Pancreatology最新文献

{"title":"Effect of selective COX-2 inhibitors and non-selective non-steroidal anti-inflammatory drugs on severity of acute pancreatitis: A systematic review and meta-analysis.","authors":"Alejandra Vargas, Priyata Dutta, Fadi Hawa, Elit Quingalahua, Ricardo Marin, Ana Vilela, Tyler Nix, Antonio Mendoza-Ladd, C Mel Wilcox, Jean M Chalhoub, Jorge D Machicado","doi":"10.1016/j.pan.2025.03.008","DOIUrl":"https://doi.org/10.1016/j.pan.2025.03.008","url":null,"abstract":"<p><strong>Background: </strong>It's been suggested that non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the inflammatory response and severity of acute pancreatitis (AP). In this systematic review and meta-analysis, we aimed to explore the impact of selective COX-2 and non-selective NSAIDs compared to non-NSAID options on the severity of AP.</p><p><strong>Methods: </strong>We searched MEDLINE, EMBASE, and Cochrane Central, from database inception through September 2023. We included RCTs and observational studies comparing NSAIDs with non-NSAID controls. The primary outcome was the development of severe acute pancreatitis (SAP) characterized by persistent organ failure lasting >48 h. Secondary outcomes included mortality, pancreatic necrosis, length of stay (LOS), pain relief, and requirement for rescue analgesia. Meta-analysis was conducted separately for selective COX-2 inhibitors and non-selective NSAIDs.</p><p><strong>Results: </strong>Eleven studies met eligibility criteria including 1830 patients with AP. Of 3 studies that used selective NSAIDs (1 RCT and 2 observational), COX-2 inhibitors significantly reduced SAP (OR = 0.38; 95 %CI 0.27-0.52; p < 0.001; I² = 0 %), pancreatic necrosis (OR = 0.48; 95 %CI 0.29-0.78; p = 0.003; I² = 0 %), LOS by 5.51 days (95 %CI -10.80 to -0.22; p = 0.04; I² = 97 %), and rescue opioids (OR = 0.32; 95 %CI 0.24-0.45; p < 0.001; I² = 0 %). However, the certainty of the evidence was graded as low to very low using GRADE methodology. There was no significant effect of COX-2 inhibitors on mortality. Of 8 studies (all RCTs) that compared non-selective NSAIDs and non-NSAIDs, there was no difference in clinical outcomes, pain relief, and need for rescue analgesia.</p><p><strong>Conclusions: </strong>Selective COX-2 inhibitors potentially mitigate disease severity and shorten hospitalization in patients with AP, while non-selective NSAIDs lack this benefit. Confirmatory large-scale RCTs are warranted to validate these findings.</p>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metallic trace elements in pancreatic tissue are associated with higher risk of pancreatic adenocarcinoma - METAPANDA study.","authors":"Mireille Simon, Aurore Meurat, Sophie Stanislas, Hervé Dréau, Geneviève Belleannée, Christophe Laurent, Jean-Frédéric Blanc, Sandra Mounicou","doi":"10.1016/j.pan.2025.03.006","DOIUrl":"https://doi.org/10.1016/j.pan.2025.03.006","url":null,"abstract":"<p><strong>Objectives: </strong>Few recent studies have indicated the possible involvement of some metallic trace element (MTE), commonly known as heavy metals, in pancreatic ductal adenocarcinoma (PDAC). To evaluate the potential role of MTE in PDAC onset, we compared concentrations of 23 MTE in healthy pancreas tissue close to the tumor, from patients who underwent pancreatic surgery for PDAC in cases group and for neuroendocrine or other lesion for controls.</p><p><strong>Methods: </strong>Samples were taken from paraffin-embedded pancreatectomy blocks of 33 PDAC cases and 29 controls. Concentrations of 23 MTE were determined by inductively coupled plasma mass spectrometry (ICP-MS).</p><p><strong>Results: </strong>In multivariate analysis, associations were found between risk of PDAC and higher tissue concentration of antimony (OR 6.31, 95 % CI 2.06-29.03; p = 0.006), thallium (OR 3.23, 95 % CI 1.35-12.07; p = 0.033) arsenic (OR 2.96, 95 % CI 1.22-10.10; p = 0.04) and lead (OR 2.27, 95 % CI 1.13-5.77; p = 0.044).</p><p><strong>Conclusions: </strong>This pilot study presents unpublished information about a large set of MTE in pancreatic tissues, confirming the possible involvement of arsenic and lead in PDAC onset and highlighting the potential role of antimony and thallium which have never been implicated before.</p>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil-to-apolipoprotein A1 ratio predicted the efficiency of chemotherapy in advanced pancreatic cancer.","authors":"Sen Lei, Yize Mao, Tao Qin, Jianyao Zhou, Zhijun Mai, Jiahui Xu, Rong Zhang, Qiuxia Yang","doi":"10.1016/j.pan.2025.03.004","DOIUrl":"https://doi.org/10.1016/j.pan.2025.03.004","url":null,"abstract":"<p><strong>Background: </strong>Identification of a biomarker predicting chemotherapy efficacy in patients with advanced pancreatic cancer (APC) is urgently needed. This study aimed to determine the association between the neutrophil-to-apolipoprotein A1 ratio (NEAPO) and chemotherapy efficacy in APC patients.</p><p><strong>Methods: </strong>This retrospective study involved 236 APC patients who underwent first-line chemotherapy, including FOLFIRINOX (FFX), nab-paclitaxel plus gemcitabine (AG), or SOXIRI. Receiver operating characteristic curve analysis was performed to determine the optimal cutoff value of NEAPO, and patients were divided into low and high NEAPO groups. Kaplan-Meier curves and Cox regression analyses were used to evaluate the effect of NEAPO on overall survival (OS) and progression-free survival (PFS).</p><p><strong>Results: </strong>The optimal cutoff of NEAPO was 4.69. High NEAPO levels were associated with shorter OS (p = 0.046) and PFS (p = 0.001). In the NEAPO low subgroup, the median PFS of SOXIRI was longer than that in AG group (7.2 months vs. 5.5 months, p = 0.029), with no significant difference of PFS between SOXIRI and FFX (p = 0.691). There is a trend but not significant difference in PFS between AG and FFX (p = 0.096). The proportion of disease control rate (DCR) was higher in SOXIRI group. In the NEAPO high subgroup, there was no significant difference in PFS among the three regimens, while the DCR was higher in AG group.</p><p><strong>Conclusions: </strong>NEAPO levels were significantly associated with OS, PFS and treatment response in APC patients who underwent chemotherapy and might be a useful biomarker for predicting chemotherapy efficacy.</p>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to the Letter to Editor regarding the role of percutaneous endoscopic necrosectomy in acute necrotizing pancreatitis.","authors":"WenHua He, Ling Ding, Yin Zhu, Nonghua Lu","doi":"10.1016/j.pan.2025.03.005","DOIUrl":"https://doi.org/10.1016/j.pan.2025.03.005","url":null,"abstract":"","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author's reply to the letter to editor regarding \"A causal relationship between distinct immune features and acute or chronic pancreatitis: Results from a Mendelian Randomization analysis\".","authors":"Rujuan Liu, Kui Wang, Li Wen","doi":"10.1016/j.pan.2025.03.003","DOIUrl":"https://doi.org/10.1016/j.pan.2025.03.003","url":null,"abstract":"","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tocilizumab for Painful Chronic Pancreatitis (TOPAC trial): Protocol for a phase 2 randomized, placebo-controlled, double-blind, investigator-initiated trial.","authors":"Rasmus Hagn-Meincke, Jens Brøndum Frøkjær, Asbjørn Mohr Drewes, Charlotte Henneberg Holmboe, Klaus Krogh, Rasmus Bach Nedergaard, Line Davidsen, Tina Okdahl, Ingfrid Salvesen Haldorsen, Walter Park, Bent Winding Deleuran, Søren Schou Olesen","doi":"10.1016/j.pan.2025.03.001","DOIUrl":"https://doi.org/10.1016/j.pan.2025.03.001","url":null,"abstract":"<p><strong>Background: </strong>Chronic pancreatitis (CP) is a fibro-inflammatory disease that damages the pancreas, leading to severe abdominal pain and metabolic complications. Activated macrophages and pancreatic stellate cells drive CP progression, and their activity is regulated by complex immune signals, including interleukin-6 (IL-6). Preclinical studies suggest that blocking IL-6 signalling may have pain-relieving effects in CP. Based on these findings, we hypothesise that tocilizumab, an anti-IL-6 receptor antibody, will reduce abdominal pain and improve physical functioning and quality of life in patients with CP. Additionally, we expect tocilizumab to decrease pancreatic inflammation, fibrosis, and systemic inflammation, as well as normalise pain processing.</p><p><strong>Methods: </strong>The TOPAC trial is a phase 2, randomised, placebo-controlled, double-blinded, investigator-initiated trial conducted at Aalborg University Hospital, Denmark. Patients with painful CP and suspicion of sustained pancreatic inflammation (n = 36) will be randomised (1:1) to receive intravenous tocilizumab (8 mg/kg) or a corresponding placebo every 4 weeks for 24 weeks. The primary endpoint is the difference between the two groups in the change of the Comprehensive Pain Assessment Tool Short Form (COMPAT-SF) score from baseline to 24 weeks. Secondary outcomes include questionnaires focused on quality of life, physical/daily functioning, and the severity of pain and its impact on functioning. Additionally, safety is a key secondary endpoint. Exploratory outcomes include soluble biomarkers of inflammation and fibrosis, multiparametric pancreatic magnetic resonance imaging, quantitative sensory testing and neurophysiological measurements of the pain processing.</p><p><strong>Conclusions: </strong>This placebo-controlled clinical trial aims to study the potential clinical benefits of blocking IL-6 signalling in painful CP.</p>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Class V pancreatic fluid cytology is associated with intrapancreatic recurrence of intraductal papillary mucinous neoplasms.","authors":"Takumi Saito, Atsushi Miki, Yasunaru Sakuma, Jun Watanabe, Hideki Sasanuma, Takumi Teratani, Wataru Nishimura, Noriyoshi Fukushima, Joji Kitayama, Naohiro Sata, Hironori Yamaguchi","doi":"10.1016/j.pan.2025.03.002","DOIUrl":"https://doi.org/10.1016/j.pan.2025.03.002","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study was to elucidate the association of pancreatic fluid cytology with intrapancreatic recurrence of intraductal papillary mucinous neoplasms (IPMNs).</p><p><strong>Materials and methods: </strong>A total of 68 patients with IPMN who underwent pancreatectomy and obtained cytologic analysis of pancreatic fluid at Jichi Medical University Hospital were included in this study. Computed tomography scan and magnetic resonance cholangiopancreatography were performed preoperatively. Endoscopic retrograde cholangiopancreatography was used to obtain pancreatic fluid. The association of recurrence with variables was determined by logistic regression multivariate analysis.</p><p><strong>Results: </strong>Class V cytology was found in 7/68 patients preoperatively. Metachronous intrapancreatic recurrences occurred in 6/68 patients, including one branched type, main pancreatic duct type in two and mixed pancreatic duct type in three. Four of seven patients with class V cytology developed intra-pancreatic recurrences as a new lesion. Class V cytology was significantly associated with intrapancreatic recurrence, compared to those with class IV or lower cytology. In univariate analysis, patients with pathological findings with high-grade dysplasia or adenocarcinoma (P = 0.0392, odds ratio (OR) 10.2, 95 % confidence interval (CI) 1.12-93.6) and class V pancreatic fluid cytology (P = 0.0005, OR 38.7, 95 % CI 4.94-302) were significant risk factors. In multivariate analysis, class V pancreatic fluid cytology was significantly associated with developing intrapancreatic recurrence (P = 0.0149, OR 22.7, 95 % CI 1.83-279).</p><p><strong>Conclusion: </strong>Preoperative class V pancreatic fluid cytology is associated with intra-pancreatic recurrence after resection of IPMN.</p>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progression of resectable pancreatic ductal adenocarcinoma during surgical delay and effects on survival – A propensity score matched study","authors":"Bojan Kovacevic ,&nbsp;Caroline Ewertsen ,&nbsp;Thomas Skårup Kristensen ,&nbsp;Luit Penninga ,&nbsp;Carsten Palnæs Hansen","doi":"10.1016/j.pan.2024.11.015","DOIUrl":"10.1016/j.pan.2024.11.015","url":null,"abstract":"<div><h3>Background</h3><div>Surgery is the only curative treatment for pancreatic cancer, but less than 25 % of the patients present with a resectable tumor at the time of diagnosis. The aim of this study is to evaluate progression during surgical treatment delay and examine any associations between surgical treatment delay and survival.</div></div><div><h3>Methods</h3><div>This is a retrospective, single center propensity score matched study including treatment naïve patients with pancreatic adenocarcinoma between 2018 and 2022. Outcomes included disease progression during surgical treatment delay in patients where follow-up imaging was performed as well as overall and recurrence-free survival for the entire cohort.</div></div><div><h3>Results</h3><div>The study cohort consisted of 290 patients of whom 129 (44.5 %) underwent follow-up imaging. Radiological progression to unresectable disease during surgical delay was seen in 14 cases (10.9 %), with another 17 cases (13.2 %) deemed unresectable during intended resection. Tumor size progression was observed in 29 patients (22.5 %) with an average tumor growth rate of 7.4 mm (95%CI 5.8–8.9, p &lt; 0.001). Median time to surgery was 37 days with no observed associations between treatment delay and overall survival (HR = 1.02, 95%CI 0.76–1.38, p = 0.996), or the risk of recurrence (HR = 1.06, 95%CI 0.77–1.48, p = 0.709).</div></div><div><h3>Conclusion</h3><div>Progression in tumor size does not seem to affect survival in our study population. In general, surgical treatment delay in up-front resectable patients does not seem to be associated with survival or the risk of recurrence, but the optimal and maximal time to surgery as well as the optimal timing of the follow-up scanning remain unclear.</div></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":"25 2","pages":"Pages 228-233"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety, tolerability and therapeutic efficacy of anti-inflammatory drug pirfenidone in acute pancreatitis patients: Protocol for a randomized pilot clinical trial","authors":"Ejas P. Bava ,&nbsp;Tejeshwar Jain ,&nbsp;Mustafa Al-Obaidi ,&nbsp;Zoe Evans ,&nbsp;Dureti Doto ,&nbsp;Santhi Swaroop Vege ,&nbsp;Vikas Dudeja","doi":"10.1016/j.pan.2025.01.004","DOIUrl":"10.1016/j.pan.2025.01.004","url":null,"abstract":"<div><h3>Background</h3><div>Acute Pancreatitis (AP) is a formidable disease with significant morbidity, mortality and healthcare expenditure. There is an emergent need to develop therapeutic agents for this disease as there are no targeted therapies available. We have recently demonstrated that pirfenidone can significantly decrease the severity of AP in animal models. Based on our preclinical findings, we decided to conduct a pilot trial to evaluate the safety, tolerability and efficacy of pirfenidone in patients with AP.</div></div><div><h3>Methods</h3><div>We have designed a multicenter, randomized, pilot clinical trial of 60 patients with blinded outcome assessment. All patients with AP<strong>,</strong> who present within 48 h of establishment of the diagnosis, will be screened for exclusion and inclusion criteria. Consenting patients will be randomized into pirfenidone or placebo within 48 h of the diagnosis of AP. The primary end points include decrease in PAN-PROMISE score after 72 h of initiation of drug, reduction in inflammatory markers, and development of serious adverse events. The secondary end points include changes in PAN-PROMISE score, discharge PASS score &lt;60, development of composite outcome of new or worsening necrotizing pancreatitis on CT scan performed 5–7 days after admission, major infection or death, and readmissions and/or ER visits within 30 days and within 6 months after discharge.</div></div><div><h3>Status</h3><div>Currently enrolling (NCT05350371).</div></div><div><h3>Conclusion</h3><div>There is an urgent need to identify novel therapies for AP. This pilot clinical trial may become the basis of a larger study to analyze the efficacy of pirfenidone in patients with AP.</div></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":"25 2","pages":"Pages 214-220"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Focal pancreatic parenchymal atrophy could be a precursor of pancreatic cancer","authors":"Masataka Kikuyama ,&nbsp;Jun Nakahodo ,&nbsp;Kazuro Chiba ,&nbsp;Goro Honda","doi":"10.1016/j.pan.2025.01.003","DOIUrl":"10.1016/j.pan.2025.01.003","url":null,"abstract":"<div><h3>Background/objectives</h3><div>We previously reported that focal pancreatic parenchymal atrophy (FPPA) indicates high-grade pancreatic intraepithelial neoplasia (HG-PanIN) or carcinoma in situ (CIS). Because HG-PanIN progresses into pancreatic ductal adenocarcinoma (PDAC), the relationship between FPPA and PDAC should be investigated.</div></div><div><h3>Methods</h3><div>We included 54 patients with PDAC, whose previous computed tomography or magnetic resonance imaging were reviewed. The existence, positional relationship between FPPA and PDAC, and time between FPPA recognition and PDAC diagnosis were all examined. Of the 54 patients, 28 underwent surgery. The remaining 26 patients were histopathologically diagnosed with PDAC using endoscopic ultrasonography-guided fine needle aspiration.</div></div><div><h3>Results</h3><div>Among the 54 patients included, 49 (83.3 %) had FPPA. The pancreatic head and body were the common sites of FPPA. In all patients with FPPA, PDAC developed near the FPPA, with an average distance of 7.93 mm between the edge of the FPPA and the center of the PDAC. The interval between FPPA recognition and PDAC diagnosis was 35.33 months, which was significantly shorter in the surgical group.</div></div><div><h3>Conclusions</h3><div>FPPA could be a precursor of PDAC and suggest the area at risk of PDAC.</div></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":"25 2","pages":"Pages 241-249"},"PeriodicalIF":2.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}