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Objective: Adrenocorticotropic hormone (ACTH) and β-endorphin are pituitary neuro-peptides released by acute stress. We determined why the prognosis of patients with subarachnoid hemorrhages (SAH) due to aneurysmal rupture is not always dependent on the Hunt–Hess grading system (HHS) and delta-National Institutes of Health Stroke Scale (NIHSS), while studying endogenous neuropeptides, including ACTH and β-endorphin.Methods: We analyzed blood samples collected from patients with SAH (SAH group; n=37) and those with unruptured intracranial aneurysms (control group; n=37). Blood sampling was performed before any procedure or chemical agents administration. The results of ACTH and β-endorphin measurements were compared using the delta-NIHSS and HHS. The data were analyzed using descriptive statistics, independent samples t-tests, and Pearson’s correlations.Results: Of the 18 patients with low-grade HHS, 13 had low delta-NIHSS and five showed high delta-NIHSS. Of the 19 patients with high-grade HHS, the delta-NIHSS was ≥14 in the other five patients. ACTH concentration was high (497.3 pg/mL) in five patients with high-grade HHS and high delta-NIHSS. β-endorphin concentration was high (159.7 pg/mL) in 13 patients with low-grade HHS and low delta-NIHSS.Conclusions: High ACTH levels in patients with massive bleeding and poor neurological status suggests increasing ACTH secretion in response to bleeding stress, which may aggravate neurological status. Contrary to ACTH, high β-endorphin levels in patients with low-grade HHS implied the involvement of additional factors in predicting fair outcomes related to low delta-NIHSS. These results may provide insight into the varying prognostic potential of HHS in SAH patients.

BACKGROUND High levels of inflammation pre- and post-percutaneous coronary intervention (PCI) are associated with worse outcomes. Recent trials have suggested a benefit from treating inflammation with colchicine in coronary artery disease. In this randomised pilot COPE-PCI sub-study, we aimed to determine if administration of colchicine pre-PCI, would attenuate the inflammatory effect of PCI. METHODS PCI patients were randomised to colchicine or placebo, 6 to 24-hours pre-procedure. Study blood samples were taken immediately pre-PCI, and 24-hours post-procedure. Samples were tested for a broad array of inflammatory biomarkers including high-sensitive(hs)-CRP, leucocyte counts, and hs-troponin-. Periprocedural Myocardial Injury (PM-Injury) was defined as per the ESC Third Universal Definitions of Myocardial Infarction. RESULTS Thirty-six were randomised to colchicine and 39 to placebo. Treatment groups were similar for baseline variables. The median time from drug administration to pre-PCI blood sampling was 18-hours. Overall inflammation was low across the patient population, pre- & post-PCI hsCRP was

Background Intravascular imaging has defined various vulnerable plaque (VP) phenotypes that predict future clinical events. Atherosclerosis is an inflammatory process and inflammation, measured by systemic biomarkers can also predict events and anti-inflammatory therapy is beneficial. We were interested to assess the relationship between plaque phenotypes and key inflammatory biomarkers, measured close to the coronary. Methods Ninety-two patients scheduled for elective percutaneous coronary intervention (PCI) underwent virtual histology intravascular ultrasound, optical coherence tomography, pressure wire and blood sampling from the guide catheter (GC), coronary sinus (CS) to determine trans-myocardial gradient (TMG = CS-GC) and from peripheral blood. Procedure related troponin release was assessed at 6-hours post-PCI from peripheral venous blood. Biomarker data were analysed and compared with coronary data. Results Interleukin (IL)-6 was associated with increased levels of tumour necrosis factor (TNF)-α and C-reactive protein (CRP) and the pre-PCI IL-6 TMG correlated with plaque features of vulnerability: plaque burden - PB (r = 0.253, p = 0.04) and minimal lumen area - MLA (r = −0.438, p = 0.007), although no relationship existed for thin-capped fibroatheroma defined by either imaging modality. Peripheral IL-6 levels had no correlation with post PCI troponin, although the pre-PCI IL-6 TMG was related (r = 0.334, p = 0.006), as was PB (r = 0.27, p = 0.029). Conclusion IL-6 TMG pre-PCI correlates with plaque burden and MLA that have been shown to predict future clinical events and is correlated with post-PCI troponin release. These associations were not apparent from peripheral blood and suggest that local coronary biomarker signatures may help further define vulnerability and risk.

The incidence and mortality rate of sepsis is increasing worldwide. Rapid and accurate detection of bacteremia and fungemia is essential to improve the patient’s condition. Health care providers, nurses, and possibly many laboratory staff are usually not well trained in proper blood culture techniques.The present guideline addresses the clinical importance of blood culture, its applications, and the correct technique for detecting pathogenic microorganisms that cause sepsis, and attempts to explain the place of blood culture in the management of sepsis and the appropriate method for obtaining a blood sample for culture. Describe false positives to reduce.Detection of bacteremia or fungi by blood culture is very important and vital in the management of patients with infection and can lead to the selection of appropriate antibiotics. Blood cultures (BCs) are important routine tests that are conducted in the clinical microbiology laboratory. Unfortunately, the common rate of BCs contamination is high which led to many clinical and economic consequences. The phlebotomy teams of blood sampling are very important to effectively reduce BCs contamination rate. Therefore, we conducted the current study to update our knowledge about the phlebotomy performances

Background Gastric and colorectal cancer (CRC) are both one of the most common cancers worldwide. In many countries fecal immunochemical tests (FIT)-based CRC screening has been implemented. We investigated if FIT can also be applied for detection of H. pylori, the main risk factor for gastric cancer. Methods This prospective study included participants over 18 years of age referred for urea breath test (UBT). Patients were excluded if they had used antibiotics/bismuth in the past 4 weeks, or a proton pomp inhibitor (PPI) in the past 2 weeks. Participants underwent UBT, ELISA stool antigen test in standard feces tube (SAT), ELISA stool antigen test in FIT tube (Hp-FIT), and blood sampling, and completed a questionnaire on user friendliness. UBT results were used as reference. Results A total of 182 patients were included (37.4% male, median age 52.4 years (IQR 22.4)). Of these, 60 (33.0%) tested H. pylori positive. SAT and Hp-FIT showed comparable overall accuracy 71.1% (95%CI 63.2–78.3) vs. 77.6% (95%CI 70.4–83.8), respectively (p = 0.97). Sensitivity of SAT was 91.8% (95%CI 80.4–97.7) versus 94.2% (95%CI 84.1–98.9) of Hp-FIT (p = 0.98). Serology scored low with an overall accuracy of 49.7% (95%CI 41.7–57.7). Hp-FIT showed the highest overall user convenience. Conclusions FIT can be used with high accuracy and sensitivity for diagnosis of H. pylori and is rated as the most convenient test. Non-invasive Hp-FIT test is highly promising for combined upper and lower gastrointestinal (pre-) cancerous screening. Further research should investigate the clinical implications, benefits and cost-effectiveness of such an approach.

OBJECTIVE 1) Describe the progression of diabetes mellitus over time in an observational study of Wolfram syndrome, a rare, genetic, neurodegenerative disorder which often includes diabetes mellitus and is typically diagnosed during childhood or adolescence. 2) Determine whether C-peptide could be used as a marker of diabetes progression in interventional trials for Wolfram syndrome. METHODS N=44 (25F/19M) participants with genetically-confirmed Wolfram syndrome attended the Washington University Wolfram Research Clinic annually from 2010-2019. Medical history, physical examinations, blood sampling, and questionnaires were used to collect data about diabetes mellitus and other components of Wolfram syndrome. Beta-cell function was assessed by determination of C-peptide during a mixed meal tolerance test. Random coefficients models evaluated the rate of progression of C-peptide over time, and power analyses were used to estimate the number of subjects needed to detect a change in C-peptide decline during an intervention trial. RESULTS 93.2% of patients had diabetes mellitus. Mean HbA1c across all study visits was 7.9%. C-peptide significantly decreased with increasing duration of diabetes mellitus (p

AIM Birth asphyxia can lead to organ dysfunction, varying from isolated biological acidosis to hypoxic-ischemic encephalopathy (HIE). Pathophysiology of moderate or severe HIE is now well known and guidelines exist regarding the care required in this situation. However, for newborns without moderate or severe HIE, no consensus is available. Our objective was to describe the immediate neonatal consequences and need for care of asphyxiated newborns without moderate or severe HIE. METHODS Multicentre retrospective study from January 2015 to December 2017 in two academic centres, including neonates ≥37 gestational weeks with pathological foetal acidemia (umbilical arterial pH

Relevance. The consumption of caffeine-containing food in the modern world must necessarily be safe for humans, including should not affect the hereditary material of the body. Objective: to determine the possible effect of caffeine at the cytogenetic level by the micronucleus method on erythrocytes. Materials and Methods. The objects for the study were non-linear mice, which were divided into 6 groups - one control group and 5 experimental groups. The first experimental group and the second in the experiment received caffeine in doses of 40 mg/kg and 100 mg/kg.The control group received saline. Caffeine was administered orally. The mutagen (dioxidine) was injected intraperitoneally. On the 5th day of the experimental study, we performed blood sampling for cytogenetic analysis. Results and Discussion. Our study of the caffeine preparation made it possible to determine the following patterns. Firstly, when administered within 5 days, caffeine at a dose of 40 and 100 mg/kg did not cause an increase in the number of micronuclei in erythrocytes in mice. Secondly, the combined use of caffeine (both at a dose of 40mg/kgand at a dose of 100 mg / kg) and dioxidine significantly increased the level of micronuclei in comparison with the control group. Thirdly, caffeine at a dose of 40mg/kgdid not increase the mutagenic activity of dioxidine, but a dose of caffeine of 100mg/kgwhen combined with a mutagen led to a significant increase in the level of cytogenetic damage. Conclusion. According to our data, caffeine in the experimental study was not a mutagen, but at a dose of 100 mg/kg it represented a comutagenic effect.

This study monitored the long-term immune response to severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection in patients who had recovered from coronavirus disease (COVID)-19. Anti-nucleocapsid immunoglobulin G (anti-N IgG) titer in serum samples collected at a single (N = 302) or multiple time points (N = 229) 3–12 months after COVID-19 symptom onset or SARS-CoV-2 detection in respiratory specimens was measured by semiquantitative chemiluminescent microparticle immunoassay. The 531 patients (966 specimens) were classified according to the presence or absence of pneumonia symptoms. Anti N IgG was detected in 87.5% of patients (328/375) at 3 months, 38.6% (93/241) at 6 months, 23.7% (49/207) at 9 months, and 26.6% (38/143) at 12 months. The anti-N IgG seropositivity rate was significantly lower at 6, 9, and 12 months than at 3 months (P P P = 0.04), and 12 months (P = 0.04). The rate started to decline 6–12 months after symptom onset. Anti-N IgG sample/cutoff index was positively correlated with age (r = 0.192, P P

Background and aims: An association between hypoglycaemia and adverse cardiovascular events has been suggested from longitudinal and retrospective cohort studies. The complement pathway proteins in hypoglycemia are not well studied. Here, we hypothesized that these circulating proteins would be elevated in response to hypoglycemia in type 2 diabetes (T2D) through the inflammatory response. Methods: A prospective, parallel study in T2D (n = 23) and controls (n = 23). Subjects underwent insulin-induced hypoglycemia with blood sampling at baseline, hypoglycemia and post-hypoglycemia; SOMAscan proteomic analysis of complement pathway-related proteins, cytokines and inflammatory proteins was undertaken. Results: At baseline: Complement C2 (p

Objective The study was performed to investigate the effect of two different lancets and heel warming during blood sampling from the heel on procedure duration and crying. Methods This was a randomized controlled trial study. The data were obtained from the Newborn Intensive Care Unit of a hospital in Istanbul between January 2015 and January 2016. One hundred twenty newborns were randomly assigned to four groups — automatic lancet with/without warming and manual lancet with/without warming. The newborns were administered heel puncture for routine blood bilirubin monitoring. Result There was no statistically significant difference between the four groups in terms of the characteristics that could affect the outcome of the study. The infants in the manual lancet group without warming were found to have longer duration of crying and longer procedure durations than the other groups. The procedure durations of infants in the manual lancet group with warming were significantly longer than those in the automatic lancet group with warming. Conclusion This study show that both heel warming and using automatic lancet are effective in reducing the durations of the procedure and crying during blood sampling from the heel.

Introduction Nurses' use of evidence-based pain treatments for newborns during needle-related procedures in China was unknown. This study aimed to ascertain knowledge and use of pain management strategies and usefulness of a publicly accessible 'BSweet2Babies' video, produced in Mandarin, demonstrating the use of breastfeeding, skin-to-skin care (SSC), and sweet solutions during painful procedures. Methods An online survey was conducted during six nursing conferences in China ascertaining nurses' previous viewing of the video and knowledge and use of the demonstrated strategies. Results 221 nurses participated. Only 25 (11.3%) had previously seen the video. Over half knew that breastfeeding (n = 138, 62.4%) and SSC (n = 173, 78.3%) reduced pain, and 89 (40.3%) knew that sucrose reduced pain, but these strategies were infrequently used. Most intended to use the strategies in the future. Discussion A knowledge-to-action gap for newborn pain management was identified. Future research is needed to improve the implementation of effective pain treatment for newborns.

Purpose Inpatient diabetes management involves frequent assessment of glucose levels for treatment decisions. Here we describe a program for inpatient real-time continuous glucose monitoring (rtCGM) at a community hospital and the accuracy of rtCGM-based glucose estimates. Methods Adult inpatients with preexisting diabetes managed with intensive insulin therapy and a diagnosis of coronavirus disease 2019 (COVID-19) were monitored via rtCGM for safety. An rtCGM system transmitted glucose concentration and trending information at 5-minute intervals to nearby smartphones, which relayed the data to a centralized monitoring station. Hypoglycemia alerts were triggered by rtCGM values of ≤85 mg/dL, but rtCGM data were otherwise not used in management decisions; insulin dosing adjustments were based on blood glucose values measured via fingerstick blood sampling. Accuracy was evaluated retrospectively by comparing rtCGM values to contemporaneous point-of-care (POC) blood glucose values. Results A total of 238 pairs of rtCGM and POC data points from 10 patients showed an overall mean absolute relative difference (MARD) of 10.3%. Clarke error grid analysis showed 99.2% of points in the clinically acceptable range, and surveillance error grid analysis showed 89.1% of points in the lowest risk category. It was determined that for 25% of the rtCGM values, discordances in rtCGM and POC values would likely have resulted in different insulin doses. Insulin dose recommendations based on rtCGM values differed by 1 to 3 units from POC-based recommendations. Conclusion rtCGM for inpatient diabetes monitoring is feasible. Evaluation of individual rtCGM-POC paired values suggested that using rtCGM data for management decisions poses minimal risks to patients. Further studies to establish the safety and cost implications of using rtCGM data for inpatient diabetes management decisions are warranted.

Occurrence of the premature birth in Ukraine is about 6%. Premature newborns are the highest risk group of developing chronic pathology of the nervous system, sensory organs, and respiratory system, causing neonatal mortality and disability; the latter is 22 times higher in premature newborns than in full-term ones. Besides, there is a large group of rare metabolic disorders that significantly disrupt the adaptation and nursing of newborns with signs of morpho-functional and enzymes immaturity. The efficacy of medical care of premature newborns to a great extent relates to prompt diagnosis as common somatic, as rare metabolic disorders.In view of the absence of specific symptoms, it is almost impossible to establish a diagnosis of inherited metabolic disordersduring the clinical examination of a neonate.Expanded newborn screening (ENBS) for inborn errors of metabolism (IEMs) proved to be an effective tool to single out newborns with genetic deficiency of certain metabolic enzymes.The practical experience of performingENBS indicates a problematic issue is the interpretation of results for preterm babies.This article is discussed the key factors affecting the predictive value of ENBS results in premature newborns, like peculiarities of blood sampling based on time intervals from delivery for certain nosologies, repeated sample taking for lab examination considering the basic principles of 2-nd Edition of CLSI "Guideline "Newborn Screening for Preterm, Low Birth Weight, and Sick Newborns, 2019". The CLSI Guideline presents the consensus solutions of a global team of neonatologists, metabolic paediatricians and medical geneticists regarding the accuracy, reliability and timing of laboratory determinations of IEM markers in the blood, as well as a set of factors to consider interpreting ENBS results for premature, low birth weight and newborns with perinatal pathology.The current procedure for neonatal screening for premature babies in Ukraine should be updated to modern requirements of the relevant clinical recommendations of world-recognized medical institutions, including CLSI. The critical issue in improving the quality and reliability of neonatal screening for preterm babies is multiple (repeated) blood sampling for laboratory determination of levels of biochemical IEM markers.A properly established and well- functioning system of expanded neonatal screening proved to be a highly effective tool for reducing early infant mortality and disability associated with inherited metabolic diseases.

Obtaining a rapid etiological diagnosis for infants with early-onset rare diseases remains a major challenge. These diseases often have a severe presentation and unknown prognosis, and the genetic causes are very heterogeneous. In a French hospital network, we assessed the feasibility of performing accelerated trio-genome sequencing (GS) with limited additional costs by integrating urgent requests into the routine workflow. In addition to evaluating our capacity for such an approach, this prospective multicentre pilot study was designed to identify pitfalls encountered during its implementation. Over 14 months, we included newborns and infants hospitalized in neonatal or paediatric intensive care units with probable genetic disease and in urgent need for etiological diagnosis to guide medical care. The duration of each step and the pitfalls were recorded. We analysed any deviation from the planned schedule and identified obstacles. Trio-GS was performed for 37 individuals, leading to a molecular diagnosis in 18/37 (49%), and 21/37 (57%) after reanalysis. Corrective measures and protocol adaptations resulted in a median duration of 42 days from blood sampling to report. Accelerated trio-GS is undeniably valuable for individuals in an urgent care context. Such a circuit should coexist with a rapid or ultra-rapid circuit, which, although more expensive, can be used in particularly urgent cases. The drop in GS costs should result in its generalized use for diagnostic purposes and lead to a reduction of the costs of rapid GS.

BACKGROUND: The prevalence of dyslipidemia, a risk factor of cardiovascular disease, is at present sufficiently high, particularly in the elderly. Health-related quality of life (HRQoL) is also an important outcome in the treatment of dyslipidemia, which is currently more targeted at lowering the low-density lipoprotein cholesterol (LDL-C) concentration. AIM: The aim of this study was to determine the relationship between the high-density lipoprotein cholesterol (HDL-C) concentration and HRQoL in community-dwelling women aged 50–70 years. METHODS: A cross-sectional study involving 137 women aged 50–70 years who underwent blood sampling for determining the concentrations of hemoglobin, total cholesterol (TC), LDL-C, and HDL-C. A questionnaire was given to all subjects regarding data on age, menopausal status, level of education, and also another questionnaire of SF-36 for evaluation HRQoL. Bivariate and multivariate logistic regression analysis was used to identify risk factors associated with HRQoL. RESULTS: In bivariate logistic regression analysis, age, menopausal status, education level, anemia, TC, and LDL-C were found to have non-statistically significant association with HRQoL, but HDL-C was significantly associated with HRQoL (odds ratio = 0.44; 95% Confidence interval [CI] = 0.20–0.97; p = 0.042). In multivariate analysis, menopausal status and education level have a non-statistically significant association with HRQoL, but those normal level of HDL cholesterol was found 0.18 times less likely to be associated with poor HRQoL (Adjusted odds ratio 0.18; 95% CI = 0.03–0.91; p = 0.038). CONCLUSION: This study showed that HDL-C levels were risk factors of HRQoL in women 50–70 years of age.

Diabetic retinopathy is the leading cause of vision loss and impairment in developed countries. Inflammation is considered one of the main reasons for the progression of diabetes complications. We investigated the relationship of monocyte/high-density lipoprotein-cholesterol ratio (MHR) with type 2 diabetes mellitus (T2DM) and diabetic retinopathy (DR). A total of 118 T2DM patients, 60 of whom had DR, and 58 age- and sex-matched healthy controls were included in this cross-sectional study. MHR was calculated by blood sampling after a complete ophthalmologic examination on all subjects. MHR was higher in T2DM patients with DR compared to both the control group and without DR (p=0.018). There was a significant positive correlation between MHR and DR (r=0.256 p=0.004). Additionally, MHR was an independent predictor of DR according to multivariate regression analysis (OR=1.197, p=0.009). DR could be predicted with 92% sensitivity and 84% specificity when MHR was 16.05, whereas DR predicted with 100% sensitivity and 98% specificity when MHR was 23 in ROC curve analysis (AUC: 0.356, 95% CI 0.251–0.460, p = 0.008). This study showed that patients with T2DM may be more likely to develop DR when they have high MHR values. Based on these results, clinicians can also use MHR as a new laboratory marker to predict DR.

BACKGROUND/AIM Prompted by the increasing demand of non-invasive diagnostic tools for screening of gastric cancer (GC) risk conditions, i.e., atrophic gastritis (AG) and Helicobacter pylori (Hp) infection, the GastroPanel® test (GP: biomarker panel of PGI, PGII, G-17, Hp IgG ELISA) that was developed in the early 2000's, was recently updated to a new-generation (unified GP) test version. This clinical validation study evaluated the diagnostic accuracy of the new-generation GP test in detection of AG and Hp among gastroscopy referral patients in a University Clinic. PATIENTS AND METHODS Altogether, 522 patients were enrolled among the patients referred for gastroscopy at the Gastro Center, Oulu University Hospital (OUH). All patients underwent gastroscopy with biopsies classified using the Updated Sydney System (USS), and blood sampling for GP testing. RESULTS Biopsy-confirmed AG was found in 10.2% (53/511) of the patients. The overall agreement between the GP and the USS classification was 92.4% (95%CI=90.0-94.6%), with the weighted kappa (κw) of 0.861 (95%CI=0.834-0.883). In ROC analysis using moderate/severe AG of the corpus (AGC2+) as the endpoint, AUC=0.952 (95%CI=0.891-1.000) and AUC=0.998 (95%CI=0.996-1.000) for PGI and PGI/PGII, respectively. Hp IgG antibody ELISA detected biopsy-confirmed Hp-infection with AUC=0.993 (95%CI=0.987-0.999). CONCLUSION The new generation GastroPanel® is a precise test for non-invasive diagnosis of atrophic gastritis and Hp-infection in dyspeptic patients referred for diagnostic gastroscopy.

Background Remdesivir is a novel broad-spectrum antiviral therapeutic with activity against several viruses that cause emerging infectious diseases. The purpose of this study is to explore how commonly utilized antiretroviral therapy (tenofovir disoproxil fumarate/lamivudine [TDF/3TC] and atazanavir/ritonavir [ATV/r]) influence plasma and intracellular concentrations of remdesivir. Methods This is an open-label, randomized, fixed sequence single intravenous dosing study to assess pharmacokinetic interactions between remdesivir and TDF/3TC (Study A, crossover design) or TDF/3TC plus ATV/r (Study B). Healthy volunteers satisfying study entry criteria will be enrolled in the study and randomized to either Study A; N=16 (Sequence 1 or Sequence 2) or Study B; N=8. Participants will receive standard adult doses of antiretroviral therapy for 7 days and a single 200mg remdesivir infusion administered over 60 min. Pharmacokinetic blood sampling will be performed relative to the start of remdesivir infusion; predose (before the start of remdesivir infusion) and 30 min after the start of remdesivir infusion. Additional blood samples will be taken at 2, 4, 6, 12, and 24 h after the end of remdesivir infusion. Discussion This study will characterize the pharmacokinetics of remdesivir from a typical African population in whom clinical use is anticipated. Furthermore, this study will deliver pharmacokinetic datasets for remdesivir drug concentrations and demographic characteristics which could support pharmacometric approaches for simulation of remdesivir treatment regimens in patients concurrently using tenofovir/lamivudine and/or atazanavir/ritonavir. Trial registration ClinicalTrials.gov NCT04385719. Registered 13 May 2020.

Introduction Serologic testing can provide a safe and fast approach for assessing SARS-CoV-2 antibodies. These tests can be utilized as a complementary method in diagnosis and patients' follow-up, and can also be helpful in epidemiological studies. This study aimed to describe temporal changes in the incidence of COVID-19 IgM and IgG antibodies in emergency medical technicians (EMTs) within a specified time period. Methods All EMTs working for Tehran Emergency Medical Service (EMS) center during May to September 2020 were eligible for this study. Those EMTs who were suspected/probable/confirmed cases of COVID-19, based on WHO defined criteria and were willing to participate, entered the study. The EMTs underwent serology testing four weeks after the occurrence of exposure (in suspected cases) or onset of their symptoms (in probable/confirmed cases). Cases were further confirmed by RT-PCR and/or lung CT, and antibody testing was performed for the second and third time with 12-week intervals. Finger-stick blood sampling was utilized for the specimen collection in three different phases. Samples were then analyzed by a commercial immunochromatography-based kit for qualitative measurement of serum IgM and IgG antibodies against the COVID-19 S-protein antigen. Results Two hundred eighty-four participants met the inclusion criteria; their mean age was 35.9 (SD = 7.6) years and consisted of 244 (85.9%) males. COVID-19 was confirmed in 169 out of 284 participants. Subsequently, 142 and 122 participants were included in phases 2 and 3 of the study, respectively. The number of seronegative patients exceeded seropositive ones in all three phases. At baseline, 162 (57%) patients were seronegative, 27 (9.5%) were only positive for IgG, 3 (1.1%) were only positive for IgM, and 92 (32.4%) were positive for both antibodies; Seventy-eight (54.9%) were seronegative, and 31 (21.8%) were positive for both antibodies in the second phase; These values were 85 (69.6%) and 8 (6.6%) for the third phase, respectively. Among the people who were positive IgG in the first phase (80 people), 56.3% were still positive in the second phase and 27.5% in both subsequent phases. Conclusion The results of our study show that there is a significant reduction in COVID-19 antibody seropositivity over time.

Objective: 5-(1-(2-[18F]fluoroethoxy))-[3-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-propyl]-5,6,7,8-tetrahydronaphthalen ([18F]MC225) is a selective substrate for P-glycoprotein (P-gp), possessing suitable properties for measuring overexpression of P-gp in the brain. This is the first-in-human study to examine safety, radiation dosimetry and P-gp function at the blood-brain barrier (BBB) of [18F]MC225 in healthy subjects.Methods: [18F]MC225 biodistribution and dosimetry were determined in 3 healthy male subjects, using serial 2 h and intermittent 4 and 6 h whole-body PET scans acquired after [18F]MC225 injection. Dynamic [18F]MC225 brain PET (90 min) was obtained in 5 healthy male subjects. Arterial blood was sampled at various time intervals during scanning and the fraction of unchanged [18F]MC225 in plasma was determined. T1-weighted MRI was performed for anatomical coregistration. Total distribution volume (VT) was estimated using 1- and 2-tissue-compartment models (1-TCM and 2-TCM, respectively). VT was also estimated using the Logan graphical method (Logan plot) (t* = 20 min). Surrogate parameters without blood sampling (area-under the curve [AUC] of regional time-activity curves [TACs] and negative slope of calculated TACs) were compared with the VT values.Results: No serious adverse events occurred throughout the study period. Although biodistribution implied hepatobiliary excretion, secretion of radioactivity from liver to small intestine through the gallbladder was very slow. Total renal excreted radioactivity recovered during 6 h after injection was < 2%ID. Absorbed dose was the highest in the pancreas (mean ± SD, 203 ± 45 μGy/MBq) followed by the liver (83 ± 11 μGy/MBq). Mean effective dose with and without urination was 17 ± 1 μSv/MBq. [18F]MC225 readily entered the brain, distributing homogeneously in grey matter regions. 2-TCM provided lower Akaike information criterion scores than did 1-TCM. VT estimated by Logan plot was well correlated with that of 2-TCM (r2 > 0.9). AUCs of TACs were positively correlated with VT (2-TCM) values (r2: AUC0-60 min = 0.61, AUC0-30 min = 0.62, AUC30-60 min = 0.59, p < 0.0001). Negative slope of SUV TACs was negatively correlated with VT (2-TCM) values (r2 = 0.53, p < 0.0001).Conclusions: This initial evaluation indicated that [18F]MC225 is a suitable and safe PET tracer for measuring P-gp function at the BBB.Keywords: Blood–Brain barrier; Dosimetry; First-in-human; P-glycoprotein; Positron emission tomography.

Exercise is beneficial for brain health, inducing neuroplasticity and vascular plasticity in the hippocampus, which is possibly mediated by brain-derived neurotrophic factor (BDNF) levels. Here we investigated the short-term effects of exercise, to determine if a 1-week intervention is sufficient to induce brain changes. Fifteen healthy young males completed five supervised exercise training sessions over seven days. This was preceded and followed by a multi-modal magnetic resonance imaging (MRI) scan (diffusion-weighted MRI, perfusion-weighted MRI, dual-calibrated functional MRI) acquired 1 week apart, and blood sampling for BDNF. A diffusion tractography analysis showed, after exercise, a significant reduction relative to baseline in restricted fraction—an axon-specific metric—in the corpus callosum, uncinate fasciculus, and parahippocampal cingulum. A voxel-based approach found an increase in fractional anisotropy and reduction in radial diffusivity symmetrically, in voxels predominantly localised in the corpus callosum. A selective increase in hippocampal blood flow was found following exercise, with no change in vascular reactivity. BDNF levels were not altered. Thus, we demonstrate that 1 week of exercise is sufficient to induce microstructural and vascular brain changes on a group level, independent of BDNF, providing new insight into the temporal dynamics of plasticity, necessary to exploit the therapeutic potential of exercise.

Introduction Direct quantification of drug concentrations allows for medication adherence monitoring (MAM) and therapeutic drug monitoring (TDM). Multiple less invasive methods have been developed in recent years: dried blood spots (DBS), saliva, and hair analyses. Aim To provide an overview of emerging drug quantification methods for MAM and TDM, focusing on the clinical validation of methods in patients prescribed chronic drug therapies. Methods A scoping review was performed using a systematic search in three electronic databases covering the period 2000–2020. Screening and inclusion were performed by two independent reviewers in Rayyan. Data from the articles were aggregated in a REDCap database. The main outcome was clinical validity of methods based on study sample size, means of cross-validation, and method description. Outcomes were reported by matrix, therapeutic area and application (MAM and/or TDM). Results A total of 4590 studies were identified and 175 articles were finally included; 57 on DBS, 66 on saliva and 55 on hair analyses. Most reports were in the fields of neurological diseases (37%), infectious diseases (31%), and transplantation (14%). An overview of clinical validation was generated of all measured drugs. A total of 62 drugs assays were applied for MAM and 131 for TDM. Conclusion MAM and TDM are increasingly possible without traditional invasive blood sampling: the strengths and limitations of DBS, saliva, and hair differ, but all have potential for valid and more convenient drug monitoring. To strengthen the quality and comparability of future evidence, standardisation of the clinical validation of the methods is recommended. Supplementary Information The online version contains supplementary material available at 10.1007/s40265-021-01618-7.

We examined in a rat model of Gulf War illness (GWI), the potential of (−)-epicatechin (Epi) to reverse skeletal muscle (SkM) atrophy and dysfunction, decrease mediators of inflammation and normalize metabolic perturbations. Male Wistar rats (n = 15) were provided orally with pyridostigmine bromide (PB) 1.3 mg/kg/day, permethrin (PM) 0.13 mg/kg/day (skin), DEET 40 mg/kg/day (skin) and were physically restrained for 5 min/day for 3 weeks. A one-week period ensued to fully develop the GWI-like profile followed by 2 weeks of either Epi treatment at 1 mg/kg/day by gavage (n = 8) or water (n = 7) for controls. A normal, control group (n = 15) was given vehicle and not restrained. At 6 weeks, animals were subjected to treadmill and limb strength testing followed by euthanasia. SkM and blood sampling was used for histological, biochemical and plasma pro-inflammatory cytokine and metabolomics assessments. GWI animals developed an intoxication profile characterized SkM atrophy and loss of function accompanied by increases in modulators of muscle atrophy, degradation markers and plasma pro-inflammatory cytokine levels. Treatment of GWI animals with Epi yielded either a significant partial or full normalization of the above stated indicators relative to normal controls. Plasma metabolomics revealed that metabolites linked to inflammation and SkM waste pathways were dysregulated in the GWI group whereas Epi, attenuated such changes. In conclusion, in a rat model of GWI, Epi partially reverses detrimental changes in SkM structure including modulators of atrophy, inflammation and select plasma metabolites yielding improved function.

A long-acting granulocyte colony-stimulating factor, tripegfilgrastim, was approved in Korea for the prevention of chemotherapy-induced neutropenia in adult patients. In this study, we evaluated the pharmacokinetics, pharmacodynamics, and safety of tripegfilgrastim in pediatric patients. A phase I, open-label, single ascending-dose study was performed in pediatric patients with solid tumors or lymphoma (ClinicalTrials.gov, NCT02963389). The patients were stratified according to age groups (aged 6 to 12 or 12 to 19 years) and received a single subcutaneous dose of tripegfilgrastim 60 μg/kg or 100 μg/kg. Tripegfilgrastim was administered 24 hours after the end of the chemotherapy, and serial blood sampling and safety monitoring were conducted. Twenty-seven patients with solid tumors were enrolled in this study. Tripegfilgrastim was detectable in plasma for an extended period (terminal half-life > 40 hours), and plasma concentrations increased slightly less than dose proportionally. The mean duration of grade 4 neutropenia was reduced as the average tripegfilgrastim concentration during the initial neutrophil recovery process increased. No substantial differences in the pharmacokinetic and pharmacodynamic responses were observed between the two age groups. When stratified by body weight, weighing more than 45 kg has a higher risk of a prolonged neutropenia period when receiving the lower dose (60 μg/kg) of tripegfilgrastim. Tripegfilgrastim was generally safe and well-tolerated in the pediatric patients. These results justify further clinical investigations of tripegfilgrastim at 100 μg/kg dose in pediatric patients.

Introduction Postpartum depression (PPD) is a multifactor disorder caused by psychological, social, and also biological factors. 5-HTTLPR polymorphism in the promoter region of serotonin transporter gene seems to influence PPD onset. In this study, we examined the effect of 5-HTTLPR polymorphism on prenatal and postnatal symptoms of depression and posttraumatic stress in women. Methods A longitudinal design with three points - time 1 (32-40 weeks gestation); time 2 (2 or 3 weeks after birth), and time 3 (3 months after birth) - was made. A total of 141 women were recruited during childbirth preparation courses. At time 1, women completed the Beck Depression Inventory (BDI) and the Los Angeles Symptoms Checklist (LASC). At time 2, they fulfilled BDI and Edinburgh Postnatal Depression Scale (EDPS), LASC and the Perinatal Posttraumatic stress disorder (PTSD) Questionnaire (PPQ); midwives and nurses collected biological test tubes by blood sampling for the genetic analysis. At time 3, the women were reassessed for BDI, LASC, EDPS, and PPQs. Analysis of variance and moderation analysis were used to correlate genotype and psychological investigations. Results Results showed that, compared with LL/LS genotypes, SS genotype moderated cognitive depressive symptoms onset at T2 and T3. Moreover, this genotype correlated, directly or indirectly, with PTSD postpartum aspects (re-experience, avoidance, and hyperarousal). Discussion Findings revealed that a lower expression of serotonin transporter gene, associated with SS genotype, seems to render women more vulnerable to depressive and PTSD symptoms after childbirth.

Background: Endarterectomy of the internal carotid artery (CEA) plays an important role in the prevention of cerebral ischemic stroke; however, this surgical procedure may cause neurological complications. The aim of this study was to evaluate changes in serum levels of the oxidative stress marker peroxiredoxin-1 (PRDX1) in patients undergoing CEA. Material and methods: Twenty-four patients undergoing endarterectomy for critical stenosis of the internal carotid artery participated in the study. Blood for testing was collected before CEA and twice after surgery. PRDX1 was determined by ELISA. Results: The timing of blood sampling did not affect PRDX1 levels (p > 0.05). There was no statistically significant difference in serum PRDX1 levels between male and female groups and depending on the age of the patients (p > 0.05). Conclusion: PRDX1 cannot be considered as a marker of neurological complications after CEA.

Xanthine oxidoreductase (XOR) is known as an enzyme related to purine metabolism, catalysing the oxidation of hypoxanthine to xanthine and of xanthine to uric acid. We investigated the relationship between plasma XOR activity in stable kidney transplantation (KT) recipients and carotid artery lesions.A total of 42 KT patients visiting our outpatient clinic on regular basis were recruited. Associations between plasma XOR activity and the existence of plaque in the common carotid artery (CCA) or internal carotid artery (ICA) and maximum intima-medial thickness (IMT) of CCA (max-CIMT) 0.9 mm were examined using univariate and multivariate analyses.At blood sampling, the mean and SD patient age was 52.7 ± 13.8 years old. Plasma XOR(pmol/h/ml) activity was significantly higher in patients with CCA/ICA plaque or max-CIMT0.9 mm than those without. [23.9 (11.8, 38.3) vs. 8.29 (6.67, 17.5), p .01, 23.9 (16.9, 71.2) vs. 9.16 (6.67, 28.2), p = .01] Univariate and multivariate logistic regression analyses revealed age and plasma XOR activity as independent predictors of CCA/ICA plaque or max-CIMT0.9 mm. Receiver operator characteristic curve analyses revealed that the cutoff value of plasma XOR activity for the diagnosis of CCA/ICA plaque or CCA-IMT 0.9 mm was 16.3 pmol/h/ml.Plasma XOR activity is associated independently with atherosclerotic changes in the carotid artery of stable post-KT patients.

Background and Objective High lipoprotein(a) is a genetically determined causal risk factor for cardiovascular disease, and 20% of the adult population has high levels (ie, >42 mg/dL, >88 nmol/L). We investigated whether early life lipoprotein(a) levels measured in cord blood may serve as a proxy for neonatal venous blood levels, whether lipoprotein(a) birth levels (ie, cord or venous) predict levels later in life, and whether early life and parental levels correlate. Methods The Compare study is a prospective cohort study of newborns (N = 450) from Copenhagen, Denmark, including blood sampling of parents. Plasma lipoprotein(a) was measured in cord blood (N = 402), neonatal venous blood (N = 356), and at 2 (N = 320) and 15 months follow-up (N = 148) of infants, and in parents (N = 705). Results Mean lipoprotein(a) levels were 2.2 (95% CI, 1.9-2.5), 2.4 (2.0-2.7), 4.1 (3.4-4.9), and 14.6 (11.4-17.9) mg/dL in cord, neonatal venous, and 2- and 15-month venous samples, respectively. Lipoprotein(a) levels in cord blood correlated strongly with neonatal venous blood levels (R2 = 0.95, P 42 mg/dL at 15 months with positive predictive values of 89% and 85% for neonatal venous and cord blood. Neonatal and infant levels correlated weakly with parental levels, most pronounced at 15 months (R2 = 0.22, P Conclusions Lipoprotein(a) levels are low in early life, cord blood may serve as a proxy for neonatal venous blood, and birth levels ≥ 90th percentile can identify newborns at risk of developing high levels.

Purpose of review To date, prognostication of patients after acute traumatic spinal cord injury (SCI) mostly relies on the neurological assessment of residual function attributed to lesion characteristics. With emerging treatment candidates awaiting to be tested in early clinical trials, there is a need for wholistic high-yield prognostic biomarkers that integrate both neurogenic and nonneurogenic SCI pathophysiology as well as premorbid patient characteristics. Recent findings It is becoming clearer that effective prognostication after acute SCI would benefit from integrating an assessment of pathophysiological changes on a systemic level, and with that, extend from a lesion-centric approach. Immunological markers mirror tissue injury as well as host immune function and are easily accessible through routine blood sampling. New studies have highlighted the value of circulating white blood cells, neutrophils and lymphocytes in particular, as prognostic systemic indicators of SCI severity and outcomes. Summary We survey recent advances in methods and approaches that may allow for a more refined diagnosis and better prognostication after acute SCI, discuss how these may help deepen our understanding of SCI pathophysiology, and be of use in clinical trials.

Objective — to improve approaches to differential diagnosis of lymphadenitis by identifying features of hematological and biochemical parameters of blood of children with nonspecific bacterial and specific tuberculous lymphadenitis. Materials and methods. Under our supervision were 45 children aged 1 to 5 years with an increase in lymph nodes (LN), who were treated in the surgical department of the Odessa Regional Children’s Clinical Hospital for the period from 2017 to 2018. Patients were assessed for general condition and affected lymph node lesions, as well as blood sampling for general and biochemical studies. Additionally, the calculation of integrated hematological indices of immunological tolerance of the organism was performed, namely the index of neutrophils to lymphocytes ratio (NLR); lymphocyte to monocyte ratio (LMR); neutrophil to monocyte ratio (NMR); lymphocyte to eosinophil ratio (LER). For comparison with the norm used the data of these indicators, established in healthy children. Results and discussion. All patients were divided into 2 clinical groups. The first group (СG-1) included 25 children with lymphadenitis caused by BCG vaccination, the second (СG-2) — 20 patients with acute purulent lymphadenitis. The study found that the condition of most children (75 %) of the second group was more severe compared with patients with CG-1, which was manifested by more pronounced manifestations of intoxication and local condition of the affected LN.Evaluation of a general blood test showed that the average number of leukocytes with specific lymphadenitis in most (80.8 %) patients was within normal limits, with purulent; on the contrary, in 71.4 % of children there was a tendency to increase. The calculations of hematological indices revealed a decrease in NLR, and, with BCG lymphadenitis, it decreased by half (to 0.96) compared with bacterial lymphade­nit (to 1.88), which indicates an increase in specific immunological reactivity in children of CG-1. ISNM in most patients with lymphadenit remained low throughout the course of the disease. This indicates the timely activation of the macrophage defense system of the body. LMR with tuberculous lymphadenit grew, while with bacterial lymphadenit, on the contrary, it decreased by half, which indicates earlier mobilization of lymphocytes as an effector immunity in children with BCG lymphadenitis. LER in all forms of the disease tended to increase, which indicates the predominance of a delayed-type hypersensitivity reaction in children of both groups.Analysis of blood biochemical parameters in patients of both clinical groups did not reveal clear differences in children with bacterial and tuberculous lymphadenitis. Conclusions. At specific defeat of LN unlike nonspecific, the clinical and laboratory picture with lack of expressive leukocytes reaction is noted. Determining the indices of the ratio of blood leukocytes makes it possible to more deeply assess the level of immunological reactivity and the general condition of the child, which increases the informative value of clinical blood tests. Analysis of blood biochemical parameters in patients with specific and nonspecific lymphadenitis, although it has no specific differential diagnostic value, however, is an important component of assessing the quality of treatment and the patient’s condition as a whole.

Background and Objective Ceftriaxone is a cornerstone antibiotic for critically ill children with severe infections. Despite its widespread use, information on the pharmacokinetics of ceftriaxone is lacking in this population. We aimed to determine ceftriaxone pharmacokinetics in critically ill children and to propose ceftriaxone dosing guidelines resulting in adequate target attainment using population pharmacokinetic modeling and simulation. Methods Critically ill children (aged 0–18 years) treated with intravenous ceftriaxone (100 mg/kg once daily, infused in 30 minutes) and a central or arterial line in place were eligible. Opportunistic blood sampling for total and unbound ceftriaxone concentrations was used. Population pharmacokinetic analysis was performed using non-linear mixed-effects modeling on NONMEM™ Version 7.4.3. Simulations were performed to select optimal doses using probability of target attainment for two pharmacokinetic targets of the minimum inhibitory concentration (MIC) reflecting the susceptibility of pathogens (f T > MIC 100% and fT > 4 × MIC 100%). Results Two hundred and five samples for total and 43 time-matched samples for unbound plasma ceftriaxone concentrations were collected from 45 patients, median age 2.5 (range 0.1–16.7) years. A two-compartment model with bodyweight as the co-variate for volume of distribution and clearance, and creatinine-based estimated glomerular filtration rate as an additional covariate for clearance, best described ceftriaxone pharmacokinetics. For a typical patient (2.5 years, 14 kg) with an estimated glomerular filtration rate of 80 mL/min/1.73 m2, the current 100-mg/kg once-daily dose results in a probability of target attainment of 96.8% and 60.8% for a MIC of 0.5 mg/L and 4 × MIC (2 mg/L), respectively, when using fT > MIC 100% as a target. For a 50-mg/kg twice-daily regimen, the probability of target attainment was 99.9% and 93.4%, respectively. Conclusions The current dosing regimen of ceftriaxone provides adequate exposure for susceptible pathogens in most critically ill children. In patients with an estimated glomerular filtration rate of > 80 mL/min/1.73 m2 or in areas with a high prevalence of less-susceptible pathogens (MIC ≥ 0.5 mg/L), a twice-daily dosing regimen of 50 mg/kg can be considered to improve target attainment. Clinical Trial Registration POPSICLE study (ClinicalTrials.gov, NCT03248349, registered 14 August, 2017), PERFORM study (ClinicalTrials.gov, NCT03502993, registered 19 April, 2018). Supplementary Information The online version contains supplementary material available at 10.1007/s40262-021-01035-9.

Introduction:\ud Malignant pleural mesothelioma (MPM) is difficult to diagnose. An accurate blood biomarker could prompt specialist referral or be deployed in future screening. In earlier retrospective studies, SOMAscan proteomics (Somalogic, Boulder, CO) and fibulin-3 seemed highly accurate, but SOMAscan has not been validated prospectively and subsequent fibulin-3 data have been contradictory.\ud \ud Methods:\ud A multicenter prospective observational study was performed in 22 centers, generating a large intention-to-diagnose cohort. Blood sampling, processing, and diagnostic assessment were standardized, including a 1-year follow-up. Plasma fibulin-3 was measured using two enzyme-linked immunosorbent assays (CloudClone [used in previous studies] and BosterBio, Pleasanton, CA). Serum proteomics was measured using the SOMAscan assay. Diagnostic performance (sensitivity at 95% specificity, area under the curve [AUC]) was benchmarked against serum mesothelin (Mesomark, Fujirebio Diagnostics, Malvern, PA). Biomarkers were correlated against primary tumor volume, inflammatory markers, and asbestos exposure.\ud \ud Results:\ud A total of 638 patients with suspected pleural malignancy (SPM) and 110 asbestos-exposed controls (AECs) were recruited. SOMAscan reliably differentiated MPM from AECs (75% sensitivity, 88.2% specificity, validation cohort AUC 0.855) but was not useful in patients with differentiating non-MPM SPM. Fibulin-3 (by BosterBio after failed CloudClone validation) revealed 7.4% and 11.9% sensitivity at 95% specificity in MPM versus non-MPM SPM and AECs, respectively (associated AUCs 0.611 [0.557–0.664], p = 0.0015) and 0.516 [0.443–0.589], p = 0.671), both inferior to mesothelin. SOMAscan proteins correlated with inflammatory markers but not with asbestos exposure. Neither biomarker correlated with tumor volume.\ud \ud Conclusions:\ud SOMAscan may prove useful as a future screening test for MPM in asbestos-exposed persons. Neither fibulin-3 nor SOMAscan should be used for diagnosis or pathway stratification.

Hyper- or hypoventilation are commonly occurring stress responses to arterial puncture around the time of blood sampling and have been shown to rapidly alter arterial blood acid-base parameters. This study aimed to evaluate a physiology-based mathematical method to transform peripheral venous blood acid-base values into mathematically arterialised equivalents following acute, transient changes in ventilation. Data from thirty patients scheduled for elective surgery were analysed using the physiology-based method. These data described ventilator changes simulating 'hyper-' or 'hypoventilation' at arterial puncture and included acid-base status from simultaneously drawn blood samples from arterial and peripheral venous catheters at baseline and following ventilatory change. Venous blood was used to calculate mathematically arterialised equivalents using the physiology-based method; baseline values were analysed using Bland-Altman plots. When compared to baseline, measured arterial and calculated arterialised values at each time point within limits of pH: ± 0.03 and PCO2: ± 0.5 kPa, were considered 'not different from baseline'. Percentage of values considered not different from baseline were calculated at each sampling timepoint following hyper- and hypoventilation. For the physiological method, bias and limits of agreement for pH and PCO2 were -0.001 (-0.022 to 0.020) and -0.02 (-0.37 to 0.33) kPa at baseline, respectively. 60 s following a change in ventilation, 100% of the mathematically arterialised values of pH and PCO2 were not different from baseline, compared to less than 40% of the measured arterial values at the same timepoint. In clinical situations where transient breath-holding or hyperventilation may compromise the accuracy of arterial blood samples, arterialised venous blood is a stable representative of steady state arterial blood.

Background Personal glucose meters, primarily designed for self-control of glucose concentration in patients with diabetes, are frequently used in clinical practice as point-of-care equipment. The procedure of washing hands with water and soap before testing, as recommended by the manufacturer of personal glucose meters, in hospital wards is often difficult to fulfil and is replaced by disinfecting the place of blood sampling with isopropyl alcohol. Aim The purpose of the research was to evaluate the effect of different disinfecting procedures on glycemia measurement in capillary blood using personal glucose meters. Materials and methods Four measurements of glycemia were taken in each of 50-volunteer group using Accu-Check Performa (Roche, Swiss) glucose meter using different procedures: washing hands with soap and drying them (1), disinfection with isopropyl alcohol and waiting for the disinfectant to evaporate (2) and the immediate puncture after disinfection. In the latter case two kind of single-use lancets were use – typical for adult (3) and smaller preferred by diabetics or children (4). Results Paired T-student test showed no statistically significant difference between measurements 1st and 2nd 95% CI (−4.282 to 0.322), p = 0.09. However, the comparison between 1st/3rd and 1st/4th showed statistically significant difference, 95% CI (−4.964 to −0.796), p = 0,0077 (p Conclusions The procedure of disinfection when fluid completely evaporates has no effect on glucose measurements. Sampling the wet finger influences results of glucose measurement but observed changes were clinically irrelevant.

OBJECTIVE While the apolipoprotein E ε4 allele (ApoE-ε4) is related to cognitive and brain decline in the general population, its effect on the brain in type 1 diabetes mellitus (T1DM) remains unclear. Therefore, the aim was to determine the interaction between ApoE-ε4 and T1DM on cognitive performance and hippocampal structure and connectivity as the brain area most vulnerable to ApoE-ε4 effects in adult patients with T1DM. RESEARCH DESIGN AND METHODS Blood sampling was performed in 104 patients with T1DM and 49 control subjects for ApoE genotyping, neuropsychology, and neuroimaging to determine hippocampal volume and resting-state connectivity. The interaction between T1DM status and ApoE-ε4 presence was investigated and adjusted for age and mean systolic blood pressure. RESULTS ApoE genotyping could not be performed for three patients with T1DM. Significant interaction effects, indicating a differential effect of ApoE-ε4 between both groups, were found for overall cognitive functioning and for the subdomains of information processing speed and attention. Additionally, interaction effects were present for right hippocampal connectivity with the right posterior cingulate and supramarginal gyri. Subsequent group analysis showed that patients with T1DM with ApoE-ε4 performed worse on these cognitive domains with increased connectivity, relative to their counterparts without ApoE-ε4. In contrast, no cognitive effects, but decreased connectivity, were observed in control subjects with ApoE-ε4. In patients with T1DM, higher right hippocampus connectivity with the posterior cingulate gyrus was related to poorer overall cognitive functioning. CONCLUSIONS The results may suggest that ApoE-ε4 presence leaves our patients with T1DM more susceptible to cognitive decrements at a younger age, possibly through vascular pathways, warranting further longitudinal studies.

Objective To understand whether polycystic ovarian morphology (PCOM) represents a transient phase, and whether an increased stroma could help to characterize the phenotype of the ovary in adolescence. Methods Cross-sectional population-based study on high-school students in Cagliari, Italy. The study population consisted of 257 normocyclic non-hyperandrogenic girls selected from a sample of 600 healthy volunteers recruited from 2012 to 2016. Clinical examination, medical history, blood sampling, and pelvic ultrasound (US) were performed. Postmenarchal years and body mass index (BMI) were estimated. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17β estradiol (E2), total testosterone (tT), delta-4-androstenedione (A), and 17-hydroxyprogesterone (17-OHP) were measured. Ovarian volume, follicular number per section (FNPS), and S/A ratio were measured by pelvic US. Results Following the Rotterdam guidelines for US PCOS diagnosis and setting the normal S/A ratio at ≤0.3, subjects were categorized into 3 groups: (1) normal ovarian morphology (NOM; n = 154, 60%); (2) polycystic ovarian morphology (PCOM) with normal S/A ratio (PCOM-NS; n = 70, 27%); and (3) PCOM with increased S/A ratio (PCOM-IS; n = 33, 13%). The NOM group had more postmenarchal years and a lower LH than both the PCOM groups, and lower A and tT than the PCOM-IS group. The PCOM-NS group had fewer postmenarchal years and lower A than the PCOM-IS group. Interestingly, unlike NOM and PCOM-NS, the prevalence of PCOM-IS remained constant among the 3 phases of postmenarchal age (10% vs 16% vs 15%, P = not significant). Conclusion This study demonstrates that PCOM can be a transient condition, whereas a high S/A ratio is a stable US alteration present from early postmenarchal years.

Daridorexant (ACT-541468) is a new dual orexin receptor antagonist being evaluated for the treatment of insomnia, which is a common comorbidity of depression and anxiety. Therefore, daridorexant is likely to be administered concomitantly with agents (e.g., citalopram) used to treat these disorders. In this single-centre, single-blind, randomized, placebo-controlled, sequential design Phase 1 study with the inclusion of two double-blind crossover parts, the pharmacokinetic (PK; blood sampling at regular intervals) and pharmacodynamic (PD; battery of objective and subjective PD tests performed at regular intervals) interactions between daridorexant (50 mg) and citalopram (20 mg, single dose and at steady state) as well as the safety/tolerability in healthy subjects were investigated. There were no relevant effects of citalopram (single dose/steady state) on daridorexant exposure and vice versa. PD variables measured after morning administration of daridorexant alone showed effects consistent with a sleep-promoting compound. Only co-administration of daridorexant with citalopram at steady state led to relevant changes in objective (unstable tracking) and subjective (visual analogue scale alertness and Karolinska Sleepiness Scale) PD endpoints compared to daridorexant alone. No serious or severe adverse events were reported, while no clinically relevant treatment-emergent effects on ECG parameters, clinical laboratory, or vital signs were observed. In conclusion, the co-administration of daridorexant and citalopram lead to only minor changes in PK parameters, while performance of PD assessments following co-administration were mainly driven by the expected central nervous system effects of daridorexant. Doses up to 50 mg daridorexant can be safely co-administered with citalopram.

The article describes a study aimed at markers that identify the surgically induced stress response and the dyna­mics of postoperative pain in ophthalmic patients after corneal transplantation. We analyzed the data of patients operated on the basis of Dnipropetrovsk Regional Clinical Ophthalmologic Hospital from 2017 to 2019. During the research, we determined such main parameters in patients as the main parameters of hemodynamics and gas exchange, the severity of the surgically induced stress response by analyzing the dynamics of the levels of leukocytes, blood glucose, and C-reactive protein, as well as the severity of postoperative pain. Blood sampling was carried out at four stages of the study. As a result, a statistically significant postoperative increase in the concentration of blood glucose and leukocytes was established compared to the preoperative level. It was also found that postoperative analgesia cannot be considered sufficient in more than 70 % of patients. The data obtained demonstrated the development of surgically induced stress response in ophthalmic patients and make a search for stress-limiting schemes for anesthetic management re­levant and requires further research., В статье представлено описание исследования, направленного на определение маркеров операционного стресс-ответа и динамики послеоперационного болевого синдрома у пациентов офтальмохирургического профиля, перенесших трансплантацию роговицы. Проанализированы данные пациентов, оперированных на базе КУ «Днепропетровская областная клиническая офтальмологическая больница» с 2017 по 2019 г. В процессе исследования у пациентов определялись основные параметры гемодинамики и газообмена, выраженность операционного стресс-ответа путем анализа динамики уровней лейкоцитов, глюкозы крови и С-реактивного белка, а также выраженность болевого синдрома в послеоперационном периоде. Забор крови осуществлялся на 4 этапах исследования. В результате было установлено статистически значимое повышение концентрации глюкозы крови и лейкоцитов у пациентов после операции в сравнении с дооперационным уровнем. Также было установлено, что послеоперационное обезболивание не может считаться адекватным более чем у 70 % пациентов. Полученные данные свидетельствуют о развитии у пациентов офтальмохирургического профиля операционного стресса и делают проблему поиска альтернативных стресс-лимитирующих схем анестезиологического обеспечения в офтальмохирургии актуальной и требующей дальнейшего исследования., У статті наведений опис дослідження, спрямованого на визначення маркерів операційної стрес-відповіді й динаміки післяопераційного больового синдрому в пацієнтів офтальмохірургічного профілю, які перенесли трансплантацію рогівки. Проаналізовані дані пацієнтів, які оперувалися на базі КЗ «Дніпропетровська обласна клінічна офтальмологічна лікарня» з 2017 по 2019 р. У процесі дослідження в пацієнтів визначалися основні параметри гемодинаміки й газообміну, вираженість операційної стрес-відповіді шляхом аналізу динаміки рівнів лейкоцитів, глюкози крові і С-реактивного білка, а також вираженість больового синдрому в післяопераційному періоді. Забір крові здійснювався на 4 етапах дослідження. У результаті було встановлено статистично значуще підвищення концентрації глюкози крові і лейкоцитів у пацієнтів після операції порівняно з доопераційним рівнем. Також було встановлено, що післяопераційне знеболювання не може вважатися адекватним більш ніж у 70 % пацієнтів. Отримані дані свідчать про розвиток у пацієнтів офтальмохірургічного профілю операційного стресу і роблять проблему пошуку альтернативних стрес-лімітуючих схем анестезіологічного забезпечення в офтальмохірургії актуальною і вимагаючою подальшого дослідження.

Исходный уровень лактата используется как один из предикторов смертности пациентов с септическим шоком. В опубликованных исследованиях измерялся уровень лактата крови, забранной из различных сосудов, в некоторых ретроспективных исследованиях приводились данные об уровне лактата крови из гетерогенных источников (артерия, центральная вена и периферическая вена). Вопрос, стоящий перед практическими врачами: какие данные имеют лучшую прогностическую ценность, могут ли они заменить друг друга? В наших наблюдениях высокая положительная линейная корреляция обнаружилась между концентрациями лактата артериальной крови и центральной венозной крови (R = 0,895; P < 0,001). Оба показателя имеют удовлетворительную ценность для прогноза исхода лечения. Концентрация лактата в артериальной крови имела несколько лучшую прогностическую ценность по сравнению с его концентрацией в центральной венозной крови.

Background: Adhesive capsulitis is common and can cause stiffness and pain. Diabetes and dyslipidemia are known to be associated with adhesive capsulitis. However, there is no report of any association between serum lipid levels accompanied by diabetes patients. Objective: To assess association between serum inflammatory lipoproteins and adhesive capsulitis accompanied by diabetes. Methods: This is a case-control study was conducted in Department of Physical Medicine and Rehabilitation, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. We investigated all the patients who visited our clinic because of their shoulder problems from January to June-2017. Among those patients, 375 were diagnosed with adhesive capsulitis. Of these, we excluded 44 patients (11%) who had no laboratory results. Individuals with normal shoulder function (bilaterally pain-free, with full range of motion and no shoulder muscle weakness), no thyroid dysfunction, and no previously diagnosed systemic diseases. Individuals in the first control group had neither adhesive capsulitis nor diabetes. Individuals in the second control group had newly diagnosed diabetes without adhesive capsulitis. Results: Demographic data, serum lipid levels, and the prevalence of dyslipidemia for the 25 patients with adhesive capsulitis accompanied by diabetes and 75 individuals of two control groups were matched by age and sex. For the patients with adhesive capsulitis, the mean duration of symptoms was 5.8±2.7 months; the median interval between initial examination and blood sampling was 6.0 days (interquartile range [IQR], 1.0–8.0). Low-density lipoprotein and non HDL were associated with adhesive capsulitis accompanied by diabetes. Specifically, patients with adhesive capsulitis and diabetes had greater odds ratios of hyperlow-density lipoproteinemia when compared with individuals with neither adhesive capsulitis nor diabetes (OR, 3.19; 95% CI, 1.21–8.38; p =0.019) and when compared with individuals without adhesive capsulitis but with newly diagnosed diabetes (OR, 5.76; 95% CI, 1.67–19.83; p= 0.005). Similarly, patients with adhesive capsulitis accompanied by diabetes had greater odds ratios of hypernonhigh-density lipoproteinemia when compared with individuals with neither adhesive capsulitis nor diabetes (OR, 7.39; 95% CI, 2.72–20.09; p < 0.001) and when compared with individuals without adhesive capsulitis but with newly diagnosed diabetes (OR, 3.26; 95% CI, 1.40–7.61; p = 0.006). Conclusions: Inflammatory lipoproteinemias, particularly hyperlow-density lipoproteinemia and hypernonhighdensity lipoproteinemia, are associated with adhesive capsulitis accompanied by diabetes. Further research is needed to evaluate whether inflammatory lipoproteinemias are a cause, a related cofactor, or an aggravating factor in the development of adhesive capsulitis in people who have diabetes.

Актуальність. Дефіцит вітаміну D поширений в усіх країнах світу. Недавні дослідження показали зв’язок між дефіцитом вітаміну D та захворюваннями кістково-м’язової системи. Метою даного дослідження є вивчення частоти дефіциту та недостатності вітаміну D у пацієнтів різного віку із захворюваннями кістково-м’язової системи, а також вплив на зазначені показники сезонності. Матеріали та методи. Обстежено 3460 пацієнтів Українського науково-медичного центру проблем остеопорозу віком від 1 до 92 років, які були направлені лікарями різного профілю з метою оцінки стану кісткової тканини. Переважну більшість становили хворі із системним остео­порозом та його ускладненнями, остеохондрозом хребта, остеоартрозом колінних та кульшових суглобів (середній вік — 52,9 ± 21,1 року). Переважну більшість становили жінки — 83,5 %. Дослідження 25(ОН)D та паратгормона проводили за допомогою електрохемілюмінесцентного методу на аналізаторі Elecsys 2010 (Roche Diagnostics, Німеччина) тест-системами cobas. При аналізі використовували пакети програм Statistica 6.0 Copyright StatSoft, Inc. 1984–2001. Результати. Серед хворих із патологією кістково-м’язової системи найвищий рівень 25(ОН)D спостерігається у віковій групі 1–9 років, найнижчий — у віковій групі 80 років та старше. Вік вірогідно впливає на рівень 25(ОН)D. Частота дефіциту вітаміну D серед обстежених із патологією кістково-м’язової системи становила 37,3 %, недостатності вітаміну D — 30,6 %, нормальні рівні показника вітаміну D спостерігали в 32,1 % випадків. Нормальний рівень вітаміну D відмічався в 38,0 % дітей, 33,2 % дорослих, 29,6 % пацієнтів літнього віку. Місяць, в якому проводилось дослідження, вірогідно впливає на рівень 25(ОН)D (F = 7,49; p < 0,0000001). Найбільші вірогідні відмінності рівня 25(ОН)D у літній період порівняно із зимовим спостерігали у вікових групах 10–19 років (18,2 %), 40–49 років (17,3 %), 30–39 років (16,2 %) та 1–9 років (16,1 %). Не відмічали відмінностей показника залежно від сезону у хворих літнього віку (60 років й старше) із патологією кістково-м’язової системи. Висновки. Незважаючи на додатковий прийом комбінованих препаратів кальцію й вітаміну D більшістю пацієнтів із патологією кістково-м’язової системи, тільки у 37,9 % дітей, 33,2 % дорослих та 29,6 % хворих літнього віку спостерігали нормальні рівні 25(ОН)D у сироватці крові, що диктує необхідність обов’язкового скринінгового визначення рівня вітаміну D у пацієнтів із захворюваннями кістково-м’язової системи та додаткового призначення вітаміну D у клінічній практиці (рекомендації для країн Центральної та Східної Європи).

BackgroundGuidelines for venous blood sampling procedure (phlebotomy) discourage tourniquet use whenever possible. Here, we aimed to assess the Biomedical Scientists capability of not using the tourniquet in phlebotomy, which we hypothesized to be equal to 50% of the patients attended, and identifying the most frequent venipuncture site.Materials and MethodsWe selected and assigned two (BMS) with the same age (41 years) and experience (20 years) to record ten phlebotomy days, the first with prioritized and the latter with non-prioritized patients. In a simple record form, each acquired daily data for the number of attended patients, age and gender, the frequency of non-tourniquet usage and the punctured vein. To test our work hypothesis we used the two-tailed single sample t-test (p < 0.05). Differences between age-group means and non-tourniquet use means by each BMS were tested by two-tailed t-test for independent means (p < 0.05).ResultsIn 10 phlebotomy days 683 patients were attended, with males representing 43,2% of the population. We found no statistically difference between age-group means. The combined capability of non-tourniquet use was 50,5%, which did not differ from our null hypothesis, but the individual group-means were statistically different, being 33% and 66.9% in the prioritized vs non-prioritized group. The medial cubital vein was the most prone to be punctured (77,7%).ConclusionsWe have shown that performing phlebotomies without tourniquet use is possible and desirable in at least half of the attended patients, though being more limited in specific group populations. Our results provide room for quality improvement in the laboratory pre-analytical phase.Key points summaryWe assessed the capability of Biomedical Scientists not using the tourniquet in real life blood sampling procedures for diagnostic purposes.Blood was collected from at least half of the attended patients without tourniquet use.Biomedical Scientists were able to prioritize the antecubital veins without tourniquet application (medial cubital vein the most prone to be punctured - 78% of attempts).

BACKGROUND Early-life diseases in dairy animals are main causes of economic loss in livestock production. Oxidative stress (OS) and thyroid hormones are important inter-related components in the normal physiology of this critical period of life. However, limited information regarding their physiology in goat kids is available. This study was conducted to investigate the age-related changes of thyroid hormones, some serum oxidative biomarkers and trace elements in healthy Saanen goat kids. METHODS Nineteen newborn healthy Saanen goat kids (14 females and five males) were studied longitudinally from birth until three months of age. Blood sampling was performed 24-48 h after birth and was repeated on 10 ± 2, 28 ± 2, 56 ± 2 and 84 ± 2 days of age. The serum levels of thyroid hormones, malondialdehyde (MDA), reduced glutathione (GSH), total antioxidant capacity (TAC), selenium (Se), manganese (Mn) and molybdenum (Mo) were measured. RESULTS Age-related changes were observed for all measured variables except for MDA (p

Bolus intravenous administration of 0.9% saline has been associated with the development of pulmonary edema, and increased mortality. An animal model has previously demonstrated that rapid intravenous administration of 0.9% saline was associated with non-hydrostatic lung injury with increased lung lavage protein. We hypothesized that this non-hydrostatic effect would also occur in human volunteers. In a randomized, cross-over study of 14 healthy male subjects, the lung lavage protein concentration and cardiorespiratory effects of an intervention with rapid intravenous administration of 30 mL/kg of 0.9% saline were compared with sham intervention. Bronchoalveolar lavage (BAL) was performed after fluid administration. Doppler echocardiography, lung ultrasound, pulmonary function tests, and blood sampling were performed before and after each intervention. The BAL total protein concentration was greater after 0.9% saline administration than with sham (196.1 µg/mL (SD 87.6) versus 129.8 µg/mL (SD 55.4), respectively (p = 0.020). Plasma angiopoietin-2 concentration was also increased to 2.26 ng/mL (SD 0.87) after 0.9% saline administration compared with sham 1.53 ng/mL (SD 0.69) (p

Female sexual dysfunction (FSD) may be a mirror of a poor cardiometabolic state. In a small pilot study enrolling 71 women with FSD, we previously demonstrated that clitoral Pulsatility Index (PI) evaluated by using color Doppler ultrasound (CDU), reflecting vascular resistance, was associated with cardiometabolic risk factors. Data on uterine CDU in this context are lacking. First, to confirm previously reported data on the direct association between clitoral PI and cardiometabolic risk factors on a larger study population of women consulting for sexual symptoms; second, to investigate eventual similar correlations between cardiometabolic risk factors and CDU parameters of the uterine artery. We also ascertained whether uterine artery PI, similarly to what had previously been observed for clitoral artery PI, was directly related to body image uneasiness and psychopathological symptoms, assessed by validated questionnaires. N = 230 women consulting our clinic for sexual symptoms were examined with clitoral CDU and blood sampling and were asked to fill out the Female Sexual Function Index, the Middlesex Hospital Questionnaire (MHQ) and the Body Uneasiness Test (BUT). In a subgroup of women (n = 164), we also performed transvaginal CDU with measurement of uterine artery parameters. At multivariate analysis, we found a direct association between clitoral PI and body mass index (BMI) (p = 0.004), waist circumference (WC) (p = 0.004), triglycerides (p = 0.006), insulin (p = 0.029) and HOMA-IR (p = 0.009). Furthermore, a correlation between obesity and Metabolic Syndrome (MetS) and a higher clitoral PI was observed (p = 0.003 and p = 0.012, respectively). Clitoral PI was also correlated with MHQ-S (p = 0.010), a scale exploring somatized anxiety symptoms, and BUT-B Positive Symptom Distress Index (p = 0.010), a measure of body image concerns. Similarly, when investigating the uterine artery, we were able to demonstrate an association between its PI and BMI (p p = 0.001), insulin (p = 0.006), glycated haemoglobin (p = p = 0.009). Women diagnosed with obesity and MetS showed significantly higher uterine PI values vs. those without obesity or MetS (p = 0.001 and p = 0.004, respectively). Finally, uterine PI was associated with BUT-A Global Severity Index (p

Glomerular filtration rate (GFR) is an important indicator of renal function. Many methods have been developed to determine GFR in clinical examinations. This study aims to correlate between radionuclide plasma sampling methods (single and double blood samples, in vitro methods) and in vivo Gate's method using 99mTc-diethylene triamine penta-acetic acid (99mTc-DTPA) renography. Materials and Methods: 43 patients underwent this study, including 31 renal donors (Group 1) and 12 patients with obstructive uropathy (Group 2). All patients were administered with a range of 5–7 mCi of 99mTc-DTPA. Then, renography performed simultaneously after injection and GFR calculation followed by Gate's method. Blood samples were collected at 60- and 120-min postinjection, samples were counted by a thyroid uptake system, and GFR was calculated using a single plasma sample method (SPSM) and a double plasma sample method (DPSM). Results: The mean GFRs calculated by Gate's method in Groups 1 and 2 were 85.8 ± 18.2 ml/min and 118.4 ± 13.9 ml/min, respectively. Meanwhile, using the in vitro blood sampling methods (DPSM and SPSM), the mean GFRs in Group 1 were 73.8 ± 15.4 ml/min and 56.4 ± 20.9 ml/min, respectively, and in Group 2 were 116.8 ± 12.9 ml/min and 106.3 ± 18.5 ml/min, respectively. There is a high correlation between Gate's method and DPSM in two groups (r = 0.86 and 0.72, respectively), and a moderate correlation was found between Gate's method and SPSM in both groups (r = 0.49 and r = 0.37, respectively). The two in vitro methods (DPSM and SPSM) revealed that moderate correlation in both groups (r = 0.74 and r = 0.67, respectively) was observed. Conclusion: Renography is a simple method but considered inaccurate for GFR determination. However, in vitro plasma sampling is rarely used in Vietnam. In this study, Gate's method correlated well with DPSM and tended to overestimate GFR. Further, the in vitro methods can be applied to correct the in vivo method as a confirmatory test in some cases.

ObjectivesTo investigate the prevalence and quantity of aortic valve calcium (AVC) in two large cohorts, stratified according to age and lipoprotein(a) (Lp(a)), and to assess the association between Lp(a) and AVC.MethodsWe included 2412 participants from the population-based Rotterdam Study (52% women, mean age=69.6±6.3 years) and 859 apparently healthy individuals from the Amsterdam University Medical Centers (UMC) outpatient clinic (57% women, mean age=45.9±11.6 years). All individuals underwent blood sampling to determine Lp(a) concentration and non-enhanced cardiac CT to assess AVC. Logistic and linear regression analyses were performed to investigate the associations of Lp(a) with the presence and amount of AVC.ResultsThe prevalence of AVC was 33.1% in the Rotterdam Study and 5.4% in the Amsterdam UMC cohort. Higher Lp(a) concentrations were independently associated with presence of AVC in both cohorts (OR per 50 mg/dL increase in Lp(a): 1.54 (95% CI 1.36 to 1.75) in the Rotterdam Study cohort and 2.02 (95% CI 1.19 to 3.44) in the Amsterdam UMC cohort). In the Rotterdam Study cohort, higher Lp(a) concentrations were also associated with increase in aortic valve Agatston score (β 0.19, 95% CI 0.06 to 0.32 per 50 mg/dL increase).ConclusionsLp(a) is robustly associated with presence of AVC in a wide age range of individuals. These results provide further rationale to assess the effect of Lp(a) lowering interventions in individuals with early AVC to prevent end-stage aortic valve stenosis.

Objective/Background Individuals with sickle cell anaemia (SCA) may manifest various forms of renal abnormalities. Proteinuria is an early marker of renal dysfunction and a strong risk factor for chronic kidney disease (CKD) progression in both patients with SCA and non-SCA population. Currently, the degree of attention given to proteinuric CKD far exceeds that of nonproteinuric CKD, and risk factors that might trigger a progressive decline of the glomerular filtration rate (GFR) in the absence of proteinuria have not been well evaluated in SCA. The aim of this study was to compare the clinical and laboratory parameters among SCA patients with proteinuric and nonproteinuric CKD. Methods This was a cross-sectional study conducted at the University of Maiduguri Teaching Hospital in north-eastern Nigeria between January 2013 and April 2018. Clinical variables including age of diagnosis of SCA, frequency of vaso-occlusive crises, number of hospitalizations per annum and transfusion therapy were collected. Laboratory data including haematological profile and renal function test were obtained from routine blood sampling. Results A total of 257 patients with SCA (HbSS) were enrolled during the study period of which 42 had proteinuric CKD, and 48 had nonproteinuric CKD. The two groups were matched for the number of hospital admission (p = .063) and blood transfusion per year (p = .450), frequency of painful crisis (p = .210), systolic blood pressure (p = .084) and diastolic blood pressure (p = .400). In the proteinuric CKD group, the mean serum creatinine was higher (332.17 µmol/L, p = .001) and the estimated GFR was lower (31.88 mL/min, p = .046). The serum alkaline phosphatase was higher in the nonproteinuric CKD group (81.81 IU/L, p = .012). Conclusion Nonproteinuric CKD was more frequent than proteinuric CKD in our study population; however, the proteinuric group presented with more advanced disease.

Background Women whose pregnancies are affected by hypertensive disorders of pregnancy, in particular preterm pre-eclampsia, are at increased risk of long-term cardiovascular morbidity and mortality. Objectives To investigate the hypothesis that prolongation of a pregnancy affected by preterm pre-eclampsia managed by expectant management compared with planned early delivery would result in worse cardiovascular function 6 months postpartum. Design A randomised controlled trial. Setting 28 maternity hospitals in England and Wales. Participants Women who were eligible for the Pre-eclampsia in HOspital: Early iNductIon or eXpectant management (PHOENIX) study were approached and recruited for the PHOEBE study. The PHOENIX (Pre-eclampsia in HOspital: Early iNductIon or eXpectant management) study was a parallel-group, non-masked, multicentre, randomised controlled trial that was carried out in 46 maternity units across England and Wales. This study compared planned early delivery with expectant management (usual care) with individual randomisation in women with late preterm pre-eclampsia who were 34 weeks’ gestation to less than 37 weeks’ gestation and having a singleton or dichorionic diamniotic twin pregnancy. Interventions Postpartum follow-up included medical history, blood pressure assessment and echocardiography. All women had blood sampling performed on at least two time points from recruitment to the 6-month follow-up for assessment of cardiac necrosis markers. Main outcome measures Primary outcome was a composite of systolic and/or diastolic dysfunction (originally by 2009 guidelines then updated by 2016 guidelines, with an amended definition of diastolic dysfunction). Analyses were by intention to treat, together with a per-protocol analysis for the primary and secondary outcomes. Results Between 27 April 2016 and 30 November 2018, 623 women were found to be eligible, of whom 420 (67%) were recruited across 28 maternity units in England and Wales. A total of 133 women were allocated to planned delivery, 137 women were allocated to expectant management and a further 150 received non-randomised expectant management within usual care. The mean time from enrolment to delivery was 2.5 (standard deviation 1.9) days in the planned delivery group compared with 6.8 (standard deviation 5.3) days in the expectant management group. There were no differences in the primary outcome between women in the planned delivery group and those in the expectant management group using either the 2009 (risk ratio 1.06, 95% confidence interval 0.80 to 1.40) or the 2016 definition (risk ratio 0.78, 95% confidence interval 0.33 to 1.86). Overall, 10% (31/321) of women had a left ventricular ejection fraction 2, 95% confidence interval 1.12 to 1.59 per 5 kg/m2) and maternal age (adjusted odds ratio 2.16, 95% confidence interval 1.44 to 3.22 per 10 years). Limitations include changing definitions regarding systolic and/or diastolic dysfunction. Conclusions Preterm pre-eclampsia results in persistence of hypertension in the majority of women with late preterm pre-eclampsia at 6 months postpartum and systolic dysfunction in 10%. Pre-eclampsia should not be considered a self-limiting disease of pregnancy alone. Future work Interventions aimed at reducing cardiovascular dysfunction. Trial registration Current Controlled Trials ISRCTN01879376. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 12. See the NIHR Journals Library website for further project information.