Pediatric Hematology and Oncology最新文献

{"title":"Utilization of supportive care medications and opportunities for pre-emptive pharmacogenomic testing in pediatric and young adults with leukemia.","authors":"Colleen M Sakon, Carmina Sales, Selsbiel Mertami, Andra Raibulet, Rachael R Schulte, James E Slaven, Emma M Tillman","doi":"10.1080/08880018.2024.2368007","DOIUrl":"10.1080/08880018.2024.2368007","url":null,"abstract":"<p><p>This study aimed to evaluate the utilization of drugs with pharmacogenomic guidelines (PGx-drugs) for personalized dosing in pediatric leukemia. A retrospective observational study of pediatric leukemia patients admitted between 2009-2019 at a single-center academic children's hospital was conducted to determine PGx-drug exposure within 3 years of diagnosis. Along with baseline demographic and clinical characteristics of these patients, data regarding dates of diagnosis, relapse, death were collected. During the study period, inclusion criteria were met by 714 patients. The most frequently given medications were ondansetron (96.1%), morphine (92.2%), and allopurinol (85.3%) during the study period. In this cohort, 82% of patients received five or more PGx-drugs. Patients diagnosed with acute myeloid leukemia and leukemia unspecified were prescribed more PGx-drugs than other types of leukemia. There was a significant relationship between age at diagnosis and the number of PGx-drugs prescribed. Adolescents and adults both received a median of 10 PGx-drugs, children received a median of 6 PGx-drugs, and infants received a median of 7 PGx-drugs (<i>p</i> < 0.001). Patients with recurrent leukemia had significantly more PGx-drugs prescribed compared to those without recurrent disease, 10 drugs and 6 drugs, respectively (<i>p</i> < 0.001). Patients diagnosed with childhood leukemia are high utilizers of PGx-drugs. There is a vital need to understand how PGx testing may be utilized to optimize treatment and enhance quality of life. Preemptive PGx testing is a tool that aids in optimization of drug therapy and decreases the need for later treatment modifications. This can result in financial savings from decreased health-care encounters.</p>","PeriodicalId":19746,"journal":{"name":"Pediatric Hematology and Oncology","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11410515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432518","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":"Pseudohyperkalemia in pediatric patients with newly diagnosed hematological malignancies.","authors":"Ting-Chu Li, Wei-Cheng Chan, Ming-Chin Tsai, Shang-Feng Tsai, Sheng-Ling Jan, Lin-Shien Fu, Fang-Liang Huang, Yung-Chieh Huang","doi":"10.1080/08880018.2024.2362157","DOIUrl":"10.1080/08880018.2024.2362157","url":null,"abstract":"<p><p>Patients with newly diagnosed hematological malignancies often present with a considerable cellular burden, leading to complications including hyperkalemia. However, pseudohyperkalemia, arising from <i>in vitro</i> cell lysis, can pose challenges in clinical practice. Although pseudohyperkalemia is frequently reported in adult hematological malignancies, its occurrence in pediatric patients is underreported, and its incidence in this demographic remains unclear. We retrospectively reviewed the medical records of pediatric patients who received a new diagnosis of hematological malignancies from 2011 to 2022 at Taichung Veterans General Hospital. Hyperkalemia was defined by a serum or plasma potassium level exceeding 5.5 mEq/L. Pseudohyperkalemia was defined by 1) a potassium decrease of over 1 mEq/L in within 4 h without intervention or 2) the absence of electrocardiography changes indicative of hyperkalemia. Cases with apparent red blood cell hemolysis were excluded. A total of 157 pediatric patients with a new diagnosis of hematological malignancies were included, 14 of whom exhibited hyperkalemia. Among these 14 cases, 7 cases (4.5%) were of pseudohyperkalemia. This rate increased to 21.2% in patients with initial hyperleukocytosis. Pseudohyperkalemia was associated with a higher initial white blood cell count and lower serum sodium level. All episodes of pseudohyperkalemia occurred in the pediatric emergency department, where samples were obtained as plasma, whereas all true hyperkalemia cases were observed in the ordinary ward or intensive care unit, where samples were obtained as serum. Timely recognition of pseudohyperkalemia is crucial to avoiding unnecessary potassium-lowering interventions in pediatric patients with newly diagnosed hematological malignancies.</p>","PeriodicalId":19746,"journal":{"name":"Pediatric Hematology and Oncology","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311269","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}

{"title":"Hospital acquired venous thromboembolism in children with sickle cell disease.","authors":"Shreya Agarwal, Kayla L Foster, Shaniqua J Anum, Mary C Shapiro, HyoJeong Han, Michael E Scheurer, Gladstone Airewele, Sarah E Sartain","doi":"10.1080/08880018.2024.2362147","DOIUrl":"10.1080/08880018.2024.2362147","url":null,"abstract":"<p><p>Sickle cell disease (SCD) is well recognized as a hypercoagulablestate, however, it remains unclear whether a subgroup of children with SCD at higher risk of venous thromboembolic event (VTE) during hospitalization may benefit from thromboprophylaxis. Our objectives were to describe the clinical characteristics, outcomes and recurrence of hospital acquired VTE in patients with SCD younger than 21 years. This was a single center retrospective study. Data regarding demographics, reason for admission, location of VTE, risk factors like central venous catheter (CVC), intensive care unit (ICU) admission among others were extracted from electronic medical records over a 10-year study period (2011-2021). Recurrence of VTE at 1 and 5 years was assessed. Descriptive statistics were used as indicated. We identified a total of 20 VTE events over the 10-year study period. Six of these events occurred in those younger than 12 years of age. Fourteen (70%) VTE events occurred in the HbSS or HbSβThal0 genotypes compared to 6 (30%) in HbSC. Most common VTE was isolated pulmonary embolism (PE) (<i>n</i> = 10, 50%). VTE were most often associated with acute chest syndrome (ACS) (<i>n</i> = 14, 70%), ICU admissions (<i>n</i> = 10, 50%) and CVC (<i>n</i> = 5/9, 55%). One patient died from the VTE event. One patient with additional underlying risk factors had a recurrent VTE at 13 months. Our study suggests that ICU admission, ACS and presence of CVC increases the risk of VTE in children and young adults with SCD, but larger studies are indicated to validate our findings.</p>","PeriodicalId":19746,"journal":{"name":"Pediatric Hematology and Oncology","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247982","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}

{"title":"Hematopoietic Stem Cell Transplantation in Children with Sickle Cell Disease and Thalassemia Major: A National Database Study.","authors":"Camila De Avila, Paul A Martinez, Prithvi Sendi, Jorge R Galvez Silva, Ossama M Maher, Balagangadhar R Totapally","doi":"10.1080/08880018.2024.2378282","DOIUrl":"10.1080/08880018.2024.2378282","url":null,"abstract":"<p><p>In patients with sickle cell disease (SCD) and beta-thalassemia major (TM), allogeneic hematopoietic stem cell transplantation (HSCT) was considered the only curative treatment option with a good survival rate. However, with the recent approval of gene therapies, more information is needed to understand the benefits and risks of these interventions. We performed a retrospective analysis of the Kids Inpatient Database to describe demographic features, short-term complications, and hospital charges of patients with SCD and TM treated with HSCT during 2006-2019 in the United States. The database was filtered using the <i>International Classification of Diseases</i>, 9^th and 10^th edition codes to identify children under 20 years of age with SCD or TM who underwent HSCT. A total of 513 children with SCD or TM who received HSCT were analyzed. The prevalence of HSCT per 1000,000 U.S. population increased from 0.31 in 2006 to 1.99 in 2019 (<i>p</i> < 0.001). The median age of children with SCD who underwent HSCT was 10 (6-15) years, and that for TM was 6 (3-11.5) years (<i>p</i> < 0.001). The combined mortality rate was 4% (2.4%-6.6%) but higher in the TM group. The length-of-stay and total charges were higher in the TM population (<i>p</i> < 0.01). This study provides national data on HSCT among hospitalized children with SCD and TM in the United States, demonstrating an increasing use of HSCT between 2006 and 2019. Although hospital mortality of HSCT in these conditions is low, it still represents a challenge, especially in TM patients.</p>","PeriodicalId":19746,"journal":{"name":"Pediatric Hematology and Oncology","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616987","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}

{"title":"Hepatic veno-occlusive disease with asparaginase products: a review of cases reported to the FDA adverse event reporting system and published in the literature.","authors":"Connie Cheng, Graça M Dores, Afrouz Nayernama, S Christopher Jones, Cara A Rabik","doi":"10.1080/08880018.2024.2395365","DOIUrl":"10.1080/08880018.2024.2395365","url":null,"abstract":"<p><p>Multiple asparaginase products have been approved by the United States (US) Food and Drug Administration (FDA) for the treatment of acute lymphoblastic leukemia in pediatric and adult patients. Hepatic veno-occlusive disease (VOD) is a potentially life-threatening disorder resulting from damage to the liver sinusoidal endothelial cells. To evaluate this safety concern with asparaginase (i.e. Asparlas, Oncaspar, Rylaze, and Erwinaze) use, we performed a postmarketing review of hepatic VOD reports retrieved from the FDA Adverse Event Reporting System database and literature with these four products. We identified 55 cases of hepatic VOD following exposure to asparaginase products. The median time to onset of hepatic VOD from the first dose of asparaginase was 18 days (interquartile range 13-24 days). Notably, 80% (44/55) of cases reported grades 3-5 VOD per the Common Terminology Criteria for Adverse Events. Although patients received asparaginase with standard chemotherapeutic agents known to induce VOD, case-level data indicates that asparaginase products may have contributed to hepatic VOD. Asparaginase products are associated with hepatotoxicity and thrombosis, suggesting a plausible mechanism for asparaginase-induced hepatic VOD. Based on the totality of data, including temporality and biologic plausibility, we determined hepatic VOD to be a class effect with asparaginase products. These data contributed to the addition of hepatic VOD to the hepatoxicity warning in the US Prescribing Information for asparaginase class products.</p>","PeriodicalId":19746,"journal":{"name":"Pediatric Hematology and Oncology","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081222","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}

{"title":"Clonal hematopoiesis of indeterminate potential is rare in pediatric patients undergoing autologous stem cell transplantation.","authors":"Mutlu Kartal-Kaess, Axel Karow, Ulrike Bacher, Thomas Pabst, Raphael Joncourt, Christiane Zweier, Claudia E Kuehni, Naomi Azur Porret, Jochen Roessler","doi":"10.1080/08880018.2024.2362885","DOIUrl":"10.1080/08880018.2024.2362885","url":null,"abstract":"<p><p>Clonal hematopoiesis of indeterminate potential (CHIP) describes recurrent somatic gene mutations in the blood of healthy individuals, associated with higher risk for hematological malignancies and higher all-cause mortality by cardiovascular disease. CHIP increases with age and is more common in adult patients after chemotherapy or radiation for cancer. Furthermore, in some adult patients undergoing autologous stem cell transplantation (ASCT) or thereafter, CHIP has been identified. In children and adolescents, it remains unclear how cellular stressors such as cytotoxic therapy influence the incidence and expansion of CHIP. We conducted a retrospective study on 33 pediatric patients mostly with solid tumors undergoing ASCT for presence of CHIP. We analyzed CD34+ selected peripheral blood stem cell grafts after several cycles of chemotherapy, prior to cell infusion, by next-generation sequencing including 18 \"CHIP-genes\". Apart from a somatic variant in <i>TP53</i> in one patient no other variants indicative of CHIP were identified. As a CHIP-unrelated finding, germline variants in <i>CHEK2</i> and in <i>ATM</i> were identified in two and four patients, respectively. In conclusion, we could not detect \"typical\" CHIP variants in our cohort of pediatric cancer patients undergoing ASCT. However, more studies with larger patient numbers are necessary to assess if chemotherapy in the pediatric setting contributes to an increased CHIP incidence and at what time point.</p>","PeriodicalId":19746,"journal":{"name":"Pediatric Hematology and Oncology","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262441","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}

{"title":"Impact of regional SARS-CoV-2 proceedings on changes in diagnoses of pediatric malignancies in Bavaria during the COVID-19 pandemic.","authors":"Mira Reger, Kirsi Manz, Theresa Kaeuferle, Ramona Coffey, Zofia Wotschofsky, Irene von Luettichau, Paul-Gerhardt Schlegel, Michael C Frühwald, Selim Corbacioglu, Markus Metzler, Tobias Feuchtinger","doi":"10.1080/08880018.2024.2393623","DOIUrl":"10.1080/08880018.2024.2393623","url":null,"abstract":"<p><p>The COVID-19 pandemic affected daily life significantly and had massive consequences for healthcare systems with tremendous regional differences. This retrospective study aimed to investigate whether the pandemic and resulting societal changes impacted the diagnosis of pediatric malignancies in a distinct region. Pediatric cancer cases in Bavaria (2016-2021) and SARS-CoV-2 proceedings during the peak phase of the pandemic (2020-2021) were retrospectively analyzed. All new diagnoses of pediatric malignancies reported from cancer centers in Bavaria were included. Clinical data from pre-pandemic years was compared to diagnoses made during the pandemic. Official SARS-CoV-2 reports were received from the Bavarian Health and Food Safety Authority and data on regional pandemic measures were obtained from the Healthcare Data Platform. With this design, a comprehensive analysis of the pandemic proceedings was performed. We found significantly decreased incidence-rate ratios for pediatric cancer diagnosis during the early spring peak of SARS-CoV-2 as it was observed in May during the pandemic, followed by non-significantly increased metastatic cancer diagnosis two months later. Additionally, the time-to-diagnosis of pediatric malignancies was significantly prolonged during the pandemic, and outpatient contacts were significantly reduced, although the availability of consultations remained the same. From our findings, we may hypothesize that there have been effects on pediatric cancer diagnosis during the COVID-19 pandemic at vulnerable times. Interpretation of changes remains speculative with potential causes from behavior patterns, such as hesitation, concerns, and potential societal changes during phases of public restrictions, rather than overwhelmed medical capacities. Nevertheless, specific awareness is needed to protect this patient population during potential future pandemics.</p>","PeriodicalId":19746,"journal":{"name":"Pediatric Hematology and Oncology","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133415","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}

{"title":"A Comparative Analysis of Low Dose Grafalon^® Versus Thymoglobuline^® as Serotherapy in Hematopoietic Stem Cell Transplant in Pediatric and Young Adult Population.","authors":"Garima Nirmal, Gaurav Kharya, Ravi Shankar, Saksham Singh, Subhasish Paul, Mohit Choudhary, Vaibhav Chadha, Kamol Iskandarov, Sayitov Begali, Atish Bakane, Goutomi Chatterjee","doi":"10.1080/08880018.2024.2398523","DOIUrl":"https://doi.org/10.1080/08880018.2024.2398523","url":null,"abstract":"<p><p>Anti-thymocyte globulin (ATG) forms an essential component of conditioning in hematopoietic stem cell transplantation (HSCT). Due to the shift of donor preference to alternate donors, reliance on rabbit-ATG (rATG) has increased. Two different forms of rATG (Thymoglobuline^® and Grafalon^®) are available for clinical use but data to support the use of one over the other is sparse. We retrospectively analyzed data of 144 patients who underwent allogenic-HSCT for benign hematological conditions at our center, from August 2019 to August 2023. Of these, 87 received Grafalon^® and 57 received Thymoglobuline^®. The majority (77.7%) underwent HSCT for hemoglobinopathies and all received pre-transplant immunosuppression. Engraftment kinetics was similar in 2 cohorts. Six patients had primary graft failure (PGF). There was no difference in the incidence of PGF stratified by serotherapy. Overall survival(OS) for the cohort was 74.9%. Kaplan-Meier estimate of OSand EFSwas significantly better in Grafalon^® group than Thymoglobuline^® (84.4 ± 0.04% vs 64.1% ±0.065%) (<i>p</i>-value= 0.04%) and (84.4 ± 0.04% and 61.2%±0.065% (<i>p</i>-value = 0.01)). Extensive chronic GVHD was (14%) higher in Thymoglobuline^® group and (2.3%) in Grafalon^®. Immune reconstitution at day + 100 was not statistically different between the two groups. On univariate analysis, Thymoglobuline^® serotherapy (OR (95% CI) =4.665 (1.2-18.04))was associated with increased risk of acute grade III-IV GvHD. In our study, Grafalon^® tended to have better OS, decreased incidence of acute grade III-IV GvHD, and extensive cGVHD. There was no difference in engraftment kinetics, PGF, and immune reconstitution between 2 cohorts of serotherapy.</p>","PeriodicalId":19746,"journal":{"name":"Pediatric Hematology and Oncology","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292896","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}

{"title":"Iron deficiency anemia among infants: a retrospective cohort study.","authors":"Vered Shkalim Zemer,Michal Barzel Weinberger,Dafna Nesselroth,Haim Bibi,Bernice Oberman,Yael Reichenberg,Yoel Levinsky,Shay Nemet,Moriya Cohen,Avner Herman Cohen","doi":"10.1080/08880018.2024.2400507","DOIUrl":"https://doi.org/10.1080/08880018.2024.2400507","url":null,"abstract":"Postnatal iron deficiency, especially from ages 6 to 24 months, has long-term consequences lasting into adolescence and adulthood. We aimed to characterize iron deficiency anemia among infants from one central Israeli district by demographic and laboratory parameters. A retrospective chart review was performed on all infants from a single district who had undergone a complete blood count as part of a routine survey for iron deficiency anemia during 2010-2021. Data retrieved included hemoglobin levels, mean corpuscular volume, and demographic features: sex, sector (non-ultraorthodox Jew, ultraorthodox Jew, and Arab), socioeconomic status, and type of residence. The study group comprised 101,650 infants, aged 9 to 18 months. Iron deficiency anemia, defined as a hemoglobin level <11 g/dL and mean corpuscular volume <70 fl was observed in 4296 (4.2%) of the study infants. Iron deficiency anemia was more prevalent among Arab and ultraorthodox Jewish infants, than non-ultraorthodox Jewish infants (6.6% vs. 6% vs. 3%, respectively). It was also more prevalent among infants of low socioeconomic status, and relatively common among infants of rural residence. We identified two specific sub-populations at risk of developing iron deficiency anemia: Arab and ultraorthodox Jewish infants. We recommend enhancing the nationwide intervention program for both clinicians and parents, thereby treating iron deficiency anemia promptly to avoid short- and long-term deleterious health consequences.","PeriodicalId":19746,"journal":{"name":"Pediatric Hematology and Oncology","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142266839","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}

{"title":"Correction.","authors":"","doi":"10.1080/08880018.2024.2322859","DOIUrl":"10.1080/08880018.2024.2322859","url":null,"abstract":"","PeriodicalId":19746,"journal":{"name":"Pediatric Hematology and Oncology","volume":null,"pages":null},"PeriodicalIF":1.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140094465","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}