Conventional Laboratory Parameters Research Articles

Transient Elastography for Noninvasive Evaluation of Posttransplant Liver Graft Fibrosis in Turkish Children, Ege University Children Hospital Experience.

The influence of advancing fibrosis on graft survival in the context of pediatric liver transplantation accentuates the critical role of protocol-driven liver biopsies, a practice adopted by numerous medical centers. Consequently, the exigency for noninvasive methodologies to assess graft fibrosis assumes heightened importance when conventional clinical and laboratory parameters fail to reveal signs of liver damage. This study aimed to assess the reliability of transient elastography (TE) in pediatric liver transplant recipients to detect graft fibrosis and compare the results of TE in patients who underwent biopsy. This prospective cohort study included liver transplanted children who underwent biopsy at Ege University Children's Hospital between October 1, 2021, and October 31, 2022, and a healthy control group. According to TE, fibrosis was detected in 40 patients, and no fibrosis was detected in 50. The median time to develop fibrosis was 100 months (95% CI [83.1-116.8]). A statistically significant positive correlation existed between LSM and METAVIR fibrosis score (r = 0.562, p = 0.001). There was a statistically significant difference in LSM between patients with F2 fibrosis (7.8-8.8kPa ± 3.2) compared to patients with F0 fibrosis (5.2kPa ± 0.7) (p = 0.005) and F1 fibrosis (6.1kPa ± 1.5) (p = 0.041), on ANOVA. Liver allograft fibrosis is common in long-term follow-up in children who have undergone liver transplantation. Abnormal TE may guide physicians to consider liver biopsy to detect late allograft fibrosis in these children.

Spleen Volume Reduction Is a Reliable and Independent Biomarker for Long-Term Risk of Leukopenia Development in Peptide Receptor Radionuclide Therapy.

177Lu-DOTATATE therapy is an effective treatment for advanced neuroendocrine tumors, despite its dose-limiting hematotoxicity. Herein, the significance of off-target splenic irradiation is unknown. Our study aims to identify predictive markers of peptide receptor radionuclide therapy-induced leukopenia. Methods: We retrospectively analyzed blood counts and imaging data of 88 patients with histologically confirmed, unresectable metastatic neuroendocrine tumors who received 177Lu-DOTATATE treatment at our institution from February 2009 to July 2021. Inclusion criterium was a tumor uptake equivalent to or greater than that in the liver on baseline receptor imaging. We excluded patients with less than 24 mo of follow-up and those patients who received fewer than 4 treatment cycles, additional therapies, or blood transfusions during follow-up. Results: Our study revealed absolute and relative white blood cell counts and relative spleen volume reduction as independent predictors of radiation-induced leukopenia at 24 mo. However, a 30% decline in spleen volume 12 mo after treatment most accurately predicted patients proceeding to leukopenia at 24 mo (receiver operating characteristic area under the curve of 0.91, sensitivity of 0.93, and specificity of 0.90), outperforming all other parameters by far. Conclusion: Automated splenic volume assessments demonstrated superior predictive capabilities for the development of leukopenia in patients undergoing 177Lu-DOTATATE treatment compared with conventional laboratory parameters. The reduction in spleen size proves to be a valuable, routinely available, and quantitative imaging-based biomarker for predicting radiation-induced leukopenia. This suggests potential clinical applications for risk assessment and management.

Longitudinal assessment of angiogenic markers in prediction of adverse outcome in women with confirmed pre-eclampsia.

Angiogenic marker assessment, such as the ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF), is known to be a useful tool in the prediction of pre-eclampsia (PE). However, evidence from surveillance strategies in pregnancies with a PE diagnosis is lacking. Therefore, we aimed to assess the predictive performance of longitudinal maternal serum angiogenic marker assessment for both maternal and perinatal adverse outcomes when compared to standard laboratory parameters in pregnancies with confirmed PE. This was a retrospective analysis of prospectively collected data from January 2013 to December 2020 at the Medical University of Vienna. The inclusion criteria were singleton pregnancy with confirmed PE and post-diagnosis maternal serum angiogenic marker assessment at a minimum of two timepoints. The primary outcome was the predictive performance of longitudinal sFlt-1 and PlGF assessment for adverse maternal and perinatal outcomes compared to conventional laboratory monitoring at the same time in pregnancies with confirmed PE. Composite adverse maternal outcome included intensive care unit admission, pulmonary edema, eclampsia and/or death. Composite adverse perinatal outcome included stillbirth, neonatal death, placental abruption, neonatal intensive care unit admission, intraventricular hemorrhage, necrotizing enterocolitis, respiratory distress syndrome and/or mechanical ventilator support. In total, 885 post-diagnosis sFlt-1/PlGF ratio measurements were obtained from 323 pregnant women with confirmed PE. For composite adverse maternal outcome, the highest standalone predictive accuracy was obtained using maternal serum sFlt-1/PlGF ratio (area under the receiver-operating-characteristics curve (AUC), 0.72 (95% CI, 0.62-0.81)), creatinine (AUC, 0.71 (95% CI, 0.62-0.81)) and lactate dehydrogenase (LDH) levels (AUC, 0.73 (95% CI, 0.65-0.81)). Maternal platelet levels (AUC, 0.65 (95% CI, 0.55-0.74)), serum alanine aminotransferase (ALT) (AUC, 0.59 (95% CI, 0.49-0.69)) and aspartate aminotransferase (AST) (AUC, 0.61 (95% CI, 0.51-0.71) levels had poor standalone predictive accuracy. The best prediction model consisted of a combination of maternal serum LDH, creatinine levels and sFlt-1/PlGF ratio, which had an AUC of 0.77 (95% CI, 0.68-0.85), significantly higher than sFlt-1/PlGF ratio alone (P = 0.037). For composite adverse perinatal outcome, the highest standalone predictive accuracy was obtained using maternal serum sFlt-1/PlGF ratio (AUC, 0.82 (95% CI, 0.75-0.89)) and creatinine (AUC, 0.74 (95% CI, 0.67-0.80)) levels, sFlt-1/PlGF ratio being superior to creatinine alone (P < 0.001). Maternal serum LDH levels (AUC, 0.65 (95% CI, 0.53-0.74)), platelet count (AUC, 0.57 (95% CI, 0.44-0.67)), ALT (AUC, 0.58 (95% CI, 0.48-0.67)) and AST (AUC, 0.58 (95% CI, 0.48-0.67)) levels had poor standalone predictive accuracy. No combination of biomarkers was superior to maternal serum sFlt-1/PlGF ratio alone for prediction of composite adverse perinatal outcome (P > 0.05 for all). In pregnancies with confirmed PE, longitudinal maternal serum angiogenic marker assessment is a good predictor of adverse maternal and perinatal outcomes and superior to some conventional laboratory parameters. Further studies should focus on optimal surveillance following diagnosis of PE. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

JAK inhibitors improve ATP production and mitochondrial function in rheumatoid arthritis: a pilot study

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease associated by inflammation of the synovial tissue and autoantibody production. Oxidative stress and free radicals are known to be indirectly implicated in joint damage and cartilage destruction in RA. Several studies describe the presence of mitochondrial dysfunction in RA, but few of them follow the dynamics in energy parameters after therapy. The aim of our investigation is to evaluate the direct effect of JAK inhibitors on cellular metabolism (and under induced oxidative stress) in RA patients. Ten newly diagnosed RA patients were included in the study. Peripheral blood mononuclear cells (PBMCs) and plasma were isolated before and 6 months after therapy with JAK inhibitors. A real-time metabolic analysis was performed to assess mitochondrial function and cell metabolism in PBMCs. Sonographic examination, DAS28 and conventional clinical laboratory parameters were determined also prior and post therapy. A significant decrease in proton leak after therapy with JAK inhibitors was found. The increased production of ATP indicates improvement of cellular bioenergetics status. These findings could be related to the catalytic action of JAK inhibitors on oxidative phosphorylation which corresponds to the amelioration of clinical and ultra-sonographic parameters after treatment. Our study is the first to establish the dynamics of mitochondrial parameters in PBMCs from RA patients before and after in vivo therapy with JAK inhibitors.

Thromboelastography (TEG) parameters as potential predictors of malignancy and tumor progression in colorectal cancer

PurposeThe purpose of this study was to investigate the use of thromboelastography (TEG) in patients with colorectal cancer and to examine whether the TEG parameters can be used as potential markers for disease screening and prediction of disease severity.MethodsOne-hundred fifteen healthy controls (HC), 43 patients with benign adenoma (BA), and 387 patients with colorectal cancers (CRC) were included in the study. TEG parameters (reaction time, R; clot kinetics, K; alpha angle, α-angle; maximum amplitude, MA), conventional laboratory parameters, and clinical information were collected and analyzed among the HC, BA, and CRC groups. Receiver operating characteristics (ROC) were used for differential analysis. The correlation between TEG parameters and pathological information of CRC (differentiation degree, vaso-nerve infiltration, TNM stage) was analyzed. The differences in TEG parameters at different stages of disease and pre-/post operation were compared.ResultsShorter K and higher α-angle/MA were found in patients with CRC compared with HC and BA (P < 0.001). TEG parameters demonstrated moderate diagnostic value (distinguish CRC from HC + BA: K-AUC = 0.693, α-angle-AUC = 0.687, MA-AUC = 0.700) in CRC but did not outperform traditional laboratory parameters. TEG hypercoagulability was closely associated with tumor markers (carcinoma embryonic antigen and carbohydrate antigen 19–9) and pathological information (differentiation degree, vaso-nerve infiltration, and TNM stage) (P < 0.05). Trend analysis showed that K decreased, but α-angle/MA increased gradually as the tumor progressed (P < 0.001). K- and α-angle showed slightly better sensitivity in predicting advanced tumors compared to traditional laboratory parameters. In CRC patients, 3–6 months after tumor resection, K [from 1.8 (1.5, 2.3) to 1.9 (1.6, 2.6)], α-angle [from 65.3 (59.0, 68.6) to 63.7 (56.6, 68.5)], and MA [from 61.0 (58.2, 66.0) to 58.9 (55.8, 61.3)] exhibited modest improvements compared to their preoperative values (P < 0.05).ConclusionTEG parameters possess moderate diagnostic value in CRC diagnosis and predicting advanced tumors, and they are closely linked to surgical interventions. Although TEG parameters do not significantly outperform traditional laboratory parameters, they still hold promise as potential alternative indicators in CRC patients.

THU207 11-oxygenated Androgens Are Strongly Associated With Treatment Quality In Children With Congenital Adrenal Hyperplasia Due To 21-Hydroxylase Deficiency

Abstract Disclosure: O. Abawi: None. T. Du Toit: None. G. Sommer: None. C.D. Vögel: None. M. Groessl: None. U. Halbsguth: None. S.E. Hannema: None. C. de Bruin: None. E. Charmandari: None. E.L. van den Akker: None. C.E. Flueck: None. Introduction: Treatment of children with Congenital Adrenal Hyperplasia (CAH) aims at balancing steroid replacement, hyperandrogenism and hypercortisolism. Optimal treatment and its assessment however remain a conundrum. Currently, specialists integrate clinical and conventional laboratory parameters such as 17-hydroxyprogesterone (17OHP) and androstenedione (A4). In recent years, 11-oxygenated androgens (11oxyAs) have been proposed as promising biomarkers, but their merit in treatment monitoring is not yet established. Aim: To investigate potential biomarkers of treatment quality in children with CAH by comprehensive serum steroid profiling. Methods: This prospective, observational cohort study was conducted at 4 academic pediatric endocrinology outpatient clinics and included children with genetically confirmed 21-hydroxylase deficiency. At 2 consecutive visits (mean 4.1 ± 0.7 months apart), a targeted and untargeted panel of conventional adrenal and additional peripheral steroids was analysed in serum using liquid chromatography-mass spectrometry. This included 11β-hydroxy (11OH)-androstenedione (11OHA4), 11keto-A4 (11KA4), 11OH-testosterone (11OHT), and 11keto-T (11KT). At each visit, the pediatric endocrinologist classified patients as undertreated, optimally treated or overtreated based on detailed clinical and endocrinologic evaluation, including serum 17OHP and A4 profiling. Mixed-effects logistic regression analyses on log-steroid concentrations adjusted for age, sex, BMI-z, pubertal status, CAH subtype (classic vs non-classic) and random effects for unique patients were performed to investigate odds ratios (OR) of being undertreated vs optimally treated. False discovery rate adjusted P&amp;lt;0.05 was considered significant. Results: We included 138 visits (86 [62%] optimal treatment, 52 [38%] undertreatment) from 72 patients, of whom 31 (43%) girls, 59 (82%) had classic CAH, and 31 (43%) were prepubertal. Mean age at first visit was 10.6 ± 5.2 years, mean BMI-z was 0.6 ± 1.1. Ten out of 17 conventional steroids, including 17OHP and 21-deoxycortisol but not A4, were associated with undertreatment. All 11oxyAs were associated with undertreatment: 11OHA4 (OR 3.64, SE 1.42, P=0.008), 11OHT (OR 2.91, SE 1.09, P=0.012), 11KT (OR 2.77, SE 1.00, P=0.01), and 11KA4 (OR 2.64, SE 0.84, P=0.009). The strongest association with undertreatment was found for the sum of 11oxyAs (OR 4.04, SE 1.70, P=0.008). Discussion: We show that 11oxyAs have the strongest association with undertreatment in children with CAH. This study supports the inclusion of 11oxyAs in the biochemical work-up of CAH to improve treatment monitoring and underscores the importance of analysing unconventional steroids in CAH by comprehensive steroid profiling. Following on, our steroid profiling can now be extended to characterise other forms of CAH and cases of suspected overtreatment. Presentation: Thursday, June 15, 2023

Role of RBC Parameters to Differentiate between Iron Deficiency Anemia and Anemia of Chronic Diseases

Introduction: In the present study we evaluated and compared RBC parameters, iron status, and ferritin for discriminating between patients with iron deficiency anemia and anemia of chronic disease. Anemia that accompanies infection, inflammation, and cancer, is commonly termed anemia of chronic disease (ACD). Methods: We compared the ability of serum ferritin concentration, using the microplate immunoenzymometric assay method with other, more traditional indicators of iron status like total iron binding capacity [TIBC], mean corpuscular volume [MCV], percent transferrin saturation [%TS], RBC distribution width [RDW], and serum iron concentration [SIC]. The ferritin concentration was determined in 80 serum samples selected from men and women above the age of 18 years. The patients were assigned to IDA and ACD groups based on serum ferritin concentration. Observation: By studying the ROC Curve for various red cell parameters for the diagnosis of IDA and ACD, we found that diagnostic accuracy of various indicators was as follows TIBC&gt;TS%&gt;MCV&gt;MCH&gt;SI&gt;MCHC for anemia of chronic diseases, and TIBC&gt;MCH&gt;MCV&gt;MCHC&gt;TS%&gt;SI for iron deficiency anemia. When both the value of AUCs (Area under Curve) of ROC were compared it is apparent that TIBC, TS%, MCV, and MCH are important discriminating factors between IDA and ACD. Conclusion: Conventional laboratory parameters play an important role in distinguishing overt causes of IDA and ACD. MCV, MCH, and TIBC were found to be (p - value &lt; .05) significantly discriminated against IDA and ACD. Serum ferritin is an important diagnostic tool with reasonable accuracy for the detection and differentiation of iron deficiency anemia and anemia of chronic disease.

High levels of exfoliated fragments following glycocalyx destruction in hemorrhagic fever with the renal syndrome are associated with mortality risk.

The glycocalyx is a gel-like structure that covers the luminal side of vascular endothelial cells. It plays an important role in maintaining the integrity of the vascular endothelial barrier structure. However, the presence or absence of glycocalyx destruction in hemorrhagic fever with renal syndrome (HFRS) and its specific mechanism and role is still unclear. In this study, we detected the levels of exfoliated glycocalyx fragments, namely, heparan sulfate (HS), hyaluronic acid (HA), and chondroitin sulfate (CS), in HFRS patients and investigated their clinical application value on the evaluation of disease severity and prognosis prediction. The expression of exfoliated glycocalyx fragments in plasma was significantly increased during the acute stage of HFRS. The levels of HS, HA, and CS in HFRS patients during the acute stage were significantly higher than in healthy controls and convalescent stages of the same type. HS and CS during the acute stage gradually increased with the aggravation of HFRS, and both fragments showed a significant association with disease severity. In addition, exfoliated glycocalyx fragments (especially HS and CS) showed a significant correlation with conventional laboratory parameters and hospitalization days. High levels of HS and CS during the acute phase were significantly associated with patient mortality and demonstrated an obvious predictive value for the mortality risk of HFRS. Glycocalyx destruction and shedding may be closely associated with endothelial hyperpermeability and microvascular leakage in HFRS. The dynamic detection of the exfoliated glycocalyx fragments may be beneficial for the evaluation of disease severity and prognosis prediction in HFRS.

Role of Procalcitonin as a Biomarker in Early Identification of Adverse Events Following Esophageal Atresia Surgery.

Surgical complication following esophageal atresia repair is one of the several factors known to influence the final outcomes. Early identification of such complications may help in timely institution of therapeutic measures and translate into improved prognosis. The objective of this study was to evaluate the role of procalcitonin in early prediction of the adverse events after surgery in patients of esophageal atresia and the temporal relationship with clinical manifestations and other inflammatory biomarkers such as C-reactive protein (CRP). This was a prospective study on consecutive patients of esophageal atresia (n = 23). Serum procalcitonin and CRP levels were assessed at baseline (prior to surgery) and on postoperative days (POD) 1, 3, 5, 7, and 14. The trends in the biomarker values and temporal relationships of deviation in trend with the clinical and conventional laboratory parameters and patient outcomes were analyzed. Baseline serum procalcitonin was elevated (n = 23; 1.7 ng/ml: min: 0.07 ng/ml-max: 24.36 ng/ml) in 18/23 (78.3%) patients. Procalcitonin nearly doubled on POD-1 (n = 22; 3.28 ng/ml: min: 0.64 ng/ml-max: 16.51 ng/ml) followed by a gradual decline. CRP was also elevated on POD-1 (three times the baseline) and depicted a delayed peak at POD-3. POD-1 procalcitonin and CRP levels correlated with survival. POD-1 procalcitonin cutoff at 3.28 ng/ml predicted mortality with a sensitivity and specificity of 100% and 57.9% (P = 0.05). Serum procalcitonin and CRP were higher for patients who sustained complications, so was the time required for hemodynamic stabilization. Procalcitonin (baseline and POD-5) and CRP (POD-3 and POD-5) values correlated with the clinical course after surgery. Baseline procalcitonin cutoff at 2.91 ng/ml predicted the possibility of a major complication with a sensitivity of 71.4% and a specificity of 93.3%. POD-5 procalcitonin cutoff at 1.38 ng/ml predicted the possibility of a major complication with a sensitivity of 83.3% and a specificity of 93.3%. Patients who sustained major complications depicted a change in serum procalcitonin trend 24-48 h ahead of clinical manifestation of an adverse event. Procalcitonin is a good indicator to identify the adverse events in neonates after surgery for esophageal atresia. The procalcitonin levels in patients who sustained a major complication depicted a reversal in trend 24-48 h of clinical manifestation. POD-1 procalcitonin correlated with survival while the baseline and POD-5 serum procalcitonin predicted the clinical course.

Potential role of circulating miRNA-146a and serum kallikrein 1 as biomarkers of renal disease in biopsy-proven lupus nephritis patients

Aim of the workTo evaluate the performance of circulating miR-146a and serum kallikrein1 (KLK1) as biomarkers for detecting disease activity and distinguishing histopathological changes associated with lupus nephritis (LN). Patients and methods90 systemic lupus erythematosus (SLE) patients (44 with active non-renal disease and 46 with LN) were examined for relative expression levels of circulating miR-146a, assessed by reverse transcription quantitative real-time PCR (RT-qPCR) and serum KLK1 levels, measured by ELISA. SLE disease activity was assessed using SLEDAI-2 k. Receiver operating characteristic curve was employed to examine the diagnostic performance of both biomarkers and established conventional laboratory parameters of renal function with specific renal histologic features seen in LN. As well, 40 apparently healthy control subjects were enrolled. ResultsCirculating miR-146a levels were significantly lower (p < 0.01), while serum KLK1 levels were significantly higher (p < 0.01) in active LN patients compared to active non-renal and controls. miR-146a levels negatively correlated with serum creatinine, Albumin/Creatinine and SLEDAI-2 k (p ≤ 0.01), while serum KLK1 significantly correlated with serum creatinine, Albumin/Creatinine and C3 (p ≤ 0.05) and inversely with miR-146a (p = 0.002). Both circulating miR-146a and KLK1 revealed an outstanding performance in predicting renal activity among SLE patients with an AUC of 0.949 and 0.947 respectively. In active LN patients, KLK1 and miR-146a exhibited good ability in differentiating proliferative from non-proliferative LN (AUC 0.73, 0.65 respectively), and in predicting biopsy activity index ≥7, surpassing conventional disease measures. ConclusionCirculating miR-146a and serum KLK1 are potential biomarkers for LN that could compete with invasive renal biopsy. Independent validation is warranted.

Evaluation of the Predictive Role of Standard Laboratory Tests for Disease Severity in Patients with Deep Venous Thrombosis

Introduction: Deep venous thrombosis (DVT) can result in fatal outcomes if it is not timely diagnosed and sufficiently treated. Some laboratory markers were identified in previous reports for predicting the disease with low sensitivity or specificity. We aimed to evaluate the predictive value of serum albumin levels and compare them with conventional laboratory parameters. Material and Methods: Fifty patients with acute lower-extremity DVT who has no previous history of malignancy or hematologic disorder were included in the study. The demographical variables and standard biomarkers of the DVT group were compared with the normal population (n:50). Thereafter patients were divided into two groups as extensive DVT (thrombosis involves popliteal, femoral, and iliac veins together) and localized DVT (thrombosis involves popliteal vein and below) and biomarkers were compared in patient groups. Results: The demographical variables and white blood cell count (WBC) found as similar between healthy groups and DVT groups. However, mean platelet volume (MPV), D-Dimer, neutrophil to lymphocyte ratio (NLR), and fibrinogen to albumin ratio (FAR) were found markedly higher in DVT patients. Moreover, statistically incremental FAR and NLR levels were detected (p &lt; 0.05) in patients with extensive DVT (involved iliac and femoral veins). Conclusion: Serum NLR and FAR levels seem to be significant predictors for the extensive thrombotic event in patients with DVT.

Comparative value of purine metabolites in preeclampsia and acute cerebral stroke

The values of the purine metabolites in preeclampsia and acute cerebral stroke were compared. A total of 33 patients with preeclampsia and 350 patients with an acute cerebral stroke were examined. The blood and liquor guanine, hypoxanthine, adenine, xanthine, and uric acid were determined by a direct spectrophotometry, in addition to conventional laboratory parameters. It has been established that there are clinicalpathobiochemical parallels between preeclampsia and the cerebral stroke, including by the features of purine metabolism. It is known that the most pronounced adverse metabolic indicator (marker, predictor) for both preeclampsia and the cerebral stroke is hyperuricemia. It was revealed that the favorable sign for stroke is the high values of oxypurines (hypoxanthine, xanthin, and uric acid) in the cerebrospinal fluid, and for preeclampsia their low levels. It has been shown that cerebrospinal fluid is not only the medium of administration of the drugs for spinal anesthesia, but also a source of valuable diagnostic and prognostic information, including in preeclampsia. Preeclampsia is metabolically like stroke with an unfavorable significance of hyperuricemia and diametrically antagonistic to stroke with a favorable value not increased, but a reduced concentration of hypoxanthine, xanthin, and uric acid in cerebrospinal fluid. The level of uric acid and other purines in patients suffering from a preeclampsia and in patients suffering from a cerebral stroke should be determined not only in the blood serum, but also, as far as possible, in cerebrospinal fluid.

Changes of pituitary adenylate cyclase activating polypeptide (PACAP) level in polytrauma patients in the early post-traumatic period

In polytrauma patients who survive the primary insult, the imbalance between the pro- and anti-inflammatory processes seems to be responsible for life-threatening complications such as sepsis or multiple organ dysfunction syndrome. Measurement of C-reactive protein (CRP) and procalcitonin (PCT) is a standard way for differentiating between infectious (bacterial) and non-infectious inflammation. Monitoring of immune cell functions, like leukocyte anti-sedimentation rate (LAR) can also be useful to diagnose infectious complications. Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with well-known immunomodulatory and anti-inflammatory effects. The aim of our study was to determine the changes of PACAP38 levels in polytrauma patients in the early post-traumatic period in intensive care unit and analyse possible correlation of its level with conventional (CRP, PCT) and unconventional (LAR) laboratory parameters. Twenty polytrauma patients were enrolled. Blood samples were taken daily for five days. We observed significant correlation between PACAP38 and CRP levels on day 4 and 5 as well as between PACAP38 and LAR levels all of the days. This could be due to the anti-inflammatory and cytoprotective functions of PACAP38 as part of an endogenous response to the trauma induced systemic inflammatory response syndrome. These significant correlations could have clinical importance in monitoring the dynamic balance of pro- and anti-inflammatory processes in case of polytraumatic patients.

Predictive value of pentraxin-3 on disease severity and mortality risk in patients with hemorrhagic fever with renal syndrome

BackgroundHemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus is characterized by systemic immunopathological injury. Pentraxin-3 is an acute-phase reactant involved in the processes of inflammation and infection. This study aimed to investigate the levels of plasma pentraxin-3 and evaluate its predictive value on disease severity and mortality risk in patients with HFRS.MethodsThis was a prospective real-world observational study. The concentrations of plasma pentraxin-3 were measured by enzyme linked immunosorbent assay (ELISA) in 105 HFRS patients and 27 healthy controls. We analyzed the clinical relevance between pentraxin-3 and clinical subtyping, hospital stay and conventional laboratory parameters of HFRS patients. Considering the prognosis (death) as the primary endpoint, the levels of pentraxin-3 between survivors and non-survivors were compared, and its association with mortality was assessed by Kaplan-Meier survival analysis. The predictive potency of pentraxin-3 for mortality risk in HFRS patients was evaluated by receiver operating characteristic (ROC) curve analysis.ResultsThe levels of pentraxin-3 during the acute phase were increased with the aggravation of the disease, and showed the highest expression in critical-type patients (P < 0.05). Pentraxin-3 demonstrated significant correlations with conventional laboratory parameters (WBC, PLT, AST, ALB, APTT, Fib) and the length of hospital stay. Compared with the survivors, non-survivors showed higher levels of pentraxin-3 and worse expressions of conventional laboratory parameters during the acute phase. The Kaplan-Meier survival curves showed that high levels of pentraxin-3 during the acute phase were significantly associated with the death in HFRS patients. Pentraxin-3 demonstrated significant predictive value for the mortality risk of HFRS patients, with the area under ROC curve (AUC) of 0.753 (95%CI: 0.593 ~ 0.914, P = 0.003).ConclusionsThe detection of plasma pentraxin-3 might be beneficial to the evaluation of disease severity and to the prediction of mortality risk in HFRS patients.

Association of a High Neutrophil-to-Lymphocyte Ratio with Hyperdense Artery Sign and Unfavorable Short-Term Outcomes in Patients with Acute Ischemic Stroke.

PurposeImmune–inflammatory processes are involved in all the stages of stroke. This study investigated the association of the neutrophil-to-lymphocyte ratio (NLR) with the hyperdense artery sign (HAS) observed on brain computed tomography (CT) and with clinical features in patients with acute ischemic stroke.MethodsWe retrospectively enrolled 2903 inpatients with acute ischemic stroke from May 2010 to May 2019. Data collected included imaging studies, risk factors, laboratory parameters, and clinical features during hospitalization.ResultsThe HAS was identified in 6% of the 2903 patients and 66% of the 236 patients with acute middle cerebral artery occlusion. Patients with the HAS had a higher NLR. HAS prevalence was higher in men and patients with cardioembolism. The NLR exhibited positive linear correlations with age, glucose and creatinine levels, length of hospital stay, initial National Institutes of Health Stroke Scale (NIHSS) scores, and mRS scores at discharge. The NLR was significantly higher in patients with large-artery atherosclerosis and cardioembolism and was the highest in patients with other determined etiology. Multivariate analysis revealed that an initial NIHSS score of ≥10 and an NLR of >3.5 were significant positive factors, whereas diabetes mellitus and age > 72 years were significant negative factors for the HAS, with a predictive performance of 0.893. An initial NIHSS score of ≥5, positive HAS, age > 75 years, diabetes mellitus, an NLR of >3.5, female sex, a white blood cell count of >8 × 103/mL, and elevated troponin I were significant predictors of unfavorable outcomes, with a predictive performance of 0.886.ConclusionAn NLR of >3.5 enabled an efficient prediction of CT HAS. In addition to conventional risk factors and laboratory parameters, both an NLR of >3.5 and CT HAS enabled improved prediction of unfavorable stroke outcomes.

HEPARIN-INDUCED THROMBOCYTOPENIA IN A PATIENT WITH ANTI-PHOSPHOLIPID SYNDROME AFTER AORTIC VALVE REPLACEMENT

SESSION TITLE: Medical Student/Resident Critical Care SESSION TYPE: Med Student/Res Case Report PRESENTED ON: October 18-21, 2020 INTRODUCTION: Heparin-induced thrombocytopenia (HIT) is a feared complication of heparin exposure due to antibodies against platelet factor 4 (PF4) and heparin. The reported incidence of HIT ranges from 0.1 to 5% in patients exposed to heparin (1). Nearly all patients undergoing cardiac surgery are exposed to heparin and up to 50% of patients who undergo cardiopulmonary bypass develop antibodies to PF4. Though this does not necessarily correlate to a higher incidence, 1-2% of cardiac patients develop HIT. In these patients, alternative agents for anticoagulation are required, presenting unique challenges in monitoring. CASE PRESENTATION: A 44-year-old female with severe aortic insufficiency and moderate aortic stenosis was scheduled for aortic valve replacement (AVR). Her history was notable for anti-phospholipid syndrome (APLS) with an extensive history of thromboses including hepatic, renal, pulmonary and placental thrombosis, maintained on chronic warfarin. The patient had a remote history of HIT; however, pre-operatively she had a negative PF4 antibody and serotonin release assay (SRA), and bridging was done with enoxaparin. She underwent successful AVR with heparin use intra-operatively. Post-operatively, her platelet counts down-trended from 166,000/μL to 78,000/μL. Given her remote history of HIT, repeat antibody and SRA were sent and argatroban was used for post-op anticoagulation. As the patient’s baseline activated partial thromboplastin time (aPTT) was prolonged, argatroban was titrated using thrombin time (TT). Argatroban was started at 0.2 mcg/kg/min. TT was assessed every 6 hours after initiation with titration by 0.1mcg/kg/min until a therapeutic goal of 30-50 seconds was achieved. DISCUSSION: In healthy patients, aPTT is recommended for monitoring the effect of argatroban. However, in the case of APLS, antibodies interfere with coagulation tests that are phospholipid dependent, resulting in a prolonged baseline aPTT. Though there is no established range for the use of TT for monitoring argatroban, a recent study of agatroban in critically ill patients found TT to correlate with plasma drug concentrations (2). Low levels of argatroban were found to correlate with TT that are 30-50 seconds and intermediate plasma levels of argatroban correlate with TT that are approximately 50-100 seconds. Other options include fixed dose argatroban without monitoring of laboratory parameters or using non-phospholipid dependent measures such as thromboelastometry (3). CONCLUSIONS: As is demonstrated in this case, suspected HIT following cardiac surgery can be difficult to manage; this is further compounded in patients with APLS with baseline altered coagulation parameters. When a direct thrombin inhibitor is used, TT monitoring can be considered in patients that cannot be monitored using aPTT. Reference #1: Pishko AM, Cuker A. Heparin-Induced Thrombocytopenia in Cardiac Surgery Patients. Semin Thromb Hemost. 2017; 43(7):691–698. Reference #2: Beiderlinden M, Werner P, Bahlmann A, et al. Monitoring of argatroban and lepirudin anticoagulation in critically ill patients by conventional laboratory parameters and rotational thromboelastometry - a prospectively controlled randomized double-blind clinical trial. BMC Anesthesiol. 2018; 18(1):18. Reference #3: Pendleton, R., Wheeler, M. M., & Rodgers, G. M. Argatroban Dosing of Patients with Heparin-Induced Thrombocytopenia and an Elevated aPTT Due to Antiphospholipid Antibody Syndrome. Annals of Pharmacotherapy. 2006; 40(5): 972–976. DISCLOSURES: No relevant relationships by Ashley Budd, source=Web Response No relevant relationships by Prachi Patel, source=Web Response

Value of S100A12 in predicting in‑stent restenosis in patients with coronary drug‑eluting stent implantation

In-stent restenosis (ISR) after drug-eluting stent (DES) placement has recently emerged as a major concern for cardiologists. Identification of biomarkers to predict ISR may be invaluable for tailored management strategies. The present study aimed to evaluate the prognostic utility of circulating S100 calcium-binding protein A12 (S100A12) for ISR. Out of 2,443 patients with DES-based percutaneous coronary intervention (PCI) and follow-up angiography at ~1 year after DES-based PCI, 258 patients were diagnosed with ISR and 258 patients without ISR were randomly selected as controls. Serum S100A12 levels were determined in the two subsets on admission. The association between ISR and the circulating levels of S100A12 was determined by constructing two multivariate stepwise logistic regression models. In addition, S100A12 was assessed for its ability to predict ISR using receiver operating characteristic (ROC) curve analysis. The serum levels of S100A12 at baseline were significantly elevated in patients in the ISR group compared with those in the non-ISR group (P<0.001). In the multivariate logistic regression analysis, after adjusting for conventional cardiovascular risk factors, laboratory parameters and medication after the procedure, the S100A12 level was revealed to be independently associated with ISR. When a cut-off for serum S100A12 levels of 34.75 ng/ml was used, the ROC curve was able to predict ISR with 72.8% sensitivity and 79.1% specificity, and the area under the ROC curve was 0.796 (95% CI: 0.757 to 0.834, P<0.001). Furthermore, addition of S100A12 to established risk factors significantly improved the predictive power of reference models for ISR. S100A12 may serve as an independent marker to predict ISR in patients undergoing coronary DES implantation.

The study of the innate and acquired cellular immunity chains indicators in the peripheral blood of patients with HIV infection.

In this study was made an attempt to reveal additional laboratory markers of white blood for preliminary estimation level of HIV-infection development. Essentially such markers these are in progress without complex equipment and expensive reagent. It was studied alterations of basic values cells of innate and acquired immunity of peripheral blood HIV-infected individuals with and without antiretroviral treatment (ART) during infection. It was estimate value leukocytes, neutrophils, monocytes, lymhpocytes, T-lymhpocytes, CD4+, CD8+ T-cells, CD4/CD8 index. It was used the first analysis in the time of registration for regular medical check-up and the intermediate derived during 2017-2018 years. Patients without ART and with ART before and after treatment had rates of leukocytes, lymhpocytes, T-lymhpocytes, monocytes and neutrophils within the normal guideline. Essential changes were observed in basic conventional laboratory parameters evaluation of HIV-infection dynamic (parameters of CD4+, CD8+ T-cells, CD4/CD8 index). Thereby it was impossible to reveal supplementary immunological markers of HIVinfection.

Characterization of circulating thrombin in patients with septic shock: a prospective observational study.

Septic shock is characterized by a dysregulated response to infection, hypotension and activation of the coagulation system. Markers of coagulation activation are commonly used to diagnose and monitor ensuing coagulopathies. In this study, we sought to determine levels of circulating thrombin in patients with septic shock. To characterize levels of circulating, active thrombin in patients with septic shock. 48 patients with septic shock were included in this prospective, observational study. Blood samples were obtained on admission, day 1, day 3 and day 6. Levels of active thrombin were measured using a standardized, clinically applicable oligonucleotide (aptamer)-based enzyme-capture assay (OECA). Thrombin levels were correlated with established indirect thrombin parameters, conventional coagulation tests, laboratory parameters, patient characteristics and outcome. Elevated levels of thrombin were detected in 27 patients (56.3%) during the course of the study. Thrombin levels were positively correlated with thrombin-antithrombin complexes (r = 0.30, p < 0.05) and negatively associated with FVII levels (r = - 0.28, p < 0.05). Thrombin levels on admission did not predict 30-day mortality (OR 0.82, 95% CI 0.23-2.92, p = 0.77). Circulating levels of active thrombin can be measured in a subset of patients with septic shock. Although thrombin levels are correlated with established markers of coagulation, they do not provide additional prognostic information.

Vanin‐1 as a novel biomarker for kidney injury for hydronephrosis

Urinary tract obstruction and the subsequent development of hydronephrosis represent a common cause of kidney injury, resulting in chronic kidney disease. Neither currently used imaging techniques nor conventional laboratory parameters are sufficient to assess the onset of this condition. The purpose of the study was to assess whether vanin‐1 could be a novel renal biomarker in kidney injury due to hydronephrosis. Male Sprague‐Dawley rats were subjected to unilateral ureteric obstruction (UUO) or sham operation. For urinalysis, renal pelvic urine and voided urine were used for the UUO, and sham‐operated rats, respectively. Urinary vanin‐1 excretion was expressed as a vanin‐1/creatinine ratio. In addition to echographic images demonstrating time‐dependent accumulation of urine in the renal pelvis, histopathological renal tubular injuries became severe and renal fibrosis eventually developed. At day 7 after UUO, the vanin‐1 level in the renal pelvic urine was significantly higher than that in voided urine from the sham‐operated rats, and remained at the same level until day 14. Immunohistochemical staining of vanin‐1 in the renal cortices revealed that vanin‐1 expression was localized not only around the injured tubules, but also within a subset of injured tubules, but not in the area with interstitial fibrosis. Vanin‐1 mRNA and protein expression significantly decreased, whereas the expression of transforming growth factor (TGF)‐β1 and snail‐1, which plays a pivotal role in the pathogenesis of renal fibrosis via the epithelial‐to‐mesenchymal transition (EMT), increased. These results suggest that vanin‐1 in the renal pelvic urine is released from the renal tubular cells in UUO rats and reflects renal tubular injury at an early stage. Hydronephrosis always involves incomplete obstruction, and urinary vanin‐1 may serve as a candidate biomarker of renal tubular injury due to hydronephrosis.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.