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1.
Article in English | MEDLINE | ID: mdl-39367870

ABSTRACT

BACKGROUND: Short bowel syndrome is considered a low prevalence disease. The scant information available about intestinal failure in Latin America was the driving force to expand this registry. METHODS: A prospective, multicenter observational registry was created for patients with chronic intestinal failure short bowel at specialized centers in Latin America. Demographics, clinical characteristics, nutrition assessment, parenteral nutrition management, intestinal rehabilitation, related complications, clinical outcome, and survival were analyzed. RESULTS: From May 2020 to July 2023, 167 patients (115 adults, 52 children) from 20 centers were enrolled. For the adults, the mean age was 37.2 ± 18 years, 48% were female, and the mean follow-up was 22.6 ± 18.3 months. The main etiology was surgical resections (postsurgical complications: 37%; ischemia: 25%); the mean intestinal length was 73 ± 55 cm. The complications were as follows: infections: 0.4/1000 catheter-days; thrombosis: 0.24/1000 catheter-days; liver disease: 2.6%. The outcomes were as follows: 28% were rehabilitated, 15% died, 9.6% were lost to follow-up, 0.9% underwent transplant, and 45.6% continued follow-up. For the children, the mean age 48 ± 52 months, 48% were female, 52% were premature. The mean follow-up was 17.2 ± 5.6 months; the mean remaining intestinal length was 38 ± 45 cm. The leading etiologies were atresia (25%), NEC (23%), and gastroschisis (21%). The complication were as follows: infections: 2/1000 catheter-days; thrombosis: 2.22/1000 catheter-day; 25% developed liver disease. The outcomes were as follows: 7.7% died, 3.8% were rehabilitated, and 88.5% continued follow-up. CONCLUSION: The RESTORE amendment served as a registry and educational tool for the participating teams. The aspiration is to objectively show current aspects of intestinal failure in the region and carry them to international standards. Including all Latin American countries and etiologies of chronic intestinal failure besides short gut would serve to complete this registry.

2.
Exp Clin Transplant ; 22(7): 487-496, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39223807

ABSTRACT

OBJECTIVES: Technical graft loss, usually thrombotic in nature, accounts for most of the pancreas grafts that are removed early after transplant. Although arterial and venous thrombosis can occur, the vein is predominantly affected, with estimated overall rate of thrombosis of 6% to 33%. In late diagnosis, the graft will need to be removed because thrombectomy will not restore its functionality. However, in early diagnosis, a salvage procedure should be attempted. MATERIALS AND METHODS: We conducted a retrospective, descriptive analysis of a prospective database of patients who underwent pancreas transplant from April 2008 to June 2020 at a single center. We evaluated post-transplant clinical glucose levels, imaging, treatment, and outcomes. We also performed a systematic review of publications for endovascular treatment of vascular graft thrombosis in pancreas transplant. RESULTS: In 67 pancreas transplants analyzed, 13 (19%) were diagnosed with venous thrombus. In 7 of 13 patients (54%), systemic anticoagulation was prescribed because of a non-occlusive thromboses, resulting in complete resolution for all 7 patients. Six patients (46%) required endovascular thrombectomy because of the presence of complete occlusive thrombosis; 4 of these patients (67%) needed a second procedure because of recurrence of the thrombosis. One of the 6 patients (17%) required a surgical approach, resulting in successful removal of the recurrent clot. Twelve of the 13 grafts (92%) were rescued. Graft survival at 1 year was 84%; graft survival at 3, 5, and 10 years remained at 70%. CONCLUSIONS: Pancreas vein thrombosis represents a frequent surgical complication and remains as a challenging problem. In our experience, early diagnoses and an endovascular approach combined with aggressive medical treatment and follow-up can be used for successful treatment and reduce graft loss.


Subject(s)
Endovascular Procedures , Pancreas Transplantation , Salvage Therapy , Splenic Vein , Thrombectomy , Venous Thrombosis , Adult , Female , Humans , Male , Middle Aged , Databases, Factual/statistics & numerical data , Endovascular Procedures/adverse effects , Endovascular Procedures/methods , Pancreas Transplantation/adverse effects , Recurrence , Retrospective Studies , Risk Factors , Salvage Therapy/adverse effects , Salvage Therapy/methods , Splenic Vein/surgery , Splenic Vein/diagnostic imaging , Thrombectomy/adverse effects , Thrombectomy/methods , Time Factors , Treatment Outcome , Venous Thrombosis/diagnosis , Venous Thrombosis/epidemiology , Venous Thrombosis/etiology , Venous Thrombosis/therapy
3.
Nutrients ; 16(16)2024 Aug 10.
Article in English | MEDLINE | ID: mdl-39203785

ABSTRACT

BACKGROUND: Chronic intestinal failure (CIF) is a heterogeneous disease that affects pediatric and adult populations worldwide and requires complex multidisciplinary management. In recent years, many advances in intravenous supplementation support, surgical techniques, pharmacological management, and intestinal transplants have been published. Based on these advances, international societies have published multiple recommendations and guidelines for the management of these patients. The purpose of this paper is to show the differences that currently exist between the recommendations (ideal life) and the experiences published by different programs around the world. METHODS: A review of the literature in PubMed from 1980 to 2024 was carried out using the following terms: intestinal failure, CIF, home parenteral nutrition, short bowel syndrome, chronic intestinal pseudo-obstruction, intestinal transplant, enterohormones, and glucagon-like peptide-2. CONCLUSIONS: There is a difference between what is recommended in the guidelines and consensus and what is applied in real life. Most of the world's countries are not able to offer all of the steps needed to treat this pathology. The development of cooperative networks between countries is necessary to ensure access to comprehensive treatment for most patients on all continents, but especially in low-income countries.


Subject(s)
Intestinal Failure , Parenteral Nutrition, Home , Humans , Chronic Disease , Adult , Intestinal Failure/therapy , Short Bowel Syndrome/therapy , Practice Guidelines as Topic , Intestinal Pseudo-Obstruction/therapy , Glucagon-Like Peptide 2
4.
Nutrients ; 16(15)2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39125394

ABSTRACT

The Short Bowel Syndrome (SBS) Registry (NCT01990040) is a multinational real-world study evaluating the long-term safety of teduglutide in patients with SBS and intestinal failure (SBS-IF) in routine clinical practice. This paper describes the study methodology and baseline characteristics of adult patients who have (ever-treated) or have never (never-treated) received teduglutide. A total of 1411 adult patients (679 ever-treated; 732 never-treated) were enrolled at 124 sites across 17 countries. The mean (standard deviation [SD]) age at enrollment was 55.4 (15.46) years, and 60.2% of patients were women. Crohn's disease was the most common cause of major intestinal resection in both ever-treated (34.1%) and never-treated patients (20.4%). A similar proportion of ever-treated and never-treated patients had a prior history of colorectal polyps (2.7% vs. 3.6%), whereas proportionally fewer ever-treated patients reported a history of colorectal cancer (1.8% vs. 6.2%) or any malignancy (17.7% vs. 30.0%) than never-treated patients. Never-treated patients received a numerically greater mean (SD) volume of parenteral nutrition and/or intravenous fluids than ever-treated patients (12.4 [8.02] vs. 10.1 [6.64] L/week). Ever-treated patients received a mean teduglutide dosage of 0.05 mg/kg/day. This is the first report of patient baseline characteristics from the SBS Registry, and the largest cohort of patients with SBS-IF to date. Overall, ever-treated and never-treated patients had similar baseline characteristics. Differences between treatment groups may reflect variations in patient selection and degree of monitoring.


Subject(s)
Gastrointestinal Agents , Peptides , Registries , Short Bowel Syndrome , Humans , Short Bowel Syndrome/drug therapy , Female , Male , Middle Aged , Peptides/therapeutic use , Adult , Aged , Gastrointestinal Agents/therapeutic use , Intestinal Failure/drug therapy , Treatment Outcome , Crohn Disease/drug therapy
5.
Rev. argent. cir ; 116(3): 215-224, ago. 2024. graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1575957

ABSTRACT

RESUMEN La comprensión de los mecanismos para el desarrollo de la ascitis ha evolucionado a lo largo de los años, involucrando al hígado, peritoneo, corazón y riñones, pero no al intestino, como responsable clave en su formación. Poco se ha descripto tanto de su papel fisiopatológico como de las posibles alternativas terapéuticas clínicas y quirúrgicas. A fin de validar empíricamente este concepto se relata la situación de un hombre de 39 años, con trombosis aislada de la vena mesentérica superior y fallo intestinal. La necesidad de realizar una derivación quirúrgica nos llevó a construir un shunt desde una vena colateral de la mesentérica superior a la vena esplénica. La reducción de la presión del sistema mesentérico superior de 35 a 6 mm Hg sirvió para la resolución de los signos y síntomas clínicos en un mes. Este caso obliga a revisar conceptos fisiopatológicos básicos sobre la producción de ascitis, contribuye a la descripción de un nuevo tipo de shunt y amplía las opciones terapéuticas quirúrgicas en el tratamiento de la hipertensión venosa esplácnica.


ABSTRACT The understanding of the mechanisms for the development of ascites has evolved over the years to include the liver, peritoneum, heart and kidneys, but not the intestine, as key players in its formation. The pathophysiological role of the intestine as well as the possible clinical and surgical therapeutic options have been poorly described. In order to empirically validate this concept, we report the situation of a 39-year-old man with isolated thrombosis of the superior mesenteric vein and intestinal failure. The need to perform a surgical shunt led us to construct a shunt from a collateral vein of the superior mesenteric vein to the splenic vein. The reduction in pressure in the superior mesenteric venous system from 35 to 6 mm Hg resulted in resolution of clinical signs and symptoms within one month. This case study forces us to review the basic pathophysiological concepts of ascites formation, contributes to the description of a new type of shunt, and expands the surgical therapeutic options in the treatment of splanchnic venous hypertension.

6.
Liver Transpl ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38949782

ABSTRACT

Advances in immunosuppression have extended patient and graft survival rates after solid organ transplantation; however, this is not free of side effects. Balancing safety and efficacy is of paramount importance, particularly in the pediatric setting. Current literature comparing different protocols is scarce, and decisions are mostly guided by physician preference. We aimed to compare 3 different protocols from 4 different centers to identify differences in outcomes after 1 year of follow-up. A retrospective analysis of the databases of the participating centers was performed. Consecutive patients aged <18 years with a first liver-only transplant and no other underlying congenital or acquired immunodeficiency were included. Patients were classified according to the immunosuppression protocol as follows: group A (prednisone + tacrolimus + basiliximab), group B (prednisone + tacrolimus + basiliximab + antithymocyte globulin), and group C (prednisone + tacrolimus). Differences in survival, frequency of rejection, infections, and other complications were analyzed in the entire group (n = 97) and the group with biliary atresia (n = 48). After 1 year of follow-up, no differences in patient or graft survival were observed when comparing either the entire group (n = 97) or patients with biliary atresia only (n = 48). The frequencies of rejection and episodes of infection were similar. Renal function showed no differences either before or after transplantation or between the groups. Immunosuppression protocols used in this study appeared to be equally safe and effective. This could offer the opportunity to tailor them to the patient's individual characteristics without compromising the outcome.

7.
Ann Hepatol ; 29(4): 101506, 2024.
Article in English | MEDLINE | ID: mdl-38710471

ABSTRACT

INTRODUCTION AND OBJECTIVES: Epigenetic changes represent a mechanism connecting external stresses with long-term modifications of gene expression programs. In solid organ transplantation, ischemia-reperfusion injury (IRI) appears to induce epigenomic changes in the graft, although the currently available data are extremely limited. The present study aimed to characterize variations in DNA methylation and their effects on the transcriptome in liver transplantation from brain-dead donors. PATIENTS AND METHODS: 12 liver grafts were evaluated through serial biopsies at different timings in the procurement-transplantation process: T0 (warm procurement, in donor), T1 (bench surgery), and T2 (after reperfusion, in recipient). DNA methylation (DNAm) and transcriptome profiles of biopsies were analyzed using microarrays and RNAseq. RESULTS: Significant variations in DNAm were identified, particularly between T2 and T0. Functional enrichment of the best 1000 ranked differentially methylated promoters demonstrated that 387 hypermethylated and 613 hypomethylated promoters were involved in spliceosomal assembly and response to biotic stimuli, and inflammatory immune responses, respectively. At the transcriptome level, T2 vs. T0 showed an upregulation of 337 and downregulation of 61 genes, collectively involved in TNF-α, NFKB, and interleukin signaling. Cell enrichment analysis individuates macrophages, monocytes, and neutrophils as the most significant tissue-cell type in the response. CONCLUSIONS: In the process of liver graft procurement-transplantation, IRI induces significant epigenetic changes that primarily act on the signaling pathways of inflammatory responses dependent on TNF-α, NFKB, and interleukins. Our DNAm datasets are the early IRI methylome literature and will serve as a launch point for studying the impact of epigenetic modification in IRI.


Subject(s)
DNA Methylation , Epigenesis, Genetic , Gene Expression Profiling , Liver Transplantation , Liver , Reperfusion Injury , Liver Transplantation/adverse effects , Reperfusion Injury/genetics , Reperfusion Injury/metabolism , Humans , Liver/metabolism , Liver/pathology , Male , Middle Aged , Female , Gene Expression Profiling/methods , Transcriptome , Adult , Aged
8.
Ann Hepatol ; 29(3): 101498, 2024.
Article in English | MEDLINE | ID: mdl-38479458

ABSTRACT

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.


Subject(s)
Ascites , Intestines , Humans , Ascites/physiopathology , Ascites/etiology , Intestines/physiopathology
9.
Rev. argent. cir ; 115(4): 320-333, dic. 2023. graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1559248

ABSTRACT

RESUMEN Antecedentes: la insuficiencia intestinal, en su grado más grave, se conoce como fallo intestinal crónico (FIC). Las últimas décadas han sido testigo de la incorporación, evolución y perfeccionamiento de tratamientos que, en su conjunto, se denominan rehabilitación intestinal y abarcan tanto procedimientos quirúrgicos como tratamientos médicos que, llevados a cabo por equipos multi e interdisciplinarios, alcanzan altas tasas de éxito. Objetivo: describir los resultados de 16 años en el tratamiento de pacientes con FIC secundario a síndrome de intestino corto (SIC), y la evolución del papel de la cirugía, la rehabilitación médica y el trasplante. Material y métodos: análisis retrospectivo de una base de datos prospectiva de pacientes con fallo intestinal crónico secundario a SIC entre febrero de 2006 y marzo de 2022. Resultados: se incluyeron 492 pacientes (368 adultos-A y 124 pediátricos-P). Grupo A: 111 pacientes recibieron cirugía de reconstrucción autóloga del tracto gastrointestinal (CRATGI), 16 péptido semisintético similar al glucagón de tipo 2 (sGLP-2); el 83% logró la rehabilitación, con un 77% de supervivencia a 10 años; el 6,8% (17 pacientes) requirió trasplante intestinal (TxI), con un 89% de independencia de la nutrición parenteral (NP) al año y supervivencia post-TxI del 29% a los 10 años. Grupo B: 18 recibieron CRATGI; 9, enteroplastia serial transversa (STEP); y 6, sGLP-2; el 52% se rehabilitó, con una supervivencia del 69% a los 10 años; 28 pacientes recibieron TxI, con 69% de independencia de nutrición parenteral (NP) al año y supervivencia del 39% a los 10 años. Conclusión: los resultados presentados resaltan el papel central de la cirugía y la rehabilitación médica para alcanzar la suficiencia intestinal.


ABSTRACT Background: Severe intestinal insufficiency is known as chronic intestinal failure (CIF). In recent decades, medical treatments and surgical procedures have been incorporated, developed and improved under the name intestinal rehabilitation. When performed by multiand interdisciplinary teams, these treatments have high success rates. Objective: The aim of present study is to describe the 16-year outcomes in the management of patients with CIF secondary to short bowel syndrome (SBS) and the role of surgery, medical rehabilitation, and transplantation. Material and methods: We conducted a retrospective analysis on a prospective database of patients treated with chronic intestinal failure due to SBS between February 2006 and March 2022. Results: A total of 492 patients (368 adults (Group A) and 124 pediatric patients (Group B)] were included. Group A: 111 patients underwent autologous gastrointestinal reconstruction surgery (AGIRS), 16 were treated with semisynthetic glucagon-like peptide-2 (sGLP2); 83% achieved rehabilitation, with 77% survival at 10 years; 6.8% (17 patients) required intestinal transplantation (ITx), with 89% independence from parenteral nutrition (PN) at 1 year and post-ITx survival of 29% at 10 years. Group B: 18 patients underwent AGIRS; 9 underwent serial transverse enteroplasty (STEP); and 6 received sGLP2; 52% were rehabilitated, with 69% survival at 10 years; 28 patients received ITx, with 69% independence from PN at 1 year and 39% survival at 10 years. Conclusion: These results highlight the central role of surgery and medical rehabilitation in the recovery of intestinal function.

10.
Rev. argent. coloproctología ; 34(3): 5-9, sept. 2023. ilus, tab
Article in Spanish | LILACS | ID: biblio-1552475

ABSTRACT

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)


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Colectomy/adverse effects , Postoperative Hemorrhage/etiology , Gastrointestinal Hemorrhage/etiology , Reoperation , Anastomosis, Surgical/adverse effects , Colon/surgery , Postoperative Hemorrhage/therapy , Gastrointestinal Hemorrhage/therapy
11.
Rev. argent. cir ; 115(3): 243-253, ago. 2023. graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1514931

ABSTRACT

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.

12.
PLoS Comput Biol ; 19(6): e1011196, 2023 06.
Article in English | MEDLINE | ID: mdl-37384797

ABSTRACT

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.


Subject(s)
Adenosine Triphosphate , Epithelial Cells , Humans , Adenosine Triphosphate/metabolism , Caco-2 Cells , Epithelial Cells/metabolism , Phospholipid Transfer Proteins
14.
JPEN J Parenter Enteral Nutr ; 46(7): 1623-1631, 2022 09.
Article in English | MEDLINE | ID: mdl-35511709

ABSTRACT

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.


Subject(s)
Intestinal Diseases , Intestinal Failure , Parenteral Nutrition, Home , Short Bowel Syndrome , Adult , Argentina/epidemiology , Chronic Disease , Humans , Intestinal Diseases/therapy , Prospective Studies , Registries , Retrospective Studies , Short Bowel Syndrome/complications , Short Bowel Syndrome/therapy
16.
Exp Clin Transplant ; 20(12): 1105-1113, 2022 12.
Article in English | MEDLINE | ID: mdl-36718010

ABSTRACT

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.


Subject(s)
Antibodies, Monoclonal , Kidney Transplantation , Humans , Graft Survival , Retrospective Studies , Kidney Transplantation/adverse effects , Immunosuppressive Agents/adverse effects , Immunosuppression Therapy/methods , Graft Rejection/drug therapy
17.
Dig Dis Sci ; 67(7): 3006-3016, 2022 07.
Article in English | MEDLINE | ID: mdl-34156590

ABSTRACT

BACKGROUND: Deregulation of immune response and oxidative stress contribute to nonalcoholic fatty liver disease (NAFLD) pathogenesis. Resistin is a physiological modulator of inflammation and redox homeostasis of different cell types. Increased resistin serum concentration and the direct association between resistin hepatic expression and NAFLD severity suggest that resistin participates in NAFLD pathogenesis. AIMS: To evaluate resistin-induced regulation of redox homeostasis in mononuclear leukocytes from NAFLD patients and controls. METHODS: We evaluated basal and resistin-mediated modulation of reactive oxygen species (ROS) and glutathione content by flow cytometry, and antioxidant enzyme activities by spectrophotometry. RESULTS: Peripheral blood mononuclear cells (PBMC) from NAFLD patients showed higher ROS content and glutathione peroxidase activity and lower glutathione content, superoxide dismutase and glutathione reductase activities than control PBMC. Resistin decreased ROS levels and superoxide dismutase activity and increased glutathione reductase and catalase activities in PBMC from controls but not from patients. Resistin decreased glutathione content in PBMC from control and NAFLD patients, with greater effect on patient cells. Basal and resistin-modulated ROS levels were directly associated with obesity-related risk factors for NAFLD. Hepatic myeloid cells and T-lymphocytes from NAFLD patients showed higher basal ROS content than cells from controls. Resistin decreased ROS levels in hepatic T-lymphocytes from controls but not from patients. CONCLUSIONS: Resistin regulates redox homeostasis in mononuclear leukocytes. A decreased response to resistin in leukocytes from NAFLD patients is associated with an impaired redox homeostasis.


Subject(s)
Non-alcoholic Fatty Liver Disease , Antioxidants/metabolism , Glutathione/metabolism , Glutathione Reductase/metabolism , Humans , Leukocytes, Mononuclear/metabolism , Non-alcoholic Fatty Liver Disease/pathology , Oxidative Stress , Reactive Oxygen Species , Resistin/metabolism , Superoxide Dismutase/metabolism
19.
Rev. argent. cir ; 113(3): 326-340, set. 2021. graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1356938

ABSTRACT

RESUMEN Antecedentes: La cirugía hepática videolaparoscópica ha experimentado un importante desarrollo; sin embargo, la mayoría de las hepatectomías continúan haciéndose por vía convencional. Objetivo: presentar la experiencia y aplicabilidad de hepatectomías videolaparoscópicas. Material y métodos: análisis retrospectivo de pacientes sometidos a una hepatectomía entre agosto de 2010 y diciembre de 2019. Analizamos variables preoperatorias, intraoperatorias y posoperatorias. Para evaluar la aplicabilidad, se dividió la muestra en: Etapa 1: agosto de 2010 a diciembre de 2013; Etapa 2: enero de 2014 a diciembre de 2016, Etapa 3: enero de 2017 a diciembre de 2019. Resultados: de 385 hepatectomías realizadas, 119 fueron videolaparoscópicas: 53 (44%) fueron to talmente laparoscópicas, 64 (54%) mano-asistidas y 2 híbridas. La aplicabilidad global fue 31%. En la etapa 1: 23% , en la 2: 30% y en la 3: 44% (p < 0,05). Fueron patología maligna en la etapa 1: 36%, en la 2: 67% y en la 3: 72% (p < 0,05). Hepatectomías mayores: 13%, 31% y 32% en etapas 1, 2, y 3, respectivamente (p < 0,05). El índice de conversión fue 12%, 0% y 11%, respectivamente (p NS). Se utilizó clampeo pedicular en: 6%, 5% y 45%; (p < 0,05). Las complicaciones en la etapa 1 fueron 30%, en la 2: 28% y en la 3: 17%, siendo complicaciones Dindo-Clavien III o más, el 6%, 13% y 5%, respectivamente, p NS. Conclusiones: Aa pesar de su complejidad, las hepatectomías videolaparoscópicas son técnicamente reproducibles. Adquiriendo experiencia, podemos aumentar la aplicabilidad, a favor de la patología oncológica y complejidad, sin comprometer la seguridad del paciente.


ABSTRACT Background: Despite laparoscopic liver resection has significantly evolved, most hepatectomies are performed by the conventional approach. Objective: The aim of this study is to present the initial experience and applicability of laparoscopic liver resections. Material and methods: We conducted a retrospective analysis of patients undergoing liver resection between August 2010 and December 2019. Perioperative, intraoperative and postoperative variables were analyzed. To evaluate applicability, the sample was divided into 3 stages: stage 1, from August 2010 to December 2013; stage 2, from January 2014 to December 2016; and stage 3, from January 2017 to December 2019. Results: Of 385 liver resections performed, 119 were laparoscopic procedures: 53 (44%) were pure laparoscopic procedures, 64 (54%) were hand-assisted (64 patients) and 2 corresponded to hybrid procedures. Global applicability was 31%. In stage 1 1: 23%, in 2: 30% and in 3: 44% (p < 0.05). Malignant lesions: stage 1: 36%, stage 2: 67% and stage 3: 72% (p < 0.05). Major liver resections: 13%, 31% and 32% in stages 1, 2, and 3, respectively (p < 0.05). Conversion rate was 12%, 0% and 11%, respectively (p NS). Hepatic pedicle clamping was used in 6%, 5% and 45%; (p < 0.05). Complications in stage 1 were 30%, in stage 2: 28% and in stage 3: 17%, and Clavien-Dindo complications grade 3 or greater were 6%, 13% and 5%, respectively, p NS. Conclusions: Laparoscopic liver resections are complex procedures but technically reproducible. Applicability increases with the acquisition of experience, not only in malignant lesions but also in complex lesions ensuring safety for the patient.

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