Pub Date : 2024-12-06DOI: 10.1016/j.transproceed.2024.10.030
Xia Zhou , Rujia Tang , Dali Zhang, Xi He, Zhenwen Liu, Yinjie Gao, Hongling Liu
Background
Tacrolimus is a substrate of CYP 3A5; to reduce the rate of liver injury and rejection in liver transplant (LT) recipients, it is feasible to optimize the administration of tacrolimus by adding CYP gene polymorphism.
Methods
We divided 151 LT recipients randomly into an optimization group and a control group. All were tested routinely for clinical indicators such as FK506 trough concentration and biochemistry, and their complications and survival were observed. The optimization group additionally detected single nucleotide polymorphisms in the CYP 3A4*1B and CYP 3A5*3 genes.
Results
There were no significant differences in tacrolimus dosage, FK506 trough concentrations, and concentration/dose value between the 2 groups. In the optimization group, all patients tested CYP 3A4*1B as wild type. CYP 3A5*3 detection classification included 35 with the G/G mutation (45.5%) and 36 A/G wild-type individuals (46.8%). The concentration/dose values of G/G mutant patients were significantly higher than those of A/G wild-type and A/A mutant patients (G/G vs. A/G; P < .05), and no significant difference in FK506.
Conclusion
The CYP 3A4*1B genotype has less influence on tacrolimus metabolism. The genetic polymorphism of CYP 3A5*3 is obvious and largely affects tacrolimus metabolism, and the variant patients need lower doses of tacrolimus to reach the target concentration.
{"title":"Effect of CYP 3A4*1B and CYP3A5*3 Gene Polymorphisms in Antirejection of Tacrolimus in Liver Transplant Patients","authors":"Xia Zhou , Rujia Tang , Dali Zhang, Xi He, Zhenwen Liu, Yinjie Gao, Hongling Liu","doi":"10.1016/j.transproceed.2024.10.030","DOIUrl":"10.1016/j.transproceed.2024.10.030","url":null,"abstract":"<div><h3>Background</h3><div>Tacrolimus is a substrate of CYP 3A5; to reduce the rate of liver injury and rejection in liver transplant (LT) recipients, it is feasible to optimize the administration of tacrolimus by adding CYP gene polymorphism.</div></div><div><h3>Methods</h3><div>We divided 151 LT recipients randomly into an optimization group and a control group. All were tested routinely for clinical indicators such as FK506 trough concentration and biochemistry, and their complications and survival were observed. The optimization group additionally detected single nucleotide polymorphisms in the CYP 3A4*1B and CYP 3A5*3 genes.</div></div><div><h3>Results</h3><div>There were no significant differences in tacrolimus dosage, FK506 trough concentrations, and concentration/dose value between the 2 groups. In the optimization group, all patients tested CYP 3A4*1B as wild type. CYP 3A5*3 detection classification included 35 with the G/G mutation (45.5%) and 36 A/G wild-type individuals (46.8%). The concentration/dose values of G/G mutant patients were significantly higher than those of A/G wild-type and A/A mutant patients (G/G vs. A/G; <em>P</em> < .05), and no significant difference in FK506.</div></div><div><h3>Conclusion</h3><div>The CYP 3A4*1B genotype has less influence on tacrolimus metabolism. The genetic polymorphism of CYP 3A5*3 is obvious and largely affects tacrolimus metabolism, and the variant patients need lower doses of tacrolimus to reach the target concentration.</div></div>","PeriodicalId":23246,"journal":{"name":"Transplantation proceedings","volume":"57 2","pages":"Pages 298-304"},"PeriodicalIF":0.8,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793089","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}
Pub Date : 2024-12-01DOI: 10.1016/j.transproceed.2024.10.045
Meng-Qi Dong , Zhi-Hao Huang , Zhi-min Liu , Yuan Lin , Feng-Yong Liu , Wei-Jie Zhou
Liver ischemia-reperfusion (I/R) injury is a critical issue in clinical settings, particularly in liver transplantation and resection, leading to severe hepatocellular dysfunction and organ failure. This study investigates the role of fibrinogen and platelets in liver I/R injury, focusing on their distribution and pathophysiological impact within liver lobules. Using a mouse model, we examined the expression and localization of fibrinogen and platelets at various time points postreperfusion. In normal liver, fibrinogen is predominantly expressed in hepatic sinusoids near the portal vein, with sparse platelet distribution. Following I/R injury, fibrinogen expression significantly increases in hepatic sinusoids and hepatocytes, accompanied by substantial platelet aggregation and embolization, particularly in Zone 1 of the liver lobules. These findings highlight the zonal heterogeneity of fibrinogen distribution and its regulatory function in platelet adhesion and microthrombi formation. This study provides crucial insights for developing therapeutic strategies targeting fibrinogen and platelet interactions to mitigate liver I/R injury.
{"title":"The Role of Fibrinogen and Platelets in Mouse Liver Ischemia-Reperfusion Injury: Distribution and Pathophysiological Insights","authors":"Meng-Qi Dong , Zhi-Hao Huang , Zhi-min Liu , Yuan Lin , Feng-Yong Liu , Wei-Jie Zhou","doi":"10.1016/j.transproceed.2024.10.045","DOIUrl":"10.1016/j.transproceed.2024.10.045","url":null,"abstract":"<div><div>Liver ischemia-reperfusion (I/R) injury is a critical issue in clinical settings, particularly in liver transplantation and resection, leading to severe hepatocellular dysfunction and organ failure. This study investigates the role of fibrinogen and platelets in liver I/R injury, focusing on their distribution and pathophysiological impact within liver lobules. Using a mouse model, we examined the expression and localization of fibrinogen and platelets at various time points postreperfusion. In normal liver, fibrinogen is predominantly expressed in hepatic sinusoids near the portal vein, with sparse platelet distribution. Following I/R injury, fibrinogen expression significantly increases in hepatic sinusoids and hepatocytes, accompanied by substantial platelet aggregation and embolization, particularly in Zone 1 of the liver lobules. These findings highlight the zonal heterogeneity of fibrinogen distribution and its regulatory function in platelet adhesion and microthrombi formation. This study provides crucial insights for developing therapeutic strategies targeting fibrinogen and platelet interactions to mitigate liver I/R injury.</div></div>","PeriodicalId":23246,"journal":{"name":"Transplantation proceedings","volume":"56 10","pages":"Pages 2263-2267"},"PeriodicalIF":0.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752307","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}
Pub Date : 2024-12-01DOI: 10.1016/j.transproceed.2024.10.034
Hani M. Wadei , Namrata Parikh , Sarah Suliman , Ahmed Abdelrheem , Walter D. Park , Byron H. Smith , Carrie A. Schinstock , Hatem Amer , Hasan Khamash , Mark D. Stegall
Background
Mycophenolate mofetil (MMF) dose is commonly reduced after kidney transplantation (KT). This study examined MMF dosing in the first 5 years after KT to determine if a lower MMF dose impacted outcomes.
Methods
We retrospectively studied 432 recipients who underwent KT between February 2012 and February 2015 in 3 centers. Induction was with IL-2 receptor blocker (23%) or depleting antibody (67%) and maintenance was with calcineurin inhibitor, MMF 1.5 to 2g/day and in 70% prednisone. MMF dose was reduced within the first post-KT year as clinically indicated or for elevated mycophenolic acid (MPA) levels. All 432 patients underwent 1-year protocol biopsy. Donor-specific antibodies (DSAs) were assessed at 1 year.
Results
At 1 year, 219 KT recipients (51%) received standard MMF (> 1 g/day) and 213 (49%) received low MMF (≤ 1 gr/d). Low MMF was for clinical indication (49%) or elevated MPA level (51%). At 1 year, there was no difference in rejection rate, type and degree of rejection, degree of inflammation, or DSA formation between the low and standard MMF groups (P = not significant [NS]). The reason for MMF dose reduction did not impact outcome. By 5 years, 69% of the KT recipients were on ≤ 1 g/d MMF. The 5-year patient and death-censored graft survival were comparable between the low and standard MMF groups.
Conclusions
Almost 50% of KT recipients were on low dose MMF at 1 year and this percentage increased by 5 years. We did not observe a difference in outcomes between those on standard or low MMF dose regardless of the reason for dose reduction. Physician-directed MMF dose-reduction may be safe but randomized studies are needed to validate this finding.
{"title":"Physician-Directed Mycophenolate Mofetil Dose Reduction After Kidney Transplantation: A Multicenter Real Word Experience","authors":"Hani M. Wadei , Namrata Parikh , Sarah Suliman , Ahmed Abdelrheem , Walter D. Park , Byron H. Smith , Carrie A. Schinstock , Hatem Amer , Hasan Khamash , Mark D. Stegall","doi":"10.1016/j.transproceed.2024.10.034","DOIUrl":"10.1016/j.transproceed.2024.10.034","url":null,"abstract":"<div><h3>Background</h3><div>Mycophenolate mofetil (MMF) dose is commonly reduced after kidney transplantation (KT). This study examined MMF dosing in the first 5 years after KT to determine if a lower MMF dose impacted outcomes.</div></div><div><h3>Methods</h3><div>We retrospectively studied 432 recipients who underwent KT between February 2012 and February 2015 in 3 centers. Induction was with IL-2 receptor blocker (23%) or depleting antibody (67%) and maintenance was with calcineurin inhibitor, MMF 1.5 to 2g/day and in 70% prednisone. MMF dose was reduced within the first post-KT year as clinically indicated or for elevated mycophenolic acid (MPA) levels. All 432 patients underwent 1-year protocol biopsy. Donor-specific antibodies (DSAs) were assessed at 1 year.</div></div><div><h3>Results</h3><div>At 1 year, 219 KT recipients (51%) received standard MMF (> 1 g/day) and 213 (49%) received low MMF (≤ 1 gr/d). Low MMF was for clinical indication (49%) or elevated MPA level (51%). At 1 year, there was no difference in rejection rate, type and degree of rejection, degree of inflammation, or DSA formation between the low and standard MMF groups (<em>P</em> = not significant [NS]). The reason for MMF dose reduction did not impact outcome. By 5 years, 69% of the KT recipients were on ≤ 1 g/d MMF. The 5-year patient and death-censored graft survival were comparable between the low and standard MMF groups.</div></div><div><h3>Conclusions</h3><div>Almost 50% of KT recipients were on low dose MMF at 1 year and this percentage increased by 5 years. We did not observe a difference in outcomes between those on standard or low MMF dose regardless of the reason for dose reduction. Physician-directed MMF dose-reduction may be safe but randomized studies are needed to validate this finding.</div></div>","PeriodicalId":23246,"journal":{"name":"Transplantation proceedings","volume":"56 10","pages":"Pages 2124-2133"},"PeriodicalIF":0.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788293","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}
Pub Date : 2024-12-01DOI: 10.1016/j.transproceed.2024.10.031
Keir Forgie , Abeline Watkins , Katie Du , Alynne Ribano , Nicholas Fialka , Sayed Himmat , Sanaz Hatami , Mubashir Khan , Xiuhua Wang , Ryan Edgar , Katie-Marie Buswell-Zuk , Darren H. Freed , Jayan Nagendran
Background
Ex-Situ Lung Perfusion (ESLP) employs a membrane deoxygenator and mixed (N2/O2/CO2) or pure sweep gas (CO2) to target venous blood gas composition with physiologic pCO2 and pH. Clinically, mild permissive alkalosis counteracts elevated pulmonary vascular resistance (PVR) to improve perfusion. Increased PVR and pulmonary artery pressure (PAP) during ESLP mirrors rising pro-inflammatory cytokines. Increased hydrostatic pressure worsens edema and lung function. We report improved ESLP outcomes using mild permissive alkalosis.
Methods
Twelve juvenile pig lungs underwent 12-hour Negative Pressure Ventilation (NPV)-ESLP with a physiologic pH (Control: pH 7.35-7.45, n=6) or mild permissive alkalosis (pH+: pH 7.45-7.55, n=6) by varying sweep CO2 delivery. Three left lungs per group were transplanted and assessed over 4-hours.
Results
Five Control lungs failed on ESLP due to high PAPs, low compliance, and poor oxygenation. Repeat Controls (n=6) were performed to attain 12-hours of ESLP. There were no failures in the pH+ group. Results are pH+ vs Control. Oxygenation (PaO2/FiO2 454.2 vs 438.2; P = .37) and dynamic compliance (21.38 vs 22.22 mL/cmH2O; P = .41) were stable over 12-hour NPV-ESLP. Mean evaluation pH/pCO2/HCO3- was 7.50/15.6/14.5 vs 7.41/38.7/24.7. Control lungs required repeat THAM and milrinone boluses on ESLP to prevent acidosis and treat elevated PVR; this was not necessary in the pH+ group. Weight-gain/hour was similar (1.23% vs 1.38%; P = .37). Mean left lung PF ratios 4-hours post-transplantation were 301 mmHg vs 196 mmHg (P = .11). Control TNF-⍺ and IL-6 perfusate concentrations were significantly greater.
Conclusions
Mild permissive alkalosis porcine NPV-ESLP demonstrated more reliable preservation with reduced inflammation compared to a physiologic pH strategy.
背景：体外肺灌注（exsitu Lung Perfusion， ESLP）采用膜式除氧器和混合（N2/O2/CO2）或纯扫气（CO2），以生理pCO2和ph为靶点，靶向静脉血气体组成。临床上，轻度容许性碱中毒可抵消肺血管阻力（PVR）升高，改善灌注。ESLP期间PVR和肺动脉压（PAP）升高反映了促炎细胞因子升高。静水压力增加会加重水肿和肺功能。我们报告轻度容许性碱中毒可改善ESLP结果。方法：对12只幼年猪肺进行12小时负压通气(NPV)-ESLP，通过不同的扫气量CO2输送，使其处于生理pH（对照：pH 7.35-7.45, n=6）或轻度容许性碱中毒（pH+: pH 7.45-7.55, n=6）。每组移植3个左肺，随访4小时。结果：5个对照肺因pap高、依从性低、氧合不良而衰竭。重复对照组（n=6）达到12小时的ESLP。pH+组无失败。结果是pH+ vs对照。氧合(PaO2/FiO2 454.2 vs 438.2；P = 0.37)和动态顺应性(21.38 vs 22.22 mL/cmH2O；P = .41)在NPV-ESLP 12小时内稳定。平均评价pH/pCO2/HCO3-为7.50/15.6/14.5 vs 7.41/38.7/24.7。控制肺需要在ESLP上重复使用THAM和米力农，以防止酸中毒和治疗PVR升高；这在pH+组中是不必要的。体重增加/小时相似(1.23% vs 1.38%；P = .37)。移植后4小时平均左肺PF比值为301 mmHg vs 196 mmHg （P = 0.11）。对照组TNF-和IL-6灌注液浓度显著升高。结论：与生理性pH策略相比，轻度容许性碱中毒猪NPV-ESLP表现出更可靠的保存和减少炎症。
{"title":"Mild Permissive Alkalosis Improves Outcomes in Porcine Negative Pressure Ventilation Ex-Situ Lung Perfusion","authors":"Keir Forgie , Abeline Watkins , Katie Du , Alynne Ribano , Nicholas Fialka , Sayed Himmat , Sanaz Hatami , Mubashir Khan , Xiuhua Wang , Ryan Edgar , Katie-Marie Buswell-Zuk , Darren H. Freed , Jayan Nagendran","doi":"10.1016/j.transproceed.2024.10.031","DOIUrl":"10.1016/j.transproceed.2024.10.031","url":null,"abstract":"<div><h3>Background</h3><div>Ex-Situ Lung Perfusion (ESLP) employs a membrane deoxygenator and mixed (N<sub>2</sub>/O<sub>2</sub>/CO<sub>2</sub>) or pure sweep gas (CO<sub>2</sub>) to target venous blood gas composition with physiologic pCO<sub>2</sub> and pH. Clinically, mild permissive alkalosis counteracts elevated pulmonary vascular resistance (PVR) to improve perfusion. Increased PVR and pulmonary artery pressure (PAP) during ESLP mirrors rising pro-inflammatory cytokines. Increased hydrostatic pressure worsens edema and lung function. We report improved ESLP outcomes using mild permissive alkalosis.</div></div><div><h3>Methods</h3><div>Twelve juvenile pig lungs underwent 12-hour Negative Pressure Ventilation (NPV)-ESLP with a physiologic pH (Control: pH 7.35-7.45, n=6) or mild permissive alkalosis (pH+: pH 7.45-7.55, n=6) by varying sweep CO<sub>2</sub> delivery. Three left lungs per group were transplanted and assessed over 4-hours.</div></div><div><h3>Results</h3><div>Five Control lungs failed on ESLP due to high PAPs, low compliance, and poor oxygenation. Repeat Controls (n=6) were performed to attain 12-hours of ESLP. There were no failures in the pH+ group. Results are pH+ vs Control. Oxygenation (PaO<sub>2</sub>/FiO<sub>2</sub> 454.2 vs 438.2; <em>P =</em> .37) and dynamic compliance (21.38 vs 22.22 mL/cmH<sub>2</sub>O; <em>P =</em> .41) were stable over 12-hour NPV-ESLP. Mean evaluation pH/pCO<sub>2</sub>/HCO<sub>3</sub><sup>-</sup> was 7.50/15.6/14.5 vs 7.41/38.7/24.7. Control lungs required repeat THAM and milrinone boluses on ESLP to prevent acidosis and treat elevated PVR; this was not necessary in the pH+ group. Weight-gain/hour was similar (1.23% vs 1.38%; <em>P =</em> .37). Mean left lung PF ratios 4-hours post-transplantation were 301 mmHg vs 196 mmHg (<em>P =</em> .11). Control TNF-⍺ and IL-6 perfusate concentrations were significantly greater.</div></div><div><h3>Conclusions</h3><div>Mild permissive alkalosis porcine NPV-ESLP demonstrated more reliable preservation with reduced inflammation compared to a physiologic pH strategy.</div></div>","PeriodicalId":23246,"journal":{"name":"Transplantation proceedings","volume":"56 10","pages":"Pages 2284-2291"},"PeriodicalIF":0.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776037","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}
Pub Date : 2024-12-01DOI: 10.1016/j.transproceed.2024.10.047
Mehmet Dokur , Erdal Uysal , Faruk Kucukdurmaz , Serdar Altinay , Sait Polat , Kadir Batcioglu , Yakup Yilmaztekin , Turkan Guney , Tugce Sapmaz Ercakalli , Asli Yaylali , Efe Sezgin , Zafer Cetin , Eyup Ilker Saygili , Osman Barut , Hatem Kazimoglu , Gokturk Maralcan , Suna Koc , Mehmet Sokucu , Sema Nur Dokur Yeni
Purpose
Reducing renal ischemia is crucial for the function and survival of grafts from nonheartbeat donors, as it leads to inflammatory responses and tubulointerstitial damage. The primary concern with organs from nonheartbeat donors is the long warm ischemia period and reperfusion injury following renal transplantation. This study had two main goals; one goal is to determine how Necrostatin-1 targeting the PANoptosome affects PANoptosis in the nonheart-beating donor rat model. The other goal is to find out if Necrostatin-1 can protect the kidney from ischemic injury for renal transplantation surgery.
Methods
Twenty-four rats were grouped randomly as control and Necrostatin-1 in this experimental animal study, and we administered 1.65 mg/kg of Necrostatin-1 intraperitoneally to the experimental group for 30 minutes before cardiac arrest. We removed the rats’ left kidneys and measured various oxidative stress marker measures such as malondialdehyde, superoxide dismutase, catalase, GPx, and 8-hydroxy-2-deoxyguanosine levels. We then subjected the tissues to immunohistochemical analysis, electron microscopy, and histopathological analysis.
Findings
The Necrostatin-1 group had a lower total tubular injury score (P < .001) and less Caspase-3, gasdermin D, and mixed lineage kinase domain-like protein expression. Additionally, the apoptotic index of the study group was lower (P < .001). Furthermore, the study group had higher levels of superoxide dismutase and GPx (P < .05), whereas malondialdehyde levels were reduced (P = .009). Electron microscopy also revealed a significant improvement in tissue structure in the Necrostatin-1 group.
Conclusion
Necrostatin-1 protects against ischemic acute kidney injury in nonheart-beating donor rats by inhibiting PANoptosis via the blockade of RIPK1. As a result of this, Necrostatin-1 may offer novel opportunities for protecting donor kidneys from renal ischemia-reperfusion injury during transplantation in patients with end-stage kidney disease requiring a renal transplantation.
{"title":"Targeting the PANoptosome Using Necrostatin-1 Reduces PANoptosis and Protects the Kidney Against Ischemia-Reperfusion Injury in a Rat Model of Controlled Experimental Nonheart-Beating Donor","authors":"Mehmet Dokur , Erdal Uysal , Faruk Kucukdurmaz , Serdar Altinay , Sait Polat , Kadir Batcioglu , Yakup Yilmaztekin , Turkan Guney , Tugce Sapmaz Ercakalli , Asli Yaylali , Efe Sezgin , Zafer Cetin , Eyup Ilker Saygili , Osman Barut , Hatem Kazimoglu , Gokturk Maralcan , Suna Koc , Mehmet Sokucu , Sema Nur Dokur Yeni","doi":"10.1016/j.transproceed.2024.10.047","DOIUrl":"10.1016/j.transproceed.2024.10.047","url":null,"abstract":"<div><h3>Purpose</h3><div>Reducing renal ischemia is crucial for the function and survival of grafts from nonheartbeat donors, as it leads to inflammatory responses and tubulointerstitial damage. The primary concern with organs from nonheartbeat donors is the long warm ischemia period and reperfusion injury following renal transplantation. This study had two main goals; one goal is to determine how Necrostatin-1 targeting the PANoptosome affects PANoptosis in the nonheart-beating donor rat model. The other goal is to find out if Necrostatin-1 can protect the kidney from ischemic injury for renal transplantation surgery.</div></div><div><h3>Methods</h3><div>Twenty-four rats were grouped randomly as control and Necrostatin-1 in this experimental animal study, and we administered 1.65 mg/kg of Necrostatin-1 intraperitoneally to the experimental group for 30 minutes before cardiac arrest. We removed the rats’ left kidneys and measured various oxidative stress marker measures such as malondialdehyde, superoxide dismutase, catalase, GPx, and 8-hydroxy-2-deoxyguanosine levels. We then subjected the tissues to immunohistochemical analysis, electron microscopy, and histopathological analysis.</div></div><div><h3>Findings</h3><div>The Necrostatin-1 group had a lower total tubular injury score (<em>P</em> < .001) and less Caspase-3, gasdermin D, and mixed lineage kinase domain-like protein expression. Additionally, the apoptotic index of the study group was lower (<em>P</em> < .001). Furthermore, the study group had higher levels of superoxide dismutase and GPx (<em>P</em> < .05), whereas malondialdehyde levels were reduced (<em>P</em> = .009). Electron microscopy also revealed a significant improvement in tissue structure in the Necrostatin-1 group.</div></div><div><h3>Conclusion</h3><div>Necrostatin-1 protects against ischemic acute kidney injury in nonheart-beating donor rats by inhibiting PANoptosis via the blockade of RIPK1. As a result of this, Necrostatin-1 may offer novel opportunities for protecting donor kidneys from renal ischemia-reperfusion injury during transplantation in patients with end-stage kidney disease requiring a renal transplantation.</div></div>","PeriodicalId":23246,"journal":{"name":"Transplantation proceedings","volume":"56 10","pages":"Pages 2268-2279"},"PeriodicalIF":0.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782146","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}
Pub Date : 2024-12-01DOI: 10.1016/j.transproceed.2024.11.014
Alberto Costa Silva , Teresa Pina-Vaz , Margarida Henriques , João Nóbrega , José La Fuente de Carvalho , Carlos Martins-Silva , Tiago Antunes-Lopes , João Alturas Silva
Objective
Kidney transplantation has been a life-changing procedure for patients with end-stage renal disease (ESRD). Portugal ranks high globally in transplantation, benefiting from an “opt-out” system that presumes consent for organ donation. The effectiveness of transplantation programs depends significantly on public knowledge and the willingness to donate, where medical students play a crucial role. This study assesses the knowledge and educational needs of medical students regarding organ transplantation and donation.
Design
A cross-sectional survey was conducted using a structured questionnaire distributed to fifth-year medical students from 2 universities in Porto, Portugal, affiliated with different hospital centers during the 2022-2023 academic year.
Results
A total of 427 students responded, with a response rate of 85.0%, higher at Center 1 (93.0%) compared to Center 2 (70.0%) (P-value < .001). The majority were aware of the opt-out legislation (92.3%) and recognized ESRD as the primary cause of kidney transplantation (96.1%). Knowledge of donation types was high, particularly for brain death (92.6%) and living donation (91.5%), but lower for donation after circulatory death (73.1%). Awareness of donation after circulatory death was significantly higher among respondents from Center 1 (79.4%) than Center 2 (59.1%; P < .001). Only a minority were familiar with immunosuppressive drugs (36.0%) and had practical exposure to transplant-related activities. Satisfaction with transplantation education was low (8.2%), with significant differences between the centers.
Conclusion
The findings suggest that medical schools should enhance educational content and provide more experiences to prepare future healthcare providers adequately.
{"title":"Knowledge Gaps and Educational Needs in Organ Transplantation: A Study of Portuguese Medical Students","authors":"Alberto Costa Silva , Teresa Pina-Vaz , Margarida Henriques , João Nóbrega , José La Fuente de Carvalho , Carlos Martins-Silva , Tiago Antunes-Lopes , João Alturas Silva","doi":"10.1016/j.transproceed.2024.11.014","DOIUrl":"10.1016/j.transproceed.2024.11.014","url":null,"abstract":"<div><h3>Objective</h3><div>Kidney transplantation has been a life-changing procedure for patients with end-stage renal disease (ESRD). Portugal ranks high globally in transplantation, benefiting from an “opt-out” system that presumes consent for organ donation. The effectiveness of transplantation programs depends significantly on public knowledge and the willingness to donate, where medical students play a crucial role. This study assesses the knowledge and educational needs of medical students regarding organ transplantation and donation.</div></div><div><h3>Design</h3><div>A cross-sectional survey was conducted using a structured questionnaire distributed to fifth-year medical students from 2 universities in Porto, Portugal, affiliated with different hospital centers during the 2022-2023 academic year.</div></div><div><h3>Results</h3><div>A total of 427 students responded, with a response rate of 85.0%, higher at Center 1 (93.0%) compared to Center 2 (70.0%) (<em>P</em>-value < .001). The majority were aware of the opt-out legislation (92.3%) and recognized ESRD as the primary cause of kidney transplantation (96.1%). Knowledge of donation types was high, particularly for brain death (92.6%) and living donation (91.5%), but lower for donation after circulatory death (73.1%). Awareness of donation after circulatory death was significantly higher among respondents from Center 1 (79.4%) than Center 2 (59.1%; <em>P</em> < .001). Only a minority were familiar with immunosuppressive drugs (36.0%) and had practical exposure to transplant-related activities. Satisfaction with transplantation education was low (8.2%), with significant differences between the centers.</div></div><div><h3>Conclusion</h3><div>The findings suggest that medical schools should enhance educational content and provide more experiences to prepare future healthcare providers adequately.</div></div>","PeriodicalId":23246,"journal":{"name":"Transplantation proceedings","volume":"56 10","pages":"Pages 2298-2301"},"PeriodicalIF":0.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775904","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}
Pub Date : 2024-12-01DOI: 10.1016/j.transproceed.2024.10.036
Dan Li , Chun Liu , Zhongyu Kang , Yan Zheng , Yuliang Wang
Background
Because cytomegalovirus (CMV) infection is one of the most common complications following liver transplantation (LT), it is important to analyze the impact of CMV infection on the LT-associated changes in T cells polarization. This study aimed to investigate T helper (Th) and T cytotoxic (Tc) cells polarization and their correlation in infant LT recipients with active CMV infection.
Methods
Twenty infant LT recipients with active CMV infection (the CMV group) and 20 recipients without CMV infection (the stable group) were enrolled. The percentages of Th1, Th2, Tc1, and Tc2 cells were detected by flow cytometry after intracellular staining for cytokines (IFN-γ and IL-10, respectively) in peripheral blood. The correlation between Th and Tc cells was analyzed by Pearson correlation coefficient.
Results
The percentages of Th1 and Tc1 cells were significantly decreased, whereas the percentages of Tc2 cells were significantly increased in CMV group compared with the stable group, along with significant reduction of Th1/Th2 and Tc1/Tc2 ratios (P < .01). The percentages of Th1 cells were positively correlated with Tc1 cells (P < .01). A higher Th1/Th2 and Tc1/Tc2 ratios were showed in the CMV group after antiviral therapy than those in the CMV group before therapy (P < .01).
Conclusions
Our findings show an imbalanced Th1/Th2 and Tc1/Tc2 immunity in infant LT recipients with active CMV infection, which were involved in the pathogenesis of CMV infection.
{"title":"Imbalances of Th1/Th2 and Tc1/Tc2 are Associated With Active Cytomegalovirus Infection in Infant Liver Transplant Recipients","authors":"Dan Li , Chun Liu , Zhongyu Kang , Yan Zheng , Yuliang Wang","doi":"10.1016/j.transproceed.2024.10.036","DOIUrl":"10.1016/j.transproceed.2024.10.036","url":null,"abstract":"<div><h3>Background</h3><div>Because cytomegalovirus (CMV) infection is one of the most common complications following liver transplantation (LT), it is important to analyze the impact of CMV infection on the LT-associated changes in T cells polarization. This study aimed to investigate T helper (Th) and T cytotoxic (Tc) cells polarization and their correlation in infant LT recipients with active CMV infection.</div></div><div><h3>Methods</h3><div>Twenty infant LT recipients with active CMV infection (the CMV group) and 20 recipients without CMV infection (the stable group) were enrolled. The percentages of Th1, Th2, Tc1, and Tc2 cells were detected by flow cytometry after intracellular staining for cytokines (IFN-γ and IL-10, respectively) in peripheral blood. The correlation between Th and Tc cells was analyzed by Pearson correlation coefficient.</div></div><div><h3>Results</h3><div>The percentages of Th1 and Tc1 cells were significantly decreased, whereas the percentages of Tc2 cells were significantly increased in CMV group compared with the stable group, along with significant reduction of Th1/Th2 and Tc1/Tc2 ratios (<em>P</em> < .01). The percentages of Th1 cells were positively correlated with Tc1 cells (<em>P</em> < .01). A higher Th1/Th2 and Tc1/Tc2 ratios were showed in the CMV group after antiviral therapy than those in the CMV group before therapy (<em>P</em> < .01).</div></div><div><h3>Conclusions</h3><div>Our findings show an imbalanced Th1/Th2 and Tc1/Tc2 immunity in infant LT recipients with active CMV infection, which were involved in the pathogenesis of CMV infection.</div></div>","PeriodicalId":23246,"journal":{"name":"Transplantation proceedings","volume":"56 10","pages":"Pages 2172-2177"},"PeriodicalIF":0.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788292","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}
Pub Date : 2024-12-01DOI: 10.1016/j.transproceed.2024.10.043
Colin Hartgerink , Avi Toiv , Arif Sarowar , Ella Todd , Shunji Nagai , Yakir Muszkat , Nemie Beltran , Syed-Mohammed Jafri
Background
As calcineurin inhibitors are associated with renal impairment post intestinal transplant, use of everolimus (EVR) may provide renal-sparing benefits.
Methods
We performed a retrospective analysis focused on EVR use and renal function after intestinal or multivisceral transplant. No prisoners were used in the study. This study is compliant with the Helsinki Congress and the Declaration of Istanbul.
Results
A total of 28 patients, 18 patients who underwent isolated intestinal transplant, and 10 patients who underwent multivisceral transplant, were included in this study. For 13 patients that never received EVR, the average change in estimated glomerular filtration rate (eGFR) compared to baseline at the time of transplant were as follows: 1 year post-transplant = –18.1%; 2 years = –43.7%; 3 years = –44.1; and 5 years = –43.3%. For 15 patients who received EVR after transplant, average duration of EVR therapy was (579.60 ± 784.15) days with 87% of patients ultimately removed from medication due to side effects. In the EVR group, the average change in eGFR compared to baseline were as follows: 1 year post-transplant = –37.5%; 2 years = –43.5%; 3 years = –54.2%; and 5 years = –42.9%. After the initiation of EVR, the average change in eGFR compared to eGFR at time of EVR initiation was as follows: 1 year = +5.9%; 2 years = –1.57%; 3 years = –5.01%; and 5 years = –1.79%.
Conclusions
This study suggests that EVR can play an important role in preserving renal function in intestinal and multivisceral transplant recipients, but tolerance of EVR is highly variable in this patient population.
{"title":"Safety and Efficacy of Everolimus Use to Preserve Renal Function in Intestinal and Multivisceral Transplantation Patients","authors":"Colin Hartgerink , Avi Toiv , Arif Sarowar , Ella Todd , Shunji Nagai , Yakir Muszkat , Nemie Beltran , Syed-Mohammed Jafri","doi":"10.1016/j.transproceed.2024.10.043","DOIUrl":"10.1016/j.transproceed.2024.10.043","url":null,"abstract":"<div><h3>Background</h3><div>As calcineurin inhibitors are associated with renal impairment post intestinal transplant, use of everolimus (EVR) may provide renal-sparing benefits.</div></div><div><h3>Methods</h3><div>We performed a retrospective analysis focused on EVR use and renal function after intestinal or multivisceral transplant. No prisoners were used in the study. This study is compliant with the Helsinki Congress and the Declaration of Istanbul.</div></div><div><h3>Results</h3><div>A total of 28 patients, 18 patients who underwent isolated intestinal transplant, and 10 patients who underwent multivisceral transplant, were included in this study. For 13 patients that never received EVR, the average change in estimated glomerular filtration rate (eGFR) compared to baseline at the time of transplant were as follows: 1 year post-transplant = –18.1%; 2 years = –43.7%; 3 years = –44.1; and 5 years = –43.3%. For 15 patients who received EVR after transplant, average duration of EVR therapy was (579.60 ± 784.15) days with 87% of patients ultimately removed from medication due to side effects. In the EVR group, the average change in eGFR compared to baseline were as follows: 1 year post-transplant = –37.5%; 2 years = –43.5%; 3 years = –54.2%; and 5 years = –42.9%. After the initiation of EVR, the average change in eGFR compared to eGFR at time of EVR initiation was as follows: 1 year = +5.9%; 2 years = –1.57%; 3 years = –5.01%; and 5 years = –1.79%.</div></div><div><h3>Conclusions</h3><div>This study suggests that EVR can play an important role in preserving renal function in intestinal and multivisceral transplant recipients, but tolerance of EVR is highly variable in this patient population.</div></div>","PeriodicalId":23246,"journal":{"name":"Transplantation proceedings","volume":"56 10","pages":"Pages 2250-2254"},"PeriodicalIF":0.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741824","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}
Pub Date : 2024-12-01DOI: 10.1016/j.transproceed.2024.10.033
Bassem S. Wadie, Ahmed S. El Hefnawy, Ayman F. Refaie
Background
The purpose of this article was to assess the recoverability of bladder, in a subset of patients with uremia, planned for live-donor kidney transplantation.
Methods
Patients referred to the Voiding Dysfunction Unit for evaluation, prior to transplantation, were included in this study during the period 2004 to 2008 in a single institution with a track record in live-donor transplantation. Defunctionalized bladder was defined as patients with complete anuria or oliguria for at least 6 months. All had stage 5 end-stage renal disease (ESRD) and were subjected to invasive urodynamics prior and 6 months after live-donor kidney transplantation. Outcome measurement and statistical method: improvement of urodynamic variables after transplantation was the principal outcome measure. Comparisons were made using the one-sample two-tailed t test. One way analysis of variance was used for comparison of continuous variables and Pearson's Correlation coefficient for studying the correlation between the duration of anuria and different continuous variables.
Results
Thirty-two patients were included in this study. The bladder underwent a significant decline of its capacity with defunctionalization with a mean cystometric capacity at baseline of 253 ± 171 mL that increased to 389 (P = .001), compliance increased from 26 to 33 (P = .001), filling pressure decreased by 12 cm H20 (P = .001) and free maximum flow rate (Q max) increased from 13 to 16 mL/s (P = .007). Detrusor overactivity decreased in prevalence (from 26 to 14 cases) and amplitude (from 21 to 12 cm H20). Our study lacks voiding cystometry variables as well as in having diverse causes for defunctionalization.
Conclusions
After transplantation, urodynamic parameters significantly improved. With caution, these defunctionalized bladders (DBs) could be utilized for live-donor transplants with favorable functional outcome.
背景：这篇文章的目的是评估尿毒症患者膀胱的恢复能力，计划进行活体肾移植。方法：在2004年至2008年期间，在同一家有活体供体移植记录的机构中，移植前向排尿功能障碍单元进行评估的患者被纳入本研究。膀胱功能障碍定义为患者完全无尿或少尿至少6个月。所有患者均患有5期终末期肾病（ESRD），并在活体肾移植前和移植后6个月接受有创尿动力学检查。结果测量和统计方法：移植后尿动力学指标的改善是主要的结果测量。采用单样本双尾t检验进行比较。采用单因素方差分析比较连续变量，Pearson相关系数研究无尿持续时间与不同连续变量的相关性。结果：本研究纳入32例患者。膀胱功能失能导致膀胱容量显著下降，膀胱容量从基线的253±171 mL增加到389 mL (P = 0.001)，膀胱顺应性从26 mL增加到33 mL (P = 0.001)，充注压力减少了12 cm H20 (P = 0.001)，自由最大流量（Q max）从13 mL/s增加到16 mL/s （P = 0.007）。逼尿肌过度活动的发生率（从26例降至14例）和幅度（从21至12 cm H20）下降。我们的研究缺乏排尿膀胱测量变量，以及有多种原因的去功能化。结论：移植后尿动力学参数明显改善。值得注意的是，这些失功能膀胱（DBs）可用于活体供体移植，具有良好的功能预后。
{"title":"Recoverability of Bladder Function in Patients With Defunctionalized Bladder and Live-Donor Kidney Transplantation","authors":"Bassem S. Wadie, Ahmed S. El Hefnawy, Ayman F. Refaie","doi":"10.1016/j.transproceed.2024.10.033","DOIUrl":"10.1016/j.transproceed.2024.10.033","url":null,"abstract":"<div><h3>Background</h3><div>The purpose of this article was to assess the recoverability of bladder, in a subset of patients with uremia, planned for live-donor kidney transplantation.</div></div><div><h3>Methods</h3><div>Patients referred to the Voiding Dysfunction Unit for evaluation, prior to transplantation, were included in this study during the period 2004 to 2008 in a single institution with a track record in live-donor transplantation. Defunctionalized bladder was defined as patients with complete anuria or oliguria for at least 6 months. All had stage 5 end-stage renal disease (ESRD) and were subjected to invasive urodynamics prior and 6 months after live-donor kidney transplantation. Outcome measurement and statistical method: improvement of urodynamic variables after transplantation was the principal outcome measure. Comparisons were made using the one-sample two-tailed <em>t</em> test. One way analysis of variance was used for comparison of continuous variables and Pearson's Correlation coefficient for studying the correlation between the duration of anuria and different continuous variables.</div></div><div><h3>Results</h3><div>Thirty-two patients were included in this study. The bladder underwent a significant decline of its capacity with defunctionalization with a mean cystometric capacity at baseline of 253 ± 171 mL that increased to 389 (<em>P</em> = .001), compliance increased from 26 to 33 (<em>P</em> = .001), filling pressure decreased by 12 cm H20 (<em>P</em> = .001) and free maximum flow rate (Q max) increased from 13 to 16 mL/s (<em>P =</em> .007). Detrusor overactivity decreased in prevalence (from 26 to 14 cases) and amplitude (from 21 to 12 cm H20). Our study lacks voiding cystometry variables as well as in having diverse causes for defunctionalization.</div></div><div><h3>Conclusions</h3><div>After transplantation, urodynamic parameters significantly improved. With caution, these defunctionalized bladders (DBs) could be utilized for live-donor transplants with favorable functional outcome.</div></div>","PeriodicalId":23246,"journal":{"name":"Transplantation proceedings","volume":"56 10","pages":"Pages 2144-2148"},"PeriodicalIF":0.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776081","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}
Pub Date : 2024-12-01DOI: 10.1016/j.transproceed.2024.11.010
Nhat-Minh Le Pham , Thinh Phuc Ong , Nguyen Lam Vuong , Thi Thu Hoai Nguyen
Human leukocyte antigen (HLA) compatibility between donors and recipients plays a critical role in graft survival in renal transplantation. This study evaluates the impact of HLA mismatching on graft survival and rejection among renal transplant recipients with related and unrelated donors, considering factors such as age, sex, ABO blood type, and anti-HLA antibodies. We investigated the graft survival rates between related and unrelated donors in a prospective cohort study conducted from 2018 to 2020 at Cho Ray Hospital and People's Hospital 115 in Vietnam, involving 126 related and 82 unrelated donor–recipient pairs. Over 32 months of follow-up, there was no significant difference in the rates of suspected graft rejection (P = .75) or graft loss (P = .095) between the 2 groups. However, related donors exhibited significantly higher overall survival (P = .0086) and better event-free survival (P = .0025) compared with unrelated donors. HLA matching and ABO type did not show any association with suspected graft rejection in either group. Notably, unrelated donors older than 5 years increased the risk of suspected graft rejection (hazard ratio, 4.22), and positive anti-HLA antibodies also increased this risk (hazard ratio, 4.5). Conversely, male–male donor–recipient pairs significantly decreased the risk of graft rejection by 88% compared with female–female pairs. The study concludes that although HLA matching is not different for related and unrelated donor groups, factors such as donor age, same-sex pairs, and the presence of anti-HLA antibodies are significant risk factors for graft rejection in unrelated donors. Enhancing monitoring and developing strategies for unrelated donors are essential to improve graft survival outcomes in renal transplantation.
{"title":"HLA Compatibility and Graft Survival Rates Among Related and Unrelated Donors in Renal Transplantation","authors":"Nhat-Minh Le Pham , Thinh Phuc Ong , Nguyen Lam Vuong , Thi Thu Hoai Nguyen","doi":"10.1016/j.transproceed.2024.11.010","DOIUrl":"10.1016/j.transproceed.2024.11.010","url":null,"abstract":"<div><div>Human leukocyte antigen (HLA) compatibility between donors and recipients plays a critical role in graft survival in renal transplantation. This study evaluates the impact of HLA mismatching on graft survival and rejection among renal transplant recipients with related and unrelated donors, considering factors such as age, sex, ABO blood type, and anti-HLA antibodies. We investigated the graft survival rates between related and unrelated donors in a prospective cohort study conducted from 2018 to 2020 at Cho Ray Hospital and People's Hospital 115 in Vietnam, involving 126 related and 82 unrelated donor–recipient pairs. Over 32 months of follow-up, there was no significant difference in the rates of suspected graft rejection (<em>P</em> = .75) or graft loss (<em>P</em> = .095) between the 2 groups. However, related donors exhibited significantly higher overall survival (<em>P</em> = .0086) and better event-free survival (<em>P</em> = .0025) compared with unrelated donors. HLA matching and ABO type did not show any association with suspected graft rejection in either group. Notably, unrelated donors older than 5 years increased the risk of suspected graft rejection (hazard ratio, 4.22), and positive anti-HLA antibodies also increased this risk (hazard ratio, 4.5). Conversely, male–male donor–recipient pairs significantly decreased the risk of graft rejection by 88% compared with female–female pairs. The study concludes that although HLA matching is not different for related and unrelated donor groups, factors such as donor age, same-sex pairs, and the presence of anti-HLA antibodies are significant risk factors for graft rejection in unrelated donors. Enhancing monitoring and developing strategies for unrelated donors are essential to improve graft survival outcomes in renal transplantation.</div></div>","PeriodicalId":23246,"journal":{"name":"Transplantation proceedings","volume":"56 10","pages":"Pages 2163-2171"},"PeriodicalIF":0.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751934","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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