Ophthalmologica最新文献

{"title":"Novel Variants in ABCA4-Related Retinopathies with Structural Re-Assessment of Variants of Uncertain Significance.","authors":"Kevin Gregory-Evans, Olubayo U Kolawole, Robert S Molday, Cheryl Y Gregory-Evans","doi":"10.1159/000540361","DOIUrl":"10.1159/000540361","url":null,"abstract":"<p><strong>Introduction: </strong>Conclusive molecular genetic diagnoses in inherited retinal diseases remains a major challenge due to the large number of variants of uncertain significance (VUS) identified in genetic testing. Here, we determined the genotypic and phenotypic spectrum of ABCA4 gene variants in a cohort of Canadian inherited retinal dystrophy subjects.</p><p><strong>Methods: </strong>This retrospective study evaluated 64 subjects with an inherited retinal dystrophy diagnosis with variants in the ABCA4 gene. Pathogenicity of variants was assessed by comparison to genetic databases and in silico modelling. ABCA4 variants classified as VUS were further evaluated using a cryo-electron structural model of the ABCA4 protein to predict impact on protein function and were also assessed for evolutionary conservation.</p><p><strong>Results: </strong>Conclusive disease-causing biallelic ABCA4 variants were detected in 52 subjects with either Stargardt's disease, cone-rod dystrophy, macular dystrophy, or pattern dystrophy. A further 14 variants were novel comprising 1 nonsense, 1 frameshift, 3 splicing, and 9 missense variants. Based on in silico modelling, protein modelling and evolutionary conservation from human to zebrafish, we re-classified 5 of these as pathogenic and a further 3 as likely pathogenic. We also added to the ABCA4 phenotypic spectrum seen with four known pathogenic variants (c.2161-2A&gt;G; Leu296Cysfs*4; Arg1640Gln; and Pro1380Leu).</p><p><strong>Conclusions: </strong>This study expands the genotypic and phenotypic spectrum of ABCA4 disease-associated variants. By panel-based genetic testing, we identified 14 novel ABCA4 variants of which 8 were determined to be disease-causing or likely disease-causing. These methodologies could circumvent somewhat the need for labour intensive in vitro and in vivo assessments of novel ABCA4 variants.</p>","PeriodicalId":19595,"journal":{"name":"Ophthalmologica","volume":" ","pages":"231-240"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752294","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":"Multimodal Imaging in Retinal Vasculitis.","authors":"Yanny Perez, Piergiorgio Neri, Francesco Pichi","doi":"10.1159/000540647","DOIUrl":"10.1159/000540647","url":null,"abstract":"<p><strong>Background: </strong>Retinal vasculitis is an inflammatory condition that affects the retinal blood vessels.</p><p><strong>Summary: </strong>It can manifest as an idiopathic disorder or be secondary to various infectious or non-infectious diseases, mimicking syndromes, isolated ocular disorders, or drug-induced reactions. Recognizing its distinctive features is crucial for early diagnosis and accurate treatment. This review aimed to demonstrate the variety of tools available to detect disease activity, assess complications, measure the extent of retinal damage, and guide therapy effectively.</p><p><strong>Key message: </strong>This review article highlights the use of multimodal imaging in the comprehensive evaluation of retinal vasculitis.</p>","PeriodicalId":19595,"journal":{"name":"Ophthalmologica","volume":" ","pages":"203-213"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889825","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":"Reconstructing Small-Medium Sized Oral Cavity Defects- Our Experience with the Versatile Famm Flap.","authors":"Kamal Kishor Lakhera, Pranav Mohan Singhal, Pinakin Patel, Agil Babu, Mahesh Daima, Aishwarya Chatterjee, Suresh Singh, Bhoopendra Singh Gora, Naina Kumar Agarwal","doi":"10.1007/s12070-023-03946-4","DOIUrl":"10.1007/s12070-023-03946-4","url":null,"abstract":"<p><strong>Background: </strong>Restoration of form and function of the oral cavity post resection for oral cavity malignancies is an enormous challenge in head and neck reconstructive surgery. The facial artery musculo-mucosal (FAMM) flap is an unexplored, underutilized yet an extremely versatile option for such defects. In this analysis we review the performance of the FAMM flap used to reconstruct tongue/floor of mouth (FOM) defects following tumor resection.</p><p><strong>Materials and methods: </strong>In this retrospective analysis, demographic and disease profiles of 15 patients with Tongue and Floor of Mouth carcinomas reconstructed with a FAMM flap between January 2019 to January 2021 were studied. Complications and functional outcomes were analyzed.</p><p><strong>Results: </strong>Fifteen patients (10 men, 5 women) were reconstructed using a FAMM flap. Mean age of the study sample was 46.46 years (28-60 years). One flap was lost due to complete flap necrosis following venous congestion, two other flaps suffered distal tip necrosis. Three patients developed an Oro-cutaneous fistula, with one going on to develop a surgical site infection of the neck wound. Patients reconstructed for FOM defects had an excellent functional outcome. For patients reconstructed for a tongue defect, 33.33% of patients complained of restricted tongue mobility and 44.44% were dissatisfied with the quality of speech post operatively.</p><p><strong>Conclusion: </strong>The versatile FAMM flap is a reliable, easy to harvest and scarless flap. It provides excellent cosmetic and functional results FAMM flap allowing early resumption of normal daily activities making it an ideal option to reconstruct small to medium sized oral cavity defects.</p>","PeriodicalId":19595,"journal":{"name":"Ophthalmologica","volume":"114 1","pages":"3432-3438"},"PeriodicalIF":2.1,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10645677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87506376","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":"Contents Vol. 246, 2023","authors":"Martin Zinkernagel, Steffen Schmitz-Valckenberg, John A. Moran, Alessandro Arrigo, Francesco Bandello – Ospedale, San Raffaele, Italy Milan, H. O. Orlans, S. Yazdouni, T. H. Williamson, R. S. Wong, D.A.H Laidlaw, K. L. Aw, W. McLoughlin, P. Cackett, García-Zamora, M. Flores-Moreno, I. Ruiz-Medrano, J. Puertas, M. Almazán-Alonso, E. Vega-González, R. González-Buendía, L. Madrid, J. Ruiz-Moreno, Madrid, Albacete","doi":"10.1159/000535354","DOIUrl":"https://doi.org/10.1159/000535354","url":null,"abstract":"","PeriodicalId":19595,"journal":{"name":"Ophthalmologica","volume":"165 1","pages":"I - IV"},"PeriodicalIF":2.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139025173","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":"Historical reconstruction of inaccessibility status in Local Government Areas (LGAs) of Borno and Yobe States, Nigeria, 2010-2020.","authors":"Joseph Che Forbi, Melton Sundu Musa, Musa Salawu, Jibrin Manu Idris, Ahmed Ibrahim Ba'aba, Jeff Higgins, Audu Idowu Musa, Bamusa Bashir, Aliyu Shettima, Nnamdi Njeakor, Iheanyichukwu Uzoma, Hyeni Mshelia, Gatei Wa Nganda, Kabiru Ibrahim Mohammed, Idriss Mohammed Bomoi, Umar Chiroma, Stephanie Diane Kovacs, Oladayo Biya, Ndadilnasiya Endie Waziri, Muyi Aina, Usman Saidu Adamu, Faisal Shuaib, Omotayo Bolu, Richard Franka, Eric Wiesen","doi":"10.11604/pamj.supp.2023.45.2.39332","DOIUrl":"10.11604/pamj.supp.2023.45.2.39332","url":null,"abstract":"<p><strong>Introduction: </strong>ultimately detected in 2016, wild poliovirus (WPV) transmission continued undetected after 2011 in Northeast Nigeria Borno and Yobe States in security-compromised areas, inaccessible due to armed insurgency. Varying inaccessibility prevented children aged <5 years in these areas from polio vaccination interventions and surveillance, while massive population displacements occurred. We examined progress in access over time to provide data supporting a very low probability of undetected WPV circulation within remaining trapped populations after 2016.</p><p><strong>Methods: </strong>to assess the extent of inaccessibility in security-compromised areas, we obtained empirical historical data in 2020 on a quarterly and annual basis from relevant polio eradication staff for the period 2010-2020. The extent of access to areas for immunization by recall was compared to geospatial data from vaccinator tracking. Population estimates over time in security-compromised areas were extracted from satellite imagery. We compared the historical access data from staff with tracking and population esimates.</p><p><strong>Results: </strong>access varied during 2010-2020, with inaccessibility peaking during 2014-2016. We observed concurrent patterns between historical recalled data on inaccessibility and contemporaneous satellite imagery on population displacements, which increased confidence in the quality of recalled data.</p><p><strong>Conclusion: </strong>staff-recalled access was consistent with vaccinator tracking and satellite imagery of population displacments. Despite variability in inaccessibility over time, innovative immunization initiatives were implemented as access allowed and surveillance initiatives were initiated to search for poliovirus transmission. Along with escape and liberation of residents by the military in some geographic areas, these initiatives resulted in a massive reduction in the size of the unvaccinated population remaining resident.</p>","PeriodicalId":19595,"journal":{"name":"Ophthalmologica","volume":"109 1","pages":"7"},"PeriodicalIF":1.2,"publicationDate":"2023-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10874094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87505332","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":"Circulating MicroRNAs as Biomarker for Vessel-Associated Retinal Diseases.","authors":"Merlin Dähmcke, Martin Busch, Johanna M Pfeil, Tara Brauckmann, Daniel Schulz, Wael Omran, Ewa Morawiec-Kisiel, Fabienne Wähler, Sebastian Paul, Allam Tayar, Marie-Christine Bründer, Bastian Grundel, Andreas Stahl","doi":"10.1159/000533481","DOIUrl":"10.1159/000533481","url":null,"abstract":"<p><strong>Introduction: </strong>Vessel-associated retinal diseases are a major cause of blindness and severe visual impairment. The identification of appropriate biomarkers is of great importance to better anticipate disease progression and establish more targeted treatment options. MicroRNAs (miRNAs) are short, single-stranded, noncoding ribonucleic acids that are involved in the posttranscriptional regulation of gene expression through hybridization with messenger RNA. The expression of certain miRNAs can be different in patients with pathological processes and can be used for the detection and differentiation of various diseases. In this study, we investigate to what extent previously in vitro identified miRNAs are present as cell-free circulating miRNAs in the serum and vitreous of human patients with and without vessel-associated retinal diseases.</p><p><strong>Methods: </strong>Relative quantification by quantitative real-time polymerase chain reaction was used to analyze miRNA expression in patients with vessel-associated retinal diseases such as age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinal vein occlusion compared with control patients.</p><p><strong>Results: </strong>In serum samples, miR-29a-3p and miR-192-5p showed increased expression in patients with neovascular AMD relative to control patients. Similarly, miR-335-5p, miR-192-5p, and miR-194-5p showed increased expression in serum from patients with proliferative DR. In vitreous samples, miR-100-5p was decreased in patients with proliferative DR. Differentially expressed miRNAs showed good diagnostic accuracy in receiver operating characteristic (ROC) and area under the ROC curve analysis.</p><p><strong>Conclusion: </strong>The miRNAs investigated in this study may have the potential to serve as biomarkers for vessel-associated retinal diseases. Combining multiple miRNAs may enhance the predictive power of the analysis.</p>","PeriodicalId":19595,"journal":{"name":"Ophthalmologica","volume":" ","pages":"227-237"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10291851","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":"Influence of Surgical Experience and Risk Factors for Surgical Failure in Primary Retinal Detachment Surgery.","authors":"Min Seok Kim,&nbsp;Jun Young Park,&nbsp;Ki Won Jin,&nbsp;Kyu Hyung Park,&nbsp;Sang Jun Park,&nbsp;Kwangsic Joo,&nbsp;Se Joon Woo","doi":"10.1159/000530526","DOIUrl":"https://doi.org/10.1159/000530526","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of this study was to report surgical outcomes and risk factors for primary surgical failure following rhegmatogenous retinal detachment (RRD) repair.</p><p><strong>Methods: </strong>In this retrospective cohort study, RRD patients who underwent primary surgery at a tertiary center between January 1, 2006, and December 31, 2020, were enrolled. Surgical failure was defined as reoperation within 60 days postoperatively due to retinal re-detachment and putative risk factors for surgical failure were analyzed.</p><p><strong>Results: </strong>Of 2,383 eyes (2,335 patients), 1,342 (56.3%) underwent vitrectomy and 1,041 (43.7%) underwent scleral buckling. The surgical failure rate was 9.1% overall, and 6.0% and 13.1% for the vitrectomy and scleral buckling groups, respectively. In the multivariate logistic regression analysis, surgical failure was associated with surgical experience (first-year fellow vs. senior professor) (odds ratio [OR]: 1.66; p = 0.018), scleral buckling (OR: 2.33; p &lt; 0.001), and longer axial length (AL; ≥26.5 mm) (OR: 1.49; p = 0.017). In each surgical approach, age &lt;40 years (OR: 2.11; p = 0.029) in the vitrectomy group and age &gt;40 years (OR, 1.84; p = 0.004), male sex (OR: 1.65; p = 0.015), and first-year fellows compared to senior professors (OR: 1.95; p = 0.013) in the scleral buckling group were associated with surgical failure. Lens status were not associated with the surgical failure rate.</p><p><strong>Conclusion: </strong>In this large retrospective study using data from Korea, vitrectomy was superior to scleral buckling in terms of primary anatomical outcomes in the management of RRD. First-year fellows were a risk factor for surgical failure, especially for scleral buckling. Longer AL was a significant parameter for predicting the success rates.</p>","PeriodicalId":19595,"journal":{"name":"Ophthalmologica","volume":"246 2","pages":"141-149"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9872893","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":"Erratum.","authors":"","doi":"10.1159/000529597","DOIUrl":"https://doi.org/10.1159/000529597","url":null,"abstract":"","PeriodicalId":19595,"journal":{"name":"Ophthalmologica","volume":"246 1","pages":"70"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9663781","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":"Atrophic, Tractional, and Neovascular Grading System in a Dome-Shaped Macula and Ridge-Shaped Macula Highly Myopic Cohort.","authors":"María García-Zamora,&nbsp;Ignacio Flores-Moreno,&nbsp;Jorge Ruiz-Medrano,&nbsp;Mariluz Puertas,&nbsp;Elena Almazán-Alonso,&nbsp;Rocío Vega-González,&nbsp;Lucía González-Buendía,&nbsp;José M Ruiz-Moreno","doi":"10.1159/000528993","DOIUrl":"https://doi.org/10.1159/000528993","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of this study was to analyze the atrophic, tractional, and neovascular (ATN) components grading in highly myopic patients with dome-shaped macula (DSM) and ridge-shaped macula (RSM).</p><p><strong>Methods: </strong>This was a cross-sectional, noninterventional study. 57 eyes of 38 different patients were included. They were classified as DSM or RSM based on the number of radial scans that showed an inward protrusion ≥50 µm in the swept-source optical coherence tomography (SS-OCT) (12 = DSM; &lt;12 = RSM). All patients underwent a complete ophthalmological examination in addition to SS-OCT. They were graded using the ATN system for myopic maculopathy by 2 masked retina specialists that assessed the atrophic (A), tractional (T), and neovascular (N) components in order to analyze the differences between the groups. As complementary measurements, age, axial length, and best-corrected visual acuity were collected. Height and orientation of the macular bulge and the presence of Bruch's membrane defects, scleral perforating vessels, and staphyloma were recorded.</p><p><strong>Results: </strong>Out of total 57 eyes, 13 eyes (22.8%) were classified as DSM. Regarding the atrophic component (A), there were statistically significant differences between groups, with DSM group showing a greater stage of atrophy (predominantly stage A3 in 69.2% of the sample) compared to the RSM group (predominantly stage A2 in 61.3% of the sample) (p &lt; 0.05). For the T and N components, there were no significant differences between groups. The presence of Bruch's membrane defects was more frequently seen in DSM (p &lt; 0.05).</p><p><strong>Conclusions: </strong>DSM group showed more Bruch's membrane defects and a greater stage of the atrophy component, based on the ATN grading system, compared with RSM group. As Bruch's membrane may have biomechanical properties in terms of strength, the defects found around the macula, added to the major atrophic component, may be a cause of a local relaxation that induce a central bulge forming the dome.</p>","PeriodicalId":19595,"journal":{"name":"Ophthalmologica","volume":"246 2","pages":"107-112"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9787722","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":"Real-Life Experience and Predictors of Visual Outcomes with Intravitreal Brolucizumab Switch for Treatment of Neovascular Age-Related Macular Degeneration.","authors":"Michele Cavalleri,&nbsp;Beatrice Tombolini,&nbsp;Riccardo Sacconi,&nbsp;Gianpaolo Gatta,&nbsp;Renato Valeri,&nbsp;Francesco Bandello,&nbsp;Giuseppe Querques","doi":"10.1159/000530544","DOIUrl":"https://doi.org/10.1159/000530544","url":null,"abstract":"<p><strong>Introduction: </strong>To analyze visual and anatomical outcomes after switch to intravitreal brolucizumab therapy in eyes affected by neovascular age-related macular degeneration (nAMD) previously treated with other intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents.</p><p><strong>Methods: </strong>Retrospective study of eyes with nAMD that underwent intravitreal brolucizumab at San Raffaele Hospital (Milan, Italy) or San Rocco Clinical Institute (Ome, Italy) between January 2021 and July 2022. All study eyes had persistent residual retinal fluid after receiving at least 3 intravitreal injections of other anti-VEGF agents prior to switch to brolucizumab.</p><p><strong>Results: </strong>Among 66 eyes from 60 patients (35 males; mean age 76.5 ± 7.4 years) with nAMD, 43 (65.2%) eyes received a complete loading dose of 3 brolucizumab injections, while 15 (22.7%) and 8 (12.1%) eyes were treated with 2 or 1 brolucizumab injections, respectively. The average number of brolucizumab injections was 2.5 during 4.0 ± 2.0 months (mean interval between two injections of 51.2 days). Lower letter gains (&lt;5 letter improvement from baseline) were found in eyes that did not complete a loading dose, after a greater number of previous anti-VEGF injections, after a longer duration of disease, and in eyes with a greater rate of macular atrophy at baseline. No serious ocular or systemic adverse events were found after switch to brolucizumab.</p><p><strong>Conclusion: </strong>nAMD eyes with persistent residual retinal fluid despite frequent anti-VEGF treatment can still gain functional and anatomical improvements after switch to brolucizumab therapy. Despite a relevant heterogeneity in patients' response to brolucizumab, we identified potential biomarkers for functional and anatomical improvement.</p>","PeriodicalId":19595,"journal":{"name":"Ophthalmologica","volume":"246 2","pages":"158-168"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9863559","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}