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2.
Ann Hepatol ; 29(3): 101498, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38479458

RESUMO

The understanding of the mechanisms for the development of ascites has evolved over the years, involving the liver, peritoneum, heart, and kidneys as key responsible for its formation. In this article, we review the pathophysiology of ascites formation, introducing the role of the intestine as a major responsible for ascites production through "a game changer" case.

3.
Hum Immunol ; : 110788, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38519405

RESUMO

The intestines have been considered the "forbidden organ" for years, and intestinal failure became the last organ failure recognized as such in the medical field. The impossibility of providing adequate nutritional support, turned these patients into recipients of just palliative comfort. In the 1960's, parenteral nutrition appeared as the most reasonable replacement therapy, but the initial success obtained with clinical kidney, heart, liver, lung and pancreas transplantation served as background to explore intestinal transplantation. The first clinical report of an isolated intestinal transplant was done by Richard Lillihei in 1967; in 1983, Thomas Starzl, performed the first multi visceral transplant, and in 1990, David Grant performed the first combined liver-intestinal transplant in an adult recipient in Canada. Since then, advances in immunosuppressive therapies and surgical innovations have allowed not only a continuous increase in indications, but also a worldwide application of all procedures, bringing clinical intestinal transplantation to reality. In this historical account, the most important contributions have been summarized, thus describing the steady progress, expansion and novelties developed over the last 56 years, since the first attempt. Clinical intestinal transplantation remains a complex and evolving field; ongoing research and technological advancements will continue shaping its future.

4.
Oncoimmunology ; 12(1): 2269634, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37876835

RESUMO

Metastasis is a cancer-related systemic disease and is responsible for the greatest mortality rate among cancer patients. Interestingly, the interaction between the immune system and cancer cells seems to play a key role in metastasis formation in the target organ. However, this complex network is only partially understood. We previously found that IL-22 produced by tissue resident iNKT17 cells promotes cancer cell extravasation, the early step of metastasis. Based on these data, we aimed here to decipher the role of IL-22 in the last step of metastasis formation. We found that IL-22 levels were increased in established metastatic sites in both human and mouse. We also found that Th22 cells were the key source of IL-22 in established metastasis sites, and that deletion of IL-22 in CD4+ T cells was protective in liver metastasis formation. Accordingly, the administration of a murine IL-22 neutralizing antibody in the establishment of metastasis formation significantly reduced the metastatic burden in a mouse model. Mechanistically, IL-22-producing Th22 cells promoted angiogenesis in established metastasis sites. In conclusion, our findings highlight that IL-22 is equally as important in contributing to metastasis formation at late metastatic stages, and thus, identify it as a novel therapeutic target in established metastasis.


Assuntos
Linfócitos T CD4-Positivos , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Interleucinas
5.
Transplantation ; 2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37723639

RESUMO

Intestinal transplant (ITx) rejection lacks a reliable noninvasive biomarker and rejection surveillance relies on serial endoscopies and mucosal biopsies followed by histologic assessment. Endoscopic biopsies are also essential for identifying other ITx-related complications such as infectious, allergic, and inflammatory graft enteritis as well as post-transplant lymphoproliferative disease or graft versus host disease. In spite of its central role in ITx, published guidelines on endoscopy and biopsy are lacking and significant variability between centers in terms of timing and technical performance exists. Therefore, an international expert group convened and discussed several aspects related to the surveillance endoscopy after ITx with the aim to summarize and standardize its practice. This article summarizes these considerations on endoscopic ITx monitoring and highlights practices of surveillance and for-cause endoscopy, biopsy techniques, pathologic evaluation, potential risks and complications, outsourcing, and less-invasive monitoring techniques.

6.
Rev. argent. coloproctología ; 34(3): 5-9, sept. 2023. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-1552475

RESUMO

Introducción: El sangrado digestivo intraluminal postoperatorio es una entidad poco frecuente y su manifestación clínica no difiere de la hemorragia digestiva baja de otra etiología. A pesar de que su presentación más habitual es la hematoquecia autolimitada en la primera deposición, en un discreto porcentaje puede requerir transfusiones, tratamiento endoscópico, hemodinámico, o incluso cirugía. Objetivo: Analizar los pacientes con sangrado digestivo intraluminal postoperatorio tratados en un centro de alta complejidad y realizar una revisión bibliográfica del tema. Diseño: Estudio retrospectivo, descriptivo. Material y métodos: Pacientes con sangrado anastomótico durante el post operatorio inmediato de una colectomía izquierda, operados en el Servicio de Cirugía General y Coloproctología desde enero del 2017 a diciembre del 2021. Las variables estudiadas fueron edad, sexo, anticoagulación y su causa, descenso de hemoglobina, cirugía realizada y su indicación, vía de abordaje, configuración de la anastomosis, electividad de la cirugía, complicaciones, días de internación y manejo terapéutico. Resultados: Se incluyeron 4 pacientes con una edad media de 72 (rango 54-87) años y una distribución por sexo de 1:1. En todos la colectomía izquierda fue programada y en 3 el abordaje fue laparoscópico. La anastomosis fue termino-terminal con sutura mecánica circular. Todos los pacientes presentaron sangrado en las primeras 24 horas postoperatorias. El tratamiento fue decidido de acuerdo a la condición hemodinámica: en los 2 pacientes con estabilidad hemodinámica fue suficiente el tratamiento conservador con reanimación y transfusiones. Los otros 2 que presentaron inestabilidad hemodinámica requirieron manejo intervencionista con endoscopía rígida, videocolonoscopía y cirugía. Conclusión: El sangrado intraluminal es una complicación poco frecuente de la anastomosis colorrectal que requiere manejo intervencionista solo en los pacientes que presentan inestabilidad hemodinámica. (AU)


Introduction: Postoperative intraluminal gastrointestinal bleeding is a rare entity and its clinical manifestation does not differ from lower gastro-intestinal bleeding of another etiology. Despite the fact that its most common presentation is self-limited hematochezia at the first stool, in a small percentage it may require transfusions, endoscopic or hemodynamic management, or even surgery. Aim: To analyze the patients with postoperative intraluminal gastrointestinal bleeding treated in a tertiary center and to carry out a bibliographic review of the subject. Design: Retrospective descriptive study. Material and methods: Patients with immediate postoperative anastomotic bleeding from a left colectomy, operated on at the General Surgery and Coloproctology Service from January 2017 to December 2021 were included. The variables recorded were age, sex, anticoagulation and its cause, decrease in hemoglobin, procedure performed and its indication, surgical approach, type of anastomosis, electiveness of surgery, complications, hospital stay and management. Results: Four patients with a mean age of 72 (range 54-87) years and a 1:1 gender distribution were included. All procedures were elective and 3 laparoscopic. All anastomoses were performed end-to-end with a circular stapler. All patients presented bleeding in the first 24 postoperative hours. The treatment was decided according to the hemodynamic condition; patients with hemodynamic stability (2) received medical treatment while those with hemodynamic instability (2) required interventional management with rigid endoscopy, colonoscopy and surgery. Conclusion: Intraluminal bleeding is a rare complication of colorectal anastomosis that requires interventional management only in patients with hemodynamic instability. (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Colectomia/efeitos adversos , Hemorragia Pós-Operatória/etiologia , Hemorragia Gastrointestinal/etiologia , Reoperação , Anastomose Cirúrgica/efeitos adversos , Colo/cirurgia , Hemorragia Pós-Operatória/terapia , Hemorragia Gastrointestinal/terapia
7.
Rev. argent. cir ; 115(3): 243-253, ago. 2023. graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1514931

RESUMO

RESUMEN Antecedentes : las ventajas de la hepatectomía videolaparoscópica (HVL) hicieron que gane cada vez más campo para el tratamiento de los tumores hepáticos benignos (THB). Objetivo : comparar los resultados perioperatorios de pacientes sometidos a HVL con los de los operados con hepatectomía abierta (HA) por THB, emparejados con propensity score matching (PSM). Material y métodos : estudio descriptivo, retrospectivo y comparativo de HA y HVL por THB entre agosto de 2010 y junio de 2021. Se analizaron variables demográficas, preoperatorias, intraoperatorias y posoperatorias. Para evitar sesgos de las distintas covariables entre los grupos se realizó un PSM 1:1. Resultados : de 403 hepatectomías, se analizaron 82 por THB. De ellas 36 (44%) fueron HA y 46 (56%) HVL. Edad media 45 ±14 años, 65% mujeres. Tras realizar el PSM, quedaron dos grupos de 28 pacientes cada uno. En HA, 5 (18%) pacientes requirieron transfusiones y ninguno en HVL (p = 0,01). Las complicaciones mayores se presentaron en 4 (14%) pacientes en HA, y ninguna en HVL (p = 0,03). Se reoperaron 4 (14%) pacientes con HA y ningún paciente con HVL (p = 0,03). La estadía hospitalaria total fue significativamente mayor en las HA (p = 0,04). No se registraron muertes a los 90 días en ninguno de los dos grupos. Conclusión : la HVL por THB es una técnica segura y eficaz, ya que los pacientes presentaron menor requerimiento transfusional, número de reoperaciones, de complicaciones mayores y de estadía hospitalaria que con HA. Por las ventajas encontradas, la HVL podría ser considerada la técnica de elección en cirugía por THB.


ABSTRACT Background : The advantages of laparoscopic liver resection (LLR) have increased its use for the treatment of benign liver tumors (BLTs). Objective : The aim of this study was to compare the perioperative outcomes of patients undergoing LLR with those operated on with open liver resection (OLR) for BLTs using propensity score matching (PSM). Material and methods : We conducted a descriptive and retrospective study comparing OLRs with LLRs performed between August 2010 and June 2021. The demographic, perioperative, intraoperative and postoperative variables were analyzed. We used PSM with 1:1 matching to avoid biases of the different covariates between the groups. Results : Of 303 liver resections, 82 corresponded to BLTs and were included in the analysis; 36 (44%) were OLRs and 46 (56%) were LLRs. Mean age was 45 ±14 years and 65% were women. After PSM, two groups of 28 patients each were constituted. Five patients (18%) in the OLR group and none in the LLR required transfusions (p = 0.01). Major complications, occurred in 4 (14%) patients in the OLR group and in no cases in the LLR group (p = 0.03). Four (14%) undergoing OLR required reoperation versus no patients with LLR (p = 0.03). Total length of hospital stay was significantly longer in OLR (p = 0.04). There were no deaths in any of the groups within 90 days. Conclusion : LLR for BLTs is a safe and effective technique, with lower requirement for transfusions, fewer reoperations and major complications and shorter length of hospital stay than OLR, Therefore, LLR could be considered the surgical technique of choice for BLTs.

8.
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.

9.
Front Oncol ; 13: 1170502, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37324022

RESUMO

Background: The immune system plays a pivotal role in cancer progression. Interleukin 22 binding protein (IL-22BP), a natural antagonist of the cytokine interleukin 22 (IL-22) has been shown to control the progression of colorectal cancer (CRC). However, the role of IL-22BP in the process of metastasis formation remains unknown. Methods: We used two different murine in vivo metastasis models using the MC38 and LLC cancer cell lines and studied lung and liver metastasis formation after intracaecal or intrasplenic injection of cancer cells. Furthermore, IL22BP expression was measured in a clinical cohort of CRC patients and correlated with metastatic tumor stages. Results: Our data indicate that low levels of IL-22BP are associated with advanced (metastatic) tumor stages in colorectal cancer. Using two different murine in vivo models we show that IL-22BP indeed controls the progression of liver but not lung metastasis in mice. Conclusions: We here demonstrate a crucial role of IL-22BP in controlling metastasis progression. Thus, IL-22 might represent a future therapeutic target against the progression of metastatic CRC.

10.
PLoS Comput Biol ; 19(6): e1011196, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37384797

RESUMO

Intestinal epithelial cells play important roles in the absorption of nutrients, secretion of electrolytes and food digestion. The function of these cells is strongly influenced by purinergic signalling activated by extracellular ATP (eATP) and other nucleotides. The activity of several ecto-enzymes determines the dynamic regulation of eATP. In pathological contexts, eATP may act as a danger signal controlling a variety of purinergic responses aimed at defending the organism from pathogens present in the intestinal lumen. In this study, we characterized the dynamics of eATP on polarized and non-polarized Caco-2 cells. eATP was quantified by luminometry using the luciferin-luciferase reaction. Results show that non-polarized Caco-2 cells triggered a strong but transient release of intracellular ATP after hypotonic stimuli, leading to low micromolar eATP accumulation. Subsequent eATP hydrolysis mainly determined eATP decay, though this effect could be counterbalanced by eATP synthesis by ecto-kinases kinetically characterized in this study. In polarized Caco-2 cells, eATP showed a faster turnover at the apical vs the basolateral side. To quantify the extent to which different processes contribute to eATP regulation, we created a data-driven mathematical model of the metabolism of extracellular nucleotides. Model simulations showed that eATP recycling by ecto-AK is more efficient a low micromolar eADP concentrations and is favored by the low eADPase activity of Caco-2 cells. Simulations also indicated that a transient eATP increase could be observed upon the addition of non-adenine nucleotides due the high ecto-NDPK activity in these cells. Model parameters showed that ecto-kinases are asymmetrically distributed upon polarization, with the apical side having activity levels generally greater in comparison with the basolateral side or the non-polarized cells. Finally, experiments using human intestinal epithelial cells confirmed the presence of functional ecto-kinases promoting eATP synthesis. The adaptive value of eATP regulation and purinergic signalling in the intestine is discussed.


Assuntos
Trifosfato de Adenosina , Células Epiteliais , Humanos , Trifosfato de Adenosina/metabolismo , Células CACO-2 , Células Epiteliais/metabolismo , Proteínas de Transferência de Fosfolipídeos
11.
Ann Surg ; 277(1): e235-e244, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34171860

RESUMO

OBJECTIVE: We aimed to assess whether native spleen preservation during visceral transplantation (VT) affects graft-versus-host-disease (GVHD) incidence. SUMMARY BACKGROUND DATA: GVHD is one of the most severe and frequently lethal hematological complications after VT procedures. Because there is no specific treatment for GVHD, it is imperative to develop a strategy to reduce donor lymphocyte engraftment and proliferation. METHODS: Our study included both clinical and experimental data. A total of 108 patients were divided into 3 groups: a native spleen preservation group, a native spleen removal with no donor spleen group, and a donor spleen included (allogeneic spleen) group. We also used an allogeneic VT rat model, in which recipients were divided into 2 groups: a native spleen preservation (+SP) group and a native spleen removal (-S) group. Skin rash appearance, histopathological changes, chimerism, and spleen effects on circulating allogeneic T-cells were assessed. RESULTS: The patients with native spleen preservation showed a lower rate of GVHD ( P <.001) and better survival ( P <.05) than those in the other groups. Skin and histological signs of GVHD were lower in the rats in the +SP group ( P <.05). The donor T-cell frequency in the bloodstream and skin was also significantly reduced when the native spleen was preserved ( P <.01 and P <.0001, respectively). CONCLUSIONS: The clinical and experimental data indicate that recipient spleen preservation protects against GVHD after VT, and donor cell clearance from the bloodstream by spleen macrophages could be the underlying mechanism. Therefore, spleen preservation should be considered in VT procedures, whenever possible.


Assuntos
Transplante de Medula Óssea , Doença Enxerto-Hospedeiro , Ratos , Animais , Camundongos , Baço , Transplante Homólogo , Linfócitos T , Camundongos Endogâmicos C57BL
12.
Transplantation ; 106(11): 2111-2117, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36279558

RESUMO

BACKGROUND: Transplant therapy is considered the best and often the only available treatment for thousands of patients with organ failure that results from communicable and noncommunicable diseases. The number of annual organ transplants is insufficient for the worldwide need. METHODS: We elaborate the proceedings of the workshop entitled "The Role of Science in the Development of International Standards of Organ Donation and Transplantation," organized by the Pontifical Academy of Sciences and cosponsored by the World Health Organization in June 2021. RESULTS: We detail the urgency and importance of achieving national self-sufficiency in organ transplantation as a public health priority and an important contributor to reaching relevant targets of the United Nations Agenda for Sustainable Development. It details the elements of a global action framework intended for countries at every level of economic development to facilitate either the establishment or enhancement of transplant activity. It sets forth a proposed plan, by addressing the technical considerations for developing and optimizing organ transplantation from both deceased and living organ donors and the regulatory oversight of practices. CONCLUSIONS: This document can be used in governmental and policy circles as a call to action and as a checklist for actions needed to enable organ transplantation as treatment for organ failure.


Assuntos
Transplante de Órgãos , Obtenção de Tecidos e Órgãos , Humanos , Transplante de Órgãos/efeitos adversos , Doadores de Tecidos , Doadores Vivos , Assistência ao Paciente
16.
JPEN J Parenter Enteral Nutr ; 46(7): 1623-1631, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35511709

RESUMO

BACKGROUND: Short bowel syndrome (SBS) is considered a low prevalence disease. In Argentina, no registries are available on chronic intestinal failure (CIF) and SBS. This project was designed as the first national registry to report adult patients with this disease. METHODS: A prospective multicenter observational registry was created including adult patients with CIF/SBS from approved centers. Demographics, clinical characteristics, nutrition assessment, home parenteral nutrition (HPN) management, surgeries performed, medical treatment, overall survival, and freedom from HPN survival were analyzed. RESULTS: Of the 61 enrolled patients, 56 with available follow-up data were analyzed. At enrollment, the mean intestinal length was 59.5 ± 47.3 cm; the anatomy was type 1 (n = 41), type 2 (n = 10), and type 3 (n = 5). At the end of the interim analysis, anatomy changed to type 1 in 31, type 2 in 17, and type 3 in 8 patients. The overall mean time on HPN before enrollment was 33.5 ± 56.2 months. Autologous gastrointestinal reconstruction surgery was performed before enrollment on 21 patients, and afterward on 11. Nine patients (16.1%) were weaned off HPN with standard medical nutrition treatment; 12 patients received enterohormones, and 2 of them suspended HPN; one patient was considered a transplant candidate. In 23.7 ± 14.5 months, 11 of 56 patients discontinued HPN; Kaplan-Meier freedom from HPN survival was 28.9%. The number of cases collected represented 19.6 new adult CIF/SBS patients per year. CONCLUSION: The RESTORE project allowed us to know the incidence, the current medical and surgical approach for this pathology, as well as its outcome and complications at dedicated centers.


Assuntos
Enteropatias , Insuficiência Intestinal , Nutrição Parenteral no Domicílio , Síndrome do Intestino Curto , Adulto , Argentina/epidemiologia , Doença Crônica , Humanos , Enteropatias/terapia , Estudos Prospectivos , Sistema de Registros , Estudos Retrospectivos , Síndrome do Intestino Curto/complicações , Síndrome do Intestino Curto/terapia
17.
Curr Opin Organ Transplant ; 27(2): 148-153, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35153280

RESUMO

PURPOSE OF REVIEW: Intestinal failure (IF) evolved from being the last recognized organ failure, to become one of the most progressive fields in terms of therapeutic alternatives and results. Short bowel syndrome (SBS) is the main cause of IF in adults and children. The use of surgery allowed patients with unfavorable anatomy type and length to be wean off parenteral nutrition. We aim to evaluate its current impact on intestinal rehabilitation. RECENT FINDINGS: Autologous gastro-intestinal reconstructive surgery (AGIRS), including bowel lengthening contributes by converting patient's anatomy to a more favorable one, improving quality of life, and modifying the natural history of the disease, allowing to recover intestinal autonomy in approximately 70% of the adults and 50% of the children's with SBS-IF. The current use of postsurgical medical rehabilitation strategies including the use of enterohormones complement the path to sufficiency, increasing the chances of success in both age group of patients. SUMMARY: The development of AGIRS has changed the outcome of SBS-IF patients, becoming the main surgical procedure prescribed in multidisciplinary units, allowing to enhance the number of patients achieving intestinal autonomy throughout rehabilitation, leaving transplantation as the last surgical alternative.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Síndrome do Intestino Curto , Adulto , Criança , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Humanos , Intestinos , Nutrição Parenteral/métodos , Qualidade de Vida , Síndrome do Intestino Curto/tratamento farmacológico , Síndrome do Intestino Curto/cirurgia , Resultado do Tratamento
18.
J Trauma Acute Care Surg ; 92(2): 380-387, 2022 02 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-35081098

RESUMO

BACKGROUND: The hemodynamic maintenance of brain-dead donors will influence the quality of the organs procured for transplantation, including the intestine. Although norepinephrine (NE) and dopamine (DA) are commonly used to sustain mean arterial pressure in humans, there are no standardized protocols for their use during maintenance of brain-dead donors. Our aim was to compare the effects of each drug, in the intestinal graft quality using a rat brain-dead donation model. METHODS: Wistar rats (N = 17) underwent brain death (BD) for 2 hours with NE (NE group) or with DA (DA group) administration; the control group was mechanically ventilated for 2 hours without BD. Jejunum biopsies were obtained at the end of the maintenance period. Histological damage was evaluated using Park-Chiu scale. Villi/crypt ratio, mucosal thickness, Goblet cell count, and villi density were evaluated using ImageJ software (US National Institutes of Health, Bethesda, MD). Barrier damage was assessed by bacterial translocation culture counting on liver samples. The inflammatory status of the intestine was evaluated by CD3+ counting by immunohistochemistry and gene expression analysis of interleukin (IL)-6, IL-22, and CXCL10. RESULTS: Norepinephrine-treated donors had higher focal ischemic injury in the intestinal mucosa without a substantial modification of morphometrical parameters compared with DA-treated donors. CD3+ mucosal infiltration was greater in intestines procured from brain-dead donors, being highest in NE (p ˂ 0.001). Local inflammatory mediators were affected in BD: DA and NE groups showed a trend to lower expression of IL-22, whereas CXCL10 expression was higher in NE versus control group. Brain death promoted intestinal bacterial translocation, but the use of NE resulted in the highest bacterial counting in the liver (p ˂ 0.01). CONCLUSION: Our results favor the use of DA instead of NE as main vasoactive drug to manage BD-associated hemodynamic instability. Dopamine may contribute to improve the quality of the intestinal graft, by better preserving barrier function and lowering immune cell infiltration.


BACKGROUND: The hemodynamic maintenance of brain-dead donors will influence the quality of the organs procured for transplantation, including the intestine. Although norepinephrine (NE) and dopamine (DA) are commonly used to sustain mean arterial pressure in humans, there are no standardized protocols for their use during maintenance of brain-dead donors. Our aim was to compare the effects of each drug, in the intestinal graft quality using a rat brain-dead donation model. METHODS: Wistar rats (N = 17) underwent brain death (BD) for 2 hours with NE (NE group) or with DA (DA group) administration; the control group was mechanically ventilated for 2 hours without BD. Jejunum biopsies were obtained at the end of the maintenance period. Histological damage was evaluated using Park-Chiu scale. Villi/crypt ratio, mucosal thickness, Goblet cell count, and villi density were evaluated using ImageJ software (US National Institutes of Health, Bethesda, MD). Barrier damage was assessed by bacterial translocation culture counting on liver samples. The inflammatory status of the intestine was evaluated by CD3 + counting by immunohistochemistry and gene expression analysis of interleukin (IL)-6, IL-22, and CXCL10. RESULTS: Norepinephrine-treated donors had higher focal ischemic injury in the intestinal mucosa without a substantial modification of morphometrical parameters compared with DA-treated donors. CD3 + mucosal infiltration was greater in intestines procured from brain-dead donors, being highest in NE ( p ˂ 0.001). Local inflammatory mediators were affected in BD: DA and NE groups showed a trend to lower expression of IL-22, whereas CXCL10 expression was higher in NE versus control group. Brain death promoted intestinal bacterial translocation, but the use of NE resulted in the highest bacterial counting in the liver ( p ˂ 0.01). CONCLUSION: Our results favor the use of DA instead of NE as main vasoactive drug to manage BD-associated hemodynamic instability. Dopamine may contribute to improve the quality of the intestinal graft, by better preserving barrier function and lowering immune cell infiltration.


Assuntos
Morte Encefálica , Dopamina/farmacologia , Hemodinâmica/efeitos dos fármacos , Intestinos/irrigação sanguínea , Intestinos/transplante , Norepinefrina/farmacologia , Animais , Quimiocina CXCL10/metabolismo , Modelos Animais de Doenças , Interleucina-6/metabolismo , Interleucinas/metabolismo , Intestinos/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar
20.
Exp Clin Transplant ; 20(12): 1105-1113, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36718010

RESUMO

OBJECTIVES: Immunosuppressive strategies for intestinal transplant have changed over time. However, specific intestinal transplant-oriented protocols and reports on long-term maintenance regimens are scarce. Our objective was to evaluate the impact of 2 different initial immunosuppressive protocols based on thymoglobulin (group A) and basiliximab (anti-interleukin 2 antibody) (group B) and of changes to maintenance immunosuppression over long-term follow-up in intestinal transplant recipients. MATERIALS AND METHODS: We performed a retrospective analysis of a prospectively established protocol for intestinal transplant immunosuppression, conducted between May 2006 and December 2020. We analyzed 51 intestinal transplant recipients, with 6 patients excluded because of early death or graft loss. Acute cellular rejection frequency and grade, number of acute cellular rejection episodes, time to the first acute cellular rejection episode, response to treatment, number of patients who progressed to chronic allograft rejection, kidney function, infections, incidence of posttransplant lymphoproliferative disorder and graft-versus-host disease, and patient and graft survival were analyzed. RESULTS: In the study groups, there were 87 acute cellular rejection episodes in 45 patients (33 in group A and 54 in group B). We found degree of acute cellular rejection to be mild in 45 patients, moderate in 18, and severe in 24 (not significant between groups). Our comparison of induction therapy (thymoglobulin [group A] vs interleukin 2 antibody [group B]) did not show any statistical difference during clinical followup. Long-term review showed that all patients were on tacrolimus. Five-year patient and graft survival rates were 62% and 45% for group A and 54% and 46% for group B, respectively (not significant). CONCLUSIONS: Long-term patient and graft outcomes reflected the use of an individualized follow-up with adjustments and changes in immunosuppressive medications according to the patient's clinical course and complications rather than based on the induction immunosuppressive protocol used.


Assuntos
Anticorpos Monoclonais , Transplante de Rim , Humanos , Sobrevivência de Enxerto , Estudos Retrospectivos , Transplante de Rim/efeitos adversos , Imunossupressores/efeitos adversos , Terapia de Imunossupressão/métodos , Rejeição de Enxerto/tratamento farmacológico
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