Clinical Chemistry Parameters Research Articles

End-user verification results of two serum separator tubes for clinical chemistry analytes according to CLSI GP34-A and CLSI GP41-A6

Tube manufacturers use different composition of gels and blood clot activator formulations in serum tube production. Our aim was to investigate the within-tube (repeatability) and between-tube variation, concordance between comparison results of BD and VacuSEL tubes. Blood samples were collected from control subjects (n = 20) and patients (n = 30) in accordance with the CLSI GP41-A6 and CLSI GP34-A guidelines. Twenty-three clinical chemistry parameters were analysed via Roche Cobas C702 Chemistry Analyzer on T0 (0 hour) and T24 (24 hour). Mean differences % were compared with Wilcoxon matched pair test. Clinical significance was evaluated based on desirable bias according to total allowable error (TEa). VacuSEL tubes demonstrated acceptable performance for the results of 20 parameters with regards to desirable bias % limits. Lactate dehydrogenase (LD) [mean difference % (%95 confidence intervals (CI) values of BD and VacuSEL tubes at T0 [6.41% (4.80–8.01%)]; sodium (Na) and total protein (TP) at T24 [-0.27% (-0.46 to −0.07%) and −1.39% (-1.87 to −0.91), respectively] were over the desirable bias limits (LD: 4.3%, Na: 0.23% and TP: 1.36%, respectively) but not exceeding total biological variation CV % [Na: 0.5 (0.0–1.0) % and TP: 2.6 (2.3–2.7) %). %95 confidence intervals (CI) of T0 LD values overlap with within-subject biological variation % (CI) limits (LD: 5.2 (4.9–5.4) %). The differences between two tubes were not medically significant and necessarily conclusive. VacuSEL serum tubes presented comparable performance with BD serum tubes.

A retrospective analysis of the application of sigma metrics for the assessment of quality assurance in selected clinical chemistry and Hematology parameters in Batangas Medical Center from january to june 2022

A retrospective analysis of the application of sigma metrics for the assessment of quality assurance in selected clinical chemistry and Hematology parameters in Batangas Medical Center from january to june 2022

Safety Assessment of Streptococcus salivarius UBSS-01 in Rats and Double-Blind Placebo-Controlled Study in Healthy Individuals.

Streptococcus salivarius is a common, harmless, and prevalent member of the oral microbiota in humans. In the present study, the safety of S. salivarius UBSS-01 was evaluated using in silico methods and preclinical and clinical studies. In an acute toxicity study, rats were administered with 5g/kg (500 × 109CFU) S. salivarius UBSS-01. The changes in phenotypic behaviors and hematological, biochemical, electrolytes, and urine analyses were monitored. No toxicity was observed at 14days post-treatment. The no observable effects limit (NOEL) of S. salivarius UBSS-01 was >5g/kg in rats. In a 28-day repeat dose toxicity study, rats were administered S. salivarius UBSS-01 once daily at doses of 0.1, 0.5, and 1g/kg (10, 50, and 100 billion CFU/kg, respectively) body weight. S. salivarius UBSS-01 did not influence any of the hematology parameters and clinical chemistry parameters in plasma and serum samples after 28-day repeated administration. No structural abnormality was observed in the histological examination of organs. Whole genome analysis revealed the absence of virulence factors or genes that may transmit antibiotic resistance. In the double-blind study with 60 human participants (aged 18-60years), consumption of S. salivarius UBSS-01 for 30days was found to be safe and results were comparable with placebo treatment These findings indicate that S. salivarius UBSS-01 may be safe for human consumption.

Comparison of the sigma metrics using the total error allowable algorithm with variation of bias source

Sigma Metrics, as a quality indicator, have been widely applied in clinical laboratories to assess the performance of analytical methods. Described in the document Clinical and Laboratory Standards Institute (CLSI) EP15- A3, the use of target values can be sourced from certified reference standards, survey materials from the Proficiency Testing (PT)/External Quality Assessment (EQA), materials used in inter-laboratory quality control programs and internal quality control materials with predetermined targets. This research aims to determine whether there is a difference in the sigma metrics between the bias derived from the manufacturer's target value and those from the peer group source in the External Quality Assurance Services (EQAS) program. The research methodology employed is descriptive comparative analysis, utilizing the results of material inspection data for 15 internal quality control parameters of Clinical Chemistry over a span of 2 years at the Pramita Laboratory in Bandung. The calculation of the sigma metrics commences with computing the coefficient of variation (CV), and the appropriate Total Error aalowable (Tea) sources for each parameter are determined beforehand using the TEa algorithm. The research findings indicate a difference between the sigma metrics derived from the manufacturer's target value and those from the EQAS-peer group target value, accounting for 33% or 10 parameters out of the total parameters with 2 levels of inspection are calculated on the sigma scale. However, in 67% or 20 parameters out of the total parameters, no such difference is observed. Bias associated with the target value from the manufacturer and the EQAS peer group shows no significant difference, suggesting that the laboratory can utilize pre-existing target values confidently.

Comparison of lipemia interference created with native lipemic material and intravenous lipid emulsion in emergency laboratory tests.

This study aimed to investigate the effects of lipemia on clinical chemistry and coagulation parameters in native ultralipemic (NULM) and intravenous lipid emulsion (IVLE) spiked samples. The evaluation of biochemistry (photometric, ion-selective electrode, immunoturbidimetric method), cardiac (electrochemiluminescence immunoassay method) and coagulation (the viscosity-based mechanical method for prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen and the immunoturbidimetric method for D-dimer) parameters were conducted. In addition to the main pools, five pools were prepared for both types of lipemia, each with triglyceride (TG) concentrations of approximately 2.8, 5.7, 11.3, 17.0 and 22.6 mmol/L. All parameters' mean differences (MD%) were presented as interferographs and compared with the desirable specification for the inaccuracy (bias%). Data were also evaluated by repeated measures of ANOVA. Prothrombin time and APTT showed no clinically relevant interference in IVLE-added pools but were negatively affected in NULM pools(P < 0.001 in both parameters). For biochemistry, the most striking difference was seen for CRP; it is up to 134 MD% value with NULM (P < 0.001) at the highest TG concentration, whereas it was up to - 2.49 MD% value with IVLE (P = 0.009). Albumin was affected negatively upward of 5.7 mmol/L TG with IVLE, while there was no effect for NULM. Creatinine displayed significant positive interferences with NULM starting at the lowest TG concentration (P = 0.028). There was no clinically relevant interference in cardiac markers for both lipemia types. Significant differences were scrutinized in interference patterns of lipemia types, emphasizing the need for careful consideration of lipemia interferences in clinical laboratories. It is crucial to note that lipid emulsions inadequately replicate lipemic samples.

Normal Clinical Laboratory Ranges by Age and Sex, and Impact on Study Screening Outcomes in Rural Mali.

The interpretation of a laboratory test result requires an appropriate reference range established in healthy subjects, and normal ranges may vary by factors such as geographic region, sex, and age. We examined hematological and clinical chemistry parameters in healthy residents at two rural vaccine trial sites: Bancoumana and Doneguebougou in Mali, West Africa. During screening of clinical studies in 2018 and 2019, peripheral blood samples from 1,192 apparently healthy individuals age 6 months to 82 years were analyzed at a laboratory accredited by the College of American Pathologists for a complete blood count, and creatinine and/or alanine aminotransferase levels. Based on manufacturers' reference range values, which are currently used in Malian clinical laboratories, abnormal values were common in this healthy population. In fact, 30.4% of adult participants had abnormal neutrophil levels and 19.8% had abnormal hemoglobin levels. Differences by sex were observed in those who were older, but not in those younger than 10 years, for several parameters, including hemoglobin, platelet, and absolute neutrophil counts in hematology, and creatinine in biochemistry. The site-specific reference intervals we report can be used in malaria vaccine clinical trials and other interventional studies, as well as in routine clinical care, to identify abnormalities in hematological and biochemical parameters among healthy Malian trial participants.

Abstract 4183: Utility of the highly immunodeficient SRG rat for combined drug efficacy, pharmacokinetics, and toxicology studies in tumor-bearing animals

Abstract Immunodeficient rodents are vital pre-clinical disease models. Historically, immunodeficient mice have been standard for hosting human cell and tissue xenografts, enabling cancer drug efficacy and tolerability testing. However, an immunodeficient rat that supports a variety of human cancer types provides a larger model for easier surgical manipulation and serial blood and tumor tissue sampling, allowing for efficacy, pharmacokinetics, and toxicology testing in the same animal. We created a Sprague Dawley Rag2 -/-, Il2rg -/- rat (SRG Rat®; SRG) that is highly supportive of human cell and tissue engraftment. The SRG rat lacks B, T, and NK cells and is more immunodeficient than the Nude rat. Here we show comparative pathology between the SRG rat and its parental strain, the CRL Sprague Dawley (CD). We also present data from an efficacy study in tumor bearing SRG rats, demonstrating that serial blood draws and tumor biopsies can be performed in tumor bearing animals to assess drug pharmacokinetics and pharmacodynamics within a single study. First, we assessed 10 SRG (5/sex) and 10 CD (5/sex) at 8-10 weeks of age. Body weight, hematology, and clinical chemistry parameters were measured. Microscopic examinations were performed on routine H&amp;E slide preparations. Male and female SRG displayed lower mean body weight when compared to sex- and age-matched CD. Compared to CD, SRG had reduced lymphoid tissue and circulating monocytes, and highly reduced circulating lymphocytes, neutrophils, eosinophils, and basophils; expected phenotypes for this severely immunodeficient rat. Thymus was not present in SRG rats, spleens were grossly smaller, and bone marrow cellularity was decreased compared to CD. Microscopically, mandibular lymph nodes and lymphoid tissue in spleen, lung, and intestine were not observed in SRG rats, consistent with the 92% decrease in circulating lymphocytes. To demonstrate the utility of the SRG for tumor inhibition, pharmacokinetics, and pharmacodynamics, we inoculated rats with human VCaP prostate cancer cell-derived tumors, then treated these animals and collected serial blood samples and tumor biopsies to assess tumor biomarkers. Treatment led to decreased PSA and AR, two key proteins expressed in prostate cancer, correlating to decreased tumor growth. These data demonstrate that the SRG rat is suitable for toxicology studies and has comparable pathology to the CD rat, except for reduced lymphoid tissue and WBCs, which are expected phenotypes. In addition, the SRG rat supports the growth of human cancer tissue for treatment studies. The large size of the SRG rat and comparative pathology to the CD rat support its value as an immunodeficient model for assessing toxicity during efficacy testing for de-risking safety concerns in the presence of the human target tissue. Citation Format: Diane Begemann, Cynthia Dunn, Darrell Robertson, Lauren Keach, Emily Baldwin, R. Grace Walton, Alex Van Engelenburg, Jessica Durrant, Laura Healy, Koh Meng Aw Yong, Michael J. Schlosser, Fallon K. Noto. Utility of the highly immunodeficient SRG rat for combined drug efficacy, pharmacokinetics, and toxicology studies in tumor-bearing animals [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4183.

Safety of Repeated Administration of Xenogeneic Human Apoptotic State (Allocetra-OTS) in Sprague Dawley Rats.

Apoptotic cells possess immunomodulatory effects that can be utilized to treat imbalanced immune conditions. Information on the preclinical safety of such treatment is sparse. In this study, the safety of apoptotic cells (Allocetra-OTS) was assessed in a GLP toxicological study on Sprague Dawley rats. Three doses of Allocetra-OTS or vehicle were administered intravenously (IV) for 3 consecutive days. Animals in the main study were sacrificed on day 4, while animals from the recovery groups were kept for 14 or 28 days. Allocetra-OTS was well tolerated, and no adverse effects were observed in terms of body weight, clinical signs, food consumption, or ophthalmologic observation. Thus, the No Observed Adverse Effect Level (NOAEL) dose was determined as the highest dose administered. An observed elevation in immune cells was suspected to be due to Allocetra-OTS, similarly to other clinical chemistry parameters; however, it was resolved in the recovery phases. Splenomegaly and dose-related extramedullary hematopoiesis (EMH) in the red pulp were observed, with no adverse events, and were considered to be a normal and expected reaction following the IV administration of cell-based therapies. In conclusion, under the conditions of this study, Allocetra-OTS was concluded to be safe, further supporting its potential candidacy for clinical studies.

Evaluation of anti-Fel d 1 IgY ingredient for pet food on growth performance in kittens.

The domestic cat (Felis catus) is one of the most common pets. Worldwide, approximately one in five adults are sensitive to cat allergens. The major cat allergen is the secretoglobulin Fel d 1, which is primarily produced in the salivary and sebaceous glands. Chickens produce IgY antibodies, which are similar in structure to mammalian IgG. When chickens are exposed to Fel d 1, anti-Fel d 1-specific IgY (AFD1) is produced and is naturally concentrated in egg yolk. The aim of this study was to evaluate the tolerability, effects on growth and food consumption, and potential adverse effects of a chicken egg product ingredient containing AFD1 in kittens. This was a blinded, controlled study. Twenty-seven (27) eight-week old kittens were randomly assigned to three feeding groups containing 0 ppm AFD1 (Group 0), 8 ppm AFD1 (Group 1), and 16 ppm AFD1 (Group 2) for 84 days. Veterinary exams and bloodwork were performed on Day 42 and Day 84, and body weight and body condition score (BCS) were monitored weekly. Throughout the study, there were no signs of nutritional deficiency or adverse clinical events in any of the subjects. Administration of a chicken egg product ingredient containing AFD1 in the diet (whether in coating or combination of coating and top dress) had no significant effect on body weight nor food consumption, and all subjects maintained a healthy Body Condition Score (BCS) throughout the study. Moreover, there were no biologically significant differences in the mean clinical chemistry and hematology parameters. This study demonstrated that a diet formulated to contain up to 16  ppm AFD1, included in the coating and the top-dress of dry kitten food, was well tolerated, promoted adequate growth, and exhibited no adverse effects.

Assessment of clinical chemistry and hematological parameters in female Sprague-Dawley rats following a 7-day oral exposure to three different species of Echinacea

Echinacea has grown in popularity due to its broad therapeutic benefits. Despite its popularity, comprehensive safety evaluations for three medicinal species are limited. In this study, female Sprague-Dawley rats received oral doses (0, 25, 50, 100, 200 mg/kg/d) of 75% (v/v) ethanol extract from the aerial parts of 9 Echinacea samples of three species - Echinacea purpurea, Echinacea angustifolia, and Echinacea pallida - over a 7-day period. Blood and serum samples, collected twenty-four hours post the final dose, were analyzed for hematology and clinical chemistry parameters. The results revealed varied effects across the tested samples, with many parameters showing no discernible impacts at administered doses. Subtle alterations were observed in parameters such as relative liver weight, alkaline phosphatase (ALP), and platelet count. Parameters like relative spleen weight, alanine transaminase (ALT), glucose, urea, hematocrit, hemoglobin, and RBC count exhibited effects in only one out of the nine samples tested. These findings emphasize the heterogeneity in the effects of Echinacea. While the results suggest that Echinacea samples might be considered relatively safe, potential clinical implications warrant caution and underscore the importance of extended testing. A comprehensive toxicity profile assessment remains paramount to conclusively ascertain the safety of three Echinacea species.

Advancing Personalized Medicine by Analytical Means: Selection of Three Metabolites That Allows Discrimination between Glaucoma, Diabetes, and Controls.

This paper aimed at devising an intelligence-based method to select compounds that can distinguish between open-angle glaucoma patients, type 2 diabetes patients, and healthy controls. Taking the concentration of 188 compounds measured in the aqueous humour (AH) of patients and controls, linear discriminant analysis (LDA) was used to identify the right combination of compounds that could lead to accurate diagnosis. All possibilities, using the leave-one-out approach, were considered through ad hoc programming and in silico massive data production and statistical analysis. Our proof of concept led to the selection of four molecules: acetyl-ornithine (Ac-Orn), C3 acyl-carnitine (C3), diacyl C42:6 phosphatidylcholine (PC aa C42:6), and C3-DC (C4-OH) acyl-carnitine (C3-DC (C4-OH)) that, taken in combination, would lead to a 95% discriminative success. 100% success was obtained with a non-linear combination of the concentration of three of these four compounds. By discarding younger controls to adjust by age, results were similar although one control was misclassified as a diabetes patient. Methods based on the consideration of individual clinical chemical parameters have limitations in the ability to make a reliable diagnosis, stratify patients, and assess disease progression. Leveraging human AH metabolomic data, we developed a procedure that selects a minimal number of metabolites (3-5) and designs algorithms that maximize the overall accuracy evaluating both positive predictive (PPV) and negative predictive (NPV) values. Our approach of simultaneously considering the levels of a few metabolites can be extended to any other body fluid and has potential to advance precision medicine. Artificial intelligence is expected to use algorithms that use the concentration of three to five molecules to correctly diagnose diseases, also allowing stratification of patients and evaluation of disease progression. In addition, this significant advance shifts focus from a single-molecule biomarker approach to that of an appropriate combination of metabolites.

Subacute Oral Toxicity Studies of Pankajakasthuri Orthoherb Tablets Formulated for Managing Pain and Inflammation of Joints

Objectives: The objective of this investigation was to assess the subacute oral toxicity of the Pankajakasthuri Orthoherb Tablets, a polyherbal formulation used to manage pain and inflammation due to various pathological reasons, including osteoarthrosis, polyarthritis, rheumatoid arthritis, and other chronic degenerative disorders. Materials and Methods: The subacute toxicity studies of Pankajakasthuri Orthoherb Tablets were conducted using Wistar albino rats of both sexes, according to Organization for Economic Cooperation and Development-approved procedures. In this study, rats were orally administered Pankajakasthuri Orthoherb Tablets daily at doses of 250, 500, and 1000 mg/kg body weight for 28 days. Throughout the study period, general behavior, mortality, and adverse effects were recorded. Body weight, selected hematological and clinical chemistry parameters were determined at the end of the investigation period. Finally, histopathological analysis was performed to determine whether the study drug was inducing any alternations in the vital organs. Results: Daily administration of Pankajakasthuri Orthoherb Tablets for a continuous 28 days did not record any major toxicity indications. Additionally, no significant variation in food and water consumption, body weight, relative organs and hematology and clinical chemistry parameters was recorded in both sexes compared to the control. Histopathological investigation of the vital organs also revealed normal architecture, which suggests no morphological alterations after the administration of Pankajakasthuri Orthoherb Tablets. Conclusion: The outcomes of this investigation confirmed that Pankajakasthuri Orthoherb Tablets did not have the potential to induce toxicity signs in the experimental rats. The No observed Adverse Effect Level (NOAEL) for female and male rats of Pankajakasthuri Orthoherb Tablets under these experimental conditions was 500 mg/kg body weight. Based on the NOAEL, the human equivalent dose of the Pankajakasthuri Orthoherb Tablet was calculated at 5.195 g/day.

The short-term toxicity and metabolome of dicyclopentadiene

Dicyclopentadiene (DCPD) was investigated in a 14-day oral rat toxicity study based on the OECD 407 guideline in combination with plasma metabolomics. Wistar rats received the compound daily via gavage at dose levels of 0, 50 and 150 mg/kg bw. The high dose induced transient clinical signs of toxicity and in males only reduced body weight gain. High dose liver changes were characterized by altered clinical chemistry parameters in both sexes and pathological changes in females. In high dose males an accumulation of alpha-2 u-globulin in the kidney was noted. Comparing the DCPD metabolome with previously established specific metabolome patterns in the MetaMap® Tox data base suggested that the high dose would result in liver enzyme induction leading to increased breakdown of thyroid hormones for males and females. An indication for liver toxicity in males was also noted. Metabolomics also suggested an effect on the functionality of the adrenals in high dose males, which together with published data, is suggestive of a stress related effect in this organ. The results of the present 14-day combined toxicity and metabolome investigations were qualitatively in line with literature data from subchronic oral studies in rats with DCPD. Importantly no other types of organ toxicity, or hormone dysregulation beyond the ones associated with liver enzyme induction and stress were indicated, again in line with results of published 90-day studies. It is therefore suggested that short term “smart” studies, combining classical toxicity with ‘omics technologies, could be a 2 R (refine and reduce) new approach method allowing for the reduction of in vivo toxicity testing.

Effects of Ostarine and Endurance Training on Some Functional, Hematological, and Biochemical Parameters in Male Rats

Background: Non-steroidal Selective Androgen Receptor Modulators (SARMs) are currently a group of drug candidates with anabolic effects, tissue selectivity, and the potential to improve the therapeutic process in a number of socially significant diseases. There is insufficient data on their effects during exercise and on their adverse side effects. Objectives: Our objective was to examine the role of selective androgen receptor modulators for the physical working capacity of the body, hematological and biochemical parameters, and to evaluate any side effects of SARMs. We studied the effects of ostarine (S-22, MK-2866, GTx-024, Enobosarm) alone or in combination with submaximal training in sexually mature male Wistar rats. Methods: The rats used were divided into a treadmill-trained group and a sedentary group. Half of each group received either ostarine or vehicle for 8 weeks (n = 10 each). We performed functional tests and blood analysis at the end of the experiment to analyze clinical chemistry and hematological indicators. Results: Ostarine did not affect maximal sprint speed, VO2max, and running economy, while submaximal training increased these parameters. Ostarine increased total plasma cholesterol and energy expenditure and decreased plasma glucose concentration. Neither treatment changed the oxygen-carrying capacity of the blood, the respiratory quotient, the concentration of triglycerides and LDL-cholesterol, or creatine kinase. Combined treatment neutralized the negative effect of ostarine on plasma total cholesterol levels. Conclusions: Ostarine did not affect the examined hematological and physical working capacity parameters, but it changed some clinical chemistry indicators. Training improved the physical working capacity but did not affect the clinical chemistry and hematological parameters. Further research is needed to clarify other aspects of the influence of non-steroidal SARMs on the physical working capacity and possible side effects during long-term use, as their administration, along with physical activity, is becoming popular among healthy adult bodybuilders in gyms.

Single and repeat-dose toxicity and local tolerance assessment of newly developed oil emulsion adjuvant formulations for veterinary purposes

Adjuvants are components of vaccines that boost the intensity, duration, and breadth of the immune response. Insight into the mechanisms responsible for the immunotoxicity of both local and systemic adverse reactions following the use of adjuvants has been gained through research over the past twenty years. In the present study, single and repeated-dose toxicity and local tolerance of newly developed Water-in-Oil (W/O) and Water-in-Oil-in-Water (W/O/W) Emulsion adjuvants (Coralvac RZ 528, Coralvac RZ 506, Coralvac AT 318, Coralvac AT 318 SIS and Coralvac 252) by Coral Biotechnology Industry and Trade Incorporated Company were demonstrated after intramuscular injection in mice. In both toxicity studies, no adverse reactions such as death, general appearance, behavior, or weight loss were observed in the mice in the experimental groups. The results indicate that clinical chemistry parameters demonstrated normal function of the major organs and no irreversible damage to the mice in all adjuvant groups compared to the control group. In histopathologic investigation of single dose toxicity study, inflammation, edema, and large amounts of lipid droplets were observed on the 7th day in all experimental groups. On the 14th day, when the control group and the experimental groups were compared, it was seen that inflammation and edema had decreased considerably. Similarly, repeated dose toxicity study showed mild inflammation and edema in the control group, while quite widespread and severe inflammation, edema, and diffuse lipid droplets of varying sizes were observed in all adjuvant groups compared to the control group. These observations would be useful for the future development of oil-based adjuvants and their use in veterinary inactive vaccines.

Intravenous Administration of Ad26.COV2.S Does Not Induce Thrombocytopenia or Thrombotic Events or Affect SARS-CoV-2 Spike Protein Bioavailability in Blood Compared with Intramuscular Vaccination in Rabbits.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a very rare but serious adverse reaction that can occur after Ad26.COV2.S vaccination in humans, leading to thrombosis at unusual anatomic sites. One hypothesis is that accidental intravenous (IV) administration of Ad26.COV2.S or drainage of the vaccine from the muscle into the circulatory system may result in interaction of the vaccine with blood factors associated with platelet activation, leading to VITT. Here, we demonstrate that, similar to intramuscular (IM) administration of Ad26.COV2.S in rabbits, IV dosing was well tolerated, with no significant differences between dosing routes for the assessed hematologic, coagulation time, innate immune, or clinical chemistry parameters and no histopathologic indication of thrombotic events. For both routes, all other non-adverse findings observed were consistent with a normal vaccine response and comparable to those observed for unrelated or other Ad26-based control vaccines. However, Ad26.COV2.S induced significantly higher levels of C-reactive protein on day 1 after IM vaccination compared with an Ad26-based control vaccine encoding a different transgene, suggesting an inflammatory effect of the vaccine-encoded spike protein. Although based on a limited number of animals, these data indicate that an accidental IV injection of Ad26.COV2.S may not represent an increased risk for VITT.

Systemic Amyloid Response in Patients with AL Amyloidosis Assessed By Serial Iodine ( 124I) Evuzamitide PET/CT Imaging

Background: Immunoglobulin light chain (AL) amyloidosis is a systemic disorder. Fibrillar aggregates of monoclonal free light chains, or fragments thereof, can deposit in any organ or tissue. Invariably, more than one anatomic site is involved, including the heart, liver, spleen, kidneys, pancreas, nerves, gastrointestinal tract and vasculature. Cardiac and renal amyloidosis are clinically most ominous; however, amyloid in other sites significantly impacts quality of life and may cause other heretofore unappreciated clinical sequelae. This is also true of the other 17 types of systemic amyloidosis. The degree of amyloid distribution and the tissue-specific amyloid load can only be achieved by nuclear imaging. Moreover, monitoring changes in amyloid load in response to therapy would benefit from whole body quantitative molecular imaging techniques. Here we report a pilot study of eight ( n=8) patients with AL amyloidosis who underwent serial PET/CT imaging using a novel amyloid-binding, iodine-124-labelled peptide, designated iodine-124-evuzamitide. Data from a cohort of ten ( n=10) patients with transthyretin associated (ATTR) amyloidosis are also described for comparison (NCT05968846). Methods: The study plans to enroll 20 ( n=20) patients with AL ( n=10) and ATTR ( n=10) amyloidosis who were previously imaged more than 12 months prior and who had positive uptake of 124I-evuzamitide in the heart. To date, eight ( n=8) patients with AL and ten ( n=10) with ATTR amyloidosis have undergone repeat imaging since 2019. Between imaging sessions, patients with AL received immunotherapy ( n=2/8) or were untreated ( n=6/8). Patients were administered 37 or 74 MBq 124I-evuzamitide, and PET/CT imaging was performed at ~5 h post injection. Clinical chemistry parameters were collected contemporaneously. Images were interpreted by a single reviewer, experienced in evaluating this tracer, for positive uptake. A fully manual 2D region of interest (ROI) analysis was performed on three representative image views of the heart in the transaxial plane as well as the liver, spleen, and kidneys. The blood pool was used as a reference tissue to determine standard uptake value ratios (SUVR mean). Cardiac uptake of radiotracer was compared with serum NT-proBNP measurements. Pearson and Spearman correlations were used to test for associations. Results: The mean time between imaging sessions for patients with AL amyloidosis was 3.21±0.95 years and 2.96±0.87 years for the entire cohort. In the AL amyloid cohort, 88% ( n=7/8) had a reduction in cardiac radiotracer uptake. In one ( n=1) patient, a 92.9% increase in cardiac uptake was seen, which was readily visible in scaled maximum intensity PET images. In this patient, the liver, spleen, and kidney uptake also increased. In contrast to the heart, renal uptake of the radiotracer was increased in 62.5% ( n=5/8) of patients with AL, with three ( n=3) patients showing a &amp;gt;20% increase in the SUVR mean. A strongly positive, significant correlation between the change in the liver and spleen uptake was observed (Pearson r=0.88, p=0.004). The change in the cardiac radiotracer uptake correlated strongly with that of the spleen (Pearson r=0.74, p=0.04). For the entire cohort, AL and ATTR patients ( n=18), there was a significant moderate correlation between the change in cardiac SUVR mean and change in single point serum NTproBNP concentration (Spearman rho=0.57, p=0.01). Conclusion: AL amyloidosis, and indeed all types of systemic amyloid disease, is a complex systemic disorder. The amyloid response to treatment, or disease progression, remains enigmatic as compared to the hematologic and biomarker responses. Appreciating the changes in amyloid load may not only improve clinical management but may also illuminate aspects of pathogenesis. PET/CT imaging using 124I-evuzamitide may, therefore, play a valuable role in understanding, diagnosing, and monitoring changes in organ-specific amyloid load and amyloid response. Additional longitudinal imaging studies are needed to investigate these possibilities further.

Comparison of Various Blood Vacuum Tubes Brand for Clinical Chemistry, Hormonal, Hematology, and Hemostasis Parameters

Link of Video Abstract: https://youtu.be/O7-fCHyvGo4   Background: Laboratory tests are integral to the medical decision-making process. Blood vacuum tubes need to be validated to increase the analytics quality. This study aimed to compare various vacuum tube brands that use serum clot activator and serum separator tube (SST) for clinical chemistry and hormonal parameters, K3EDTA anticoagulant for hematological parameters, and citrate for hemostasis parameters. Methods: The comparative study was carried out cross-sectional in the Department of Clinical Pathology, Dr. Cipto Mangunkusumo National Public Hospital, on June 20, 2020. There were 20 subjects for each type of tube. The control tube was BD Vacutainer®, and the test tubes were Samplix®, VACUETTE®, Vacusera®, and YCHD. Results: Underfilling was the most common problem in preanalytical observation. This problem for citrate tubes was most frequently found in Vacusera® tubes. The possible cause of underfilling is the expiration date, which was close to the date of the experiment. There was a significant difference in PT results (p &lt;0.0001) in the Vacusera® citrate tube. All tube brands had no significant differences in all clinical chemistry, hormonal, and hematological parameters (P&gt;0.05). After 24 hours at room temperature, the results of hematological parameters showed statistically significant differences in MCV and hematocrit parameters, while other parameters were still within the CV limit of the instrument. Conclusion: There were no significant differences in the results of clinical chemistry, hormonal, and hematological parameters for all tube brands. A hematology parameters test should be done immediately as the delay may affect the MCV and hematocrit parameters.

B-300 Importance of Clinical Chemistry and Metabolism Parameters for the Management of Patient With Chronic Nitrous Oxide Intoxication

Abstract Background Recreational use of nitrous oxide (N2O) has increased exponentially recently and leads to severe neurological disorders. A recent report from European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) showed that the recreational use of N2O is a growing and became a major health issue in Europe. For biological monitoring, serum or urine N2O assays are not routinely performed because they do not allow to ensure a real exposure due to the very short half-life of this gas in the body. Functional disorders of vitamin B12 metabolism, characteristic of N2O intoxication, could be explored by two markers: homocysteine (Hcys) and methylmalonic acid (MMA). We experimented here, management of N2O abused patient thanks to functional markers as Hcys and MMA. Methods We collected clinical and biological data from patients with declared chronic N2O consumption. The patients treated in Lille University Hospital between september 2020 and december 2022 were included in the study. The clinical evaluation included the Peripheral Neuropathy Disability (PND) score which was evaluated by a neurologist. Results Our study included 202 patients with N2O abused, Globally, plasma functional markers concentration are increased in case on consumption (Table). We noticed that clinical sign of patient evaluated by PND score correlated with plasma MMA (P-value &amp;lt; 0.01) but not with plasma hcys (P-value &amp;gt; 0.05). Conclusion The use of functional markers as Hcys and MMA makes it possible to follow the metabolic disturbances of nitrous oxide abused patients and evaluated clinical outcomes. However, in view of the thrombotic risk related to high Hcys and the need to quickly adapt the nutritional treatment, biological and in particular Hcys, current reporting time is not satisfactory using mass spectrometry method. Hence, our medical laboratory aim to improve our method evaluating immunoassay techniques in order to reduce the turnaround time while maintaining analytical reliability.

Comprehensive prediction of urolithiasis based on clinical factors, blood chemistry and urinalysis: UROLITHIASIS score

Comprehensive prediction of urolithiasis using available factors obtained in the emergency department may aid in patient-centered diagnostic imaging decisions. This retrospective study analyzed the clinical factors, blood chemistry and urine parameters of patients who underwent nonenhanced urinary computed tomography for suspected urolithiasis. A scoring system was developed from a logistic regression model and was tested using the area under the curve (AUC). The prevalence of urolithiasis and important possible causes in the three risk subgroups were determined. Finally, the scoring model was validated. In the derivation cohort (n = 673), 566 patients were diagnosed with urolithiasis. Age > 35 years, history of urolithiasis, pain duration < 8 h, nausea/vomiting, costovertebral angle tenderness, serum creatinine ≥ 0.92 mg/dL, erythrocytes ≥ 10/high power field, no leukocytes ≤  + , and any crystalluria were retained in the final multivariable model and became part of the score. This scoring model demonstrated good discrimination (AUC 0.808 [95% CI, 0.776–0.837]). In the validation cohort (n = 336), the performance was similar (AUC 0.803 [95% CI, 0.756–0.844]), surpassing that of the STONE score (AUC 0.654 [95% CI, 0.601–0.705], P < 0.001). This scoring model successfully stratified patients according to the probability of urolithiasis. Further validation in various settings is needed.