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1.
Transpl Int ; 37: 12601, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694492

RESUMO

Controlled hypothermic storage (CHS) is a recent advance in lung transplantation (LTx) allowing preservation at temperatures higher than those achieved with traditional ice storage. The mechanisms explaining the benefits of CHS compared to conventional static ice storage (SIS) remain unclear and clinical data on safety and feasibility of lung CHS are limited. Therefore, we aimed to provide a focus review on animal experiments, molecular mechanisms, CHS devices, current clinical experience, and potential future benefits of CHS. Rabbit, canine and porcine experiments showed superior lung physiology after prolonged storage at 10°C vs. ≤4°C. In recent molecular analyses of lung CHS, better protection of mitochondrial health and higher levels of antioxidative metabolites were observed. The acquired insights into the underlying mechanisms and development of CHS devices allowed clinical application and research using CHS for lung preservation. The initial findings are promising; however, further data collection and analysis are required to draw more robust conclusions. Extended lung preservation with CHS may provide benefits to both recipients and healthcare personnel. Reduced time pressure between procurement and transplantation introduces flexibility allowing better decision-making and overnight bridging by delaying transplantation to daytime without compromising outcome.


Assuntos
Transplante de Pulmão , Pulmão , Preservação de Órgãos , Animais , Preservação de Órgãos/métodos , Transplante de Pulmão/métodos , Humanos , Suínos , Pulmão/fisiologia , Cães , Coelhos , Criopreservação/métodos
2.
World J Surg Oncol ; 22(1): 96, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38622623

RESUMO

BACKGROUND: Pleural neoplasms are rare and can be subdivided into pleural metastasis and primary pleural neoplasms. Non-mesothelioma primary pleural neoplasms are a diverse group of extremely rare pathologies. CASE PRESENTATION: In this case series, we describe the presentation and management of two rare primary pleural neoplasms. A first case describes a primary pleural yolk sac tumor treated with neoadjuvant chemotherapy, extended pleurectomy decortication, and hyperthermic intrathoracic chemotherapy. In a second case we describe the management of a primary pleural synovial sarcoma by neoadjuvant chemotherapy and extrapleural pneumonectomy. A complete resection was obtained in both cases and the post-operative course was uncomplicated. No signs of tumor recurrence were noted during follow-up in the first patient. In the second patient a local recurrence was diagnosed 6 months after surgery. CONCLUSION: Neo-adjuvant chemotherapy followed by extensive thoracic surgery, including hyperthermic intrathoracic chemotherapy, is a feasible treatment strategy for non-mesothelioma primary pleural neoplasms, but careful follow-up is required.


Assuntos
Tumor do Seio Endodérmico , Neoplasias Pleurais , Sarcoma Sinovial , Humanos , Sarcoma Sinovial/cirurgia , Tumor do Seio Endodérmico/cirurgia , Resultado do Tratamento , Recidiva Local de Neoplasia/cirurgia , Neoplasias Pleurais/cirurgia , Neoplasias Pleurais/patologia , Pneumonectomia
3.
Am J Physiol Lung Cell Mol Physiol ; 325(5): L675-L688, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37724349

RESUMO

Lung transplantation (LTx) is a challenging procedure. Following the process of ischemia-reperfusion injury, the transplanted pulmonary graft might become severely damaged, resulting in primary graft dysfunction. In addition, during the intraoperative window, the right ventricle (RV) is at risk of acute failure. The interaction of right ventricular function with lung injury is, however, poorly understood. We aimed to address this interaction in a translational porcine model of pulmonary ischemia-reperfusion injury. Advanced pulmonary and hemodynamic assessment was used, including right ventricular pressure-volume loop analysis. The acute model was based on clamping and unclamping of the left lung hilus, respecting the different hemodynamic phases of a clinical lung transplantation. We found that forcing entire right ventricular cardiac output through a lung suffering from ischemia-reperfusion injury increased afterload (pulmonary vascular resistance from baseline to end experiment P < 0.0001) and induced right ventricular failure (RVF) in 5/9 animals. Notably, we identified different compensation patterns in failing versus nonfailing ventricles (arterial elastance P = 0.0008; stroke volume P < 0.0001). Furthermore, increased vascular pressure and flow produced by the right ventricle resulted in higher pulmonary injury, as measured by ex vivo CT density (correlation: pressure r = 0.8; flow r = 0.85). Finally, RV ischemia as measured by troponin-T was negatively correlated with pulmonary injury (r = -0.76); however, troponin-T values did not determine RVF in all animals. In conclusion, we demonstrate a delicate balance between development of pulmonary ischemia-reperfusion injury and right ventricular function during lung transplantation. Furthermore, we provide a physiological basis for potential benefit of extracorporeal life support technology.NEW & NOTEWORTHY In contrast to the abundant literature of mechanical pulmonary artery clamping to increase right ventricular afterload, we developed a model adding a biological factor of pulmonary ischemia-reperfusion injury. We did not only focus on the right ventricular behavior, but also on the interaction with the injured lung. We are the first to describe this interaction while addressing the hemodynamic intraoperative phases of clinical lung transplantation.


Assuntos
Insuficiência Cardíaca , Lesão Pulmonar , Transplante de Pulmão , Traumatismo por Reperfusão , Disfunção Ventricular Direita , Suínos , Animais , Função Ventricular Direita , Troponina T , Pulmão , Hemodinâmica/fisiologia
4.
Am J Transplant ; 23(1): 111-114, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36695613

RESUMO

Pulmonary vein stenosis (PVS) and pulmonary vein occlusion (PVO) represent rare complications after lung transplantation (LTx), with limited therapeutic options and a high risk of graft loss. We present 2 cases of successful endovascular transatrial stenting following double LTx. A 60-year-old woman with chronic obstructive pulmonary disease who underwent double lobar LTx was diagnosed at postoperative day 72 with a high-grade PVS on the left side. A 22-year-old woman with idiopathic pulmonary arterial hypertension who underwent double LTx was diagnosed 9 days later with PVO of the left upper lobe vein. To avoid surgical reintervention, endovascular transatrial dilatation and stenting were performed successfully in both cases. Transatrial endovascular stenting of PVS or PVO after LTx seems an effective and safe treatment option that should be considered for these life-threatening complications and executed with care.


Assuntos
Pneumopatias , Transplante de Pulmão , Veias Pulmonares , Pneumopatia Veno-Oclusiva , Estenose de Veia Pulmonar , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Adulto , Estenose de Veia Pulmonar/cirurgia , Estenose de Veia Pulmonar/complicações , Veias Pulmonares/cirurgia , Pneumopatia Veno-Oclusiva/etiologia , Pneumopatia Veno-Oclusiva/cirurgia , Pulmão , Pneumopatias/complicações , Transplante de Pulmão/efeitos adversos , Resultado do Tratamento , Estudos Retrospectivos
5.
Ann Surg ; 278(5): 807-814, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37497671

RESUMO

OBJECTIVE: To describe the worldwide experience with living donation (LD) in intestinal transplantation (ITx) and compare short-term and long-term outcomes to a propensity-matched cohort of deceased donors. BACKGROUND: ITx is a rare life-saving procedure for patients with complicated intestinal failure (IF). Living donation (LD)-ITx has been performed with success, but no direct comparison with deceased donation (DD) has been performed. The Intestinal Transplant Registry (ITR) was created in 1985 by the Intestinal Transplant Association to capture the worldwide activity and promote center's collaborations. METHODS: Based on the ITR, 4156 ITx were performed between January 1987 and April 2019, of which 76 (1.8%) were LD, including 5 combined liver-ITx, 7 ITx-colon, and 64 isolated ITx. They were matched with 186 DD-ITx for recipient age/sex, weight, region, IF-cause, retransplant, pretransplant status, ABO compatibility, immunosuppression, and transplant date. Primary endpoints were acute rejection and 1-/5-year patient/graft survival. RESULTS: Most LDs were performed in North America (61%), followed by Asia (29%). The mean recipient age was: 22 years; body mass index: 19kg/m²; and female/male ratio: 1/1.4. Volvulus (N=17) and ischemia (N=17) were the most frequent IF-causes. Fifty-two percent of patients were at home at the time of transplant. One-/5-year patient survival for LD and DD was 74.2/49.8% versus 80.3/48.1%, respectively ( P =0.826). One-/5-year graft survival was 60.3/40.6% versus 69.2/36.1%, respectively ( P =0.956). Acute rejection was diagnosed in 47% of LD versus 51% of DD ( P =0.723). CONCLUSION: Worldwide, LD-ITx has been rarely performed. This retrospective matched ITR analysis revealed no difference in rejection and in patient/graft survival between LD and DD-ITx.

6.
Ann Surg ; 278(3): e641-e649, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36735450

RESUMO

OBJECTIVE: To describe our experience with lung transplantation (LTx) from donors ≥70 years and compare short and long-term outcomes to a propensity-matched cohort of donors <70 years. BACKGROUND: Although extended-criteria donors have been widely used to enlarge the donor pool, the experience with LTx from older donors (≥70 years) remains limited. METHODS: All single-center bilateral LTx between 2010 and 2020 were retrospectively analyzed. Matching (1:1) was performed for the donor (type, sex, smoking history, x-ray abnormalities, partial pressure of oxygen/fraction of inspired oxygen ratio, and time on ventilator) and recipient characteristics (age, sex, LTx indication, perioperative extracorporeal life support, and cytomegalovirus mismatch). Primary graft dysfunction grade-3, 5-year patient, and chronic lung allograft dysfunction-free survival were analyzed. RESULTS: Out of 647 bilateral LTx, 69 were performed from donors ≥70 years. The mean age in the older donor cohort was 74 years (range: 70-84 years) versus 49 years (range: 12-69 years) in the matched younger group. No significant differences were observed in the length of ventilatory support, intensive care unit, or hospital stay. Primary graft dysfunction-3 was 26% in the older group versus 29% in younger donor recipients ( P = 0.85). Reintervention rate was comparable (29% vs 16%; P = 0.10). Follow-up bronchoscopy revealed no difference in bronchial anastomotic complications ( P = 1.00). Five-year patient and chronic lung allograft dysfunction-free survivals were 73.6% versus 73.1% ( P = 0.72) and 51.5% versus 59.2% ( P = 0.41), respectively. CONCLUSIONS: LTx from selected donors ≥70 years is feasible and safe, yielding comparable short and long-term outcomes in a propensity-matched analysis with younger donors (<70 years).


Assuntos
Transplante de Pulmão , Disfunção Primária do Enxerto , Humanos , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Resultado do Tratamento , Doadores de Tecidos , Oxigênio
7.
Radiology ; 307(1): e221145, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36537894

RESUMO

Background Interstitial lung abnormalities (ILAs) reflect imaging features on lung CT scans that are compatible with (early) interstitial lung disease. Despite accumulating evidence regarding the incidence, risk factors, and prognosis of ILAs, the histopathologic correlates of ILAs remain elusive. Purpose To determine the correlation between radiologic and histopathologic findings in CT-defined ILAs in human lung explants. Materials and Methods Explanted lungs or lobes from participants with radiologically documented ILAs were prospectively collected from 2010 to 2021. These specimens were air-inflated, frozen, and scanned with CT and micro-CT (spatial resolution of 0.7 mm and 90 µm, respectively). Subsequently, the lungs were cut and sampled with core biopsies. At least five samples per lung underwent micro-CT and subsequent histopathologic assessment with semiquantitative remodeling scorings. Based on area-specific radiologic scoring, the association between radiologic and histopathologic findings was assessed. Results Eight lung explants from six donors (median age at explantation, 71 years [range, 60-83 years]; four men) were included (unused donor lungs, n = 4; pre-emptive lobectomy for oncologic indications, n = 2). Ex vivo CT demonstrated ground-glass opacification, reticulation, and bronchiectasis. Micro-CT and histopathologic examination demonstrated that lung abnormalities were frequently paraseptal and associated with fibrosis and lymphocytic inflammation. The histopathologic results showed varying degrees of fibrosis in areas that appeared normal on CT scans. Regions of reticulation on CT scans generally had greater fibrosis at histopathologic analysis. Vasculopathy and bronchiectasis were also often present at histopathologic examination of lungs with ILAs. Fully developed fibroblastic foci were rarely observed. Conclusion This study demonstrated direct histologic correlates of CT-defined interstitial lung abnormalities. © RSNA, 2022 Supplemental material is available for this article. See also the editorial by Jeudy in this issue.


Assuntos
Bronquiectasia , Doenças Pulmonares Intersticiais , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Pulmão/diagnóstico por imagem , Pulmão/patologia , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Fibrose , Microtomografia por Raio-X
8.
J Med Virol ; 95(4): e28736, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37185854

RESUMO

Rates and modulators of SARS-CoV-2 vaccine nonresponse and breakthrough infections remain unclear in serially vaccinated transplant recipients. In a prospective, mono-centric, observational study, 1878 adult solid organ and hematopoietic cell transplant recipients, with prior SARS-CoV-2 vaccination, were included between March 2021 and February 2022. SARS-CoV-2 anti-spike IgG antibodies were measured at inclusion and details on SARS-CoV-2 vaccine doses and infection were collected. No life-threatening adverse events were reported after a total of 4039 vaccine doses. In transplant recipients without prior SARS-CoV-2 infection (n = 1636), antibody response rates ranged widely, from 47% in lung transplant to 90% in liver transplant and 91% in hematopoietic cell transplant recipients after third vaccine dose. Antibody positivity rate and levels increased after each vaccine dose in all types of transplant recipients. In multivariable analysis, older age, chronic kidney disease and daily dose of mycophenolate and corticosteroids were negatively associated with antibody response rate. Overall rate of breakthrough infections was 25.2% and mainly (90.2%) occurred after third and fourth vaccine dose. Lung transplant recipients had the highest rates of severe breakthrough infection (10.5%) and death (2.5%). In multivariable analysis, older age, daily dose of mycophenolate and corticosteroids were associated with severe breakthrough infection. Transplant recipients with infection before first vaccine dose (n = 160) had higher antibody response rates and levels after each vaccine dose, and a significantly lower overall rate of breakthrough infections compared to those without prior infection. Antibody response after SARS-CoV-2 vaccination and rate of severe breakthrough infections vary largely between different transplant types and are modulated by specific risk factors. The observed heterogeneity supports a tailored approach against COVID-19 in transplant recipients.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Transplante de Células-Tronco Hematopoéticas , Adulto , Humanos , Anticorpos Antivirais , Formação de Anticorpos , Infecções Irruptivas , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Imunoglobulina G , Imunossupressores/efeitos adversos , Estudos Prospectivos , SARS-CoV-2 , Transplantados
9.
Ann Surg Oncol ; 30(1): 543-560, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36151429

RESUMO

BACKGROUND: Optimal treatment for thymoma with pleural dissemination (TPD) remains unclear. Extended radical resection is the cornerstone for local treatment but the need for pleuro-pneumonectomy is debatable. Cytoreductive surgery with intraoperative hyperthermic intrathoracic chemotherapy (HITHOC) provides an alternative strategy to reduce tumor load and prevent pleural recurrence. OBJECTIVE: The aim of this review was to provide an overview of current literature regarding HITHOC for TPD. METHODS: A systematic literature review (PRISMA) was performed in the EMBASE, MEDLINE, Cochrane and Web of Science databases, resulting in 154 papers selected for screening (PROSPERO: CRD42020208242). Title, abstract, and full-text screening resulted in 13 papers subjected to structured data extraction and methodological quality assessment. One additional case from our department was included. Inclusion criteria were original research reporting on patients diagnosed with TPD; oncological outcome reporting; intraoperative HITHOC; and papers written in English, Dutch or German. Methodological quality was assessed using the Risk-of-Bias (RoB)-2 Tool and the Newcastle-Ottawa scale. RESULTS: HITHOC for TPD was reported in 171 cases. HITHOC-related mortality was absent and morbidity was reported in three cases. Intrathoracic perfusion of a platinum-derivative, often combined with other chemotherapeutic drugs at >40°C for 60 min or longer was always used. Post-HITHOC recurrence was reported in 37/120 cases (31%). In patients with a minimal 1-year follow-up, average time to recurrence was 68.5 months. CONCLUSION: Combining cytoreductive surgery and HITHOC is feasible and safe for TPD. The strong heterogeneity in the literature impedes proper outcome analysis. More research is needed to better understand the additional benefit of HITHOC in the TPD setting.

10.
Transpl Int ; 36: 11371, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37671117

RESUMO

Intestinal donor criteria are classically kept strict, thereby limiting donor supply. Indications for intestinal transplantation (ITx) are rare, but improved outcome and new emerging indications lead to increased demand and relaxing donor criteria should be considered. We sought to compare the donor criteria of intestines transplanted at our center with predefined (per protocol) criteria, and to determine how relaxing donor criteria could impact the potential donor pool. Donor criteria used in 22 consecutive ITx at our center between 2000 and 2020 were compared with predefined criteria. Next, multiorgan donors effectively offered by our Donor Network to Eurotransplant between 2014 and 2020 were retrospectively screened, according to predefined and effectively used intestinal donation criteria. Finally, utilization rate of offered intestines was calculated. In our ITx series, the effectively used donor criteria were less strict than those initially predefined. With these relaxed criteria, a favorable 5-year graft/patient survival of 75% and 95%, respectively was reached. Applying these relaxed criteria would lead to a 127% increase in intestinal offers. Paradoxically, 70% of offered intestines were not used. In conclusion, a significant increase in intestinal donation could be obtained by relaxing donor criteria, while still achieving excellent outcome. Offered intestines are underutilized.


Assuntos
Doadores de Tecidos , Transplantes , Humanos , Estudos Retrospectivos , Sobrevivência de Enxerto , Intestinos
11.
Transpl Int ; 36: 10768, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36873745

RESUMO

Fungal exposure and sensitization negatively affect outcomes in various respiratory diseases, however, the effect of fungal sensitization in lung transplant (LTx) recipients is still unknown. We performed a retrospective cohort study of prospectively collected data on circulating fungal specific IgG/IgE antibodies, and their correlation with fungal isolation, chronic lung allograft dysfunction (CLAD) and overall survival after LTx. 311 patients transplanted between 2014 and 2019 were included. Patients with elevated Aspergillus fumigatus or Aspergillus flavus IgG (10%) had more mold and Aspergillus species isolation (p = 0.0068 and p = 0.0047). Aspergillus fumigatus IgG was specifically associated with Aspergillus fumigatus isolation in the previous or consecutive year (AUC 0.60, p = 0.004 and AUC 0.63, p = 0.022, respectively). Elevated Aspergillus fumigatus or Aspergillus flavus IgG was associated with CLAD (p = 0.0355), but not with death. Aspergillus fumigatus, Aspergillus flavus or Aspergillus niger IgE was elevated in 19.3% of patients, but not associated with fungal isolation, CLAD or death. Mold isolation and Aspergillus species isolation from respiratory cultures were associated with CLAD occurrence (p = 0.0011 and p = 0.0005, respectively), and Aspergillus species isolation was also associated with impaired survival (p = 0.0424). Fungus-specific IgG could be useful in long-term follow-up post-LTx, as a non-invasive marker for fungal exposure, and thus a diagnostic tool for identifying patients at risk for fungal-related complications and CLAD.


Assuntos
Transplante de Pulmão , Humanos , Estudos Retrospectivos , Imunoglobulina G , Imunoglobulina E , Pulmão , Aloenxertos
12.
Int J Mol Sci ; 24(3)2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36768910

RESUMO

Animal research in intestinal ischemia-reperfusion injury (IRI) is mainly performed in rodent models. Previously, intraperitoneal (I.P.) injections with ketamine-xylazine mixtures were used. Nowadays, volatile anesthetics (isoflurane) are more common. However, the impact of the anesthetic method on intestinal IRI has not been investigated. We aim to analyze the different anesthetic methods and their influence on the extent of intestinal IRI in a rat model. Male Sprague-Dawley rats were used to investigate the effect of I.P. anesthesia on 60 min of intestinal ischemia and 60 min of reperfusion in comparison to hyperoxygenation (100% O2) and volatile isoflurane anesthesia. In comparison to I.P. anesthesia with room air (21% O2), supplying 100% O2 improved 7-day survival by cardiovascular stabilization, reducing lactic acidosis and preventing vascular leakage. However, this had no effect on the intestinal epithelial damage, permeability, and inflammatory response observed after intestinal IRI. In contrast to I.P. + 100% O2, isoflurane anesthesia reduced intestinal IRI by preventing ongoing low-flow reperfusion hypotension, limiting intestinal epithelial damage and permeability, and by having anti-inflammatory effects. When translating the aforementioned results of this study to clinical situations, such as intestinal ischemia or transplantation, the potential protective effects of hyperoxygenation and volatile anesthetics require further research.


Assuntos
Anestésicos Inalatórios , Isoflurano , Traumatismo por Reperfusão , Ratos , Masculino , Animais , Isoflurano/farmacologia , Anestésicos Inalatórios/farmacologia , Roedores , Oxigênio , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Isquemia
13.
Int J Mol Sci ; 24(13)2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37445954

RESUMO

Intestinal ischemia-reperfusion injury (IRI) is a common clinical entity, and its outcome is unpredictable due to the triad of inflammation, increased permeability and bacterial translocation. Polyethylene glycol (PEG) is a polyether compound that is extensively used in pharmacology as an excipient in various products. More recently, this class of products have shown to have potent anti-inflammatory, anti-apoptotic, immunosuppressive and cell-membrane-stabilizing properties. However, its effects on the outcome after intestinal IRI have not yet been investigated. We hypothesized that PEG administration would reduce the effects of intestinal IRI in rodents. In a previously described rat model of severe IRI (45 min of ischemia followed by 60 min of reperfusion), we evaluated the effect of IV PEG administration at different doses (50 and 100 mg/kg) before and after the onset of ischemia. In comparison to control animals, PEG administration stabilized the endothelial glycocalyx, leading to reduced reperfusion edema, bacterial translocation and inflammatory reaction as well as improved 7-day survival. These effects were seen both in a pretreatment and in a treatment setting. The fact that this product is readily available and safe should encourage further clinical investigations in settings of intestinal IRI, organ preservation and transplantation.


Assuntos
Traumatismo por Reperfusão , Roedores , Ratos , Animais , Polietilenoglicóis/farmacologia , Polietilenoglicóis/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Intestinos , Preservação de Órgãos
14.
Int J Mol Sci ; 24(19)2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37834329

RESUMO

Intestinal ischemia is a potentially catastrophic emergency, with a high rate of morbidity and mortality. Currently, no specific pharmacological treatments are available. Previous work demonstrated that pre-treatment with obeticholic acid (OCA) protected against ischemia reperfusion injury (IRI). Recently, a more potent and water-soluble version has been synthesized: Intercept 767 (INT-767). The aim of this study was to investigate if intravenous treatment with INT-767 can improve outcomes after IRI. In a validated rat model of IRI (60 min ischemia + 60 min reperfusion), three groups were investigated (n = 6/group): (i) sham: surgery without ischemia; (ii) IRI + vehicle; and (iii) IRI + INT-767. The vehicle (0.9% NaCl) or INT-767 (10 mg/kg) were administered intravenously 15 min after start of ischemia. Endpoints were 7-day survival, serum injury markers (L-lactate and I-FABP), histology (Park-Chiu and villus length), permeability (transepithelial electrical resistance and endotoxin translocation), and cytokine expression. Untreated, IRI was uniformly lethal by provoking severe inflammation and structural damage, leading to translocation and sepsis. INT-767 treatment significantly improved survival by reducing inflammation and preserving intestinal structural integrity. This study demonstrates that treatment with INT-767 15 min after onset of intestinal ischemia significantly decreases IRI and improves survival. The ability to administer INT-767 intravenously greatly enhances its clinical potential.


Assuntos
Ácidos e Sais Biliares , Intestinos , Receptores Citoplasmáticos e Nucleares , Receptores Acoplados a Proteínas G , Traumatismo por Reperfusão , Animais , Ratos , Inflamação/tratamento farmacológico , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Traumatismo por Reperfusão/tratamento farmacológico , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Ácidos e Sais Biliares/uso terapêutico , Intestinos/irrigação sanguínea
15.
Am J Transplant ; 22(5): 1418-1429, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35029023

RESUMO

Primary graft dysfunction (PGD) is a major obstacle after lung transplantation (LTx), associated with increased early morbidity and mortality. Studies in liver and kidney transplantation revealed prolonged anastomosis time (AT) as an independent risk factor for impaired short- and long-term outcomes. We investigated if AT during LTx is a risk factor for PGD. In this retrospective single-center cohort study, we included all first double lung transplantations between 2008 and 2016. The association of AT with any PGD grade 3 (PGD3) within the first 72 h post-transplant was analyzed by univariable and multivariable logistic regression analysis. Data on AT and PGD was available for 427 patients of which 130 (30.2%) developed PGD3. AT was independently associated with the development of any PGD3 ≤72 h in uni- (odds ratio [OR] per 10 min 1.293, 95% confidence interval [CI 1.136-1.471], p < .0001) and multivariable (OR 1.205, 95% CI [1.022-1.421], p = .03) logistic regression analysis. There was no evidence that the relation between AT and PGD3 differed between lung recipients from donation after brain death versus donation after circulatory death donors. This study identified AT as an independent risk factor for the development of PGD3 post-LTx. We suggest that the implantation time should be kept short and the lung cooled to decrease PGD-related morbidity and mortality post-LTx.


Assuntos
Transplante de Pulmão , Disfunção Primária do Enxerto , Anastomose Cirúrgica/efeitos adversos , Estudos de Coortes , Humanos , Transplante de Pulmão/efeitos adversos , Disfunção Primária do Enxerto/etiologia , Estudos Retrospectivos , Fatores de Risco
16.
Transpl Int ; 35: 10048, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35497884

RESUMO

Objective: The impact of previous lung volume reduction surgery (LVRS) or endoscopic lung volume reduction (ELVR) on lung transplantation (LuTX) remains unclear. This study assesses the risk of previous lung volume reduction on the outcome of a later LuTX. Methods: Patients suffering from emphysema who underwent bilateral LuTX were included in this multicenter analysis. Study groups were defined as: previous LVRS, previous ELVR, controls. Imbalances were corrected by coarsened exact matching for center, gender, age, diagnosis, and BMI. A comparative analysis of intraoperative characteristics, perioperative outcome and long-term survival was performed. Results: 615 patients were included (LVRS = 26; ELVR = 60). Compared to controls, LVRS patients had a higher rate of postoperative ECMO (15.4 vs. 3.9%; p = 0.006), whereas ELVR patients suffered more often from wound infections (8.9% vs. 2.5%; p = 0.018). Perioperative outcome, duration of ventilation, ICU stay, and hospital stay were comparable between groups. Bacterial colonization of the airway differed significantly between both LVR groups and controls in pre- and post-LuTX cultures. Survival was not impacted (1-/3-/5-year survival for LVRS: 92.3%/85.7%/77.1%; controls: 91.3%/82.4%/76.3%; p = 0.58 | ELVR: 93.1%/91%/91%; controls 91.2%/81.7%/75.3%; p = 0.17). Conclusion: Lung volume reduction does not impact short and long-time survival after bilateral LuTX. Due to differences in airway colonization after LVR, caution to prevent infectious complications is warranted.


Assuntos
Enfisema , Transplante de Pulmão , Humanos , Tempo de Internação , Pneumonectomia , Período Pós-Operatório
17.
Transpl Int ; 35: 10159, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35651878

RESUMO

The MUC5B promoter polymorphism (rs35705950) has been associated with interstitial lung disease (ILD) and with prolonged pre-transplant survival in idiopathic pulmonary fibrosis (IPF), but no information is available regarding its prevalence in other respiratory diseases and its influence on post-transplant outcome. We included the Leuven lung transplantation cohort between 1991 and 2015 (n = 801). We assessed the minor allele frequency (MAF) of the MUC5B variant in the entire study cohort and investigated the influence of recipient MUC5B promoter polymorphism on post-transplant outcome in patients who were transplanted after 2004. MUC5B was successfully genotyped in 746 patients. The MAF was significantly higher in ILD (17.6%) compared to chronic obstructive pulmonary disease (COPD)/emphysema (9.3%), cystic fibrosis (CF)/bronchiectasis (BRECT) (7.5%) and pulmonary hypertension (PHT) (7.4%) (p < 0.001). No association was observed between rs35705950 and chronic lung allograft dysfunction (CLAD)/graft loss in the ILD population [CLAD: HR 1.37 95% CI (0.70-2.68); graft loss: HR 1.02 95% CI (0.55-1.89)], nor the entire study cohort [CLAD: HR 0.96 95% CI (0.69-1.34); graft loss: HR 0.97 95% CI (0.70-1.35)]. The MUC5B promoter polymorphism is a very specific predictive factor for the presence of pulmonary fibrosis as it is only associated with pulmonary fibrosis and not with other chronic respiratory diseases. While the MUC5B promoter variant is associated with better pre-transplant survival among IPF patients, recipient MUC5B promoter variant does not play a role in post-transplant outcome.


Assuntos
Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Predisposição Genética para Doença , Humanos , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/cirurgia , Doenças Pulmonares Intersticiais/genética , Doenças Pulmonares Intersticiais/cirurgia , Mucina-5B/genética , Polimorfismo Genético , Regiões Promotoras Genéticas
18.
Int J Hyperthermia ; 39(1): 1153-1157, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36049823

RESUMO

Aim: Pleural dissemination of pseudomyxoma peritonei (PMP) is an extremely rare diagnosis, for which no standard therapy is available.Methods: We describe the successful treatment of a 67-year-old male diagnosed with left-sided intrapleural dissemination of PMP (low-grade appendiceal mucinous neoplasm), 2 years after treatment of abdominal PMP with cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy. Treatment consisted of extended pleural decortication (ePD) and oxaliplatin-based hyperthermic intrathoracic chemotherapy (HITHOC). The patient is doing well without complications or signs of recurrence, 26 months after thoracic surgery.Conclusion: ePD in combination with HITHOC is a valuable treatment for thoracic PMP.


Assuntos
Neoplasias do Apêndice , Hipertermia Induzida , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Idoso , Neoplasias do Apêndice/terapia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Humanos , Masculino , Neoplasias Peritoneais/diagnóstico por imagem , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Pseudomixoma Peritoneal/diagnóstico por imagem , Pseudomixoma Peritoneal/tratamento farmacológico , Pseudomixoma Peritoneal/cirurgia , Estudos Retrospectivos
19.
Curr Opin Organ Transplant ; 27(2): 106-111, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35191400

RESUMO

PURPOSE OF REVIEW: Intestinal donation is currently restricted to 'perfect' donors, as the intestine is extremely vulnerable to ischemia. With generally deteriorating donor quality and increasing indications for intestinal transplantation (ITx), the potential to safely increase the donor pool should be evaluated. RECENT FINDINGS: Increasing awareness on intestinal donation (often forgotten) and cautiously broadening the strict donor criteria (increasing age, resuscitation time and ICU stay) could expand the potential donor pool. Donors after circulatory death (DCD) have so far not been considered for ITx, due to the particularly detrimental effect of warm ischemia on the intestine. However, normothermic regional perfusion might be a well tolerated strategy to render the use of DCD intestinal grafts feasible. Furthermore, machine perfusion is under continuous development and might improve preservation of the intestine and potentially offer a platform to modulate the intestinal graft. Lastly, living donation currently represents only a minority of all ITxs performed worldwide. Various studies and registry analysis show that it can be performed safely for the donor and successfully in the recipient. SUMMARY: Several potential strategies are available to expand the current intestinal donor pool. Most of them require further investigation or technical developments before they can be implemented in the clinical routine.


Assuntos
Obtenção de Tecidos e Órgãos , Morte , Sobrevivência de Enxerto , Humanos , Intestinos , Preservação de Órgãos/efeitos adversos , Perfusão , Doadores de Tecidos
20.
Acta Chir Belg ; 121(4): 254-260, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32022643

RESUMO

INTRODUCTION: Extrahepatic portal vein thrombosis (PVT) is the most common cause of portal hypertension (PH), particularly in children. PH-related manifestations include refractory variceal bleeding, splenomegaly and ascites. Albeit more rarely performed, the distal splenorenal shunt (Warren's shunt) has proven to be effective in selectively decompressing the collateral circulation. The aim of our study was to describe our experience with the distal splenorenal shunt and to determine the long-term effect on PH-related side-effects. METHODS: Distal splenorenal shunt operations performed at our institution between 2000 and 2014 were reviewed for: age, male/female ratio, children/adults ratio, body mass index, indications, grade of PVT (Yerdel classification), maximal shunt-flow velocity, shunt patency and thrombosis, re-intervention for variceal bleeding and survival. Complications of PH (esophageal variceal bleeding and ascites) were compared pre- versus post-operatively (last follow-up). Paired student t-test and fisher's exact were applied for pre- versus post-operative comparison. Results are reported as median [range]. RESULTS: Fourteen patients with PVT and refractory complications of PH underwent distal splenorenal shunt surgery. Age was 15 years [4.5-66]. Male/female ratio was 7/7. PVT -grade was 2 [1-4]. Follow-up was 3 [0.5-14]. All shunts were patent (100%) with no shunt thrombosis (0%) at last follow-up. There was no re-intervention for variceal bleeding (0%) and survival at last follow-up was 100%. Occurrence of esophageal variceal bleeding was higher pre-operatively (57%) than postoperatively (0%) (p = .0032) and also the incidence of ascites was higher pre-operatively (79%) than postoperatively (0%) (p < .0001). CONCLUSIONS: Based on our experience, the distal splenorenal shunt can be considered a valuable surgical technique for PVT-induced PH, with excellent post-operative prevention of complications of PH.


Assuntos
Varizes Esofágicas e Gástricas , Hipertensão Portal , Derivação Esplenorrenal Cirúrgica , Adolescente , Adulto , Criança , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/cirurgia , Feminino , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/cirurgia , Hospitais Universitários , Humanos , Hipertensão Portal/complicações , Hipertensão Portal/cirurgia , Masculino
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