42 The accuracy and clinical implications of point-of-care testing in children

Primary Subject area Nephrology Background Point-of-care testing (POCT) is commonly used at our institution to gather data quickly for sick patients, including electrolytes, glucose, and hemoglobin. Serum electrolytes, hemoglobin, and glucose are the gold standard of testing, but the results often lag POCT by a significant time period. Management decisions are made on the results returned by POCT. Thus, it is imperative to determine the accuracy of POCT at our institution. Objectives Determining whether POCT is an accurate and clinically appropriate method to measure electrolytes, glucose, and hemoglobin compared to standard serum testing. Design/Methods This study retrospectively reviewed 128 consecutive patients either assessed in the emergency department or admitted prior to November 1, 2019 who had both POCT and serum electrolytes (+/- glucose, hemoglobin, and lactate) performed within 4 hours of each other. A sample size of 128 was required to determine a difference of 3 mmol/L in sodium for an effect size of 0.5, with 0.05 level of significance and 80% statistical power. Patient demographics and additional labs drawn within 4 hours of POCT were extracted. Paired t-tests were used to compare values between serum testing and POCT for each patient. Secondary kappa coefficient analyses were performed to look at agreement within clinically-determined normal ranges. POCT was performed on Radiometer ABL835 FLEX analyzers, and serum testing on Beckman Coulter DxC 800 analyzers. Results There were 56 males and 72 females; age range 0.01–17.93 years. There were statistically significant differences between POCT and serum values for all electrolytes and hemoglobin, with POCT over-estimating, but not for glucose (Table 1). Within clinically determined normal ranges, there was substantial agreement between POCT and serum potassium, glucose, and hemoglobin, and fair agreement for sodium and bicarbonate (Table 2). Conclusion Our study highlights the importance of verifying abnormal POCT electrolytes and hemoglobin with serum values. Even when POCT values are normal, clinically significant hyponatremia and hypokalemia may not be detected, and when abnormal, hypernatremia and hyperkalemia may be overestimated. In patients with dysnatremia, if diagnosed with serum sodium and monitored with POCT (or vice versa), there is potential for incorrect diagnosis and/or rate of correction with clinical impact. Thus, when following electrolytes and hemoglobin values in a patient, POCT and serum should not be interchanged, and if there is clinical suspicion for these to be abnormal, verification with serum is warranted. Our study is limited to the specific POCT analyzer used, and behaviour of another analyzer may be different.

Binding Strength and Hydrogen Bond Numbers between COVID-19 RBD and HVR of Antibody

The global battle against the COVID-19 pandemic relies strongly on the human defense of antibody, which is assumed to bind the antigen’s receptor binding domain (RBD) with its hypervariable region (HVR). Due to the similarity to other viruses such as SARS, however, our understanding of the antibody-virus interaction has been largely limited to the genomic sequencing, which poses serious challenges to containment and rapid serum testing. Based on the physical/chemical nature of the interaction, infrared spectroscopy was employed to reveal the binding disparity, the real cause of the antibody-virus specificity at the molecular level, which is inconceivable to be investigated otherwise. Temperature dependence was discovered in the absorption value from the 1550 cm−1 absorption band, attributed to the hydrogen bonds by carboxyl/amino groups, binding the SARS-CoV-2 spike protein and closely resembled SARS-CoV-2 or SARS-CoV-1 antibodies. The infrared absorption intensity, associated with the number of hydrogen bonds, was found to increase sharply between 27 °C and 31 °C, with the relative absorbance matching the hydrogen bonding numbers of the two antibody types (19 vs. 12) at 37 °C. Meanwhile, the ratio of bonds at 27 °C, calculated by thermodynamic exponentials, produces at least 5% inaccuracy. Beyond genomic sequencing, the temperature dependence, as well as the bond number match at 37 °C between relative absorbance and the hydrogen bonding numbers of the two antibody types, is not only of clinical significance in particular but also as a sample for the physical/chemical understanding of vaccine–antibody interactions in general.

Severe Vitamin K-dependent Coagulopathy from Rodenticide-contaminated Synthetic Cannabinoids: Emergency Department Presentations

Introduction: Synthetic cannabinoids are a rapidly expanding subset of designer drugs widely available in the United States since 2008. In Illinois during the spring of 2018, over 160 documented cases of bleeding and prolonged coagulopathy occurred secondary to contaminated synthetic cannabinoids. Methods: We conducted a retrospective cohort study consisting of 38 patients to describe the initial emergency department (ED) presentation, diagnosis, and treatment. Results: Through serum testing we found that three long-acting anticoagulant rodenticides (LAAR) were detected in patients who had inhaled these tainted products: brodifacoum, difenacoum, and bromodialone. Discussion: This study encompasses the largest ED presentation of LAAR poisoning via the inhalational route known to date. Conclusion: The emergency physician should be aware of the potential for tainted coingestants as the cause of undifferentiated coagulopathy.

N-Acetylcysteine Improves Inflammatory Response in COPD Patients by Regulating Th17/Treg Balance through Hypoxia Inducible Factor-1α Pathway

Introduction. This study was aimed to investigate the effects of N-acetylcysteine (NAC) on chronic obstructive pulmonary disease (COPD) and the change of Th17/Treg cytokine imbalance. Material and Methods. A total of 121 patients with stable COPD at the stage of C or D were consecutively enrolled and randomly divided into 2 groups. Patients in the treatment group received NAC granules ( 0.2 g × 10 bags , 0.4 g each time, 3 times/d) for half a year. The control group was treated with the same amount of placebo therapy. The peripheral blood of the patient was collected and the cytokine, T lymphocyte subsets were detected. Results. We found the oral administration of NAC could regulate Th17/Treg balance to resist inflammation in COPD patients. Serum testing showed that the proportion of Treg in CD4+ T cells has increased and the Th17/Treg ratio has decreased during the NAC treatment. In vitro studies, we found that NAC regulated Th17/Treg balance through Hypoxia Inducible Factor-1α pathway. Conclusions. Our result could provide new diagnosis and treatment for elderly patients with COPD from the perspective of immunity ideas.

Serum-Based KRASG12/G13 Mutation Detection Using Droplet Digital PCR: Clinical Implications and Limitations in Colorectal Adenocarcinoma With Tumor Heterogeneity

BackgroundCell-free DNA (cfDNA) has arisen as an alternative target for evaluating somatic mutations in cancer. KRAS mutation status is critical for targeted therapy in colorectal adenocarcinoma (CRAC). We evaluated KRASG12/G13 mutations in cfDNA extracted from serum and compared the results with KRASG12/G13 mutations detected in tissue samples. We assessed the clinical significance of KRASG12/G13 mutation in serum in regard to recurrence and metastasis of CRAC.MethodsA total of 146 CRAC patients were enrolled, and KRASG12/G13 mutations were evaluated in 146 pairs of serum and tissue samples. In addition, 35 pairs of primary and metastatic CRAC tissue samples were evaluated for KRASG12/G13 mutational status.ResultsDetection of KRASG12/13 mutation from serum and tissue had a 55% concordance rate, and serum detection had a sensitivity of 39.8%. Detection of the KRASG12/13 mutation yielded a 14% discordance rate between primary and metastatic tissue. CRAC patients with mutant KRASG12/13 mutation in serum but wild-type KRASG12/13 in tissue had concurrent KRASG12/13-mutant metastatic tumors, indicating spatial genetic heterogeneity. Changes in serum KRASG12/G13 mutation status during postoperative follow-up were associated with recurrence. Conclusion: Although serum detection of the KRASG12/13 mutation cannot substitute for detection in tissue, serum testing can support the interpretation of a CRAC patient’s status in regard to concurrent metastasis. Dynamic changes in serum KRASG12/13 mutation status during follow-up indicated that cfDNA from serum represents a potential source for monitoring recurrence in CRAC patients.

Binding strength and hydrogen bond numbers between Covid-19 RBD and HVR of antibody

The global battle against the Covid-19 pandemic relies strongly on the human defence of antibody, which is assumed to bind the antigen’s Receptor Binding Domain with its Hypervariable Region. Due to the similarity to other viruses such as SARS, however, our understanding of the antibody-virus interaction has been largely limited to the genomic sequencing, which poses serious challenges to the containment, vaccine exploration and rapid serum testing. Based on the physical/chemical nature of the interaction, infrared spectroscopy was employed to reveal the binding disparity, when unusual temperature dependence was discovered from the 1550cm-1 absorption band, attributed to the hydrogen bonds by carboxyl/amino groups, binding the SARS-CoV-2 spike protein and closely resembled SARS-CoV-2 or SARS-CoV-1 antibodies. The infrared absorption intensity, associated with the number of hydrogen bonds, was found to increase sharply between 27°C and 31°C, with the relative absorbance matches at 37°C the hydrogen bonding numbers of the two antibody types (19 vs 12). Meanwhile the ratio of bonds at 27°C, calculated by thermodynamic exponentials rather than by the layman’s guess, produces at least 5% inaccuracy. As a result, the specificity of the SARS-CoV-2 antibody will be more conclusive beyond 31°C, instead of at the usual room temperature of 20°C - 25°C, when the vaccine research and antibody diagnosis would likely be undermined. Beyond genomic sequencing, the temperature dependence, as well as the bond number match at 37°C between relative absorbance and the hydrogen bonding numbers of the two antibody types, are not only of clinical significance in particular, but also of a sample for the physical/chemical understanding of the vaccine-antibody interactions in general.

GAD65 antibody-associated neurologic disease presenting with hemiparkinsonism at onset

A 60-year old previously healthy left-handed man presented to clinic with 6 months of progressive slowness and stiffness on the left side. He described loss of dexterity in the left hand and feeling of “heaviness” in the left leg. On exam, he exhibited mild bradyphrenia and hypophonia, moderate left arm and leg bradykinesia and rigidity, and left leg hesitations and reduced left arm-swing upon walking (video 1). A month prior, he had undergone MRIs of the brain and cervical spine with and without gadolinium that were unremarkable. Initial serum testing including complete blood count, comprehensive metabolic panel, thyroid stimulating hormone, ceruloplasmin, and vitamin B12 levels were all unremarkable. The differential diagnosis at presentation included the spectrum of parkinsonian disorders with Parkinson's Disease being the most likely given his age group and the asymmetric parkinsonism. He was diagnosed with suspected Parkinson's Disease and levodopa therapy was initiated as the he felt his symptoms were functionally-limiting.

MOG-IgG1 and co-existence of neuronal autoantibodies

Background: The presence of co-existent neuronal antibodies (neuronal-IgG) in patients with myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG1) is not yet well understood. Objectives: The aim of this study was to investigate the co-existence of a broad range of neuronal-IgG in MOG-IgG1+ patients. Methods: MOG-IgG1+ patients were tested for 17 neuronal-IgGs in cerebrospinal fluid (CSF) and serum including NMDA-R-IgG, AMPA-R-IgG, GABAB-R-IgG, LGI1-IgG, CASPR2-IgG, GABAA-R-IgG, GAD65-IgG, mGLUR1-IgG, DPPX-IgG, CRMP5-IgG, amphiphysin-IgG, PCA1,2,Tr, and ANNA1,2,3. Clinical and radiological features of MOG-IgG1+ with NMDA-R-IgG in CSF were compared to a control cohort of MOG-IgG1+ patients without NMDA-R-IgG. Results: A total of 376 MOG-IgG1+ patients underwent testing for neuronal-IgGs. Serum testing for neuronal-IgGs (113 adults, 142 children) identified one child with NMDA-R-IgG (0.7%), one child with CASPR2-IgG (0.7%), one adult with LGI1-IgG (0.9%) and one adult with GABAA-R-IgG (0.9%). CSF testing for neuronal-IgGs (97 adults, 169 children) identified seven children (4%) and seven adults (7%) with NMDA-R-IgG, and one adult with GABAA-R-IgG (1%). The MOG-IgG1+/NMDA-R-IgG+ patients had a median age of 17 (range: 2–39) years. Features associated with MOG-IgG1+/NMDA-R-IgG+ included encephalopathy ( p = 0.001), seizures ( p = 0.045), and leptomeningeal enhancement ( p = 0.045). Conclusion: NMDA-R-IgG was the most frequently detected neuronal-IgG to co-exist with MOG-IgG1. MOG-IgG1+/NMDA-R-IgG+ patients most often presented with encephalopathy and seizures. Testing for MOG-IgG1 and NMDA-R-IgG may be warranted in patients with encephalopathy and inflammatory demyelinating syndromes.