Pub Date : 2023-09-28eCollection Date: 2023-10-01DOI: 10.1097/TXD.0000000000001525
Jana Ekberg, Marie Hjelmberg, Åsa Norén, Mats Brännström, Gustaf Herlenius, Seema Baid-Agrawal
Background: Chronic kidney disease is common after non-renal solid organ transplantation, mainly secondary to calcineurin inhibitors toxicity. Uterus transplantation (UTx) is an innovative treatment for women with absolute uterine factor infertility. UTx is exclusive because it is transient with the absence of lifelong immunosuppression and is performed in young healthy participants. Therefore, UTx provides a unique setting for evaluating the effect of time-limited calcineurin inhibitors treatment on recipients' kidney function.
Methods: In the first UTx cohort worldwide, we studied kidney function using estimated glomerular filtration rate (eGFR) in 7 women over a median follow-up of 121 (119-126) mo.
Results: Median eGFR (mL/min/1.73 m2) of the cohort was 113 at UTx, which declined to 74 during month 3, 71 at months 10-12, 76 at hysterectomy (HE), and 83 at last follow-up. Median duration of tacrolimus exposure was 52 (22-83) mo, and median trough levels (µg/L) were 10 during month 3 and 5.8 at HE. Between UTx and month 3, decline in kidney function was observed in all 7 participants with a median eGFR slope for the whole cohort of -24 mL/min/1.73 m2, which declined further by -4 mL/min/1.73 m2 until months 10-12. Thereafter, eGFR slope improved in 3 participants, remained stable in 3, and worsened in 1 until HE/tacrolimus discontinuation, after which it improved in 2. Eventually, between UTx and last follow-up, 4 of 7 participants had a decline in their eGFR, the median annual eGFR slope being negative at -1.9 mL/min/1.73 m2/y for the whole group.
Conclusions: Kidney function declined in all recipients early after UTx followed by a persistent long-term decrease in majority, despite transplantectomy and discontinuation of immunosuppression. Thus, UTx may incur an increased risk of chronic kidney disease even in this young and healthy population, highlighting the importance of close surveillance of kidney function and minimization of tacrolimus exposure.
{"title":"Long-term Course of Kidney Function in Uterus Transplant Recipients Under Treatment With Tacrolimus and After Transplantectomy: Results of the First Clinical Cohort.","authors":"Jana Ekberg, Marie Hjelmberg, Åsa Norén, Mats Brännström, Gustaf Herlenius, Seema Baid-Agrawal","doi":"10.1097/TXD.0000000000001525","DOIUrl":"https://doi.org/10.1097/TXD.0000000000001525","url":null,"abstract":"<p><strong>Background: </strong>Chronic kidney disease is common after non-renal solid organ transplantation, mainly secondary to calcineurin inhibitors toxicity. Uterus transplantation (UTx) is an innovative treatment for women with absolute uterine factor infertility. UTx is exclusive because it is transient with the absence of lifelong immunosuppression and is performed in young healthy participants. Therefore, UTx provides a unique setting for evaluating the effect of time-limited calcineurin inhibitors treatment on recipients' kidney function.</p><p><strong>Methods: </strong>In the first UTx cohort worldwide, we studied kidney function using estimated glomerular filtration rate (eGFR) in 7 women over a median follow-up of 121 (119-126) mo.</p><p><strong>Results: </strong>Median eGFR (mL/min/1.73 m<sup>2</sup>) of the cohort was 113 at UTx, which declined to 74 during month 3, 71 at months 10-12, 76 at hysterectomy (HE), and 83 at last follow-up. Median duration of tacrolimus exposure was 52 (22-83) mo, and median trough levels (µg/L) were 10 during month 3 and 5.8 at HE. Between UTx and month 3, decline in kidney function was observed in all 7 participants with a median eGFR slope for the whole cohort of -24 mL/min/1.73 m<sup>2</sup>, which declined further by -4 mL/min/1.73 m<sup>2</sup> until months 10-12. Thereafter, eGFR slope improved in 3 participants, remained stable in 3, and worsened in 1 until HE/tacrolimus discontinuation, after which it improved in 2. Eventually, between UTx and last follow-up, 4 of 7 participants had a decline in their eGFR, the median annual eGFR slope being negative at -1.9 mL/min/1.73 m<sup>2</sup>/y for the whole group.</p><p><strong>Conclusions: </strong>Kidney function declined in all recipients early after UTx followed by a persistent long-term decrease in majority, despite transplantectomy and discontinuation of immunosuppression. Thus, UTx may incur an increased risk of chronic kidney disease even in this young and healthy population, highlighting the importance of close surveillance of kidney function and minimization of tacrolimus exposure.</p>","PeriodicalId":23225,"journal":{"name":"Transplantation Direct","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/05/1b/txd-9-e1525.PMC10540914.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41171135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-28eCollection Date: 2023-10-01DOI: 10.1097/TXD.0000000000001544
Kiran Gajurel, Tue Ngo, Robert T Fairman, Lewis H McCurdy
Background: Kidney transplant (KT) candidates have historically low immunization rates against recommended vaccines. A retrospective single-center study of contemporary KT candidates was conducted to assess vaccination rates and vaccine uptake.
Methods: All KT candidates ≥18 y evaluated between January 1, 2020, and December 31, 2020, were retrospectively reviewed for history of prior vaccination against tetanus, diphtheria, and pertussis; 13-valent pneumococcal conjugate vaccine; 23-valent pneumococcal polysaccharide vaccine; and recombinant zoster vaccine. Positive hepatitis A IgG total, hepatitis B surface antibody, measles, mumps, rubella, and varicella IgG were assessed as surrogate markers of immunity. Vaccine uptake among vaccine-eligible candidates was also assessed.
Results: Among 150 KT candidates, the rate of prior vaccination against tetanus, diphtheria, and pertussis; 13-valent pneumococcal conjugate vaccine; 23-valent pneumococcal polysaccharide vaccine; and recombinant zoster vaccine (latter among patients ≥50 y) was found to be as low as 11%. Hepatitis A IgG total, hepatitis B surface antibody, measles, mumps, rubella, and varicella IgG seropositivity rates were 30%, 66%, 88%, 78%, 90%, and 96%, respectively. Only 7 (5%) of 150 patients had complete immunization or seropositivity. Five (3%) of 143 vaccine-eligible patients declined vaccination. Hepatitis A vaccine declination was relatively common with 15 (16%) of 94 vaccine-eligible patients declining it.
Conclusions: KT candidates have low baseline rates of prior immunization/seropositivity against most recommended vaccines. Overall vaccine uptake among eligible candidates was high.
{"title":"Vaccination in Kidney Transplant Candidates.","authors":"Kiran Gajurel, Tue Ngo, Robert T Fairman, Lewis H McCurdy","doi":"10.1097/TXD.0000000000001544","DOIUrl":"https://doi.org/10.1097/TXD.0000000000001544","url":null,"abstract":"<p><strong>Background: </strong>Kidney transplant (KT) candidates have historically low immunization rates against recommended vaccines. A retrospective single-center study of contemporary KT candidates was conducted to assess vaccination rates and vaccine uptake.</p><p><strong>Methods: </strong>All KT candidates ≥18 y evaluated between January 1, 2020, and December 31, 2020, were retrospectively reviewed for history of prior vaccination against tetanus, diphtheria, and pertussis; 13-valent pneumococcal conjugate vaccine; 23-valent pneumococcal polysaccharide vaccine; and recombinant zoster vaccine. Positive hepatitis A IgG total, hepatitis B surface antibody, measles, mumps, rubella, and varicella IgG were assessed as surrogate markers of immunity. Vaccine uptake among vaccine-eligible candidates was also assessed.</p><p><strong>Results: </strong>Among 150 KT candidates, the rate of prior vaccination against tetanus, diphtheria, and pertussis; 13-valent pneumococcal conjugate vaccine; 23-valent pneumococcal polysaccharide vaccine; and recombinant zoster vaccine (latter among patients ≥50 y) was found to be as low as 11%. Hepatitis A IgG total, hepatitis B surface antibody, measles, mumps, rubella, and varicella IgG seropositivity rates were 30%, 66%, 88%, 78%, 90%, and 96%, respectively. Only 7 (5%) of 150 patients had complete immunization or seropositivity. Five (3%) of 143 vaccine-eligible patients declined vaccination. Hepatitis A vaccine declination was relatively common with 15 (16%) of 94 vaccine-eligible patients declining it.</p><p><strong>Conclusions: </strong>KT candidates have low baseline rates of prior immunization/seropositivity against most recommended vaccines. Overall vaccine uptake among eligible candidates was high.</p>","PeriodicalId":23225,"journal":{"name":"Transplantation Direct","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1c/8e/txd-9-e1544.PMC10540912.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41154024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-20eCollection Date: 2023-10-01DOI: 10.1097/TXD.0000000000001534
Anu K Kaskinen, Juuso Tainio, Jaana I Pihkala, Juha P Peräsaari, Jouni Lauronen, Alireza Raissadati, Jussi M Merenmies, Hannu J Jalanko, Timo Jahnukainen
Background: Immune-mediated factors such as acute cellular rejections and donor-specific antibodies (DSAs) are risk factors for cardiac allograft vasculopathy (CAV). We studied a national cohort with a unified setting and thorough protocol endomyocardial biopsy (EMB) data for an association between cellular rejections, especially when mild and recurrent, and DSAs with CAV in pediatric heart transplant (HTx) patients.
Methods: This is a retrospective, national cohort study of 94 pediatric HTxs performed between 1991 and 2019 and followed until December 31, 2020. Diagnosis of CAV was based on reevaluation of angiographies. Protocol and indication EMB findings with other patient data were collected from medical records. Associations between nonimmune and immune-mediated factors and CAV were analyzed with univariable and multivariable Cox regression analyses.
Results: Angiographies performed on 76 patients revealed CAV in 23 patients (30%). Altogether 1138 EMBs (92% protocol biopsies) were performed on 78 patients (83%). During the first posttransplant year, grade 1 rejection (G1R) appeared in 45 patients (58%), and recurrent (≥2) G1R findings in 14 patients (18%). Pretransplant DSAs occurred in 13 patients (17%) and posttransplant DSAs in 37 patients (39%). In univariable analysis, pretransplant DSAs, appearance and recurrence of G1R findings, and total rejection score during the first posttransplant year, as well as recurrent G1R during follow-up, were all associated with CAV. In multivariable analysis, pretransplant DSAs and recurrent G1R during the first posttransplant year were found to be associated with CAV.
Conclusions: Our results indicate that pretransplant DSA and recurrent G1R findings, especially during the first posttransplant year, are associated with CAV after pediatric HTx.
{"title":"Recurrent Mild Acute Rejections and Donor-specific Antibodies as Risk Factors for Cardiac Allograft Vasculopathy in a National Pediatric Heart Transplant Cohort.","authors":"Anu K Kaskinen, Juuso Tainio, Jaana I Pihkala, Juha P Peräsaari, Jouni Lauronen, Alireza Raissadati, Jussi M Merenmies, Hannu J Jalanko, Timo Jahnukainen","doi":"10.1097/TXD.0000000000001534","DOIUrl":"https://doi.org/10.1097/TXD.0000000000001534","url":null,"abstract":"<p><strong>Background: </strong>Immune-mediated factors such as acute cellular rejections and donor-specific antibodies (DSAs) are risk factors for cardiac allograft vasculopathy (CAV). We studied a national cohort with a unified setting and thorough protocol endomyocardial biopsy (EMB) data for an association between cellular rejections, especially when mild and recurrent, and DSAs with CAV in pediatric heart transplant (HTx) patients.</p><p><strong>Methods: </strong>This is a retrospective, national cohort study of 94 pediatric HTxs performed between 1991 and 2019 and followed until December 31, 2020. Diagnosis of CAV was based on reevaluation of angiographies. Protocol and indication EMB findings with other patient data were collected from medical records. Associations between nonimmune and immune-mediated factors and CAV were analyzed with univariable and multivariable Cox regression analyses.</p><p><strong>Results: </strong>Angiographies performed on 76 patients revealed CAV in 23 patients (30%). Altogether 1138 EMBs (92% protocol biopsies) were performed on 78 patients (83%). During the first posttransplant year, grade 1 rejection (G1R) appeared in 45 patients (58%), and recurrent (≥2) G1R findings in 14 patients (18%). Pretransplant DSAs occurred in 13 patients (17%) and posttransplant DSAs in 37 patients (39%). In univariable analysis, pretransplant DSAs, appearance and recurrence of G1R findings, and total rejection score during the first posttransplant year, as well as recurrent G1R during follow-up, were all associated with CAV. In multivariable analysis, pretransplant DSAs and recurrent G1R during the first posttransplant year were found to be associated with CAV.</p><p><strong>Conclusions: </strong>Our results indicate that pretransplant DSA and recurrent G1R findings, especially during the first posttransplant year, are associated with CAV after pediatric HTx.</p>","PeriodicalId":23225,"journal":{"name":"Transplantation Direct","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d1/f2/txd-9-e1534.PMC10513139.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41155092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-20eCollection Date: 2023-10-01DOI: 10.1097/TXD.0000000000001537
Eunice X Tan, Wen Hui Lim, Elizabeth Thong, Jean-Marc Chavatte, Jinyan Zhang, Jonathan Lim, Jocelyn Y Jin, Daniel R X Lim, Jaclyn Y T Kang, Ansel Shao Pin Tang, Kai En Chan, Caitlyn Tan, Shi Ni Tan, Benjamin Nah, Daniel Q Huang, Lin-Fa Wang, Paul A Tambyah, Jyoti Somani, Barnaby Young, Mark D Muthiah
Background: Immunocompromised individuals have been excluded from landmark studies of messenger RNA vaccinations for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). In such patients, the response to vaccination may be blunted and may wane more quickly compared with immunocompetent patients. We studied the factors associated with decreased antibody response to SARS-CoV-2 vaccination and risk factors for subsequent breakthrough infections in liver transplant (LT) patients undergoing coronavirus disease 2019 vaccination with at least 2 doses of messenger RNA vaccine from April 28, 2021, to April 28, 2022.
Methods: All LT recipients received at least 2 doses of the BNT162b2 (Pfizer BioNTech) vaccine 21 d apart. We measured the antibody response against the SARS-CoV-2 spike protein using the Roche Elecsys immunoassay to the receptor-binding domain of the SARS-CoV-2 spike protein, and the presence of neutralizing antibodies was measured by the surrogate virus neutralization test (cPass) before first and second doses of vaccination and also between 2 and 3 mo after the second dose of vaccination.
Results: Ninety-three LT recipients who received 2 doses of BNT162b2 were included in the analysis. The mean time from LT was 110 ± 154 mo. After 2-dose vaccination, 38.7% of LT recipients (36/93) were vaccine nonresponders on the cPass assay compared with 20.4% (19/93) on the Roche S assay. On multivariable analysis, increased age and increased tacrolimus trough were found to be associated with poor neutralizing antibody response (P = 0.038 and 0.022, respectively). The use of antimetabolite therapy in conjunction with tacrolimus approached statistical significance (odds ratio 0.21; 95% confidence interval, 0.180-3.72; P = 0.062). Breakthrough infection occurred in 18 of 88 LT recipients (20.4%). Female gender was independently associated with breakthrough infections (P < 0.001).
Conclusions: Among LT recipients, older age and higher tacrolimus trough levels were associated with poorer immune response to 2-dose SARS-CoV-2 vaccination. Further studies are needed to assess variables associated with breakthrough infections and, hence, who should be prioritized for booster vaccination.
{"title":"Clinical Course, Immunogenicity, and Efficacy of BNT162b2 mRNA Vaccination Against SARS-CoV-2 Infection in Liver Transplant Recipients.","authors":"Eunice X Tan, Wen Hui Lim, Elizabeth Thong, Jean-Marc Chavatte, Jinyan Zhang, Jonathan Lim, Jocelyn Y Jin, Daniel R X Lim, Jaclyn Y T Kang, Ansel Shao Pin Tang, Kai En Chan, Caitlyn Tan, Shi Ni Tan, Benjamin Nah, Daniel Q Huang, Lin-Fa Wang, Paul A Tambyah, Jyoti Somani, Barnaby Young, Mark D Muthiah","doi":"10.1097/TXD.0000000000001537","DOIUrl":"10.1097/TXD.0000000000001537","url":null,"abstract":"<p><strong>Background: </strong>Immunocompromised individuals have been excluded from landmark studies of messenger RNA vaccinations for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). In such patients, the response to vaccination may be blunted and may wane more quickly compared with immunocompetent patients. We studied the factors associated with decreased antibody response to SARS-CoV-2 vaccination and risk factors for subsequent breakthrough infections in liver transplant (LT) patients undergoing coronavirus disease 2019 vaccination with at least 2 doses of messenger RNA vaccine from April 28, 2021, to April 28, 2022.</p><p><strong>Methods: </strong>All LT recipients received at least 2 doses of the BNT162b2 (Pfizer BioNTech) vaccine 21 d apart. We measured the antibody response against the SARS-CoV-2 spike protein using the Roche Elecsys immunoassay to the receptor-binding domain of the SARS-CoV-2 spike protein, and the presence of neutralizing antibodies was measured by the surrogate virus neutralization test (cPass) before first and second doses of vaccination and also between 2 and 3 mo after the second dose of vaccination.</p><p><strong>Results: </strong>Ninety-three LT recipients who received 2 doses of BNT162b2 were included in the analysis. The mean time from LT was 110 ± 154 mo. After 2-dose vaccination, 38.7% of LT recipients (36/93) were vaccine nonresponders on the cPass assay compared with 20.4% (19/93) on the Roche S assay. On multivariable analysis, increased age and increased tacrolimus trough were found to be associated with poor neutralizing antibody response (<i>P</i> = 0.038 and 0.022, respectively). The use of antimetabolite therapy in conjunction with tacrolimus approached statistical significance (odds ratio 0.21; 95% confidence interval, 0.180-3.72; <i>P</i> = 0.062). Breakthrough infection occurred in 18 of 88 LT recipients (20.4%). Female gender was independently associated with breakthrough infections (<i>P</i> < 0.001).</p><p><strong>Conclusions: </strong>Among LT recipients, older age and higher tacrolimus trough levels were associated with poorer immune response to 2-dose SARS-CoV-2 vaccination. Further studies are needed to assess variables associated with breakthrough infections and, hence, who should be prioritized for booster vaccination.</p>","PeriodicalId":23225,"journal":{"name":"Transplantation Direct","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/12/bd/txd-9-e1537.PMC10513132.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41152359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-20eCollection Date: 2023-10-01DOI: 10.1097/TXD.0000000000001535
Verena Broecker, Mats Brännström, Hans Bösmüller, Eva Sticová, Jana Malušková, Andres Chiesa-Vottero, Johan Mölne
Background: Diagnosis of rejection after uterus transplantation is based on histopathological examination of ectocervical biopsies. Inflammation at the stromal-epithelial interface is the backbone of the histopathological classification proposed by our group in 2017. However, the reproducibility of this grading scheme has not been tested, and it is unclear whether it covers the full morphological spectrum of rejection.
Methods: We present a multicenter study in which 5 pathologists from 4 uterus transplantation centers performed 2 rounds of grading on 145 and 48 cervical biopsies, respectively. Three of the centers provided biopsies. Additionally, the presence of perivascular stromal inflammation was recorded. During discussions after the first round, further histological lesions (venous endothelial inflammation and apoptosis) were identified for closer evaluation and added to the panel of lesions to score in the second round. All participants completed a questionnaire to explore current practices in handling and reporting uterus transplant biopsies.
Results: Cervical biopsies were commonly performed in all centers to monitor rejection. Intraobserver reproducibility of rejection grading (performed by 1 rater) was excellent, whereas interobserver reproducibility was moderate and did not improve in the second round. Reproducibility of perivascular stromal inflammation was moderate but unsatisfactory for venous endothelial inflammation and apoptosis. All lesions were more frequent in, but not restricted to, biopsies with rejection patterns.
Conclusions: Grading of rejection in cervical biopsies is reproducible and applicable to biopsies from different centers. Diagnosis of rejection may be improved by adding further histological lesions to the grading system; however, lesions require rigorous consensus definition.
{"title":"Reproducibility of Rejection Grading in Uterus Transplantation: A Multicenter Study.","authors":"Verena Broecker, Mats Brännström, Hans Bösmüller, Eva Sticová, Jana Malušková, Andres Chiesa-Vottero, Johan Mölne","doi":"10.1097/TXD.0000000000001535","DOIUrl":"https://doi.org/10.1097/TXD.0000000000001535","url":null,"abstract":"<p><strong>Background: </strong>Diagnosis of rejection after uterus transplantation is based on histopathological examination of ectocervical biopsies. Inflammation at the stromal-epithelial interface is the backbone of the histopathological classification proposed by our group in 2017. However, the reproducibility of this grading scheme has not been tested, and it is unclear whether it covers the full morphological spectrum of rejection.</p><p><strong>Methods: </strong>We present a multicenter study in which 5 pathologists from 4 uterus transplantation centers performed 2 rounds of grading on 145 and 48 cervical biopsies, respectively. Three of the centers provided biopsies. Additionally, the presence of perivascular stromal inflammation was recorded. During discussions after the first round, further histological lesions (venous endothelial inflammation and apoptosis) were identified for closer evaluation and added to the panel of lesions to score in the second round. All participants completed a questionnaire to explore current practices in handling and reporting uterus transplant biopsies.</p><p><strong>Results: </strong>Cervical biopsies were commonly performed in all centers to monitor rejection. Intraobserver reproducibility of rejection grading (performed by 1 rater) was excellent, whereas interobserver reproducibility was moderate and did not improve in the second round. Reproducibility of perivascular stromal inflammation was moderate but unsatisfactory for venous endothelial inflammation and apoptosis. All lesions were more frequent in, but not restricted to, biopsies with rejection patterns.</p><p><strong>Conclusions: </strong>Grading of rejection in cervical biopsies is reproducible and applicable to biopsies from different centers. Diagnosis of rejection may be improved by adding further histological lesions to the grading system; however, lesions require rigorous consensus definition.</p>","PeriodicalId":23225,"journal":{"name":"Transplantation Direct","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9d/89/txd-9-e1535.PMC10513355.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41163704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-20eCollection Date: 2023-10-01DOI: 10.1097/TXD.0000000000001536
Mario Fernández-Ruiz, Patricia Almendro-Vázquez, Natalia Redondo, Tamara Ruiz-Merlo, Sandra Abella, Adán Somoza, Francisco López-Medrano, Rafael San Juan, Carmelo Loinaz, Amado Andrés, Estela Paz-Artal, José María Aguado
Background: The immunogenicity elicited by the Omicron BA.4/BA.5-adapted bivalent booster vaccine after solid organ transplantation (SOT) has not been characterized.
Methods: We assessed cell-mediated and neutralizing IgG antibody responses against the BA.4/BA.5 spike receptor-binding domain at baseline and 2 wk after the administration of an mRNA-based bivalent (ancestral strain and BA.4/BA.5 subvariants) vaccine among 30 SOT recipients who had received ≥3 monovalent vaccine doses. Previous coronavirus disease 2019 history was present in 46.7% of them. We also recruited a control group of 19 nontransplant healthy individuals. Cell-mediated immunity was measured by fluorescent ELISpot assay for interferon (IFN)-γ secretion, whereas the neutralizing IgG antibody response against the BA.4/BA.5 spike receptor-binding domain was quantified with a competitive ELISA.
Results: The median number of BA.4/BA.5 spike-specific IFN-γ-producing spot-forming units (SFUs) increased from baseline to 2 wk postbooster (83.8 versus 133.0 SFUs/106 peripheral blood mononuclear cells; P = 0.0017). Seropositivity rate also increased (46.7%-83.3%; P = 0.001), as well as serum neutralizing activity (4.2%-78.3%; P < 0.0001). Patients with no prior coronavirus disease 2019 history experienced higher improvements in cell-mediated and neutralizing responses after booster vaccination. There was no correlation between BA.4/BA.5 spike-specific IFN-γ-producing SFUs and neutralizing activity. Nontransplant controls showed more robust postbooster cell-mediated immunity than SOT recipients (591.1 versus 133.0 IFN-γ-producing SFUs/106 peripheral blood mononuclear cells; P < 0.0001), although no differences were observed for antibody responses in terms of postbooster seropositivity rates or neutralizing activity.
Conclusions: Booster with the BA.4/BA.5-adapted bivalent vaccine generated strong subvariant-specific responses among SOT recipients. Booster-induced cell-mediated immunity, however, remained lower than in immunocompetent individuals.
{"title":"Cell-mediated and Neutralizing Antibody Responses to the SARS-CoV-2 Omicron BA.4/BA.5-adapted Bivalent Vaccine Booster in Kidney and Liver Transplant Recipients.","authors":"Mario Fernández-Ruiz, Patricia Almendro-Vázquez, Natalia Redondo, Tamara Ruiz-Merlo, Sandra Abella, Adán Somoza, Francisco López-Medrano, Rafael San Juan, Carmelo Loinaz, Amado Andrés, Estela Paz-Artal, José María Aguado","doi":"10.1097/TXD.0000000000001536","DOIUrl":"10.1097/TXD.0000000000001536","url":null,"abstract":"<p><strong>Background: </strong>The immunogenicity elicited by the Omicron BA.4/BA.5-adapted bivalent booster vaccine after solid organ transplantation (SOT) has not been characterized.</p><p><strong>Methods: </strong>We assessed cell-mediated and neutralizing IgG antibody responses against the BA.4/BA.5 spike receptor-binding domain at baseline and 2 wk after the administration of an mRNA-based bivalent (ancestral strain and BA.4/BA.5 subvariants) vaccine among 30 SOT recipients who had received ≥3 monovalent vaccine doses. Previous coronavirus disease 2019 history was present in 46.7% of them. We also recruited a control group of 19 nontransplant healthy individuals. Cell-mediated immunity was measured by fluorescent ELISpot assay for interferon (IFN)-γ secretion, whereas the neutralizing IgG antibody response against the BA.4/BA.5 spike receptor-binding domain was quantified with a competitive ELISA.</p><p><strong>Results: </strong>The median number of BA.4/BA.5 spike-specific IFN-γ-producing spot-forming units (SFUs) increased from baseline to 2 wk postbooster (83.8 versus 133.0 SFUs/10<sup>6</sup> peripheral blood mononuclear cells; <i>P</i> = 0.0017). Seropositivity rate also increased (46.7%-83.3%; <i>P</i> = 0.001), as well as serum neutralizing activity (4.2%-78.3%; <i>P</i> < 0.0001). Patients with no prior coronavirus disease 2019 history experienced higher improvements in cell-mediated and neutralizing responses after booster vaccination. There was no correlation between BA.4/BA.5 spike-specific IFN-γ-producing SFUs and neutralizing activity. Nontransplant controls showed more robust postbooster cell-mediated immunity than SOT recipients (591.1 versus 133.0 IFN-γ-producing SFUs/10<sup>6</sup> peripheral blood mononuclear cells; <i>P</i> < 0.0001), although no differences were observed for antibody responses in terms of postbooster seropositivity rates or neutralizing activity.</p><p><strong>Conclusions: </strong>Booster with the BA.4/BA.5-adapted bivalent vaccine generated strong subvariant-specific responses among SOT recipients. Booster-induced cell-mediated immunity, however, remained lower than in immunocompetent individuals.</p>","PeriodicalId":23225,"journal":{"name":"Transplantation Direct","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ff/09/txd-9-e1536.PMC10513127.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41172077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-20eCollection Date: 2023-10-01DOI: 10.1097/TXD.0000000000001533
Nynke Wijbenga, Nadine L A de Jong, Rogier A S Hoek, Bas J Mathot, Leonard Seghers, Joachim G J V Aerts, Daniel Bos, Olivier C Manintveld, Merel E Hellemons
Background: Bacterial colonization (BC) of the lower airways is common in lung transplant recipients (LTRs) and increases the risk of chronic lung allograft dysfunction. Diagnosis often requires bronchoscopy. Exhaled breath analysis using electronic nose (eNose) technology may noninvasively detect BC in LTRs. Therefore, we aimed to assess the diagnostic accuracy of an eNose to detect BC in LTRs.
Methods: We performed a cross-sectional analysis within a prospective, single-center cohort study assessing the diagnostic accuracy of detecting BC using eNose technology in LTRs. In the outpatient clinic, consecutive LTR eNose measurements were collected. We assessed and classified the eNose measurements for the presence of BC. Using supervised machine learning, the diagnostic accuracy of eNose for BC was assessed in a random training and validation set. Model performance was evaluated using receiver operating characteristic analysis.
Results: In total, 161 LTRs were included with 80 exclusions because of various reasons. Of the remaining 81 patients, 16 (20%) were classified as BC and 65 (80%) as non-BC. eNose-based classification of patients with and without BC provided an area under the curve of 0.82 in the training set and 0.97 in the validation set.
Conclusions: Exhaled breath analysis using eNose technology has the potential to noninvasively detect BC.
{"title":"Detection of Bacterial Colonization in Lung Transplant Recipients Using an Electronic Nose.","authors":"Nynke Wijbenga, Nadine L A de Jong, Rogier A S Hoek, Bas J Mathot, Leonard Seghers, Joachim G J V Aerts, Daniel Bos, Olivier C Manintveld, Merel E Hellemons","doi":"10.1097/TXD.0000000000001533","DOIUrl":"https://doi.org/10.1097/TXD.0000000000001533","url":null,"abstract":"<p><strong>Background: </strong>Bacterial colonization (BC) of the lower airways is common in lung transplant recipients (LTRs) and increases the risk of chronic lung allograft dysfunction. Diagnosis often requires bronchoscopy. Exhaled breath analysis using electronic nose (eNose) technology may noninvasively detect BC in LTRs. Therefore, we aimed to assess the diagnostic accuracy of an eNose to detect BC in LTRs.</p><p><strong>Methods: </strong>We performed a cross-sectional analysis within a prospective, single-center cohort study assessing the diagnostic accuracy of detecting BC using eNose technology in LTRs. In the outpatient clinic, consecutive LTR eNose measurements were collected. We assessed and classified the eNose measurements for the presence of BC. Using supervised machine learning, the diagnostic accuracy of eNose for BC was assessed in a random training and validation set. Model performance was evaluated using receiver operating characteristic analysis.</p><p><strong>Results: </strong>In total, 161 LTRs were included with 80 exclusions because of various reasons. Of the remaining 81 patients, 16 (20%) were classified as BC and 65 (80%) as non-BC. eNose-based classification of patients with and without BC provided an area under the curve of 0.82 in the training set and 0.97 in the validation set.</p><p><strong>Conclusions: </strong>Exhaled breath analysis using eNose technology has the potential to noninvasively detect BC.</p>","PeriodicalId":23225,"journal":{"name":"Transplantation Direct","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a0/37/txd-9-e1533.PMC10513211.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41172135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1097/TXD.0000000000001530
Eswari Vilayur, Anita van Zwieten, Mingxing Chen, Anna Francis, Melanie Wyld, Siah Kim, Tess Cooper, Germaine Wong
Background: Women are more likely than men to be living kidney donors. We summarized the evidence concerning the reasons behind sex and gender disparities in living kidney donation (LKD).
Methods: A scoping review of quantitative and qualitative evidence on reasons for sex and gender disparities in LKD was conducted from inception to March 2023.
Results: Of 1123 studies screened, 45 were eligible for inclusion. Most studies were from North America, Europe, and Central Asia (n = 33, 73%). A predominance of women as living donors (55%-65%) was observed in 15 out of 18 (83%) studies. Reasons for sex and gender disparities in LKD included socioeconomic, biological, and cognitive or emotional factors. A gendered division of roles within the families was observed in most studies, with men being the primary income earner and women being the main caregiver. Fear of loss of income was a barrier to male donation. Human leukocyte antigen sensitization through pregnancy in female recipients precluded male partner donation, whereas female donation was supported by altruism and a positive attitude toward LKD.
Conclusions: Sex imbalance in LKD is prevalent, with a predominance of women as living donors. Such disparities are driven by societal and cultural perceptions of gender roles, pregnancy-induced sensitization, and attitudes toward donation and at least some of these factors are modifiable. Donor compensation to support predonation assessments and income loss, implementation of innovative desensitization treatments, promotion of paired kidney exchange program, and targeted educational initiatives to promote equitable living donation may help to close the gender gap in LKD.
{"title":"Sex and Gender Disparities in Living Kidney Donation: A Scoping Review.","authors":"Eswari Vilayur, Anita van Zwieten, Mingxing Chen, Anna Francis, Melanie Wyld, Siah Kim, Tess Cooper, Germaine Wong","doi":"10.1097/TXD.0000000000001530","DOIUrl":"https://doi.org/10.1097/TXD.0000000000001530","url":null,"abstract":"<p><strong>Background: </strong>Women are more likely than men to be living kidney donors. We summarized the evidence concerning the reasons behind sex and gender disparities in living kidney donation (LKD).</p><p><strong>Methods: </strong>A scoping review of quantitative and qualitative evidence on reasons for sex and gender disparities in LKD was conducted from inception to March 2023.</p><p><strong>Results: </strong>Of 1123 studies screened, 45 were eligible for inclusion. Most studies were from North America, Europe, and Central Asia (n = 33, 73%). A predominance of women as living donors (55%-65%) was observed in 15 out of 18 (83%) studies. Reasons for sex and gender disparities in LKD included socioeconomic, biological, and cognitive or emotional factors. A gendered division of roles within the families was observed in most studies, with men being the primary income earner and women being the main caregiver. Fear of loss of income was a barrier to male donation. Human leukocyte antigen sensitization through pregnancy in female recipients precluded male partner donation, whereas female donation was supported by altruism and a positive attitude toward LKD.</p><p><strong>Conclusions: </strong>Sex imbalance in LKD is prevalent, with a predominance of women as living donors. Such disparities are driven by societal and cultural perceptions of gender roles, pregnancy-induced sensitization, and attitudes toward donation and at least some of these factors are modifiable. Donor compensation to support predonation assessments and income loss, implementation of innovative desensitization treatments, promotion of paired kidney exchange program, and targeted educational initiatives to promote equitable living donation may help to close the gender gap in LKD.</p>","PeriodicalId":23225,"journal":{"name":"Transplantation Direct","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4d/e2/txd-9-e1530.PMC10455160.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10482371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1097/TXD.0000000000001512
Joshua Weiner, Nathaly Llore, Dylan Ormsby, Masato Fujiki, Maria Cristina Segovia, Mark Obri, Syed-Mohammed Jafri, Jedson Liggett, Alexander H K Kroemer, Cal Matsumoto, Jang Moon, Pierpaolo Di Cocco, Gennaro Selvaggi, Jennifer Garcia, Armando Ganoza, Ajai Khanna, George Mazariegos, Danielle Wendel, Jorge Reyes
Background: Unlike other solid organs, no standardized treatment algorithms exist for intestinal transplantation (ITx). We established a consortium of American ITx centers to evaluate current practices.
Methods: All American centers performing ITx during the past 3 y were invited to participate. As a consortium, we generated questions to evaluate and collect data from each institution. The data were compiled and analyzed.
Results: Ten centers participated, performing 211 ITx during the past 3 y (range, 3-46; mean 21.1). Induction regimens varied widely. Thymoglobulin was the most common, used in the plurality of patients (85/211; 40.3%), but there was no consensus regimen. Similarly, regimens for the treatment of acute cellular rejection, antibody-mediated rejection, and graft-versus-host disease varied significantly between centers. We also evaluated differences in maintenance immunosuppression protocols, desensitization regimens, mammalian target of rapamycin use, antimetabolite use, and posttransplantation surveillance practices. Maintenance tacrolimus levels, stoma presence, and scoping frequency were not associated with differences in rejection events. Definitive association between treatments and outcomes, including graft and patient survival, was not the intention of this initial collaboration and is prevented by the lack of patient-level data and the presence of confounders. However, we identified trends regarding rejection episodes after various induction strategies that require further investigation in our subsequent collaborations.
Conclusions: This initial collaboration reveals the extreme heterogeneity of practices among American ITx centers. Future collaboration will explore patient-level data, stratified by age and transplant type (isolated intestine versus multivisceral), to explore the association between treatment regimens and outcomes.
{"title":"The First Collective Examination of Immunosuppressive Practices Among American Intestinal Transplant Centers.","authors":"Joshua Weiner, Nathaly Llore, Dylan Ormsby, Masato Fujiki, Maria Cristina Segovia, Mark Obri, Syed-Mohammed Jafri, Jedson Liggett, Alexander H K Kroemer, Cal Matsumoto, Jang Moon, Pierpaolo Di Cocco, Gennaro Selvaggi, Jennifer Garcia, Armando Ganoza, Ajai Khanna, George Mazariegos, Danielle Wendel, Jorge Reyes","doi":"10.1097/TXD.0000000000001512","DOIUrl":"https://doi.org/10.1097/TXD.0000000000001512","url":null,"abstract":"<p><strong>Background: </strong>Unlike other solid organs, no standardized treatment algorithms exist for intestinal transplantation (ITx). We established a consortium of American ITx centers to evaluate current practices.</p><p><strong>Methods: </strong>All American centers performing ITx during the past 3 y were invited to participate. As a consortium, we generated questions to evaluate and collect data from each institution. The data were compiled and analyzed.</p><p><strong>Results: </strong>Ten centers participated, performing 211 ITx during the past 3 y (range, 3-46; mean 21.1). Induction regimens varied widely. Thymoglobulin was the most common, used in the plurality of patients (85/211; 40.3%), but there was no consensus regimen. Similarly, regimens for the treatment of acute cellular rejection, antibody-mediated rejection, and graft-versus-host disease varied significantly between centers. We also evaluated differences in maintenance immunosuppression protocols, desensitization regimens, mammalian target of rapamycin use, antimetabolite use, and posttransplantation surveillance practices. Maintenance tacrolimus levels, stoma presence, and scoping frequency were not associated with differences in rejection events. Definitive association between treatments and outcomes, including graft and patient survival, was not the intention of this initial collaboration and is prevented by the lack of patient-level data and the presence of confounders. However, we identified trends regarding rejection episodes after various induction strategies that require further investigation in our subsequent collaborations.</p><p><strong>Conclusions: </strong>This initial collaboration reveals the extreme heterogeneity of practices among American ITx centers. Future collaboration will explore patient-level data, stratified by age and transplant type (isolated intestine versus multivisceral), to explore the association between treatment regimens and outcomes.</p>","PeriodicalId":23225,"journal":{"name":"Transplantation Direct","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/03/ca/txd-9-e1512.PMC10455426.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10160439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1097/TXD.0000000000001510
John Fallon, Anito Rendek, Paul Harden, Venkatesha Udupa
E pstein-Barr virus (EBV) is pervasive, with a significant proportion of humans being asymptomatic carriers. Latent infection risk is an issue in the immunosuppressed because of the exerted effects of expressed viral proteins on B-lymphocyte maturation and proliferation or because of T-lymphocyte reaction. 1,2 This interaction produces a spectrum of lymphoproliferative disorders that includes EBV-mucocutaneous ulcer (MCU), in which the most severe disease process on the spectrum is posttransplant lymphoproliferative disorder (PTLD). 3 EBV-MCU is separate from PTLD, because of its indolent clinical course, without its progression to disseminated disease, and despite a significant degree of cytological atypia seen histologically. 4 Although it may not disseminate, it can be locally destructive and, in the case we discuss here, is the only EBV-MCU in the literature in the rectal mucosa to pre-sent with rectal hemorrhage. Hemorrhage in a young post-transplant patient is difficult to manage, given reluctance for multiple sensitizing blood transfusions, especially if, as in this case, they are reliant on anticoagulation.
{"title":"Donor-derived Epstein-Barr Virus Mucocutaneous Ulceration: A Unique and Complex Case of Rectal Hemorrhage.","authors":"John Fallon, Anito Rendek, Paul Harden, Venkatesha Udupa","doi":"10.1097/TXD.0000000000001510","DOIUrl":"https://doi.org/10.1097/TXD.0000000000001510","url":null,"abstract":"E pstein-Barr virus (EBV) is pervasive, with a significant proportion of humans being asymptomatic carriers. Latent infection risk is an issue in the immunosuppressed because of the exerted effects of expressed viral proteins on B-lymphocyte maturation and proliferation or because of T-lymphocyte reaction. 1,2 This interaction produces a spectrum of lymphoproliferative disorders that includes EBV-mucocutaneous ulcer (MCU), in which the most severe disease process on the spectrum is posttransplant lymphoproliferative disorder (PTLD). 3 EBV-MCU is separate from PTLD, because of its indolent clinical course, without its progression to disseminated disease, and despite a significant degree of cytological atypia seen histologically. 4 Although it may not disseminate, it can be locally destructive and, in the case we discuss here, is the only EBV-MCU in the literature in the rectal mucosa to pre-sent with rectal hemorrhage. Hemorrhage in a young post-transplant patient is difficult to manage, given reluctance for multiple sensitizing blood transfusions, especially if, as in this case, they are reliant on anticoagulation.","PeriodicalId":23225,"journal":{"name":"Transplantation Direct","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bb/1f/txd-9-e1510.PMC10414712.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9998228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}