This study investigated the impact of immunosuppressive drug concentrations on microvascular inflammation (MVI) in kidney transplant recipients with negative donor-specific antibodies (DSA) against human leukocyte antigen (HLA) and negative C4d deposition in peritubular capillaries.
Methods
We analyzed data from 268 living kidney transplant recipients at the Department of Urology, University of Osaka, Japan. Patients received immunosuppressive therapy comprising extended-release tacrolimus, mycophenolate mofetil (MMF), and/or everolimus, with or without steroids. Graft biopsies were routinely performed at 3, 12, 36 and 60 months post-surgery.
Results
No significant differences were observed between the MVI+DSA-C4d- and MVI-DSAC4d groups regarding graft survival rates (95.5% vs. 96.6%, p = 0.772) or patient survival rates (95.7% vs. 95.9%, p = 0.735). Lower tacrolimus and everolimus concentrations were significantly associated with an increased risk of MVI+DSA-C4d- (tacrolimus: OR, 0.169; 95% CI, 0.055–0.515; p = 0.002; everolimus: OR, 0.386; 95% CI, 0.171–0.874; p = 0.022). In contrast, MPA concentration was not significantly associated with MVI+DSA-C4d- (OR, 0.994; 95% CI, 0.554–1.780; p = 0.984). Steroid discontinuation did not significantly impact the risk of MVI+DSA-C4d- (OR, 1.980; 95% CI, 0.318–12.000; p = 0.470).
Conclusion
Lower trough levels of tacrolimus and everolimus correlated with a higher incidence of antibody-independent MVI, supporting the need for tailored immunosuppressive regimens in kidney transplantation.
{"title":"Impact of Immunosuppressive Drug Concentrations on Microvascular Inflammation, Negative Donor-Specific Antibodies, and C4d-Negative Status in Kidney Transplant Recipients","authors":"Yoichi Kakuta, Yoko Maegawa-Higa, Soichi Matsumura, Shota Fukae, Ryo Tanaka, Hiroaki Yonishi, Shigeaki Nakazawa, Tomoko Namba-Hamano, Yoshitaka Isaka, Norio Nonomura","doi":"10.1111/ctr.70112","DOIUrl":"https://doi.org/10.1111/ctr.70112","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>This study investigated the impact of immunosuppressive drug concentrations on microvascular inflammation (MVI) in kidney transplant recipients with negative donor-specific antibodies (DSA) against human leukocyte antigen (HLA) and negative C4d deposition in peritubular capillaries.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed data from 268 living kidney transplant recipients at the Department of Urology, University of Osaka, Japan. Patients received immunosuppressive therapy comprising extended-release tacrolimus, mycophenolate mofetil (MMF), and/or everolimus, with or without steroids. Graft biopsies were routinely performed at 3, 12, 36 and 60 months post-surgery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No significant differences were observed between the MVI+DSA-C4d- and MVI-DSAC4d groups regarding graft survival rates (95.5% vs. 96.6%, <i>p</i> = 0.772) or patient survival rates (95.7% vs. 95.9%, <i>p</i> = 0.735). Lower tacrolimus and everolimus concentrations were significantly associated with an increased risk of MVI+DSA-C4d- (tacrolimus: OR, 0.169; 95% CI, 0.055–0.515; <i>p</i> = 0.002; everolimus: OR, 0.386; 95% CI, 0.171–0.874; <i>p</i> = 0.022). In contrast, MPA concentration was not significantly associated with MVI+DSA-C4d- (OR, 0.994; 95% CI, 0.554–1.780; <i>p</i> = 0.984). Steroid discontinuation did not significantly impact the risk of MVI+DSA-C4d- (OR, 1.980; 95% CI, 0.318–12.000; <i>p</i> = 0.470).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Lower trough levels of tacrolimus and everolimus correlated with a higher incidence of antibody-independent MVI, supporting the need for tailored immunosuppressive regimens in kidney transplantation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"39 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ctr.70112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143455769","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}
David M. Salerno, Mia Genovese, Arun Jesudian, Erica Roman, Mashal Khan, Benjamin Samstein, Danielle Brandman
Enhanced recovery after surgery protocols have been shown to reduce length of stay in transplant patients. The purpose of our study was to evaluate the impact of a standardized protocol in liver transplant recipients (LTR) on length of stay (LOS) and delirium during the index hospitalization post-LT. Elements of the protocol included reduced intraoperative corticosteroids (from methylprednisolone 1000 to 250 mg), conversion of steroid taper to be administered once-daily instead of BID, optimal end-of-case intraoperative extubation, multimodal analgesia, early removal of surgical drains, implementation of dietary and physical therapy plans and education for multidisciplinary providers and patients about expected LOS. The primary outcome was post-LT LOS. Secondary outcomes included incidence of delirium, ICU LOS, rejection at 60 days and readmission within 30 days of discharge. A total of 125 LTRs were included. Baseline characteristics were similar between groups. The median LOS was 12 days (IQR, 9–19) and 10 days (IQR, 8–15) in the pre- and post-implementation groups, respectively (p = 0.025). ICU LOS was 2.9 (IQR, 2.1–4) and 2.7 (IQR, 1.9–3.7) in the pre- and post-implementation groups, respectively (p = 0.525). In the pre- and post-implementation groups, the incidence of delirium was 17 (25.8%) and 5 (8.6%), respectively (p = 0.013). The incidence of treated rejection at 60 days was 3% (0.0–10.1) and 5.2% (2.9–15.2) in the pre- and post-implementation groups, respectively (p = 0.550). Implementation of a Fast Track protocol in a high acuity LTR was feasible and safe and was associated with a reduction in LOS.
{"title":"Liver Transplant Fast-Track With an Emphasis on Reduced Delirium: A Multidisciplinary Approach to Reducing Length of Stay","authors":"David M. Salerno, Mia Genovese, Arun Jesudian, Erica Roman, Mashal Khan, Benjamin Samstein, Danielle Brandman","doi":"10.1111/ctr.70111","DOIUrl":"https://doi.org/10.1111/ctr.70111","url":null,"abstract":"<div>\u0000 \u0000 <p>Enhanced recovery after surgery protocols have been shown to reduce length of stay in transplant patients. The purpose of our study was to evaluate the impact of a standardized protocol in liver transplant recipients (LTR) on length of stay (LOS) and delirium during the index hospitalization post-LT. Elements of the protocol included reduced intraoperative corticosteroids (from methylprednisolone 1000 to 250 mg), conversion of steroid taper to be administered once-daily instead of BID, optimal end-of-case intraoperative extubation, multimodal analgesia, early removal of surgical drains, implementation of dietary and physical therapy plans and education for multidisciplinary providers and patients about expected LOS. The primary outcome was post-LT LOS. Secondary outcomes included incidence of delirium, ICU LOS, rejection at 60 days and readmission within 30 days of discharge. A total of 125 LTRs were included. Baseline characteristics were similar between groups. The median LOS was 12 days (IQR, 9–19) and 10 days (IQR, 8–15) in the pre- and post-implementation groups, respectively (<i>p</i> = 0.025). ICU LOS was 2.9 (IQR, 2.1–4) and 2.7 (IQR, 1.9–3.7) in the pre- and post-implementation groups, respectively (<i>p</i> = 0.525). In the pre- and post-implementation groups, the incidence of delirium was 17 (25.8%) and 5 (8.6%), respectively (<i>p</i> = 0.013). The incidence of treated rejection at 60 days was 3% (0.0–10.1) and 5.2% (2.9–15.2) in the pre- and post-implementation groups, respectively (<i>p</i> = 0.550). Implementation of a Fast Track protocol in a high acuity LTR was feasible and safe and was associated with a reduction in LOS.</p>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"39 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Flying Kidneys or Flying Donors: What Do Prior Canadian Living Kidney Donors Think?","authors":"Katya Loban, Kathleen Gaudio, Shaifali Sandal","doi":"10.1111/ctr.70115","DOIUrl":"https://doi.org/10.1111/ctr.70115","url":null,"abstract":"","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"39 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431340","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}
Amiti Jain, Christopher Pritting, Andrew Brodie, Daler Rahimov, Danial Ahmad, J. Eduardo Rame, Rene Alvarez, Keshava Rajagopal, John W. Entwistle, Vakhtang Tchantchaleishvili
Background
Predicted heart mass (PHM) ratio is a commonly used metric for donor-to-recipient size matching that has been associated with survival after heart transplantation (HTx). PHM represents a sum of two separate statistical models for predicted left ventricular mass (PLVM) and predicted right ventricular mass (PRVM); however, their individual contributions have not been sufficiently studied. We sought to assess the association of donor-to-recipient PLVM (PLVMR) and PRVM ratios (PRVMR) with overall posttransplant survival individually.
Methods
Adult heart transplant recipients from 2005 to 2021 were queried from the UNOS database. A three-dimensional tensor product spline model assessed the association of PLVMR and PRVMR with survival simultaneously on a continuous distribution. Subsequently, PLVMR and PRVMR were explored individually using individual restricted cubic spline models.
Results
A total of 25 549 patients were analyzed. Of these, female recipients comprised 26.7% (n = 6818), and the median age was 56 [IQR 46–63] years. In the three-dimensional restricted cubic spline (3D-RCS) model, PLVMR and PRVMR were significantly associated with survival (p value: overall = 0.002, PLVMR = 0.0006, PRVMR = 0.0006, PLVMR*PRVMR = 0.0002). When analyzed with two-dimensional restricted cubic spline (2D-RCS) models, PLVMR was not associated with survival (p = 0.59), while PRVMR retained its significant association (p = 0.04).
Conclusion
While both PLVMR and PRVMR appear to be associated with posttransplant survival, the effect of PRVMR might be disproportionately high as PRVM makes up a much smaller fraction of PHM than PLVM.
{"title":"Individual Association of Predicted Left and Right Ventricular Mass Ratios With Survival After Heart Transplantation: A UNOS Database Analysis","authors":"Amiti Jain, Christopher Pritting, Andrew Brodie, Daler Rahimov, Danial Ahmad, J. Eduardo Rame, Rene Alvarez, Keshava Rajagopal, John W. Entwistle, Vakhtang Tchantchaleishvili","doi":"10.1111/ctr.70113","DOIUrl":"https://doi.org/10.1111/ctr.70113","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Predicted heart mass (PHM) ratio is a commonly used metric for donor-to-recipient size matching that has been associated with survival after heart transplantation (HTx). PHM represents a sum of two separate statistical models for predicted left ventricular mass (PLVM) and predicted right ventricular mass (PRVM); however, their individual contributions have not been sufficiently studied. We sought to assess the association of donor-to-recipient PLVM (PLVMR) and PRVM ratios (PRVMR) with overall posttransplant survival individually.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Adult heart transplant recipients from 2005 to 2021 were queried from the UNOS database. A three-dimensional tensor product spline model assessed the association of PLVMR and PRVMR with survival simultaneously on a continuous distribution. Subsequently, PLVMR and PRVMR were explored individually using individual restricted cubic spline models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 25 549 patients were analyzed. Of these, female recipients comprised 26.7% (<i>n</i> = 6818), and the median age was 56 [IQR 46–63] years. In the three-dimensional restricted cubic spline (3D-RCS) model, PLVMR and PRVMR were significantly associated with survival (<i>p</i> value: overall = 0.002, PLVMR = 0.0006, PRVMR = 0.0006, PLVMR*PRVMR = 0.0002). When analyzed with two-dimensional restricted cubic spline (2D-RCS) models, PLVMR was not associated with survival (<i>p</i> = 0.59), while PRVMR retained its significant association (<i>p</i> = 0.04).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>While both PLVMR and PRVMR appear to be associated with posttransplant survival, the effect of PRVMR might be disproportionately high as PRVM makes up a much smaller fraction of PHM than PLVM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"39 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431393","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}
Anaïs R. Briant, Rémy Morello, Olivier Sérée, Nicolas Vigneron, Sarah Wilson, Camille Besch, Pauline Houssel-Debry, Georges-Philippe Pageaux, Audrey Coilly, Jérôme Dumortier, Mario Altieri
Background and Aim
De novo cancers after liver transplantation (LT) are major causes of complications and mortality after LT. No report was found in the literature on several successive cancers (SSC). The aim of this study was to see if the survival of one or more cancers was different and to study the survival prognostic factors of patients with one cancer or SSC after LT.
Methods
Using data from the French national database, 114 French patients who underwent LT between 1993 and 2012 were followed up until their death or until June 2016. The Cox model performed to analyze potential risk factors (cancer characteristics, immunosuppressive therapy (IT), smoking, and alcohol use).
Results
After an average follow-up of 9.8 ± 5.1 years, 52 patients developed 1 cancer, 49 had 2 cancers, and 13 had 3 cancers. The reduction in survival time was significantly and independently associated with the metastatic stage (hazard ratio (HR) = 3.98, 95% confidence interval (95% CI) = [1.45–10.93], p < 0.001), ENT (otolaryngology), and respiratory cancer versus genitourinary (HR = 8.28, 95% CI = [3.12–22.02], p < 0.001), and SSC (HR = 2.54, 95% CI = [1.39–4.65], p = 0.014).
Conclusion
The patients with ENT, respiratory cancers have a shorter survival. The stage of cancer and SSC reduces median survival at 10 years. The earliness of the first cancer should be taken as a warning signal of risk of SSC and impaired survival.
{"title":"Is Survival Impacted by One or Several Successive Cancers After Liver Transplantation? A French National Study","authors":"Anaïs R. Briant, Rémy Morello, Olivier Sérée, Nicolas Vigneron, Sarah Wilson, Camille Besch, Pauline Houssel-Debry, Georges-Philippe Pageaux, Audrey Coilly, Jérôme Dumortier, Mario Altieri","doi":"10.1111/ctr.70109","DOIUrl":"https://doi.org/10.1111/ctr.70109","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aim</h3>\u0000 \u0000 <p>De novo cancers after liver transplantation (LT) are major causes of complications and mortality after LT. No report was found in the literature on several successive cancers (SSC). The aim of this study was to see if the survival of one or more cancers was different and to study the survival prognostic factors of patients with one cancer or SSC after LT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using data from the French national database, 114 French patients who underwent LT between 1993 and 2012 were followed up until their death or until June 2016. The Cox model performed to analyze potential risk factors (cancer characteristics, immunosuppressive therapy (IT), smoking, and alcohol use).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After an average follow-up of 9.8 ± 5.1 years, 52 patients developed 1 cancer, 49 had 2 cancers, and 13 had 3 cancers. The reduction in survival time was significantly and independently associated with the metastatic stage (hazard ratio (HR) = 3.98, 95% confidence interval (95% CI) = [1.45–10.93], <i>p</i> < 0.001), ENT (otolaryngology), and respiratory cancer versus genitourinary (HR = 8.28, 95% CI = [3.12–22.02], <i>p</i> < 0.001), and SSC (HR = 2.54, 95% CI = [1.39–4.65], <i>p</i> = 0.014).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The patients with ENT, respiratory cancers have a shorter survival. The stage of cancer and SSC reduces median survival at 10 years. The earliness of the first cancer should be taken as a warning signal of risk of SSC and impaired survival.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"39 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397177","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}
Suad Esayed, Ellie Kim, Hannah C. Sung, Abdula Al-Seraji, Simeon Adeyemo, Hayden Troutt, Ekamol Tantisattamoa, Antoney Ferrey, Uttam G. Reddy, Fatima T. Malik, Robert R. Redfield III, Hirohito Ichii, Abimereki D. Muzaale, Divyanshu Malhotra, Fawaz Al Ammary
Background
Kidney transplant recipients are immunocompromised and require lifelong follow-up. Recipients face geographic, socioeconomic, and logistical challenges when seeking follow-up that can be alleviated using telemedicine. We aimed to understand patient experiences and preferences regarding telemedicine video visits and highlight insights to advance adopting hybrid telemedicine/in-person transplant care.
Methods
We conducted qualitative in-depth, semi-structured interviews with kidney transplant recipients between November 18, 2022, and January 11, 2023. Participants had follow-up at ≥12 months post-transplant via telemedicine at a tertiary transplant center. Study enrollment continued until data saturation was reached (n = 20 participants) when no new information emerged from additional interviews. Transcripts were analyzed using inductive thematic analysis.
Results
Participants median age was 58 years (IQR, 52–72), and 50% were female, 45% were White, 30% were Black, 15% were Asian, 10% were Hispanic/Other persons, and 30% were out-of-state residents. We identified the following seven themes: (1) reducing travel time, (2) minimizing financial burden (decreasing travel-related expenses and lost wages), (3) engaging patients within their comfort space, (4) establishing rapport with patients, (5) limitations of the virtual physical exam, (6) enhancing access to transplant providers (maximizing adherence to follow-up), and (7) lowering risk of communicable diseases.
Conclusions
Integrating telemedicine with in-person visits enhances post-transplant follow-up care. A hybrid model should leverage the strengths of both modalities, ensuring patient access to care and being patient-centered and flexible. Efforts are needed to advance technological tools in physical examination and human connection, and assess patient outcomes. Policymakers and healthcare systems need to incentivize the adoption and expansion of telemedicine in transplant care.
{"title":"Hybrid Telemedicine and In-Person Care for Kidney Transplant Follow-Up: A Qualitative Study","authors":"Suad Esayed, Ellie Kim, Hannah C. Sung, Abdula Al-Seraji, Simeon Adeyemo, Hayden Troutt, Ekamol Tantisattamoa, Antoney Ferrey, Uttam G. Reddy, Fatima T. Malik, Robert R. Redfield III, Hirohito Ichii, Abimereki D. Muzaale, Divyanshu Malhotra, Fawaz Al Ammary","doi":"10.1111/ctr.70106","DOIUrl":"https://doi.org/10.1111/ctr.70106","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Kidney transplant recipients are immunocompromised and require lifelong follow-up. Recipients face geographic, socioeconomic, and logistical challenges when seeking follow-up that can be alleviated using telemedicine. We aimed to understand patient experiences and preferences regarding telemedicine video visits and highlight insights to advance adopting hybrid telemedicine/in-person transplant care.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted qualitative in-depth, semi-structured interviews with kidney transplant recipients between November 18, 2022, and January 11, 2023. Participants had follow-up at ≥12 months post-transplant via telemedicine at a tertiary transplant center. Study enrollment continued until data saturation was reached (<i>n</i> = 20 participants) when no new information emerged from additional interviews. Transcripts were analyzed using inductive thematic analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Participants median age was 58 years (IQR, 52–72), and 50% were female, 45% were White, 30% were Black, 15% were Asian, 10% were Hispanic/Other persons, and 30% were out-of-state residents. We identified the following seven themes: (1) reducing travel time, (2) minimizing financial burden (decreasing travel-related expenses and lost wages), (3) engaging patients within their comfort space, (4) establishing rapport with patients, (5) limitations of the virtual physical exam, (6) enhancing access to transplant providers (maximizing adherence to follow-up), and (7) lowering risk of communicable diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Integrating telemedicine with in-person visits enhances post-transplant follow-up care. A hybrid model should leverage the strengths of both modalities, ensuring patient access to care and being patient-centered and flexible. Efforts are needed to advance technological tools in physical examination and human connection, and assess patient outcomes. Policymakers and healthcare systems need to incentivize the adoption and expansion of telemedicine in transplant care.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"39 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ctr.70106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397176","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}
Farid Foroutan, Daniel G Rayner, Shelly Oss, Marco Straccia, Rienk de Vries, Shilpa Raju, Farhin Ahmed, Jennifer Kingdon, Sai Bhagra, Shafrina Tarani, Sabina Herrera, Rahima Bhanji, Heather Ross, Timothy Pruett, Sandy Feng, Marcus Pereira, Coleman Rotstein, Gordon Guyatt, Natasha Aleksova
Introduction
Solid organ transplant (SOT) recipients were excluded from clinical trials evaluating the efficacy of COVID-19 vaccines. There is uncertainty about the number of doses required to prevent life-threatening infection, as well as uncertainty in the optimal vaccine type and their durability. Our objectives were to provide recommendations on the number of COVID-19 vaccination doses, type of vaccine, dose of vaccine administered, and timing of vaccination in SOT recipients.
Methods
We commissioned a systematic review on COVID-19 vaccination in SOT, focusing on patient-important outcomes. We recruited an international, multidisciplinary panel of 18 stakeholders, including patient partners to summarize our findings using the GRADE (grading of recommendation, assessment, development, and evaluation) framework, rate certainty in the evidence, and develop recommendations.
Results
Our panel recommends the routine provision of additional COVID-19 doses after the primary series to SOT recipients with variant-appropriate vaccines (strong recommendation, low certainty evidence). We suggest using any available WHO-approved vaccine rather than selectively choosing a specific type and receiving a single dose rather than a double dose of any COVID-19 vaccine booster (weak recommendation, low certainty evidence). Lastly, we suggest vaccination before transplantation when possible (weak recommendation, low certainty evidence).
Conclusion
The evidence used to guide these recommendations is limited by the paucity of robust randomized trials evaluating COVID-19 vaccination strategies and clinical outcomes in the SOT population. The provision of higher-quality evidence of the overall effects of COVID-19 vaccination in SOT to inform clinical practice will require large, randomized trials.
{"title":"Clinical Practice Recommendations on the Effect of COVID-19 Vaccination Strategies on Outcomes in Solid Organ Transplant Recipients","authors":"Farid Foroutan, Daniel G Rayner, Shelly Oss, Marco Straccia, Rienk de Vries, Shilpa Raju, Farhin Ahmed, Jennifer Kingdon, Sai Bhagra, Shafrina Tarani, Sabina Herrera, Rahima Bhanji, Heather Ross, Timothy Pruett, Sandy Feng, Marcus Pereira, Coleman Rotstein, Gordon Guyatt, Natasha Aleksova","doi":"10.1111/ctr.70100","DOIUrl":"https://doi.org/10.1111/ctr.70100","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Solid organ transplant (SOT) recipients were excluded from clinical trials evaluating the efficacy of COVID-19 vaccines. There is uncertainty about the number of doses required to prevent life-threatening infection, as well as uncertainty in the optimal vaccine type and their durability. Our objectives were to provide recommendations on the number of COVID-19 vaccination doses, type of vaccine, dose of vaccine administered, and timing of vaccination in SOT recipients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We commissioned a systematic review on COVID-19 vaccination in SOT, focusing on patient-important outcomes. We recruited an international, multidisciplinary panel of 18 stakeholders, including patient partners to summarize our findings using the GRADE (grading of recommendation, assessment, development, and evaluation) framework, rate certainty in the evidence, and develop recommendations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our panel recommends the routine provision of additional COVID-19 doses after the primary series to SOT recipients with variant-appropriate vaccines (strong recommendation, low certainty evidence). We suggest using any available WHO-approved vaccine rather than selectively choosing a specific type and receiving a single dose rather than a double dose of any COVID-19 vaccine booster (weak recommendation, low certainty evidence). Lastly, we suggest vaccination before transplantation when possible (weak recommendation, low certainty evidence).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The evidence used to guide these recommendations is limited by the paucity of robust randomized trials evaluating COVID-19 vaccination strategies and clinical outcomes in the SOT population. The provision of higher-quality evidence of the overall effects of COVID-19 vaccination in SOT to inform clinical practice will require large, randomized trials.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"39 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389281","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}
Gabriel Rice, Nicholas Douville, Sathish Kumar, Patricia Bloom
Background and Aims
Frontal electroencephalogram (fEEG) is a novel tool to monitor intraoperative sedation and may reduce anesthetic requirements. The utility of fEEG during liver transplantation has not been studied. The primary aim was to determine the association of fEEG with anesthetic requirement. Secondary aims included the effect of fEEG on intraoperative hemodynamics and postoperative outcomes.
Methods
We performed a single-center retrospective cohort study of first-time, liver-alone transplant patients. Anesthetic requirement was measured by the mean minimum alveolar concentration of inhaled anesthetic. Hemodynamics were assessed by mean arterial pressure and total norepinephrine equivalents. Postoperative outcomes included time to extubation, mean postoperative sedation score, and incidence of delirium within five days of transplant. Both univariable and multivariable analysis was used.
Results
There were 37 fEEG-guided and 40 standard-of-care patients included in analysis. fEEG was associated with a 15% decrease of mean minimum alveolar concentration compared to standard-of-care (p < 0.01). There was no association between fEEG and mean arterial pressure or total norepinephrine equivalents. fEEG-guided and standard-of-care patients had similar time-to-extubation (10 h vs. 10 h, p = 0.98) and incidence of post-operative delirium (19% vs. 10%, p = 0.43). fEEG was associated with a lower average postoperative sedation score (Beta = −0.2, p = 0.03).
Conclusions
Our study demonstrated an association of fEEG with a reduced anesthetic requirement while maintaining adequate sedation. Patients monitored with fEEG had lower postoperative sedation scores, but no changes in other postoperative outcomes. Future prospective studies are needed to better elucidate the role of fEEG in liver transplantation, its impact on patient outcomes, and its implications for healthcare costs.
{"title":"Optimizing Anesthesia Management in Liver Transplantation With Use of Real Time Frontal Electroencephalogram","authors":"Gabriel Rice, Nicholas Douville, Sathish Kumar, Patricia Bloom","doi":"10.1111/ctr.70110","DOIUrl":"https://doi.org/10.1111/ctr.70110","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Frontal electroencephalogram (fEEG) is a novel tool to monitor intraoperative sedation and may reduce anesthetic requirements. The utility of fEEG during liver transplantation has not been studied. The primary aim was to determine the association of fEEG with anesthetic requirement. Secondary aims included the effect of fEEG on intraoperative hemodynamics and postoperative outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a single-center retrospective cohort study of first-time, liver-alone transplant patients. Anesthetic requirement was measured by the mean minimum alveolar concentration of inhaled anesthetic. Hemodynamics were assessed by mean arterial pressure and total norepinephrine equivalents. Postoperative outcomes included time to extubation, mean postoperative sedation score, and incidence of delirium within five days of transplant. Both univariable and multivariable analysis was used.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There were 37 fEEG-guided and 40 standard-of-care patients included in analysis. fEEG was associated with a 15% decrease of mean minimum alveolar concentration compared to standard-of-care (<i>p</i> < 0.01). There was no association between fEEG and mean arterial pressure or total norepinephrine equivalents. fEEG-guided and standard-of-care patients had similar time-to-extubation (10 h vs. 10 h, <i>p</i> = 0.98) and incidence of post-operative delirium (19% vs. 10%, <i>p</i> = 0.43). fEEG was associated with a lower average postoperative sedation score (Beta = −0.2, <i>p</i> = 0.03).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study demonstrated an association of fEEG with a reduced anesthetic requirement while maintaining adequate sedation. Patients monitored with fEEG had lower postoperative sedation scores, but no changes in other postoperative outcomes. Future prospective studies are needed to better elucidate the role of fEEG in liver transplantation, its impact on patient outcomes, and its implications for healthcare costs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"39 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ctr.70110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389282","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}
Milan Mohammad, Anna W. Kristensen, Jacob P. Hartmann, Neval E. Wareham, Sana N. Buttar, Anders M. Greve, Thomas K. Lund, Kristine Jensen, Hans H. L. Schultz, Michael Perch, Ronan M. G. Berg, Jann Mortensen
Background
Patients who have undergone double lung transplantation (DLTx) are at increased risk of pulmonary thromboembolism (PTE). Although the presence of clinically overt PTE can adversely affect short-term mortality, the prognostic impact of asymptomatic (silent) PTE detected by routine imaging after DLTx is unclear. This study aimed to determine whether PTE identified by routine ventilation-perfusion single-photon emission computed tomography (V̇-Q̇ SPECT) 12 weeks post-DLTx is associated with subsequent all-cause and graft-related mortality.
Methods
Single-center retrospective cohort study evaluating 130 DLTx recipients who underwent routine V̇-Q̇ SPECT imaging 12 weeks posttransplant between 2012 and 2017. V̇-Q̇ SPECT scans were assessed for perfusion and ventilation defects indicative of PTE. The association between PTE and mortality outcomes was analyzed using multivariable Cox regression, Kaplan-Meier survival curves, and cumulative incidence functions.
Results
PTE was identified in 24.6% (n = 32) of the patients 12 weeks post-DLTx. After 3 months of follow-up, there was no detectable difference in lung function between patients with and without PTE. Moreover, the presence of PTE was not associated with increased hazard ratios for all-cause mortality (HR = 0.72; 95% CI: 0.37–1.41; p = 0.34) or graft-specific mortality (HR = 0.95; 95% CI: 0.42–2.16; p = 0.91).
Conclusions
PTE is a frequent finding on routine V̇-Q̇ SPECT 12 weeks post-DLTx that does not inform risk of all-cause or graft-related mortality. These findings suggest that an incidentally detected PTE in asymptomatic patients may not necessitate changes in clinical management for asymptomatic DLTx patients.
{"title":"Survival in Patients With Evidence of Pulmonary Thromboembolism on Ventilation-Perfusion SPECT 12 Weeks After Double Lung Transplantation: A Retrospective Cohort Study","authors":"Milan Mohammad, Anna W. Kristensen, Jacob P. Hartmann, Neval E. Wareham, Sana N. Buttar, Anders M. Greve, Thomas K. Lund, Kristine Jensen, Hans H. L. Schultz, Michael Perch, Ronan M. G. Berg, Jann Mortensen","doi":"10.1111/ctr.70103","DOIUrl":"https://doi.org/10.1111/ctr.70103","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Patients who have undergone double lung transplantation (DLTx) are at increased risk of pulmonary thromboembolism (PTE). Although the presence of clinically overt PTE can adversely affect short-term mortality, the prognostic impact of asymptomatic (silent) PTE detected by routine imaging after DLTx is unclear. This study aimed to determine whether PTE identified by routine ventilation-perfusion single-photon emission computed tomography (V̇-Q̇ SPECT) 12 weeks post-DLTx is associated with subsequent all-cause and graft-related mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Single-center retrospective cohort study evaluating 130 DLTx recipients who underwent routine V̇-Q̇ SPECT imaging 12 weeks posttransplant between 2012 and 2017. V̇-Q̇ SPECT scans were assessed for perfusion and ventilation defects indicative of PTE. The association between PTE and mortality outcomes was analyzed using multivariable Cox regression, Kaplan-Meier survival curves, and cumulative incidence functions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PTE was identified in 24.6% (<i>n</i> = 32) of the patients 12 weeks post-DLTx. After 3 months of follow-up, there was no detectable difference in lung function between patients with and without PTE. Moreover, the presence of PTE was not associated with increased hazard ratios for all-cause mortality (HR = 0.72; 95% CI: 0.37–1.41; <i>p</i> = 0.34) or graft-specific mortality (HR = 0.95; 95% CI: 0.42–2.16; <i>p</i> = 0.91).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>PTE is a frequent finding on routine V̇-Q̇ SPECT 12 weeks post-DLTx that does not inform risk of all-cause or graft-related mortality. These findings suggest that an incidentally detected PTE in asymptomatic patients may not necessitate changes in clinical management for asymptomatic DLTx patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"39 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ctr.70103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143379990","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}
The demand for organ transplantation has exceeded the global supply of available organs. Donation after circulatory death (DCD) is considered an effective method to solve the disparity between the supply and demand of organs, by expanding the donor pool. However, DCD organs experience long-term damage caused by warm ischemia (WI) and microthrombosis caused by diffuse intravascular coagulation. Unfortunately, because of concerns about post-transplantation complications, most organs considered high-risk are discarded, resulting in wasted medical resources and economic losses. However, thrombolytic therapy before transplantation may dissolve microthrombosis in DCD organs, improve organ microcirculation, and increase organ use. Herein, we review the current status and potential value of thrombolytic therapy before DCD organ transplantation, summarize the progress of thrombolytic therapy for DCD organ transplantation according to preclinical and clinical research, and emphasize the heterogeneity and limitations of studies that have caused some controversies associated with this therapy. Overall, the role of thrombolytic therapy should not be overlooked. We anticipate that thrombolytic therapy combined with machine perfusion will provide an opportunity to improve inferior-quality DCD grafts, resulting in their becoming more widely available and safer for transplantation, thus solving the urgent problem of organ shortage.
{"title":"Advances and Challenges of Thrombolytic Therapy for Donation After Circulatory Death Organs","authors":"Peng Zhang, Han Liang, Yanfeng Wang","doi":"10.1111/ctr.70099","DOIUrl":"https://doi.org/10.1111/ctr.70099","url":null,"abstract":"<div>\u0000 \u0000 <p>The demand for organ transplantation has exceeded the global supply of available organs. Donation after circulatory death (DCD) is considered an effective method to solve the disparity between the supply and demand of organs, by expanding the donor pool. However, DCD organs experience long-term damage caused by warm ischemia (WI) and microthrombosis caused by diffuse intravascular coagulation. Unfortunately, because of concerns about post-transplantation complications, most organs considered high-risk are discarded, resulting in wasted medical resources and economic losses. However, thrombolytic therapy before transplantation may dissolve microthrombosis in DCD organs, improve organ microcirculation, and increase organ use. Herein, we review the current status and potential value of thrombolytic therapy before DCD organ transplantation, summarize the progress of thrombolytic therapy for DCD organ transplantation according to preclinical and clinical research, and emphasize the heterogeneity and limitations of studies that have caused some controversies associated with this therapy. Overall, the role of thrombolytic therapy should not be overlooked. We anticipate that thrombolytic therapy combined with machine perfusion will provide an opportunity to improve inferior-quality DCD grafts, resulting in their becoming more widely available and safer for transplantation, thus solving the urgent problem of organ shortage.</p>\u0000 </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"39 2","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362968","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}
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