Transplant Infectious Disease最新文献

{"title":"Barriers and facilitators to routine revaccination among adult Hematopoietic Cell Transplant survivors in the United States: A convergent mixed methods analysis.","authors":"Mihkai Wickline, Paul A Carpenter, Jeffrey R Harris, Sarah J Iribarren, Kerryn W Reding, Kenneth C Pike, Stephanie J Lee, Rachel B Salit, Masumi Ueda Oshima, Phuong T Vo, Donna L Berry","doi":"10.1111/tid.14388","DOIUrl":"10.1111/tid.14388","url":null,"abstract":"<p><strong>Background: </strong>Hematopoietic cell transplant (HCT) survivorship care includes recommendations for post-HCT revaccination to restore immunity to vaccine-preventable diseases (VPDs). However, not all survivors agree to be vaccinated. No existing studies have comprehensively reported barriers and facilitators to adult HCT survivors completing revaccination.</p><p><strong>Methods: </strong>A cross-sectional survey of 194 adult HCT survivors was analyzed using convergent mixed methods. The analysis used various statistical methods to determine the prevalence of barriers and facilitators and the association between revaccination and the number and specific type of barriers and facilitators. Content analysis was applied to open-ended item responses. Integrated analysis merged quantitative and qualitative findings.</p><p><strong>Results: </strong>The most frequent barriers included the inability to receive live vaccines because of immunosuppression, identifying a suitable community location for administering childhood vaccines to adults, and delayed immune recovery. The most frequent facilitators were having healthcare insurance and a clear calendar of the revaccination schedule. Complete revaccination rates were lower with each additional reported barrier (OR = 0.58; 95% CI 0.459-0.722) and higher with each additional reported facilitator (OR = 1.31; 95% CI 1.05-1.63). Content analysis suggested that most barriers were practical issues. One significant facilitator highlighted by respondents was for the transplant center to coordinate and serve as the vaccination location for revaccination services. Merged analysis indicated convergence between quantitative and qualitative data.</p><p><strong>Conclusion: </strong>Practical barriers and facilitators played a consequential role in revaccination uptake, and survivors would like to be revaccinated at the transplant center.</p>","PeriodicalId":23318,"journal":{"name":"Transplant Infectious Disease","volume":" ","pages":"e14388"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381729","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":"Cytomegalovirus viral load at initiation of pre-emptive antiviral therapy impacts cytomegalovirus dynamics in pediatric allogeneic hematopoietic cell transplantation recipients.","authors":"Valentina Gutierrez, Joseph Stanek, Monica I Ardura, Eunkyung Song","doi":"10.1111/tid.14358","DOIUrl":"10.1111/tid.14358","url":null,"abstract":"<p><strong>Background: </strong>Cytomegalovirus (CMV) contributes to morbidity and mortality in allogeneic hematopoietic cell transplantation (allo-HCT) recipients. Pre-emptive antiviral therapy (PET) reduces the incidence of CMV end-organ disease (EOD), though relevant viral thresholds to initiate PET remain undefined. We evaluated the impact of viral loads (VLs) at PET initiation on virologic and clinical outcomes following pediatric allo-HCT.</p><p><strong>Methods: </strong>Single-center retrospective cohort analysis of children who underwent their first allo-HCT from January 2014 to December 2020. Weekly quantitative plasma CMV polymerase chain reaction was performed until Day +100 and PET was initiated once VL exceeded a pre-defined threshold per institutional guidelines. Patients were followed for 1-year post-HCT to evaluate virologic and clinical outcomes including end-organ disease (EOD), overall survival (OS), and non-relapse mortality (NRM).</p><p><strong>Results: </strong>Among 146 allo-HCT recipients, CMV DNAemia occurred in 40 patients (27%) at a median of 15 days post-HCT (interquartile range 6-28.5). Ten percent (n = 4) had spontaneous resolution of DNAemia, while 90% (n = 36) required PET. PET initiated when CMV VL was ≥ 1000 IU/mL (n = 21) vs when VL < 1000 IU/mL (n = 15) resulted in higher peak CMV VL (12,670 vs. 1284 IU/mL, p = 0.0001) and longer time to CMV DNAemia resolution (36 vs. 24 days, p = 0.035). There were no differences in EOD, OS, or NRM at 12 months post-HCT based on VL at PET initiation.</p><p><strong>Conclusions: </strong>Initiating PET when CMV VL was ≥1000 IU/mL resulted in significantly higher peak VL and prolonged DNAemia, with no differences in EOD, OS, or NRM at 12 months post pediatric HCT.</p>","PeriodicalId":23318,"journal":{"name":"Transplant Infectious Disease","volume":" ","pages":"e14358"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056533","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":"Real-world experience in treatment of donor-derived Hepatitis C virus in kidney transplant recipients with delayed initiation, shortened course glecaprevir/pibrentasvir versus standard of care.","authors":"Johanna Papanikolla, Melissa McGowan, Mythili Chunduru, Holli Winters, Todd Pesavento, Rachel Smith, Navdeep Singh, Michael Wellner, Lindsay Sobotka, Annelise Nolan","doi":"10.1111/tid.14366","DOIUrl":"10.1111/tid.14366","url":null,"abstract":"<p><strong>Background: </strong>There is limited literature describing the real-world practice of delayed initiation and shortened duration direct-acting antiviral (DAA) in kidney transplant recipients. We compared Hepatitis C virus (HCV) cure rates among kidney transplant recipients who received an HCV nucleic acid test positive (NAT +) kidney and were treated with sofosbuvir/velpatasvir (SOF/VEL) for 12 weeks or glecaprevir/pibrentasvir (G/P) for 8 weeks, a duration that is 4 weeks shorter than the guideline recommendation for treatment delay beyond 1-week post-transplant.</p><p><strong>Methods: </strong>Retrospective study of HCV-negative adult patients who received a kidney transplant from an HCV NAT+ donor between April 2019 and April 2022 treated with either SOF/VEL for 12 weeks or G/P for 8 weeks. The primary outcome was sustained virologic response 12 weeks after completion of therapy (SVR12). Secondary outcomes included time to DAA initiation, renal function, graft loss, patient death, liver function tests, and opportunistic infections.</p><p><strong>Results: </strong>102 kidney transplant recipients were included with 36 treated with G/P and 66 treated with SOF/VEL. All 36 (100%) treated with G/P achieved SVR12. One patient in the SOF/VEL group failed to achieve SVR12 but received additional therapy and was cured. Time to DAA initiation was similar with a mean of 4 weeks. There was no difference in AST/ALT > 3x ULN or renal function. One rejection occurred in each group. No patient death or graft loss was observed. There was no difference in cytomegalovirus and BK viremia between groups.  CONCLUSION: Delayed initiation of DAA therapy with 12 weeks of SOF/VEL or 8 weeks of G/P achieves SVR12 in kidney transplant recipients without significant adverse effects.</p>","PeriodicalId":23318,"journal":{"name":"Transplant Infectious Disease","volume":" ","pages":"e14366"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126800","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":"Which allogeneic hematopoietic cell transplant recipients have an increased risk for delayed-onset clinically significant cytomegalovirus infection after letermovir prophylaxis?","authors":"Maria Alejandra Mendoza, Eric Bhaimia, Hassan B Alkhateeb, Raymund R Razonable, Matthew Thoendel","doi":"10.1111/tid.14377","DOIUrl":"10.1111/tid.14377","url":null,"abstract":"<p><strong>Introduction: </strong>Cytomegalovirus (CMV) reactivation is one of the most common complications after allogeneic hematopoietic stem cell transplantation (HSCT). Letermovir is approved for CMV prophylaxis among high-risk recipients. However, delayed-onset post-prophylaxis clinically significant CMV infection (csCMVi) has been observed, suggesting the potential for extending letermovir prophylaxis beyond the first one hundred days post-HSCT.</p><p><strong>Methods: </strong>Retrospective multicenter cohort study of allogeneic HSCT patients from August 2018 to March 2023. The primary aim of this study was to identify the risk factors at day 100 associated with delayed onset csCMVi, in patients who received letermovir prophylaxis up to day 100. Competing risk analysis was used to evaluate incidence with specific risk factors, using Gray's Test comparing groups for each event.</p><p><strong>Results: </strong>Among 166 eligible allogeneic HSCT recipients, the most common primary hematological diagnosis was acute myelogenous leukemia (AML) (42.2%). Twenty-six (15.7%) developed a breakthrough csCMVi. Delayed-onset csCMVi occurred in 23.5%, at a median time of 133 days after SCT. On multivariate analysis, having a matched unrelated donor (odds ratio [OR] 2.46) and a CMV donor negative/recipient positive status (OR 3.47) were associated with delayed onset csCMVi. In contrast, AML had a lower odd of having delayed-onset csCMVi (OR 0.23).</p><p><strong>Conclusions: </strong>Having a matched unrelated donor, a CMV donor negative/recipient positive status, and a non-AML underlying disease were associated with delayed onset csCMVi. Prospective studies are needed to evaluate whether extended letermovir prophylaxis is beneficial for these patients.</p>","PeriodicalId":23318,"journal":{"name":"Transplant Infectious Disease","volume":" ","pages":"e14377"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354591","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 Scoping Review of Arthropod-Borne Flavivirus Infections in Solid Organ Transplant Recipients.","authors":"Seohyeon Im, Fadie Altuame, Isabel H Gonzalez-Bocco, Cilomar Martins de Oliveira Filho, Andrea Goldstein Shipper, Maricar Malinis, Carlo Foppiano Palacios","doi":"10.1111/tid.14400","DOIUrl":"10.1111/tid.14400","url":null,"abstract":"<p><p>Arthropod-borne flaviviruses (ABFs), transmitted by mosquitoes or ticks, are increasing due to climate change and globalization. This scoping review examines the epidemiology, clinical characteristics, diagnostics, treatment, and outcomes of ABF infection in solid organ transplant recipients (SOTRs). A database search up to January 25, 2024, focused on ABFs such as West Nile virus (WNV), dengue virus (DENV), Japanese encephalitis virus (JEV), Powassan virus (POWV), yellow fever virus (YFV), and Zika virus (ZIKV), limited to SOTRs. We identified 173 WNV cases from 84 studies, with 28 donor-derived infections (DDIs). Common clinical features included fever (78.5%), altered mental status (65.1%), and weakness or paralysis (45.6%). Treatment involved reducing immunosuppression (IS) in 93 cases, with intravenous immunoglobulin (IVIG), interferon alfa-2b, and ribavirin used in 75 cases. Seven cases involved graft loss or rejection post-infection. WNV infection had a 23.7% mortality rate, with severe neurological complications in 43.9% For DENV infection, 386 cases from 47 studies were identified, including 14 DDI cases. Symptoms included fever (85%), myalgias (56.4%), and headache or retro-orbital pain (34.6%). Severe dengue occurred in 50 cases (13.0%). IVIG was administered in six cases. Reduction in IS was reported in 116 patients. DENV mortality rate was 4.9%. Additionally, 26 cases of less common ABFs such as JEV, POWV, YFV, and ZIKV were described. In summary, ABF infections among SOTRs are associated with higher morbidity and mortality compared to the general population, emphasizing the need for improved preventive strategies, timely diagnosis, and optimized management protocols.</p>","PeriodicalId":23318,"journal":{"name":"Transplant Infectious Disease","volume":" ","pages":"e14400"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569448","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":"Pre-engraftment bacteremia after allogeneic hematopoietic cell transplantation without primary fluoroquinolone antibacterial prophylaxis.","authors":"Aude Nguyen, Jordan Fender, Johan Courjon, Adrien Fischer, Maria Mappoura, Sarah Morin, Federica Giannotti, Anne-Claire Mamez, Yves Chalandon, Stavroula Masouridi-Levrat, Dionysios Neofytos","doi":"10.1111/tid.14375","DOIUrl":"10.1111/tid.14375","url":null,"abstract":"<p><strong>Background: </strong>Bacteremia is a common complication in allogeneic hematopoietic cell transplant recipients (alloHCTr), especially during the pre-engraftment period. International guidelines recommend antibacterial prophylaxis (ABP), despite potential selection for multidrug-resistant organisms (MDRO). Limited contemporary data exist on the epidemiology of pre-engraftment bacteremia in alloHCTr, who do not receive ABP.</p><p><strong>Methods: </strong>We performed a retrospective observational single-center cohort study including all consecutive adult alloHCTr (2015-2021), investigating the incidence, risk factors, and outcomes of bacteremia during the engraftment period. Primary fluoroquinolone (FQ) ABP is not routinely administered in our center.</p><p><strong>Results: </strong>Among 421 patients identified, 124 bacteremia episodes were observed in 121/421 (29%) alloHCTr. The median time to the 1st bacteremia episode was 9 days (IQR 6-11). Most (105/124, 85%) episodes were monomicrobial, while >1 pathogens were identified in 19/124 (15%) episodes. Overall, 152 pathogens were isolated, with a predominance of Gram-positive (118/152, 78%), including coagulase-negative staphylococci (n:47), streptococci (n:46), and enterococci (n:15), followed by Gram-negative bacteria (GNB, 30/152, 20%), and anaerobes (4/152, 3%). There were 2/152 (1%) MDRO (extended-spectrum beta-lactamase producing) GNB. Multivariable analyses identified age >40-year-old (OR 2.4, P = 0.02), male gender (OR 1.8, P = 0.02), and a haploidentical/mismatched unrelated donor (OR 2.5, P < 0.001) as independent risk factors for bacteremia. All cause 30-day mortality among alloHCTr with bacteremia was 0.8% (1/121): one patient died due to an HCT-related complication.</p><p><strong>Conclusion: </strong>Despite lack of primary FQ ABP, low rates of bacteremia were observed during the pre-engraftment period, with low MDRO prevalence and mortality. Our findings may allow to revisit the need for primary universal FQ ABP in high-risk neutropenic hematology patients.</p>","PeriodicalId":23318,"journal":{"name":"Transplant Infectious Disease","volume":" ","pages":"e14375"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296427","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":"Nitazoxanide for Enterocytozoon bieneusi intestinal microsporidiosis.","authors":"Danielle J Fitzpatrick, Alex Chaudhuri, Bradley J Gardiner","doi":"10.1111/tid.14378","DOIUrl":"10.1111/tid.14378","url":null,"abstract":"","PeriodicalId":23318,"journal":{"name":"Transplant Infectious Disease","volume":" ","pages":"e14378"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296425","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":"Simultaneous invasive aspergillosis and mucormycosis after orthotopic liver transplant.","authors":"Cole T Bredehoeft, Sajed Sarwar, Nicholas Marschalk","doi":"10.1111/tid.14381","DOIUrl":"10.1111/tid.14381","url":null,"abstract":"","PeriodicalId":23318,"journal":{"name":"Transplant Infectious Disease","volume":" ","pages":"e14381"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354589","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":"Brain abscess following solid organ transplantation: A 21-year retrospective study.","authors":"Leah M Grant, Pool J Tobar Vega, Reena N Yaman, Marlene E Girardo, Elena Beam, Raymund R Razonable, Christopher F Saling, Holenarasipur R Vikram","doi":"10.1111/tid.14394","DOIUrl":"10.1111/tid.14394","url":null,"abstract":"<p><strong>Background: </strong>Development of brain abscess following solid organ transplantation is associated with significant morbidity and mortality. We undertook a descriptive study to evaluate the etiology, clinical manifestations, diagnosis, management, and outcomes of brain abscess in solid organ transplant (SOT) recipients at three major transplant centers in the United States.</p><p><strong>Methods: </strong>This is a retrospective study of adults with brain abscess following SOT between January 2000 and June 2021 at Mayo Clinic sites in Arizona, Minnesota, and Florida.</p><p><strong>Results: </strong>A total of 39 patients were diagnosed with a brain abscess following SOT. The most common pathogens were Nocardia sp. (24 cases, 61.5% [Nocardia farcinica, 37.5%]), followed by fungi (12 cases, 30.7% [Aspergillus sp., 83.3%]). The majority were kidney transplant recipients (59%). Median time to brain abscess diagnosis was 1.3 years (range, 29 days-12 years) after SOT; 10 of 12 patients (83%) with fungal brain abscess were diagnosed within 1 year after SOT. Twelve patients underwent brain biopsy for diagnosis (25% Nocardia vs. 50% fungal), eight (20.5%) underwent surgical resection of the abscess, and 31 (79.5%) received antimicrobial therapy alone. Median time to brain abscess resolution was 166 days for Nocardia and 356 days for fungal pathogens. Eleven of 39 patients (28.2%) died as a result of their brain abscess, including four of 24 patients (16%) with Nocardia and six of 10 patients (60%) with Aspergillus brain abscess. All-cause mortality was 43.6%.</p><p><strong>Conclusion: </strong>Brain abscess remains an uncommon infectious complication following SOT. Nocardia and fungi accounted for 92% of pathogens in our cohort. Fungal brain abscess portends a poor prognosis.</p>","PeriodicalId":23318,"journal":{"name":"Transplant Infectious Disease","volume":" ","pages":"e14394"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475773","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":"Prevention and management of infectious and tropical diseases in kidney transplant recipients residing in European outermost and overseas territories.","authors":"Laurène Cachera, Erwan Oehler, Karim Abdelmoumen, Laurène Tardieu, Ian Thomas, Marie Lagrange, Rodolphe Manaquin, Nicolas Quirin, Mohamed Sidibe, Tanguy Gbaguidi, Timoté Davodoun, Joelle Claudeon, Henri Vacher, Pierre-Marie Roger, Samuel Markowicz, André Cabié, Anne Scemla, Romain Manchon, Olivier Paccoud, Benoît Pilmis, Fanny Lanternier, Olivier Lortholary, Loïc Epelboin","doi":"10.1111/tid.14386","DOIUrl":"10.1111/tid.14386","url":null,"abstract":"<p><strong>Background: </strong>The European Union encompasses 30 outermost and overseas countries and territories (OCTs). Despite a recent increasing activity of renal transplantation in these territories, many patients still undergo transplantation in continental Europe, with follow-up care coordinated between health professionals from both their transplant center and their home region. Each territory has its unique infectious epidemiology which must be known to ensure appropriate care for kidney transplant recipients (KTRs).</p><p><strong>Aims: </strong>This paper proposes a pragmatic approach to optimize pre-transplant check-up and to provide an overview of the specific epidemiological features of each region. It offers practical algorithms to help practitioners in managing infected KTR living in these territories. This work advocates for increased collaborative research among European OCTs.</p>","PeriodicalId":23318,"journal":{"name":"Transplant Infectious Disease","volume":" ","pages":"e14386"},"PeriodicalIF":2.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475775","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}