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1.
Am J Transplant ; 22(11): 2529-2547, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35851547

RESUMO

Donor age is a major risk factor for allograft outcome in kidney transplantation. The underlying cellular mechanisms and the recipient's immune response within an aged allograft have yet not been analyzed. A comprehensive immunophenotyping of naïve and transplanted young versus aged kidneys revealed that naïve aged murine kidneys harbor significantly higher frequencies of effector/memory T cells, whereas regulatory T cells were reduced. Aged kidney-derived CD8+ T cells produced more IFNγ than their young counterparts. Senescent renal CD8+ T and NK cells upregulated the cytotoxicity receptor NKG2D and the enrichment of memory-like CD49a+ CXCR6+ NK cells was documented in aged naïve kidneys. In the C57BL/6 to BALB/c kidney transplantation model, recipient-derived T cells infiltrating an aged graft produced significantly more IFNγ, granzyme B and perforin on day 7 post-transplantation, indicating an enhanced inflammatory, cytotoxic response towards the graft. Pre-treatment of aged kidney donors with the senolytic drug ABT-263 changed the recipient-derived effector molecule profile to significantly reduced levels of IFNγ and IL-10 compared to controls. Graft function after ABT-263 pre-treatment was significantly improved 28 days post kidney transplantation. In conclusion, renal senescence also occurs at the immunological level (inflamm-aging) and aged organs provoke an altered recipient-dominated immune response in the graft.


Assuntos
Transplante de Rim , Camundongos , Animais , Transplante de Rim/efeitos adversos , Linfócitos T CD8-Positivos , Rim , Envelhecimento/fisiologia , Inflamação/etiologia , Rejeição de Enxerto/etiologia
2.
Pediatr Transplant ; 26(2): e14188, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34719848

RESUMO

INTRODUCTION: In pediatric liver transplantation (pLT), hepatic artery thrombosis (HAT) is associated with inferior transplant outcome. Hepatic artery reconstruction (HAR) using an operating microscope (OM) is considered to reduce the incidence of HAT. METHODS: HAR using an OM was compared to a historic cohort using surgical loupes (SL) in pLT performed between 2009 and 2020. Primary endpoint was the occurrence of HAT. Secondary endpoints were 1-year patient and graft survival determined by Kaplan-Meier analysis and complications. Multivariate analysis was used to identify independent risk factors for HAT and adverse events. RESULTS: A total of 79 pLTs were performed [30 (38.0%) living donations; 49 (62.0%) postmortem donations] divided into 23 (29.1%) segment 2/3, 32 (40.5%) left lobe, 4 (5.1%) extended right lobe, and 20 (25.3%) full-size grafts. One-year patient and graft survival were both 95.2% in the OM group versus 86.2% and 77.8% in the SL group (p = .276 and p = .077). HAT rate was 0% in the OM group versus 24.1% in the SL group (p = .013). One-year patient and graft survival were 64.3% and 35.7% in patient with HAT, compared to 93.9% and 92.8% in patients with no HAT (both p < .001). Multivariate analysis revealed HAR with SL (p = .022) and deceased donor liver transplantation (DDLT) (p = .014) as independent risk factors for HAT. The occurrence of HAT was independently associated with the need for retransplantation (p < .001) and biliary leakage (p = .045). CONCLUSION: In pLT, the use of an OM is significantly associated to reduce HAT rate, biliary complications, and graft loss and outweighs the disadvantages of delayed arterial perfusion and prolonged warm ischemia time (WIT).


Assuntos
Artéria Hepática/cirurgia , Transplante de Fígado , Trombose/prevenção & controle , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Humanos , Lactente , Masculino , Procedimentos de Cirurgia Plástica , Fatores de Risco , Taxa de Sobrevida , Procedimentos Cirúrgicos Vasculares
3.
BMC Surg ; 22(1): 86, 2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35246086

RESUMO

BACKGROUND: Robotic-assisted pancreatic surgery is limited to specialized high-volume centers and selected patient cohorts. Especially for patients with a history of previous abdominal surgeries, the standard procedure remains open surgery due to the fear of complications caused by abdominal adhesions. METHODS: Clinical data of all consecutive patients undergoing robotic-assisted pancreatic surgery using the daVinci Xi system (Intuitive Surgical) at our center (Department of Surgery, Universitätsmedizin Berlin, Germany) were collected prospectively and further analyzed from October 2017 to October 2020. Prior abdominal surgeries were specified according to the surgical approach and localization. In univariate and multivariate analysis, baseline and perioperative parameters of patients with a history of prior abdominal surgeries (PS) were compared to those of patients with no history of prior abdominal surgeries (NPS). RESULTS: Out of 131 patients undergoing robotic-assisted pancreatic surgery, 62 (47%) had a history of abdominal surgery. Previous procedures included most often appendectomy (32%) followed by gynecological surgery (29%) and cholecystectomy (27%). 24% of PS had received multiple surgeries prior to the robotic-assisted pancreatic resections. Baseline characteristics and comorbidities were comparable between the groups. We did not detect differences in the duration of surgery (262 min), conversion rates (10%), and postoperative complications between NPS and PS. Postoperative pancreatic fistula (POPF), postpancreatectomy hemorrhage (PPH), and in-house mortality showed no significant differences between the two groups. Multivariate analysis revealed male sex and high BMI as a potential predictive factor for severe postoperative complications. Other characteristics like the type of pancreatic resection, ASA, and underlying malignancy showed no difference in the multivariable analysis. CONCLUSIONS: We propose robotic-assisted pancreatic surgery to be safe and feasible for patients with a history of minor prior abdominal surgery. Hence, each patient should individually be evaluated for a minimally invasive approach regardless of a history of previous operations.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Abdome , Estudos de Viabilidade , Feminino , Humanos , Laparoscopia/métodos , Masculino , Pancreatectomia/métodos , Fístula Pancreática , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento
4.
Transpl Infect Dis ; 23(4): e13696, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34288294

RESUMO

BACKGROUND: Since phase III trials for the most prominent vaccines excluded immunocompromised or immunosuppressed patients, data on safety and efficacy of SARS-CoV-2 vaccines for recipients of solid organ transplantations are scarce. AIMS: Our study offers a synthesis of expert opinions aligned with available data addressing key questions of the clinical management of SARS-CoV-2 vaccinations for transplant patients. METHOD: An online research was performed retrieving available recommendations by national and international transplantation organizations and state institutions on SARS-CoV2 vaccination management for transplant recipients. RESULTS: Eleven key statements were identified from recommendations by 18 national and international societies, and consensus for the individual statements was evaluated by means of the Society Recommendation Consensus score. The highest consensus level (SRC A) was found for prioritized access to vaccination for transplant patients despite anticipation of a weakened immune response. All currently authorized vaccines can be considered safe for transplant patients (SRC A). The handling of immunosuppressive medication, the timely management of vaccines, and other aspects were aligned with available expert opinions. CONCLUSION: Expert consensus can be determined for crucial aspects of the implementation of SARS-CoV-2 vaccination programs. We hereby offer a tool for immediate decision-making until empirical data becomes available.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Consenso , Humanos , RNA Viral , SARS-CoV-2 , Vacinação
5.
BMC Surg ; 21(1): 135, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33726727

RESUMO

BACKGROUND: The best treatment for perforated colonic diverticulitis with generalized peritonitis is still under debate. Concurrent strategies are resection with primary anastomosis (PRA) with or without diverting ileostomy (DI), Hartmann's procedure (HP), laparoscopic lavage (LL) and damage control surgery (DCS). This review intends to systematically analyze the current literature on DCS. METHODS: DCS consists of two stages. Emergency surgery: limited resection of the diseased colon, oral and aboral closure, lavage, vacuum-assisted abdominal closure. Second look surgery after 24-48 h: definite reconstruction with colorectal anastomosis (-/ + DI) or HP after adequate resuscitation. The review was conducted in accordance to the PRISMA-P Statement. PubMed/MEDLINE, Cochrane central register of controlled trials (CENTRAL) and EMBASE were searched using the following term: (Damage control surgery) AND (Diverticulitis OR Diverticulum OR Peritonitis). RESULTS: Eight retrospective studies including 256 patients met the inclusion criteria. No randomized trial was available. 67% of the included patients had purulent, 30% feculent peritonitis. In 3% Hinchey stage II diverticulitis was found. In 49% the Mannheim peritonitis index (MPI) was greater than 26. Colorectal anastomosis was constructed during the course of the second surgery in 73%. In 15% of the latter DI was applied. The remaining 27% received HP. Postoperative mortality was 9%, morbidity 31% respectively. The anastomotic leak rate was 13%. 55% of patients were discharged without a stoma. CONCLUSION: DCS is a safe technique for the treatment of acute perforated diverticulitis with generalized peritonitis, allowing a high rate of colorectal anastomosis and stoma-free hospital discharge in more than half of the patients.


Assuntos
Doença Diverticular do Colo , Peritonite , Anastomose Cirúrgica , Doença Diverticular do Colo/complicações , Doença Diverticular do Colo/cirurgia , Humanos , Peritonite/complicações , Peritonite/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
6.
Zentralbl Chir ; 146(1): e1-e6, 2021 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-32785899

RESUMO

BACKGROUND: The new COVID-19 pandemic has an impact on routine thoracic surgery. Various concepts and recommendations are being pursued to protect patients and hospital staff. However, the implementation of these recommendations may depend on the existing infrastructure, local conditions and in-house procedural instructions. MATERIAL AND METHOD: Between 11th May and 26th May 2020, an anonymous online survey on the topic of COVID-19 was conducted among thoracic surgeons in Germany. The survey consisted of 16 questions on the local COVID-19 case numbers, protective measures, procedural instructions and treatment concepts. The results were summarised, descriptively analysed and discussed. RESULTS: The response rate of 42.6% (n = 66), included replies from 23 (34.8%) specialised hospitals, 18 (27.3%) maximum care hospitals and 14 (21.2%) university clinics. COVID-19-positive patients were treated in 65 (99%) clinics and 37.9% of the clinics also performed surgery on COVID-19-positive patients. Nasopharyngeal swabs were the main instrument for COVID-19 patient testing (in 95.4% of the clinics). Test results influenced decisions on treatment in 71.2% of the clinics. In 59.1% of clinics, safety equipment was supplemented with FFP2 masks and eye protection during thoracic surgeries due to the COVID-19 pandemic. DISCUSSION: Almost all thoracic surgeons reported that they had treated patients with COVID-19 and half of them also had performed surgery on COVID-19-positive patients. The applied procedural instructions as well as the effects of COVID-19 on treatment decisions and patient-doctor contact differed between the reporting clinics.


Assuntos
COVID-19 , Cirurgia Torácica , Alemanha , Humanos , Pandemias , SARS-CoV-2
7.
Am J Transplant ; 20(7): 1826-1836, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32323460

RESUMO

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has a drastic impact on national health care systems. Given the overwhelming demand on facility capacity, the impact on all health care sectors has to be addressed. Solid organ transplantation represents a field with a high demand on staff, intensive care units, and follow-up facilities. The great therapeutic value of organ transplantation has to be weighed against mandatory constraints of health care capacities. In addition, the management of immunosuppressed recipients has to be reassessed during the ongoing coronavirus disease 2019 (COVID-19) pandemic. In addressing these crucial questions, transplant physicians are facing a total lack of scientific evidence. Therefore, the aim of this study was to offer an approach of consensus-based guidance, derived from individual information of 22 transplant societies. Key recommendations were extracted and the degree of consensus among different organizations was calculated. A high degree of consensus was found for temporarily suspending nonurgent transplant procedures and living donation programs. Systematic polymerase chain reaction-based testing of donors and recipients was broadly recommended. Additionally, more specific aspects (eg, screening of surgical explant teams and restricted use of marginal donor organs) were included in our analysis. This study offers a novel approach to informed guidance for health care management when a priori no scientific evidence is available.


Assuntos
Técnicas de Laboratório Clínico , Infecções por Coronavirus/prevenção & controle , Transplante de Órgãos/normas , Transplante de Órgãos/tendências , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Betacoronavirus , COVID-19 , Teste para COVID-19 , Consenso , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Cuidados Críticos , Medicina Baseada em Evidências , Política de Saúde , Humanos , Hospedeiro Imunocomprometido , Internacionalidade , Doadores Vivos , Transplante de Órgãos/métodos , Equipamento de Proteção Individual , Pneumonia Viral/epidemiologia , Reação em Cadeia da Polimerase , Radiografia Torácica , Alocação de Recursos , SARS-CoV-2 , Sociedades Médicas , Doadores de Tecidos , Tomografia Computadorizada por Raios X , Transplantados
8.
Liver Transpl ; 26(5): 628-639, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32159923

RESUMO

In contrast to donor factors predicting outcomes of liver transplantation (LT), few suitable recipient parameters have been identified. To this end, we performed an in-depth analysis of hospitalization status and duration prior to LT as a potential risk factor for posttransplant outcome. The pretransplant hospitalization status of all patients undergoing LT between 2005 and 2016 at the Charité-Universitätsmedizin Berlin was analyzed retrospectively using propensity score matching. At the time of organ acceptance, 226 of 1134 (19.9%) recipients were hospitalized in an intensive care unit (ICU), 146 (12.9%) in a regular ward (RW) and 762 patients (67.2%) were at home. Hospitalized patients (RW and ICU) compared with patients from home showed a dramatically shorter 3-month survival (78.7% versus 94.4%), 1-year survival (66.3% versus 87.3%), and 3-year survival (61.7% versus 81.7%; all P < 0.001), whereas no significant difference was detected for 3-year survival between ICU and RW patients (61.5% versus 62.3%; P = 0.60). These results remained significant after propensity score matching. Furthermore, in ICU patients, but not in RW patients, survival correlated with days spent in the ICU before LT (1-year survival: 1-6 versus 7-14 days: 73.7% versus 60.5%, P = 0.04; 7-14 days versus >14 days, 60.5% versus 51.0%, P = 0.006). In conclusion, hospitalization status before transplantation is a valuable predictor of patient survival following LT.


Assuntos
Transplante de Fígado , Hospitalização , Humanos , Transplante de Fígado/efeitos adversos , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco
9.
BMC Gastroenterol ; 20(1): 265, 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32787947

RESUMO

BACKGROUND: MELD score and MELD score derivates are used to objectify and grade the risk of liver-related death in patients with liver cirrhosis. We recently proposed a new predictive model that combines serum creatinine levels and maximum liver function capacity (LiMAx®), namely the CreLiMAx risk score. In this validation study we have aimed to reproduce its diagnostic accuracy in patients with end-stage liver disease. METHODS: Liver function of 113 patients with liver cirrhosis was prospectively investigated. Primary end-point of the study was liver-related death within 12 months of follow-up. RESULTS: Alcoholic liver disease was the main cause of liver disease (n = 51; 45%). Within 12 months of follow-up 11 patients (9.7%) underwent liver transplantation and 17 (15.1%) died (13 deaths were related to liver disease, two not). Measures of diagnostic accuracy were comparable for MELD, MELD-Na and the CreLiMAx risk score as to power in predicting short and medium-term mortality risk in the overall cohort: AUROCS for liver related risk of death were for MELD [6 months 0.89 (95% CI 0.80-0.98) p < 0.001; 12 months 0.89 (95% CI 0.81-0.96) p < 0.001]; MELD-Na [6 months 0.93 (95% CI 0.85-1.00) p < 0.001 and 12 months 0.89 (95% CI 0.80-0.98) p < 0.001]; CPS 6 months 0.91 (95% CI 0.85-0.97) p < 0.01 and 12 months 0.88 (95% CI 0.80-0.96) p < 0.001] and CreLiMAx score [6 months 0.80 (95% CI 0.67-0.96) p < 0.01 and 12 months 0.79 (95% CI 0.64-0.94) p = 0.001]. In a subgroup analysis of patients with Child-Pugh Class B cirrhosis, the CreLiMAx risk score remained the only parameter significantly differing in non-survivors and survivors. Furthermore, in these patients the proposed score had a good predictive performance. CONCLUSION: The CreLiMAx risk score appears to be a competitive and valid tool for estimating not only short- but also medium-term survival of patients with end-stage liver disease. Particularly in patients with Child-Pugh Class B cirrhosis the new score showed a good ability to identify patients not at risk of death.


Assuntos
Cirrose Hepática , Transplante de Fígado , Humanos , Cirrose Hepática/complicações , Testes de Função Hepática , Prognóstico , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de Doença
10.
Pediatr Transplant ; 24(3): e13683, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32166860

RESUMO

Abdominal wall closure after pediatric liver transplantation (pLT) in infants may be hampered by graft-to-recipient size discrepancy. Herein, we describe the use of a porcine dermal collagen acellular graft (PDCG) as a biological mesh (BM) for abdominal wall closure in pLT recipients. Patients <2 years of age, who underwent pLT from 2011 to 2014, were analyzed, divided into definite abdominal wall closure with and without implantation of a BM. Primary end-point was the occurrence of postoperative abdominal wall infection. Secondary end-points included 1- and 5-year patient and graft survival and the development of abdominal wall hernia. In five out of 21 pLT recipients (23.8%), direct abdominal wall closure was achieved, whereas 16 recipients (76.2%) received a BM. BM removal was necessary in one patient (6.3%) due to abdominal wall infection, whereas no abdominal wall infection occurred in the no-BM group. No significant differences between the two groups were observed for 1- and 5-year patient and graft survival. Two late abdominal wall hernias were observed in the BM group vs none in the no-BM group. Definite abdominal wall closure with a BM after pLT is feasible and safe when direct closure cannot be achieved with comparable postoperative patient and graft survival rates.


Assuntos
Parede Abdominal/cirurgia , Técnicas de Fechamento de Ferimentos Abdominais , Derme Acelular , Colágeno , Transplante de Fígado , Telas Cirúrgicas , Infecção da Ferida Cirúrgica/prevenção & controle , Estudos de Viabilidade , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Hérnia Incisional/epidemiologia , Hérnia Incisional/prevenção & controle , Lactente , Recém-Nascido , Masculino , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/epidemiologia
11.
Z Gastroenterol ; 58(10): 945-954, 2020 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-32838433

RESUMO

BACKGROUND: The lack of suitable allografts limits the availability of liver transplantation in Germany. The quality of potentially available German donor livers has to date not been analyzed. METHODS: Analysis of all donors for potential liver transplantations reported to the Eurotransplant by the German Organ Transplantation Foundation from 2010 to 2018. Categorization of transplanted and discarded organs utilizing available histopathological reports and predefined extended criteria for organ donation. RESULTS: A total of 8594 livers were offered for transplantation, of which 15.2 % were discarded. During the analysis period the proportion of donor livers from extended criteria donors increased from 65 % to 70 % (p = 0.005). In 2018, 21.3 % of offered donor livers were discarded, more than half (56.4 %) of these organs came from donors meeting multiple extended criteria. Livers were significantly more likely to be not transplanted, when from donors of older age (> 65 years; 41 vs. 28 %), BMI > 30 kg/m2 (29 vs. 14 %) or elevated transaminase levels (all p < 0,001). CONCLUSION: Despite the consistent organ scarcity in Germany, a relevant amount of livers cannot be transplanted due to a multitude of organ quality limitations. This should stimulate the search for concepts such as normothermic ex vivo machine perfusion to evaluate, protect and potentially improve organ quality.


Assuntos
Rejeição de Enxerto , Hepatopatias/cirurgia , Transplante de Fígado , Fígado/fisiopatologia , Perfusão/métodos , Doadores de Tecidos/estatística & dados numéricos , Alemanha , Humanos , Fígado/cirurgia , Preservação de Órgãos
12.
Transpl Int ; 32(10): 1074-1084, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31099091

RESUMO

Expansions of donor pools have a controversial impact on healthcare expenditures. The aim of this study was to investigate the emerging costs of expanded criteria donor (ECD) kidney transplantations (KT) and to identify independent risk factors for increased transplant-related costs. We present a retrospective explorative analysis of hospital costs and reimbursements of KTs performed between 2012 and 2016 in a German university hospital. A total of 174 KTs were examined, including 92 (52.9%) ECD organ transplantations. The ECD group comprised 43 (24.7%) 'old-for-old' transplantations. Median healthcare costs were 19 570€ (IQR 18 735-27 405€) in the standard criteria donor (SCD) group versus 25 478€ (IQR 19 957-29 634€) in the ECD group (+30%; P = 0.076). 'Old-for-old' transplantations showed the highest healthcare expenditures [26 702€ (19 570-33 940€)]. Irrespective of the allocation group, transplant-related costs increased significantly in obese (+6221€; P = 0.009) and elderly recipients (+6717€; P = 0.019), in warm ischaemia time exceeding 30 min (+3212€; P = 0.009) and in kidneys with DGF or surgical complications (+8976€ and +10 624€; both P < 0.001). Transplantation of ECD organs is associated with incremental costs, especially in elderly and obese recipients. A critical patient selection, treatment of obesity before KT and keeping warm ischaemia times short seem to be crucial, in order to achieve a cost-effective KT regardless of the allocation group.


Assuntos
Transplante de Rim/economia , Obtenção de Tecidos e Órgãos , Adulto , Idoso , Feminino , Humanos , Transplante de Rim/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
13.
Dig Dis Sci ; 64(2): 576-584, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30406480

RESUMO

BACKGROUND: MELD attempts to objectively predict the risk of mortality of patients with liver cirrhosis and is commonly used to prioritize organ allocation. Despite the usefulness of the MELD, updated metrics could further improve the accuracy of estimates of survival. AIMS: To assess and compare the prognostic ability of an enzymatic 13C-based liver function test (LiMAx) and distinct markers of liver function to predict 3-month mortality of patients with chronic liver failure. METHODS: We prospectively investigated liver function of 268 chronic liver failure patients without hepatocellular carcinoma. Primary study endpoint was liver-related death within 3 months of follow-up. Prognostic values were calculated using Cox proportional hazards and logistic regression analysis. RESULTS: The Cox proportional hazard model indicated that LiMAx (p < 0.001) and serum creatinine values (p < 0.001) were the significant parameters independently associated with the risk of liver failure-related death. Logistic regression analysis revealed LiMAx and serum creatinine to be independent predictors of mortality. Areas under the receiver-operating characteristic curves for MELD (0.86 [0.80-0.92]) and for a combined score of LiMAx and serum creatinine (0.83 [0.76-0.90]) were comparable. CONCLUSIONS: Apart from serum creatinine levels, enzymatic liver function measured by LiMAx was found to be an independent predictor of short-term mortality risk in patients with liver cirrhosis. A risk score combining both determinants allows reliable prediction of short-term prognosis considering actual organ function. Trial Registration Number (German Clinical Trials Register) # DRKS00000614.


Assuntos
Doença Hepática Terminal/enzimologia , Cirrose Hepática/enzimologia , Acetamidas , Testes Respiratórios , Dióxido de Carbono/análise , Isótopos de Carbono , Estudos de Coortes , Creatinina/metabolismo , Citocromo P-450 CYP1A2/metabolismo , Doença Hepática Terminal/metabolismo , Doença Hepática Terminal/mortalidade , Feminino , Humanos , Cirrose Hepática/metabolismo , Cirrose Hepática/mortalidade , Testes de Função Hepática , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Índice de Gravidade de Doença , Taxa de Sobrevida
14.
Kidney Int ; 91(6): 1447-1463, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28233611

RESUMO

The definition of biological donor organ age rather than chronological age seems obvious for the establishment of a valid pre-transplant risk assessment. Therefore, we studied gene expression for candidate markers in 60 zero-hour kidney biopsies. Compared with 29 younger donors under age 55, 31 elderly donors age 55 and older had significant mRNA expression for immunoproteasome subunits (PSMB8, PSMB9 and PSMB10), HLA-DRB, and transcripts of the activating cytotoxicity receptor NKG2D. Gene expression was validated in an independent donor cohort consisting of 37 kidneys from donors 30 years and under (Group I), 75 kidneys from donors age 31-54 years (Group II) and 75 kidneys from donors age 55 and older (Group III). Significant gene induction was confirmed in kidneys from Group III for PSMB9 and PSMB10. Strikingly, transcripts of NKG2D had the significantly highest gene induction in Group III versus Group II and Group I. Similar results were obtained for CDKN2A, but not for telomere length. Both NKG2D and CDKN2A mRNA expression were significantly correlated with creatinine levels at 24 months after transplantation. Univariate regression analysis showed significant predictive power regarding graft function at 6 and 12 months for NKG2D and CDKN2A. However, only NKG2D remained significantly predictive in the multivariate model at 12 months. Thus, our results reveal novel candidate markers in aged renal allografts, which could be helpful in the assessment of organ quality.


Assuntos
Senescência Celular , Seleção do Doador , Transplante de Rim/métodos , Rim/química , Subfamília K de Receptores Semelhantes a Lectina de Células NK/genética , Doadores de Tecidos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Áustria , Biópsia , Inibidor p16 de Quinase Dependente de Ciclina , Inibidor de Quinase Dependente de Ciclina p18/genética , Cisteína Endopeptidases/genética , Função Retardada do Enxerto/genética , Feminino , Regulação da Expressão Gênica , Marcadores Genéticos , Alemanha , Rejeição de Enxerto/genética , Sobrevivência de Enxerto , Cadeias beta de HLA-DR/genética , Humanos , Rim/patologia , Transplante de Rim/efeitos adversos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Complexo de Endopeptidases do Proteassoma/genética , RNA Mensageiro/genética , Fatores de Risco , Homeostase do Telômero , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
15.
Am J Transplant ; 17(12): 3199-3209, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28805342

RESUMO

It has already been shown that neutralization of the activating NK cell receptor NKG2D in combination with co-stimulation blockade prolongs graft survival of vascularized transplants. In order to clarify the underlying cellular mechanisms, we transplanted complete MHC-disparate BALB/c-derived cardiac grafts into C57BL/6 wildtypes or mice deficient for NKG2D (Klrk1-/- ). Although median survival was 8 days for both recipient groups, we detected already at day 5 posttransplantation significantly greater intragraft frequencies of NKp46+ NK cells in Klrk1-/- recipients than in wildtypes. This was followed by a significantly greater infiltration of CD4+ , but a lesser infiltration of CD8+ T cell frequencies. Contrary to published observations, co-stimulation blockade with CTLA4-Ig resulted in a significant acceleration of cardiac rejection by Klrk1-/- recipients, and this result was confirmed by applying a neutralizing antibody against NKG2D to wildtypes. In both experimental setups, grafts derived from Klrk1-/- recipients were characterized by significantly higher levels of interferon-γ mRNA, and both CD4+ and CD8+ T cells displayed a greater capacity for degranulation and interferon-γ production. In summary, our results clearly illustrate that NKG2D expression in the recipient is important for cardiac allograft survival, thus supporting the hypothesis that impairment of NK cells prevents the establishment of graft acceptance.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto/imunologia , Transplante de Coração/efeitos adversos , Subfamília K de Receptores Semelhantes a Lectina de Células NK/fisiologia , Animais , Rejeição de Enxerto/metabolismo , Rejeição de Enxerto/patologia , Interferon gama/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Complicações Pós-Operatórias , Taxa de Sobrevida , Transplante Homólogo
16.
J Pathol ; 239(1): 84-96, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26890577

RESUMO

A comparative analysis of inflammation between solid organs following donor brain death (BD) is still lacking and the detailed influence of BD accelerating ischaemia-reperfusion injury (IRI) post-transplantation remains to be addressed. Applying a murine model of BD, we demonstrated that 4 h after BD organs were characterized by distinct inflammatory expression patterns. For instance, lipocalin 2 (LCN2), a marker of acute kidney injury, was selectively induced in BD livers but not in kidneys. BD further resulted in significantly reduced frequencies of CD3(+) CD4(+) , CD3(+) CD8(+) T cells and NKp46(+) NK cells in the liver, whereas BD kidneys and hearts were characterized by significantly lower frequencies of conventional dendritic cells (cDCs). Syngeneic models of kidney (KTx) and heart transplantation (HTx) illustrated stronger gene expression in engrafted BD hearts only, but 20 h post-transplantation both organs displayed comparable intragraft lymphocyte frequencies, except for NK cells and graft function. Moreover, the complement factor C3d deposit detected in small vessels and capillaries in cardiac syngrafts did not significantly differ between BD and sham-transplanted groups. Finally, no further influence of donor BD on graft survival was detected in an allogeneic heart transplantation setting (C57BL/6 grafts into BALB/c recipients). We show for the first time that BD organs are characterized by a varying inflammatory profile; however, BD does not accelerate IRI in syngeneic KTx and HTx.


Assuntos
Morte Encefálica/imunologia , Transplante de Coração , Transplante de Rim , Traumatismo por Reperfusão/etiologia , Animais , Antígenos CD/metabolismo , Citocinas/metabolismo , Rejeição de Enxerto/imunologia , Imunidade Celular/fisiologia , Rim/metabolismo , Fígado/metabolismo , Linfócitos/imunologia , Masculino , Camundongos Endogâmicos C57BL , Nefrite/etiologia , Traumatismo por Reperfusão/imunologia , Imunologia de Transplantes/imunologia
17.
Transpl Int ; 27(10): 987-93, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24890468

RESUMO

A joint meeting organized by the European (ESOT) and The Transplantation (TTS) Societies for basic science research was organized in Paris, France, on November 7-9, 2013. Focused on new ideas and concepts in translational transplantation, the meeting served as a venue for state-of-the-art developments in basic transplantation immunology, such as the potential for tolerance induction through regulation of T-cell signaling. This meeting report summarizes important insights which were presented in Paris. It not only offers an overview of established aspects, such as the role of Tregs in transplantation, presented by Nobel laureate Rolf Zinkernagel, but also highlights novel facets in the field of transplantation, that is cell-therapy-based immunosuppression or composite tissue transplantation as presented by the emotional story given by Vasyly Rohovyy, who received two hand transplants. The ESOT/TTS joint meeting was an overall productive and enjoyable platform for basic science research in translational transplantation and fulfilled all expectations by giving a promising outlook for the future of research in the field of immunological transplantation research.


Assuntos
Imunidade Inata/imunologia , Transplante de Órgãos/normas , Imunologia de Transplantes/fisiologia , Tolerância ao Transplante/imunologia , Animais , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , França , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Imunidade Inata/fisiologia , Camundongos , Transplante de Órgãos/tendências , Sociedades Médicas , Linfócitos T/imunologia , Pesquisa Translacional Biomédica
18.
J Clin Med ; 13(6)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38541786

RESUMO

Background: Disruptions to surgical care for cancer patients during the COVID-19 pandemic remain an ongoing debate. This study assesses the effects of the COVID-19 pandemic on perioperative outcomes in a continuous series of surgically treated esophageal and gastric carcinoma patients at a large university hospital in Europe over 48 months. Methods: We conducted a retrospective single-center cohort study at a tertiary referral center. All patients who underwent oncologic esophageal or gastric resection between March 2018 and February 2022 were included in the analysis. The sample was split into a 24 months COVID-19 and an equivalent pre-COVID-19 control period. Outcome variables included caseload, in-hospital mortality, morbidity, treatment course, and disease stage at presentation. Results: Surgeons performed 287 operations, with around two-thirds (62%) of the cohort undergoing esophagectomy and one-third (38%) gastrectomy. The in-hospital mortality was 1% for the COVID-19 and the control periods. Patients did not present at a later disease stage nor did they wait longer for treatment. There was no decrease in caseload, and patients did not suffer from more perioperative complications during COVID-19. Conclusions: Esophageal and gastric carcinoma patients received safe and timely surgical care during the pandemic. Future pandemic protocols may streamline oncologic care towards tertiary referral centers.

19.
Cancers (Basel) ; 16(1)2023 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-38201540

RESUMO

In recent decades, robotic-assisted minimally invasive esophagectomy (RAMIE) has been increasingly adopted for patients with esophageal cancer (EC) or cancer of the gastroesophageal junction (GEJ). However, concerns regarding its costs compared to conventional minimally invasive esophagectomy (MIE) have emerged. This study examined outcomes and costs of RAMIE versus total MIE in 128 patients who underwent Ivor Lewis esophagectomy for EC/GEJ at our department between 2017 and 2021. Surgical costs were higher for RAMIE (EUR 12,370 vs. EUR 10,059, p < 0.001). Yet, median daily (EUR 2023 vs. EUR 1818, p = 0.246) and total costs (EUR 30,510 vs. EUR 29,180, p = 0.460) were comparable. RAMIE showed a lower incidence of postoperative pneumonia (8% vs. 25%, p = 0.029) and a trend towards shorter hospital stays (15 vs. 17 days, p = 0.205), which may have equalized total costs. Factors independently associated with higher costs included readmission to the intensive care unit (hazard ratio [HR] = 7.0), length of stay (HR = 13.5), anastomotic leak (HR = 17.0), and postoperative pneumonia (HR = 5.4). In conclusion, RAMIE does not impose an additional financial burden. This suggests that RAMIE may be considered as a valid alternative approach for esophagectomy. Attention to typical cost factors can enhance postoperative care across surgical methods.

20.
Hepatol Commun ; 7(1): e0012, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36633496

RESUMO

A growing number of clinical risk scores have been proposed to predict allograft failure after liver transplantation. However, validation of currently available scores in the Eurotransplant region is still lacking. We aimed to analyze all clinically relevant donor and recipient risk scores on a large German liver transplantation data set and performed a retrospective cohort analysis of liver transplantations performed at the Charité-Universitätsmedizin Berlin from January 2007 until December 2021 with organs from donation after brain death. We analyzed 9 previously published scores in 906 liver transplantations [Eurotransplant donor risk index (ET-DRI/DRI), donor age and model for end-stage liver disease (D-MELD), balance of risk (BAR), early allograft dysfunction (EAD), model for early allograft function (MEAF), liver graft assessment following transplantation (L-GrAFT7), early allograft failure simplified estimation (EASE), and a score by Rhu and colleagues). The EASE score had the best predictive value for 3-month, 6-month, and 12-month graft survival with a c-statistic of 0.8, 0.77, and 0.78, respectively. In subgroup analyses, the EASE score was suited best for male recipients with a high-MELD (>25) and an EAD organ. Scores only based on pretransplant data performed worse compared to scores including postoperative data (eg, ET-DRI vs. EAD, p<0.001 at 3-month graft survival). Out of these, the BAR score performed best with a c-statistic of 0.6. This a comprehensive comparison of the clinical utility of risk scores after liver transplantation. The EASE score sufficiently predicted 12-month graft and patient survival. Despite a relatively complex calculation, the EASE score provides significant prognostic value for patients and health care professionals in the Eurotransplant region.


Assuntos
Doença Hepática Terminal , Transplante de Fígado , Humanos , Masculino , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/cirurgia , Índice de Gravidade de Doença , Fatores de Risco , Estudos de Coortes , Alemanha/epidemiologia , Aloenxertos
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