Clinical biochemistry最新文献

{"title":"A survey of Canadian neurologists' perspectives and preferences for laboratory reporting of CSF oligoclonal banding.","authors":"Victoria Higgins, Michelle L Parker, Daniel R Beriault, Ahmed Mostafa, Mathew P Estey, Terence Agbor, Ola Z Ismail","doi":"10.1016/j.clinbiochem.2024.110855","DOIUrl":"10.1016/j.clinbiochem.2024.110855","url":null,"abstract":"<p><strong>Introduction: </strong>Cerebrospinal fluid (CSF) oligoclonal banding (OCB) analysis aids in the diagnosis of multiple sclerosis (MS). Despite its clinical importance, there is profound variation in processes, reporting, and interpretation of CSF OCB and associated tests/indices across Canadian laboratories. This is likely due to the lack of clear, evidence-based recommendations on CSF OCB analysis processes and reporting. Here, we assessed the CSF OCB reporting needs and preferences of Canadian neurologists as a first step in clinical stakeholder engagement to aid in the development of CSF OCB reporting recommendations.</p><p><strong>Methods: </strong>A 16-question survey was sent to neurologists across Canada in January 2022, and it closed in March 2022. The survey included questions regarding location and length of clinical practice; preferred maximum time limit for paired CSF and serum samples; reporting preferences for CSF-specific OCB, banding patterns, and associated tests/indices; as well as the clinical utility of CSF OCB and associated tests/indices.</p><p><strong>Results: </strong>Twenty-two neurologists from nine provinces participated, with a median practice length of 13 years. Most (64 %) preferred a 24-hour limit for paired serum and CSF sample collection. The majority (73 %) favored a cutoff of ≥ 2 CSF-specific bands for positivity, aligning with the 2017 McDonald criteria. Opinions varied on reporting the number of bands and listing specific conditions in the interpretive comments. Some highlighted the need for further research on band count interpretation and its clinical implications. All respondents found CSF OCB results useful, with 64 % valuing it more than other CSF tests for MS evaluation.</p><p><strong>Conclusions: </strong>Our survey reveals diverse preferences among Canadian neurologists for CSF OCB reporting. Stakeholder engagement and further research are crucial for standardized, improved MS diagnostic practices.</p>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":" ","pages":"110855"},"PeriodicalIF":2.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biochemical exploration of cholestasis: interpretation, traps and interferences.","authors":"Nicolas Stojkoski, Maylis Bertrand, Khaled Messaoudi, Claude Bendavid, Redwan Al-Shami, Caroline Moreau","doi":"10.1016/j.clinbiochem.2024.110852","DOIUrl":"https://doi.org/10.1016/j.clinbiochem.2024.110852","url":null,"abstract":"<p><p>We described the case of a 33-year-old patient who presented to the emergency department with non-febrile jaundice associated with epigastric pain. He suffered from acute non-severe alcoholic hepatitis and cholestasis. Biochemical investigations highlighted a huge elevation of the alpha-1-globulins fraction with an unexpected peak in the alpha-1-globulins area in serum protein electrophoresis, a severe hypercholesterolemia without xanthelasmas nor cholesterolomas. Investigations revealed an abnormal lipoprotein, Lipoprotein X (LpX) that can be responsible for the hypercholesterolemia, but also interferes with biochemical tests like direct low-density lipoprotein cholesterol, albumin, and serum electrolytes assays. LpX is an abnormal lipoprotein, which can be present in patients with liver dysfunction, notably in cholestasis-related conditions where the metabolism of plasma lipoproteins is altered. Cholestasis prevents the normal formation of bile acids, leading to the formation of LpX, which is rich in phospholipids and unesterified cholesterol, but poor in esterified cholesterol, triglycerides and proteins. The accumulation of LpX can lead to severe hypercholesterolemia, but this remains uncommon and data regarding the pathophysiology and incidence of this disease is scarce. The laboratory investigation of patients with suspected Lpx can be challenging, due to the lack of available methods for measurement of LpX. In conclusion, LpX-induced hyperlipidemia must be identified to prevent interference in results for a number of biochemical tests, and additionally to improve patient care.</p>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":" ","pages":"110852"},"PeriodicalIF":2.5,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discordance between creatinine and cystatin C-based estimation of glomerular filtration rate (eGFR) in solid organ transplant patients.","authors":"Mary Kathryn Bohn, Meshach Asare-Werehene, Felix Leung, Davor Brinc, Rajeevan Selvaratnam","doi":"10.1016/j.clinbiochem.2024.110853","DOIUrl":"https://doi.org/10.1016/j.clinbiochem.2024.110853","url":null,"abstract":"<p><strong>Background: </strong>Estimation of glomerular filtration rate is a critical component of assessing kidney function post-solid organ transplantation and in monitoring risk of acute injury. Our objective was to evaluate estimated glomerular filtration rate (eGFR) as derived from creatinine (eGFR_cr), cystatin C (eGFR_cys), and both (eGFR_cr-cys) in a cohort of transplant recipients.</p><p><strong>Methods: </strong>A total of 47 unique post-solid organ transplant patients receiving tacrolimus were included. Residual specimens were assayed for creatinine (Jaffe and enzymatic), cystatin C, and tacrolimus. eGFR was estimated using the 2021 chronic kidney disease (CKD)-EPI formulae. Results were compared by Deming regression and bias was assessed using non-parametric cumulative distribution plots. Percent agreement in chronic kidney disease (CKD) by stage was evaluated across equations.</p><p><strong>Results: </strong>eGFR_cr relative to eGFR_cys estimates demonstrated a median bias of -22 mL/min/1.73 m² and an overall 21.3 % [95 % CI: 12.1, 35.0] agreement in CKD staging. eGFR_cr-cys demonstrated a median bias of -14 mL/min/1.73 m² and overall agreement of 34.0 % [95 % CI: 22.3, 48.4] relative to eGFR_cr (enzymatic). Discordance increased proportionally with eGFR and did not differ by creatinine assay (Jaffe or enzymatic).</p><p><strong>Conclusion: </strong>Cystatin C incorporation leads to markedly negative biases between eGFR estimates in patients with solid organ transplant, implying lack of applicability in the transplant setting. This highlights the dependency of patient characteristics on equation performance and the need to consider confounding factors in interpretation and utilization of cystatin C based equations.</p>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":" ","pages":"110853"},"PeriodicalIF":2.5,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the applicability of urine lateral flow immunochromatography tests for the detection of cocaine in plasma samples.","authors":"Isabella Almeida Millan de Souza, Bruno Pereira Dos Santos, Sabrina Nunes do Nascimento, Letícia Birk, Viviane Cristina Sebben, Sarah Eller, Tiago Franco de Oliveira","doi":"10.1016/j.clinbiochem.2024.110854","DOIUrl":"https://doi.org/10.1016/j.clinbiochem.2024.110854","url":null,"abstract":"<p><strong>Introduction: </strong>Qualitative analysis of cocaine in urine is a common practice in emergency settings. However, positive results from urine screening tests do not necessarily indicate recent exposure. In this context, plasma is considered a more appropriate option due to its shorter detection window and better correlation with symptomatology. Therefore, the availability of rapid tests for this biological matrix is extremely relevant in the clinical and emergency context.</p><p><strong>Methods: </strong>A lateral flow immunochromatography test designed for analyzing cocaine in urine was evaluated for use with plasma samples. A total of 412 samples from suspected cases of intoxication were processed and tested. Concurrently, the samples were analyzed for cocaine and its metabolites, benzoylecgonine and ecgonine methyl ester, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Reliability parameters, including sensitivity, specificity, positive predictive value, negative predictive value, and efficiency, were calculated considering different cutoff values.</p><p><strong>Results: </strong>Approximately 8.3 % of the samples tested positive in the immunoassay, while 10.2 % had a concentration greater than 5 ng/mL for at least one analyte in the LC-MS/MS analysis. Using benzoylecgonine as the target analyte with a cutoff of 40 ng/mL yielded the best reliability results, with 96.3 % sensitivity and 97.9 % specificity. Cocaine did not show satisfactory results, whereas ecgonine methyl ester, despite having 92.9 % sensitivity and 94.7 % specificity at its best cutoff (20 ng/mL), had a positive predictive value of only 38.2 %.</p><p><strong>Conclusions: </strong>The study evaluated the suitability of using rapid urine tests for cocaine detection in plasma, offering a simple and quick drug screening method that is particularly useful in toxicological emergencies.</p>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":" ","pages":"110854"},"PeriodicalIF":2.5,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased monocytic HLA-DR in patients with sepsis: Prediction of diagnosis, severity and prognosis","authors":"Juanjuan Cui ,&nbsp;Wen Cai ,&nbsp;Li Zhang ,&nbsp;Yueyuan Wu ,&nbsp;Yan Huang ,&nbsp;Weifeng Zhao","doi":"10.1016/j.clinbiochem.2024.110851","DOIUrl":"10.1016/j.clinbiochem.2024.110851","url":null,"abstract":"<div><h3>Objective</h3><div>Sepsis is characterized by high incidence and mortality rates, making early recognition and risk stratification critical for preventing delayed treatment and overtreatment. This study investigated the potential of monocytic (m) HLA-DR as a diagnostic and prognostic biomarker of sepsis.</div></div><div><h3>Methods</h3><div>In this prospective study, we collected blood in EDTA-anticoagulated tubes within 48 h from patients diagnosed with sepsis or infection and analyzed the percentage of mHLA-DR in peripheral blood mononuclear cells, C-reactive protein, and procalcitonin within 2 h of collection. We gathered clinical and laboratory data, including sex, age, and comorbidities, calculated the number of dysfunctional organs and sequential organ failure assessment (SOFA) score, and recorded the survival status of patients with sepsis on the 30th day after admission.</div></div><div><h3>Results</h3><div>mHLA-DR levels were lower in patients with sepsis (median 46.60 [interquartile range 23.86–66.51]%) than infection (75.44 [52.13–91.50]%). mHLA-DR could distinguish sepsis from infection with an area under the curve (AUC) of 0.724 (95 %CI 0.624–0.824). Decreased mHLA-DR levels have been found in septic patients with shock or secondary infections. mHLA-DR expression decreased with an increasing number of dysfunctional organs and higher SOFA score. In 30-day non-survivors, mHLA-DR levels were 26.94 (12.06–44.45)%, significantly lower than in survivors (55.20 [24.83–72.37]%). mHLA-DR predicted sepsis prognosis with an AUC of 0.750 (95 %CI 0.623–0.877). When the cut-off value was &lt;52.29 %, the sensitivity and specificity of mHLA-DR for prognosis were 100 % and 52.83 %, respectively. The 30-day survival rate of septic patients with mHLA-DR ≥ 52.29 % was 6.798 (95 %CI 2.075–22.27) times higher than that of patients with mHLA-DR &lt; 52.29 %.</div></div><div><h3>Conclusion</h3><div>mHLA-DR negatively correlates with the severity of sepsis and could be used as a diagnostic and prognostic biomarker for sepsis.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"135 ","pages":"Article 110851"},"PeriodicalIF":2.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential of anti-glutamic acid decarboxylase antibodies to support a diagnosis of autoimmune diabetes mellitus.","authors":"Maryah Liepert, Shamayel Alhaqqan, Alaa Husain, Heather Lochnan, Ronald A Booth, Julie Shaw, Cathy J Sun","doi":"10.1016/j.clinbiochem.2024.110842","DOIUrl":"https://doi.org/10.1016/j.clinbiochem.2024.110842","url":null,"abstract":"<p><strong>Objective: </strong>Anti-glutamic acid decarboxylase (anti-GAD) antibodies are a frequently used diagnostic marker for autoimmune forms of diabetes mellitus (DM), namely, type 1 diabetes mellitus (T1DM) and latent autoimmune diabetes in adults (LADA). We sought to provide insight into a unique diagnostic application of anti-GAD antibodies in patients potentially misdiagnosed with type 2 diabetes mellitus (T2DM).</p><p><strong>Methods: </strong>We present a case series of patients who had a change in diagnosis from T2DM to autoimmune DM that was supported by positive anti-GAD antibodies. Patients were identified via a retrospective chart review of all anti-GAD antibodies tests ordered between 1 January 2020 and 31 December 2021 at a tertiary care academic hospital.</p><p><strong>Results: </strong>Of the 23 patients with previous diagnosis of T2DM, positive anti-GAD antibodies supported the clinician's decision to change the diagnosis to autoimmune DM. The prominent clinical reasons for ordering anti-GAD antibodies in patients previously diagnosed as T2DM were patient presentation with diabetic ketoacidosis, features of insulin insufficiency, inadequate effect of oral diabetes mellitus medications, young age at diagnosis, and a family history of autoimmune conditions.</p><p><strong>Conclusion: </strong>Anti-GAD antibodies' positivity can support a change in diagnosis from T2DM to autoimmune DM, which has substantial impact on patient care. Timely and reliable clinical laboratory reporting of anti-GAD antibodies is highly recommended.</p>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":" ","pages":"110842"},"PeriodicalIF":2.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Malignant pleural effusion risk based on a novel tool using homocysteine and carcinoembryonic antigen in pleural fluid: A multicenter study","authors":"Jose D. Santotoribio ,&nbsp;Juan Corral-Pérez ,&nbsp;David Nuñez-Jurado ,&nbsp;Daniel Fatela-Cantillo ,&nbsp;Ángela García-De La Torre ,&nbsp;Gabriel Orantes-Maroto ,&nbsp;Luis Del Valle-Vázquez ,&nbsp;Daniel Del Castillo-Otero ,&nbsp;Nieves Maira-Gonzalez ,&nbsp;Andrés Cobos-Díaz ,&nbsp;Juan M. Guerrero ,&nbsp;Juan-Bosco Lopez-Saez","doi":"10.1016/j.clinbiochem.2024.110841","DOIUrl":"10.1016/j.clinbiochem.2024.110841","url":null,"abstract":"<div><h3>Introduction</h3><div>This multicenter study aimed to evaluate the Malignant Pleural Effusion Risk (MPER) diagnostic accuracy in distinguishing between benign and malign pleural effusion. Methods: MPER is based on pleural fluid Homocysteine (HCY) and carcinoembryonic antigen (CEA) that were measured using three different methods. MPER was calculated by assessing a previously published probabilistic model: Probability (%) = 100× (1 + e-z)-1, where Z = 0.5471 × [HCY] + 0.3846 × [CEA]–8.2671.</div></div><div><h3>Results</h3><div>A total of 301 patients were included (140 MPE). MPER demonstrated a high AUC (0.891), sensitivity (84.3 %), and specificity (80.7 %) with a cut-off &gt; 35.3 %.</div></div><div><h3>Conclusions</h3><div>The MPER model demonstrated a high diagnostic accuracy supporting its use as a novel and powerful tool.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"135 ","pages":"Article 110841"},"PeriodicalIF":2.5,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ROC of SII and FIB-4 index for predicting mortality in idiopathic pulmonary fibrosis patients.","authors":"Guo-Ming Zhang, Xu-Xiao Guo","doi":"10.1016/j.clinbiochem.2024.110836","DOIUrl":"10.1016/j.clinbiochem.2024.110836","url":null,"abstract":"","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":" ","pages":"110836"},"PeriodicalIF":2.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to Letter to the Editor “The importance of SII and FIB-4 scores in predicting mortality in idiopathic pulmonary fibrosis patients”","authors":"Gorkem Berna Koyun,&nbsp;Serdar Berk,&nbsp;Omer Tamer Dogan","doi":"10.1016/j.clinbiochem.2024.110837","DOIUrl":"10.1016/j.clinbiochem.2024.110837","url":null,"abstract":"","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"135 ","pages":"Article 110837"},"PeriodicalIF":2.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carrier frequency and molecular basis of hemoglobinopathies among blood donors in eastern Morocco: Implications for blood donation and genetic diagnosis","authors":"Ihab Belmokhtar ,&nbsp;Karam Yahya Belmokhtar ,&nbsp;Saida Lhousni ,&nbsp;Majida Charif ,&nbsp;Zaina Sidqi ,&nbsp;Rachid Seddik ,&nbsp;Mohammed Choukri ,&nbsp;Mohammed Bellaoui ,&nbsp;Redouane Boulouiz","doi":"10.1016/j.clinbiochem.2024.110840","DOIUrl":"10.1016/j.clinbiochem.2024.110840","url":null,"abstract":"<div><h3>Background</h3><div>Hemoglobinopathies represent the most commonly inherited autosomal recessive blood disorders in the world. The aim of this study was to determine the carrier frequency and molecular basis of hemoglobinopathies among blood donors in eastern Morocco. This is the first study of its kind for this country.</div></div><div><h3>Methods</h3><div>Healthy blood donors of the BRO Biobank were included in this study. Blood samples were analyzed using an automatic blood cell analyzer for complete blood counts. Hemoglobin fractions were analyzed by capillary electrophoresis and serum ferritin was measured on a chemical and immunological analyzer. Suspected hemoglobinopathy carriers were further characterized by Sanger sequencing, Gap PCR and PCR-RFLP.</div></div><div><h3>Results</h3><div>The study involved 2013 blood donors, of whom 1063 were male and 950 were female (sex ratio male-to-female of 1.1). The median age of these donors was 35 years. The overall carrier frequency of hemoglobinopathies was 1.84 %, with β-thalassemia carriers being the most prevalent (0.65 %) followed by HbAC (0.55 %), α-thalassemia carriers (0.30 %), HbAS (0.1 %), HbAG-Philadelphia (0.1 %), HbAD-Ouled Rabah (0.05 %) and HbAO-Arab (0.05 %). Additionally, novel β-thalassemia variants (C6(−G) and −83(A &gt; G)) and a structural variant (Hb D-Ouled Rabah) were discovered for the first time in Morocco.</div></div><div><h3>Conclusions</h3><div>This study provided the first report on carrier frequency and molecular basis of hemoglobinopathies among healthy donors in Morocco. These findings are valuable for the implementation of carrier screening and genetic diagnosis for hemoglobinopathies. Furthermore, these results justify the need to introduce pre-donation screening for hemoglobinopathy carriers in Morocco, particularly in areas with a high prevalence of carriers to enhance the overall quality of the national blood supply.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"135 ","pages":"Article 110840"},"PeriodicalIF":2.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}