the Quarterly Journal of Nuclear Medicine and Molecular Imaging最新文献

{"title":"Metabolic brain connectivity reorganization in Alzheimer's disease patients: a systematic review.","authors":"Sébastien Heyer, Matthieu Doyen, Antoine Verger","doi":"10.23736/S1824-4785.24.03570-2","DOIUrl":"10.23736/S1824-4785.24.03570-2","url":null,"abstract":"<p><strong>Introduction: </strong>Metabolic connectivity has been studied in various neurodegenerative diseases, particularly Alzheimer's disease (AD), but there is a wealth of accumulated evidence and sometimes conflicting results, depending on the methodology applied. Therefore, the aim of this systematic review was to summarize the results obtained regarding metabolic brain connectivity using [¹⁸F]-FDG-PET in AD patients compared to cognitively normal subjects.</p><p><strong>Evidence acquisition: </strong>A systematic and exhaustive search of data available in the literature was carried out by querying the PubMed and Web of Science databases. Studies had to meet the following criteria: 1) a metabolic connectivity study with [¹⁸F]-FDG-PET in AD patients; 2) the inclusion of a control group of healthy subjects or cognitively normal controls; and 3) use of seed-based, independent/principal component analyses or methods derived from graph theory. This systematic review followed the PRISMA method.</p><p><strong>Evidence synthesis: </strong>A total of 49 full-text publications were included, involving 3589 AD patients, 3272 prodromal AD patients and 3898 cognitively normal subjects. These results show that AD patients have a reorganization of metabolic connectivity on a global scale, with a decrease in or even the loss of networks seen in the healthy brain and an increase in more local, less efficient connectivity. This reorganization affects not only areas commonly affected in AD but also remote regions known to be usually spared in this pathology.</p><p><strong>Conclusions: </strong>Changes in metabolic connectivity in AD patients do not simply constitute a decrease in global connectivity but rather more complex local and global changes ultimately affecting all brain regions.</p>","PeriodicalId":49135,"journal":{"name":"the Quarterly Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":"207-216"},"PeriodicalIF":1.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141628141","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":"Metabolic and dopaminergic correlates of intellectual enrichment in de-novo Parkinson's disease patients.","authors":"Stefano Raffa, Luca Sofia, Nicola Girtler, Matteo Pardini, Dario Arnaldi, Beatrice Orso, Maria I Donegani, Francesca D'Amico, Francesco Lanfranchi, Guido Rovera, Federico Massa, Pietro Mattioli, Gianmario Sambuceti, Matteo Bauckneht, Silvia Morbelli","doi":"10.23736/S1824-4785.24.03585-4","DOIUrl":"10.23736/S1824-4785.24.03585-4","url":null,"abstract":"<p><strong>Background: </strong>Cognitive reserve (CR) is an expression of brain resilience in response to damage. Education, occupational experience and leisure activities are thought to increase CR and have beneficial effects on global cognition and cognitive decline in Parkinson's disease (PD). We aimed to disclose brain metabolic and dopaminergic correlates of CR in de-novo PD patients.</p><p><strong>Methods: </strong>Sixty-two drug-naïve de-novo PD patients underwent [¹⁸F]FDG-PET and DAT-SPECT. CR was quantified through the Cognitive-Reserve-Index questionnaire including total-CR and 3 subscores (educational-CR, occupational-CR, leisure-CR). Specific binding ratios (SBRs) and Z-scores in basal ganglia were obtained with 'BasGan-V2'. Z-scores were used as dependent variables in general linear models to assess the interaction between dopaminergic function and CR. Voxel-based correlation between brain metabolism and CR-scores and between SBR and [¹⁸F]FDG-PET was evaluated using SPM12 (P<0.05 FWE-corrected at peak and cluster level considered significant).</p><p><strong>Results: </strong>Dopaminergic deficit in the most affected hemisphere (MAH) putamen was significantly less marked in higher CR patients (Z-score -1.7±0.1 highly-educated versus -2.1±0.1 poorly-educated, P<0.02). Total and leisure-related-CR resulted correlated directly with z-scores of the MAH putamen (P<0.018 and P<0.003) and inversely with brain metabolism in both cerebellar hemispheres (P<0.001). MAH-putamen SBR correlated directly with metabolism in occipital and parietal cortex (P<0.003) and inversely in cerebellar hemispheres (P<0.02).</p><p><strong>Conclusions: </strong>CR proxies demonstrated to correlate directly with dopaminergic function and inversely with metabolism in cerebellar hemispheres in de-novo PD patients. The present multi-modal approach including both metabolic and dopaminergic correlates of CR allowed to identify possible compensation mechanisms, highlighting a potential role of the cerebellum that deserves further investigation.</p>","PeriodicalId":49135,"journal":{"name":"the Quarterly Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":"187-193"},"PeriodicalIF":1.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142299324","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":"Correlation of FDG PET/CT, tumor markers and Ki-67 index with EGFR mutation or positive ALK expression in patients with non-small cell lung cancer.","authors":"Hui C Wang, Zhi M Wang, Wei D Hu, Xiao Q Liang, Lan L Cui","doi":"10.23736/S1824-4785.24.03535-0","DOIUrl":"10.23736/S1824-4785.24.03535-0","url":null,"abstract":"<p><strong>Background: </strong>Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are the two most common druggable targets in non-small cell lung cancer (NSCLC). To investigate whether the EGFR mutation and ALK rearrangement could be predicted by the combination of FDG avidity, tumor markers and Ki-67 Index.</p><p><strong>Methods: </strong>A total of 168 newly diagnosed NSCLC patients who had undergone ¹⁸F-FDG PET/CT for staging were enrolled. PET/CT parameters of primary tumors including maximum standardized uptake value (pSUVmax), metabolic tumor volume (pMTV) and total lesion glycolysis (pTLG) were measured. Five serous tumor markers for lung cancer were recorded. Ki-67 labeling index was counted by immunohistochemical staining. EGFR mutation and ALK status were detected by ARMS-PCR and RT-PCR, respectively. Univariate and multivariate analyses were applied to identify the predictors of EGFR mutation and ALK positivity.</p><p><strong>Results: </strong>EGFR mutation rate was 38.1% (64/168), which were found more frequently in female, ≤60 years old, non-smokers and adenocarcinoma patients, and were not related to lymph node involvements, distant metastases, stage and serum tumor markers. Low pSUVmax, pMTV, pTLG and Ki-67 were significantly associated with EGFR mutation. Logistic regression demonstrated that pSUVmax <6.75 and gender (female) were the independent factors affecting EGFR mutation, and the combination of them had a certain predictive value with the area under the curve of 0.784. ALK positive rate was 6.0% (10/168), all of them were adenocarcinoma patients, which were more common in non-smokers, low serum cytokeratin-19 fragment antigen (CYFRA21-1) and low Ki-67, and were not related to FDG activity. No independent factor for ALK positivity was found on Logistic regression.</p><p><strong>Conclusions: </strong>Low pSUVmax, rather than tumor markers or Ki-67, was correlated with EGFR mutation independently, which could be integrated with gender (female) to improve the identification for EGFR mutation in NSCLC patients.</p>","PeriodicalId":49135,"journal":{"name":"the Quarterly Journal of Nuclear Medicine and Molecular Imaging","volume":" ","pages":"169-175"},"PeriodicalIF":1.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617476","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":"New target therapies in prostate cancer: from radioligand therapy, to PARP-inhibitors and immunotherapy.","authors":"Francesco Ceci, Lighea S Airò Farulla, Elena Bonatto, Laura Evangelista, Marta Aliprandi, Luigi G Cecchi, Francesco Mattana, Alessandro Bertocchi, Fabio DE Vincenzo, Matteo Perrino, Nadia Cordua, Federica Borea, Paolo A Zucali","doi":"10.23736/S1824-4785.24.03575-1","DOIUrl":"10.23736/S1824-4785.24.03575-1","url":null,"abstract":"<p><p>Prostate cancer (PCa) remains a significant global health challenge, particularly in its advanced stages. Despite progress in early detection and treatment, PCa is the second most common cancer diagnosis among men. This review aims to provide an overview of current therapeutic approaches and innovations in PCa management, focusing on the latest advancements and ongoing challenges. We conducted a narrative review of clinical trials and research studies, focusing on PARP inhibitors (PARPis), phosphoinositide 3 kinase-protein kinase B inhibitors, immunotherapy, and radioligand therapies (RLTs). Data was sourced from major clinical trial databases and peer-reviewed journals. Androgen deprivation therapy and androgen-receptor pathway inhibitors remain foundational in managing castration-sensitive and early-stage castration-resistant PCa (CRPC). PARPi's, such as olaparib and rucaparib, have emerged as vital treatments for metastatic CRPC with homologous recombination repair gene mutations, highlighting the importance of personalized medicine. Immune checkpoint inhibitors (ICIs) have shown clinical benefit limited to specific subgroups of PCa, demonstrating significant improvement in efficacy in patients with microsatellite instability/mismatch repair or cyclin-dependent kinase 12 alteration, highlighting the importance of focusing ongoing research on identifying and characterizing these subgroups to maximize the clinical benefits of ICIs. RLTs have shown effectiveness in treating mCRPC. Different alpha emitters (like [²²⁵Ac]PSMA) and beta emitters compounds (like [¹⁷⁷Lu]PSMA) impact treatment differently due to their energy transfer characteristics. Clinical trials like VISION and TheraP have demonstrated positive outcomes with RLT, particularly [¹⁷⁷Lu]PSMA-617, leading to FDA approval. Ongoing trials and future perspectives explore the potential of [²²⁵Ac]PSMA, aiming to improve outcomes for patients with mCRPC. The landscape of PCa treatment is evolving, with significant advancements in both established and novel therapies. The combination of hormonal therapies, chemotherapy, PARPis, immunotherapy, and RLTs, guided by genetic and molecular insights, opens new possibilities for personalized treatment.</p>","PeriodicalId":49135,"journal":{"name":"the Quarterly Journal of Nuclear Medicine and Molecular Imaging","volume":"68 2","pages":"101-115"},"PeriodicalIF":1.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301912","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":"Prostate cancer: nuclear medicine imaging in the biochemical recurrence and in oligometastatic disease.","authors":"Lorenzo Muraglia, Egesta Lopci, Jelena Jandric, Roberta Zanca, Marcello Rodari, Matteo Perrino, Raffaella Lucchini, Davide Baldaccini, Francesco Ceci, Laura Evangelista","doi":"10.23736/S1824-4785.24.03569-6","DOIUrl":"10.23736/S1824-4785.24.03569-6","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of this article was to offer a comprehensive non-systematic review of the literature about the use of Nuclear Medicine imaging exams for the evaluation of prostate cancer (PCa) in the recurrent setting, with a particular regard to positron emission tomography/computed tomography (PET/CT) imaging.</p><p><strong>Evidence acquisition: </strong>A comprehensive nonsystematic literature review was performed in March 2024. Literature search was updated until March 2024. The most relevant studies have been summarized, giving priority to registered clinical trials and multicenter collaborations.</p><p><strong>Evidence synthesis: </strong>Restaging BCR with advanced Nuclear Medicine Imaging, such as prostate-specific membrane antigen-PET/CT could lead to stage migration and pave the way for additional management strategies, such as stereotactic ablative radiotherapy in patients with low-burden or oligometastatic disease, potentially delaying the need of systemic therapies. While OS benefits of targeting PET/CT positive disease are still lacking, data on progression- and metastasis-free-survival are emerging. Improvements in quality-of-life assessments are already evident.</p><p><strong>Conclusions: </strong>PCa is one of the most common malignancy in men. In the last 10 years PCa imaging has become significantly more accurate and is now essential for the definition of the extent of the disease in different phases of its natural history. This opened the road to novel management strategies, especially in the recurrent setting, in which the oligometastatic state is now being explored in several trials regarding the prognostic significance of metastasis directed therapies aimed at personalizing the treatment for every single patient.</p>","PeriodicalId":49135,"journal":{"name":"the Quarterly Journal of Nuclear Medicine and Molecular Imaging","volume":"68 2","pages":"95-100"},"PeriodicalIF":1.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301978","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":"Predictive value of 18F-fluorodeoxyglucose PET/CT in histological grade of incidental colorectal adenoma.","authors":"Yushi Peng, Nina Xu, Yinuo Fu, Ling Wang, Fangansheng Chen, Beihui Xue, Junping Lan, Xiangwu Zheng, Kun Tang","doi":"10.23736/S1824-4785.24.03554-4","DOIUrl":"https://doi.org/10.23736/S1824-4785.24.03554-4","url":null,"abstract":"<p><strong>Background: </strong>¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron-emission tomography/computed tomography (PET/CT) as an imaging modality for the whole body has shown its value in detecting incidental colorectal adenoma. In clinical practice, adenomatous polyps can be divided into three groups: low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN) and cancer, which can lead to different clinical management. However, the relationship between the <inf>18</inf>F-FDG PET/CT SUV<inf>max</inf> and the histological grade of adenomatous polyps is still not established, which is a challenging but valuable task.</p><p><strong>Methods: </strong>This retrospective study included 255 patients with colorectal adenoma (CRA) or colorectal adenocarcinomas (AC) who had corresponding ¹⁸F-FDG uptake incidentally found on PET/CT. The correlations of SUV<inf>max</inf> with pathological characteristics and tumor size were assessed. Neoplasms were divided into LGIN, HGIN, and AC according to histological grade. Receiver operating characteristic (ROC) analysis was applied to evaluate the predictive value of the SUV<inf>max</inf>-only model and comprehensive models which were established with imaging and clinical predictors identified by univariate and multivariate analysis.</p><p><strong>Results: </strong>The SUV<inf>max</inf> was positively correlated with histological grades (r=0.529, P<0.001). Univariate and multivariate analysis showed that SUV<inf>max</inf> was an independent risk factor among all groups except between HGIN and AC. The area under the curves (AUCs) of the comprehensive model for distinguishing between AC and adenoma, LGIN and HIGN, LGIN and AC, and HGIN and AC were 0.886, 0.780, 0.945, 0.733, respectively, which is statistically higher than the AUCs of the SUV<inf>max</inf>-only model with 0.812, 0.733, 0.863, and 0.688, respectively.</p><p><strong>Conclusions: </strong>As an independent risk factor, SUV<inf>max</inf> based on ¹⁸F-FDG PET/CT is highly associated with the histological grade of CRA. Thus, ¹⁸F-FDG PET/CT can serve as a noninvasive tool for precise diagnosis and assist in the preoperative formulation of treatment strategies for patients with incidental CRA.</p>","PeriodicalId":49135,"journal":{"name":"the Quarterly Journal of Nuclear Medicine and Molecular Imaging","volume":"68 2","pages":"143-151"},"PeriodicalIF":1.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301914","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":"The revolution of prostate cancer management with nuclear medicine: transforming diagnosis and treatment.","authors":"Laura Evangelista, Francesco Ceci","doi":"10.23736/S1824-4785.24.03578-7","DOIUrl":"https://doi.org/10.23736/S1824-4785.24.03578-7","url":null,"abstract":"","PeriodicalId":49135,"journal":{"name":"the Quarterly Journal of Nuclear Medicine and Molecular Imaging","volume":"68 2","pages":"93-94"},"PeriodicalIF":1.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301979","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":"Next-level precision medicine: why the theragnostic approach is the future.","authors":"Aniello Iacomino, Marco Rapa, Gianluca Gatta, Graziella DI Grezia, Vincenzo Cuccurullo","doi":"10.23736/S1824-4785.24.03519-2","DOIUrl":"10.23736/S1824-4785.24.03519-2","url":null,"abstract":"<p><p>Theragnostics represents one of the most innovative fields of precision medicine with a huge potential in the field of oncology in the next years. The use of a pair of selective radiopharmaceuticals for cellular receptors, used for diagnostic and therapeutic purposes (PRRT), finds applications in the Neuroendocrine tumors and metastatic Castration-Resistant prostate cancer (mCRPC) thanks, respectively, to somatostatin receptor agonists and PSMA-based peptides. Further evolutions of theragnostics will be possible to the radioimmunoconjugates used both in the diagnostic (Immuno-PET) and in the therapeutic fields (radioimmunotherapy). It is evident that in the \"omics-era,\" theragnostics could become a necessary method, not only in order to improve our knowledge of tumor biology, but also, to find more and more targeted therapies in a multidisciplinary context and in a tailor-based approach.</p>","PeriodicalId":49135,"journal":{"name":"the Quarterly Journal of Nuclear Medicine and Molecular Imaging","volume":"68 2","pages":"152-159"},"PeriodicalIF":1.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301913","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":"Gastrointestinal radionuclide imaging in pediatric age group.","authors":"Maria C Garganese, Milena Pizzoferro","doi":"10.23736/S1824-4785.24.03548-9","DOIUrl":"https://doi.org/10.23736/S1824-4785.24.03548-9","url":null,"abstract":"<p><p>Pediatric gastrointestinal imaging plays a crucial role in evaluating and managing digestive system disorders in children. This comprehensive review dives into the nuances of pediatric gastrointestinal imaging techniques, focusing on three specific modalities: gastric emptying scintigraphy (GES), intestinal transit scintigraphy (ITS), and gastrointestinal bleeding scintigraphy. GES involves real-time monitoring of stomach emptying using radiotracers and gamma camera technology. While challenges exist in standardizing protocols due to age-specific meal compositions, GES remains pivotal in diagnosing motility disorders, gastroesophageal reflux, and abdominal pain in children. ITS, utilizing [⁶⁷Ga], provides insights into gastrointestinal motility disorders such as Hirschsprung disease. It aids in whole-gut transit evaluation, guiding surgical interventions and improving long-term clinical outcomes. Gastrointestinal bleeding scintigraphy, employing [⁹⁹mTc], assists in diagnosing conditions like Meckel's diverticulum and occult bleeding, offering continuous monitoring to pinpoint the bleeding site along the entire gastrointestinal tract. SPECT-CT improves the accuracy and the standards of care. Each technique's protocol details, clinical indications, and diagnostic capabilities are thoroughly discussed, highlighting the importance of these non-invasive, functional imaging modalities in pediatric gastroenterology.</p>","PeriodicalId":49135,"journal":{"name":"the Quarterly Journal of Nuclear Medicine and Molecular Imaging","volume":"68 1","pages":"23-31"},"PeriodicalIF":1.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140859233","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":"Pediatric nuclear medicine: continuing the evolution.","authors":"Pinar Ozgen Kiratli, Pietro Zucchetta","doi":"10.23736/S1824-4785.24.03562-3","DOIUrl":"https://doi.org/10.23736/S1824-4785.24.03562-3","url":null,"abstract":"","PeriodicalId":49135,"journal":{"name":"the Quarterly Journal of Nuclear Medicine and Molecular Imaging","volume":"68 1","pages":"1-2"},"PeriodicalIF":1.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140872443","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}