Standard Laboratory Assessments Research Articles

Dietary Omega-3 PUFA Intake in Patients with Chronic Kidney Disease: The Association with Vitamin D Deficiency, Intima-Media Thickness and Blood Pressure.

Background/Objectives: Numerous risk factors associated with development of cardiovascular disease (CVD) have been unfavorably altered in patients with chronic kidney disease (CKD). Low omega-3 polyunsaturated fatty acid (PUFA) intake and vitamin D deficiency are potential cardiometabolic risk factors in patients with CKD. The aim of this study was to evaluate dietary intake and status of omega-3 PUFA and vitamin D in pre-dialysis and hemodialysis patients and to examine the association of dietary α-linolenic acid (ALA) and fish consumption with blood pressure and carotid intima-media thickness (C-IMT), representing a non-invasive marker of atherosclerosis in CKD patients. Methods: All 77 selected patients (36 pre-dialysis, 41 on hemodialysis) underwent standardized clinical, nutritional, and laboratory assessments. Repeated 24 h recalls were performed to assess dietary intake. The fatty acid profile was determined by gas-liquid chromatography. Results: Inadequate vitamin D intake and vitamin D status were found in 95% of patients. PUFA profiles did not differ between hemodialysis and pre-dialysis participants. Dietary intake of ALA was negatively correlated with systolic blood pressure (SBP) (p = 0.013), C-IMT (p = 0.002), serum CRP (p = 0.044), iPTH (p = 0.01), and 25(OH)D3 (p = 0.006). ALA intake of more than 0.23 g daily was linked with lower SBP (p = 0.001), serum 25(OH)D3 (p = 0.004), and C-IMT (p = 0.002). Conclusions: This study contributes to a better understanding of the relationship between dietary ALA intake and C-IMT in CKD. The results of this study could emphasize the significant role of the high prevalence of vitamin D deficiency and inadequate omega-3 PUFA intake and status regarding CVD health in CKD patients.

Standardized observation of temperament in Lebanese toddlers using the laboratory temperament assessment battery (Lab-TAB)

BackgroundTemperament is the difference between individuals’ emotional and behavioral responses to diverse external events. It is a complex interplay between genetic and environmental factors. Hence, the need to assess temperament objectively and better understand its impact on developmental and interpersonal outcomes. Measuring temperament in early childhood can be challenging since parents will report their subjective perceptions about their toddlers. While surveys are quick instruments that require less clinical involvement, standardized laboratory assessments secure a relatively high level of objective observation. Since no published studies were conducted in Arab countries, the current research focuses on examining temperament in a sample of twenty mother-toddler dyads using the Laboratory Temperament Assessment Battery (Lab-TAB) locomotor version.Interrater reliability and validity were assessed. Higher-order temperament components were determined by principal component analysis. T test and one-way ANOVA examined the association between demographics and temperament components.ResultsThe retained variables ranged between fair (> 0.43) and good (< 0.98) for all Lab-TAB episodes. Three higher-order temperament components were obtained. Age was significantly negatively correlated with Lab-TAB Fear dimension, r = − .47, p > .05, and Lab-TAB temperament component 3, r = .45, p > .05. Male toddlers (M = .55, SD = 1.055) had significantly higher levels of temperament component 3 compared to female (M = − .45, SD = .718), t(18) = 2.52, p < .05. There was a significant effect of time spent with mother on temperament component 3, F(2,17) = 7.01, p < .05.ConclusionAfter exploring the temperament factor structure, we found that the Lab-TAB locomotor version was a valid tool to be used to observe temperament in toddlers living in Lebanon, a Middle Eastern culture. Some gender significant differences would deserve deeper exploration in future research. A replication of this study would also strengthen its findings.

Prognostic utility of point-of-care measured bioadrenomedullin in patients presenting with acute heart failure at the emergency department

Abstract Funding Acknowledgements None. Background Acute heart failure (AHF) is a severe condition that is frequently encountered in the emergency department (ED). We aimed to investigate the role of bioadrenomedullin (bio-ADM)- a molecule previously shown to be associated with clinical congestion- as an early prognostic marker for short-term outcomes in patients presenting with AHF in the ED. Methods Seventy-six AHF patients were prospectively enrolled upon ED presentation. Clinical, echocardiography, standard laboratory and cardiac biomarker assessments were performed. Bio-ADM was measured from whole blood sample using a commercially available point-of-care immunoassay. We examined prognostic utility of bio-ADM for predicting 30-day mortality. Results Study group consisted of 61% males, of mean(±SD) age 71±13years, systolic blood pressure (SBP) 140±41mmHg, categorized according to AHF clinical phenotypes as 15(20%) pulmonary edema, 53(70%) decompensated chronic HF and 8(10%) cardiogenic shock. Median (IQR) creatinine, NTproBNP, hsTroponinT and bio-ADM were: 1.15(0.90-1.83)mg/dl, 5094(2836-12816)pg/ml, 38(24-91)pg/ml and 52.3(45-113)pg/ml, respectively. Levels of bio-ADM were higher in patients with cardiogenic shock compared to acute pulmonary edema and decompensated chronic HF [median (IQR): 266.8(101.9-500)pg/ml, 49.8(45-67.5)pg/ml and 47.4(45-97.5)pg/ml, respectively], (p=0.019). Log(bio-ADM) was significantly correlated with SBP (Spearman rho= -0.387, p=0.003), logCreatinine (rho=0.430, p&amp;lt;0.001), log(NTproBNP) (rho=0.430, p=0.003) and log(hsTroponinT) (rho= 0.386, p=0.003). During 30-days follow-up, 15 patients died. In ROC analysis, a bio-ADM cutoff of 64.8pg/ml predicted 30-day mortality with 75% sensitivity and 65% specificity (AUC 0.763, p=0.017). In a multivariable Cox proportional hazards model that included log(bio-ADM), log(NTproBNP) and logCreatinine and adjusted for AHF phenotype, only log(bio-ADM) seemed to be independently prognostic of 30-day mortality (HR,95%CI: 5.80, 0.97-34.66, p=0.054). Conclusions In a broad AHF population, point-of-care bio-ADM measured upon presentation at the ED is associated with worse clinical and biochemical AHF profiles and may provide independent prognostic information for 30-day mortality.30-day mortality by bio-ADM ≥ vs &amp;lt;64.8

Relationship between Triglyceride-Glucose Index and Disease Activity and Subclinical Atherosclerosis in Rheumatoid Arthritis.

In rheumatoid arthritis (RA), insulin resistance (IR) is related to inflammatory markers, disease activity, and progression of atherosclerotic changes. Triglyceride-glucose (TyG) index is a relatively new indicator of IR. The present study aimed to investigate the relationship between TyG index, disease activity and subclinical atherosclerosis (SCA) in RA patients. The present case-control study included 100 RA patients and 50 age- and sex-matched healthy controls. All participants were subjected to careful history taking through clinical examination and standard laboratory assessment. The TyG index was calculated as TyG index = ln (Fasting triglyceride (mg/dL) × fasting glucose (mg/dL))/2. Carotid intima-media thickness (CIMT) measurement was done using B-mode ultrasound. Patients had significantly higher TyG index as compared to controls. Patients with high disease activity had significantly higher frequency of extraarticular manifestations (39.6% versus 51.6%, p = 0.028), higher Larsen score (3.8 ± 1.3 versus 2.8 ± 1.2, p < 0.001), higher anti-cyclic citrullinated peptide (anti-CCP) levels (median (IQR): 243.1 (205.0-408.0) U/ml versus 99.0 (78.0-332.5), p < 0.001), higher TyG index (4.8 ± 0.22 versus 4.67 ± 0.24, p = 0.006), and higher CIMT (0.87 ± 0.22 versus 0.77 ± 0.17 mm, p = 0.018). Patients with SCA had higher BMI (34.6 ± 6.2 versus 30.5 ± 5.3 Kg/m2, p < 0.001), higher Larsen score (3.7 ± 1.4 versus 3.1 ± 1.3, p = 0.028) and higher TyG index (4.89 ± 0.23 versus 4.64 ± 0.19, p < 0.001). Binary logistic regression analysis identified patients' age (OR (95% CI): 0.94 (0.89-0.99), p = 0.018), Larsen score (OR (95% CI): 1.93 (1.32-2.82), p = <0.001), anti-CCP (OR (95%): 1.04 (1.02-1.07), p = 0.032), and TyG index (OR (95% CI): 22.67 (2.14-240.4), p = 0.01) as significant predictors of high disease activity in multivariate analysis. IR estimated by the TyG index is related to disease activity and SCA in RA patients.

Relationship between Subclinical Hypothyroidism and Uremic Pruritis in Hemodialysis Patients.

Uremic pruritus (UP) is one of the most distressing symptoms in hemodialysis (HD) patients. Subclinical hypothyroidism (SCH) is a biochemical condition with high prevalence in HD patients. The present multicentric study aimed to assess the relationship between UP and SCH in HD patients. The present cross-sectional study included 328 HD patients. All patients were submitted to careful history through clinical examination and standard laboratory assessment. Pruritis was evaluated using the pruritis visual analog scale (VAS). Patients were diagnosed with SCH if they had TSH levels above the upper limit of the normal reference range in association with normal free thyroxine (FT4) levels. Among the studied patients, there were 196 patients (59.8 %) with UP. Comparison between patients with UP and patients without revealed that patients in the former group had significantly longer HD duration (median (IQR): 47.5 (27.0-72.5) versus 36.0 (23.0-50.5) months, p < 0.001) and lower Kt/v (median (IQR): 1.4 (1.09-1.7) versus 1.54 (1.12-1.91), p = 0.009). Moreover, they had significantly higher ferritin (median (IQR): 653.0 (526.0-800.0) versus 628.0 (470.8- 716.0) ng/mL), hsCRP (median (IQR): 12.0 (8.0-14.0) versus 8.0 (6.0-9.0) mg/dL, p < 0.001) and TSH levels (median (IQR): 4.34 (1.98-5.2) versus 3.34 (1.9-4.85) μIU/ml) with a significantly higher frequency of SCH (45.9 % versus 28.8 %, p = 0.002). Logistic regression analysis identified hemodialysis duration (OR (95%) CI): 1.02 (1.009-1.028), p < 0.001), ferritin levels (OR (95% CI): 1.002 (1.001-1.003), p < 0.001), and SCH (OR (95% CI): 0.54 (0.32-0.89), p = 0.016) as significant predictors of UP. The present study suggested a possible link between SCH and the development of UP in HD patients.

Clinical value of RANKL, OPG, IL-6 and sclerostin as biomarkers for fibrous dysplasia/McCune-Albright syndrome.

Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare genetic bone disease caused by a somatic mutation in the GNAS gene. Currently used bone turnover markers (BTMs) do not correlate with the clinical picture and are not useful to predict or monitor therapy success. This study assessed the correlation of RANKL, OPG, RANKL/OPG ratio, IL-6 and sclerostin with the classic BTMs alkaline phosphatase (ALP), procollagen type 1 propeptide (P1NP) and beta crosslaps (CTX), with pain, skeletal burden score (SBS) and response to bisphosphonate or denosumab treatment. Ninety-six serum samples of adult patients >18years of age with any subtype of FD/MAS were included from the biobank facility of the Leiden University Medical Center, Center for Bone Quality between 2015 and 2021. Standard laboratory assessments were assessed as part of usual care. The concentrations of potential biomarkers RANKL, OPG, sclerostin, IL-6 were analyzed. Data on FD/MAS subtype, age, pain, treatment history and treatment response were retrieved from the electronic patient files. Baseline characteristics were summarized by descriptive statistics. Correlations of the concentrations of the potential biomarkers with classic bone turnover markers, SBS and pain scores were cross-sectionally assessed by Spearman rank order correlation. Correction for multiple testing was performed by Benjamini and Hochberg False Discovery Rate. A sensitivity analyses was performed by excluding patients with SBS below 15 and patients using antiresorptive medication at the time of blood withdrawal or within the wash-out period. In patients treated with bisphosphonates or denosumab after blood withdrawal, pre-treatment concentrations were compared in patients with and without therapy response by Mann Whitney U test. The median age of the patients was 41.2 (Q1-Q3 25.9-52.2) years, 62.5% was female. Median SBS was 2.5 (Q1-Q3 0.5-7.8). RANKL level correlated weakly with ALP (Spearman rho 0.309, p=0.004, n=84), but not with P1NP or CTX. The RANKL/OPG ratio, OPG, IL-6 and sclerostin did not correlate with ALP, P1NP or CTX. None of the potential biomarkers correlated with SBS or pain. Results of the sensitivity analyses were comparable. Pre-treatment biomarker levels were similar in patients with and without improvement in pain scores following bisphosphonate therapy. Pre-treatment RANKL and sclerostin were comparable between patients with and without improvement in pain scores after denosumab therapy. Pre-treatment IL-6 level and the RANKL/OPG ratio seemed to be higher in patients with response to denosumab (IL-6: median 0.64 (Q1-Q3 0.53-0.74) pg/mL, n=6, RANKL/OPG: median 0.062 (Q1-Q3 0.016-0.331), n=5) compared to patients without response (IL-6: median 0.35 (0.20-0.54) pg/mL, n=5, RANKL/OPG: 0.027 (0.024-0.046), n=4). Pre-treatment IL-6 correlated with the improvement in maximum pain scores (rho 0.962, p<0.001, n=9) and average pain scores (rho 0.895, p=0.001, n=9) reported during denosumab therapy. Increased concentrations of RANKL, IL-6, sclerostin and of the RANKL/OPG ratio do not indicate severity of FD/MAS, as no correlation was observed of these potential biomarkers with the classic BTMs and SBS. Biomarker levels did not correlate with pain and had no value in predicting bisphosphonate treatment response. These biomarkers are not superior over the currently used methods of assessing ALP, P1NP and CTX or evaluating SBS to establish disease extent or activity and provide no reliable results. Yet, possibly pre-treatment IL-6 and the RANKL/OPG ratio may have some predictive value for clinical response to denosumab. Therefore, studies investigating disease activity and treatment response should include lesional imaging and patient-reported outcome measures.

Cerebral oximetry and autoregulation monitoring in shock patients

Background: Data on regional cerebral oxygen saturation (rSO2) and cerebral autoregulation monitoring in shock patients are limited. This study aimed to find the optimal range of rSO2 and cerebral oximetry index (COx), an autoregulation index correlated with adequate tissue perfusion determined by standard clinical and laboratory assessment. Method: We plan to monitor cerebral oximetry using near-infrared spectroscopy in shock patients admitted to the medical intensive care unit (MICU) at Siriraj Hospital. The rSO2 are continuously recorded for 72 hours [48] after admission or 24 hours after cessation of vasopressor infusion. The COx is calculated from the correlation coefficient between rSO2 and MAP. Data on patient demographics, treatments, physiologic parameters, and outcomes are recorded. The primary objective is to identify the optimal rSO2 and COx correlated with adequate tissue perfusion assessed by the current standard method. Adequate tissue perfusion as is defined as MAP ≥65 mmHg and two of the following criteria: urine ≥0.5 ml/kg/hour, capillary refill time ≤3 seconds, improvement in consciousness, lactate reduction ≥10% in 1 hour, serum lactate &lt;2 mmol/L, or central venous oxygen saturation (ScVO2) ≥70%. Since the optimal values of rSO2 and COx in shock patients are unknown, we are unable to perform the sample size calculation. Thus, for this study, we plan to collect data on rSO2 and COx in 30 patients. Hypothesis: We hypothesize that the values of rSO2 and COx are different between patients with adequate and inadequate tissue perfusion. Ethics statement: The study was reviewed and approved by the Human Research Protection Unit of Siriraj Hospital, Mahidol University (certificate of approval no. si 410/2022).

Abstract OT3-16-01: On-going prospective study to measure serum progranulin/GP88 levels in metastatic breast cancer patients in association with disease status

Abstract The ability to monitor response to therapy and disease progression in metastatic breast cancer (MBC) patients is a major step in patient management. Imaging is the method of choice for the assessment of disease status and the monitoring of disease progression. However, this approach remains expensive, expose patients to radiation and thus is mainly performed every 2-3 months. During this time interval, the disease may progress significantly on ineffective treatment and the patient may present treatment related toxicities due to the inability to detect progression at earlier times. Circulating levels of tumor associated biomarkers such as CA15-3 and CEA are often determined to track disease status of MBC. However, even though they can provide information about disease progression, they do not always provide a reliable measure of response to therapy. The monitoring of disease status and progression through the measurement of drivers of disease should provide an alternative and complementary approach to existing strategies in order to better to monitor the disease status and enable proactive management of MBC patients. Progranulin also called Glycoprotein 88kDa (PGRN/GP88) is an autocrine growth factor overexpressed in breast cancer. Biological studies have established GP88 as a critical player in breast tumorigenesis. GP88 overexpression is associated with the malignant phenotype, estrogen independence, increased proliferation, survival, and drug resistance. High PGRN/GP88 tumor expression measured by immunohistochemistry in invasive ductal carcinoma is an independent prognostic marker associated with increased risk of recurrence and mortality. Clinical studies have demonstrated that GP88 circulating levels as measured by enzyme immunoassay are elevated in breast cancer patients, compared to healthy individuals. In MBC patients, circulating GP88 levels correlate with overall survival. These facts are supportive of the hypothesis that the measurement of circulating GP88 levels in MBC patients can serve as an additional biomarker to monitor MBC disease status and be predictive to outcome. A prospective study was established is to identify whether there is a statistically significant change in serum GP88 levels associated with time to progression of breast cancer as measured by RECIST 1.1 criteria in MBC patients. With the assumptions that patients will provide a baseline and four follow up visits and that 20% of the visits record a disease progression, time to progression. Taking the plausible and clinically relevant performance to be 75% sensitivity and 46% false positive, a sample of ninety patients would give 85% power. Under IRB approved protocols at the University of Maryland Greenebaum Comprehensive Cancer Center and at two Baltimore Medstar Health Facilities, a total of 103 female breast cancer patients with measurable or evaluable metastatic disease will be consented and enrolled. The patients have been re-staged within 4 weeks and will continue or begin new therapy. Currently, we have enrolled sixty-five subjects at the three facilities. In addition to standard laboratory assessment and radiographic imaging/staging every 2-3 months on study, blood samples will be collected from each patient. The samples are stored at -70C until evaluated for GP88 using a GP88 enzyme linked immunoassay. We will analyze the GP88 serum level in correlation with survival and with disease status determined as responder, stable or progressing based on the RECIST criteria. This study is supported by grant R44CA210817 from the National Cancer Institute to Ginette Serrero Principal Investigator. Citation Format: Ginette Serrero, Paula Rosenblatt, Nancy Tait, Barbara Rector, Jennifer A. Latteri, Binbin Yue, Katherine Tkaczuk. On-going prospective study to measure serum progranulin/GP88 levels in metastatic breast cancer patients in association with disease status [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-16-01.

Clinical and Prognostic Significance of Baseline Serum Vitamin D Levels in Hospitalized Egyptian Covid-19 Patients.

Vitamin D is a hormone with essential roles in both cellular metabolism and immunity. It controls calcium homeostasis and modulates innate and adaptive immune system responses. Many studies suggested an association between vitamin D deficiency and clinical outcomes of covid-19 infection, while others failed to document such a relation. The present study aimed to evaluate the clinical and prognostic significance of baseline vitamin D levels in hospitalized Egyptian covid-19 patients. The present retrospective study included 300 hospitalized covid-19 patients. Patients were submitted to standard clinical, laboratory, and radiological assessment. According to vitamin D levels, patients were classified to have normal levels (≥30), insufficient levels (20-29) or deficient levels (<20). According to their vitamin D levels, patients were classified into those with normal vitamin D (n=135), others with vitamin D insufficiency (n=114), and a third group with vitamin D deficiency (n=51). Patients with normal vitamin D levels and vitamin D insufficiency are significantly younger [median (IQR): 49.0 (39.0-57.0) versus 51.0 (40.0-61.0) and 55.0 (43.0-62.0) years, respectively, p=0.012] and had less frequency of severe disease (24.4% versus 40.4% and 51.0%, respectively) when compared with those with vitamin D deficiency. Moreover, they had significantly lower levels of D dimer [median (IQR): 1.5 (0.9-2.5) versus 1.8 (0.9-3.1) and 2.0 (1.0-3.2)], CRP [median (IQR): 58.0 (30.0-120.0) versus 76.0 (42.5-160.0) and 105.0 (74.0-208.0), respectively, p<0.001], ferritin [median (IQR): 458.0 (240.0-759.0) versus 606.0 (433.8-897.8) and 820.0 (552.0-1087.0), respectively, p<0.001], and procalcitonin [median (IQR): 290.0 (152.0-394.0) versus 372.5 (227.0-530.5) and 443.0 (272.0-575.0), respectively, p<0.001]. Only lower vitamin D levels were significant predictors of mortality in multivariate analysis [OR (95% CI): 0.88 (0.84-0.92), p<0.001]. Low vitamin D levels are related to exaggerated inflammatory response, disease severity, and poor clinical outcome in hospitalized covid-19 patients.

Pregnancy loss and subsequent risk of prediabetes, diabetes and metabolic syndrome in couples: Tehran lipid and glucose study

BackgroundThere is limited evidence regarding the impact of pregnancy loss on the subsequent risk of metabolic disorders. We aimed to investigate whether history of pregnancy loss is associated with the subsequent risk of prediabetes (pre-DM), diabetes (DM), and metabolic syndrome (METs) among couples.MethodIn this population-based cohort study, 2765 couples with and without history of pregnancy loss and free of DM, pre-DM, and METs at baseline were included and followed for incidents of DM, pre-DM, and METs by 3-year intervals visits from 1999 to 2018. Detailed data of variables was collected using standard questionnaires, interviews, clinical and laboratory assessments. A modified Poisson regression for binary outcome data with a log link function and robust error variance was used to estimate relative risks (RRs) in couples with and without history of pregnancy loss. Both unadjusted and adjusted models were fitted, and effect measures were calculated.ResultDuring a median follow-up of 15 years, females with history of pregnancy loss were experienced more pre-DM (50% vs. 45.5%), DM (28.9% vs. 21.3%), and METs (70% vs. 60.1%) than females without such history. Moreover, history of pregnancy loss increased the risk of METs by 8% among females. The incidence of DM in males with history of pregnancy loss in their spouses was higher than in males without it (28.8% vs. 23.5%). Among males, having a spouse with history of pregnancy loss was positively associated with the risk of pre-DM (RR = 1.12; 95%CI: 1.02, 1.23, p = 0.02); furthermore, they were more prone to the risk of METs than females with a history of pregnancy loss (RR = 1.13; 95%CI: 1.07, 1.20, p < 0.001).ConclusionAlthough pregnancy loss is a female-specific factor, may foreshadow the subsequent METs, our study identified a higher risk of subsequent pre-DM and METs in males with history of pregnancy loss in their spouses. Pregnancy loss could be considered a possible future risk factor for metabolic disorders in couples.

Individual and joint effects of trehalose and glutamate on diabetic retinopathy: a propensity score-matched case–control study

Although previous studies demonstrate that trehalose can help maintain glucose homeostasis in healthy humans, its role and joint effect with glutamate on diabetic retinopathy (DR) remain unclear. We aimed to comprehensively quantify the associations of trehalose and glutamate with DR. This study included 69 pairs of DR and matched type 2 diabetic (T2D) patients. Serum trehalose and glutamate were determined via ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry system. Covariates were collected by a standardized questionnaire, clinical examinations and laboratory assessments. Individual and joint association of trehalose and glutamate with DR were quantified by multiple conditional logistic regression models. The adjusted odds of DR averagely decreased by 86% (odds ratio (OR): 0.14; 95% CI: 0.06, 0.33) with per interquartile range increase of trehalose. Comparing with the lowest quartile, adjusted OR (95% CI) were 0.20 (0.05, 0.83), 0.14 (0.03, 0.63) and 0.01 (<0.01, 0.05) for participants in the second, third and fourth quartiles of trehalose, respectively. In addition, as compared to their counterparts, T2D patients with lower trehalose (<median) and higher glutamate (≥median) had the highest odds of DR (OR: 36.81; 95% CI: 6.75, 200.61). An apparent super-multiplicative effect of trehalose and glutamate on DR was observed, whereas relative excess risk due to interaction was not significant. The study suggests that trehalose is beneficial to inhibit the occurrence of DR and synergistically decreases the risk of DR with reduced glutamate. Our findings also provide new insights into the mechanisms of DR and further longitudinal studies are required to confirm these findings.

Ethiopathogenetic features and course of ischemic stroke associated with COVID-19

To analyze etiopathogenetic factors and course of ischemic stroke associated with new coronavirus infection (COVID-19). A retrospective clinical study of 173 patients with ischemic stroke and COVID-19 (main group) and 86 patients with ischemic stroke without COVID-19 (comparison group) was carried out. There were no statistically significant differences in age and gender. All patients underwent standard clinical-instrumental, laboratory and neuroimaging assessments. Compared with the comparison group, patients with COVID-19 were less likely to have cardiovascular risk factors, the difference being statistically significant. Stroke in the main group was more severe than in the comparison group. According to the TOAST classification, an unknown stroke subtype significantly predominated in the main group. Laboratory data in the main group indicated the significance of an increase in renal-hepatic markers (creatinine, aspartate aminotransferase) and systemic inflammatory response syndrome (C-reactive protein). The development of cardiovascular diseases in patients with COVID-19 is an important negative prognostic factor that requires further study to determine the optimal management strategy.

Development and Preliminary Validation of an Electromyography-Scoring Protocol for the Assessment and Grading of Muscle Involvement in Patients With Juvenile Idiopathic Inflammatory Myopathies

IntroductionWe performed a pilot study in order to investigate the feasibility of an electromyography (EMG)-scoring protocol for the assessment of disease activity in juvenile idiopathic inflammatory myopathies (JIIM). MethodsChildren with JIIM followed up in a tertiary-level care center underwent standardized clinical, laboratory, and EMG assessment. An EMG-scoring protocol was devised by a consensus panel including a pediatric neurophysiologist and two pediatric rheumatologists, based on a combined score obtained as the sum of (1) the presence of denervation signs (fibrillation potentials) and (2) motor unit remodeling (mixed pattern of short- and long-duration motor unit action potentials). The EMG-scoring protocol was then validated following the Outcome Measures in Rheumatoid Arthritis Clinical Trials filter for outcome measures in rheumatology and the consensus-based standards for the selection of health measurement instruments methodology. ResultsThirteen children (77% females) were included in the study, with a median age of 10 years (interquartile range: 7-17 years) and median disease duration of 11.8 months (interquartile range: 2.1-44.5). A total of 39 EMG examinations were evaluated. A strong positive association between a standardized tool for muscle strength assessment and the combined score was observed. No significant associations were found with both creatine kinase and erythrocyte sedimentation rate levels. DiscussionOur EMG-scoring protocol is the first standardized and reproducible tool for the neurophysiologic evaluation and grading of muscle involvement in patients with JIIM and could provide relevant additional information in the assessment and follow-up of these rare conditions.

Enteral and supplemental parenteral nutrition enriched with omega-3 polyunsaturated fatty acids in intensive care patients – A randomized, controlled, double-blind clinical trial

Enteral nutrition (EN) and parenteral nutrition (PN) enriched with omega-3 polyunsaturated fatty acids (PUFA) have beneficial effects in critical illness. This study aimed to assess the combined effect of EN and supplemental PN enriched with omega-3 PUFA on blood oxygenation in intensive care unit (ICU) patients. Single-center, prospective, randomized, controlled, double-blind, phase III trial conducted from 10/2013 to 11/2017. A total of 100 ICU patients (18-85 years, APACHE II score>15) requiring mechanical ventilation were randomly assigned to received combined EN and PN either with omega-3 PUFA (omega-3 group) or without (control group) for up to 28 days. Primary endpoint: 'change of PaO2/FiO2 from day (D) 1 to D4'. Secondary endpoints: lung function parameters, ICU complications, length of hospital stay, days free of ICU care/ventilation/sedation/catecholamine treatment, mortality, erythrocyte fatty acid composition, inflammatory parameters. Safety parameters: standard laboratory assessment, vital signs, physical examination, SOFA score, adverse events. Combined EN and PN covered energy requirements to more than 80%. Blood oxygenation (ΔPaO2/FiO2 from D1 to D4:-1.3±83.7, n=42, and 13.3±86.1, n=39, in omega-3 and control group, respectively, p=0.7795) and other lung function parameters did not differ between groups but days free of catecholamine treatment were significantly higher in the omega-3 group (~4 days, p=0.0481). On D6, significantly more patients in the omega-3 group tolerated EN alone (51.0% vs. 29.8%, p=0.0342).Eicosapentaenoic acid (EPA) content in erythrocytes was significantly increased in the omega-3 group at last observation compared with the control group (ΔEPA: 0.928±0.808% vs.-0.024±0.190%, p<0.0001). No further significant group differences were detected. Enteral and supplemental PN both enriched with omega-3 PUFA did not improve lung function but allowed earlier weaning from catecholamine treatment and PN. Supplemental PN succeeded to adequately cover energy requirements in critically ill patients. www.clinicaltrials.gov, registration number: NCT01162928.

Safety and tolerability of Miltuximab® - a first in human study in patients with advanced solid cancers.

Miltuximab® is a chimeric antibody targeting Glypican-1 (GPC-1), a cell surface antigen which is overexpressed in solid cancers. Miltuximab® has shown promising safety and efficacy in radioimmunotherapy models of prostate cancer. This first in human study used Miltuximab® radiolabelled with Gallium-67 ([67Ga]Ga-DOTA-Miltuximab®). The primary study endpoint was to establish safety and tolerability of Miltuximab®. Secondary endpoints were biodistribution, tumour targeting and pharmacokinetic analysis. Four cohorts of three patients (9 with advanced prostate cancer, 2 with pancreatic and 1 with bladder cancer) were dosed with 1 mg, ~250 MBq of [67Ga]Ga-DOTA-Miltuximab®. Cohort 1 received [67Ga]Ga-DOTA-Miltuximab® alone, while cohorts 2-4 were pre-infused with increasing doses (3.5, 11.5 and 24 mg, respectively) of unlabelled Miltuximab®-DOTA 1 hour prior to [67Ga]Ga-DOTA-Miltuximab®. Safety and tolerability were assessed by clinical and standard laboratory assessments. Patients underwent whole body gamma-camera scans and SPECT/CT scans up to 144 h post-infusion. Total organ radiation exposure was determined by dosimetry of whole-body gamma scans. The dosing regimen was well tolerated, with no drug-related adverse events observed. Liver and spleen uptake of [67Ga]Ga-DOTA-Miltuximab® was observed. Liver uptake was reduced by pre-infusion of unlabelled Miltuximab®-DOTA. Dosimetry analysis showed a favorable exposure profile. [67Ga]Ga-DOTA-Miltuximab® targeting to tumour sites was observed in two prostate cancer patients who had failed enzalutamide treatment. Higher doses of unlabelled antibody achieved lower liver uptake and increased antibody serum half life. This study is the first in human for Miltuximab® a first in class antibody targeting GPC-1. The trial met its primary endpoint of safety, demonstrating its potential as a safe and tolerable monoclonal antibody. This safety data, together with targeting to tumour lesions and biodistribution information supports the further clinical development of Miltuximab® as a theranostic agent in a planned Phase I human trial.

Serum Neurofilament Levels in Children With Febrile Seizures and in Controls

ObjectiveNeuroaxonal damage is reflected by serum neurofilament light chain (sNfL) values in a variety of acute and degenerative diseases of the brain. The aim of this study was to investigate the impact of febrile and epileptic seizures on sNfL, serum copeptin, and prolactin levels in children compared with children with febrile infections without convulsions.MethodsA prospective cross-sectional study was performed in children aging 6 months to 5 years presenting with fever (controls, n = 61), febrile seizures (FS, n = 78), or epileptic seizures (ES, n = 16) at our emergency department. sNfL, copeptin, and prolactin were measured within a few hours after the event in addition to standard clinical, neurophysiological, and laboratory assessment. All children were followed up for at least 1 year after presentation concerning recurrent seizures.ResultsSerum copeptin values were on average 4.1-fold higher in FS and 3.2-fold higher in ES compared with controls (both p < 0.01). Serum prolactin values were on average 1.3-fold higher in FS compared with controls ( p < 0.01) and without difference between ES and controls. There was no significant difference of mean sNfL values (95% CI) between all three groups, FS 21.7 pg/ml (19.6–23.9), ES 17.7 pg/ml (13.8–21.6), and controls 23.4 pg/ml (19.2–27.4). In multivariable analysis, age was the most important predictor of sNfL, followed by sex and C reactive protein. Neither the duration of seizures nor the time elapsed from seizure onset to blood sampling had an impact on sNfL. None of the three biomarkers were related to recurrent seizures.SignificanceSerum neurofilament light is not elevated during short recovery time after FS when compared with children presenting febrile infections without seizures. We demonstrate an age-dependent decrease of sNfL from early childhood until school age. In contrast to sNfL levels, copeptin and prolactin serum levels are elevated after FS.

Choose your words wisely: Optimizing impacts on standardized performance testing

BackgroundThe OPTIMAL theory of motor learning identifies motivational (enhanced expectancies, EE, and autonomy support, AS) and attentional (an external attentional focus, EF) factors that affect motor performance and learning [1]. One implication of this theory is that standardized clinical and laboratory assessments of physical capacity and motor performance that do not incorporate optimizing conditions may underestimate true maximal capabilities. The influence of "optimized" conditions on a clinical-applied test of balance control was examined with healthy participants. Given the motor performance benefits of optimized conditions predicted by the OPTIMAL theory, it was hypothesized that providing participants with information that induced EE, provided them with AS, and promoted their use of EF would reduce balance errors and postural sway. MethodsWe used as an exemplar assessment, the Balance Error Scoring System (BESS), and center-of-pressure (COP) velocity measurements of postural sway. Participants performed under two different conditions, separated by two days: an optimized (EE, AS, and EF) condition and a control (“neutral”) condition, with sample-wide order counterbalancing. In each condition, participants performed three stances (double-leg, single-leg, and tandem) on two support surfaces (firm and foam). Stance order was participant-determined in the optimized condition and, for the control condition, yoked to a participant in the optimized condition. ResultsParticipants committed fewer balance errors in the optimized condition than in the control condition (p < .001) and their resultant COP velocity in the optimized condition was lower than that in the control condition (p = .004). BESS scores were correlated with resultant COP velocity (r = .593, p < .001). SignificanceOur results demonstrated the impact of implementing optimized, as opposed to “neutral” control, conditions for better insight into balance capabilities in normal and challenging situations. Practitioners’ roles in mediating test situations and using subtle wording to promote optimized performance may have consequential impacts on motor assessment outcomes.

Differential Composition of Vaginal Microbiome, but Not of Seminal Microbiome, Is Associated With Successful Intrauterine Insemination in Couples With Idiopathic Infertility: A Prospective Observational Study.

BackgroundVaginal and seminal microbiomes have gained increasing interest for their involvement in reproductive health and fertility. However, their role in reproductive outcome is not fully understood yet. In this study, we aimed to correlate the vaginal and the seminal microbiome of 23 couples with idiopathic infertility to the clinical pregnancy rate after intrauterine insemination (IUI).MethodsVaginal swabs and seminal fluids were collected on the day of IUI procedure and analyzed through polymerase chain reaction amplification of variable regions 3 and 4 (V3–V4) of 16S ribosomal ribonucleic acid genes and Illumina MiSeq sequencing. The taxonomic data were then correlated to IUI success.ResultsIdiopathic infertile women showed a different average composition of vaginal microbiome compared with control sequences, whereas for seminal counterpart no relevant differences were observed. Furthermore, among idiopathic infertile women, different patterns of Lactobacillus species dominations were observed, with a predominance either of Lactobacillus crispatus, a marker of a healthy vaginal ecosystem, or of Lactobacillus iners and Lactobacillus gasseri, associated with a more dysbiosis-prone environment. More important, considering all investigated variables, vaginal L crispatus domination was the only factor strongly associated to IUI success (P = .0002).ConclusionsOur results strengthen the potential role of L crispatus in promoting a favorable environment for pregnancy and suggest that microbiome characterization could be useful, together with standard clinical and laboratory assessments, in the pre-IUI evaluation of infertile couples.

Assessing the Safety of Various VWF Regimens in Patients with Clinically Severe VWD: A Natural History Study

Background: Von Willebrand disease (VWD) is the most common inherited bleeding disorder in humans affecting up to 1% of the population, while symptomatic prevalence is likely closer to 0.1%. A deficiency of von Willebrand factor (VWF) can be quantitative (type 1 or type 3) or qualitative (type 2) and lead to a bleeding diathesis of variable intensity roughly correlating with functional activity. Diagnosis can be challenging due to variable penetrance and large influence of multiple pre-analytic variables and a wide testing coefficient of variation. Treatment for VWD is focused on replacement of defective or deficient VWF with a plasma-derived or recombinant VWF-containing product, release and elevation of endogenous stores of VWF with Desmopressin (DDAVP), or prevention of premature fibrinolysis with an antifibrinolytic, such as aminocaproic acid. Although there is relative consensus on the management of mild VWD, there is scarce literature about the optimal treatment of patients with severe disease, especially in regard to factor replacement. Real World evidence for the use of primary (prior to significant bleeding) or secondary (following development of significant bleeding) prophylaxis is lacking with the majority of studies relying heavily on retrospective data. Additionally, ongoing VWD prophylaxis studies typically only allow participants to enroll if they previously have not been on prophylaxis, limiting our ability to learn about this growing population of patients. Study Design and Methods: Approximately 1,900 VWD patients were identified in the ATHNdataset with a VWF:Ag or VWF:RCo of ≤ 30%, with ~170 of these on prophylaxis. This group, in addition to those VWD patients with clinically significant bleeding and ≤ 40% of normal VWF:Ag or VWF:RCo, provide a potential unmet opportunity to examine prophylaxis and treatment patterns. Furthermore, a standardized laboratory assessment (including a standardized diagnostic battery, genetic evaluation of VWF gene, and inhibitor testing) will provide significant enrichment of the ATHNdataset by fully characterizing patients that are highly likely to utilize factor concentrates. Inclusion criteria are patients with severe VWD defined as type 3 VWD, or VWF:RCo, VWF:GP1bM or VWF:Ag≤ 30%, patients with clinically severe VWD as defined by VWF:Rco, VWF:GP1bM or VWF:Ag ≤ 40% with severe bleeding phenotype requiring recurrent use of factor concentrates, and co-enrollment in the ATHNdataset. Patients with platelet-type or acquired VWD are excluded. The primary objective is to assess the safety of various VWF regimens for different indications (on-demand, surgery, and prophylaxis) in adult and pediatric patients with clinically severe VWD. Safety is measured by the number of reported events as defined by the European Haemophilia Safety Surveillance (EUHASS) program. Secondary objectives are to enrich and analyze data from clinically severe congenital VWD patients by collecting laboratory data; to establish sub-studies for patients who are treated with VWF products on demand or who have started on or switched to a particular VWF containing product; to evaluate the use of factor replacement as prophylaxis in a cohort of severe VWD participants over 6 month time periods; to describe bleeding events, changes in overall bleeding, and annualized bleed rate as measured by the International Society on Thrombosis and Haemostasis (ISTH) Bleeding Assessment Tool (BAT) and if applicable the Pictorial Bleed Assessment Chart (PBAC); and to describe real-world effectiveness of VWD treatment as measured by health care utilization and quality of life measures (PROMIS® and V-WIQ questionnaires). Descriptive statistics will be calculated to analyze the primary and secondary outcomes. For each categorical variable, its frequency and percentage will be reported. In terms of a continuous measurement, its mean, median, standard deviation, interquartile range, minimum, and maximum values will be disclosed. The study will attempt to enroll a target number of at least 50 participants who are receiving VONVENDI but will not mandate the use of VONVENDI. More study design details are outlined in Table 1. Disclosures Sidonio: Genetech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda-Shire: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bioverativ: Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Grifols: Membership on an entity's Board of Directors or advisory committees, Research Funding; Biomarin: Membership on an entity's Board of Directors or advisory committees; Uniqure: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Kedrion: Research Funding.

Diet barriers in type 2 diabetic patients and their coping strategies

Background: Factors hindering effective nutritional therapy (diet barriers, DB) in type 2 diabetes mellitus (DM2), their coping strategies and association with biomedical and psychosocial characteristics of the Russian patients have not been studied.Aim: To identify the role and clinical correlates of DB and diet coping in various categories of patients with DM2.Materials and methods: This cross-sectional cohort study included 297 consecutively recruited out- and in-patients with DM2 (mean age 61±10.1 years, diabetes duration 1 to 35 years). All patients had standard clinical and laboratory assessments and filled in questionnaires on DB, diet coping, level of knowledge on DM, state/trait anxiety scale, depression scale (modified Zung), Diabetes Treatment Satisfaction questionnaire (DTSQ), Audit of Diabetes-dependent Quality of Life questionnaire (Ru-ADDoQL). Mann-Whitney, chi-square and Fischer's exact test were used for group comparisons. Final analysis was based on multiple and logistic regression models.Results: Mean (±SD) number of DB per patient was 8.4±4.9 and similar in insulin-treated and non-insulin-treated patients. The most prevalent were DB related to poor physical well-being (51% of the patients), additional financial burden (54%) and decreased food variety (41%). The highest weighted prevalence was identified for 6 DB, such as “difficulties to adhere to the diet in unexpected situations” (1.8 scores), “having to spend a lot for the diet” (1.4), “if I eat not regularly, I feel unwell”, “I cannot eat tasty foods and enjoy them” (1.3 each), “when I eat more than I am allowed, I feel unwell”, “I would like to eat what it is not allowed for me” (1.2 each), and “it is difficult to fully abstain from sweets” (1.1). Number of DB per patient increased significantly with age and decreased with higher educational level and social status. There were differences in types of DB between male and female patients, between those currently employed and non-employed, and between highly compliant and non-compliant to their diabetes regimen. There was an inverse correlation between DB numbers and total dietary adherence score, diabetes-dependent quality of life score, subjective assessment of personal health status and a direct correlation between DB number and trait anxiety. No impact of past participation in a diabetes education program or of the level of knowledge on diabetes on DB number was found. For most DB the patients demonstrated the socalled compliant coping (i.e., adherence to the diet recommendations), excluding the DB “I am not allowed to eat when I am hungry”, which was associated mostly with intermediate coping styles that might unfavorably influence one's health status. The compliant diet coping scores were in a weak negative correlation with DB number and with the patient's level of knowledge on diabetes. DTSQ score weakly but significantly correlated with the total score of compliant and intermediate diet coping.Conclusion: Main DB in DM2 are related to physical discomfort, financial problems and limitations in food choices. Individual DB content depends on age, gender, educational level, social status and employment. Higher numbers of DB per patient is associated with decreased possibility of compliant diet coping style. Overloaded diet recommendations are associated with an increase in DB number that may lead to poorer patient compliance to diabetes treatment in general, as well as to poorer diabetes-dependent quality of life. Elderly patients, as well as those with lower educational level, unemployed, with uncontrolled diabetes, poor general compliance and higher levels of anxiety and depression have the highest DB numbers. Individual DB are to be considered during therapeutic patient education in DM2 and patient-tailored approach to therapy.