Angela D Burns, Christina Kanonidou, Jane McNeilly
{"title":"Misleading thyroid function tests in congenital dysfibrinogenemia.","authors":"Angela D Burns, Christina Kanonidou, Jane McNeilly","doi":"10.1177/00045632241263494","DOIUrl":"10.1177/00045632241263494","url":null,"abstract":"<p><p>The presence of latent fibrin clots is a recognised pre-analytical factor that causes inaccurate immunoassay results. This report details a case of a patient with Graves' disease and congenital dysfibrinogenemia (CD) that had serum thyroid function test results (TFTs) that were not in keeping with clinical signs or symptoms. Analysis of plasma samples taken from the patient was shown to provide more accurate results than those obtained using serum samples. Further cases of patients with CD, all sharing the same genetic mutation of fibrinogen, and discordant TFTs are described, where TFTs measurement in serum samples proved to be unreliable. Despite evidence of fibrin effecting immunoassays, this is the first report of its kind linking CD to erroneous immunoassay results. The mechanism is postulated to be related to atypical forms of fibrinogen resulting in latent fibrin in serum samples blocking the antigen binding site and leading to incorrect results. Congenital dysfibrinogenemia is asymptomatic in most patients and therefore abnormal, albeit inaccurate, TFTs may be the first finding. Recognition of CD as a cause of discordant results is important when interpreting TFTs to avoid unnecessary investigations and inappropriate clinical interventions to those with the disorder and potentially identify undiagnosed cases.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"474-479"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Divya N Mallikarjun, Shubham Jain, Palash Kumar Malo, Bratati Kahali, Jonas S Sundarakumar, Latha Diwakar, Vijayalakshmi Ravindranath
{"title":"Distribution of biochemical and haematological parameters in an aging population from southern India: A cross-sectional analysis.","authors":"Divya N Mallikarjun, Shubham Jain, Palash Kumar Malo, Bratati Kahali, Jonas S Sundarakumar, Latha Diwakar, Vijayalakshmi Ravindranath","doi":"10.1177/00045632241267905","DOIUrl":"10.1177/00045632241267905","url":null,"abstract":"<p><strong>Background: </strong>Examining the distribution of biochemical and haematological tests in different age groups of rural population is necessary to ensure that health care facilities are equipped to address the prevalent health conditions and manage age-related illness effectively. Hence, this study is aimed at seeing the distributions of blood biochemical and haematological parameters in rural population.</p><p><strong>Methods: </strong>This cross-sectional study investigated the distribution of 26 different haematological and biochemical parameters in longitudinal cohort study (Srinivaspura Aging, NeuoSenescence and COGnition - SANSCOG), from the villages of Srinivaspura, Kolar district, India. A total of 2592 participants (1240 males and 1352 females), aged ≥45 years who are cognitively healthy were included for the analysis. Mean, 2.5<sup>th</sup>, 5<sup>th</sup>, 25<sup>th</sup>, 50<sup>th</sup>, 75<sup>th</sup>, 95<sup>th</sup> and 97.5<sup>th</sup> percentiles were calculated for the entire sample. Additionally, median and percentiles were determined for both gender and age categories (45-54, 55-64, 65-74, and ≥75 years).</p><p><strong>Results: </strong>We observed the distinct distributions of various haematological and biochemical parameters, with elevated levels of glycaemic, lipid, liver, and thyroid parameters.</p><p><strong>Conclusion: </strong>Findings revealed the notable variations from the established reference ranges, indicating the potential undiagnosed cases and highlighting the gaps in health awareness and health seeking behaviour.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"451-458"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Esmond Urwin, Joanne Martin, Neil Sebire, Andy Harris, Jenny Johnson, Erum Masood, Gordon Milligan, Lucy Mairs, Antony Chuter, Michael Ferguson, Philip Quinlan, Emily Jefferson
{"title":"A SARS-CoV-2 minimum data standard to support national serology reporting.","authors":"Esmond Urwin, Joanne Martin, Neil Sebire, Andy Harris, Jenny Johnson, Erum Masood, Gordon Milligan, Lucy Mairs, Antony Chuter, Michael Ferguson, Philip Quinlan, Emily Jefferson","doi":"10.1177/00045632241261274","DOIUrl":"10.1177/00045632241261274","url":null,"abstract":"<p><strong>Background: </strong>Healthcare laboratory systems produce and capture a vast array of information, yet do not always report all of this to the national infrastructure within the United Kingdom. The global COVID-19 pandemic brought about a much greater need for detailed healthcare data, one such instance being laboratory testing data. The reporting of qualitative laboratory test results (e.g. positive, negative or indeterminate) provides a basic understanding of levels of seropositivity. However, to better understand and interpret seropositivity, how it is determined and other factors that affect its calculation (i.e. levels of antibodies), quantitative laboratory test data are needed.</p><p><strong>Method: </strong>36 data attributes were collected from 3 NHS laboratories and 29 CO-CONNECT project partner organisations. These were assessed against the need for a minimum dataset to determine data attribute importance. An NHS laboratory feasibility study was undertaken to assess the minimum data standard, together with a literature review of national and international data standards and healthcare reports.</p><p><strong>Results: </strong>A COVID serology minimum data standard (CSMDS) comprising 12 data attributes was created and verified by 3 NHS laboratories to allow national granular reporting of COVID serology results. To support this, a standardised set of vocabulary terms was developed to represent laboratory analyser systems and laboratory information management systems.</p><p><strong>Conclusions: </strong>This paper puts forward a minimum viable standard for COVID-19 serology data attributes to enhance its granularity and augment the national reporting of COVID-19 serology laboratory results, with implications for future pandemics.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"418-445"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141160438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Impact of Hub & Spoke organization on the measurement of plasma ammonia.","authors":"Davide Camerlengo, Valentina Moioli, Claudia Arrigo, Silvio Contorno, Felicia Stefania Falvella, Alberto Dolci","doi":"10.1177/00045632241266169","DOIUrl":"10.1177/00045632241266169","url":null,"abstract":"","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"490-491"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ingo Mrosewski, Viola Dannheim, Robert Klett, Matthias Urbank, Silvia Stobbe, Jochen R Ittner, Martin Bidlingmaier
{"title":"Rare coincidence: Macro-thyroid-stimulating hormone and multiple manufacturer-specific interferences in thyroid hormone immunoassays.","authors":"Ingo Mrosewski, Viola Dannheim, Robert Klett, Matthias Urbank, Silvia Stobbe, Jochen R Ittner, Martin Bidlingmaier","doi":"10.1177/00045632241262920","DOIUrl":"10.1177/00045632241262920","url":null,"abstract":"<p><p>Immunoassays are widely used for laboratory assessment of endocrine functions including thyroid hormones. While usually adequate for patient evaluation, they are known to potentially suffer from interference from a variety of factors. We report the case of a 44 year-old male patient without clinical symptoms of thyroid disease who presented for specialist evaluation after pathological thyroid function tests prompted a transferal by his primary care practitioner. Thyroid function tests showed discrepant results across immunoassays and platforms of different manufacturers. Polyethylene glycol precipitation prompted the diagnosis of macro-thyroid-stimulating hormone, while heterophilic and non-specific antibody blocking reagents proved ineffective in eliminating the interference in thyroid-stimulating hormone, free triiodothyronine and free thyroxine measurements. Further assessment ruled out a diagnosis of familial dysalbuminemic hyperthyroxinemia, leaving an exclusion diagnosis of manufacturer-specific interference in free triiodothyronine and free thyroxine assays due to unknown factors. Both clinicians and laboratory specialists must be aware of potential interference in immunoassays which otherwise might be misleading, potentially triggering unnecessary (invasive) follow-up procedures or therapeutic interventions. Close communication is required for successful troubleshooting. To our knowledge, no other case of both macro-thyroid-stimulating hormone and manufacturer-specific interference in a single patient has been documented thus far.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"484-489"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141436556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Charlotte Evans, Finlay MacKenzie, Rachel Marrington
{"title":"Variation in liver function testing and the effect of pyridoxal-5-phosphate on ALT, AST and FIB-4 results.","authors":"Charlotte Evans, Finlay MacKenzie, Rachel Marrington","doi":"10.1177/00045632241269741","DOIUrl":"10.1177/00045632241269741","url":null,"abstract":"<p><strong>Background: </strong>As one of the most requested profiles of blood tests, there is a need for standardization among liver function tests (LFT). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are key markers of hepatocellular injury. ALT and AST are used to calculate a Fibrosis-4 (FIB-4) score for assessing liver fibrosis. Despite recommendations by the International Federation of Clinical Chemistry (IFCC) to include pyridoxal-5-phosphate in ALT and AST assay methodologies, most laboratories continue to omit this.</p><p><strong>Methods: </strong>Data from the UK NEQAS for Clinical Chemistry Scheme, Distribution 1160 (November 2023), was reviewed to investigate variation in practice regarding liver blood tests in relation to ALT, AST and FIB-4. In addition, a series of questions audited laboratory practice in relation to liver enzymes.</p><p><strong>Results: </strong>Wide variation was seen in LFT profiles offered by laboratories, with 32 different combinations of tests used. The IFCC-recommended methods for ALT and AST are used by one-third of laboratories and give significantly higher results than non-IFCC methods. Laboratories using IFCC methods also reported significantly higher FIB-4 scores. Reference ranges and cut-offs for these tests also varied, and did not account for method-related differences in results.</p><p><strong>Conclusions: </strong>The lack of standardization of LFTs can have a significant impact on patient care. The difference in results for ALT, AST and FIB-4 in laboratories not using IFCC-recommended methods may lead to misdiagnosis. This issue should be addressed by laboratories using methods including pyridoxal-5-phosphate. Until then, method-related reference ranges and cut-offs for ALT, AST and FIB-4 are required.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"459-468"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dominic J Harrington, Emma Stevenson, Agata Sobczyńska-Malefora
{"title":"The application and interpretation of laboratory biomarkers for the evaluation of vitamin B12 status.","authors":"Dominic J Harrington, Emma Stevenson, Agata Sobczyńska-Malefora","doi":"10.1177/00045632241292432","DOIUrl":"10.1177/00045632241292432","url":null,"abstract":"<p><p>Vitamin B<sub>12</sub> (cobalamin; B<sub>12</sub>) is an essential micronutrient, but deficiency is common. The prompt diagnosis and treatment of B<sub>12</sub> deficiency protects against megaloblastic anaemia, neuropathy and neuropsychiatric changes. Biomarkers of B<sub>12</sub> status include the measurement of serum B<sub>12</sub> (also known as total B<sub>12</sub> or serum cobalamin), holotranscobalamin (holoTC or 'active B12'), methylmalonic acid (MMA) and total plasma homocysteine (Hcy). There is no 'gold standard' test for deficiency and the sensitivity and specificity of each biomarker for the evaluation of B<sub>12</sub> status is affected by analytical and biological factors that may confer a high degree of diagnostic uncertainty. Limited access to technical and clinical expertise can lead to an over-reliance on the serum B<sub>12</sub> test, which is readily available and highly automated. In some cases, the sequential use of different B<sub>12</sub> status biomarkers or the calculation of a composite B<sub>12</sub> status score, derived from a panel of B<sub>12</sub> biomarkers and adjusted for folate status and age, can be used to detect deficient states that may otherwise be overlooked when using a single biomarker approach. This review summarizes the utility of B<sub>12</sub>-related biomarkers and describes approaches to their application and interpretation.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632241292432"},"PeriodicalIF":2.1,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142374913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elisa Caravaggi, Federico Serana, Mattia Carini, Fabiana Ferrari, Daniela Tregambe, Moira Micheletti, Giovanni Martellosio, Duilio Brugnoni, Roberto Bresciani, Giorgio Biasiotto
{"title":"Diagnostic accuracy of bone marrow blood evaluation in haemophagocytic lymphohistiocytosis paediatric patients.","authors":"Elisa Caravaggi, Federico Serana, Mattia Carini, Fabiana Ferrari, Daniela Tregambe, Moira Micheletti, Giovanni Martellosio, Duilio Brugnoni, Roberto Bresciani, Giorgio Biasiotto","doi":"10.1177/00045632241295694","DOIUrl":"10.1177/00045632241295694","url":null,"abstract":"<p><strong>Introduction: </strong>Haemophagocytic lymphohistiocytosis (HLH) is a rare and serious immunological syndrome that involves a strong activation of cytotoxic T lymphocytes and macrophages. HLH determines a cytokine-mediated tissue injury with a contemporary multi-organ failure and a high fatality rate.</p><p><strong>Material and methods: </strong>A retrospective study was performed considering the medical records of paediatric patients who underwent a bone marrow aspirate for suspect HLH. The biomarkers evaluated were among those included in the HLH-2004. Lactate dehydrogenase (LD) was also evaluated. Haemophagocytosis was evaluated in bone marrow blood smear slides.</p><p><strong>Results: </strong>Enrolled were 11 patients included in the HLH group and 8 patients as controls. Haemoglobin and fibrinogen resulted lower in HLH patients than in controls, while blood triglycerides, serum ferritin and LD resulted increased. Blood triglycerides and fibrinogen discriminated HLH cases perfectly, with a sensitivity and specificity of 100%. Ferritin had a sensitivity of 100% and a specificity of 83% (cut off ≥3,721 µg/L) and LD of 73% and of 100% (the cut off ≥1,903 U/L). Haemoglobin was found to have a sensitivity of 75% and a specificity of 100% (cut off ≤ 96 g/L). Total haemophagocytes cell counts were not different between patients and controls. Only the increased number of phagocytized nucleated red blood cells (NRBC) was found to be significantly increased in the patients. Erythrocytes phagocytosis (≥4/1,000 cells) only tended towards significance.</p><p><strong>Conclusions: </strong>The blood biomarkers showed better diagnostic performance than the morphological evaluation. Among the different cell lineages engulfed by haemophagocytes, the best diagnostic performance was obtained by phagocytosed mature erythrocytes and immature nucleated erythrocytes.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632241295694"},"PeriodicalIF":2.1,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alice A Stephenson, Chris G Robinson, Rachel Marrington, James M Hawley
{"title":"Investigation into the linearity of the Roche c 702 carbamazepine assay.","authors":"Alice A Stephenson, Chris G Robinson, Rachel Marrington, James M Hawley","doi":"10.1177/00045632241292510","DOIUrl":"10.1177/00045632241292510","url":null,"abstract":"<p><strong>Background: </strong>Carbamazepine is an anticonvulsant drug which is monitored in patients due to toxic side effects. At Manchester University NHS Foundation Trust (MFT), carbamazepine is measured using Roche's Kinetic Interaction of Microparticles in Solution (KIMS) method on the c 702 platform. The assay has an upper limit of linearity of 20 mg/L. Samples with concentrations above this limit should be identified and manually diluted. However, a poor EQA return from UK NEQAS for Tox and TDM Distribution 456 has highlighted an issue with the Roche KIMS assay. Sample A of the distribution had a carbamazepine concentration of 36 mg/L but was underreported by several Roche users. This indicated that the assay was not consistently identifying high concentration samples which required a dilution.</p><p><strong>Method: </strong>In this investigation, fresh frozen plasma was spiked with carbamazepine concentrations ranging from 15 to 40 mg/L. The spiked samples and EQA material were analysed at two clinical laboratories using the Roche KIMS assay.</p><p><strong>Results: </strong>Samples spiked with concentrations 20-30 mg/L were not consistently identified for dilution by the analyser. This was observed at both hospital sites. Spike samples and EQA with concentrations >30 mg/L were correctly identified at both sites.</p><p><strong>Conclusion: </strong>The manual dilution policy has been changed at MFT, so all samples with a carbamazepine level ≥15 mg/L will be manually diluted. The problem was reported to Roche who are investigating the issue further. We would suggest that other laboratories look at validating their dilution protocols.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632241292510"},"PeriodicalIF":2.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142374911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sheila X Soh, Tze Ping Loh, Sharon Saw, Ai Teng Chong, Jia Sing Yap, Sunil K Sethi, Lizhen Ong
{"title":"A curious case of a negative control line on a dengue duo assay due to interference - A case report.","authors":"Sheila X Soh, Tze Ping Loh, Sharon Saw, Ai Teng Chong, Jia Sing Yap, Sunil K Sethi, Lizhen Ong","doi":"10.1177/00045632241292430","DOIUrl":"https://doi.org/10.1177/00045632241292430","url":null,"abstract":"<p><p>An elderly patient who presented with 1 week of fever and respiratory symptoms was tested for dengue infection with an Abbott Bioline™ Dengue Duo immunochromatographic assay. Unexpectedly, the control line of the dengue non-structural protein 1 (NS1) component was absent, necessitating result invalidation. It remained absent when the test was repeated on the SD Biosensor Standard™ Q Dengue Duo, but present on the Wells Bio careUS<sup>TM</sup> Dengue Combo and Asan Easy Test® Dengue DUO assays, suggesting potential interference. Dilution, polyethylene glycol (PEG) precipitation and centrifugation with a 100 kDa filter were performed to reduce/remove the potential interferent. Sera from other patients that showed a control line, and a test line that was either positive or negative for NS1, were used as controls. Upon dilution with negative control serum, a faint control line emerged. PEG precipitation resulted in disappearance of control and test lines in the positive control. Filtration led to emergence of the control line for the patient's serum but caused the test line for the positive control serum to disappear. Overall, investigations suggested the presence of a high molecular weight (>100 kDa) substance which interferes with chicken IgY-anti-chicken IgY binding at the control line of affected assays. Our results highlight two important points: firstly, some commonly used laboratory procedures (e.g. PEG or filtration) may inadvertently remove the target biomarker (e.g. multimeric NS1) and should be interpreted with appropriate controls. Secondly, alternative kits that use a different antigen-antibody combination for the control line can be considered when similar patients are encountered in future.</p>","PeriodicalId":8005,"journal":{"name":"Annals of Clinical Biochemistry","volume":" ","pages":"45632241292430"},"PeriodicalIF":2.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}