Paulo Lisboa Bittencourt, Mateus Jorge Nardelli, Luísa Leite Barros, Guilherme Grossi Lopes Cançado, Eduardo Luiz Rachid Cançado, Débora Raquel Benedita Terrabuio, Cristiane Alves Villela-Nogueira, Maria Lucia Gomes Ferraz, Liana Codes, Vivian Rotman, Rodrigo Rocco, Guilherme Eduardo Felga, Diogo Delgado Dotta, Adrielly de Souza Martins, Liliana Sampaio Costa Mendes, Marlone Cunha da Silva, Elodie Bonfim Hyppolito, Geisa Perez Medina Gomide, Izabelle Venturini Signorelli, Maria Beatriz de Oliveira, Claudia Alexandra Pontes Ivantes, Maria Chiara Chindamo, Valéria Ferreira de Almeida e Borges, Luciana Costa Faria, Claudia Alves Couto
Background and Aim
Primary sclerosing cholangitis (PSC) has been shown to recur after liver transplantation (LT). Some studies have identified certain clinical and laboratory variables associated with an increased risk for recurrent PSC (rPSC) in Caucasians. Furthermore, de novo cholangiocarcinoma (CCA) has been reported anecdotally in patients with rPSC. This study aims to assess the prevalence of rPSC, identify its associated risk factors, and investigate the occurrence of de novo CCA in a highly admixed population from Brazil.
Methods
All patients submitted to LT for PSC enrolled in the Brazilian Cholestasis Study Group database were retrospectively reviewed for the occurrence of rPSC and de novo CCA.
Results
Ninety-six (58 males, mean age 32 ± 13 years) patients with PSC underwent LT. After 90 (39–154) months of follow-up (FU), rPSC was observed in 29 (30%) subjects. There were no significant associations between rPSC and age, gender, concurrent or de novo inflammatory bowel disease, MELD score at the time of LT or allograft rejection. The only factor associated with an increased risk of disease recurrence was time after LT. Although survival was decreased in patients who developed rPSC, this difference was not significant. Only one female patient developed de novo CCA after rPSC, 11 years after LT.
Conclusions
Recurrent PSC was observed in one-third of PSC LT patients in Brazil and was associated with longer time after LT. Despite its frequency, rPSC was not associated with a higher risk of graft loss or a significant reduction in posttransplant survival.
{"title":"Recurrence of Primary Sclerosing Cholangitis and De Novo Cholangiocarcinoma After Liver Transplantation: Results From the Brazilian Cholestasis Consortium","authors":"Paulo Lisboa Bittencourt, Mateus Jorge Nardelli, Luísa Leite Barros, Guilherme Grossi Lopes Cançado, Eduardo Luiz Rachid Cançado, Débora Raquel Benedita Terrabuio, Cristiane Alves Villela-Nogueira, Maria Lucia Gomes Ferraz, Liana Codes, Vivian Rotman, Rodrigo Rocco, Guilherme Eduardo Felga, Diogo Delgado Dotta, Adrielly de Souza Martins, Liliana Sampaio Costa Mendes, Marlone Cunha da Silva, Elodie Bonfim Hyppolito, Geisa Perez Medina Gomide, Izabelle Venturini Signorelli, Maria Beatriz de Oliveira, Claudia Alexandra Pontes Ivantes, Maria Chiara Chindamo, Valéria Ferreira de Almeida e Borges, Luciana Costa Faria, Claudia Alves Couto","doi":"10.1111/ctr.70002","DOIUrl":"10.1111/ctr.70002","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aim</h3>\u0000 \u0000 <p>Primary sclerosing cholangitis (PSC) has been shown to recur after liver transplantation (LT). Some studies have identified certain clinical and laboratory variables associated with an increased risk for recurrent PSC (rPSC) in Caucasians. Furthermore, de novo cholangiocarcinoma (CCA) has been reported anecdotally in patients with rPSC. This study aims to assess the prevalence of rPSC, identify its associated risk factors, and investigate the occurrence of de novo CCA in a highly admixed population from Brazil.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>All patients submitted to LT for PSC enrolled in the Brazilian Cholestasis Study Group database were retrospectively reviewed for the occurrence of rPSC and de novo CCA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Ninety-six (58 males, mean age 32 ± 13 years) patients with PSC underwent LT. After 90 (39–154) months of follow-up (FU), rPSC was observed in 29 (30%) subjects. There were no significant associations between rPSC and age, gender, concurrent or de novo inflammatory bowel disease, MELD score at the time of LT or allograft rejection. The only factor associated with an increased risk of disease recurrence was time after LT. Although survival was decreased in patients who developed rPSC, this difference was not significant. Only one female patient developed de novo CCA after rPSC, 11 years after LT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Recurrent PSC was observed in one-third of PSC LT patients in Brazil and was associated with longer time after LT. Despite its frequency, rPSC was not associated with a higher risk of graft loss or a significant reduction in posttransplant survival.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"38 10","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459685","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}
Shigeo Fuji, Makiko Suga, Yuma Tada, Yasuhiro Shingai, Hidenori Kasahara, Sayako Yuda, Takafumi Yokota, Jun Ishikawa
Background
Infectious diseases remain a major cause of morbidity and mortality after hematopoietic cell transplantation (HCT). Secondary hypogammaglobulinemia is a risk factor for infectious diseases. Total immunoglobulin G (IgG) levels and the history of infectious diseases are an integral part of determining the indication for immunoglobulin replacement therapy. The clinical significance of IgG2 levels is not well established. Guidelines recommend using pathogen-specific IgG to evaluate patients with potential secondary immunodeficiency. However, it is difficult in practice to perform such testing. IgG2 may correlate well with pathogen-specific IgG but the clinical significance of IgG2 is not well established.
Methods
To assess the prevalence of low IgG2 levels with normal IgG after HCT, we cross-sectionally measured the levels of several immunoglobulins, including IgG, IgA, IgM, and IgG2, after HCT, and we assessed the correlation between them.
Results
Among 121 patients who underwent cross-sectional measurements of IgG, IgA, IgM, and IgG2 levels after HCT, 114 had normal IgG2 levels (normal IgG2 group, ≥ 100 mg/dL) and 7 had low IgG2 levels (low IgG2 group, < 100 mg/dL). These 7 patients were allogeneic HCT recipients. All 7 patients with low IgG2 had cGVHD and 4/7 patients had normal total IgG levels.
Conclusion
IgG2 levels may be low even in patients with normal IgG levels years after allogeneic HCT. Therefore, our study suggests that when patients develop infectious diseases, especially multiple episodes, it is recommended to measure IgG2 levels to exclude the possibility of secondary hypogammaglobulinemia after allogeneic HCT.
{"title":"Persistently Low IgG2 Levels in a Subset of Patients Following Hematopoietic Cell Transplantation","authors":"Shigeo Fuji, Makiko Suga, Yuma Tada, Yasuhiro Shingai, Hidenori Kasahara, Sayako Yuda, Takafumi Yokota, Jun Ishikawa","doi":"10.1111/ctr.70010","DOIUrl":"10.1111/ctr.70010","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Infectious diseases remain a major cause of morbidity and mortality after hematopoietic cell transplantation (HCT). Secondary hypogammaglobulinemia is a risk factor for infectious diseases. Total immunoglobulin G (IgG) levels and the history of infectious diseases are an integral part of determining the indication for immunoglobulin replacement therapy. The clinical significance of IgG2 levels is not well established. Guidelines recommend using pathogen-specific IgG to evaluate patients with potential secondary immunodeficiency. However, it is difficult in practice to perform such testing. IgG2 may correlate well with pathogen-specific IgG but the clinical significance of IgG2 is not well established.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To assess the prevalence of low IgG2 levels with normal IgG after HCT, we cross-sectionally measured the levels of several immunoglobulins, including IgG, IgA, IgM, and IgG2, after HCT, and we assessed the correlation between them.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 121 patients who underwent cross-sectional measurements of IgG, IgA, IgM, and IgG2 levels after HCT, 114 had normal IgG2 levels (normal IgG2 group, ≥ 100 mg/dL) and 7 had low IgG2 levels (low IgG2 group, < 100 mg/dL). These 7 patients were allogeneic HCT recipients. All 7 patients with low IgG2 had cGVHD and 4/7 patients had normal total IgG levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>IgG2 levels may be low even in patients with normal IgG levels years after allogeneic HCT. Therefore, our study suggests that when patients develop infectious diseases, especially multiple episodes, it is recommended to measure IgG2 levels to exclude the possibility of secondary hypogammaglobulinemia after allogeneic HCT.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"38 10","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459684","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}
Erin Harris, Nikil Prasad, Devin Skoll, Sambhavi Sneha Kumar, Justin Fried, Veli Topkara, Jayant K. Raikhelkar, Ersilia M. DeFilippis, Farhana Latif, Melana Yuzefpolskaya, Paolo C. Colombo, Nir Uriel, Koji Takeda, Gabriel T. Sayer, Kevin J. Clerkin
Cardiac allograft vasculopathy (CAV) is a major cause of morbidity and mortality following heart transplantation (HT). Prior studies identified distinct CAV trajectories in the early post-HT period with unique predictors, but the evolution of CAV in later periods is not well-described. This study assessed the prevalence of late CAV progression and associated risk factors in HT recipients with ISHLT CAV 0/1 at 10 years post-HT. Consecutive adult patients who underwent HT from January 2000 to December 2008 were evaluated and grouped by CAV trajectories into progressors (developed ISHLT CAV 2/3) or nonprogressors (remained ISHLT CAV 0/1). A total of 130 patients were included with a median age at angiography of 61.7 years and a median follow-up time of 4.8 years. 8.5% progressed to CAV 2/3, while the remaining 91.5% were nonprogressors. Progression was not associated with death or retransplantation (27.3% [progressor] vs. 21.0% [nonprogressor], p = 0.70). These data may inform shared decision-making about late CAV screening.
{"title":"CAV Trajectories Among Patients With No or Mild CAV at 10 Years Posttransplant","authors":"Erin Harris, Nikil Prasad, Devin Skoll, Sambhavi Sneha Kumar, Justin Fried, Veli Topkara, Jayant K. Raikhelkar, Ersilia M. DeFilippis, Farhana Latif, Melana Yuzefpolskaya, Paolo C. Colombo, Nir Uriel, Koji Takeda, Gabriel T. Sayer, Kevin J. Clerkin","doi":"10.1111/ctr.70009","DOIUrl":"10.1111/ctr.70009","url":null,"abstract":"<div>\u0000 \u0000 <p>Cardiac allograft vasculopathy (CAV) is a major cause of morbidity and mortality following heart transplantation (HT). Prior studies identified distinct CAV trajectories in the early post-HT period with unique predictors, but the evolution of CAV in later periods is not well-described. This study assessed the prevalence of late CAV progression and associated risk factors in HT recipients with ISHLT CAV 0/1 at 10 years post-HT. Consecutive adult patients who underwent HT from January 2000 to December 2008 were evaluated and grouped by CAV trajectories into progressors (developed ISHLT CAV 2/3) or nonprogressors (remained ISHLT CAV 0/1). A total of 130 patients were included with a median age at angiography of 61.7 years and a median follow-up time of 4.8 years. 8.5% progressed to CAV 2/3, while the remaining 91.5% were nonprogressors. Progression was not associated with death or retransplantation (27.3% [progressor] vs. 21.0% [nonprogressor], <i>p</i> = 0.70). These data may inform shared decision-making about late CAV screening.</p>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"38 10","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459681","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}
In this study, prenatal and postnatal blood samples were taken from pregnant women who had 35 or more gestational weeks and had not developed anti-HLA positivity yet. The aim of this study was to evaluate the factors that may be effective in the development of panel reactive antibody (PRA) positivity during pregnancy.
Methods
PRA testing was studied by taking the blood of 86 pregnant women 1 month before birth. Blood was taken again 1 month after birth from these women with prenatal PRA negative and it was checked whether PRA positivity developed. As a control group, 40 women without pregnancy were selected for the study.
Results
Of the 86 pregnant, 42 (48.8%) had cesarean sections, 44 (51.2%) had normal births, and PRA positivity developed in 14 (32.5%) of cesarean deliveries and three (8.0%) of normal births. In the control group, there were three (7.5%) PRA positivity. A statistically significant difference was found between cesarean delivery, normal delivery, and control group. Moreover, when compared with the control group, it was found statistically significant that all deliveries increased the development of HLA Class II antibodies.
Discussion
Cesarean delivery was associated with increased PRA positivity compared to normal birth. The new information presented in this study will pave the way for further research and enable healthcare professionals to consider both the individual's potential future need for organ transplantation and the positive impact on public health and more effective management of healthcare costs when making decisions regarding cesarean section.
研究背景在这项研究中，产前和产后血液样本取自妊娠周数为 35 周或 35 周以上且尚未出现抗-HLA 阳性的孕妇。本研究的目的是评估在妊娠期间可能有效导致面板反应性抗体（PRA）阳性的因素：方法：在分娩前 1 个月抽取 86 名孕妇的血液进行 PRA 检测。产前 PRA 阴性的孕妇在产后 1 个月再次抽血，检查是否出现 PRA 阳性。研究还选取了 40 名未怀孕的妇女作为对照组：在 86 名孕妇中，42 人（48.8%）剖宫产，44 人（51.2%）顺产，其中 14 人（32.5%）剖宫产，3 人（8.0%）顺产，PRA 阳性。对照组中有 3 例（7.5%）PRA 阳性。在统计学上，剖宫产组、顺产组和对照组之间存在明显差异。此外，与对照组相比，所有分娩均增加了 HLA II 类抗体的产生，这在统计学上有显著意义：讨论：与顺产相比，剖腹产与 PRA 阳性增加有关。本研究提供的新信息将为进一步的研究铺平道路，并使医护人员在做出剖腹产决定时，既能考虑到个人未来对器官移植的潜在需求，又能考虑到对公共卫生的积极影响以及更有效的医疗成本管理。
{"title":"Cesarean Section Is a Risk Factor That Prevents Organ Transplantation by Increasing the Development of Anti-HLA Antibodies in Women","authors":"Gökhan Akyüz, Hasan Doğan","doi":"10.1111/ctr.70005","DOIUrl":"10.1111/ctr.70005","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In this study, prenatal and postnatal blood samples were taken from pregnant women who had 35 or more gestational weeks and had not developed anti-HLA positivity yet. The aim of this study was to evaluate the factors that may be effective in the development of panel reactive antibody (PRA) positivity during pregnancy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>PRA testing was studied by taking the blood of 86 pregnant women 1 month before birth. Blood was taken again 1 month after birth from these women with prenatal PRA negative and it was checked whether PRA positivity developed. As a control group, 40 women without pregnancy were selected for the study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 86 pregnant, 42 (48.8%) had cesarean sections, 44 (51.2%) had normal births, and PRA positivity developed in 14 (32.5%) of cesarean deliveries and three (8.0%) of normal births. In the control group, there were three (7.5%) PRA positivity. A statistically significant difference was found between cesarean delivery, normal delivery, and control group. Moreover, when compared with the control group, it was found statistically significant that all deliveries increased the development of HLA Class II antibodies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Cesarean delivery was associated with increased PRA positivity compared to normal birth. The new information presented in this study will pave the way for further research and enable healthcare professionals to consider both the individual's potential future need for organ transplantation and the positive impact on public health and more effective management of healthcare costs when making decisions regarding cesarean section.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"38 10","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ctr.70005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459682","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}
Emily A. Johnston, Jingyao Hong, Akanksha Nalatwad, Yiting Li, Byoungjun Kim, Jane J. Long, Nicole M. Ali, Barbara Krawczuk, Aarti Mathur, Babak J. Orandi, Joshua Chodosh, Dorry L. Segev, Mara A. McAdams-DeMarco
Introduction
Dietary restrictions for patients with end-stage kidney disease (ESKD) are burdensome. Kidney transplantation (KT) candidates who lack neighborhood resources and are burdened by dietary restrictions may have decreased access to KT.
Methods
In our two-center prospective cohort study (2014–2023), 2471 ESKD patients who were evaluated for KT (candidates) reported their perceived burden of dietary restrictions (not at all, somewhat/moderately, or extremely bothered). Neighborhood-level socioeconomic factors were derived from residential ZIP codes. We quantified the association of perceived burden of the dietary restrictions with a chance of listing using Cox models and risk of waitlist mortality using competing risks models. Then we tested whether these associations differed by neighborhood-level socioeconomic factors.
Results
At evaluation, 18% of KT candidates felt extremely bothered by dietary restrictions. Those who felt extremely bothered were less likely to be listed for KT (adjusted hazard ratio [aHR] = 0.75, 95% confidence interval [CI]: 0.64–0.87); this association did not differ by neighborhood-level socioeconomic factors. Overall, the burden of dietary restrictions was not associated with waitlist mortality (p = 0.62). However, among candidates living in high food insecurity neighborhoods, those who felt extremely bothered had higher waitlist mortality (adjusted subhazard ratio [aSHR] = 2.07, 95% CI: 1.14–3.75, p[interaction] = 0.02). The association between dietary burden and waitlist mortality did not differ by neighborhood-level healthy food access.
Conclusion
The perceived burden of dietary restrictions is associated with a lower chance of listing for KT, and higher waitlist mortality only among candidates residing in neighborhoods with high food insecurity. Transplant centers should identify vulnerable patients and support them with nutrition education and access to food assistance programs.
{"title":"Dietary Restriction, Socioeconomic Factors, Access to Kidney Transplantation, and Waitlist Mortality","authors":"Emily A. Johnston, Jingyao Hong, Akanksha Nalatwad, Yiting Li, Byoungjun Kim, Jane J. Long, Nicole M. Ali, Barbara Krawczuk, Aarti Mathur, Babak J. Orandi, Joshua Chodosh, Dorry L. Segev, Mara A. McAdams-DeMarco","doi":"10.1111/ctr.70001","DOIUrl":"https://doi.org/10.1111/ctr.70001","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Dietary restrictions for patients with end-stage kidney disease (ESKD) are burdensome. Kidney transplantation (KT) candidates who lack neighborhood resources and are burdened by dietary restrictions may have decreased access to KT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In our two-center prospective cohort study (2014–2023), 2471 ESKD patients who were evaluated for KT (candidates) reported their perceived burden of dietary restrictions (not at all, somewhat/moderately, or extremely bothered). Neighborhood-level socioeconomic factors were derived from residential ZIP codes. We quantified the association of perceived burden of the dietary restrictions with a chance of listing using Cox models and risk of waitlist mortality using competing risks models. Then we tested whether these associations differed by neighborhood-level socioeconomic factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At evaluation, 18% of KT candidates felt extremely bothered by dietary restrictions. Those who felt extremely bothered were less likely to be listed for KT (adjusted hazard ratio [aHR] = 0.75, 95% confidence interval [CI]: 0.64–0.87); this association did not differ by neighborhood-level socioeconomic factors. Overall, the burden of dietary restrictions was not associated with waitlist mortality (<i>p</i> = 0.62). However, among candidates living in high food insecurity neighborhoods, those who felt extremely bothered had higher waitlist mortality (adjusted subhazard ratio [aSHR] = 2.07, 95% CI: 1.14–3.75, <i>p</i><sub>[interaction]</sub> = 0.02). The association between dietary burden and waitlist mortality did not differ by neighborhood-level healthy food access.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The perceived burden of dietary restrictions is associated with a lower chance of listing for KT, and higher waitlist mortality only among candidates residing in neighborhoods with high food insecurity. Transplant centers should identify vulnerable patients and support them with nutrition education and access to food assistance programs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"38 10","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451765","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}
Vivek B. Beechar, Varun K. Phadke, Stephanie M. Pouch, Aneesh K. Mehta, Geeta Karadkhele, Christian P. Larsen, Michael H. Woodworth
Introduction
Maribavir was recently approved by the FDA, expanding treatment options for post–solid-organ transplant refractory/resistant CMV. We sought to describe the post–marketing experience with maribavir at a large academic transplant center.
Methods
This was a retrospective observational study of all renal transplant recipients treated with maribavir for refractory/resistant CMV DNAemia/disease. CMV viral loads, immunosuppression regimens and management, resistance testing, and antiviral therapy durations were reviewed. Outcomes of interest included treatment success, defined as undetectable CMV DNAemia for two consecutive weeks or detected but unquantifiable DNAemia for five consecutive weeks, as well as the emergence of antiviral resistance, and recurrent DNAemia.
Results
From 2021 to 2023, 5/10 (50%) patients achieved durable virologic suppression with maribavir (classified as responders). Among responders, 2/5 (40%) experienced low-level CMV DNAemia recurrence (defined as a viral load less than 1000 IU/mL) within 8 weeks of antiviral discontinuation. Among nonresponders, 2/3 (66.7%) were found to have UL97 protein mutations associated with maribavir resistance identified 85 and 75 days after initiation of maribavir. Two patients are currently on maribavir with clinical outcomes that are yet to be determined. Responders had a mean reduction of 200 mg (SD—274 mg) in mycophenolate dosing with nonresponders having a mean increase of 167 mg (SD—764 mg).
Conclusions
Maribavir, often in conjunction with mycophenolate dose reduction, was effective for many patients with refractory/resistant CMV DNAemia at our transplant center, though several experienced recurrent DNAemia. In patients who did not respond to therapy, resistance to maribavir was frequently detected. Clinicians treating these patients should remain vigilant for rebound CMV DNAemia and consider repeat antiviral resistance testing.
导言：美国食品药品管理局最近批准了马利巴韦，扩大了实体器官移植后难治/耐药 CMV 的治疗选择范围。我们试图描述一家大型学术移植中心使用马利巴韦的上市后经验。 方法 这是一项回顾性观察研究，研究对象是所有接受马利巴韦治疗的肾移植受者，他们都曾接受过难治/耐药 CMV DNA 血症/疾病的治疗。研究回顾了 CMV 病毒载量、免疫抑制方案和管理、耐药性检测和抗病毒治疗持续时间。研究结果包括治疗成功（定义为连续两周检测不到 CMV DNA 血症或连续五周检测到但无法量化的 DNA 血症）、抗病毒耐药性的出现以及 DNA 血症的复发。 结果 从 2021 年到 2023 年，5/10（50%）名患者在使用马利巴韦后实现了持久的病毒学抑制（被归类为应答者）。在应答者中，2/5（40%）的患者在停药 8 周内出现低水平 CMV DNA 血症复发（定义为病毒载量低于 1000 IU/mL）。在无应答患者中，2/3（66.7%）的患者在开始服用马利巴韦 85 天和 75 天后发现与马利巴韦耐药相关的 UL97 蛋白突变。两名患者目前仍在服用马利巴韦，临床结果尚待确定。应答者的霉酚酸盐用量平均减少了 200 毫克（标度值为 274 毫克），而无应答者的用量平均增加了 167 毫克（标度值为 764 毫克）。 结论 在我们的移植中心，马利巴韦通常与降低霉酚酸酯剂量相结合，对许多难治/耐药CMV DNA血症患者有效，但也有一些患者出现了DNA血症复发。在对治疗无反应的患者中，经常检测到对马利巴韦的耐药性。治疗这些患者的临床医生应时刻警惕CMV DNA血症的反弹，并考虑重复进行抗病毒耐药性检测。
{"title":"Evaluating Real-World Experience With Maribavir for Treatment of Refractory/Resistant Cytomegalovirus in Renal Transplant Recipients","authors":"Vivek B. Beechar, Varun K. Phadke, Stephanie M. Pouch, Aneesh K. Mehta, Geeta Karadkhele, Christian P. Larsen, Michael H. Woodworth","doi":"10.1111/ctr.15480","DOIUrl":"https://doi.org/10.1111/ctr.15480","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Maribavir was recently approved by the FDA, expanding treatment options for post–solid-organ transplant refractory/resistant CMV. We sought to describe the post–marketing experience with maribavir at a large academic transplant center.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This was a retrospective observational study of all renal transplant recipients treated with maribavir for refractory/resistant CMV DNAemia/disease. CMV viral loads, immunosuppression regimens and management, resistance testing, and antiviral therapy durations were reviewed. Outcomes of interest included treatment success, defined as undetectable CMV DNAemia for two consecutive weeks or detected but unquantifiable DNAemia for five consecutive weeks, as well as the emergence of antiviral resistance, and recurrent DNAemia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>From 2021 to 2023, 5/10 (50%) patients achieved durable virologic suppression with maribavir (classified as responders). Among responders, 2/5 (40%) experienced low-level CMV DNAemia recurrence (defined as a viral load less than 1000 IU/mL) within 8 weeks of antiviral discontinuation. Among nonresponders, 2/3 (66.7%) were found to have UL97 protein mutations associated with maribavir resistance identified 85 and 75 days after initiation of maribavir. Two patients are currently on maribavir with clinical outcomes that are yet to be determined. Responders had a mean reduction of 200 mg (SD—274 mg) in mycophenolate dosing with nonresponders having a mean increase of 167 mg (SD—764 mg).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Maribavir, often in conjunction with mycophenolate dose reduction, was effective for many patients with refractory/resistant CMV DNAemia at our transplant center, though several experienced recurrent DNAemia. In patients who did not respond to therapy, resistance to maribavir was frequently detected. Clinicians treating these patients should remain vigilant for rebound CMV DNAemia and consider repeat antiviral resistance testing.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"38 10","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451733","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}
Allison Drury, Sarah Huber, Elena Loya, John A. Powelson, Andrew Lutz, Kelly Kasper, Jeffrey M. Rothenberg, Jonathan A. Fridell
Introduction
With the growing population of pancreas transplant recipients followed long-term, some female recipients are going to require surgical intervention for gynecologic symptoms and pathologies. Currently, there is a lack of literature describing how to approach this population and whether pelvic gynecologic procedures (GYN) can be performed safely given the proximity of the pancreatic (and possibly renal) allograft. In this single-center retrospective analysis, all pancreas transplant recipients that subsequently underwent GYN were reviewed.
Methods
Subjects were identified by cross-referencing all pancreas transplants performed between January 2003 and December 2022 for any subsequent GYN. Demographics at transplant and GYN, indications and procedure performed, operative time, presence and involvement of a transplant surgeon, complications length of stay, and readmissions were reviewed.
Results
Seventeen patients who underwent a total of 19 GYN after pancreas transplantation were identified. Operations performed included tubal ligation (n = 2), total abdominal hysterectomy with (n = 6) or without bilateral salpingectomy (n = 2), oophorectomy versus cyst drainage (n = 2), bilateral oophorectomy (n = 1), and unilateral (n = 4) versus bilateral (n = 2) salpingectomy. Four were performed through an open laparotomy and 15 were performed laparoscopically. In 11 cases, a transplant surgeon was involved intra-operatively. Eight of the 17 patients developed post-operative complications including post-operative fevers, fluid overload, neutropenia, elevated creatinine (n = 2), nephrolithiasis, urinary tract infection, and incisional hernia. Five required readmission.
Conclusion
GYN can be performed safely following pancreas transplantation, but careful planning and the involvement of the transplant surgery team are advised.
{"title":"Abdominal Gynecologic Procedures in Pancreas Transplant Recipients","authors":"Allison Drury, Sarah Huber, Elena Loya, John A. Powelson, Andrew Lutz, Kelly Kasper, Jeffrey M. Rothenberg, Jonathan A. Fridell","doi":"10.1111/ctr.70004","DOIUrl":"https://doi.org/10.1111/ctr.70004","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>With the growing population of pancreas transplant recipients followed long-term, some female recipients are going to require surgical intervention for gynecologic symptoms and pathologies. Currently, there is a lack of literature describing how to approach this population and whether pelvic gynecologic procedures (GYN) can be performed safely given the proximity of the pancreatic (and possibly renal) allograft. In this single-center retrospective analysis, all pancreas transplant recipients that subsequently underwent GYN were reviewed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Subjects were identified by cross-referencing all pancreas transplants performed between January 2003 and December 2022 for any subsequent GYN. Demographics at transplant and GYN, indications and procedure performed, operative time, presence and involvement of a transplant surgeon, complications length of stay, and readmissions were reviewed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seventeen patients who underwent a total of 19 GYN after pancreas transplantation were identified. Operations performed included tubal ligation (<i>n</i> = 2), total abdominal hysterectomy with (<i>n</i> = 6) or without bilateral salpingectomy (<i>n</i> = 2), oophorectomy versus cyst drainage (<i>n</i> = 2), bilateral oophorectomy (<i>n</i> = 1), and unilateral (<i>n</i> = 4) versus bilateral (<i>n</i> = 2) salpingectomy. Four were performed through an open laparotomy and 15 were performed laparoscopically. In 11 cases, a transplant surgeon was involved intra-operatively. Eight of the 17 patients developed post-operative complications including post-operative fevers, fluid overload, neutropenia, elevated creatinine (<i>n</i> = 2), nephrolithiasis, urinary tract infection, and incisional hernia. Five required readmission.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>GYN can be performed safely following pancreas transplantation, but careful planning and the involvement of the transplant surgery team are advised.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"38 10","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ctr.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451766","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}
Cathrine M. Moeller, Daniel Oren, Andrea Fernandez Valledor, Gal Rubinstein, Dor Lotan, Yonatan Mehlman, Sharon Slomovich, Salwa Rahman, Changhee Lee, Julia Baranowska, Matthew Regan, Boaz Elad, Ersilia M. DeFilippis, Carolyn Hennecken, Ruben Salazar, Jayant Raikhelkar, Kevin J. Clerkin, Justin Fried, Edward Lin, David Bae, Kyung T. Oh, Farhana Latif, Veli K. Topkara, Yoshifumi Naka, Koji Takeda, David Majure, Nir Uriel, Gabriel Sayer
Background
Donor-derived cell-free DNA (dd-cfDNA) has emerged as a reliable, noninvasive method for the surveillance of allograft rejection in heart transplantation (HT) patients, but its utility in multi-organ transplants (MOT) is unknown. We describe our experience using dd-cfDNA in simultaneous MOT recipients.
Methods
A single-center retrospective review of all HT recipients between 2018 and 2022 that had at least one measurement of dd-cfDNA collected. Patients who had simultaneous MOT were identified and included in this study. Levels of dd-cfDNA were paired with endomyocardial biopsies (EMB) performed within 1 month of blood testing if available. Acute cellular rejection (ACR) was defined as ISHLT (International Society for Heart and Lung Transplantation) grade ≥ 2R. and antibody-mediated rejection (AMR) was defined as pAMR grade > 0. The within-patient variability score of the dd-cfDNA was calculated by the variance/average.
Results
The study included 25 multiorgan transplant recipients: 13 heart–kidney (H-K), 8 heart–liver (H-Li), and 4 heart–lung (H-Lu). The median age was 55 years, 44% were female; the median time from HT until the first dd-cfDNA measurement was 4.5 months (IQR 2, 10.5). The median dd-cfDNA level was 0.18% (IQR 0.15%, 0.27%) for H-K, 1.15% (IQR 0.77%, 2.33%) for H-Li, and 0.69% (IQR 0.62%, 1.07%) for H-Lu patients (p < 0.001). Prevalence of positive dd-cfDNA tests (threshold of 0.20%) were 42.2%, 97.3%, and 92.3% in the H-K, H-Li, and H-Lu groups, respectively. The within-patient variability score was highest in the H-Li group (median of 0.45 [IQR 0.29, 0.94]) and lowest in the H-K group (median of 0.09 [IQR 0.06, 0.12]); p = 0.002. No evidence of cardiac ACR or AMR was found. Three patients experienced renal allograft ACR and/or AMR, two patients experienced rejection of the liver allograft, and one patient experienced an episode of AMR-mediated lung rejection. One person in the H-K group experienced an episode of cardiac allograft dysfunction that was not associated with biopsy-confirmed rejection.
Conclusion
Dd-cfDNA is chronically elevated in most MOT recipients. There is a high degree of within-patient variability in levels (particularly for H-Li and H-Lu recipients), which may limit the utility of this assay in monitoring MOT recipients.
{"title":"Clinical Utility of Donor-Derived Cell-Free DNA in Heart Transplant Recipients With Multi-Organ Transplants","authors":"Cathrine M. Moeller, Daniel Oren, Andrea Fernandez Valledor, Gal Rubinstein, Dor Lotan, Yonatan Mehlman, Sharon Slomovich, Salwa Rahman, Changhee Lee, Julia Baranowska, Matthew Regan, Boaz Elad, Ersilia M. DeFilippis, Carolyn Hennecken, Ruben Salazar, Jayant Raikhelkar, Kevin J. Clerkin, Justin Fried, Edward Lin, David Bae, Kyung T. Oh, Farhana Latif, Veli K. Topkara, Yoshifumi Naka, Koji Takeda, David Majure, Nir Uriel, Gabriel Sayer","doi":"10.1111/ctr.15479","DOIUrl":"https://doi.org/10.1111/ctr.15479","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Donor-derived cell-free DNA (dd-cfDNA) has emerged as a reliable, noninvasive method for the surveillance of allograft rejection in heart transplantation (HT) patients, but its utility in multi-organ transplants (MOT) is unknown. We describe our experience using dd-cfDNA in simultaneous MOT recipients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A single-center retrospective review of all HT recipients between 2018 and 2022 that had at least one measurement of dd-cfDNA collected. Patients who had simultaneous MOT were identified and included in this study. Levels of dd-cfDNA were paired with endomyocardial biopsies (EMB) performed within 1 month of blood testing if available. Acute cellular rejection (ACR) was defined as ISHLT (International Society for Heart and Lung Transplantation) grade ≥ 2R. and antibody-mediated rejection (AMR) was defined as pAMR grade > 0. The within-patient variability score of the dd-cfDNA was calculated by the variance/average.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study included 25 multiorgan transplant recipients: 13 heart–kidney (H-K), 8 heart–liver (H-Li), and 4 heart–lung (H-Lu). The median age was 55 years, 44% were female; the median time from HT until the first dd-cfDNA measurement was 4.5 months (IQR 2, 10.5). The median dd-cfDNA level was 0.18% (IQR 0.15%, 0.27%) for H-K, 1.15% (IQR 0.77%, 2.33%) for H-Li, and 0.69% (IQR 0.62%, 1.07%) for H-Lu patients (<i>p</i> < 0.001). Prevalence of positive dd-cfDNA tests (threshold of 0.20%) were 42.2%, 97.3%, and 92.3% in the H-K, H-Li, and H-Lu groups, respectively. The within-patient variability score was highest in the H-Li group (median of 0.45 [IQR 0.29, 0.94]) and lowest in the H-K group (median of 0.09 [IQR 0.06, 0.12]); <b><i>p</i> = 0.002</b>. No evidence of cardiac ACR or AMR was found. Three patients experienced renal allograft ACR and/or AMR, two patients experienced rejection of the liver allograft, and one patient experienced an episode of AMR-mediated lung rejection. One person in the H-K group experienced an episode of cardiac allograft dysfunction that was not associated with biopsy-confirmed rejection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Dd-cfDNA is chronically elevated in most MOT recipients. There is a high degree of within-patient variability in levels (particularly for H-Li and H-Lu recipients), which may limit the utility of this assay in monitoring MOT recipients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"38 10","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142449202","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}
Miriam Vélez-Bermúdez, Heidi Rishel Brakey, Larissa Myaskovsky, Mark Unruh, Pooja P. Singh, Nancy Pandhi
Introduction
Although living kidney donation is generally considered a safe procedure, it is ethically critical that prospective donors are fully informed before consent. However, prospective donors lack a deep understanding of the donation experience, making the postdonation aftermath feel unanticipated. We sought to gain in-depth qualitative descriptions of the short- and long-term risks and benefits associated with kidney donation among an ethnically diverse group of donors to offer a balanced view of the positive and negative experiences that may occur postdonation.
Methods
We conducted individual narrative in-depth interviews (September 2020–March 2021) using the DIPEx (database of individual patient experiences) method with former living kidney donors primarily via Zoom.
Results
Fourteen donors (10 women; 8 White, 5 Hispanic, and 1 Native American) completed interviews. Interactions with healthcare providers leading up to donation were largely positive; however, lack of clarity regarding postdonation laboratory values among primary care providers led three participants to be erroneously told they developed kidney disease. Most experienced unanticipated outcomes, including postsurgical complications (e.g., hernia), long-term fatigue (i.e., ≥12 weeks), emotional distress (e.g., depression), hypertension, and gout. Difficulty obtaining life insurance following donation was an unexpected challenge. Despite these issues, participants were unanimously enthusiastic about living kidney donation and reported no regrets.
Conclusions
Enthusiasm for living kidney donation remained high among all participants despite most experiencing negative outcomes. These findings suggest that greater transparency regarding postdonation experiences may not preclude the decision to move forward with living kidney donation. These narratives will be utilized for an online module of lived experiences of donation.
{"title":"Experiences of Unanticipated Outcomes Among Ethnically Diverse Living Kidney Donors: A Qualitative Pilot Study","authors":"Miriam Vélez-Bermúdez, Heidi Rishel Brakey, Larissa Myaskovsky, Mark Unruh, Pooja P. Singh, Nancy Pandhi","doi":"10.1111/ctr.15476","DOIUrl":"https://doi.org/10.1111/ctr.15476","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Although living kidney donation is generally considered a safe procedure, it is ethically critical that prospective donors are fully informed before consent. However, prospective donors lack a deep understanding of the donation experience, making the postdonation aftermath feel unanticipated. We sought to gain in-depth qualitative descriptions of the short- and long-term risks and benefits associated with kidney donation among an ethnically diverse group of donors to offer a balanced view of the positive and negative experiences that may occur postdonation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted individual narrative in-depth interviews (September 2020–March 2021) using the DIPEx (database of individual patient experiences) method with former living kidney donors primarily via Zoom.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fourteen donors (10 women; 8 White, 5 Hispanic, and 1 Native American) completed interviews. Interactions with healthcare providers leading up to donation were largely positive; however, lack of clarity regarding postdonation laboratory values among primary care providers led three participants to be erroneously told they developed kidney disease. Most experienced unanticipated outcomes, including postsurgical complications (e.g., hernia), long-term fatigue (i.e., ≥12 weeks), emotional distress (e.g., depression), hypertension, and gout. Difficulty obtaining life insurance following donation was an unexpected challenge. Despite these issues, participants were unanimously enthusiastic about living kidney donation and reported no regrets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Enthusiasm for living kidney donation remained high among all participants despite most experiencing negative outcomes. These findings suggest that greater transparency regarding postdonation experiences may not preclude the decision to move forward with living kidney donation. These narratives will be utilized for an online module of lived experiences of donation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"38 10","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142449198","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}
Jens Böhmer, Håkan Wåhlander, Kristjan Karason, Jan Sunnegårdh, Carina Wasslavik, Marianne Jonsson, Julia Asp, Anne Ricksten, Göran Dellgren
Objective
Cell-free DNA (cfDNA) is used as a biomarker after transplantation to detect graft injury, relying on the donor fraction (DF). We have established a PCR-based approach allowing us to separately quantify absolute values of dd-cfDNA and recipient-derived cfDNA (rd-cfDNA). We aimed to present typical clinical scenarios after heart transplantation (HTx) to illustrate the advantages of absolute cfDNA values over DF.
Methods
We used the cfDNA results of our cohort (509 samples of 52 patients followed during the first year after HTx) as background and determined the trajectories of cfDNA in specific clinical situations. We profiled an uncomplicated clinical course, viral and bacterial infections, acute and chronic rejection, and false-negative and false-positive rejections in six patients (five adults, one child).
Results
There was a substantial discrepancy between relative (DF) and absolute cfDNA-levels in several clinical situations. Rd- and dd-cfDNA were independently elevated during episodes of rejection and infection and were better suited to depict treatment response than DF alone.
Conclusions
Absolute quantification of cfDNA may offer clinically relevant information additive to DF in various situations after HTx and could be helpful for more accurate monitoring of diagnosis and treatment of rejection.
{"title":"Clinical Examples of the Additive Value of Absolute Quantification of Cell-Free DNA After Heart Transplantation","authors":"Jens Böhmer, Håkan Wåhlander, Kristjan Karason, Jan Sunnegårdh, Carina Wasslavik, Marianne Jonsson, Julia Asp, Anne Ricksten, Göran Dellgren","doi":"10.1111/ctr.15477","DOIUrl":"https://doi.org/10.1111/ctr.15477","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Cell-free DNA (cfDNA) is used as a biomarker after transplantation to detect graft injury, relying on the donor fraction (DF). We have established a PCR-based approach allowing us to separately quantify absolute values of dd-cfDNA and recipient-derived cfDNA (rd-cfDNA). We aimed to present typical clinical scenarios after heart transplantation (HTx) to illustrate the advantages of absolute cfDNA values over DF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used the cfDNA results of our cohort (509 samples of 52 patients followed during the first year after HTx) as background and determined the trajectories of cfDNA in specific clinical situations. We profiled an uncomplicated clinical course, viral and bacterial infections, acute and chronic rejection, and false-negative and false-positive rejections in six patients (five adults, one child).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There was a substantial discrepancy between relative (DF) and absolute cfDNA-levels in several clinical situations. Rd- and dd-cfDNA were independently elevated during episodes of rejection and infection and were better suited to depict treatment response than DF alone.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Absolute quantification of cfDNA may offer clinically relevant information additive to DF in various situations after HTx and could be helpful for more accurate monitoring of diagnosis and treatment of rejection.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"38 10","pages":""},"PeriodicalIF":1.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ctr.15477","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451186","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}
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