without gel separators. Methods Drug-free blood was spiked and stored for up to 7 d in non-gel tubes and gel tubes from two manufacturers (Vacuette and Vacutainer). The samples were analyzed in triplicates using ultra high pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Results At ambient temperature conditions, the serum concentrations of apixaban, edoxaban, and rivaroxaban in a tube with acrylic-based gel had already decreased at baseline, while it took 6 h to observe the same result in a tube with olefin-based gel. At 4 °C, the reduction in serum concentration was considerably slower. For flecainide, the gel tube concentrations were stable at ambient temperature for 3 d, but decreased after 7 d in acrylic-based gel tubes. Amiodarone and desethylamiodarone stored in gel tubes at 4 °C showed decrease in concentrations after 24 h and 6 h, respectively. Conclusion Acrylic-based gel tubes should not be used for any of the tested drugs. Although olefin-based gel tubes may be used for anticoagulants and flecainide, it is advisable to prefer non-gel tubes as a general precaution.

To evaluate the ocular and systemic determinants of the choriocapillaris flow deficits percentage (CC FD%) in normal eyes.Observational cross-sectional study.Healthy Chinese participants without ocular or systemic diseases underwent detailed ophthalmic evaluations, including swept-source optical coherence tomography angiography (SS-OCTA) with 6- × 6-mm macular choriocapillaris images. The CC FD% was assessed in circular regions with diameters of 1.0 and 5.0 mm, rings with 1.0- to 2.5-mm diameters, and rings with 2.5- to 5.0-mm diameters.The study included 830 individuals (mean ± SD age 58.66 ± 8.75 years). CC FD% (mean ± SD 22.05% ± 1.13%) was the lowest in the 2.5- to 5.0-mm ring, followed by the 1.0- to 2.5-mm ring, and highest in the 1.0-mm circle. In multivariable analysis, a higher CC FD% was associated with older age (β = 0.16 [95% confidence interval {CI}] 0.08-0.24, P.001), higher intraocular pressure (β = 0.34 [95% CI 0.25-0.42], P.001), higher serum concentrations of high-density lipoprotein cholesterol (β = 0.24 [95% CI 0.17-0.32], P.001), and lower image quality score (β = -0.22 [95% CI -0.30 to -0.14], P.001). CC FD% was also independent of axial length.In healthy adult Chinese individuals, a higher CC FD% was associated with older age, higher intraocular pressure, and higher high-density lipoprotein cholesterol serum concentration. These factors may influence clinical assessments of the choriocapillaris. The lack of an association between CC FD% and axial length is consistent with similar findings for Bruch membrane thickness, macular retinal thickness, and macular retinal pigment epithelium cell density.

Aim Matrix metalloproteinases (MMPs) play critical roles in acute myocardial infarction (AMI). This trial was conducted to determine the potential effects of higher-dose rosuvastatin on circulating MMP levels in patients with AMI. Methods This was a multicenter, open-label, 1:1 randomized, parallel-group study. Patients with AMI were randomly assigned to the appropriate-dose group (10 mg rosuvastatin once daily) or the low-dose group (2.5 mg rosuvastatin once daily) within 24 hours after percutaneous coronary intervention. MMP-2 and MMP-9 levels were measured on day 1 and at week 4, 12, and 24 after enrollment. The primary endpoint was the change in MMP levels at 24 weeks after enrollment. The secondary endpoints were change in MMP levels at day 1 and weeks 4 and 12 after enrollment. Results Between August 2017 and October 2018, 120 patients with AMI from 19 institutions were randomly assigned to either the appropriate-dose or the low-dose group. There were 109 patients who completed the 24-week follow-up. The primary endpoint for both MMP-2 and MMP-9 was not significantly different between the two groups. The change in the active/total ratio of MMP-9 at week 12 after baseline was significantly lower in the appropriate-dose group compared with the low-dose group (0.81 [-52.8-60.1]% vs. 70.1 [-14.5-214.2]%, P=0.004), while the changes in MMP-2 were not significantly different between the two groups during the study period. Conclusions This study could not demonstrate the superiority of appropriate-dose of rosuvastatin in inhibiting serum MMPs levels in patients with AMI.

Stem cell factor (SCF) and its receptor (c-kit) signaling play important role in normal brain physiology including neurogenesis, synapse formation and spatial learning function of the hippocampal region of the brain. Autism spectrum disorder (ASD) is believed to result from abnormal development of neuronal networks and synaptic function. The aim of this study was to evaluate the SCF and its soluble receptor (s-ckit) serum concentrations in ASD. We also studied the serum SCF and s-ckit concentration with the severity of ASD (Levels 1–3; Mild, Moderate and severe, respectively). Ninety five patients with ASD (Mild; n = 33, Moderate; n = 32 and severe; n = 30) and 82 normal controls age matched were included in this study. The serum concentration of SCF and s-ckit were measured by enzyme-linked immunosorbent assay (ELISA). The SCF serum concentration in control subjects was 3.45 ± 1.06 ng/ml and in ASD was 3.41 ± 0.92 ng/ml (P = 0.88). The serum levels of s-ckit in control and ASD groups were 56.82 ± 13.22 ng/ml and 67.11 ± 12.00, respectively (P = 001). We have also studied serum SCF and s-ckit concentrations with the severity of ASD. The serum concentration of SCF in mild, moderate and severe ASD groups was 3.45 ± 0.93, 3.4 ± 0.87 and 3.43 ± 0.98 ng/ml, respectively (P > 0.05) and for s-ckit was 48.77 ± 9.28, 61.66 ± 12.18 and 93.11 ± 14.81ng/ml, respectively (P

Background and Aim: Placental Growth Factor (PlGF) plays a crucial role in angiogenesis and was identified as a potential prognostic biomarker in various types of cancer. Therefore, we evaluated the diagnostic accuracy and prognostic value of PlGF serum concentration in patients with clear cell renal cell carcinoma (ccRCC). Patients and Methods: A total of 49 patients subjected to partial or radical nephrectomy for ccRCC [localized without relapse (lccRCC; n=31), localized with later relapse (rccRCC; n=8), primary metastatic cancer (mccRCC; n=10); median of follow-up 4.4 years] were enrolled in a prospective study to assess the significance of PlGF serum concentration. PlGF was measured prior to surgery and 3 months postoperatively. Our control group consisted of 38 healthy subjects. Results: PlGF serum concentration was significantly higher in ccRCC compared to controls (P=0.002). The cut-off value of PlGF concentration for the risk of ccRCC was determined at 12.71 pg/mL (AUC=0.729; P=0.0001). Prior to surgery, among ccRCC subgroups, significantly higher PlGF concentration was detected in mccRCC compared to lccRCC (P=0.002). Postoperatively, we observed a tendency to higher PlGF serum concentration in rccRCC compared to lccRCC subgroup, however without significance (P=0.17). The cut-off value for the risk of relapse was 11.41 pg/mL (AUC=0.792; P=0.0003). In subjects with localized ccRCC with PlGF concentration below 11.41 pg/mL 3-years cancer specific survival was 93% compared to 61% in subject with concentration above the cut-off value (P=0.018). Conclusion: Based on our findings, PlGF serum concentration seems to be a useful biomarker in diagnostics and prediction of prognosis in ccRCC.

Essential trace metals (ETMs) may play important roles in the pathophysiology of benign and malignant breast cancers. Our study aimed to find associations between ETMs and benign and malignant breast cancers. We recruited 146 patients with benign (n = 73) and malignant (n = 73) breast tumors and 95 healthy controls (HCs) from Peking University Third Hospital, Beijing, China. The serum concentrations of seven ETMs (Zn, Mn, Cu, Fe, Co, Ni, and Mo) were evaluated using inductively coupled plasma mass spectrometry (ICP-MS). The serum concentrations of Zn were significantly lower in the malignant group than in the HC group, whereas the concentrations of Cu (p

Background The optimal use of infliximab depends on the measurement of trough levels with subsequent appropriate dose adjustment. With the introduction of biosimilars, it is important to demonstrate that the biosimilar behaves similarly in the assay utilized as the originator-infliximab, for which the assays were developed. In this study, the authors aimed to compare the concentrations of SB2-infliximab (Renflexis®) with that of originator-infliximab (Remicade®) when added to serum from healthy subjects and those with inflammatory bowel disease (IBD) when measured by commonly employed commercial assays. Methods Sera from two healthy controls, two patients with ulcerative colitis (one with quiescent disease, one with active disease), and two patients with Crohn's disease (one with quiescent disease, one with active disease) were spiked with SB2-infliximab or originator-infliximab at 0-20 μg/mL. Concentrations were measured using three commonly used assay kits (Lisa-Tracker®, Shikari Q-Inflix®, Promonitor IFX®) and one rapid test (Quantum Blue®). The results were compared using Bland-Altman techniques. Results Close agreement was observed between measured concentrations for all assays, irrespective of the origin of the serum. Limits of agreement varied between at worst -0.302 and 0.465 μg/mL, with the mean difference between the molecules being at worst 0.04 μg/mL (95% confidence intervals -0.011, 0.093). Conclusions The originator and SB-2 biosimilar-infliximab behaved similarly in several currently utilized assays in terms of their concentrations in biological fluids. Clinicians can be confident that therapeutic drug monitoring using platforms designed and developed for the originator-infliximab can be applied to SB-2-infliximab.

Clozapine (CLZ) is the superior drug in treatment of schizophrenia. Serum concentration of CLZ is associated with clinical response and dose-dependents side effects, where generalized tonic-clonic seizures are most critical. Thus, therapeutic drug monitoring (TDM) of CLZ may guide individual dosing to reach target exposure and prevent dose-dependent side effects. However, current TDM methods are not capable of predicting the risk of agranulocytosis, which is a dose-The article provides an overview of clinical, pharmacological, and toxicological aspects of CLZ, and the role of TDM as a tool for dose titration and follow-up in patients with TRS. Main focus is on current challenges and strategies in CLZ TDM, including future perspectives on potential identification/analysis of CLZ metabolite biomarkers reflecting the risk of granulocyte toxicity.The association between CLZ serum concentration, clinical response and risk of seizures is indisputable. TDM should therefore always guide CLZ dose titration. Development of advanced TDM methods, including biomarkers predicting the risk of granulocyte toxicity might extend TDM to be a tool for deciding which patients that can be treated safely with CLZ, potentially increasing its utility beyond TRS.

Background The creatinine-based CKD EPI equation is the most widely used method to estimate glomerular filtration rate (eGFRcr) in clinical practice. Here, we focus on African American (AA) participants to determine whether the race eGFRcr calibration factor contributes to poor accuracy and bias in AAs living with HIV. Methods Annually, we measured GFR by iohexol disappearance from plasma (iGFR) and serum concentrations of creatinine and cystatin C. We calculated eGFRcr and the creatinine-cystatin C combination equation (eGFRcr-cys) with and without race adjustment. We used multilevel mixed models to account for the within-visit linked structure of the multiple GFR measures, further nested within repeated observations for individuals. We examined the association between lean mass, HIV status, and eGFRcr bias in a subset with body composition measures. Results 207 HIV-positive and 107 HIV-negative AA participants contributed 781 and 376 study visits, respectively, with valid measures of iGFR, creatinine, and cystatin C. Among PLWH, omitting the race adjustment (compared with retaining it) changed average eGFRcr bias from 9.1 to -3.9 ml/min/1.73 m2. Moreover, estimation accuracy improved significantly when race adjustment was omitted rather than retained: 86% vs. 78% for eGFRcr (P

Data availability: The authors do not have permission to share data. Copyright © 2022 The Authors. Objectives: To investigate the association of exposure to per- and polyfluoroalkyl substances (PFAS) during early pregnancy with markers of the maternal thyroid system. Methods: Serum concentrations of seven PFAS as well as thyroid stimulating hormone (TSH), free and total thyroxine (FT4 and TT4), free and total triiodothyronine (FT3 and TT3) were measured in pregnant women in early pregnancy in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study. Outcomes were concentrations of TSH and thyroid hormones, FT4/FT3 or TT4/TT3 ratios, TSH/FT4 ratio as a marker of the negative feedback loop, TT4/FT4 or TT3/FT3 ratios as markers of the binding of thyroid hormones to binding proteins. Results: The study population comprised 2,008 women with median (95% range) gestational age of 10 (6–14) weeks. There was no association between PFAS and TSH. Higher PFNA, PFDA, PFHpA and PFOA levels were associated with a higher FT4 (largest effect estimate for PFDA: β [95% CI]: 0.27 [0.10 to 0.45], P = 0.002). Higher PFUnDA levels, but no other PFAS, were associated with a lower FT3 (β [95% CI]: −0.05 [-0.09 to −0.01], P = 0.005). Higher PFUnDA levels were associated with lower TT4 (β [95% CI]: −1.58 [-3.07 to −0.09]) and there was an inverted U-shaped association of PFOS with TT4 (P = 0.03). Higher PFDA, PFUnDA, PFHpA levels were associated with a lower TT3. Overall, higher PFAS concentrations were associated with a higher FT4/FT3 ratio and a higher TT4/TT3 ratio. There was no association of PFAS with the TSH/FT4 ratio. Higher concentrations of several PFAS were associated with lower TT4/FT4 and TT3/FT3 ratios. Conclusions: These findings translate results from experimental studies suggesting that exposure to PFAS may interfere with the thyroid system during pregnancy. Further experimental studies should take into account human evidence to better understand the potential underlying mechanisms of thyroid disruption by PFAS exposure. This project has been supported by the Exchange in Endocrinology Expertise (3E) program of the European Union of Medical Specialists (UEMS), Section and Board of Endocrinology and the ATHENA project, funded under the European Union’s Horizon 2020 Programme for research, technological development and demonstration, grant agreement no. 825161. The SELMA study was funded by grants from the Swedish Research Council (Formas).

Objective The relationship between 25-hydroxyvitamin D3 (25(OH)D), the surrogate marker for vitamin D3, serum concentration and COVID-19 has come to the forefront as a potential pathway to improve COVID-19 outcomes. The current evidence remains unclear on the impact of vitamin D status on the severity and outcomes of COVID-19 infection. To explore possible association between low 25(OH)D levels and risk of developing severe COVID-19 (i.e. need for invasive mechanical ventilation, the length of hospital stay, total deaths). We also aimed to understand the relationship between vitamin D insufficiency and elevated inflammatory and cardiac biomarkers. Methods We conducted a comprehensive electronic literature search for any original research study published up to March 30, 2021. For the purpose of this review, low vitamin D status was defined as a range of serum total 25(OH)D levels of

Introduction The randomized PRAGUE-17 trial demonstrated non-inferiority of LAAC to NOAC for the prevention of major cardiovascular or cerebrovascular events. However, the LAA is an important source of natriuretic peptides and plays a role in left atrial reservoir function. Changes of HF biomarkers after LAAC compared to NOAC has not been studied. The aim of the study was to compare the changes in concentrations of heart failure (HF) biomarkers between left atrial appendage closure (LAAC) and non-vitamin K anticoagulants (NOAC) patients. Methods Of 402 patients randomized in the PRAGUE-17 trial, biomarkers were analyzed in 144 patients (73 in the NOAC and 71 in the LAAC group). Both groups had similar baseline characteristics. Serum concentration of NT-proBNP, NT-proANP, Galectin-3, and GDF-15 were measured at baseline (before the procedure in the LAAC group), at the 6-month (and at 24-month for NT-proBNP) follow-up timepoint. Results There were no significant differences in baseline, 6-month, and delta (δ = baseline - 6-month) concentrations of NT-proANP between the groups (NOAC: baseline 2.6 (0.5; 4.9), 6-month 3.1 (1.8; 4.8), p=0.068; LAAC: baseline 3.3 (1.1; 4.6), 6-month 2.6 (0.9; 5.3), p=0.51; p value for δ in concentrations between groups = 0.42). Similarly, there were no significant differences in baseline, 6-month, 24-monht and delta concentrations of NT-proBNP between the groups (NOAC: baseline 461.0 (113.5; 1342.0), 6-month 440.0 (120.5; 1291.5), 24-month 798 (274; 2236), p = 0.39; LAAC: baseline 421.0 (100.0; 1320.0), 6-month 601.0 (145.0; 1230.0), 24-month 855 (410; 1367), p=0.28; p value for δ in concentrations between groups = 0.73 at 6 months, and 0.58 at 24 months). Finally, no significant differences were present in baseline, 6-month, and δ concentrations of Galectin-3 and GDF-15 between the two groups. Conclusion LAAC did not significantly influence the levels of HF biomarkers 6 months after the procedure. This article is protected by copyright. All rights reserved.

There are not data on blood B-cell lymphoma 2 (Bcl-2) concentrations (one of the antiapoptotic molecules of the Bcl-2 family in the intrinsic apoptosis pathway) in septic patients. Therefore, this study was carried with the aims to explore whether blood Bcl-2 concentrations at diagnosis of sepsis are different in survivor and non-survivor septic patients, are associated with mortality, and are useful for the mortality prediction.Intensive Care Units from 3 Spanish hospitals participated in this observational and prospective study with septic patients and serum Bcl-2 concentrations at diagnosis of sepsis were determined. Mortality at 30 days was as outcome variable.We found that 30-day non-surviving patients (n=81) showed lower serum Bcl-2 levels (p=0.003) than surviving patients (n=140). We found that serum concentrations of Bcl-24.4ng/mL were associated with mortality (OR=3.228; 95% CI=1.406-7.415; p=0.006) in the multiple logistic regression analysis, and that showed an area under the curve for mortality prediction of 62% (95% CI=55-68%; p=0.003).In our study appears novel findings such as higher blood Bcl-2 concentrations in survivor than in non-survivor septic patients, the association between low blood Bcl-2 concentrations and mortality of septic patients, and the ability of blood Bcl-2 concentrations for the prediction of septic patient mortality.

Objective The purpose of this clinical trial was to examine the effect of omega-3 fatty acids (W-3 FAs), nanocurcumin and their combination on serum levels and gene expression of VCAM in patients with episodic migraine. Results In this study, 80 patients were randomly divided in to 4 groups to receive for 2 months. Both serum levels and gene expression of VCAM showed remarkable decreases after single W-3 and after combined W-3 and nanocurcumin interventions. However, a borderline significant change and no remarkable change were observed after single nanocurcumin supplementation and in control group, respectively. While a significant difference between study groups in VCAM concentrations existed, there was no meaningful difference in VCAM gene expression among groups. It appears that the W-3 and combined W-3 and nanocurcumin can relieve VCAM serum level and its gene expression in patients with episodic migraine. Moreover, the combination of W-3 with nanocurcumin might cause more significant declines in VCAM level in the serum of migraine patients than when W-3 is administered alone. Trial Registration: This study was registered in Iranian Registry of Clinical Trials (IRCT) with ID number: NCT02532023.

Objective: To detect antibodies against p53 in serum of patients of oral squamous cell carcinoma and oral potentially malignant disorders compared to healthy individuals. Method: The descriptive cross-sectional study was conducted at the departments of Oral and Maxillofacial Surgery, Peshawar Dental College, Peshawar, Khyber College of Dentistry, Peshawar, and the Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from April2016 to March2017, and comprised serum of oral squamous cell carcinoma patients in group A, oral potentially malignant disorder patients in group B and healthy individuals in group C. Serum concentrations of anti-p53 antibodies were determined by enzyme-linked immunosorbent assay. Data was analysed using SPSS 20. Results: Of the180 subjects, there were 60(33.3%) in each of the three groups. Circulating serum p53 antibodies were detected in 59(98.3%) cases in group A, 58(96.6%) in group B and in 20(33.3%) individuals in group C (p=0.001). Conclusion: The expression of circulating p53 antibodies in serum samples of squamous cell carcinoma and oral potentially malignant disorders patients indicates the potential to be a probable candidate for being taken as a diagnostic or prognostic biomarker. Key Words: Tumour suppressor genes, TSGs, Oral squamous cell carcinoma, OSCC, Oral potentially malignant disorders, OPMDs, p53, ELISA. Continuous...

Background: There are no data on circulating concentrations of sFas (proapoptotic protein of extrinsic pathway) and Bcl2 (antiapoptotic protein of intrinsic pathway) in COVID-19 patients. Thus, our objective study was to determine whether an association exists between serum concentrations of sFas and Bcl2 and COVID-19 patient mortality. Methods: This observational and prospective study of COVID-19 patients was performed in eight Intensive Care Units (ICU) from Canary Islands (Spain). Serum levels of sFas and Bcl2 at ICU admission were determined. Mortality at 30 days was the end-point study. Results: Surviving patients (n = 42) compared to non-surviving (n = 11) had lower APACHE-II (p

The effect of intermittent hemodialysis (IHD) on nivolumab serum concentrations in patients with severe renal impairment is largely unknown. Here, we present a 79-year-old patient with metastatic melanoma and end-stage renal disease on IHD three times a week, treated with 480 mg nivolumab every 4 weeks. A serum trough concentration of nivolumab was determined before the start of the third cycle, and two samples were taken immediately before and after a hemodialysis session during this cycle. All nivolumab serum concentrations were within a similar range as those previously measured among patients without renal insufficiency, after a comparable duration of nivolumab treatment. Therefore, we conclude that IHD does not influence nivolumab exposure. Furthermore, nivolumab treatment was continued without complications and appears to be well tolerated for patients on IHD.

Objective:The aims of this study were to examine the efficacy among various vitamin D supplementation regimens on serum 25-hydroxyvitamin D (25(OH)D) concentrations and determine the minimal dose rate required to achieve sufficient serum concentrations (≥75 nmol/l) among older adults in long-term care (LTC).Design:A 1-year medical history was abstracted from medical records, and a one-time blood draw to measure serum 25(OH)D concentrations was obtained. Individuals were stratified into vitamin D-supplemented and non-supplemented groups. The supplemented group was further categorised into four treatment forms: single-ingredient vitamin D2or3, multivitamin, Ca with vitamin D or combination of the three, and by daily prescribed doses: 0–9·9, 10–19·9, 20–49·9, 50–99·9 and >100 μg/d.Setting:Five LTC communities in Austin, Texas.Participants:One hundred seventy-three older (≥65 years) adults.Results:Of the participants, 62% received a vitamin D supplement and 55% had insufficient (≤75 nmol/l) 25(OH)D serum concentrations. Individuals receiving single-ingredient vitamin D2or3 supplementation received the highest daily vitamin D mean dose (72·5 μg/d), while combination of forms was the most frequent treatment (44%) with the highest mean serum concentration (108 nmol/l). All supplementation doses were successful at reaching sufficient serum concentrations, except thoseConclusions:Based on the predictive equation, results suggest that supplementation of 37·5 μg/d of vitamin D2or3 or combination of vitamin D is most likely to achieve sufficient serum 25(OH)D concentrations in older adults in LTC.

Aldehydes are known carcinogens and irritants that can negatively impact health. They are present in tobacco smoke, the environment, and food. The prevalence of aldehyde exposure and potential health impact warrants a population-wide study of serum aldehydes as exposure biomarkers. We analyzed 12 aldehydes in sera collected from 1843 participants aged 12 years or older in the 2013-2014 National Health and Nutrition Examination Survey. Several aldehydes were detected at high rates, such as isopentanaldehyde (99.2%) and propanaldehyde (88.3%). We used multiple linear regression models to examine the impact of tobacco smoke and dietary variables on serum concentrations of isopentanaldehyde and propanaldehyde. Although 12 serum aldehydes were analyzed and compared to tobacco smoke exposure, only isopentanaldehyde and propanaldehyde showed any significant association with tobacco smoke exposure. Survey participants who smoked 1-10 cigarettes per day (CPD) had 168% higher serum isopentanaldehyde and 28% higher propanaldehyde compared with nonusers. Study participants who smoked 11-20 CPD had higher serum isopentanaldehyde (323%) and propanaldehyde (70%). Similarly, study participants who smoked >20 CPD had 399% higher serum isopentanaldehyde and 110% higher serum propanaldehyde than nonexposed nonusers. The method could not, however, differentiate between nonexposed nonusers and nonusers exposed to secondhand smoke for either of these two aldehydes. No dietary variables were consistently predictive of serum isopentanaldehyde and propanaldehyde concentrations. This report defines baseline concentrations of serum aldehydes in the U.S. population and provides a foundation for future research into the potential health effects of aldehydes. In addition, this study suggests that tobacco smoke is a significant source of exposure to some aldehydes such as isopentanaldehyde and propanaldehyde.

Background: Neuron-specific enolase (NSE) is one of the biomarkers of neuroendocrine neoplasms (NEN). Its level of evidence is significantly lower than some other biomarkers. However, the ratio of NSE serum concentration (NSE ratio) before and after the treatment cycle may be a good tool for evaluating the therapeutic effect of metastatic neuroendocrine neoplasms of the liver (MNENOL). Methods: We collected clinical cases of NEN with liver metastases, calculating the ratio of NSE in each case before and after the treatment cycle, using thin-slice computed tomography or magnetic resonance imaging as a reference to evaluate the therapeutic effect. We analyzed the correlation between NSE ratio and NSE serum concentration and curative effect, and then compared the evaluation performance of the two. Results: We found that increase in the NSE ratio is a risk factor for the progression of MNENOL. Compared with NSE, NSE ratio has a greater advantage in evaluating the effect of MNENOL. NSE ratio is related to the curative effect of NEN, and the correlation is better than that of NSE. When judging whether NEN has new metastasis, the NSE ratio shows a similar effect to NSE, and there is no significant difference between the two. Conclusion: NSE ratio is more effective than NSE in evaluating the therapeutic effect of MNENOL, but it is not significantly different from NSE in terms of predicting new metastases.

Background It has been suggested that premenstrual syndrome (PMS) may derive from either elevated oxidative stress or reduced antioxidant vitamin levels in the body; however, these relationships have been minimally studied in a large cohort of healthy women. Our objective was to estimate the association between serum concentrations of antioxidant vitamins (A, C, and E) and markers of oxidative stress (F2-isoprostane) with symptoms and severity of PMS. Methods The BioCycle study was a prospective cohort study following 259 healthy premenopausal women aged 18–44 years for up to 2 menstrual cycles. Frequency/severity of 20 PMS symptoms were assessed via questionnaires 4 times/cycle, and antioxidant vitamins and oxidative stress biomarkers were measured up to 8 times/cycle to correspond with specific cycle phases. Generalized linear models were used to estimate associations between mean antioxidant concentrations and oxidative stress biomarkers with PMS symptoms and severity; linear mixed models were used to evaluate associations with symptom severity scores within groups (e.g. depression, cravings, pain). Results Higher concentrations of serum antioxidant vitamins were largely not associated with prevalence or severity of PMS symptoms. Though a few associations were observed, only associations between mean γ-tocopherol and decreased odds of swelling of the hands/feet survived adjustment for multiple comparisons (OR 0.33, 95% CI 0.16, 0.65, per ug/dL). However, F2-isoprostanes were associated with prevalence and severity of several symptoms specifically related to depression and cravings (depression score β = 0.07, 95% CI 0.02, 0.12, per 10 ug/dL; cravings score β = 0.16, 95% CI 0.10, 0.22, per 10 ug/dL), as well as with classification of PMS severity (OR 1.07, 95% CI 1.01, 1.14, per 10 pg/dL), with these associations surviving adjustment for false discovery rate. Conclusions F2-isoprostanes, but not antioxidant vitamins, were associated with select PMS symptoms, as well as symptom and severity categories. Specific symptom relationships merit further research.

Context Data on the presence/quantification of the neurotrophic adipokines retinol-binding protein-4 (RBP4), clusterin, and pigment epithelium-derived factor (PEDF) in human cerebrospinal fluid (CSF) are scarce and migration of these adipokines across of the blood-brain barrier (BBB) is uncertain. Objective This work aimed to quantify RBP4, PEDF, and clusterin in paired serum and CSF samples of patients undergoing neurological evaluation. Methods A total of 268 patients (109 male, 159 female) were included. Adipokine serum and CSF concentrations were measured by enzyme-linked immunosorbent assay in duplicate. Results RBP4 was abundant in serum (mean, 31.9 ± 24.2 μg/mL). The serum concentrations were approximately 145 times higher than in CSF (CSF to serum RBP4 ratio, 8.2 ± 4.3 × 10–3). PEDF was detectable in serum (mean, 30.2 ± 11.7 μg/mL) and concentrations were approximately 25 times higher than in CSF (CSF to serum PEDF ratio, 42.3 ± 15.6 × 10–3). Clusterin serum concentrations were abundant with mean levels of 346.0 ± 114.6 μg/mL, which were approximately 40 times higher than CSF levels (CSF to serum clusterin ratio, 29.6 ± 23.4 × 10–3). RBP4 and PEDF serum levels correlated positively with CSF levels, which were increased in overweight/obese patients and in type 2 diabetic patients. The CSF concentrations of all 3 adipokines increased with BBB dysfunction. RBP4 in CSF correlated positively with inflammatory parameters. In detail, only RBP4 showed the kinetics and associations that are mandatory for a putative mediator of the fat-brain axis. Conclusion RBP4, PEDF, and clusterin are permeable to the BBB and increase with the measure of BBB dysfunction. RBP4 represents an inflammatory neurotrophic adipokine and is a promising mediator of the fat-brain axis.

Background Detailed insights in temporal evolution of high‐sensitivity cardiac troponin following acute coronary syndrome (ACS) are currently missing. We aimed to describe and compare the post‐ACS kinetics of high‐sensitivity cardiac troponin I (hs‐cTnI) and high‐sensitivity cardiac troponin T (hs‐cTnT), and to determine their intra‐ and interindividual variation in clinically stable patients. Methods and Results We determined hs‐cTnI (Abbott) and hs‐cTnT (Roche) in 1507 repeated blood samples, derived from 191 patients with ACS (median, 8/patient) who remained free from adverse cardiac events during 1‐year follow‐up. Post‐ACS kinetics were studied by linear mixed‐effect models. Using the samples collected in the 6‐ to 12‐month post‐ACS time frame, patients were then considered to have chronic coronary syndrome. We determined (differences between) the average hs‐cTnI and average hs‐cTnT concentration, and the intra‐ and interindividual variation for both biomarkers. Compared with hs‐cTnT, hs‐cTnI peaked higher (median 3506 ng/L versus 494 ng/L; P P r spearman =0.60), whereas the average hs‐cTnT concentration was 5 times more likely to be above the upper reference limit than hs‐cTnI. The intraindividual variations of hs‐cTnI and hs‐cTnT were 14.0% and 18.1%, while the interindividual variations were 94.1% and 75.9%. Conclusions Hs‐cTnI peaked higher after ACS and was quicker below the upper reference limit. In the post–6‐month samples, hs‐cTnI and hs‐cTnT were clearly not interchangeable, and average hs‐cTnT concentrations were much more often above the upper reference limit than hs‐cTnI. For both markers, the within‐patient variation fell largely below beween‐patient variation. Registration URL: https://www.trialregister.nl ; unique identifiers: NTR1698 and NTR1106.

What is known and objective While bioavailability of oral voriconazole is known to be >90%, several reports have observed much lower oral bioavailability. The aim of the present study was to assess the oral bioavailability of voriconazole in clinical use by evaluating the change in serum voriconazole concentration in patients who received intravenous-to-oral switch therapy with the same dose of voriconazole. Methods A single-centre, retrospective cohort study was conducted at the 614-bed Gifu University Hospital in Japan. Patients who received intravenous-to-oral switch therapy with the same dose of voriconazole between 1 January 2011 and 31 December 2018 were enrolled in the present study. We evaluated changes in serum voriconazole concentration before and after switch therapy. Results Voriconazole trough concentrations significantly decreased following oral compared to intravenous treatment (2.5 ± 1.5 µg/mL vs 3.3 ± 2.0 µg/mL, p = 0.021). The median change rate of serum concentration by switching the route of administration was 82.7%, with wide inter-individual variability (range 27.2-333.3%). Further, concomitant glucocorticoid administration was a significant protective factor for reducing serum concentration (OR 0.16, 95% CI 0.03-0.79, p = 0.025). What is new and conclusion Switching from intravenous to oral treatment resulted in a significant decline in voriconazole trough concentrations with wide inter-individual variability. Therefore, measurement of serum concentration for dose adjustment should be performed after switching to the oral form.

In a group of 208 patients with chronic ischaemic heart disease, the variation of A2-associated-LDL phosphatase (Lp-PLA2) serum concentration values was analysed in dynamics at a two-week interval. The conclusion of the study is that the values of serum concentration of Lp-PLA2 can be accepted as a biomarker with diagnostic specificity for chronic ischaemic heart disease, a parameter of real utility in medical practice, both in situations where the patient, although clinically reporting the existence of angina pectoris, does not show specific changes on an EKG, and for the assessment of the response to personalised therapy.

Objectives To evaluate acute changes in serum brain-derived neurotrophic factor (BDNF) concentration following combined endurance exercise and heat stress through head-out water immersion (HOI). Setting Observational study with crossover design. Methods Ten healthy young male participants performed HOI at 40 °C (40 °C HOI) or continuous cycling at 60% of maximal oxygen uptake while immersed in 40 °C (40 °C HOI-ex) or 23 °C water (23 °C HOI-ex) for 15 min. Serum BDNF, cortisol and lactate concentrations, and core temperature (Tcore) were measured pre, immediately post, and 15 and 30 min post-immersion. Results BDNF concentration increased immediately and 15 min after 40 °C HOI-ex, but not after 40 °C or 23 °C HOI-ex. No changes in Tcore concentration were observed during 23 °C HOI-ex (Pre; 37.3 °C ± 0.3 °C, Post; 37.8 °C ± 0.2 °C, Post 15; 37.4 °C ± 0.3 °C, Post 30; 37.2 °C ± 0.2 °C). Tcore increased significantly post, post 15, and post 30 min of 40 °C HOI (Pre; 37.1 °C ± 0.4 °C, Post; 38.8 °C ± 0.5 °C, Post 15; 37.9 °C ± 0.4 °C, Post 30; 37.9 °C ± 0.2 °C) and 40 °C HOI-ex (Pre; 37.2 °C ± 0.2 °C, Post; 40.2 °C ± 0.7 °C, Post 15; 38.9 °C ± 0.5 °C, Post 30; 38.3 °C ± 0.5 °C). Tcore was higher in 40 °C HOI-ex compared with 40 °C HOI and 23 °C HOI-ex immediately post and post 15 min. Plasma lactate and cortisol were significantly higher in 40 °C HOI-ex compared with 40 °C HOI and 23 °C HOI-ex after immersion (p = 0.001). Conclusion While 15 min HOI alone or thermoneutral exercise do not increase BDNF concentration, both combined may form a time-efficient strategy to acutely elevate BDNF.

AIMS The aim of this study was to establish the pharmacokinetic profile of serum oestriol (E3 ) concentrations over 24 h following application of vaginal E3 in chronic users (>12 weeks of E3 use). The interindividual and intraindividual differences before and after E3 were examined. METHODS Ten women participated. Vaginal cream was omitted for ≥36 h prior to the study days. Blood sampling was performed for E3 , oestradiol and oestrone concentrations prior to cream application and at 1, 2, 3, 5, 8, 10, 12 and 24 h afterwards. In five women, all samples were repeated on a separate day. RESULTS E3 was absorbed rapidly in most women. Peak serum E3 concentration occurred around 2 h (range 1-5 h). The decline in E3 concentrations was also rapid: falling

STUDY OBJECTIVES: We aimed to investigate whether improvements in the symptoms of circadian rhythm sleep-wake disorder after treatment were associated with an increase in serum insulin-like growth factor-1 (IGF-1) concentration. METHODS: Eighty-seven school-aged children (32 males, 55 females), aged 14.31 ± 1.50 years (mean ± standard deviation), who were admitted to our hospital with circadian rhythm sleep-wake disorder received treatment for 6–8 weeks consisting of the following protocol: (1) lights-out for sleep occurred at 21:00, (2) phototherapy for waking started at 06:00 or 07:00, and (3) light exercise was required every day (eg, a 20- to 30-minute walk). Blood samples were collected at 08:00 am to measure the serum concentrations of IGF-1, pre- and posttreatment. RESULTS: The mean times of day of sleep onset and offset at the pre- and posttreatment timepoints were 23:32 ± 4.21 and 10:27 ± 2.98, and 21:26 ± 0.55 and 06:50 ± 0.70, respectively. The mean times of day of sleep onset and offset measured at the posttreatment timepoint were significantly earlier compared with the pretreatment baselines (P < .01). The mean serum levels of IGF-1 significantly increased from 315.59 ± 68.26 ng/mL at pretreatment to 335.09 ± 69.78 ng/mL at posttreatment (P < .01). CONCLUSIONS: Improvements in the symptoms of patients with circadian rhythm sleep-wake disorders were associated with increased serum concentrations of IGF-1, suggesting that serum IGF-1 may be a biomarker of improvements in school-aged children with circadian rhythm sleep-wake disorder. CITATION: Kimura S, Toyoura M, Toyota Y, Takaoka Y. Serum concentrations of insulin-like growth factor-1 as a biomarker of improved circadian rhythm sleep-wake disorder in school-aged children. J Clin Sleep Med. 2020;16(12):2073–2078.

Per- and polyfluoroalkyl substances (PFAS) exposure may increase adiposity and obesity risk in children. However, no studies have extended these findings into adolescence or identified periods of heightened susceptibility. We estimated associations of repeated pre- and postnatal serum PFAS concentrations with adolescent adiposity and risk of overweight/obesity. We studied 212 mother–offspring pairs from the HOME Study. We quantified serum concentrations of four PFAS in mothers at ~16 week gestation and their children at birth and ages 3, 8, and 12 years. We assessed adiposity at 12 years using anthropometry and dual-energy X-ray absorptiometry. Using multiple informant models, we estimated covariate-adjusted associations of an interquartile range (IQR) increase in log(2)-transformed PFAS for each time period with adiposity measures and tested differences in these associations. Serum perfluorooctanoate (PFOA) and perfluorohexane sulfonate (PFHxS) concentrations during pregnancy were associated with modest increases in central adiposity and risk of overweight/obesity, but there was no consistent pattern for postnatal concentrations. We observed nonlinear associations between PFOA in pregnancy and some measures of adiposity. Overall, we observed a pattern of modest positive associations of gestational PFOA and PFHxS concentrations with central adiposity and the risk of obesity in adolescents, while no pattern was observed for postnatal PFAS concentrations.

Brain-derived neurotrophic factor (BDNF) plays a role in different neurophysiological processes, including those involved in alcohol- and anxiety-related behaviors. Preclinical and clinical studies indicate that chronic excessive alcohol use leads to a downregulation of BDNF production in the periphery and in the brain. In addition, a decrease in BDNF concentrations in the blood has been reported to be associated with increased anxiety levels. Non-treatment-seeking alcohol-dependent individuals with high trait anxiety were studied to assess whether serum BDNF concentrations may be linked to self-reported levels of alcohol drinking, anxiety, and other behavioral measures. Participants had a current diagnosis of alcohol dependence, high trait anxiety score, and were not seeking treatment for alcohol dependence or anxiety. A fasting blood sample was collected from each participant and serum BDNF was measured using an enzyme-linked immunosorbent assay (ELISA). Behavioral data were collected on the same day, including measures of alcohol drinking, craving, dependence severity, and anxiety. Bivariate correlations were run between BDNF levels and behavioral measures. Serum BDNF concentrations were negatively correlated with average drinks per drinking days (r = −0.41, p = 0.02) and positively correlated with obsessive-compulsive drinking scale (r = 0.48, p = 0.007) and state-trait anxiety inventory (r = 0.52, p = 0.003) scores. These findings shed light on the possible role of the BDNF system in the neurobiology of alcohol- and anxiety-related behaviors.

Objective: To compare the effect of Pakistani and American almonds on serum concentration of liver enzymes in coronary artery disease patients. Methods: The randomised controlled trial was conducted at the Cardiology Clinics of Aga Khan University Hospital, Karachi, from February to July, 2012, and comprised patients who were randomised into intervention PA and AA groups and the control NI groups. Subjects in the intervention groups were provided Pakistani and American varieties of almonds 10g/day respectively with instructions to soak them overnight, remove the skin and eat them before breakfast for 12 weeks. The control group underwent no intervention. Serum concentrations of aspartate transaminase, Alanine transaminase and gamma-glutamyl transferase were analysed and compared. Results: Of the 150 subjects, 110(73.3%) completed the study. Of them, there were 38(34.5%) in PA group, 41(37.3%) in AA, and 31(28.2%) in the NI group. Dietary almonds significantly reduced serum concentrations of aspartate transaminase, alanine transaminase and gamma-glutamyl transferase in the two intervention groups compared to the controls group (p

Aims To investigate the impact of cytochrome P450 2D6 (CYP2D6) on dose‐adjusted serum concentrations of flupentixol, haloperidol, perphenazine and zuclopenthixol in a therapeutic drug monitoring (TDM) cohort of psychiatric patients. We also studied the functional impact of CYP2D6*41 on dose‐adjusted serum concentrations in the perphenazine‐treated patients. Methods Serum concentrations of flupentixol, haloperidol, perphenazine and zuclopenthixol from CYP‐genotyped patients were extracted retrospectively from a routine TDM database in the period March 2005 to May 2019. Samples were divided into three CYP2D6 phenotype subgroups according to genotype; normal metabolizers (NMs), intermediate metabolizers (IMs) and poor metabolizers (PMs). The effect of CYP2D6 phenotype on dose‐adjusted serum concentrations of the four antipsychotics was evaluated by multivariable mixed model analyses. Results Mean dose‐adjusted serum concentrations of perphenazine (564 samples) were 3.9‐fold and 1.6‐fold higher in CYP2D6 PMs and IMs, respectively, compared with NMs (P < .001 and P < .01). For zuclopenthixol (658 samples), mean dose‐adjusted serum concentrations were about 1.5‐fold and 1.3‐fold higher in CYP2D6 PMs and IMs, respectively, compared with NMs (P < .01 and P < .001). CYP2D6 was of minor or no importance to haloperidol (320 samples) and flupentixol (115 samples). In our data material, the genotype CYP2D6 *1/*41 appears to have a similar impact on dose‐adjusted serum concentrations of perphenazine as *1/null (null = variant allele encoding no enzyme function). Conclusions This study shows that CYP2D6 is important for the metabolism of perphenazine and zuclopenthixol, but not for haloperidol and flupentixol. The CYP2D6*41 allele appears to have a reduced function close to nonfunctional variant alleles.

The blood brain barrier (BBB) is a major obstacle to the delivery of therapeutics to the brain. Focused ultrasound (FUS) in combination with microbubbles can non-invasively open the BBB in a targeted manner. Bolus intravenous injections of microbubbles are standard practice, but dynamic influx and clearance mechanisms prevent delivery of a uniform dose with time. When multiple targets are selected for sonication in a single treatment, uniform serum concentrations of microbubbles are important for consistent BBB opening. Herein, we show that bubble infusions were able to achieve consistent BBB opening at multiple target sites. FUS exposures were conducted with different Definity microbubble concentrations at various acoustic pressures. To quantify the effects of infusion on BBB opening, we calculated the MRI contrast enhancement rate. When infusions were performed at rates of 7.2 µl microbubbles/kg/min or below, we were able to obtain consistent BBB opening without injury at all pressures. However, when infusion rates exceeded 20 µl/kg/min, signs of injury occurred at pressures from 0.39 to 0.56 MPa. When compared to bolus injections, a bubble infusion offers a more controlled and consistent approach to multi-target BBB disruption.

Purpose Tiapride is commonly used in Europe for the treatment of tics. The aim of this study was to examine the relationship between dose and serum concentrations of tiapride and potential influential pharmacokinetic factors in children and adolescents. In addition, a preliminary therapeutic reference range for children and adolescents with tics treated with tiapride was calculated. Methods Children and adolescents treated with tiapride at three university hospitals and two departments of child and adolescents psychiatry in Germany and Austria were included in the study. Patient characteristics, doses, serum concentrations, and therapeutic outcome were assessed during clinical routine care using standardised measures. Results In the 49 paediatric patients (83.7% male, mean age = 12.5 years), a positive correlation was found between tiapride dose (median 6.9 mg/kg, range 0.97–19.35) and serum concentration with marked inter-individual variability. The variation in dose explained 57% of the inter-patient variability in tiapride serum concentrations; age, gender, and concomitant medication did not contribute to the variability. The symptoms improved in 83.3% of the patients. 27.1% of the patients had mild or moderate ADRs. No patient suffered from severe ADRs. Conclusions This study shows that tiapride treatment was effective and safe in most patients with tics. Compared with the therapeutic concentration range established for adults with Chorea Huntington, our data hinted at a lower lower limit (560 ng/ml) and similar upper limit (2000 ng/ml).

In this study, we aimed to determine serum concentrations of carotenoids and fat-soluble vitamins (FSVs) in ovarian cancer (OC) patients categorized by clinical and nutritional status and to compare obtained results with healthy controls. We used single-step extraction methods throughout the study. Serum concentrations of the bioactive compounds were measured using HPLC. The evaluation of the nutritional status of patients was performed with scored PG-SGA questionnaire.The serum bioactive compound levels were significantly lower in early-stage OC patients (FIGO I/II) when compared to healthy controls for

Objective: To determine whether changes in serum galectin-3 (gal-3) concentrations in schizophrenia patients have etiopathogenetic importance. Since very little research has assessed the connection between galectins and schizophrenia, we wanted to examine alterations in the inflammatory marker gal-3 in schizophrenia and investigate possible correlations between clinical symptomatology and serum concentrations. Methods: Forty-eight schizophrenia patients and 44 healthy controls were included in this study. The Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS) were administered to determine symptom severity. Venous blood samples were collected, and serum gal-3 levels were measured. Results: Mean serum gal-3 levels were significantly lower in schizophrenia patients, and there were no significant differences in age or sex with the control group. There was also a significant positive correlation between serum gal-3 concentrations and negative schizophrenia symptoms according to the SANS. Conclusion: The results indicate that gal-3 is decreased in schizophrenia patients, which could contribute to inflammation in the pathogenesis of schizophrenia.

Measuring handgrip strength is the initial step to diagnose sarcopenia. To investigate whether the serum creatinine (Cr)/cystatin C (CysC) ratio could serve as a case-finding tool for low handgrip strength, we conducted a diagnostic accuracy study. Adults (aged ≥ 40 years) with normal renal function were recruited. Trained nurses collected blood samples and conducted the anthropometric measurements and handgrip strength test. The serum concentrations of Cr, CysC, and other biomarkers were measured. We recruited 1098 men and 1241 women. The Cr/CysC ratio was significantly associated with AWGS-defined low handgrip strength among men and women. The areas under the receiver operating characteristic curves were 0.79 among men and 0.78 among women for using the Cr/CysC ratio to identify AWGS-defined low handgrip strength. We set the Cr/CysC ratio cut-off values at

Photodynamic therapy (PDT) schedules are based on sensitiser dose, light dose, and drug-light interval. The aim of the phase Ι study was to choose optimal dose and drug-light interval for PDT with photocyanine using pharmacokinetics (PK) and pharmacodynamics (PD). Twenty-eight cancer patients were enrolled. In trial A, 12 patients received one of four ascending doses of photocyanine intravenously 24 h prior to 180–270 J/cm2 illumination. 0.2 mg/kg dose was infused to ten patients 12–48 h prior to 120 J/cm2 illumination in trial B. In trial C, 0.1 mg/kg dose was infused to six patients 6 or 12 h prior to 180–270 J/cm2 illumination. Serum concentrations of photocyanine were measured, and simulations were performed to assess the effect of drug exposure in tissue on responses. Analysis of photocyanine levels of patients indicated that the two-compartment model best fit the data. Simulations showed that the rates of the drug entering tissues and leaving tissues were equal at 8–12 h after injection. Patients experienced pain which was related to photocyanine serum levels, especially with serum levels above 2500 ng/ml. Fewer non-responders were observed at serum levels higher than 1000 ng/ml for illumination at least 12 h after administration. It is the first report of human trials of photocyanine, and the results suggested that patients receive 180 J/cm2 illumination about 20–30 min at serum concentrations of photocyanine between 1000 and 2500 ng/ml at least 10 h after administration.

Background:The therapeutic reference range for venlafaxine in antidepressant treatment has been defined as 100 to 400 ng/mL. However, in an everyday setting active moiety concentrations above the therapeutic reference range were often reported.Aim:The aim of this study was to re-evaluate the therapeutic reference range of venlafaxine.Methods:In-patients (⩽60 years) with major depressive episodes receiving antidepressant monotherapy with venlafaxine during routine clinical treatment were included in this observational study. Depressive symptom severity was evaluated on a weekly basis using the Hamilton Depression Rating Scale (HAMD-21), and therapeutic drug monitoring analyses were performed. Resting electrocardiograms were analyzed in week 3, week 5 and week 7 of study participation.Results:Clinical improvement from baseline to week 4 was significantly associated with increasing serum concentrations of the active moiety of venlafaxine ( N = 23, Pearson correlation, p = 0.009), but not with the dose of venlafaxine. Patients achieving remission showed significantly higher serum concentrations than patients achieving response/non-response (Kruskal–Wallis test, p = 0.019). Moreover, in patients with serum concentrations above 400 ng/mL time to remission and time to response was significantly shorter than in patients with concentrations below 400 ng/mL (Mantel–COX test, p = 0.001; p = 0.010). QTc time was below the upper limit of a normal QTc time (450 ms) for all patients.Conclusion:The serum concentration of the active moiety and not the dose determined the effect of venlafaxine. Shorter remission times without ECG alterations in patients with serum concentrations above the therapeutic reference range suggest a re-evaluation of the therapeutic reference range for venlafaxine in larger studies.

Background: Case reports and pharmacokinetic data suggest off-label echinocandin dosing may be needed to reach adequate serum concentrations in obese patients. Few outcome studies exist evaluating this population. Objectives: Of this study were to (1) determine the association of body mass index (BMI) with clinical outcomes of candidemia patients on standard doses of anidulafungin and (2) characterize fungal infections by body weight. Methods: A retrospective cohort was conducted to evaluate hospitalized patients treated for candidemia with anidulafungin at Food and Drug Administration–labeled dosing for at least 72 hours from January 1, 2014, through January 31, 2018. Candidemia was diagnosed by blood culture or T2 magnetic resonance (T2MR). Patients were compared according to BMI category. Results: One hundred seventy-three patients were included. Candida albicans and Candida glabrata were identified in 58 (33%) and 57 (33%) patients, respectively. Mortality was comparable according to BMI category: 4 (36.4%) underweight, 8 (25.8%) normal weight, 16 (32.0%) overweight, 20 (33.9%) obese, and 7 (31.8%) morbidly obese, P = .976. Variables associated with mortality included: severe sepsis (adjusted odds ratio [OR] = 5.1, 95% CI: 1.7-14.8) and liver disease (adjusted OR = 3.2, 95% CI: 1.1-9.4). Variables that were protective of mortality included: line removal (adjusted OR = 0.05, 95% CI: 0.02-0.2) and receipt of anidulafungin for at least 5 days (adjusted OR = 0.35, 95% CI: 0.15-0.8). Conclusion: There was no difference detected in mortality among patients with candidemia across BMI category. Larger studies are needed to confirm whether standard doses of anidulafungin are sufficient for candidemia in obese patients.

Summary. Background: This study attempted to correlate neurological symptoms in awake patients undergoing carotid endarterectomy (CEA) under local anaesthesia (LA) with serum concentration of S100B protein and measurement of cerebral oximetry with near-infrared spectroscopy (NIRS). Patients and methods: A total of 64 consecutive CEAs in 60 patients operated under LA during an 18-month period were prospectively evaluated. A cerebral oximeter was used to measure cerebral oxygen saturation (rSO2) before and after cross-clamping along with serum concentration of the S100B protein. Selective shunting was performed when neurological changes occurred, regardless of NIRS. Neurological deterioration occurred (neurological symptoms group) in 7 (10.9 %) operations. In 57 (89.1 %) operations, the patients were neurologically stable (no neurological symptoms group). Results: The neurological symptoms that occurred after clamping correlated with an increase in the serum level of S100B ( P = .040). The cut-off of 22.5 % of S100B increase was determined to be optimal for identifying patients with neurological symptoms. There was no correlation between rSO2 decline and neurological symptoms ( P = .675). Two (3.1 %) perioperative strokes occurred. Conclusions: We found a correlation between neurological symptoms and serum S100B protein increase. However, because of the long evaluation time of serum S100B, this monitoring technique cannot be performed during CEA.

Comparative analysis of serum concentrations of chorionic gonadotropin (hCG) associated with the pregnancy of plasma protein A (PAPP-A) and alpha-fetoprotein (AFP), based on the results of a survey of women as part of a standard screening program (the results were expressed as a MoM - multiply of the median), found a significant increase in the performance of all the studied specific pregnancy proteins in women with a scar on the uterus and placenta acctera (75 patients) compared with the data of the group of pregnant women without scar on the uterus and without abnormalities of attachment of the placenta (150 women). AFP indices were 1.68 ± 0.76 and 1.19 ± 0.43 MoM (p = 0.0018), hCG - 1.62 ± 1.48 and 1.23 ± 0.76 MoM (p = 0, 0112), PAPP-A - 1.93 ± 1.24 and 1.23 ± 0.67 MoM (p

Objective:Studies have reported an inverse association between a diet rich in fruits and vegetables and type 2 diabetes (T2D), but data on high-risk ethnic minority groups is limited. We investigated whether serum carotenoids, as biomarkers for fruit and vegetable intake, mediate ethnic differences in the prevalence of T2D.Design:Age-adjusted serum carotenoid concentrations were compared using ANCOVA. A cross-sectional analysis was performed using Cox regression to estimate prevalence ratios (PR) and their 95 % CI of the association between serum carotenoid concentrations and T2D. To study whether serum carotenoids potentially mediate the differences in the prevalence of T2D across ethnic groups, we compared PR of the model including known risk factors and the model additionally adjusted for serum carotenoid concentrations using the Dutch group as reference.Setting:A study among six ethnic groups living in Amsterdam, the Netherlands.Participants:Data on 204 Dutch, 203 South Asian Surinamese, 204 African Surinamese, 203 Turkish and 200 Moroccan-origin participants from the Healthy Life in an Urban Setting (HELIUS) study were used.Results:Serum carotenoid concentrations differed across ethnic groups. After adjusting for confounders, the serum concentrations of total carotenoids (PR 0·67, 95 % CI 0·54, 0·84), α-carotene (PR 0·57, 95 % CI 0·42, 0·77), β-carotene (PR 0·45, 95 % CI 0·32, 0·63) and β-cryptoxanthin (PR 0·73, 95 % CI 0·58, 0·92) were inversely associated with T2D. Despite the associations, serum carotenoids did not mediate the ethnic differences in the prevalence of T2D.Conclusions:The limited contribution of serum carotenoids to ethnic differences in T2D suggests that a focus on increasing fruit and vegetable intake alone will not likely eliminate ethnic differences in T2D prevalence.

Background Vitamin D insufficiency and deficiency in childhood are common. However, the status and influential factors of vitamin D during different ages are not clear. This study aimed to survey vitamin D concentrations in children aged 0 to 6 years and explore its influential factors. Methods A total of 6953 children were recruited in Wuxi City of East China from January to December in 2016. Enzyme-linked immunosorbent assay was used to determine the serum concentrations of 25-hydroxyvitamin D [25(OH)D]. Results The median vitamin D concentrations in the infant group (0–1 years of age) was 69.40 nmol/L, which were higher than that in both the toddlerhood group (1–3 years of age; 62.30 nmol/L) and the preschool group (3–6 years of age; 50.85 nmol/L). In addition, the median vitamin D concentrations were 71.70 nmol/L in summer, which was higher than that in spring (64.25 nmol/L), autumn (62.95 nmol/L) and winter (64.10 nmol/L). However, no difference was observed between genders (P = 0.974). Furthermore, the prevalence of vitamin D deficiency ( Conclusions A high prevalence of vitamin D deficiency was common in a Chinese population of children 0–6 years old, especially in the preschool-aged children. Therefore, we suggested that we should pay more attention to vitamin D supplementation in Chinese young children.

Objective Inflammation has been proposed to have a pathophysiological role in anorexia nervosa (AN) and to contribute to the maintenance of the disorder. Longitudinal cytokine research in AN has focused on only a few pro-inflammatory cytokines. We assessed a broad range of cytokines over time in people undergoing specialised treatment for AN. Method We measured serum concentrations of 27 cytokines in people with AN (n = 23). Body mass index (BMI), eating disorder (ED) symptoms and general psychopathology were assessed and blood samples were collected within four weeks of the commencement of specialised ED treatment (baseline) and at 12- and 24-week follow-ups. Results Both BMI and ED symptoms improved over the assessment period. Linear mixed models showed that log IL-6 decreased between baseline and week 12 assessments. By week 12, log IL-6 values were comparable to levels in healthy individuals. Log IL-7 increased from week 12 to week 24. Discussion Initially elevated IL-6 serum concentrations appear to ‘normalize’ during the first 3-months of specialised treatment for AN and this co-occurs with improvements in ED symptoms. Therefore, IL-6 has the potential to be a state biomarker for AN.

PURPOSE To analyze the relevance between serum IL-6 with the early postoperative (post-op) knee joint range of motion (ROM) in the elderly undergoing total knee arthroplasty (TKA). To evaluate the factors affecting early post-op knee joint ROM in the elderly after TKA. METHODS One hundred and forty-three patients undergoing TKA were included. The patients' general data, perioperative knee joint ROM and serum IL-6, pre-op HSS, WOMAC, SF-36 scores and Wells scores were collected. Repeated data variance analyses were performed to analyze the relevance between serum IL-6 with post-op knee joint ROM. Correlative regression and regression analysis were performed to evaluate the multiple factors affecting knee joint ROM in the elderly undergoing TKA. RESULTS The 2-week-post-op (2w-post-op) knee joint ROM was significantly higher in the low IL-6 serum concentration group (< 46.45 ng/L) than in the high group (⩾ 46.45 ng/L) (97.78 ± 7.44∘VS 91.85 ± 7.42∘, F= 16.860, P= 0.000). A significant negative correlation was found between 1d-post-op serum IL-6 concentration with 2w-post-op knee joint ROM (R=-0.513, P= 0.000). The factors influencing the 2w-post-op knee joint ROM included pre-op HSS scores, pre-op WOMAC scores and whether to retain PCL (posterior cruciate ligament) (R2= 0.451, P= 0.009). CONCLUSION A higher 1d-post-op IL-6 serum concentration indicated a lower knee joint ROM in the elderly two weeks after TKA.