Blood Purification最新文献

{"title":"Retraction Statement.","authors":"","doi":"10.1159/000537697","DOIUrl":"10.1159/000537697","url":null,"abstract":"","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":" ","pages":"1"},"PeriodicalIF":3.0,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721480","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":"Seraph 100 Microbind Affinity Blood Filter Does Not Clear Antibiotics: An Analysis of Antibiotic Concentration Data from PURIFY-OBS.","authors":"Jesse P DeLuca, Daniel J Selig, Pooja Vir, Chau V Vuong, Jeffrey Della-Volpe, Ian M Rivera, Caroline Park, Benjamin Levi, Kathleen P Pratt, Ian J Stewart","doi":"10.1159/000531951","DOIUrl":"10.1159/000531951","url":null,"abstract":"<p><strong>Introduction: </strong>Novel hemoperfusion systems are emerging for the treatment of sepsis. These devices can directly remove pathogens, pathogen-associated molecular patterns, cytokines, and other inflammatory markers from circulation. However, significant safety concerns such as potential antibiotic clearance need to be addressed prior to these devices being used in large clinical studies.</p><p><strong>Methods: </strong>Prospective, observational study of 34 participants undergoing treatment with the Seraph 100® Microbind Affinity Blood Filter (Seraph 100) device at 6 participating sites in the USA. Patients were included for analysis if they had a record of receiving an antibiotic concurrent with Seraph 100 treatment. Patients were excluded if there was missing information for blood flow rate. Blood samples were drawn pre- and post-filter at 1 h and 4 h after treatment initiation. These average pre- and post-filter time-concentration observations were then used to estimate antibiotic clearance in L/h (CLSeraph) due to the Seraph 100 device.</p><p><strong>Results: </strong>Of the 34 participants in the study, 17 met inclusion and exclusion criteria for the antibiotic analysis. Data were obtained for 7 antibiotics (azithromycin, cefazolin, cefepime, ceftriaxone, linezolid, piperacillin, and vancomycin) and one beta-lactamase inhibitor. Mean CLSeraph for the antibiotics investigated ranged from -0.57 to 0.47 L/h. No antibiotic had a CLSeraph statistically significant from 0.</p><p><strong>Discussion/conclusion: </strong>The Seraph 100 did not significantly clear any measured antibiotic in clinical samples. These data give further evidence to suggest that these therapies may be safely administered to critically ill patients and will not impact concentrations of administered antibiotics.</p>","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":" ","pages":"379-385"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139466056","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":"Protein Kinase N1 Level Predicts Acute Kidney Injury in Patients Undergoing Cardiac Surgery: A Prospective Cohort Study.","authors":"Lianjiu Su, Fangfang Zhu, Jiahao Zhang, Edward Z Cao, Cheng Yang, Haibing Sun, Xiaofang Jiang, Xiaozhan Wang, Jing Wang, Zhiyong Peng","doi":"10.1159/000536225","DOIUrl":"10.1159/000536225","url":null,"abstract":"<p><strong>Introduction: </strong>The objective of this study was to examine the utility of protein kinase N1 (PKN1) as a biomarker of cardiac surgery-associated AKI (CSA-AKI).</p><p><strong>Methods: </strong>A prospective cohort study of 110 adults undergoing on-pump cardiac surgery was conducted. The associations between post-operative PKN1 and CSA-AKI, AKI severity, need for renal replacement therapy (RRT), duration of AKI, length of ICU stay, and post-operative hospital stay were evaluated.</p><p><strong>Results: </strong>Patients were categorized into three groups according to PKN1 tertiles. The incidence of CSA-AKI in the third tertile was 3.4-fold higher than that in the first. PKN1 was an independent risk factor for CSA-AKI. The discrimination of PKN1 to CSA-AKI assessed by ROC curve indicated that the AUC was 0.70, and the best cutoff was 5.025 ng/mL. This group (&gt;5.025 ng/mL) was more likely to develop CSA-AKI (p &lt; 0.001). The combined AUC of EuroSCORE, aortic cross-clamp time, and PKN1 was 0.82 (p &lt; 0.001). A higher level of PKN1 was related to increased need for RRT, longer duration of AKI, and length of ICU and post-operative hospital stays.</p><p><strong>Conclusions: </strong>PKN1 could be a potential biomarker for the prediction of CSA-AKI. The combination of PKN1, EuroSCORE, and aortic cross-clamp time was likely to predict the occurrence of CSA-AKI.</p>","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":" ","pages":"465-475"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11151993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139477915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Proenkephalin A 119-159 (penKid) in Extracorporeal Therapies: Ex vivo Sieving Coefficient, Diffusive Clearance, and Hemoadsorption Kinetics.","authors":"Anna Lorenzin, Massimo de Cal, Natascha Perin, Niccolò Morisi, Alessandra Brendolan, Paolo Lentini, Monica Zanella, Claudio Ronco","doi":"10.1159/000540061","DOIUrl":"10.1159/000540061","url":null,"abstract":"<p><strong>Introduction: </strong>Enkephalins, endogenous opioid peptides, are involved in the regulation of renal function. One derived molecule, proenkephalin A, also known as penKid, has been demonstrated to be a reliable biomarker for kidney function and its plasma concentration correlates with measured glomerular filtration rate. penKid is used for prediction and diagnosis of AKI and need of renal replacement therapy (RRT). penKid has also been used to predict the successful weaning from RRT in patients with AKI. Whether the concentration of penKid is affected or not by RRT is a controversial point and there are no studies describing the kinetics of the molecule in such conditions. The low molecular weight (4.5 kDa) would imply free removal by the glomerulus and the dialysis membranes. During RRT, this reduction could not be detected in clinical practice due to the complex kinetics involving either low dialytic clearance or increased production in response to impaired kidney function. The aim of this study was to determine the sieving coefficient and the diffusive clearance of the penKid molecule in conditions of in vitro continuous veno-venous hemofiltration (CVVH) and continuous veno-venous hemodialysis (CVVHD), respectively, and also the penKid removal ratio in conditions of in vitro hemoadsorption (HA) using a synthetic microporous resin.</p><p><strong>Methods: </strong>Blood spiked with a lyophilized penKid peptide solved in 20 m<sc>m</sc> dipotassium phosphate and 6 m<sc>m</sc> disodium EDTA [pH 8] to reach target concentrations is used as testing solution. In each experiment, the blood batch was adjusted at a volume of 1,000 mL, maintained at 37°, and continuously stirred. Samples were collected from blood, ultrafiltrate, and spent dialysate at different times during the experiments. Sieving, clearance, and removal ratio were calculated.</p><p><strong>Results: </strong>Significant removal of penKid was observed in CVVH (sieving 1.04 ± 0.27), in CVVHD (clearance 23.08 ± 0.89), and in HA (removal ratio 76.1 ± 1% after 120 min).</p><p><strong>Conclusion: </strong>penKid is effectively removed by extracorporeal therapies. In presence of anuria, penKid generation kinetics can be calculated based on extracorporeal removal and volume variation. In steady state conditions, declining values may be the result of an initial renal function recovery and may suggest discontinuation and successful liberation from RRT.</p>","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":" ","pages":"773-780"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787241","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":"Construction of Risk-Prediction Models for Autogenous Arteriovenous Fistula Thrombosis in Patients on Maintenance Hemodialysis.","authors":"Xiaoyu Jin, Yuying Fan, Jingshu Li, Xiaona Qi, Xue Li, Hongyi Li","doi":"10.1159/000540543","DOIUrl":"10.1159/000540543","url":null,"abstract":"<p><strong>Introduction: </strong>Autogenous arteriovenous fistula (AVF) is the preferred vascular access in patients undergoing maintenance hemodialysis (MHD). However, complications such as thrombosis may occur. This study aimed to construct and validate a machine learning-based risk-prediction model for AVF thrombosis, hypothesizing that such a model can effectively predict occurrences, providing a foundation for early clinical intervention.</p><p><strong>Methods: </strong>The retrospective longitudinal study included a total of 270 patients who underwent MHD at the Hemodialysis Center of the Second Affiliated Hospital of Harbin Medical University between March 2021 and December 2022. During this study, baseline data and scale information of patients between March 2020 and December 2021 were collected. We recorded outcome indicators between March 2021 and December 2022 for subsequent analyses. Five machine learning models were developed (artificial neural network, logistic regression, ridge classification, random forest, and adaptive boosting). The sensitivity (recall), specificity, accuracy, and precision of each model were evaluated. The effect size of each variable was analyzed and ranked. Models were assessed using the area under the receiver-operating characteristic (AUROC) curve.</p><p><strong>Results: </strong>Among the 270 included patients, 105 had AVF thrombosis (55 male and 50 female patients; age range, 29-79 years; mean age, 56.72 years; standard deviation [SDs], ±13.10 years). Conversely, 165 patients did not have AVF thrombosis (99 male and 66 female patients; age range, 23-79 years; mean age, 53.58 years; SD, ± 13.33 years). During the observation period, approximately 52.6% of patients with AVF experienced long-term complications. The most common complications associated with AVF were thrombosis (105; 38.9%), aneurysm formation (27; 10%), and excessively high output flow (10; 3.7%). Fifty-four (20%) patients with AVF required intervention because of complications associated with vascular access. The AUROC curve of the testing set was between 0.858 and 0.903.</p><p><strong>Conclusion: </strong>In this study, we developed five machine learning models to predict the risk of AVF thrombosis, providing a reference for early clinical intervention.</p>","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":" ","pages":"813-823"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874076","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":"\"Renal\": The First Forbidden Word in the Medical Lexicon.","authors":"Rinaldo Bellomo, John A Kellum, Thiago Reis, Lui G Forni, Claudio Ronco","doi":"10.1159/000536677","DOIUrl":"10.1159/000536677","url":null,"abstract":"","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":" ","pages":"686-690"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857128","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 Role of Early Hemoadsorption in Severe COVID-19 Treatment: A Pilot Randomized Controlled Trial.","authors":"Karjbundid Surasit, Nattachai Srisawat","doi":"10.1159/000540584","DOIUrl":"10.1159/000540584","url":null,"abstract":"<p><strong>Introduction: </strong>Hemoadsorption, an extracorporeal apheresis technique, is reportedly used in severe COVID-19 patients. However, limited evidence from randomized clinical trials supports this practice.</p><p><strong>Methods: </strong>In this single-center study, severe COVID-19 patients requiring ICU admission were randomly assigned (1:1) to receive HA-330 hemoadsorption in combination with standard treatment or standard therapy alone. Both groups received tocilizumab intravenously if their clinical conditions worsened within 24-48 h. The primary outcome was mortality from any cause within 28 days after randomization. Secondary outcomes included mechanical ventilator-free days, daily C-reactive protein levels, oxygenation (defined by PaO2/FiO2 ratio), daily sequential organ failure assessment score, and severity score of lung infiltration on chest X-rays (CXR RALE score).</p><p><strong>Results: </strong>A total of 28 patients underwent randomization, with 14 (50%) receiving HA-330 hemoadsorption. Only 9 out of 14 patients (64.3%) in the control group experienced clinical worsening and were subsequently administered intravenous tocilizumab. At 28 days, the mortality rate was significantly lower in the intervention group (28.57% vs. 78.57%, p = 0.021), with a hazard ratio of death of 0.26 (95% CI = 0.08-0.81; p = 0.021). All of secondary outcomes were comparable in both groups.</p><p><strong>Conclusion: </strong>Based on our pilot randomized trial, the early application of HA-330 hemoadsorption in patients with severe COVID-19 may establish a favorable outcome in term of mortality. These data provide the initial proof of concept for conducting a large-scale study in the future.</p>","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":" ","pages":"793-803"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892808","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":"Efficacy of Therapeutic Apheresis for Cryoglobulinemic Vasculitis Patients with Renal Involvement: A Systematic Review.","authors":"Jing Miao, Pajaree Krisanapan, Supawit Tangpanithandee, Charat Thongprayoon, Wisit Cheungpasitporn","doi":"10.1159/000534102","DOIUrl":"10.1159/000534102","url":null,"abstract":"<p><strong>Introduction: </strong>Therapeutic apheresis (TA) is commonly used for cryoglobulinemic vasculitis (CV) patients, but its efficacy remains uncertain. This systematic review aimed to assess the efficacy of different TA modalities, such as plasma exchange (PE), plasmapheresis (PP), and cryofiltration (CF), in treating CV patients with renal involvement.</p><p><strong>Methods: </strong>Literature search of MEDLINE, EMBASE, and Cochrane Databases was conducted up to December 2022. Studies that reported the outcomes of TA in adult CV patients with renal involvement were assessed. The protocol for this systematic review has been registered with PROSPERO (No. CRD42023417727). The quality of each study was evaluated by the investigators using the validated methodological index for non-randomized studies (minors) quality score.</p><p><strong>Results: </strong>154 patients who encountered 170 episodes of serious events necessitating TA were evaluated across 76 studies. Among them, 51% were males, with a mean age ranging from 49 to 58 years. The CV types included 15 type I, 97 type II, and 13 type III, while the remaining patients exhibited mixed (n = 17) or undetermined CV types (n = 12). Among the treatment modalities, PE, PP, and CF were performed in 85 (56%), 52 (34%), and 17 patients (11%), respectively, with no identical protocol for TA treatment. The overall response rate for TA was 78%, with response rates of 84%, 77%, and 75% observed in type I, II, and III patients respectively. Most patients received steroids, immunosuppressants, and treatment targeting the underlying causative disease. The overall long-term renal outcome rate was 77%, with type I, II, and III patients experiencing response rates of 89%, 76%, and 90%, respectively. The renal outcomes in patients receiving PE, PP, and CF were comparable, with rates of 78%, 76%, and 81%, respectively.</p><p><strong>Conclusions: </strong>This study presents compelling evidence that combination of TA with other treatments, especially immunosuppressive therapy, is a successful strategy for effectively managing severe renal involvement in CV patients. Among the TA modalities studied, including PE, PP, and CF, all demonstrated efficacy, with PE being the most frequently employed approach.</p>","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":" ","pages":"1-9"},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49673958","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 Impact of Early Positive Studies on the Evolution of Extracorporeal Albumin Dialysis Literature: A Bibliometric Analysis.","authors":"Anis Chaba, Stephen Warrillow, Caleb Fisher, Akinori Maeda, Sofia Spano, Rinaldo Bellomo","doi":"10.1159/000534915","DOIUrl":"10.1159/000534915","url":null,"abstract":"<p><strong>Introduction: </strong>Liver failure is a life-threatening condition characterized by the accumulation of metabolic toxins. Extracorporeal albumin dialysis (ECAD) has been promoted as a possible therapy.</p><p><strong>Methods: </strong>We employed bibliometric analysis to scrutinize the conceptual, intellectual, and social structure of the ECAD literature including its co-citation network and thematic analysis to explore its evolution and organization.</p><p><strong>Results: </strong>We identified 784 documents with a mean of 30.25 citations per document in a corpus of 15,191 references. The average citation rate peaked in 1998 at 280.75 citations/year before a second 2013 peak of 54.81 citations/year and then progressively decreased to its nadir in 2022 (1.48 yearly citations). We identified four primary co-citation clusters, with the most impactful publications being small \"positive\" manuscripts by Mitzner et al. (2000) and Heemann et al. (2002) (Cluster 1). This first cluster had several relational citations with clusters 2 and 3, but almost no citation link with cluster 4 represented by Bañares et al. (2013), Saliba et al. (2013), and Larsen et al. (2016), with their three negative randomized controlled trials. Finally, the thematic map revealed a shift in focus over time, with inflammation and ammonia as recent emergent themes.</p><p><strong>Conclusions: </strong>This bibliometric analysis provided a transparent and reproducible longitudinal assessment of ECAD literature and demonstrated how positive studies with low levels of evidence can dominate a research field and overshadow negative findings from higher quality studies. These insights hold significant implications for future research and clinical practice within this domain.</p>","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":" ","pages":"279-287"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71420375","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":"Chemokine (C-C Motif) Ligand 14 to Predict Persistent Severe Acute Kidney Injury: A Systematic Review and Meta-Analysis.","authors":"Nicolas Tebib, Céline Monard, Thomas Rimmelé, Antoine Schneider","doi":"10.1159/000541058","DOIUrl":"10.1159/000541058","url":null,"abstract":"<p><strong>Introduction: </strong>In this systematic review and meta-analysis, we aimed to review available data and provide pooled estimates of the predictive performance of urinary chemokine (C-C motif) ligand (uCCL14) for persistent (≥48 h) severe acute kidney injury (PS-AKI).</p><p><strong>Methods: </strong>We searched MEDLINE, PubMed, Cochrane Library, and EMBASE for studies published up to April 11, 2023. We considered all studies including adults and reporting on the ability of uCCL14 to predict PS-AKI as defined by AKI persisting for 48 or 72 h. Data extraction was performed by one investigator using a standardized form. It was checked for adequacy and completeness by another investigator.</p><p><strong>Results: </strong>After screening, we identified 13 relevant studies. Among those, four (561 patients) provided sufficient data regarding the outcome of interest and were included. Considering each study cutoff value, pooled sensitivity and specificity were 0.85 (95% CI: 0.77-0.90, I2 = 34.1%) and 0.96 (95% CI: 0.94-0.98, I2 = 53.7%), respectively. Pooled positive likelihood ratio (LR), negative LR, and diagnostic odds ratio were 8.98 (95% CI: 4.92-16.37, I2 = 23%), 0.25 (95% CI: 0.17-0.37, I2 = 0%), and 14.98 (95% CI: 3.55-63.27, I2 = 72.9%), respectively. The area under the curve estimated by summary receiver operating characteristics was 0.86 (95% CI: 0.70-0.95). Heterogeneity induced by the threshold effect was low (Spearman's correlation coefficient: -0.30, p value = 0.62) but significant for non-threshold effect. Risk of bias and concern for applicability according to the QUADAS-2 criteria was generally low. High risk in the index test due to the absence of prespecified thresholds was a concern for most studies.</p><p><strong>Conclusion: </strong>Based on current evidence, uCCL14 appears to have a good predictive performance for the occurrence of PS-AKI. Interventional trials to study a biomarker-guided application of AKI care bundles and RRT are indicated.</p>","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":" ","pages":"860-870"},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054862","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}