Acta Haematologica最新文献

{"title":"Waldenström Macroglobulinemia and Non-IgM-Type Lymphoplasmacytic Lymphoma Are Genetically Similar.","authors":"Maaya Awata-Shiraiwa,&nbsp;Akihiko Yokohama,&nbsp;Yukihiro Kanai,&nbsp;Nanami Gotoh,&nbsp;Tetsuhiro Kasamatsu,&nbsp;Hiroshi Handa,&nbsp;Takayuki Saitoh,&nbsp;Hirokazu Murakami,&nbsp;Junko Hirato,&nbsp;Hayato Ikota,&nbsp;Norifumi Tsukamoto","doi":"10.1159/000530100","DOIUrl":"10.1159/000530100","url":null,"abstract":"<p><strong>Introduction: </strong>Waldenström macroglobulinemia (WM) represents a subset of lymphoplasmacytic lymphoma (LPL) with the immunoglobulin (Ig)M paraprotein. MYD88 L265P and CXCR4 mutations are common mutations in WM patients, and mutations in ARID1A and KMT2D (MLL2) have also been reported. However, little information has been accumulated on genetic changes in LPL with other paraproteins like IgG.</p><p><strong>Methods: </strong>We therefore aimed to evaluate genetic differences between WM and LPL with non-IgM paraprotein (non-IgM-type LPL) using targeted next-generation sequencing (NGS) in 20 Japanese patients (10 with WM, 10 with non-IgM-type LPL).</p><p><strong>Results: </strong>Mutations were detected in ARID1A (10%), CXCR4 (20%), MYD88 (90%), and KMT2D (0%) for WM patients and in ARID1A (10%), CXCR4 (20%), MYD88 (70%), and KMT2D (10%) for non-IgM-type LPL patients. No significant differences were identified. No mutations were detected in NOTCH2, PRDM1, CD274 (PD-L1), PDCD1LG2 (PD-L2), RAG2, MYBBP1A, TP53, or CD79B.</p><p><strong>Discussion: </strong>Mutant allele frequency in MYD88 L265P did not differ significantly between WM and non-IgM-type LPL. Most mutations detected by NGS were subclonal following MYD88 L265P, although one non-IgM-type LPL patient harbored only CXCR4 S338X mutation. Our NGS analyses reveal genetic characteristics in LPL patients and suggest genetic similarities between these two subsets of LPL, WM and non-IgM-type.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"384-390"},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9465826","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":"Acute Myeloid Leukemia with NPM1 Mutation and Disseminated Leukemia Cutis: Achievement of Molecular Complete Remission by Venetoclax/Azacitidine Combination in a Very Old Patient.","authors":"Pasquale Niscola,&nbsp;Carla Mazzone,&nbsp;Stefano Fratoni,&nbsp;Nicolina Rita Ardu,&nbsp;Laura Cesini,&nbsp;Marco Giovannini,&nbsp;Tiziana Ottone,&nbsp;Lucia Anemona,&nbsp;Maria Teresa Voso,&nbsp;Paolo de Fabritiis","doi":"10.1159/000531101","DOIUrl":"10.1159/000531101","url":null,"abstract":"<p><p>We describe a case of acute myeloid leukemia with NPM1 mutation and disseminated leukemia cutis in a very old patient, who achieved a long-lasting response to the azacitidine/venetoclax combination with molecular complete remission, given the potential value of this rarely observed clinical outcome.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"408-412"},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9522852","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 Longitudinal Assessment of the Natural Change in Haemoglobin, Haematocrit, and Mean Corpuscular Volume with Age.","authors":"Idan Goldberg,&nbsp;Eytan Cohen,&nbsp;Anat Gafter-Gvili,&nbsp;Tzippy Shochat,&nbsp;Eitan Kugler,&nbsp;Ili Margalit,&nbsp;Elad Goldberg,&nbsp;Pia Raanani,&nbsp;Ilan Krause","doi":"10.1159/000529356","DOIUrl":"https://doi.org/10.1159/000529356","url":null,"abstract":"<p><strong>Introduction: </strong>We aimed to assess the natural annual trends in the levels of haemoglobin, haematocrit, and mean corpuscular volume (MCV) in a population of adults, together with the influence of different clinical parameters on these trends.</p><p><strong>Methods: </strong>A retrospective analysis was carried out on data from a large cohort of subjects attending a screening centre in Israel. For each subject, the yearly average change of haemoglobin, haematocrit, and MCV was calculated. Statistical analysis was performed for the whole cohort and for different subgroups.</p><p><strong>Results: </strong>The study included 3,551 subjects. The average annual rates of decline were found to be -0.0550 g/dL (95% confidence interval [CI] -0.0590 g/dL to -0.0503 g/dL) and -0.097% (95% CI -0.112% to -0.083%) for haemoglobin and haematocrit, respectively. An average annual increase in the MCV level by 0.184 fL (95% CI 0.168 fL-0.200 fL) was found. Among men, the rate of decline in haemoglobin was found to be twice as high compared with women -0.06 g/dL versus -0.03 g/dL, respectively (p = 0.0063). In a multivariate analysis, gender remained the only parameter significantly associated with the annual decline of haemoglobin (p = 0.0001).</p><p><strong>Conclusion: </strong>An annual average decrease in the levels of haemoglobin and haematocrit together with an annual increase in MCV was found. These changes were more prominent in men.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":"146 3","pages":"206-213"},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9568688","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":"Once Monthly Elotuzumab and Lenalidomide Plus Dexamethasone for Multiple Myeloma: A Multicenter Observation Study.","authors":"Kazuhito Suzuki,&nbsp;Morio Matsumoto,&nbsp;Yasushi Hiramatsu,&nbsp;Naoki Takezako,&nbsp;Yotaro Tamai,&nbsp;Kenshi Suzuki","doi":"10.1159/000528700","DOIUrl":"https://doi.org/10.1159/000528700","url":null,"abstract":"<p><strong>Introduction: </strong>Elotuzumab and lenalidomide plus dexamethasone (ERd) is a standard salvage chemotherapy for multiple myeloma, and elotuzumab is commonly administered every 2 weeks after cycle 3 (conventional ERd). Alternatively, elotuzumab may often be used every 4 weeks (monthly ERd) in real-world practice. The purpose of this multicenter observational study was to investigate the efficacy and tolerability of monthly ERd.</p><p><strong>Methods: </strong>We investigated the efficacy and tolerability between conventional and monthly ERd regimens for the myeloma patients in six institutes retrospectively.</p><p><strong>Results: </strong>Seventy-five patients were included in this study. The median patient age was 68 years. The median number of prior chemotherapies was two (1-5). The number of patients with prior lenalidomide exposure was 57 (76.0%). The numbers of progressive disease (PD) and non-PD before ERd were 23 (30.7%) and 52 (69.3%), respectively. The frequency of PD before ERd was significantly lower in the monthly ERd group than in the conventional ERd group. In 26.9 months of median follow-up period, the 2-year progression-free survival (PFS) rate in the monthly ERd group was significantly longer than that in the conventional ERd group (95.0% and 62.0%, hazard ratio 0.082, p = 0.002). However, no significant difference in PFS between these two ERd groups was found using multivariate analysis. The complete response rates were similar between the monthly and conventional ERd groups (55.0% and 32.7%, p = 0.109). There was no significant difference in the incidence of adverse events between the monthly and conventional ERd groups (35.0% and 54.5%, p = 0.192). There was no significant difference in the kinetics of the mean absolute lymphocyte count, CD4, CD8, CD16, CD56, and CD57 positive lymphocyte counts, and CD4 to CD8 ratio between the monthly and conventional ERd groups.</p><p><strong>Discussion: </strong>The efficacy and tolerability of monthly ERd were similar to those of conventional ERd. Thus, monthly ERd might be a reasonable option, considering the quality of life of patients and convenience.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":"146 2","pages":"125-136"},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9245375","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":"Clinical Outcomes of COVID-19 in Mycosis Fungoides and Sezary Syndrome.","authors":"Ilana Levy Yurkovski, Lior Rokach, Guy Melamed, Hillel Alapi, Sivan Gazit, Tal Patalon, Tamar Tadmor","doi":"10.1159/000531831","DOIUrl":"10.1159/000531831","url":null,"abstract":"<p><strong>Introduction: </strong>Haemato-oncologic patients are more susceptible to severe infections with SARS-CoV-2. We aimed to assess the clinical outcomes of SARS-CoV-2 infection among patients with Mycosis Fungoides and Sezary Syndrome (MF/SS).</p><p><strong>Methods: </strong>The data were retrieved from anonymized electronic medical records of Maccabi Healthcare Services (MHS), the second-largest healthcare organization in Israel. Patients diagnosed with MF/SS were included in the study. COVID-19 PCR test results together with sociodemographic and clinical data were extracted and analyzed to evaluate the association of COVID-19 with clinical outcomes.</p><p><strong>Results: </strong>In the period of 2020-2022, 1,472 MF/SS patients were included in the study. Among them, 768 (52%) had SARS-CoV-2 infection. The hospitalization rate was 2.9% and infection by the Delta variant was associated with the highest hospitalization rate (7.7%). The hospitalization rate was lower among fully vaccinated patients (p = 0.032) but higher for patients older than 65 (p &lt; 0.001) and patients with SS (vs. MF) (p &lt; 0.001) or COPD (p = 0.024) diagnosis. There was a tendency for decreased hospitalization among patients treated with nirmatrelvir + ritonavir within 5 days of infection, with a 79% risk reduction, although it was not statistically significant (p = 0.164).</p><p><strong>Conclusion: </strong>Patients with MF/SS do not necessarily have worse COVID-19 outcomes compared to the general population.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"497-504"},"PeriodicalIF":1.7,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9894513","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":"Make Family Caregivers Visible, Valued, and Supported: An Interview with Patients' Caregivers' Advocate.","authors":"Pia Raanani,&nbsp;Rachel Ledany","doi":"10.1159/000527734","DOIUrl":"https://doi.org/10.1159/000527734","url":null,"abstract":"<p><p>Many people will need support and help with their daily functioning during their adult life. The solution to this need for support might be either by using a formal or an informal care and support system. Informal care is delivered by nonprofessionals (usually family members) not paid for their duty, defined as the caregivers. The care provided by relatives requires understanding, knowledge, and skills in a wide variety of fields. In this interview, we try to shed light on the place and role of the caregiver, sometimes an invisible major player in the patient's journey.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":"146 1","pages":"47-51"},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10663847","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 Retrospective Chart Review of 809 Patients with Physician-Diagnosed Essential Thrombocythemia Receiving Cytoreductive Therapy in US Community Oncology Practices.","authors":"Jingbo Yu,&nbsp;Dilan Paranagama,&nbsp;Becky Hanna,&nbsp;Jackson Tang,&nbsp;Aleksander Chojecki","doi":"10.1159/000526599","DOIUrl":"https://doi.org/10.1159/000526599","url":null,"abstract":"<p><strong>Introduction: </strong>This analysis reports demographic and clinical characteristics of patients with physician-diagnosed essential thrombocythemia (ET) receiving cytoreductive therapy in US community clinical practice.</p><p><strong>Methods: </strong>Patient characteristics, medical history, diagnostic test results, signs/symptoms, treatment patterns, and physician practice settings were extracted from medical charts for patients with physician-diagnosed ET receiving cytoreductive therapy.</p><p><strong>Results: </strong>Among 809 patients (51.1% female; 75.4% White; median age, 69 years) from 50 community practices, 64.5% had physician-reported diagnosis per World Health Organization criteria. Only 48.8% underwent diagnostic bone marrow biopsies; 87.5% had JAK2 mutation testing. Among those tested, 512/708 (72.3%), 57/213 (26.8%), and 37/213 (17.4%) had JAK2, CALR, and MPLmutations, respectively. Of physician-assigned risk assessments, 41.8% were misclassifications based on data-derived risk assessment. Most patients (93.3%) received first-line hydroxyurea (HU) cytoreductive therapy. Discontinuations were primarily for intolerance (35.4%) and resistance (23.8%). Of those who discontinued, 65.9% received no subsequent therapy and had higher ET symptom rates at last visit versus patients continuing HU (48.8% vs. 25.0%).</p><p><strong>Conclusion: </strong>This study shows notable gaps in ET diagnosis and management. Half of patients were diagnosed without bone marrow biopsy, many received incorrect risk assignment, and the majority who discontinued HU received no subsequent therapy despite continued need.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":"146 1","pages":"26-36"},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10666204","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":"Association between Thrombin Generation and Clinical Characteristics in COVID-19 Patients.","authors":"Omri Cohen,&nbsp;Nitsan Landau,&nbsp;Einat Avishai,&nbsp;Tami Brutman-Barazani,&nbsp;Ivan Budnik,&nbsp;Tami Livnat,&nbsp;Keren Asraf,&nbsp;Ram Doolman,&nbsp;Sarina Levy-Mendelovich,&nbsp;Orly Efros,&nbsp;Uri Manor,&nbsp;Eyal Meltzer,&nbsp;Gad Segal,&nbsp;Galia Rahav,&nbsp;Gili Kenet","doi":"10.1159/000527581","DOIUrl":"https://doi.org/10.1159/000527581","url":null,"abstract":"<p><strong>Introduction: </strong>Coronavirus disease 2019 (COVID-19) disease is associated with coagulopathy and an increased risk of thrombosis. An association between thrombin generation (TG) capacity, disease severity, and outcomes has not been well described.</p><p><strong>Methods: </strong>We assessed the correlation of TG with sequential organ failure assessment (SOFA) and sepsis-induced coagulopathy (SIC) scores and clinical outcomes by analysis of plasma samples obtained from hospitalized COVID-19 patients.</p><p><strong>Results: </strong>32 patients (68.8% male), whose median age was 69 years, were assessed, of whom only 3 patients did not receive anticoagulant therapy. D-dimers were uniformly increased. During hospitalization, 2 patients suffered thrombosis, 3 experienced bleeding, and 12 died. TG parameters from anticoagulated COVID-19 patients did not significantly differ from the values obtained from non-anticoagulated healthy controls. Patients who received higher than prophylactic doses of anticoagulant therapy had increased lag time (p = 0.003), lower endogenous thrombin potential (ETP) (p = 0.037), and a reduced peak height (p = 0.006). ETP correlated with the SIC score (p = 0.038). None of the TG parameters correlated with the SOFA score or were associated with mortality.</p><p><strong>Conclusion: </strong>TG was not associated with disease severity among patients hospitalized with COVID-19. However, a correlation between ETP and the SIC score was noted and deserves attention.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":"146 2","pages":"151-160"},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10137312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9728923","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":"High Expression of CD300A Predicts Poor Survival in Acute Myeloid Leukemia.","authors":"Haihui Zhuang,&nbsp;Fenglin Li,&nbsp;Ting Si,&nbsp;Renzhi Pei,&nbsp;Mengxia Yu,&nbsp;Dong Chen,&nbsp;PeiPei Ye,&nbsp;Ying Lu","doi":"10.1159/000529078","DOIUrl":"https://doi.org/10.1159/000529078","url":null,"abstract":"<p><strong>Introduction: </strong>Recent studies have suggested that CD300A was an oncogene in acute myeloid leukemia (AML) development. However, the clinical relevance and biological insight into CD300A expression in AML are still not well understood. The present study aimed to examine the expression characteristics of CD300A in AML and confirmed its clinical significance for AML.</p><p><strong>Methods: </strong>Quantification of the CD300A transcript was performed in 119 AML patients by real-time quantitative PCR in bone marrow blasts. The predictive significance of CD300A expression on the clinical outcomes of AML was assessed using overall survival (OS) and relapse-free survival (RFS). The published Cancer Genome Atlas (TCGA) data were used as an external validation for survival analysis and pathway analyses.</p><p><strong>Results: </strong>In comparison with monocytes from healthy peripheral blood cells, the expression levels of CD300A in AML cells were higher. Patients in the intermediate and adverse risk categories by WHO criteria (2018) had higher CD300A expression levels than those in the favorable risk category (p < 0.001). AML patients with high expression of CD300A had a higher early death rate (p = 0.029), lower complete remission rate (p = 0.042), higher death rate (p < 0.001) and relapse rate (p = 0.002), and shorter OS (p < 0.0001) and RFS (p < 0.0001). Through multivariable analysis, high CD300A expression in AML was also an independent poor prognostic factor. The CAMP and CGMP-PKG signaling pathways may be stimulated by increased CD300A expression levels, which may be important for the development of AML.</p><p><strong>Conclusions: </strong>The expression levels of CD300A were associated with risk stratification and the clinical relevance of AML. High CD300A expression may act as an independent adverse prognostic factor for OS and RFS in AML.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":"146 3","pages":"196-205"},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9570894","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":"Pregnancy Course of 10 Women Diagnosed with Chronic Lymphocytic Leukemia.","authors":"Tamar Tadmor,&nbsp;Guy Melamed,&nbsp;Hillel Alapi,&nbsp;Sivan Gazit,&nbsp;Tal Patalon,&nbsp;Lior Rokach","doi":"10.1159/000531400","DOIUrl":"10.1159/000531400","url":null,"abstract":"<p><p>Pregnancies following diagnosis of chronic lymphocytic leukemia (CLL) are rare events, mainly because the disease is typically diagnosed in the elderly. Literature on the topic is based only on case reports, and limited data are available on the influence of pregnancy on CLL course. In this retrospective study, we aimed to summarize the clinical and laboratory course of 10 women with CLL who became pregnant. None of the patients had significant changes in blood count during or after pregnancy or had complications such as infection, autoimmune phenomenon, or preeclampsia. Four out of 10 pregnancies were terminated with an early miscarriage. Following labor, 1 patient started anti-CLL treatment due to preexisting anemia, but none of the women required therapy during CLL progression during the first 2 years of follow-up. We conclude that based on our serial, pregnancy does not negatively impact on CLL course.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"379-383"},"PeriodicalIF":2.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9577461","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}